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1. Effect of Denosumab on Glucose Homeostasis in Postmenopausal Women with Breast Cancer Treated with Aromatase Inhibitors: A Pilot Study

Author: Sofia Frigerio, Alessandro Rossini, Roberto Trevisan, Sabrina Corbetta, Gianluca Perseghin, Elena Dozio, Rossini, A, Frigerio, S, Dozio, E, Trevisan, R, Perseghin, G, and Corbetta, S
Subjects: medicine.medical_specialty, FGF21, Article Subject, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Carbohydrate metabolism, Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Insulin resistance, Breast cancer, Internal medicine, medicine, Glucose homeostasis, Aromatase, MED/13 - ENDOCRINOLOGIA, biology, diabetes mellitu, Endocrine and Autonomic Systems, business.industry, Osteoporosi, Cancer, RC648-665, medicine.disease, Denosumab, 030220 oncology & carcinogenesis, biology.protein, business, Research Article, medicine.drug
Abstract: Background. Aromatase inhibitors in women with breast cancer have been associated with cancer treatment-induced bone loss (CTIBL), increased fracture risk, and impairment of glucose metabolism. Denosumab (Dmab), a monoclonal antibody against RANKL, which is a key regulator of the osteoclast activity, is effective as an antiresorptive agent in the treatment of CTIBL. Since RANKL/RANK pathway may contribute to the pathogenesis of glucometabolic disorders, it has been suggested that Dmab may improve glucose homeostasis. Our pilot study evaluated the effect of a single administration of 60 mg Dmab on glucose metabolism in a cohort of women with breast cancer treated with aromatase inhibitors. Methods. Fifteen postmenopausal nondiabetic women were prospectively enrolled. Oral glucose tolerance test (OGTT) and metabolic parameters, including FGF21, were assessed at baseline and one month after Dmab injection. Midterm glucose control was evaluated by measuring glycated haemoglobin (HbA1c) levels 5 months after Dmab. Results. Parameters of glucose metabolism were not different one month after Dmab but circulating FGF21 levels significantly decreased (128.5 ± 46.8 versus 100.2 ± 48.8 pg/mL; p = 0.016 ). Considering patients with insulin resistance at baseline (HOMA-IR > 2.5 and Matsuda Index p = 0.029 ) and increased insulin sensitivity index QUICKI (0.317 ± 0.013 versus 0.327 ± 0.009; p = 0.025 ) were found. Nonetheless, HbA1c increased 5 months after Dmab (36.0 ± 2.3 versus 39.6 ± 3.1 mmol/mol; p = 0.01 ). Conclusions. Although RANKL blockade induced a short-term positive effect on insulin sensitivity, particularly in insulin-resistant patients, a benefit on long-term glucose metabolism was not evident. In conclusion, Dmab is safe for glucose metabolism in aromatase inhibitor-treated women with breast cancer.
Published: 2020
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2. Sitagliptin Treatment at the Time of Hospitalization Was Associated With Reduced Mortality in Patients With Type 2 Diabetes and COVID-19: A Multicenter, Case-Control, Retrospective, Observational Study

Author: Marco Mirani, Riccardo Colombo, Ida Pastore, Rosalia Bellante, Francesca D'Addio, Angelo Corsico, Alessandro Roberto Dodesini, Cristiana Scaranna, Silvia Galliani, Sebastiano Bruno Solerte, Roberto Trevisan, Elisabetta Lovati, Giuseppe Lepore, Franco Folli, Emanuele Catena, Salvatore Endrio Oleandri, Marco Dell’Acqua, Antonio Rossi, Elio Ippolito, Francesca Geni, Antonio Di Sabatino, Carlo De Riva, Gian Vincenzo Zuccotti, Paolo Fiorina, Roberta Maria Fiorina, Reza Abdi, Massimo Galli, Joseph V. Bonventre, Stefano Rusconi, Solerte, S, D'Addio, F, Trevisan, R, Lovati, E, Rossi, A, Pastore, I, Acqua, M, Ippolito, E, Scaranna, C, Bellante, R, Galliani, S, Dodesini, A, Lepore, G, Geni, F, Fiorina, R, Catena, E, Corsico, A, Colombo, R, Mirani, M, Riva De, C, Oleandri, S, Abdi, R, Bonventre, J, Rusconi, S, Folli, F, Sabatino, A, Zuccotti, G, Galli, M, and Fiorina, P
Subjects: medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Coronaviru, Pneumonia, Viral, Population, 030209 endocrinology & metabolism, Type 2 diabetes, Dipeptidyl peptidase-4 inhibitor, Sitagliptin Phosphate, 03 medical and health sciences, 0302 clinical medicine, Retrospective Studie, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, 030212 general & internal medicine, education, Advanced and Specialized Nursing, education.field_of_study, Betacoronaviru, Pandemic, Emerging Therapies: Drugs and Regimens, SARS-CoV-2, Coronavirus Infection, business.industry, Hazard ratio, COVID-19, Retrospective cohort study, medicine.disease, Hospitalization, Italy, Diabetes Mellitus, Type 2, Sitagliptin, business, Human, medicine.drug
Abstract: OBJECTIVE Poor outcomes have been reported in patients with type 2 diabetes and coronavirus disease 2019 (COVID-19); thus, it is mandatory to explore novel therapeutic approaches for this population. RESEARCH DESIGN AND METHODS In a multicenter, case-control, retrospective, observational study, sitagliptin, an oral and highly selective dipeptidyl peptidase 4 inhibitor, was added to standard of care (e.g., insulin administration) at the time of hospitalization in patients with type 2 diabetes who were hospitalized with COVID-19. Every center also recruited at a 1:1 ratio untreated control subjects matched for age and sex. All patients had pneumonia and exhibited oxygen saturation RESULTS Of the 338 consecutive patients with type 2 diabetes and COVID-19 admitted in Northern Italy hospitals included in this study, 169 were on sitagliptin, while 169 were on standard of care. Treatment with sitagliptin at the time of hospitalization was associated with reduced mortality (18% vs. 37% of deceased patients; hazard ratio 0.44 [95% CI 0.29–0.66]; P = 0.0001), with an improvement in clinical outcomes (60% vs. 38% of improved patients; P = 0.0001) and with a greater number of hospital discharges (120 vs. 89 of discharged patients; P = 0.0008) compared with patients receiving standard of care, respectively. CONCLUSIONS In this multicenter, case-control, retrospective, observational study of patients with type 2 diabetes admitted to the hospital for COVID-19, sitagliptin treatment at the time of hospitalization was associated with reduced mortality and improved clinical outcomes as compared with standard-of-care treatment. The effects of sitagliptin in patients with type 2 diabetes and COVID-19 should be confirmed in an ongoing randomized, placebo-controlled trial.
Published: 2020

3. Switching from Suspend-Before-Low Insulin Pump Technology to a Hybrid Closed-Loop System Improves Glucose Control and Reduces Glucose Variability: A Retrospective Observational Case–Control Study

Author: Giuseppe Lepore, Anna Maria Corsi, Alessandro Roberto Dodesini, Roberto Trevisan, Cristiana Scaranna, Lepore, G, Scaranna, C, Corsi, A, Dodesini, A, and Trevisan, R
Subjects: Adult, Blood Glucose, Male, medicine.medical_specialty, Glucose control, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Glycemic Control, Low insulin, 03 medical and health sciences, Insulin Infusion Systems, 0302 clinical medicine, Endocrinology, Diabetes mellitus, Internal medicine, Hybrid closed-loop system, Predictive low glucose suspend, Sensor-augmented pump, Type 1 diabetes mellitus, medicine, Humans, Hypoglycemic Agents, Insulin, 030212 general & internal medicine, Low glucose suspend, Retrospective Studies, business.industry, Blood Glucose Self-Monitoring, Case-control study, Middle Aged, medicine.disease, Hypoglycemia, Medical Laboratory Technology, Diabetes Mellitus, Type 1, Treatment Outcome, Feature (computer vision), Case-Control Studies, Cardiology, Female, Observational study, business, Closed loop
Abstract: There are no data whether hybrid closed-loop (HCL) systems are superior to sensor-augmented pump (SAP) therapy with predictive low glucose suspend (PLGS) feature in improving glucose control. Aim of our study was to evaluate the effect on metabolic control and glucose variability of the switch from SAP therapy with PLGS to a HCL system in type 1 diabetic individuals. Forty adults with type 1 diabetes, who had been using SAP therapy with PLGS feature (Minimed 640G; Medtronic, Northridge, CA) for at least 12 months were evaluated in a 6-month case-control observational retrospective study. Twenty subjects who consecutively switched from Minimed 640G to a HCL system (Minimed 670G; Medtronic) (670G group) were compared with a control group consisting of 20 subjects who continued with the MiniMed 640G pump (640G group) matched for age, gender, and HbA1c. At the end of the study there was a significant reduction in average HbA1c levels (-4.9 ± 6.4 mmol/mol [-0.4% ± 0.6%], P < 0.01), sensor glucose concentrations (-15.4 ± 17.7 mg/dL, P < 0.005), coefficient of variation of sensor glucose concentrations (-3.8% ± 3.6%, P < 0.01), percentage time spent in both hyperglycemic range 181-250 mg/dL (-5.1% ± 4.5%, P < 0.05), and >250 mg/dL (-6.1% ± 6.9%, P < 0.05) in the 670G group, whereas they remained unchanged in the 640G group. Percentage of time spent in euglycemic range significantly increased (11.6% ± 8.3%, P < 0.005) only in the 670G group. There was no change in time spent in hypoglycemic range in both groups. In adults with type 1 diabetes, switching from a 640G to a 670G system significantly improved glucose control and reduced glucose variability, thus reaching in most cases the recommended targets for time spent in euglycemic and hyperglycemic ranges without increasing the risk of hypoglycemia.
Published: 2020
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4. Association between inhibitors of the renin-angiotensin system and lung function in elderly patients recovered from severe COVID-19

Author: Marco Rizzi, Stefano Fagiuoli, Sandro Sironi, Tiziano Barbui, Alessandra Carobbio, Emilia D'Elia, Roberto Trevisan, Gianpaolo Mangia, Antonello Gavazzi, Michele Senni, Luca Novelli, Arianna Ghirardi, Gianluca Imeri, Roberto Cosentini, Bianca Magro, Federico Raimondi, Ferdinando Luca Lorini, Andrea Giammarresi, Giulio Balestrieri, Mariangela Amoroso, Mauro Gori, Fabiano Di Marco, Gori, M, Ghirardi, A, D'Elia, E, Imeri, G, Di Marco, F, Gavazzi, A, Carobbio, A, Balestrieri, G, Giammarresi, A, Trevisan, R, Amoroso, M, Raimondi, F, Novelli, L, Magro, B, Mangia, G, Lorini, F, Fagiuoli, S, Barbui, T, Rizzi, M, Cosentini, R, Sironi, S, and Senni, M
Subjects: 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Epidemiology, business.industry, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19, Angiotensin-Converting Enzyme Inhibitors, Renin-Angiotensin System, Renin–angiotensin system, Immunology, Hypertension, Medicine, Humans, COVID 19, renin–angiotensin system inhibitors, angiotensin-converting enzyme 2 (ACE2) receptor, Cardiology and Cardiovascular Medicine, business, Lung, Lung function, Aged
Published: 2022

5. Glomerular resistances predict long-term GFR decline in type 2 diabetic patients without overt nephropathy: a longitudinal subgroup analysis of the DEMAND trial

Author: Giuseppe Remuzzi, Flavio Gaspari, Ilian Iliev, Annalisa Perna, Roberto Trevisan, Silvia Ferrari, Aneliya Parvanova, Fabiola Carrara, Nadia Stucchi, Antonio Bossi, Piero Ruggenenti, Carrara, F, Ruggenenti, P, Perna, A, Iliev, I, Gaspari, F, Ferrari, S, Stucchi, N, Bossi, A, Trevisan, R, Remuzzi, G, and Parvanova, A
Subjects: Arterial hypertension, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Hydrostatic pressure, Kidney Glomerulus, Hemodynamics, Renal function, Type 2 diabetes, Glomerular hypoperfusion, urologic and male genital diseases, Type 2 diabete, Endocrinology, Pre- and post-glomerular resistance, Internal medicine, Internal Medicine, Medicine, Humans, Diabetic Nephropathies, business.industry, General Medicine, Odds ratio, medicine.disease, Diabetes Mellitus, Type 2, Renal blood flow, Cardiology, GFR decline, Iohexol, business, Glomerular hyperfiltration, medicine.drug, Glomerular Filtration Rate
Abstract: Aims: Investigating whether and to what extent changes in glomerular hemodynamic parameters, beyond glomerular hyperfiltration, could predict glomerular filtration rate (GFR) decline in hypertensive, non-proteinuric type 2 diabetic patients. Materials and methods: We estimated baseline afferent (Ra) and efferent (Re) arteriolar resistances and glomerular hydrostatic pressure in 60 consecutive patients from DEMAND study, using the Gomez’ equations. Baseline renal plasma flow was measured by para-aminohippurate plasma clearance, and GFR was measured by iohexol plasma clearance at baseline and every 6 months for a median of 4.0 years [IQR 3.5–4.0 years]. Patients with a GFR decline > or ≤ 3 mL/min/1.73 m2/year were categorized as “Progressors” and “Non-progressors,” respectively. Predictors of GFR decline were studied by univariable and multivariable logistic regression analysis. Results: •The GFR declined by a median [IQR] of 4.06 [5.46–2.00] mL/min/1.73 m2/year in the study group as a whole and by 5.35 [6.60–4.48] mL/min/1.73 m2/year and 1.71 [2.14–1.33] mL/min/1.73 m2/year in Progressors and Non-progressors, considered separately. Progressors had a higher baseline Ra (3487.3 ± 1349.3 dyne•sec•cm−5 vs. 2877.0 ± 668.9 dyne•sec•cm−5, p < 0.05) and higher Ra/Re ratio (1.4 ± 0.5 vs. 1.1 ± 0.3, p < 0.01) than Non-progressors. At multivariable logistic regression analysis, Ra/Re ratio and arterial hypertension duration were independently associated with GFR decline (odds ratio [95% CI] 8.50 [1.56–46.28] and 1.14 [1.01–1.28]), respectively. Conclusions: Increased Ra/Re ratio and arterial hypertension duration predict early GFR decline in hypertensive non-proteinuric type 2 diabetic patients. These findings could be explained by glomerular hypoperfusion and chronic ischemic injury related to pre-glomerular arteriolar narrowing. Clinical trial registration: DEMAND, NCT00157586, September 12, 2005.
Published: 2021

6. Effects of valsartan, benazepril and their combination in overt nephropathy of type 2 diabetes: A prospective, randomized, controlled trial

Author: Olimpia Diadei, Eleonora Riccio, Paolo Manunta, Giovanni Giorgio Battaglia, Antonio Bossi, Fabiola Carrara, Aneliya Parvanova, Nadia Stucchi, Francesco Peraro, Antonio Belviso, Andrea Satta, Piero Ruggenenti, Annalisa Perna, Nadan Gregorič, Maria Carolina Aparicio, Salvatore David, Barbara Ruggiero, Matias Trillini, Davide Martinetti, Ilian Iliev, Stefano Rota, Roberto Trevisan, Antonio Pisani, Filippo Aucella, Monica Cortinovis, Giuseppe Remuzzi, Flavio Gaspari, Andrej Janez, Drazenka Pongrac Barlovic, Ruggenenti, P., Trillini, M., P. Barlovic, D., Cortinovis, M., Pisani, A., Parvanova, A., Iliev, I. P., Ruggiero, B., Rota, S., Aparicio, M. C., Perna, A., Peraro, F., Diadei, O., Gaspari, F., Carrara, F., Stucchi, N., Martinetti, D., Janez, A., Gregoric, N., Riccio, E., Bossi, A. C., Trevisan, R., Manunta, P., Battaglia, G., David, S., Aucella, F., Belviso, A., Satta, A., Remuzzi, G., Ruggenenti, P, Trillini, M, P. Barlovic, D, Cortinovis, M, Pisani, A, Parvanova, A, Iliev, I, Ruggiero, B, Rota, S, Aparicio, M, Perna, A, Peraro, F, Diadei, O, Gaspari, F, Carrara, F, Stucchi, N, Martinetti, D, Janez, A, Gregoric, N, Riccio, E, Bossi, A, Trevisan, R, Manunta, P, Battaglia, G, David, S, Aucella, F, Belviso, A, Satta, A, and Remuzzi, G
Subjects: Adult, Male, medicine.medical_specialty, Combination therapy, Endocrinology, Diabetes and Metabolism, Slovenia, Urology, Benazepril, Blood Pressure, 030209 endocrinology & metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, Kidney Function Tests, Nephropathy, Diabetic nephropathy, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Internal Medicine, medicine, Humans, Diabetic Nephropathies, Aged, type 2 diabete, Creatinine, business.industry, diabetic nephropathy, Benzazepines, Middle Aged, diabetic nephropathy, phase III study, type 2 diabetes, Adult, Aged, Benzazepines, Biomarkers, Blood Pressure, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Drug Therapy, Combination, Female, Humans, Italy, Kidney Function Tests, Male, Middle Aged, Slovenia, Treatment Outcome, Valsartan, medicine.disease, phase III study, Treatment Outcome, Diabetes Mellitus, Type 2, Italy, chemistry, Valsartan, ACE inhibitor, Drug Therapy, Combination, Female, type 2 diabetes, business, Biomarkers, medicine.drug
Abstract: Aims: To evaluate whether angiotensin-converting enzyme (ACE) inhibitor and angiotensin II receptor blocker (ARB) combination therapy is more nephroprotective than ACE inhibitor or ARB monotherapy in people with type 2 diabetes and overt nephropathy. Materials and methods: In this prospective, randomized, open, blind-endpoint phase III trial sponsored by the Italian Drug Agency, 103 consenting patients with type 2 diabetes, aged >40 years, with serum creatinine levels 159 to 309 μmol/L, spot morning urinary albumin–creatinine ratio > 1000 mg/g (or > 500 mg/g in those on ACE inhibitor or ARB therapy at inclusion) were stratified by centre and randomized to 4.5-year treatment with valsartan 320 mg/d (n = 36), benazepril 20 mg/d (n = 34) or halved doses of both medications (n = 33). The primary endpoint was end-stage renal disease (ESRD). Modified intention-to-treat analyses were performed. Results: Recruitment took place between June 2007 and February 2013 at 10 centres in Italy and one in Slovenia. A total of 77 participants completed the study and 26 were prematurely withdrawn. During a median (interquartile range) of 41 (18–54) months, 12 participants on benazepril (35.3%) and nine on combination therapy (27.3%) progressed to ESRD, versus five on valsartan (13.9%). Differences between benazepril (hazard ratio [HR] 3.59, 95% confidence interval [CI] 1.25–10.30; P = 0.018) or combination therapy (HR 3.28, 95% CI 1.07–10.0; P = 0.038) and valsartan were significant, even after adjustment for age, gender and baseline serum creatinine, systolic blood pressure and 24-hour proteinuria (HR 5.16, 95% CI 1.50–17.75, P = 0.009 and HR 4.75, 95% CI 1.01–22.39, P = 0.049, respectively). Adverse events were distributed similarly among the groups. Conclusions: In people with type 2 diabetes with nephropathy, valsartan (320 mg/d) safely postponed ESRD more effectively than benazepril (20 mg/d) or than halved doses of both medications.
Published: 2019
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7. Metabolic Syndrome, and Not Obesity, Is Associated with Chronic Kidney Disease

Author: Gianluca Perseghin, Roberto Trevisan, Cinzia Ballabeni, Stefano Ciardullo, Ciardullo, S, Ballabeni, C, Trevisan, R, and Perseghin, G
Subjects: Adult, Male, medicine.medical_specialty, Population, Renal function, Gastroenterology, chemistry.chemical_compound, Internal medicine, medicine, CKD, Humans, Obesity, Renal Insufficiency, Chronic, education, Metabolic Syndrome, education.field_of_study, Creatinine, business.industry, health, Middle Aged, medicine.disease, Cross-Sectional Studies, chemistry, Nephrology, Albuminuria, Microalbuminuria, epidemiology, Female, medicine.symptom, Metabolic syndrome, business, Body mass index, Kidney disease
Abstract: Introduction: Obese (OB) patients are at increased risk of chronic kidney disease, but it is still unclear whether this can be attributed to obesity per se or to the associated metabolic derangements. The aim of this study was to evaluate the relative impact of obesity and metabolic syndrome (MS) on kidney disease. Methods: This is a cross-sectional study based on data obtained in the 2005–2016 cycles of the National Health and Nutrition Examination Survey. We included all adult participants with available data on body mass index, estimated glomerular filtration rate (eGFR), urine albumin to creatinine ratio (UACR), and each of the MS components. Primary outcomes were eGFR Results: The studied population comprised 12,335 participants. OB participants without MS (OB+ MS−) were younger and more commonly female. After adjustment for potential confounders, compared with OB− MS− participants, an increased prevalence of albuminuria and reduced eGFR were present in both OB− MS+ groups and the OB+ MS+ groups, but not in the OB+ MS− groups. When each of the MS components was evaluated separately, elevated blood pressure and low high-density lipoprotein cholesterol were associated with both UACR and reduced eGFR, while elevated blood glucose and triglycerides were only associated with UACR. Waist circumference was not associated with any of the renal outcomes. Discussion/Conclusion: This large cross-sectional study suggests that MS and not obesity is associated with kidney damage and that the OB+ MS− phenotype does not seem to carry an increased risk of kidney disease.
Published: 2021

8. Switching to Once-Weekly Insulin Icodec Versus Once-Daily Insulin Glargine U100 in Type 2 Diabetes Inadequately Controlled on Daily Basal Insulin: A Phase 2 Randomized Controlled Trial

Author: Richard M. Bergenstal, Julio Rosenstock, Ildiko Lingvay, Roberto Trevisan, Harpreet S. Bajaj, Joakim Isendahl, Melanie J. Davies, Peter A. Senior, Andreas Christoffersen, Robert Silver, Amoolya Gowda, Bajaj, H, Bergenstal, R, Christoffersen, A, Davies, M, Gowda, A, Isendahl, J, Lingvay, I, Senior, P, Silver, R, Trevisan, R, and Rosenstock, J
Subjects: medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030209 endocrinology & metabolism, Type 2 diabetes, Hypoglycemia, Gastroenterology, Loading dose, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, 030212 general & internal medicine, MED/13 - ENDOCRINOLOGIA, Glycemic, Advanced and Specialized Nursing, business.industry, Insulin glargine, Insulin, medicine.disease, once-weekly insulin analog, glargine, type 2 diabetes, Basal (medicine), business, medicine.drug
Abstract: OBJECTIVE Insulin icodec (icodec) is a novel once-weekly basal insulin analog. This trial investigated two approaches for switching to icodec versus once-daily insulin glargine 100 units/mL (IGlar U100) in people with type 2 diabetes receiving daily basal insulin and one or more oral glucose-lowering medications. RESEARCH DESIGN AND METHODS This multicenter, open-label, treat-to-target phase 2 trial randomized (1:1:1) eligible basal insulin–treated (total daily dose 10–50 units) people with type 2 diabetes (HbA1c 7.0–10.0% [53.0–85.8 mmol/mol]) to icodec with an initial 100% loading dose (in which only the first dose was doubled [icodec LD]), icodec with no loading dose (icodec NLD), or IGlar U100 for 16 weeks. Primary end point was percent time in range (TIR; 3.9–10.0 mmol/L [70–180 mg/dL]) during weeks 15 and 16, measured using continuous glucose monitoring. Key secondary end points included HbA1c, adverse events (AEs), and hypoglycemia. RESULTS Estimated mean TIR during weeks 15 and 16 was 72.9% (icodec LD; n = 54), 66.0% (icodec NLD; n = 50), and 65.0% (IGlar U100; n = 50), with a statistically significant difference favoring icodec LD versus IGlar U100 (7.9%-points [95% CI 1.8–13.9]). Mean HbA1c reduced from 7.9% (62.8 mmol/mol) at baseline to 7.1% (54.4 mmol/mol icodec LD) and 7.4% (57.6 mmol/mol icodec NLD and IGlar U100); incidences and rates of AEs and hypoglycemic episodes were comparable. CONCLUSIONS Switching from daily basal insulin to once-weekly icodec was well tolerated and provided effective glycemic control. Loading dose use when switching to once-weekly icodec significantly increased percent TIR during weeks 15 and 16 versus once-daily IGlar U100, without increasing hypoglycemia risk.
Published: 2021
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9. Reply to 'Liver fibrosis assessed by transient elastography and albuminuria'

Author: Roberto Trevisan, Gianluca Perseghin, Stefano Ciardullo, Cinzia Ballabeni, Ciardullo, S, Ballabeni, C, Trevisan, R, and Perseghin, G
Subjects: Liver Cirrhosis, medicine.medical_specialty, Hepatology, business.industry, Liver fibrosis, Gastroenterology, Liver, Internal medicine, NAFLD, medicine, Albuminuria, Elasticity Imaging Techniques, Humans, medicine.symptom, business, Transient elastography, CKD, UACR
Published: 2021

10. Liver fibrosis assessed by transient elastography is independently associated with albuminuria in the general United States population

Author: Stefano Ciardullo, Cinzia Ballabeni, Gianluca Perseghin, Roberto Trevisan, Ciardullo, S, Ballabeni, C, Trevisan, R, and Perseghin, G
Subjects: medicine.medical_specialty, Population, MAFLD, Type 2 diabetes, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, NAFLD, Nonalcoholic fatty liver disease, medicine, education, education.field_of_study, Hepatology, business.industry, medicine.disease, Fibroscan, 030220 oncology & carcinogenesis, Albuminuria, 030211 gastroenterology & hepatology, Microalbuminuria, Steatosis, medicine.symptom, Transient elastography, business, Kidney disease
Abstract: Background Nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are frequent and progressive conditions that share traditional risk factors: obesity, type 2 diabetes and hypertension. Aims To evaluate whether an independent relationship exists between liver steatosis and fibrosis and different CKD phenotypes. Methods Cross sectional study based on data from the 2017–18 cycle of the National Health and Nutrition Examination Survey. Vibration controlled transient elastography (VCTE) was performed in a US representative sample allowing the simultaneous assessment of liver steatosis (CAP: controlled attenuation parameter) and fibrosis (LSM: liver stiffness measurement) and their relationships with CKD phenotypes (albuminuria and reduced estimated glomerular filtration rate, eGFR). Results 4746 adult participants had a complete VCTE exam. Prevalence of liver steatosis and significant fibrosis was 33.7% (95%CI: 30.9–36.6%) and 8.9% (95%CI: 7.5–10.5%), respectively. Logistic regression analysis showed that liver fibrosis, but not steatosis, was associated with albuminuria (OR 2.19, 95%CI: 1.49–3.20) and albuminuria or reduced eGFR (OR 2.18, 95%CI: 1.59–3.00) also when adjusted for age, sex, ethnicity, BMI, diabetes, blood pressure categories, glycated haemoglobin, use of renin-angiotensin-aldosterone system blockers and CAP. Conclusions In the general US population liver fibrosis assessed using VCTE is associated with CKD, and in particular with the albuminuric phenotype, regardless of traditional risk factors.
Published: 2021

11. Sodium-glucose transporter 2 inhibitors for renal and cardiovascular protection in US adults with type 2 diabetes: impact of the 2020 KDIGO clinical practice guidelines

Author: Roberto Trevisan, Stefano Ciardullo, Gianluca Perseghin, Ciardullo, S, Trevisan, R, and Perseghin, G
Subjects: Adult, Male, 0301 basic medicine, Sodium glucose transporter 2, medicine.medical_specialty, National Health and Nutrition Examination Survey, Population, Type 2 diabetes, urologic and male genital diseases, Diabete, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Internal medicine, medicine, CKD, Humans, Renal Insufficiency, Chronic, education, Sodium-Glucose Transporter 2 Inhibitors, CREDENCE, Aged, Retrospective Studies, Pharmacology, KDIGO, Kidney, education.field_of_study, Proteinuria, business.industry, DAPA-CKD, Middle Aged, medicine.disease, United States, 030104 developmental biology, medicine.anatomical_structure, Diabetes Mellitus, Type 2, Cardiovascular Diseases, 030220 oncology & carcinogenesis, Practice Guidelines as Topic, Female, medicine.symptom, business, SGLT2-i, EMPA-KIDNEY, Kidney disease
Abstract: Background Sodium glucose transporter 2 inhibitors (SGLT2-i) reduce renal and cardiovascular events in patients with type 2 diabetes (T2D) and their use is recommended by the 2020 KDIGO guidelines in patients with T2D and chronic kidney disease (CKD). The aim of this study is to estimate the proportion of patients with T2D and CKD in the US that should be treated with these agents for renal and cardiovascular protection. Methods We conducted a retrospective analysis of 2005–2018 National Health and Nutrition Examination Survey (NHANES) data. We focused on participants with a prior diagnosis of diabetes or that met diagnostic criteria for diabetes during the survey, with the exclusion of probable type 1 diabetic patients. Inclusion criteria for completed and ongoing renal and cardiovascular outcome trials in patients with CKD were applied. Results We estimated that 35.3% of patients with T2D in the US (projected to 8.96 million) should be treated with SGLT2-i according to the 2020 KDIGO guidelines. Moreover, 2.9–10.1% (projected to 0.75–2.55 million) met the inclusion criteria for dedicated kidney outcome trials, which were focused on a population of individuals with proteinuria. Conclusions About a third of patients with T2D in the US should be treated with an SGLT2-i. While compelling evidence of renal protection is present for patients with proteinuria, all patients with CKD obtain a cardiovascular benefit with this class of drugs.
Published: 2021

12. Exposure to Renin-Angiotensin System Inhibitors Is Associated with Reduced Mortality of Older Hypertensive Covid-19 Patients

Author: Antonello Gavazzi, Bianca Magro, Stefano Fagiuoli, Gianfranco Parati, Antonio Bellasi, Roberto Trevisan, Gianpaolo Mangia, Luisa Bernardinelli, Carlo Berzuini, Luca Novelli, Mauro Gori, Arianna Ghirardi, Ferdinando Luca Lorini, Emilia D'Elia, Giulio Balestrieri, Mariangela Amoroso, Federico Raimondi, Michele Senni, Giulio Guagliumi, Andrea Giammarresi, and Fabiano Di Marco
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Internal medicine, Propensity score matching, Cohort, Renin–angiotensin system, Hospital admission, medicine, Absolute risk reduction, Medical history, Disease, business
Abstract: From a cohort of 1352 consecutive patients admitted with coronavirus disease (Covid-19) to Papa Giovanni XXIII Hospital in Bergamo, Italy, between February and April 2020, we selected and studied 688 patients with arterial hypertension (254 deaths) to assess whether use of renin-angiotensin system inhibitors (RASIs) prior to hospital admission affects mortality from Covid-19. Prior use of RASIs was associated with a lower mortality in the over-68 group of patients, whereas no evidence of a similar effect (whether protective or adverse) was found in the younger group. There was positive relative excess due to a statistically significant (p =0.001) interaction between prior RASI exposure and an age greater than 68 years, corresponding to a positive relative excess risk. Next we used the subgroup of 411 hypertensive patients older than 68 yrs to separately assess the effects prior use of two RASI drug subclasses, angiotensin-converting enzyme inhibitors (ACEIs) and angiogiotensin receptor blockers (ARBs), by comparing these two exposures with no exposure to RASIs. We found both prior use of ACEIs and prior use of ARBs to be associated with a lower Covid-19 mortality, after adjusting for 32 medical history variables via propensity score matching. (ORACEI = 0.57, 95%CI 0.36 to 0.91, p =0.018) (ORARB = 0.49, 95%CI 0.29 to 0.82, p =0.006).
Published: 2020
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13. Pre-gestational diabetes during the COVID-19 pandemic in Bergamo, Italy

Author: Rosalia Bellante, Alessandro Roberto Dodesini, Roberto Trevisan, Silvia Galliani, Elena Ciriello, Dodesini, A, Galliani, S, Ciriello, E, Bellante, R, and Trevisan, R
Subjects: Pediatrics, medicine.medical_specialty, education.field_of_study, Coronavirus disease 2019 (COVID-19), business.industry, Population, Obstetrics and Gynecology, Outbreak, General Medicine, medicine.disease, Northern italy, Infectious disease (medical specialty), Diabetes mellitus, Obstetrics and Gynaecology, Pandemic, medicine, Bergamo, COVID-19, Pre-gestational diabetes, business, education, Pre-Gestational Diabetes
Abstract: The COVID-19 pandemic has caused the proliferation of a highly contagious and frequently fatal pneumonia around the world.[1] COVID-19 has severely affected Italy, and at the onset of this crisis, Bergamo, a city in northern Italy, regularly reported the highest number of cases in the country for many weeks. During outbreaks of infectious disease, pregnant women represent a high-risk population due to their increased susceptibility to infections, particularly when comorbidities such as pre-gestational diabetes (present in 0.5% of pregnant populations) are present.[2,3] Few data are available on pregnant women with pre-gestational diabetes during the COVID-19 pandemic.
Published: 2020

14. Association between On-Treatment Haemoglobin A1c and All-Cause Mortality in Individuals with Type 2 Diabetes: Importance of Personalized Goals and Type of Anti-Hyperglycaemic Treatment

Author: Antonio Nicolucci, Susanna Morano, Giuseppe Penno, Enzo Bonora, Cecilia Fondelli, Anna Solini, Franco Cavalot, Monica Vedovato, Roberto Trevisan, Emanuela Orsi, Gianpaolo Zerbini, Giuseppe Pugliese, Orsi, E, Bonora, E, Solini, A, Fondelli, C, Trevisan, R, Vedovato, M, Cavalot, F, Zerbini, G, Morano, S, Nicolucci, A, Penno, G, and Pugliese, G
Subjects: medicine.medical_specialty, endocrine system diseases, lcsh:Medicine, Type 2 diabetes, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, 030212 general & internal medicine, Adverse effect, HbA1c all-cause mortality, Haemoglobin A1c, business.industry, Hazard ratio, lcsh:R, nutritional and metabolic diseases, General Medicine, medicine.disease, Comorbidity, Confidence interval, Anti hyperglycaemic, adverse treatment effects, hypoglycaemia, type 2 diabetes, HbA1c all-cause mortality, adverse treatment effects, hypoglycaemia, type 2 diabetes, Complication, business
Abstract: The increased mortality reported with intensive glycaemic control has been attributed to an increased risk of treatment-related hypoglycaemia. This study investigated the relationships of haemoglobin (Hb) A1c, anti-hyperglycaemic treatment, and potential risks of adverse effects with all-cause mortality in patients with type 2 diabetes. Patients (n = 15,773) were stratified into four categories according to baseline HbA1c and then assigned to three target categories, based on whether HbA1c was &le, 0.5% below or above (on-target), &gt, 0.5% below (below-target) or &gt, 0.5% above (above-target) their HbA1c goal, personalized according to the number of potential risks among age &gt, 70 years, diabetes duration &gt, 10 years, advanced complication(s), and severe comorbidity (ies). The vital status was retrieved for 15,656 patients (99.26%). Over a 7.4-year follow-up, mortality risk was increased among patients in the highest HbA1c category (&ge, 8.5%) (adjusted hazard ratio, 1.34 (95% confidence interval, 1.22&ndash, 1.47), p &lt, 0.001) and those above-target (1.42 (1.29&ndash, 1.57), p &lt, 0.001). Risk was increased among individuals in the lowest HbA1c category (&lt, 6.5%) and those below-target only if treated with agents causing hypoglycaemia (1.16 (1.03&ndash, 1.29), p = 0.01 and 1.10 (1.01&ndash, 1.22), p = 0.04, respectively). These data suggest the importance of setting both upper and lower personalized HbA1c goals to avoid overtreatment in high-risk individuals with type 2 diabetes treated with agents causing hypoglycaemia.
Published: 2020
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15. Renal hyperfiltration is independently associated with increased all-cause mortality in individuals with type 2 diabetes. a prospective cohort study

Author: Luigi Laviola, Antonio Nicolucci, Giuseppe Penno, Gabriella Gruden, Giuseppe Pugliese, Enzo Bonora, Cecilia Fondelli, Roberto Trevisan, Anna Solini, Monica Vedovato, Emanuela Orsi, Franco Cavalot, Penno, G, Orsi, E, Solini, A, Bonora, E, Fondelli, C, Trevisan, R, Vedovato, M, Cavalot, F, Gruden, G, Laviola, L, Nicolucci, A, and Pugliese, G
Subjects: diabetes mellitus, type 2, kidney diseases, mortality, Albuminuria, Glomerular Filtration Rate, Humans, Italy, Prospective Studies, Diabetes Mellitus, Type 2, Cardiovascular and Metabolic Risk, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Renal function, Type 2 diabetes, 030204 cardiovascular system & hematology, Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Medicine, 030212 general & internal medicine, Prospective cohort study, Creatinine, business.industry, Mortality rate, RC648-665, medicine.disease, chemistry, type 2, diabetes mellitus, medicine.symptom, business, Kidney disease
Abstract: IntroductionIn addition to favoring renal disease progression, renal ‘hyperfiltration’ has been associated with an increased risk of death, though it is unclear whether and how excess mortality is related to increased renal function. We investigated whether renal hyperfiltration is an independent predictor of death in patients with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events Italian multicenter study.Research design and methodsThis observational, prospective cohort study enrolled 15 773 patients with type 2 diabetes consecutively attending 19 Italian diabetes clinics in 2006–2008. Serum creatinine, albuminuria, cardiovascular risk factors, and complications/comorbidities were assessed at baseline. Vital status on 31 October 2015 was retrieved for 15 656 patients (99.26%). Patients were stratified (A) by absolute estimated glomerular filtration rate (eGFR) values in eGFR deciles or Kidney Disease: Improving Global Outcomes (KDIGO) categories and (B) based on age-corrected thresholds or age and gender-specific 95th and 5th percentiles in hyperfiltration, hypofiltration, and normofiltration groups.ResultsThe highest eGFR decile/category and the hyperfiltration group included (partly) different individuals with similar clinical features. Age and gender-adjusted death rates were significantly higher in deciles 1, 9, and 10 (≥103.9, 50.9–62.7, and 2, respectively) versus the reference decile 3 (92.9–97.5 mL/min/1.73 m2). Mortality risk, adjusted for multiple confounders, was also increased in deciles 1 (HR 1.461 (95% CI 1.175 to 1.818), p=0.001), 9 (1.312 (95% CI 1.107 to 1.555), p=0.002), and 10 (1.976 (95% CI 1.673 to 2.333), pConclusionsIn type 2 diabetes, both high-normal eGFR and hyperfiltration are associated with an increased risk of death from any cause, independent of confounders that may directly impact on mortality and/or affect GFR estimation. Further studies are required to clarify the nature of this relationship.Trial registration numberNCT00715481.
Published: 2020

16. Blood Pressure and Metabolic Effects of Acetyl-l-Carnitine in Type 2 Diabetes: DIABASI Randomized Controlled Trial

Author: Sidy Mohamed Seck, Giuseppe Remuzzi, Luca Perico, Flavio Gaspari, Francesco Peraro, Roberto Trevisan, Kanishka Sharma, Antonio Cannata, Nadia Rubis, Annalisa Perna, Silvia Ferrari, Ilian Iliev, Aneliya Parvanova, Jonathan S Chávez-Iñiguez, Matias Trillini, Piero Ruggenenti, Monica Cortinovis, Manuel Alfredo Podestà, Carolina Aparicio, David G. Warnock, Teerayuth Jiamjariyaporn, Antonio Bossi, Sreejith Parameswaran, Fahrudin Masnic, Parvanova, A, Trillini, M, Podesta, M, Iliev, I, Aparicio, C, Perna, A, Peraro, F, Rubis, N, Gaspari, F, Cannata, A, Ferrari, S, Bossi, A, Trevisan, R, Parameswaran, S, Chavez-Iniguez, J, Masnic, F, Seck, S, Jiamjariyaporn, T, Cortinovis, M, Perico, L, Sharma, K, Remuzzi, G, Ruggenenti, P, and Warnock, D
Subjects: medicine.medical_specialty, Diabetes, Pancreatic and Gastrointestinal Hormones, type 2 diabetes mellitus, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, Gastroenterology, insulin-resistance, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Insulin resistance, Lipid oxidation, Internal medicine, medicine, MED/13 - ENDOCRINOLOGIA, acetyl-l-carnitine, Clinical Research Articles, Glycemic, business.industry, dyslipidemia, statin, blood pressure, medicine.disease, Type 2 diabetes mellitu, Blood pressure, chemistry, Homeostatic model assessment, Glycated hemoglobin, business, Dyslipidemia
Abstract: Context Acetyl-l-carnitine (ALC), a mitochondrial carrier involved in lipid oxidation and glucose metabolism, decreased systolic blood pressure (SBP), and ameliorated insulin sensitivity in hypertensive nondiabetic subjects at high cardiovascular risk. Objective To assess the effects of ALC on SBP and glycemic and lipid control in patients with hypertension, type 2 diabetes mellitus (T2D), and dyslipidemia on background statin therapy. Design After 4-week run-in period and stratification according to previous statin therapy, patients were randomized to 6-month, double-blind treatment with ALC or placebo added-on simvastatin. Setting Five diabetology units and one clinical research center in Italy. Patients Two hundred twenty-nine patients with hypertension and dyslipidemic T2D >40 years with stable background antihypertensive, hypoglycemic, and statin therapy and serum creatinine, In a prospective randomized controlled trial in 229 patients with hypertension and T2D, 6-month oral acetyl-L-carnitine (1000 mg twice daily) or placebo treatment had similar effects on blood pressure, metabolic control, lipids, and GFR.
Published: 2018
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17. Moderate salt restriction with or without paricalcitol in type 2 diabetes and losartan-resistant macroalbuminuria (PROCEED)

Author: Aneliya Parvanova, Matias Trillini, Manuel A Podestà, Ilian Petrov Iliev, Barbara Ruggiero, Manuela Abbate, Annalisa Perna, Francesco Peraro, Olimpia Diadei, Nadia Rubis, Flavio Gaspari, Fabiola Carrara, Nadia Stucchi, Antonio Belviso, Antonio C Bossi, Roberto Trevisan, Giuseppe Remuzzi, Martin de Borst, Piero Ruggenenti, Norberto Perico, Stefano Rota, Maria Carolina Aparicio, Silvia Prandini, Daniela Cugini, Giulia Gherardi, Anna Corsi, Antonio C. Bossi, S Yakymchuk, Veruscka Lecchi, Ruggero Mangili, Wally Calini, Bogdan Ene-Iordache, Sergio Carminati, Davide Martinetti, Giovanni Antonio Giuliano, Angela Russo, Silvia Ferrari, Antonio Nicola Cannata, Paola Boccardo, Sara Peracchi, Martin De Borst, Serena Bettoni, Irene Cattaneo, Davide Franchina, Haian Ha Phan, Grace Igiraneza, Tamas Kaucsár, Sergio Luis Lima, Meg Lunney, Huong Tran, Groningen Kidney Center (GKC), Lifestyle Medicine (LM), Groningen Institute for Organ Transplantation (GIOT), Parvanova, A, Trillini, M, Podesta, M, Iliev, I, Ruggiero, B, Abbate, M, Perna, A, Peraro, F, Diadei, O, Rubis, N, Gaspari, F, Carrara, F, Stucchi, N, Belviso, A, Bossi, A, Trevisan, R, Remuzzi, G, de Borst, M, Ruggenenti, P, Perico, N, Rota, S, Aparicio, M, Prandini, S, Cugini, D, Gherardi, G, Corsi, A, Yakymchuk, S, Lecchi, V, Mangili, R, Calini, W, Ene-Iordache, B, Carminati, S, Martinetti, D, Giuliano, G, Russo, A, Ferrari, S, Cannata, A, Boccardo, P, Peracchi, S, Bettoni, S, Cattaneo, I, Franchina, D, Ha Phan, H, Igiraneza, G, Kaucsar, T, Lima, S, Lunney, M, and Tran, H
Subjects: Male, Paricalcitol, Endocrinology, Diabetes and Metabolism, Drug Resistance, 030232 urology & nephrology, PROGRESSION, Type 2 diabetes, 030204 cardiovascular system & hematology, THERAPY, 0302 clinical medicine, Endocrinology, Outpatient clinic, VITAMIN-D, ACE-INHIBITION, education.field_of_study, Cross-Over Studies, Cross-Over Studie, Middle Aged, Diet, Sodium-Restricted, Treatment Outcome, Losartan, Italy, D-RECEPTOR ACTIVATION, Ergocalciferols, Female, medicine.symptom, Human, medicine.drug, medicine.medical_specialty, NEPHROPATHY, Population, Urology, DIETARY-SODIUM RESTRICTION, Placebo, Ergocalciferol, 03 medical and health sciences, Double-Blind Method, Internal medicine, Internal Medicine, medicine, Humans, Albuminuria, MED/13 - ENDOCRINOLOGIA, education, Aged, business.industry, KIDNEY-DISEASE, medicine.disease, Crossover study, MED/14 - NEFROLOGIA, Diabetes Mellitus, Type 2, RESIDUAL PROTEINURIA, CHRONIC RENAL-DISEASE, business
Abstract: Background Macroalbuminuria predicts renal and cardiovascular events in patients with type 2 diabetes. We aimed to assess the albuminuria-lowering effects of salt restriction, paricalcitol therapy, or both, in this population.Methods In this randomised, double-blind, placebo-controlled, crossover trial, we recruited adult patients with type 2 diabetes from six diabetology outpatient clinics in northern Italy, with 24 h albuminuria of more than 300 mg despite 100 mg per day losartan therapy, blood pressure of less than 140/90 mm Hg, serum creatinine concentration of less than 2 mg/dL, stable renal function on stable renin-angiotensin system inhibitor therapy with a fixed dose of losartan, parathyroid hormone concentration of 20 pg/mL to 200 mEq [4.8 g] per day) or low-sodium (Findings Between Dec 13, 2011, and Feb 17, 2015, we randomly allocated 57 (50%) patients to a low-sodium diet (28 [49%] to paricalcitol then placebo and 29 [51%] to placebo then paricalcitol) and 58 (50%) to a high-sodium diet (29 [50%] to paricalcitol then placebo and 29 [50%] to placebo then paricalcitol). In the low-sodium group (30 mEq of daily sodium intake reduction, equivalent to approximately 1.7-1.8 g per day), 24 h albuminuria was reduced by 36.6% (95% CI 28.5-44.9) from 724 mg (441-1233) at baseline to 481 mg (289-837) at month 3 (pInterpretation In patients with macroalbuminuria and type 2 diabetes, moderate salt restriction enhances the antialbuminuric effect of losartan, an effect that could be nephroprotective and cardioprotective in the long term. The finding that paricalcitol prevents a sodium-induced increase in albuminuria provides support for trials to test the longterm risk-benefit profile of paricalcitol add-on therapy in patients with type 2 diabetes and macroalbuminuria refractory to dietary salt restriction, including patients refractory to even moderate salt restriction.
Published: 2018
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18. Preventing microalbuminuria with benazepril, valsartan, and benazepril–valsartan combination therapy in diabetic patients with high-normal albuminuria: A prospective, randomized, open-label, blinded endpoint (PROBE) study

Author: Piero Ruggenenti, Monica Cortinovis, Aneliya Parvanova, Matias Trillini, Ilian P Iliev, Antonio C Bossi, Antonio Belviso, Maria C Aparicio, Roberto Trevisan, Stefano Rota, Annalisa Perna, Tobia Peracchi, Nadia Rubis, Davide Martinetti, Silvia Prandini, Flavio Gaspari, Fabiola Carrara, Salvatore De Cosmo, Giancarlo Tonolo, Ruggero Mangili, Giuseppe Remuzzi, VARIETY Study Organization, Ruggenenti, P, Cortinovis, M, Parvanova, A, Trillini, M, Iliev, I, Bossi, A, Belviso, A, Aparicio, M, Trevisan, R, Rota, S, Perna, A, Peracchi, T, Rubis, N, Martinetti, D, Prandini, S, Gaspari, F, Carrara, F, De Cosmo, S, Tonolo, G, Mangili, R, and Remuzzi, G
Subjects: Male, ACE inhibitors, Physiology, microalbuminuria, type 2 diabetes, ACE inhibitors, glomerular filtration rate, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, ACE inhibitor therapy, Biochemistry, Lung and Intrathoracic Tumors, Endocrinology, Medical Conditions, 0302 clinical medicine, Medicine, 030212 general & internal medicine, biology, Pharmaceutics, Drugs, Cardiovascular therapy, Enzyme inhibitors, General Medicine, Middle Aged, Type 2 Diabetes, Oncology, Valsartan, Nephrology, Drug Therapy, Combination, Female, Drug therapy, medicine.symptom, Research Article, Glomerular Filtration Rate, medicine.drug, medicine.medical_specialty, Combination therapy, Endocrine Disorders, Urology, Benazepril, 03 medical and health sciences, Diabetes Mellitus, Albuminuria, Humans, MED/13 - ENDOCRINOLOGIA, Aged, Medicine and health sciences, Pharmacology, Renal Physiology, Intention-to-treat analysis, business.industry, Biology and Life Sciences, Cancers and Neoplasms, Angiotensin-converting enzyme, Benzazepines, medicine.disease, Diabetes Mellitus, Type 2, Metabolic Disorders, ACE inhibitor, Enzymology, biology.protein, Microalbuminuria, business, Angiotensin II Type 1 Receptor Blockers
Abstract: Background Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) prevent microalbuminuria in normoalbuminuric type 2 diabetic patients. We assessed whether combined therapy with the 2 medications may prevent microalbuminuria better than ACE inhibitor or ARB monotherapy. Methods and findings VARIETY was a prospective, randomized, open-label, blinded endpoint (PROBE) trial evaluating whether, at similar blood pressure (BP) control, combined therapy with benazepril (10 mg/day) and valsartan (160 mg/day) would prevent microalbuminuria more effectively than benazepril (20 mg/day) or valsartan (320 mg/day) monotherapy in 612 type 2 diabetic patients with high-normal albuminuria included between July 2007 and April 2013 by the Istituto di Ricerche Farmacologiche Mario Negri IRCCS and 8 diabetology or nephrology units in Italy. Time to progression to microalbuminuria was the primary outcome. Analyses were intention to treat. Baseline characteristics were similar among groups. During a median [interquartile range, IQR] follow-up of 66 [42 to 83] months, 53 patients (27.0%) on combination therapy, 57 (28.1%) on benazepril, and 64 (31.8%) on valsartan reached microalbuminuria. Using an accelerated failure time model, the estimated acceleration factors were 1.410 (95% CI: 0.806 to 2.467, P = 0.229) for benazepril compared to combination therapy, 0.799 (95% CI: 0.422 to 1.514, P = 0.492) for benazepril compared to valsartan, and 1.665 (95% CI: 1.007 to 2.746, P = 0.047) for valsartan compared to combination therapy. Between-group differences in estimated acceleration factors were nonsignificant after adjustment for predefined confounders. BP control was similar across groups. All treatments were safe and tolerated well, with a slight excess of hyperkalemia and hypotension in the combination therapy group. The main study limitation was the lower than expected albuminuria at inclusion. Conclusions Risk/benefit profile of study treatments was similar. Dual renin–angiotensin system (RAS) blockade is not recommended as compared to benazepril or valsartan monotherapy for prevention of microalbuminuria in normoalbuminuric type 2 diabetic patients. Trial registration EudraCT 2006-005954-62; ClinicalTrials.gov NCT00503152., Piero Ruggenenti and co-workers study prevention of microalbuminuria in patients with type 2 diabetes., Author summary Why was this study done? Renin–angiotensin system (RAS) blockade with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) prevents the onset of microalbuminuria in patients with type 2 diabetes and normoalbuminuria. Some studies found that ACE inhibitor and ARB combination therapy reduced urinary albumin excretion (UAE) more effectively than ACE inhibitor or ARB monotherapy in type 2 diabetic patients with microalbuminuria or macroalbuminuria. Treatment effect was, however, associated with greater blood pressure (BP) reduction. Whether, at comparable BP control, dual RAS inhibition with an ACE inhibitor and an ARB could be more renoprotective than either monotherapy in diabetic patients with no evidence of kidney disease is unknown. What did the researchers do and find? In this prospective, randomized, open-label, blinded endpoint (PROBE) trial, we evaluated whether, at similar BP control, combination therapy with the ACE inhibitor benazepril and the ARB valsartan would reduce the incidence of microalbuminuria more effectively than benazepril or valsartan monotherapy in 612 patients with type 2 diabetes and high-normal albuminuria. Secondarily, we compared the effects of the 2 monotherapies on the primary prevention of microalbuminuria in this population. We found that during a median follow-up of 66 months, combined treatment with half of the standard manufacturer-recommended antihypertensive doses of benazepril and valsartan had no superior effect against progression to microalbuminuria as compared to monotherapy with full recommended doses of either benazepril or valsartan. The protective effects of benazepril and valsartan monotherapies against progression to microalbuminuria were also similar. All treatments were safe and well tolerated, with a slight excess of hyperkalemia and hypotension episodes in the combination therapy group. What do these findings mean? Dual RAS blockade should not be preferred to ACE inhibitor or ARB monotherapy for the primary prevention of microalbuminuria in patients with type 2 diabetes and normoalbuminuria. Recent studies showing that sodium–glucose co-transporter 2 (SGLT2) inhibitors may afford substantial nephro- and cardioprotection to patients with type 2 diabetes and varying degrees of albuminuria might pave the way to novel prevention strategies based upon the integrated use of these novel medications with an ACE inhibitor or an ARB, but not with their combination.
Published: 2021
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19. The Role of Vildagliptin in the Therapy of Type 2 Diabetic Patients with Renal Dysfunction

Author: Roberto Trevisan and Trevisan, R
Subjects: medicine.medical_specialty, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Renal function, 030209 endocrinology & metabolism, Type 2 diabetes, Review, 030204 cardiovascular system & hematology, Hypoglycemia, Dipeptidyl peptidase-4 inhibitor, urologic and male genital diseases, Type 2 diabete, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Diabetes mellitus, Internal medicine, Chronic kidney disease, Dipeptidyl peptidase-4 inhibitors, Internal Medicine, medicine, Vildagliptin, MED/13 - ENDOCRINOLOGIA, Intensive care medicine, business.industry, nutritional and metabolic diseases, medicine.disease, MED/14 - NEFROLOGIA, chemistry, Albuminuria, Glycated hemoglobin, medicine.symptom, business, medicine.drug, Kidney disease
Abstract: Diabetes is the leading cause of chronic kidney disease, and even in the absence of albuminuria, decreased renal function in type 2 diabetes mellitus (T2DM) patients increases the risk for major adverse cardiovascular events and death. The evidence derived from recent studies suggests that intensive glucose control not only reduces the risk for microalbuminuria and macroalbuminuria but may also decrease the rate of decline of glomerular filtration rate (GFR). Although insulin therapy is widely used in patients with T2DM and renal disease, metabolic control is particularly difficult to achieve and manage because of the limited therapeutic options and the frequent comorbidities seen in this population. Recent evidence suggests that dipeptidyl peptidase-4 (DPP-4) inhibitors may offer a better choice for improving glycemic control in T2DM patients with low GFR. This review will focus on vildagliptin, a DPP-4 inhibitor with a large body of evidence in patients with moderate to severe renal failure and a good clinical profile in terms of efficacy and safety. In particular, vildagliptin, with appropriate dose adjustment, provides clinically important reductions in glycated hemoglobin, without increasing weight and the risk of hypoglycemia even in patients with severe chronic kidney disease.
Published: 2017

20. Contents Vol. 136, 2017

Author: Xuelian Ma, Gaetano Alfano, Maria Dolores Sanchez-Niño, David G. Warnock, Andreas Kjaer, Norberto Perico, Enrique Morales, Monica Cortinovis, Sergio Luis-Lima, Manuel Praga, Gianni Cappelli, Hans Pottel, Jia-qi He, Druckerei Stückle, Raul Fernandez-Prado, Niels Obel, Tatsuo Shimosawa, Bo Feldt-Rasmussen, Esteban Porrini, Maria Soledad Pizarro-Sánchez, Francesco Fontana, Jan Gerstoft, Conghui Wang, Ana Belen Sanz, Beatriz Fernandez-Fernandez, Li-juan Liang, Alessandro Roberto Dodesini, Pierre Delanaye, Roberto Trevisan, Zheng Wang, Alberto Ortiz, Esmeralda Castillo-Rodriguez, Mads Hornum, Beibei Liu, Xiangting Wang, Etienne Cavalier, Magnus Glindvad Ahlström, Catalina Martin-Cleary, Giuseppe Remuzzi, Qingyou Xu, and Richard J. Glassock
Subjects: Traditional medicine, business.industry, Medicine, business
Published: 2017
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21. Continuous subcutaneous insulin infusion reduces maternal and neonatal risk in pregnant women with type 1 diabetes: An observational cohort study of 122 pregnancies

Author: Silvia Galliani, Giorgia Cavalli, Cristiana Scaranna, Anna Maria Corsi, Giuseppe Lepore, Mascia Albizzi, Rosalia Bellante, G. Mangili, Alessandro Roberto Dodesini, Elena Ciriello, Roberto Trevisan, Dodesini, A, Cavalli, G, Ciriello, E, Lepore, G, Corsi, A, Scaranna, C, Bellante, R, Albizzi, M, Galliani, S, Mangili, G, and Trevisan, R
Subjects: Adult, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Infusions, Subcutaneous, Injections, Cohort Studies, Insulin Infusion Systems, Pregnancy, Diabetes mellitus, continuous subcutaneous insulin infusion, large for gestational age, multiple daily injections, pregnancy, type 1 diabetes, medicine, Humans, Hypoglycemic Agents, Insulin, Aged, Type 1 diabetes, business.industry, Obstetrics, Infant, Newborn, medicine.disease, Subcutaneous insulin, Diabetes Mellitus, Type 1, Treatment Outcome, Female, business, Cohort study
Published: 2020
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22. Renal insufficiency and linagliptin therapy: a case report

Author: Anna Maria Corsi and Roberto Trevisan
Subjects: Kidney, Pediatrics, medicine.medical_specialty, Dose, business.industry, General Medicine, Type 2 diabetes, medicine.disease, Linagliptin, Metformin, medicine.anatomical_structure, Pharmacotherapy, Lactic acidosis, Medicine, business, medicine.drug, Glycemic
Abstract: The presence of severe renal insufficiency in type 2 diabetes patients often challenges the diabetologist to prescribe a drug therapy, leading to a satisfactory glycemic balance with the minimal risk of hypoglycaemia. Diabetics with renal dysfunction present an increased risk of hypoglycemic episodes, and oral drugs are often ìcontraindications in these patients , especially if they are eliminated by the kidney. This last class of drugs requires a reduction in dosages to avoid the risk of prolonged hypoglycaemic episodes. In particular, in patients with severe renal insufficiency, metformin must be suspended in order to avoid the risk of lactic acidosis. Here we report the case of a young woman with type 2 diabetes, who quickly developed severe renal failure, unfortunately without remission. This case emphasizes the efficacy and safety of insulin-associated linagliptin for good glycemic control in patients with severe renal impairment, with marked reduction in hypoglycaemic episodes (Diabetology).
Published: 2018
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23. Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial

Author: Ruilope, Luis M, Agarwal, Rajiv, Anker, Stefan D, Bakris, George L, Filippatos, Gerasimos, Nowack, Christina, Kolkhof, Peter, Joseph, Amer, Mentenich, Nicole, Pitt, Bertram, Diego, Besada, Alfredo, Wassermann, Julio, Bittar, Alicia, Elbert, Augusto, Vallejos, Gloria, Viñes, Hugo, Sanabria, Federico Pérez Manghi, Alberto, Liberman, Inés, Bartolacci, Diego, Aizenberg, Mariano, Chahin, Laura, Maffei, Elizabeth, Gelersztein, Bernhard, Ludvik, Hans-Robert, Schönherr, Heinz, Drexel, Wolfgang, Preiß, Ursula, Hanusch, Peter, Neudorfer, Friedrich, Prischl, Bernhard, Paulweber, Christoph, Ebenbichler, Rudolf, Prager, Harald, Sourij, Gerit-Holger, Schernthaner, Martin, Clodi, Evelyn, Fliesser-Görzer, Elif, Ekinci, Richard, Macisaac, David, Packham, Hugo, Stephenson, Michael, Suranyi, Gary, Wittert, Katie-Jane, Wynne, Alexia, Pape, Duncan, Topliss, Peter, Colman, Craig, Nelson, James, Vandeleur, David, Colquhoun, Simon, Roger, Peak Mann Mah, Walter, Abhayaratna, Luc VAN Gaal, Pieter, Gillard, Jean-Michel, Hougardy, Marijn, Speeckaert, Koen, Stas, Wendy, Engelen, Francis, Duyck, André, Scheen, Hilde, Vanbelleghem, Peter, Doubel, Svetla, Vasileva, Rosen, Rashkov, Boyan, Nonchev, Theodora, Temelkova-Kurktschieva, Mariana, Yoncheva-Mihaylova, Rangel, Rangelov, Neli, Klyuchkova, Pavel, Stanchev, Zhivko, Tagarev, Radostina, Boshnyashka, Petya, Manova, Zhulieta, Prakova, Mariya, Lucheva, Valentina, Gushterova, Ghassan, Farah, Dimitar, Georgiev, Mariyana, Pichmanova, Dotska, Minkova, Bilyana, Stoyanovska-Elencheva, Maria Eugenia Canziani, Miguel, Hissa, Irene, Noronha, Joao Eduardo Salles, Daniela, Antunes, Freddy, Eliaschewitz, Carlos Eduardo Figueiredo, Rogerio de Paula, Luis, Canani, Maurilo Leite Jr, Bruno, Paolino, Rosangela, Rea, Sergio, Vencio, Claudia, Brito, Raphael, Paschoalin, Roberto Pecoits Filho, Eduardo, Vasconcellos, Nathalia, Paschoalin, Adriana, Forti, Roberto, Botelho, Miguel, Riella, Dalton, Precoma, Maria, Cerqueira, Lilia, Maia, Evandro, Portes, Marcio, Pereira, Joanne, Liutkus, Dennis, O Keefe, Richard, Tytus, Brian, Carlson, James, Conway, Michael, Walsh, Igor, Wilderman, Andrew, Steele, Sheldon, Tobe, Louise, Vitou, Karthik, Tennankore, Valdemar, Martinho, Philip, Mcfarlane, Daniel, Shu, Serge, Cournoyer, Richard, Dumas, Giuseppe, Mazza, Guy, Tellier, George, Tsoukas, Stanley, Weisnagel, Jean-Francois, Yale, Sameh, Fikry, Randolph, Hart, Pavel, Hamet, Francois, Madore, Paul, Barre, Daniel, Schwartz, Allan, Kelly, Ivor, Teitelbaum, Sean, Peterson, Sam, Henein, Richard, Goluch, Gregoire, Wuerzner, Markus, Laimer, Stefan, Bilz, Marc, Donath, Gottfried, Rudofsky, Christopher, Strey, Antoinette, Pechère-Bertschi, Paola, Varleta, Fernando, González, Marcelo, Medina, Carmen, Romero, Victor, Saavedra, Juan Carlos Prieto, Eliana, Reyes, Juan Carlos Palma, Jorge, Cobos, Zhihong, Liu, Dalong, Zhu, Nan, Chen, Fang, Liu, Wang, Li, Qing, Su, Bingyin, Shi, Aiping, Yin, Hao, Wang, Yan, Li, Jianying, Niu, Chaoqing, Wu, Xinjun, Wang, Ying, 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Boonstra, A, C Bakker, R, Marielle, Krekels, B Brouwer, C, T Luik, P, J N, M Barendregt, Bert-Jan van den Born, Trine, Finnes, Thomas, Karlsson, Hilde, Selsås, Emil, Asprusten, Robert, Hagemeier, Erik, Eriksen, Knut, Risberg, Hans, Høivik, Leidulv, Solnør, Frode, Thorup, Jan, Rocke, Rick, Cutfield, Peter, Dunn, Jeremy, Krebs, Russell, Scott, Kingsley, Nirmalaraj, Nine, Smuts, John, Baker, Veronica, Crawford, Albert, Bautista, Roberto, Mirasol, Elizabeth, Catindig, Glenda, Pamugas, Louie, Tirador, Maribel, Tanque, Janusz, Gumprecht, Piotr, Napora, Edward, Franek, Andrzej, Stankiewicz, Katarzyna, Landa, Agnieszka, Tiuryn-Petrulewicz, Kazimierz, Ciechanowski, Bogna, Wierusz-Wysocka, Barbara, Rewerska, Grazyna, Cieslik, Michal, Hoffmann, Michal, Nowicki, Jolanta, Krzykowska, Stanislaw, Mazur, Katarzyna, Wasilewska, Anna, Ocicka-Kozakiewicz, Ewa, Skokowska, Renata, Wnetrzak-Michalska, Jan, Ruxer, Patrycja, Butrymowicz, Katarzyna, Madziarska, Ilona, Kurnatowska, Teresa, Rusicka, Adam, 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Idalia, Acosta, Atoya, Adams, William, Sanchez, Rosa, Suarez, Efrain, Reisin, Carlos, Herrera, Keung, Lee, Csaba, Kovesdy, Adam, Whaley-Connell, Aldo, Peixoto, Ronald, Mayfield, Mahendra, Jain, Earl, Martin, Paul, Norwood, Jonathan, Wise, Hugo, Romeu, Stephen, Halpern, Mustafa, Mandviwala, Thomas, Turk, Anna, Burgner, David, Bleich, Ankur, Doshi, Jose, Carpio, Jorge, Posada, Alexander, Magno, Samer, Nakhle, Gary, Goldstein, Caroline, Mbogua, Dierdre, Mcmullen, Dilawar, Ajani, Wayne, Kotzker, Nelson, Kopyt, Richard, Treger, Yusuf, Ruhullah, Sharon, Adler, Harjeet, Brar, Marc, Rendell, Dennis, Ross, Srinivasan, Beddhu, German, Hernandez, Sylvia, Rosas, M Sue Kirkman, Mohammed, El-Shahawy, Jeffrey, Rothman, Ahmad, Barakzoy, Aparna, Tamirisa, Sabrina, Benjamin, Michael, Bahrami, Prabir, Roy-Chaudhury, Ramprasad, Dandillaya, Gretel, Trullenque, Jose, Birriel, John, Flack, Karen, Johnson, Brenda, Lemus, Guillermo, Umpierrez, Geetha, Maddukuri, Kenneth, Jamerson, Christopher, Case, Patrick, Fluck, Saeed, Kronfli, Violet, Habwe, Bala, Subramanian, Tariq, Shafi, Rupesh, Raina, Roland, Fernando, Sourabh, Kharait, Carlos, Hernandez-Cassis, Raymond, Fink, Jamal, Hammoud, Amer, Al-Karadsheh, Manuel, Montero, Philip, Nicol, Jesus, Navarro, Michael, Shanik, Zia, Din, Francisco, Gonzalez-Abreu, Sam, Lerman, Claude, Galphin, John, Evans, Ashwini, Gore, Radica, Alicic, Mandeep, Sahani, Roberto, Pisoni, Tuan-Huy, Tran, Jeffrey, Ryu, Harvey, Serota, Nilda, Neyra, Richard, O Donovan, Sreedhar, Mandayam, Moustafa, Moustafa, Mark, Smith, Arvind, Krishna, Arjun, Sinha, Anuj, Bhargava, Kodangudi, Ramanathan, Soni, Dhanireddy, Stephen, Thomson, Romanita, Nica, Emaad, Abdel-Rahman, Mark, Barney, Mariana, Markell, Nauman, Shahid, David, Oliver, Tran, Khanh, Pham Nguyen Son, Lam VAN Hoang, Boi Ngoc Nguyen, Nguyen Minh Nui, Lan Phuong Tran, Fayzal, Ahmed, Dorothea, Urbach, Dirkie Jansen van Rensburg, Gracjan, Podgorski, Aslam, Amod, Sindeep, Bhana, Shaifali, Joshi, Essack, Mitha, Deepak, Lakha, Louis van Zyl, Trokis, J, Naresh, Ranjith, Mary, Seeber, Mohamed, Sarvan, Mohammed, Tayob, Brian, Rayner, Larry, Distiller, Heidi, Siebert, Mukesh, Joshi, Paul, Rheeder, Magdalena Madero Rovalo, Gustavo Solache Ortiz, Gustavo Méndez Machado, Rafael Valdez Ortiz, Juan Villagordoa Mesa, Saúl Irizar Santana, Sandro Avila Pardo, Jorge Escobedo de la Peña, Guillermo González Gálvez, Leobardo Sauque Reyna, Miriam Bastidas Adrian, Guillermo Fanghänel Salmón, Ramiro Gutiérrez Ochoa, Luis Nevarez Ruiz, Gabriel Ramos López, Alfredo Chew Wong, Arturo Saldaña Mendoza, Pedro García Hernández, José González González, Melchor Alpizar Salazar, José Lazcano Soto, Amaury, Roman-Miranda, Gregorio, Cortes-Maisonet, Liana, Turcu, Adriana, Dumitrescu, Gabriela, Radulian, Hortensia, Barbonta, Cristina, Mistodie, Georgeta, Vacaru, Alexandrina, Popescu, Adrian, Vlad, Silvia, Paveliu, Nicoleta, Mindrescu, Adrian, Albota, Ella, Pintilei, Lavinia, Pop, Gabriela, Negrisanu, Doina, Catrinoiu, Cornelia, Bala, Amorin, Popa, Iosif, Szilagyi, Ciprian, Constantin, Elena, Caceaune, Adriana, Onaca, Li Yuan Lee, Nor Azizah Aziz, Wan Mohd Izani Wan Mohamed, Wan Hasnul Halimi Bin Wan Hasan, Jeyakantha, Ratnasingam, Nik Nur Fatnoon Nik Ahmad, Rizmy Najme Khir, Norhaliza Mohd Ali, Masni, Mohamad, Chek Loong Loh, Joe, Eustace, John, Holian, Donal, Reddan, Yvonne, O Meara, Mensud, Hatunic, Zuzana, Ochodnicka, Dalibor, Sosovec, Andrej, Dzupina, Ingrid, Buganova, Jana, Babikova, Denisa, Spodniakova, Ruilope, L, Agarwal, R, Anker, S, Bakris, G, Filippatos, G, Nowack, C, Kolkhof, P, Joseph, A, Mentenich, N, Pitt, B, Trevisan, R, Pathology/molecular and cellular medicine, Diabetes Pathology & Therapy, and Diabetes Clinic
Subjects: Male, Endocrinology, Diabetes and Metabolism, Enfermedad cardiovascular, 030232 urology & nephrology, BAY 94-8862, Type 2 diabetes, 030204 cardiovascular system & hematology, Diabete, Kidney, Aparato circulatorio, Azúcar, chemistry.chemical_compound, Mineralocorticoid Receptor Antagonists/therapeutic use, 0302 clinical medicine, Medicine and Health Sciences, Diabetic Nephropathies, Myocardial infarction, Renal Insufficiency, Chronic, Aldosterone, Outcome, Mineralocorticoid Receptor Antagonists, RISK, COMPLICATIONS, Diabetes, Middle Aged, SPIRONOLACTONE, CHRONIC HEART-FAILURE, Treatment Outcome, Mineralocorticoid, Nephrology, Cardiovascular Diseases, Research Design, Disease Progression, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, Type 2, Glomerular Filtration Rate, medicine.medical_specialty, Finerenone, Naphthyridines/therapeutic use, Renal function, Outcomes, 03 medical and health sciences, Clinical, Double-Blind Method, Diabetes mellitus, Internal medicine, medicine, Diabetes Mellitus, Humans, Naphthyridines, Renal Insufficiency, Chronic, ANTAGONIST, Sistema cardiovascular, Aged, Patient-Oriented, Translational Research: Research Article, Diabetic Nephropathies/complications, Renal Insufficiency, Chronic/drug therapy, RECEPTOR, Aldosterone, Clinical, Diabetes, Kidney, Mineralocorticoid, Outcomes, business.industry, Cardiovascular Diseases/epidemiology, Diabetes Mellitus, Type 2/complications, MILD, WORSENING RENAL-FUNCTION, EFFICACY, medicine.disease, chemistry, Diabetes Mellitus, Type 2, Spironolactone, Albuminuria, business, Kidney disease, Follow-Up Studies
Abstract: Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m2 and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
Published: 2019
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24. Impact of a Complement Factor H Gene Variant on Renal Dysfunction, Cardiovascular Events, and Response to ACE Inhibitor Therapy in Type 2 Diabetes

Author: Elisabetta Valoti, Marina Noris, Annalisa Perna, Erica Rurali, Giulia Gherardi, Matteo Breno, Aneliya Parvanova Ilieva, Ilian Petrov Iliev, Antonio Bossi, Roberto Trevisan, Alessandro Roberto Dodesini, Silvia Ferrari, Nadia Stucchi, Ariela Benigni, Giuseppe Remuzzi, Piero Ruggenenti, Valoti, E, Noris, M, Perna, A, Rurali, E, Gherardi, G, Breno, M, Parvanova, A, Iliev, I, Bossi, A, Trevisan, R, Dodesini, A, Ferrari, S, Stucchi, N, Benigni, A, Remuzzi, G, and Ruggenenti, P
Subjects: 0301 basic medicine, Trandolapril, medicine.medical_specialty, ACE inhibitors, lcsh:QH426-470, Complement, Type 2 diabetes, Diabete, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, ACE inhibitor, Diabetes Complication, Internal medicine, Diabetes mellitus, Atypical hemolytic uremic syndrome, Genetics, medicine, Genetics (clinical), Original Research, diabetes, business.industry, Factor H, diabetes complications, Cardiovascular risk, ACE inhibitors, Cardiovascular risk, Complement, Diabetes, Diabetes Complications, Factor H, Microalbuminuria, medicine.disease, Complement system, lcsh:Genetics, 030104 developmental biology, 030220 oncology & carcinogenesis, Molecular Medicine, Microalbuminuria, business, medicine.drug
Abstract: Complement activation has been increasingly implicated in the pathogenesis of type 2 diabetes and its chronic complications. It is unknown whether complement factor H (CFH) genetic variants, which have been previously associated with complement-mediated organ damage likely due to inefficient complement modulation, influence the risk of renal and cardiovascular events and response to therapy with angiotensin-converting enzyme inhibitors (ACEi) in type 2 diabetic patients. Here, we have analyzed the c.2808G> T, (p.Glu936Asp) CFH polymorphism, which tags the H3 CFH haplotype associated to low plasma factor H levels and predisposing to atypical hemolytic uremic syndrome, in 1,158 type 2 diabetics prospectively followed in the Bergamo nephrologic complications of type 2 diabetes randomized, controlled clinical trial (BENEDICT) that evaluated the effect of the ACEi trandolapril on new onset microalbuminuria. At multivariable Cox analysis, the p.Glu936Asp polymorphism (Asp/Asp homozygotes, recessive model) was associated with increased risk of microalbuminuria [adjusted hazard ratio (HR) 3.25 (95% CI 1.46-7.24), P = 0.0038] and cardiovascular events [adjusted HR 2.68 (95% CI 1.23-5.87), P = 0.013]. The p.Glu936Asp genotype significantly interacted with ACEi therapy in predicting microalbuminuria. ACEi therapy was not nephroprotective in Asp/Asp homozygotes [adjusted HR 1.54 (0.18-13.07), P = 0.691 vs. non-ACEi-treated Asp/Asp patients], whereas it significantly reduced microalbuminuria events in Glu/Asp or Glu/Glu patients [adjusted HR 0.38 (0.24-0.60), P < 0.0001 vs. non-ACEi-treated Glu/Asp or Glu/Glu patients]. Among ACEi-treated patients, the risk of developing cardiovascular events was higher in Asp/Asp homozygotes than in Glu/Asp or Glu/Glu patients [adjusted HR 3.26 (1.29-8.28), P = 0.013]. Our results indicate that type 2 diabetic patients Asp/Asp homozygotes in the p.Glu936Asp CFH polymorphism are at increased risk of microalbuminuria and cardiovascular complications and may be less likely to benefit from ACEi therapy. Further studies are required to confirm our findings.
Published: 2019
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25. Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI): a phase 3, placebo-controlled, randomised trial

Author: Deepak L Bhatt, Philippe Gabriel Steg, Shamir R Mehta, Lawrence A Leiter, Tabassome Simon, Kim Fox, Claes Held, Marielle Andersson, Anders Himmelmann, Wilhelm Ridderstråle, Jersey Chen, Yang Song, Rafael Diaz, Shinya Goto, Stefan K James, Kausik K Ray, Alexander N Parkhomenko, Mikhail N Kosiborod, Darren K McGuire, Robert A Harrington, Vladimir Santos, Ashit Jain, Irina Lendel, Michael Russo, W H Haught, Manuel Bouza, Harinder Gogia, Supratim Banerjee, George Kichura, Louis Kantaros, Francisco Padron, Rakesh Passi, Jay Stone, Michael Pursley, Michael D'Urso, Timothy Gardner, James Bennett, Khaled Nour, Satinder Saini, Wenwu Zhang, Dharam Kumbhani, Dustin Thomas, Dominick Angiolillo, Barry Bertolet, Amaury Roman-Miranda, Robert Black, Ramin Manshadi, Carlos Vaca, Antonio Blanco, Mark Napoli, David Brabham, Ayim Akyea-Djamson, Pratik Desai, Sudhir Prasada, Ajit Khaira, Leslie Forgosh, Ira Lieber, Guillermo Umpierrez, Dinesh Singal, Juan Londono, Neil Fraser, Jose Ruiz, Damaris Vega, Lilia Rodriguez, Christopher Brown, Faizullah Syed, Guarav Aggarwala, William Eaves, Michael Foster, Dinesh Gupta, David Avino, Wail Asfour, Glen Tonnessen, Xue-Qiao Zhao, Narendra Singh, Andrew Brockmyre, Norman Lepor, Nicolas Shammas, David Blick, Steven Hearne, John Prodafikas, Edgar Carell, Mark Izzo, Amin Karim, Bosh Zakhary, Mahmoud Atieh, Steven Leichter, Charles Meadows, David Hotchkiss, Mazen Abu-Fadel, Alan Wiseman, Jeffrey Bander, Mahesh Shah, Subhash Banerjee, Ricky Ganim, Karen Sopko, Misal Khan, Ramon Lloret, Troy Weirick, Rajendra Mehta, Udho Thadani, Anuj Bhargava, Mikhail Kosiborod, Jaynier Moya, Cezar Staniloae, Yamirka D Guerra, Anil Chhabra, Douglas Kosmicki, Wassim Shaheen, Akber Mohammed, J'Cinda Bitters, Jan Pattanayak, Julian Javier, Sunny Srivastava, Roland Phillips, Jessie Al-Amin, Michael Lillestol, Patrick Simpson, Lydie Hazan, Amit Amin, Gopi Shah, Denes Korpas, Bruce Platt, Jim Dickert, Orlando Puente, Louis Hiotis, Timothy Doyle, Raj Rajan, Alan Meholick, Christian Gring, Elie Hage-Korban, Robert Feldman, Harry Colfer, Samuel Butman, Malcolm Foster, Terence Hart, Randall Huling, Shervin Eshaghian, Ofsman Quintana, Deanna Cheung, Franklin Handel, Mara Rodriguez, David Suh, Paul Gordon, Gregg Pressman, Michael Bauer, William French, Mark Barettella, Sridhar Chatrathi, Damodhar Suresh, Ronald Goldberg, Mark Huth, Liwa Younis, Aref Rahman, Richard Mascolo, Michelle Welch, Randeep Suneja, Stephen Smith, Scott Shurmur, John Agaiby, Ahmad Jingo, Janice Johnston, Mary Beth, Anthony Vlastaris, Susan Kemp, Hamid Taheri, Edward Pereira, Michael Deyoung, Zafir Hawa, Ray Smith, Thomas Galski, Samer Garas, M Reddy, Susheel Sharma, Joeseph Hargrove, Charles Treasure, Ronald Emerson, Tariq Haddad, Kathryn Rohr, Larry Levinson, Raul Gaona, Barry Uretsky, Hiralal Maheshwari, Denny Lee, Stephanie Kinnaman, Robert Singal, Jeffrey Geohas, Osvaldo Gigliotti, Ajit Raisinghani, Charanjit Khurana, Brent Hella, Michael Kelberman, Steven Voyce, Sanjay Singh, Eric Lo, Pradeep Singh, Ross Goodfellow, Stuart Fischer, Richard Lorraine, Traci Turner, Jeffrey Shanes, Robert Busch, Robert Broker, Michelle Zaniewski, Kevin Pounds, Giselle Debs-Perez, Stephen Ong, Brad Frandsen, Douglas Fullington, Naseem Jaffrani, Ahtaram Khan, Marcus Lee, Joe Pouzar, George Revtyak, Julian Gonzalez, Samer Nakhle, Abel Murillo, Douglas Young, Sashi Makam, Mushtaq Syed, Kevin Woolf, Paul Grena, Sarab Alfata, Sharan Mahal, David Hoffman, Tinoy Kizhakekuttu, Joseph Deering, Janak Bhavsar, Scott Mikesell, William Wilson, Vance Wilson, Salah El, Francis Spinale, Vinod Kannarkat, Sunder Rao, Lenita Hanson, John Bertsch, Elena Gonzalez-Ortiz, Norma Severino, John Willis, Joel Schock, Ladan Bakhtari, Raul Gazmuri, Saadat Ansari, Jason Hall, Arvind Mehta, Neal Shealy, Stuart Zarich, Deovrat Singh, Kishor Vora, Nabil Andrawis, Darron Molter, David Maron, Jose Cardona, Ronald D'Agostino, Tamjeed Arshad, Rodney Samaan, David Jones, Dale Presser, John Heath, Sandy Green, George Bittar, Sheldon Henry, David Korn, John Schmedtje, Venkatesh Nadar, Bruce Graham, Ajay Labroo, Leonardo Clavijo, Hal Roseman, Gilbert Ledesma, Robert Rosen, Isaac Dor, William Kirby, Jennefer Sutton, Frank Eder, Bruce Iteld, Jose Gomez-Cortes, Maurice Buchbinder, Joseph Kasper, Antonio Terrelonge, Gustavo Torres, Ted Jagielo, Jose Alvarez, Yehuda Handelsman, Mario Guillen, Randall Richwine, Lorena Lewy-Alterbaum, Clinton Corder, Moogali Arvind, David Bolshoun, Magdy Mikhail, Stephen Minton, Odilon Alvarado, J Abbott, Brett Cauthen, Ryan Welter, Randy Mintz, John Cox, Annette Quick, Melvin Weiss, Johnny Dy, James Zebrack, Glenn Gandelman, Vinayak Hegde, Marc Silver, Michele DeGregorio, William Lawson, Christopher Paa, Anna Bortnick, Merrill Krolick, Rodolfo Sotolongo, Jorge Cheirif, Priya Kumar, Preetham Jetty, Ambar Patel, Mariusz Kruk, Iwona Kobielusz-Gembala, Barbara Rewerska, Adam Madrzejewski, Krzysztof Milewski, Jerzy Cygler, Joanna Petryka-Mazurkiewicz, Waldemar Jastrzebski, Janusz Korecki, Wojciech Fil, Janusz Prokopczuk, Anna Bochenek, Marek Wujkowski, Robert Witek, Piotr Konczakowski, Pawel Miekus, Marcin Szczasny, Wlodzimierz Musial, Krzysztof Cymerman, Jacek Lampart, Jacek Mikosinski, Slawomir Szynal, Issa Fares, Grzegorz Opolski, Stanislaw Mazur, Beata Wozakowska-Kaplon, Renata Bijata-Bronisz, Lukasz Wierucki, Beata Losa, Grzegorz Drelich, Marek Konieczny, Pawel Starczewski, Lidia Pawlowicz, Pawel Jesionowski, Jaroslaw Jurowiecki, Jacek Gniot, Mariusz Czyzycki, Karol Stania, Izabela Kucharczyk-Bauman, Benita Busz-Papiez, Agnieszka Karczmarczyk, Wanda Sudnik, Alina Koszek, Piotr Kolodziej, Bartosz Skwarna, Nicolás Jaramillo, Maciej Jankowski, Wojciech Czochra, Leszek Kinasz, Beata Miklaszewicz, Teresa Stasinska, Wladyslaw Pluta, Marcin Basiak, Teresa Rusicka, Izabela Niedbal-Yahfouf, Grazyna Popenda, Romuald Korzeniak, Agnieszka Mirek, Rafal Mariankowski, Lukasz Wojnowski, Marek Korol, Jacek Baszak, Piotr Podolec, Wojciech Piesiewicz, Aleksander Zurakowski, Carlos Luengas, Marek Skura, Piotr Pilecki, Piotr Majchrzak, Ewa Krzyzagórska, Marcin Drozd, Barbara Kaczmarek, Teresa Sliwinska, Katarzyna Zelazowska, Rafal Sztembis, Katarzyna Landa, Lidia Matyszczak-Toniak, Krzysztof Strojek, Marek Piepiorka, Robert Malinowski, Maria Górska, Edyta Stolarczyk-Sowa, Leszek Romanowski, Elzbieta Zinka, Zygfryd Reszka, Joanna Skierkowska, Anna Uzunow, Ewa Laskowska-Derlaga, Ekaterina Puntus, Elena D Kosmacheva, Natalia Koziolova, Prokhor Pavlov, Tatiana Supryadkina, Yury Didenko, Philipp Kopylov, Andrei Kazakov, Sergei Aksentiev, Elena Vishneva, Alexey Repin, Olga Smolenskaya, Olga Mantserova, Oleg Khrustalev, Elena Privalova, Vladimir Konstantinov, Svetlana Boldueva, Andrey Ezhov, Alexander Chernyavsky, Gadel Kamalov, Albert Galyavich, Galina Zubeeva, Galina Nechaeva, Sergey Shustov, Nino Dzhaiani, Tatiana Treshkur, Nataliya Osokina, Alexey Panov, Elena Shutemova, Valeriy Makukhin, Tatiana Kropotina, Larisa Tsyba, Yuri Karpov, J M 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Rusev, Nikolina Georgieva, Rumen Kondov, Veselin Rusinov, Ivo Petrov, Georgi Stanchev, Mariana Konteva, Adriana Dincheva, Zdravka Yaneva, Ralitsa Vatova, Katya Ilieva, Nikolai Runev, Borislav Kolomanov, Ivan Petrov, Nikolay Iliev, Snezhanka Tisheva, Boryana Chompalova, Maria Tokmakova, Dimitar Raev, Kolyo Byanov, Dimitar Markov, Lenko Mihov, Atanas Mihov, Nora Milcheva, Milen Minchev, Mihail Mollov, Borislav Borisov, Tihomir Tihchev, Venelin Karakolev, Bojidar Dimov, Svetoslav Georgiev, Lachezar Smilov, Bon K Koo, Taehoon Ahn, Soon J Hong, Junghan Yoon, Seok K Oh, Myung H Jeong, Doo-Il Kim, Kiyuk Chang, Weon Kim, Joo-Yong Hahn, Kwang S Cha, Jung-Hee Lee, Si-Wan Choi, Chang-Wook Nam, In-Ho Chae, Yong H Park, Seung-Jea Tahk, Won-Yong Shin, Jei-Keon Chae, Byung J Kim, Jang-Whan Bae, Woo J Park, Seung W Rha, Young J Choi, Jin-Yong Hwang, Hun S Park, Luciano Baracioli, Fabio Guimaraes, Eduardo Vasconcellos, José Saraiva, Adamastor Pereira, Queulla Santos, Paulo Rossi, Lilia Maia, Miguel Madeira, Marcio Pereira, Roberto Botelho, Gilmar Reis, Freddy Eliaschewitz, Joao Borges, Carlos Nascimento, Jose A Fortes, Weimar de Souza, Pedro Pimentel, Miguel Hissa, Marcos Franchetti, Dalton Precoma, Costantino Ortiz, Mauro Hernandes, Wladmir Saporito, Fabio R dos Santos, Adrian Kormann, Fernando Neuenschwander, Oscar Dutra, Nelson Rassi, Luiz Tanajura, Juliana Souza, Delcio S Junior, Paulo Leaes, Adriana Forte, Teresa C Bonansea, Jose Marin, Bruno Machado, Maria J Cerqueira, Frederico Silva, Yorghos Michalaros, Euler Manenti, Cintia Cercato, Estevao Figueiredo, Ming-En Liu, Yi-Chih Wang, Tsung-Ming Lee, Chih Fang, Yen-Wen Wu, Kwo-Chang Ueng, Huey-Herng Sheu, Wen T Lai, I-Chang Hsieh, Zhih-Cherng Chen, Mu-Jang Lee, Chern Chiang, Kou-Gi Shyu, Chien-Hsun Hsia, Guang-Yuan Mar, Shih-Hung Chan, Chih-Cheng Wu, Wei-Kung Tseng, Kuan-Cheng Chang, Hung-I Yeh, Ji-Hung Wang, Charles Hou, Inna Sorokina, Maryna Dolzhenko, Olha Horoshko, Oleksandr Karpenko, Leonid Rudenko, Igor Vakaliuk, Anna Kulyk, Olena Levchenko, Oleksandr Prokhorov, Dmytro Reshotko, Mykhaylo Sorokivskyy, Nataliia Velichko, Valentyn Maslovskyi, Zinaida Teliatnikova, Sergiy Dotsenko, Olena Krakhmalova, Igor Kraiz, Viktoria Zharinova, Larysa Bula, Igor Kaydashev, Valeriy Molodtsov, Lesya Rasputina, Viktoriya Pidlisna, Olena Lysunets, Anatoliy Kravchenko, Liubomyr Glushko, Tetyana Khomazyuk, Yevgeniya Svyshchenko, Oleksandr Parkhomenko, Boris Mankovsky, Orest Abrahamovych, Andriy Yagensky, Mykola Stanislavchuk, Larisa Vasilyeva, Liubov Sokolova, Oleg Sychov, Vira Tseluyko, Igor Kyrychenko, Mykola Rishko, Sergiy Furkalo, Richard Gallo, Olivier Bertrand, Shamir Mehta, Christian Constance, Bruce Sussex, Remo Zadra, Simon Kouz, Raja Chehayeb, Amritanshu Pandey, Danielle Dion, Gordon Bailey, Laurie Hill, Krishnan Ramanathan, Micha Dorsch, Alykhan Nanji, Mohan Babapulle, Martine Montigny, Gilbert Gosselin, Payam Dehghani, Dennis Rupka, Michel Le May, Francis Pichette, Francois St-Maurice, Patrick Teefy, Samer Mansour, Saleem Kassam, Stephen Cheung, Anthony D Siega, Dennis O'Keefe, Eric Sabbah, Alan Bell, Guy Chouinard, Brian Wong, Mark Miller, Daniel Gaudet, Pierre Lachance, Iqbal Bata, Robert Petrella, Denis Gossard, Richard Dumas, Douglas Ing, Hagop Boyrazian, Ricardo Bessoudo, Thao T Huynh, Randy Hart, Jasmin Belle-Isle, Dinkar Shukla, Allan Kelly, Giuseppe Mazza, James Cha, Sam Henein, Andre Frechette, Saul Vizel, Joanne F Liutkus, Michael O'Mahony, Frank Halperin, Jacobus Kooy, John Graham, Allan Bailey, Ronald Wojcik, Igor Wilderman, Tibor Turi, Ákos Motyovszki, Béla Merkely, Csaba Király, Péter Andrássy, Zsolt Sárszegi, Tibor Fülöp, Zsolt Zilahi, István Édes, Andras Papp, Gábor Müller, Anna Czigány, Szilárd Zólyomi, László Korányi, János Takács, Ferenc Juhász, Bela Benczur, Sándor Kancz, András Földi, András C Nagy, Judit Bakai, István Greschik, László Püski, László Nagy, Róbert Kirschner, Roman Kuchar, Petr Hajek, Ladislav Busak, Daniel Michalik, Ivo Matyasek, Ivana Marusincova, Dusan Kucera, Ondrej Jerabek, Michaela Honkova, Vratislav Dedek, Ivan Rihacek, Pavel Kos, Josef Slaby, Martina Machkova, Eva Zidkova, Lubomir Elbl, Hana Grunfeldova, Jiri Carda, Vladimir Mrozek, Jiri Maly, Richard Milkovic, Jan Malecha, Hana Skalicka, Ivo Oral, Eva Krcova, Libor Lisa, Jan Belohlavek, Roman Miklik, Ondrej Cermak, Jana Bednarova, Zdenek Peroutka, Jindrich Spinar, Andreas Wilke, Karl-Friedrich Appel, Jens Taggeselle, Andreas Förster, Nicole Toursarkissian, Ekkehard Schmidt, Jochen Bott, Ayham Al-Zoebi, Dirk Hennig, Sabine Fischer, Norbert Schön, Joachim Sauter, Gregor Simonis, Ruth Nischik, Werner Rieker, Isabelle Schenkenberger, Thomas Behnke, Gerhard Klausmann, Michael Jeserich, Dietmar Trenk, Ingo Weigmann, Hannes Reuter, Reinhard Rummel, Candy von Münchhausen, Charlotte von Engelhardt, Eishun Horibe, Taro Shibasaki, Tomohiko Sato, Tsunekazu Kakuta, Ichiro Michishita, Michinao Tan, Ryoji Ishiki, Takahiko Aoyama, Shinichi Higashiue, Yawara Niijima, Akira Idogaki, Toru Hasegawa, Arihiro Kiyosue, Yoshiaki Tomobuchi, Katsunori Kawamitsu, Satsuki Kawasaki, Yoshiki Hata, Kazuki Fukui, Kozaburo Seki, Takashi Takenaka, Mitsuru Abe, Noriaki Utsu, Atsuyuki Oono, Kazuhisa Mitsuo, Atsushi Sueyoshi, Atsushi Hirohata, Mitsuru Tsujimoto, Osamu Ueda, Shinichi Takase, Masahiro Suzuki, Satoru Sakuragi, Fumi Yamamoto, Noritaka Fujimoto, Shigeo Kakinoki, Tatsushi Sugiura, Hiroshi Sugino, Toshihiro Nakamura, Toshiaki Kadokami, Hiroki Uehara, Masahiro Ono, Koichi Yokoya, Akihiro Koike, Sei Komatsu, Masahiro Sonoda, Hideki Ueno, Tomofumi Doi, Yuichiro Takagi, Kazuteru Fujimoto, Yutaka Eki, Munenori Okubo, Kenichiro Sasaki, Martijn van Eck, Eelko Ronner, Salem The, Ruud van de Wal, Pieter Nierop, Cornelis de Nooijer, Henri Werner, Iris Westendorp, Coen van der Zwaan, Hendrikus Crijns, Jan H Cornel, Sipke Strikwerda, Robert Bos, Edwin de Melker, Adrianus Kuijper, Hans Louwerenburg, Jacobus Plomp, Jan-Melle Dantzig, Francisco Prins, Henricus van Kesteren, Frank Willems, Giovanni Amoroso, Gabriela Carnero, Ernesto Duronto, Diego Besada, Carolina Chacon, Pedro Zangroniz, Silvana Solis, Alberto Liberman, Virginia Sernia, Andres Alvarisqueta, Laura Maffei, Oscar G Vilamajo, Celso García, Maximiliano Sicer, Juan Muntaner, Anselmo Bordonava, Juan Albisu, Alejandra Zanini, Lucas Rista, Miguel Hominal, José N Estrada, Aldo Prado, Diego M Gosparini, Beatriz Schiavi, Armando G Castillo, José G Ruíz, Guillermo R Martinez, Víctor G López, Enrique L Rosas, Gabriel R Lopez, Elias G Cantu, Manuel de los Ríos Ibarra, Francisco P Padilla, Jose P Carrasco, Luis V Carrillo, Joel D García, Alfredo N Askar, Carlos A Salinas, Marco A Gamba, Carlos G Sanchez, Arnulfo G Cantú, Raul V Sánchez, Jaime C Madrigal, Rafael H Urbano, Andrés Í Romo, José R González Juanatey, Paolo Racugno, Angel C Fillat, José M de la Torre Hernández, Juan A Peláez, Jorge B Cortada, Pablo G Pavia, Manuel J Navarro, Roberto M Asenjo, Francisco F Díaz, Eduard B Peligero, Fernando A Manterola, Antonio F Ortiz, Juan D Mediavilla García, Francisco M Ortuño, Tomás R Vera, Alfonso S González, Jaime A Viñas, Francisco J Fernández Portales, Petra S Mayordomo, Francisco B Ojeda, Antonio R Domínguez, Rosa S González, Diego B Guerrero, Juan M Ruiz Nodar, Xavier G Marimon, José G Margáez, Roberto M Aguilera, José F Díaz Fernández, José L Zamorano Gómez, Vicente B González, Bruno G del Blanco, Ignacio P Pérez, Mercé R Moreno, Ainhoa R Ereño, José A García Lledó, Juan Prieto, Alex Villablanca, Carlos Raffo, Christian Pincetti, Carlos Conejeros, Oscar Roman, Manuel Rodriguez, Paola Varleta, Cindy Goldberg, Jorge Sandoval, German Arriagada, Lucio Leon, Sergio Potthoff, Jorge Cobos, Christian Figueroa, Ellen Makotoko, Nyda Fourie, Lesley Burgess, Hendrik Nortje, Rust Theron, Perumal Pillai, Naresh Ranjith, Julien Trokis, Soobramoney Pillay, Jeevren Reddy, Theema Nunkoo, Cornelia Kapp, Dorothea Urbach, Lawrence Distiller, Adrian Horak, Louis van Zyl, Kathleen Coetzee, Zelda Punt, Junaid Bayat, Saleem Dawood, Ismail Mitha, Trevenesan Padayachee, Farzana Hoosen, Anthony Dalby, null Prabhavathi, Prakash Gowdaiah, Vimal Mehta, Milan Chag, Milind Gadkari, Kannaiyan Ramamurthee, Asit Das, Jitendra S Sawhney, Suvro Banerjee, Prachee Sathe, Srilakshmi Adhyapak, Tuan Nguyen, Vinh Pham, Huan Do, Anh Nguyen, Hien Nguyen, Binh Truong, Shahnaz Jamil-Copley, Chim Lang, Alastair Pell, Azfar Zaman, Robert Storey, Neil Swanson, Simon Smith, David Sharman, Denise Braganza, Peter Hammond, Andrew Moriarty, Stephen Bain, Maurice Pye, Andrew Sharp, Mark Blagden, Harpal Randeva, Timothy Myhill, Girish Viswanathan, Philip Keeling, Piers Clifford, Manish Saxena, Kristopher Lyons, John McMurray, Feeroz Jaafar, Clare Murphy, Simon Cartwright, Kamal Abouglila, Lubomir Antalik, Peter Krajci, Miroslav Urban, Frantisek Fazekas, Daniel Pella, Daniel Koleny, Tatiana Vykoukalova, Vladimir Macek, Daniela Vinanska, Livia Jamriskova, Slavomir Such, Peter Fulop, Stefan Farsky, Viliam Bugan, Jaroslava Strbova, Karol Micko, Juraj Palka Jr, Vladimir Sivak, Dalby Kristensen, Jens Refsgaard, Lene Holmvang, Ulrik Dixen, Henrik Nielsen, Kenneth Egstrup, Lisette O Jensen, Roman Sykulski, Ole Rasmussen, Alin Andries, Anders Luckow, Gitte Nielsen, Torben Sørensen, Chaiyasith Wongvipaporn, Noppadol Chamnarnphol, Suphot Srimahachota, Nakarin Sansanayudh, Srun Kuanprasert, Damras Tresukosol, Bancha Sookananchai, Mehmet Kanadasi, Turkay Ozcan, Murathan Kucuk, Zeki Ongen, Ertugrul Okuyan, Alev Arat, Sadik Acikel, Ahmet Yalcin, Umit Guray, Ceyhun Ceyhan, Necla Ozer, Sakir Arslan, Oskar Angerås, Nina Johnston, Ann-Charlotte Weiderman, Stellan Bandh, Ole Hansen, Hans Larnefeldt, Dawid Kusiak, Carl-Johan Lindholm, Anders Hedman, David Erlinge, Dan Curiac, Pia Lundman, Roberto Zucconi-Mazzini, Layth Aladellie, Jens Jensen, Jan Verwerft, Mathias Vrolix, Dirk Faes, Harry Striekwold, Peter Sinnaeve, Patrick Timmermans, Antoine Guedes, Marc Delforge, Jan Nimmegeers, Francis Stammen, Ian Buysschaert, Etienne Hoffer, Geert Hollanders, Geert Vervoort, Patrick Coussement, Stefan de Maeseneire, Luc Janssens, Stein A Gravdal, Knut Risberg, Lars Gullestad, Ola D Hofseth, Dennis Nilsen, Knut T Lappegård, Christian van den Heuvel, Charlotte Gibbs, Alamdar Khusrawi, Satish Arora, Tadeusz Tomala, Thorbjørn Kjærnli, Jan Berg-Johansen, Robert Hagemeier, Gunnar Skjelvan, David Colquhoun, John Amerena, Claire Morbey, Christopher Hammett, Anthony Dart, Ronald Lehman, Andrew Hamilton, Matthew Worthley, Peter Purnell, Alan Whelan, Richard MacIsaac, Ktut Arya, Sultan Linjawi, Joseph Proietto, Lakshman Prasad, Aldo Rodriguez, Armando Godoy, Victor Rodriguez, Percy Berrospi, Carlos Chavez, Sandra Negron, Javier Heredia, Felix Medina, Helard Manrique, Walter Cabrera, Fernando Cordova, Trinidad Quinteros, Jaime M Haro, Susana Regalado, Javier Guitton, Hugo Arbanil, Michel Pansieri, Eric Decoulx, Pascal Goube, Axel de Labriolle, Jean N Labeque, Gregoire Range, Yves Cottin, Gilles Montalescot, Guillaume Cayla, Nicolas Danchin, Denis Angoulvant, Emile Ferrario, Meyer Elbaz, Olivier Dubreuil, Philippe G Steg, Caroline Fontaine, Emmanuel Sorbets, Hafiz Omer, Shukri Al-Saif, Hussam Al-Faleh, Abdullah Al-Shehri, Halia Alshehri, Rasha Bazari, Pak Hei, Man Ying, Michael Chan, Michelle Wong, Ronald Ma, Shing C Siu, Chiu C Tsang, Maurizio Ferrario, Emilio Assanelli, Michele Senni, Piermarco Piatti, Paolo Calabrò, Stefano Urbinati, Massimo Michisanti, Ferdinando Varbella, Salvatore de Cosmo, Roberto Trevisan, Sandro Bellotti, Giuseppe Di Pasquale, Angelo S Bongo, Massimo Uguccioni, Edoardo Mannucci, Ciro Mauro, Mauro Ragonese, Claudio Fresco, Maurizio Turturo, Rossella Marcucci, Manuel J Lievano Triana, Camilo Arana, Jose Accini, Rodrigo Botero, Marlena Muzyk-Osikowicz, Fredy T Dada, Gregorio S Vallejo, Fernando Manzur, Daniel Isaza, Dora Molina, Juan G Mesa, Alvaro Quintero, Kai Nyman, Jyrki Mäkelä, Jorma Strand, Sakari Nieminen, Jyrki Taurio, Matti Kuusela, Timo Valle, Mikko Pietilä, Sakari Kekki, Timo Strandberg, Marc Klutstein, Gabriel Greenberg, Yoseph Rozenman, Ehud Chorin, Ariel Roguin, Basil Lewis, Amir Bashkin, Edgar Tan, Jose P Prado, Arthur Ferrolino, Noe Babilonia, Benny Barbas, Generoso Matiga, Raul M Coching, Heinz Drexel, Helmut Brath, Christoph Schnack, Ursula Hanusch, Evelyn Fließer-Görzer, Bernhard Paulweber, Christoph Ebenbichler, Rudolf Prager, Kurt Huber, Michael Wolzt, Johann Auer, Rudolf Berger, Gerit-Holger Schernthaner, Gabriela Stanciulescu, Mihai Creteanu, Marilena Spiridon, Viorica Dobreanu, Dragos Vinereanu, Laura C Iosipescu, Octavian Istratoaie, Ioan Coman, Constantin Militaru, Mircea Cinteza, Peter R Sinnaeve, José C Nicolau, José F Kerr Saraiva, Ramón Corbalán, Petr Widimský, Steen D Kristensen, Juha Hartikainen, Harald Darius, Hung F Tse, Robert G Kiss, Prem Pais, Eli Lev, Leonardo de Luca, Gabriel A Ramos López, Frederic Kontny, Noe A Babilonia, Dmitry A Zateyshchikov, Mikhail Ruda, Omer Elamin, František Kovář, Anthony J Dalby, Héctor Bueno, Chern-En Chiang, Alexander Parkhomenko, Tuan Q Nguyen, Maria Leonsson-Zachrisson, Herrada, Anthony, Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Royal Brompton Hospital, McMaster University [Hamilton, Ontario], Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], St. Michael's Hospital, University of Toronto, Service de Pharmacologie médicale = service de pharmacologie - Dosage de médicaments [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Uppsala University Hospital, Uppsala Universitet [Uppsala], AstraZeneca, Tokai University, Uppsala University, Imperial College London, Saint Luke's Mid America Heart Institute, University of Missouri [Kansas City] (UMKC), University of Missouri System, University of New South Wales [Sydney] (UNSW), University of Texas Southwestern Medical Center [Dallas], Stanford University, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université de Montpellier (UM), Bhatt, D, Steg, P, Mehta, S, Leiter, L, Simon, T, Fox, K, Held, C, Andersson, M, Himmelmann, A, Ridderstrale, W, Chen, J, Song, Y, Diaz, R, Goto, S, James, S, Ray, K, Parkhomenko, A, Kosiborod, M, Mcguire, D, Harrington, R, Santos, V, Jain, A, Lendel, I, Russo, M, Haught, W, Bouza, M, Gogia, H, Banerjee, S, Kichura, G, Kantaros, L, Padron, F, Passi, R, Stone, J, Pursley, M, D'Urso, M, Gardner, T, Bennett, J, Nour, K, Saini, S, Zhang, W, Kumbhani, D, Thomas, D, Angiolillo, D, Bertolet, B, Roman-Miranda, A, Black, R, Manshadi, R, Vaca, C, Blanco, A, Napoli, M, Brabham, D, Akyea-Djamson, A, Desai, P, Prasada, S, Khaira, A, Forgosh, L, Lieber, I, Umpierrez, G, Singal, D, Londono, J, Fraser, N, Ruiz, J, Vega, D, Rodriguez, L, Brown, C, Syed, F, Aggarwala, G, Eaves, W, Foster, M, Gupta, D, Avino, D, Asfour, W, Tonnessen, G, Zhao, X, Singh, N, Brockmyre, A, Lepor, N, Shammas, N, Blick, D, Hearne, S, Prodafikas, J, Carell, E, Izzo, M, Karim, A, Zakhary, B, Atieh, M, Leichter, S, Meadows, C, Hotchkiss, D, Abu-Fadel, M, Wiseman, A, Bander, J, Shah, M, Ganim, R, Sopko, K, Khan, M, Lloret, R, Weirick, T, Mehta, R, Thadani, U, Bhargava, A, Moya, J, Staniloae, C, Guerra, Y, Chhabra, A, Kosmicki, D, Shaheen, W, Mohammed, A, Bitters, J, Pattanayak, J, Javier, J, Srivastava, S, Phillips, R, Al-Amin, J, Lillestol, M, Simpson, P, Hazan, L, Amin, A, Shah, G, Korpas, D, Platt, B, Dickert, J, Puente, O, Hiotis, L, Doyle, T, Rajan, R, Meholick, A, Gring, C, Hage-Korban, E, Feldman, R, Colfer, H, Butman, S, Hart, T, Huling, R, Eshaghian, S, Quintana, O, Cheung, D, Handel, F, Rodriguez, M, Suh, D, Gordon, P, Pressman, G, Bauer, M, French, W, Barettella, M, Chatrathi, S, Suresh, D, Goldberg, R, Huth, M, Younis, L, Rahman, A, Mascolo, R, Welch, M, Suneja, R, Smith, S, Shurmur, S, Agaiby, J, Jingo, A, Johnston, J, Beth, M, Vlastaris, A, Kemp, S, Taheri, H, Pereira, E, Deyoung, M, Hawa, Z, Smith, R, Galski, T, Garas, S, Reddy, M, Sharma, S, Hargrove, J, Treasure, C, Emerson, R, Haddad, T, Rohr, K, Levinson, L, Gaona, R, Uretsky, B, Maheshwari, H, Lee, D, Kinnaman, S, Singal, R, Geohas, J, Gigliotti, O, Raisinghani, A, Khurana, C, Hella, B, Kelberman, M, Voyce, S, Singh, S, Lo, E, Singh, P, Goodfellow, R, Fischer, S, Lorraine, R, Turner, T, Shanes, J, Busch, R, Broker, R, Zaniewski, M, Pounds, K, Debs-Perez, G, Ong, S, Frandsen, B, Fullington, D, Jaffrani, N, Khan, A, Lee, M, Pouzar, J, Revtyak, G, Gonzalez, J, Nakhle, S, Murillo, A, Young, D, Makam, S, Syed, M, Woolf, K, Grena, P, Alfata, S, Mahal, S, Hoffman, D, Kizhakekuttu, T, Deering, J, Bhavsar, J, Mikesell, S, Wilson, W, Wilson, V, El, S, Spinale, F, Kannarkat, V, Rao, S, Hanson, L, Bertsch, J, Gonzalez-Ortiz, E, Severino, N, Willis, J, Schock, J, Bakhtari, L, Gazmuri, R, Ansari, S, Hall, J, Mehta, A, Shealy, N, Zarich, S, Singh, D, Vora, K, Andrawis, N, Molter, D, Maron, D, Cardona, J, D'Agostino, R, Arshad, T, Samaan, R, Jones, D, Presser, D, Heath, J, Green, S, Bittar, G, Henry, S, Korn, D, Schmedtje, J, Nadar, V, Graham, B, Labroo, A, Clavijo, L, Roseman, H, Ledesma, G, Rosen, R, Dor, I, Kirby, W, Sutton, J, Eder, F, Iteld, B, Gomez-Cortes, J, Buchbinder, M, Kasper, J, Terrelonge, A, Torres, G, Jagielo, T, Alvarez, J, Handelsman, Y, Guillen, M, Richwine, R, Lewy-Alterbaum, L, Corder, C, Arvind, M, Bolshoun, D, Mikhail, M, Minton, S, Alvarado, O, Abbott, J, Cauthen, B, Welter, R, Mintz, R, Cox, J, Quick, A, Weiss, M, Dy, J, Zebrack, J, Gandelman, G, Hegde, V, Silver, M, Degregorio, M, Lawson, W, Paa, C, Bortnick, A, Krolick, M, Sotolongo, R, Cheirif, J, Kumar, P, Jetty, P, Patel, A, Kruk, M, Kobielusz-Gembala, I, Rewerska, B, Madrzejewski, A, Milewski, K, Cygler, J, Petryka-Mazurkiewicz, J, Jastrzebski, W, Korecki, J, Fil, W, Prokopczuk, J, Bochenek, A, Wujkowski, M, Witek, R, Konczakowski, P, Miekus, P, Szczasny, M, Musial, W, Cymerman, K, Lampart, J, Mikosinski, J, Szynal, S, Fares, I, Opolski, G, Mazur, S, Wozakowska-Kaplon, B, Bijata-Bronisz, R, Wierucki, L, Losa, B, Drelich, G, Konieczny, M, Starczewski, P, Pawlowicz, L, Jesionowski, P, Jurowiecki, J, Gniot, J, Czyzycki, M, Stania, K, Kucharczyk-Bauman, I, Busz-Papiez, B, Karczmarczyk, A, Sudnik, W, Koszek, A, Kolodziej, P, Skwarna, B, Jaramillo, N, Jankowski, M, Czochra, W, Kinasz, L, Miklaszewicz, B, Stasinska, T, Pluta, W, Basiak, M, Rusicka, T, Niedbal-Yahfouf, I, Popenda, G, Korzeniak, R, Mirek, A, Mariankowski, R, Wojnowski, L, Korol, M, Baszak, J, Podolec, P, Piesiewicz, W, Zurakowski, A, Luengas, C, Skura, M, Pilecki, P, Majchrzak, P, Krzyzagorska, E, Drozd, M, Kaczmarek, B, Sliwinska, T, Zelazowska, K, Sztembis, R, Landa, K, Matyszczak-Toniak, L, Strojek, K, Piepiorka, M, Malinowski, R, Gorska, M, Stolarczyk-Sowa, E, Romanowski, L, Zinka, E, Reszka, Z, Skierkowska, J, Uzunow, A, Laskowska-Derlaga, E, Puntus, E, Kosmacheva, E, Koziolova, N, Pavlov, P, Supryadkina, T, Didenko, Y, Kopylov, P, Kazakov, A, Aksentiev, S, Vishneva, E, Repin, A, Smolenskaya, O, Mantserova, O, Khrustalev, O, Privalova, E, Konstantinov, V, Boldueva, S, Ezhov, A, Chernyavsky, A, Kamalov, G, Galyavich, A, Zubeeva, G, Nechaeva, G, Shustov, S, Dzhaiani, N, Treshkur, T, Osokina, N, Panov, A, Shutemova, E, Makukhin, V, Kropotina, T, Tsyba, L, Karpov, Y, Sizova, J, Ballyuzek, M, Tarasov, N, Demchenko, E, Barbarash, O, Moiseev, V, Markov, V, Kuznetsov, V, Viktorova, I, Sergienko, I, Ermoshkina, L, Khasanov, N, Khlevchuk, T, Baglikov, A, Shalaev, S, Zonova, E, Reznik, E, Haisheva, L, Morugova, T, Lomakin, N, Vishnevsky, A, Shvarts, Y, Magnitskaya, O, Mikhailusova, M, Pavlysh, E, Libov, I, Zateyschikova, A, Kostenko, V, Edin, A, Khovaeva, Y, Zakharov, K, Stryuk, R, Khirmanov, V, Kanorskiy, S, Yakushin, S, Barabashkina, A, Li, H, Zhao, Q, Zhang, J, Ma, J, He, Y, Luo, M, Zhang, A, Zhang, N, Chai, Y, Ma, G, Wang, H, Liu, Z, He, L, Song, Z, Dong, X, Tao, L, Li, Z, Su, X, Kong, X, Niu, H, Ge, J, Luo, Z, Huang, W, Peng, D, Yuan, Z, Milanova, M, Tenev, D, Gogov, A, Karageorgiev, D, Kolchev, T, Rusev, N, Georgieva, N, Kondov, R, Rusinov, V, Petrov, I, Stanchev, G, Konteva, M, Dincheva, A, Yaneva, Z, Vatova, R, Ilieva, K, Runev, N, Kolomanov, B, Iliev, N, Tisheva, S, Chompalova, B, Tokmakova, M, Raev, D, Byanov, K, Markov, D, Mihov, L, Mihov, A, Milcheva, N, Minchev, M, Mollov, M, Borisov, B, Tihchev, T, Karakolev, V, Dimov, B, Georgiev, S, Smilov, L, Koo, B, Ahn, T, Hong, S, Yoon, J, Oh, S, Jeong, M, Kim, D, Chang, K, Kim, W, Hahn, J, Cha, K, Lee, J, Choi, S, Nam, C, Chae, I, Park, Y, Tahk, S, Shin, W, Chae, J, Kim, B, Bae, J, Park, W, Rha, S, Choi, Y, Hwang, J, Park, H, Baracioli, L, Guimaraes, F, Vasconcellos, E, Saraiva, J, Pereira, A, Santos, Q, Rossi, P, Maia, L, Madeira, M, Pereira, M, Botelho, R, Reis, G, Eliaschewitz, F, Borges, J, Nascimento, C, Fortes, J, de Souza, W, Pimentel, P, Hissa, M, Franchetti, M, Precoma, D, Ortiz, C, Hernandes, M, Saporito, W, dos Santos, F, Kormann, A, Neuenschwander, F, Dutra, O, Rassi, N, Tanajura, L, Souza, J, Junior, D, Leaes, P, Forte, A, Bonansea, T, Marin, J, Machado, B, Cerqueira, M, Silva, F, Michalaros, Y, Manenti, E, Cercato, C, Figueiredo, E, Liu, M, Wang, Y, Lee, T, Fang, C, Wu, Y, Ueng, K, Sheu, H, Lai, W, Hsieh, I, Chen, Z, Chiang, C, Shyu, K, Hsia, C, Mar, G, Chan, S, Wu, C, Tseng, W, Yeh, H, Wang, J, Hou, C, Sorokina, I, Dolzhenko, M, Horoshko, O, Karpenko, O, Rudenko, L, Vakaliuk, I, Kulyk, A, Levchenko, O, Prokhorov, O, Reshotko, D, Sorokivskyy, M, Velichko, N, Maslovskyi, V, Teliatnikova, Z, Dotsenko, S, Krakhmalova, O, Kraiz, I, Zharinova, V, Bula, L, Kaydashev, I, Molodtsov, V, Rasputina, L, Pidlisna, V, Lysunets, O, Kravchenko, A, Glushko, L, Khomazyuk, T, Svyshchenko, Y, Parkhomenko, O, Mankovsky, B, Abrahamovych, O, Yagensky, A, Stanislavchuk, M, Vasilyeva, L, Sokolova, L, Sychov, O, Tseluyko, V, Kyrychenko, I, Rishko, M, Furkalo, S, Gallo, R, Bertrand, O, Constance, C, Sussex, B, Zadra, R, Kouz, S, Chehayeb, R, Pandey, A, Dion, D, Bailey, G, Hill, L, Ramanathan, K, Dorsch, M, Nanji, A, Babapulle, M, Montigny, M, Gosselin, G, Dehghani, P, Rupka, D, Le May, M, Pichette, F, St-Maurice, F, Teefy, P, Mansour, S, Kassam, S, Cheung, S, Siega, A, O'Keefe, D, Sabbah, E, Bell, A, Chouinard, G, Wong, B, Miller, M, Gaudet, D, Lachance, P, Bata, I, Petrella, R, Gossard, D, Dumas, R, Ing, D, Boyrazian, H, Bessoudo, R, Huynh, T, Hart, R, Belle-Isle, J, Shukla, D, Kelly, A, Mazza, G, Cha, J, Henein, S, Frechette, A, Vizel, S, Liutkus, J, O'Mahony, M, Halperin, F, Kooy, J, Graham, J, Bailey, A, Wojcik, R, Wilderman, I, Turi, T, Motyovszki, A, Merkely, B, Kiss, R, Kiraly, C, Andrassy, P, Sarszegi, Z, Fulop, T, Zilahi, Z, Edes, I, Papp, A, Muller, G, Czigany, A, Zolyomi, S, Koranyi, L, Takacs, J, Juhasz, F, Benczur, B, Kancz, S, Foldi, A, Nagy, A, Bakai, J, Greschik, I, Puski, L, Nagy, L, Kirschner, R, Kuchar, R, Hajek, P, Busak, L, Michalik, D, Matyasek, I, Marusincova, I, Kucera, D, Jerabek, O, Honkova, M, Dedek, V, Rihacek, I, Kos, P, Slaby, J, Machkova, M, Zidkova, E, Elbl, L, Grunfeldova, H, Carda, J, Mrozek, V, Maly, J, Milkovic, R, Malecha, J, Skalicka, H, Oral, I, Krcova, E, Lisa, L, Belohlavek, J, Miklik, R, Cermak, O, Bednarova, J, Peroutka, Z, Spinar, J, Wilke, A, Appel, K, Taggeselle, J, Forster, A, Toursarkissian, N, Schmidt, E, Bott, J, Al-Zoebi, A, Hennig, D, Schon, N, Sauter, J, Simonis, G, Nischik, R, Rieker, W, Schenkenberger, I, Behnke, T, Klausmann, G, Jeserich, M, Trenk, D, Weigmann, I, Reuter, H, Rummel, R, von Munchhausen, C, von Engelhardt, C, Horibe, E, Shibasaki, T, Sato, T, Kakuta, T, Michishita, I, Tan, M, Ishiki, R, Aoyama, T, Higashiue, S, Niijima, Y, Idogaki, A, Hasegawa, T, Kiyosue, A, Tomobuchi, Y, Kawamitsu, K, Kawasaki, S, Hata, Y, Fukui, K, Seki, K, Takenaka, T, Abe, M, Utsu, N, Oono, A, Mitsuo, K, Sueyoshi, A, Hirohata, A, Tsujimoto, M, Ueda, O, Takase, S, Suzuki, M, Sakuragi, S, Yamamoto, F, Fujimoto, N, Kakinoki, S, Sugiura, T, Sugino, H, Nakamura, T, Kadokami, T, Uehara, H, Ono, M, Yokoya, K, Koike, A, Komatsu, S, Sonoda, M, Ueno, H, Doi, T, Takagi, Y, Fujimoto, K, Eki, Y, Okubo, M, Sasaki, K, van Eck, M, Ronner, E, The, S, van de Wal, R, Nierop, P, de Nooijer, C, Werner, H, Westendorp, I, van der Zwaan, C, Crijns, H, Cornel, J, Strikwerda, S, Bos, R, de Melker, E, Kuijper, A, Louwerenburg, H, Plomp, J, Dantzig, J, Prins, F, van Kesteren, H, Willems, F, Amoroso, G, Carnero, G, Duronto, E, Besada, D, Chacon, C, Zangroniz, P, Solis, S, Liberman, A, Sernia, V, Alvarisqueta, A, Maffei, L, Vilamajo, O, Garcia, C, Sicer, M, Muntaner, J, Bordonava, A, Albisu, J, Zanini, A, Rista, L, Hominal, M, Estrada, J, Prado, A, Gosparini, D, Schiavi, B, Castillo, A, Martinez, G, Lopez, V, Rosas, E, Lopez, G, Cantu, E, de los Rios Ibarra, M, Padilla, F, Carrasco, J, Carrillo, L, Garcia, J, Askar, A, Salinas, C, Gamba, M, Sanchez, C, Cantu, A, Sanchez, R, Madrigal, J, Urbano, R, Romo, A, Gonzalez Juanatey, J, Racugno, P, Fillat, A, de la Torre Hernandez, J, Pelaez, J, Cortada, J, Pavia, P, Navarro, M, Asenjo, R, Diaz, F, Peligero, E, Manterola, F, Ortiz, A, Mediavilla Garcia, J, Ortuno, F, Vera, T, Gonzalez, A, Vinas, J, Fernandez Portales, F, Mayordomo, P, Ojeda, F, Dominguez, A, Gonzalez, R, Guerrero, D, Ruiz Nodar, J, Marimon, X, Margaez, J, Aguilera, R, Diaz Fernandez, J, Zamorano Gomez, J, Gonzalez, V, del Blanco, B, Perez, I, Moreno, M, Ereno, A, Garcia Lledo, J, Prieto, J, Villablanca, A, Raffo, C, Pincetti, C, Conejeros, C, Roman, O, Varleta, P, Goldberg, C, Sandoval, J, Arriagada, G, Corbalan, R, Leon, L, Potthoff, S, Cobos, J, Figueroa, C, Makotoko, E, Fourie, N, Burgess, L, Nortje, H, Theron, R, Pillai, P, Ranjith, N, Trokis, J, Pillay, S, Reddy, J, Nunkoo, T, Kapp, C, Urbach, D, Distiller, L, Horak, A, van Zyl, L, Coetzee, K, Punt, Z, Bayat, J, Dawood, S, Mitha, I, Padayachee, T, Hoosen, F, Dalby, A, Prabhavathi, Gowdaiah, P, Mehta, V, Chag, M, Gadkari, M, Ramamurthee, K, Das, A, Sawhney, J, Sathe, P, Adhyapak, S, Nguyen, T, Pham, V, Do, H, Nguyen, A, Nguyen, H, Truong, B, Jamil-Copley, S, Lang, C, Pell, A, Zaman, A, Storey, R, Swanson, N, Sharman, D, Braganza, D, Hammond, P, Moriarty, A, Bain, S, Pye, M, Sharp, A, Blagden, M, Randeva, H, Myhill, T, Viswanathan, G, Keeling, P, Clifford, P, Saxena, M, Lyons, K, Mcmurray, J, Jaafar, F, Murphy, C, Cartwright, S, Abouglila, K, Antalik, L, Krajci, P, Urban, M, Fazekas, F, Pella, D, Koleny, D, Vykoukalova, T, Macek, V, Vinanska, D, Jamriskova, L, Such, S, Fulop, P, Farsky, S, Bugan, V, Strbova, J, Micko, K, Palka Jr, J, Sivak, V, Kristensen, D, Refsgaard, J, Holmvang, L, Dixen, U, Nielsen, H, Egstrup, K, Jensen, L, Sykulski, R, Rasmussen, O, Andries, A, Luckow, A, Nielsen, G, Sorensen, T, Wongvipaporn, C, Chamnarnphol, N, Srimahachota, S, Sansanayudh, N, Kuanprasert, S, Tresukosol, D, Sookananchai, B, Kanadasi, M, Ozcan, T, Kucuk, M, Ongen, Z, Okuyan, E, Arat, A, Acikel, S, Yalcin, A, Guray, U, Ceyhan, C, Ozer, N, Arslan, S, Angeras, O, Johnston, N, Weiderman, A, Bandh, S, Hansen, O, Larnefeldt, H, Kusiak, D, Lindholm, C, Hedman, A, Erlinge, D, Curiac, D, Lundman, P, Zucconi-Mazzini, R, Aladellie, L, Jensen, J, Verwerft, J, Vrolix, M, Faes, D, Striekwold, H, Sinnaeve, P, Timmermans, P, Guedes, A, Delforge, M, Nimmegeers, J, Stammen, F, Buysschaert, I, Hoffer, E, Hollanders, G, Vervoort, G, Coussement, P, de Maeseneire, S, Janssens, L, Gravdal, S, Risberg, K, Gullestad, L, Hofseth, O, Nilsen, D, Lappegard, K, van den Heuvel, C, Gibbs, C, Khusrawi, A, Arora, S, Tomala, T, Kjaernli, T, Berg-Johansen, J, Hagemeier, R, Skjelvan, G, Colquhoun, D, Amerena, J, Morbey, C, Hammett, C, Dart, A, Lehman, R, Hamilton, A, Worthley, M, Purnell, P, Whelan, A, Macisaac, R, Arya, K, Linjawi, S, Proietto, J, Prasad, L, Rodriguez, A, Godoy, A, Rodriguez, V, Berrospi, P, Chavez, C, Negron, S, Heredia, J, Medina, F, Manrique, H, Cabrera, W, Cordova, F, Quinteros, T, Haro, J, Regalado, S, Guitton, J, Arbanil, H, Pansieri, M, Decoulx, E, Goube, P, de Labriolle, A, Labeque, J, Range, G, Cottin, Y, Montalescot, G, Cayla, G, Danchin, N, Angoulvant, D, Ferrario, E, Elbaz, M, Dubreuil, O, Fontaine, C, Sorbets, E, Omer, H, Al-Saif, S, Al-Faleh, H, Al-Shehri, A, El-Amin, O, Alshehri, H, Bazari, R, Hei, P, Ying, M, Chan, M, Wong, M, Ma, R, Siu, S, Tsang, C, Ferrario, M, Assanelli, E, Senni, M, Piatti, P, Calabro, P, Urbinati, S, Michisanti, M, Varbella, F, de Cosmo, S, Trevisan, R, Bellotti, S, Di Pasquale, G, Bongo, A, Uguccioni, M, Mannucci, E, Mauro, C, Ragonese, M, Fresco, C, Turturo, M, Marcucci, R, Lievano Triana, M, Arana, C, Accini, J, Botero, R, Muzyk-Osikowicz, M, Dada, F, Vallejo, G, Manzur, F, Isaza, D, Molina, D, Mesa, J, Quintero, A, Nyman, K, Makela, J, Strand, J, Nieminen, S, Taurio, J, Kuusela, M, Valle, T, Pietila, M, Kekki, S, Strandberg, T, Klutstein, M, Greenberg, G, Rozenman, Y, Chorin, E, Roguin, A, Lewis, B, Bashkin, A, Tan, E, Prado, J, Ferrolino, A, Babilonia, N, Barbas, B, Matiga, G, Coching, R, Drexel, H, Brath, H, Schnack, C, Hanusch, U, Fliesser-Gorzer, E, Paulweber, B, Ebenbichler, C, Prager, R, Huber, K, Wolzt, M, Auer, J, Berger, R, Schernthaner, G, Stanciulescu, G, Creteanu, M, Spiridon, M, Dobreanu, V, Vinereanu, D, Iosipescu, L, Istratoaie, O, Coman, I, Militaru, C, Cinteza, M, Nicolau, J, Kerr Saraiva, J, Widimsky, P, Kristensen, S, Hartikainen, J, Darius, H, Tse, H, Pais, P, Lev, E, de Luca, L, Ramos Lopez, G, Kontny, F, Zateyshchikov, D, Ruda, M, Elamin, O, Kovar, F, Bueno, H, Leonsson-Zachrisson, M, Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pharmacologie - Dosage de médicaments [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Royal Brompton and Harefield NHS Foundation Trust-Imperial College London
Subjects: Male, Platelet Aggregation Inhibitors/therapeutic use, THEMIS Steering Committee and Investigators, medicine.medical_treatment, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], 030204 cardiovascular system & hematology, Coronary Angiography, Stroke/epidemiology, Coronary artery disease, DOUBLE-BLIND, 0302 clinical medicine, Hemorrhage/chemically induced, acetylsalicylic acid, antidiabetic agent, placebo, ticagrelor, Secondary Prevention, Medicine, 030212 general & internal medicine, Myocardial infarction, Coronary Artery Bypass, Cardiovascular Diseases/mortality, 11 Medical and Health Sciences, OUTCOMES, Aspirin, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, General Medicine, Middle Aged, Clopidogrel, 3. Good health, Ticagrelor/therapeutic use, DRUG-ELUTING STENTS, CLOPIDOGREL, Cardiology, PLATELET INHIBITION, Drug Therapy, Combination, Female, Life Sciences & Biomedicine, Ticagrelor, TIMI, medicine.drug, Coronary Artery Disease/complications, medicine.medical_specialty, Hypoglycemic Agents/therapeutic use, POOLED ANALYSIS, 03 medical and health sciences, Medicine, General & Internal, Percutaneous Coronary Intervention, Double-Blind Method, General & Internal Medicine, Internal medicine, Myocardial Infarction/epidemiology, Humans, Aged, Science & Technology, ANTIPLATELET THERAPY, business.industry, Diabetes Mellitus, Type 2/complications, ELEVATION MYOCARDIAL-INFARCTION, RIVAROXABAN, Percutaneous coronary intervention, medicine.disease, ASPIRIN, Coronary Stenosis/diagnostic imaging, Aspirin/therapeutic use, Conventional PCI, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Contains fulltext : 215333.pdf (Publisher’s version ) (Closed access) BACKGROUND: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. METHODS: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). FINDINGS: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3.3 years (IQR 2.8-3.8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7.3%] of 5558 vs 480 [8.6%] of 5596; HR 0.85 [95% CI 0.74-0.97], p=0.013). The same effect was not observed in patients without PCI (p=0.76, pinteraction=0.16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3.1%] with ticagrelor vs 183 (3.3%) with placebo; HR 0.96 [95% CI 0.78-1.18], p=0.68), as well as all-cause death (282 [5.1%] vs 323 [5.8%]; 0.88 [0.75-1.03], p=0.11). TIMI major bleeding occurred in 111 (2.0%) of 5536 patients receiving ticagrelor and 62 (1.1%) of 5564 patients receiving placebo (HR 2.03 [95% CI 1.48-2.76], p
Published: 2019
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26. Severe Fasting Hypoglycemia Mimicking Insulinoma in Three Patients With Insulin Autoimmune Syndrome

Author: Sara Cassibba, Alessandro Rossini, Roberto Trevisan, Cristiana Scaranna, Anna Maria Corsi, and Rosalia Bellante
Subjects: medicine.medical_specialty, Diabetes Case Reports, Fasting Hypoglycemia, business.industry, Endocrinology, Diabetes and Metabolism, medicine.disease, Diabetes Mellitus and Glucose Metabolism, Endocrinology, Internal medicine, Insulin autoimmune syndrome, medicine, business, Insulinoma, AcademicSubjects/MED00250
Abstract: Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia characterized by the presence of insulin autoantibodies (IAA) in patients without prior exposure to exogenous insulin. Differential diagnosis with other causes of hypoglycemia may be complex. We report three IAS cases with severe fasting hypoglycemia, referred to our Unit for the diagnostic workup of insulinoma. All three patients (two women and a man, age 66, 44, and 50 years) had history of severe fasting hypoglycemia leading to loss of consciousness along with weight gain. Both insulin and C-peptide were high, but their levels varied greatly among patients, ranging from 24 to 1500 μU/ml (n.v.
Published: 2021

27. Non-albuminuric renal impairment is a strong predictor of mortality in individuals with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicentre study

Author: Franco Cavalot, Antonio Nicolucci, Giuseppe Pugliese, Olga Lamacchia, Cecilia Fondelli, Giuseppe Penno, Anna Solini, Marco Scardapane, Roberto Trevisan, Enzo Bonora, Monica Vedovato, Emanuela Orsi, Penno, G, Solini, A, Orsi, E, Bonora, E, Fondelli, C, Trevisan, R, Vedovato, M, Cavalot, F, Lamacchia, O, Scardapane, M, Nicolucci, A, and Pugliese, G
Subjects: Male, Endocrinology, Diabetes and Metabolism, Disease, Type 2 diabetes, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Gastroenterology, Type 2 diabete, 0302 clinical medicine, Endocrinology, Diabetic Nephropathies, Renal Insufficiency, Prospective Studies, Chronic, Prospective cohort study, Albuminuria, All-cause mortality, Diabetic kidney disease, Glomerular filtration rate, Aged, Diabetes Mellitus, Type 2, Female, Glomerular Filtration Rate, Humans, Middle Aged, Proportional Hazards Models, Renal Insufficiency, Chronic, Confounding, Diabetes and Metabolism, Internal Medicine, medicine.symptom, Type 2, Retinopathy, Human, medicine.medical_specialty, Renal function, 030209 endocrinology & metabolism, 03 medical and health sciences, Internal medicine, Diabetes Mellitus, medicine, MED/13 - ENDOCRINOLOGIA, Proportional hazards model, business.industry, medicine.disease, Prospective Studie, Diabetic Nephropathie, Proportional Hazards Model, business
Abstract: Aims/hypothesis: Non-albuminuric renal impairment has become the prevailing diabetic kidney disease (DKD) phenotype in individuals with type 2 diabetes and an estimated GFR (eGFR)
Published: 2018

28. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Author: Adrian F Hernandez, Jennifer B Green, Salim Janmohamed, Ralph B D'Agostino, Christopher B Granger, Nigel P Jones, Lawrence A Leiter, Anne E Rosenberg, Kristina N Sigmon, Matthew C Somerville, Karl M Thorpe, John J V McMurray, Stefano Del Prato, John J.V. McMurray, Ralph B. D'Agostino, Christopher B. Granger, Adrian F. Hernandez, Lawrence A. Leiter, Robert M Califf, Rury Holman, David DeMets, Matthew Riddle, Shaun Goodman, Darren McGuire, Karen Alexander, Adam Devore, Chiara Melloni, Chetan Patel, David Kong, Gerald Bloomfield, Matthew Roe, Pierluigi Tricoci, Rob Harrison, Renato Lopes, Robin Mathews, Rajendra Mehta, William Schuyler Jones, Sreekanth Vemulapalli, Thomas Povsic, Zubin Eapen, Keith Dombrowski, Brad Kolls, Dedrick Jordan, Andrew Ambrosy, Stephen Greene, Aditya Mandawat, Jay Shavadia, Lauren Cooper, Abhinav Sharma, Patricia Guimaraes, Daniel Friedman, Matt Wilson, Patricia Endsley, Tracy Gentry, Jeannie Collier, Kathleen Perez, Kourtnei James, Jennifer Roush, Connie Pope, Christina Howell, Megan Johnson, Matt Bailey, Joanna Cole, Teresa Akers, Beth Vandyne, Betsy Thomas, Jenny Rich, Susan Bartone, Gail Beaulieu, Kim Brown, Tuan Chau, Tamra Christian, Rebecca Coker, Deb Greene, Trevorlyn Haddock, Wendy Jenkins, Ghazala Haque, Marsha Marquess, Jean Pesarchick, Renee Rethaford, Allegra Stone, Firas Al Kawas, Michelle Anderson, Robert Enns, Isaac Sinay, Chantal Mathieu, Victor Yordanov, Irene Hramiak, Martin Haluzik, Søren Galatius, Bruno Guerci, Michael Nauck, Ilias Migdalis, Choon Beng Kathryn Tan, Gyozo Kocsis, Andrea Giaccari, Moon Kyu Lee, Ernesto German Cardona Muñoz, Jan Cornel, Kare Birkeland, Miguel Pinto, Louie Tirador, Martyna Olesinska-Mader, Marina Shestakova, Larry Distiller, Jose Lopez-Sendon, Bjorn Eliasson, Chern-En Chiang, Suphot Srimahachota, Boris Mankovsky, M Angelyn Bethel, Kathleen Dungan, Mikhail Kosiborod, Andres Alvarisqueta, Jorge Baldovino, Diego Besada, Pedro Calella, Maria Cecilia Cantero, Patricia Castaño, Alejandro Chertkoff, Jesus Cuadrado, Luis De Loredo, Andrea Dominguez, Maria Vanesa Español, Hernan Finkelstein, Gustavo Frechtel, Jose Fretes, Natalia Garrido Santos, Joaquin Gonzalez, Marcos Litvak, Juan Loureyro, Laura Maffei, Natacha Maldonado, Diego Mohr Gasparini, Silvia Orio, Federico Perez Manghi, Nelson Rodriguez Papini, Jorgelina Sala, Pablo Schygiel, Georgina Sposetti, Maria Ulla, Fernando Verra, Silvina Zabalua, Cesar Zaidman, Laurent Crenier, Corinne Debroye, Francis Duyck, André Scheen, Luc Van Gaal, Chris Vercammen, Velichka Damyanova, Stefan Dimitrov, Snezhina Kovacheva, Lachezar Lozanov, Viktor Margaritov, Rositsa Mihaylova-Shumkova, Antoaneta Nikolaeva, Zhasmina Stoyanova, Ronald Akhras, Yves Beaudry, Jacques Bedard, Joseph Berlingieri, Raja Chehayeb, Stephen Cheung, James Conway, Jean Cusson, Anthony Della Siega, Richard Dumas, Peter Dzongowski, Murdo Ferguson, Daniel Gaudet, Francois Grondin, Anil Gupta, Milan Gupta, Frank Halperin, Pierre-Alain Houle, Michael Jones, Simon Kouz, Christopher Kovacs, Daniel Landry, Eva Lonn, William O'Mahony, Sean Peterson, Dennis Reich, Alan Rosenbloom, Francois St-Maurice, Barna Tugwell, Saul Vizel, Vincent Woo, Tomas Brychta, Vladimir Cech, Eva Dvorakova, Tomas Edelsberger, Katarina Halciakova, Jarmila Krizova, Jiri Lastuvka, Martin Piperek, Vera Prymkova, Lea Raclavska, Elena Silhova, Robin Urbanek, Jan Vrkoc, Ulla Andersen, Jens Brønnum-Schou, Jens Hove, Jan Skov Jensen, Lars Kober, Ole Peter Kristiansen, Per Lund, Thomas Melchior, Ole Nyvad, Morten Schou, Alain Boye, Didier Cadinot, Didier Gouet, Patrick Henry, Laurence Kessler, Jean-Daniel Lalau, Catherine Petit, Jean-Francois Thuan, Christel Voinot, Julien Vouillarmet, Christoph Axthelm, Dirk Berger, Tasso Bieler, Andreas Birkenfeld, Jochen Bott, Klaus Busch, Karel Caca, Julia Chevts, Torsten Donaubauer, Rudolf Erlinger, Klaus Funke, Josef Grosskopf, Andreas Hagenow, Monika Hamann, Manfred Hartard, Peter Heymer, Wolfgang Huppertz, Gabriele Illies, Stephan Jacob, Thomas Jung, Gerd Kahrmann, Petra Kast, Monika Kellerer, Hans-Peter Kempe, Andrei Khariouzov, Gerhard Klausmann, Christiane Klein, Uwe Kleinecke-Pohl, Klaus Kleinertz, Thorsten Koch, Christine Kosch, Babette Lorra, Joerg Luedemann, Matthias Luttermann, Stephan Maxeiner, Karsten Milek, Andrea Moelle, Gerhard Neumann, Ruth Nischik, Edith Oehrig-Pohl, Georg Plassmann, Lars Pohlmeier, Felix Proepper, Stefan Regner, Werner Rieker, Ludger Rose, Holger Samer, Joachim Sauter, Frank Schaper, Clemens Schiffer, Juergen Schmidt, Bernd-M. Scholz, Joerg Schulze, Alexander Segner, Jochen Seufert, Helena Sigal, Joerg Steindorf, Juergen Stockhausen, Petra Stuebler, Heidrun Taeschner, Dietrich Tews, Diethelm Tschoepe, Karl Wilhelm, Helga Zeller-Stefan, Iakovos Avramidis, Stavros Bousboulas, Magdalini Bristianou, Georgios Dimitriadis, Moses Elisaf, Kalliopi Kotsa, Andreas Melidonis, Asimina Mitrakou, Emmanouil Pagkalos, Nikolaos Papanas, Angelos Pappas, Christos Sampanis, Nikolaos Tentolouris, Apostolos Tsapas, Glykeria Tzatzagou, Risa Ozaki, Csaba Hajdú, Eleonóra Harcsa, Laszlo Konyves, János Mucsi, Zsolt Pauker, Gizella Petró, Zsolt Plés, Katalin Revesz, Vangel Sándor, Viktor Vass, Angelo Avogaro, Massimo Boemi, Riccardo Bonadonna, Agostino Consoli, Salvatore De Cosmo, Paolo Di Bartolo, Francesco Dotta, Simona Frontoni, Marianna Galetta, Alessandra Gambineri, Carmine Gazzaruso, Francesco Giorgino, Davide Lauro, Emanuela Orsi, Giuseppe Paolisso, Gabriele Perriello, Piermarco Piatti, Antonio Pontiroli, Paola Ponzani, Angela Albarosa Rivellese, Giorgio Sesti, Giancarlo Tonolo, Roberto Trevisan, Chul Woo Ahn, Sei-Hyun Baik, Bong-Soo Cha, Choon-Hee Chung, Hak Chul Jang, Chong-Jin Kim, Hye Soon Kim, In Joo Kim, Eun Young Lee, Hyoung Woo Lee, Kwan-Woo Lee, Keon-Woong Moon, June Namgung, Kyong Soo Park, Soon Jib Yoo, Jaemyung Yu, Edmundo-Alfredo Bayram Llamas, Jose-Luis Cervantes-Escárcega, Luis Fernando Flota-Cervera, José Gerardo González-González, Sara Pascoe-Gonzalez, Emilia Susana Pelayo-Orozco, Santiago-Paulino Ramirez-Diaz, Arturo Saldana-Mendoza, Carlos Sánchez Jerjes-Díaz, Jose Juan Torres-Colores, Maricela Vidrio-Velázquez, Juan Villagordoa-Mesa, Hugo Peter Beijerbacht, Reginald G.E.J. Groutars, Boudewijn A Hoek, Pieter A.M. Hoogslag, Adriaan Kooy, Johannes A. Kragten, Aloysius G. Lieverse, Hendrik P. Swart, Eric P. Viergever, Jørn Ahlqvist, John Cooper, Hanne Gulseth, Gaute Guttormsen, Cecilie Wium, Hugo Arbañil, Jorge Calderon, Luis Camacho, Augusto Dextre Espinoza, Elizabeth Garrido, Alejandro Luna, Helard Manrique, Frederick Massucco Revoredo, Rolando Vargas Gonzales, Luis Zapata Rincon, Carlos Zubiate, Geraldine Ebo, Ellen Morales-Palomares, Malgorzata Arciszewska, Marek Banach, Renata Bijata-Bronisz, Tadeusz Derezinski, Waldemar Gadzinski, Jacek Gajek, Katarzyna Klodawska, Ewa Krzyzagorska, Andrzej Madej, Pawel Miekus, Jaroslaw Opiela, Piotr Romanczuk, Anna Siegel, Ewa Skokowska, Andrzej Stankiewicz, Teresa Stasinska, Iwona Trznadel-Morawska, Robert Witek, Sergey Aksentyev, Irina Bondar, Irina Demidova, Alexander Dreval, Olga Ershova, Gagik Galstyan, Alla Garganeeva, Nadezhda Izmozherova, Victoria Karetnikova, Marina Kharakhulakh, Aleksandr Khokhlov, Zhanna Kobalava, Olga Koshelskaya, Elena Kosmacheva, Vladimir Kostin, Natalia Koziolova, Anatoly Kuzin, Victor Lesnov, Tatyana Lysenko, Valentin Markov, Alexander Mayorov, Sergey Moiseev, Svetlana Myasoedova, Nina Petunina, Andrey Rebrov, Ludmila Ruyatkina, Julia Samoylova, Olga Sazonova, Natalia Shilkina, Nadezhda Sokolova, Olga Vasilevskaya, Nelli Verbovaya, Elena Vishneva, Sergey Vorobyev, Natalya Vorokhobina, Olga Zanozina, Elena Zhdanova, Tatyana Zykova, Lesley Burgess, Kathleen Coetzee, Saleem Dawood, Landman Lombard, Ellen Makotoko, Rajendran Moodley, Wessels Oosthuysen, Mohamed Sarvan, Carlos Calvo Gómez, Isidoro Cano Rodríguez, Almudena Castro Conde, Angel Cequier Fillat, Guillem Cuatrecasas Cambra, Fernando de Álvaro Moreno, Luis De Teresa Parreño, Javier Delgado Lista, José Ramón Domínguez Escribano, Santiago Durán García, Javier Elvira González, José María Fernández Rodríguez, Alberto Goday Arno, Ricardo Gomez Huelgas, José Ramón González Juanatey, Antonio Hernandez Mijares, Víctor Alfonso Jiménez Díaz, Esteban Jodar Gimeno, Tomás Lucas Morante, Monica Marazuela, Nieves Martell Claros, Didac Mauricio Puente, Elena Mena Ribas, Juan Francisco Merino Torres, Pedro Mezquita Raya, Andreu Nubiola Calonge, Xavier Ordoñez Sánchez, Jose Maria Pascual Izuel, Verónica Perea Castilla, Antonio Pérez Pérez, Isabel Perez Soto, Miguel Quesada Charneco, Angustias Quesada Simón, Josep Redón Mas, Antonia Rego Iraeta, Maria Rodriguez Alvarez, Irene Rodríguez Rodríguez, José Sabán Ruiz, Alfonso Soto González, Francisco Tinahones Madueno, Carlos Trescoli Serrano, Angels Ulied Armiñana, Erasmus Bachus, Katarina Berndtsson Blom, Ken Eliasson, Pekka Koskinen, Hans Larnefeldt, Cornelia Lif-Tiberg, Carina Linderfalk, Gustav Lund, Pia Lundman, Linda Moris, Åke Olsson, Staffan Salmonsson, Johan Sanmartin Berglund, Folke Sjöberg, Stefan Söderberg, Ingemar Torstensson, Jung-Fu Chen, Kai Jen Tien, Shih-Ting Tseng, Shih-Te Tu, Chih-Yuan Wang, Ji-Hung Wang, Arintaya Phrommintikul, Sukit Yamwong, Woravut Jintapakorn, Pisit Hutayanon, Nakarin Sansanayudh, Larysa Bazhan, Ivan Fushtey, Mariya Grachova, Vitaliy Katerenchuk, Vadym Korpachev, Nonna Kravchun, Oleksandr Larin, Galyna Mykhalchyshyn, Halyna Myshanych, Olga Oleksyk, Valeriia Orlenko, Nataliia Pashkovska, Nataliia Pertseva, Olena Petrosyan, Ivan Smirnov, Maryna Vlasenko, Tetiana Zlova, Myint Aye, Arun Baksi, Mathangi Balasubramani, Ronnie Beboso, Mark Blagden, Charles Bundy, Tobias Cookson, Allan Copland, Alistair Emslie-Smith, Fiona Green, Anthony Gunstone, Basil Issa, Ewart Jackson-Voyzey, Andrew Johnson, Malcolm Maclean, John McKnight, Solomon Muzulu, Ian O'Connell, Babatunde Oyesile, Catherine Patterson, Ewan Pearson, Sam Philip, Paul Smith, Usha Sukumaran, Jalal Abbas, Gaurav Aggarwala, Faiq Akhter, James Andersen, Moise Anglade, Georges Argoud, Mehrdad Ariani, Reswan Ashdji, Ladan Bakhtari, Subhash Banerjee, Andrew Bartlett, Howard Baum, Harold Bays, Richard Beasley, Renata Belfort de Aguiar, Sabrina Benjamin, Ravi Bhagwat, Anuj Bhargava, Bruce Bode, Christina Bratcher, Toby Briskin, Andrew Brockmyre, Raymond Broughton, Judith Brown, Madhusudan Budhraja, Kevin Cannon, Jewell Carr, Harold Cathcart, Arvind Cavale, Louis Chaykin, Deanna Cheung, Richard Childress, Allan Cohen, Jonathan Condit, Erin Cooksey, George Mitchell Cornett, Ira Dauber, William Davila, Luis De Armas, Julius Dean, Robert Detweiler, Ernesto Diaz, Michael Di Giovanna, Isaac Dor, Waymon Drummond, Donald Eagerton, John Earl, Charles Eaton, Howard Ellison, Neil Farris, Thomas Fiel, Anthony Firek, Brian First, Les Forgosh, William French, Winston Gandy, Ronald Garcia, Santosh Gill, Murray Gordon, Michael Guice, Siva Gummadi, Jonathan Hackenyos, Kristen Hairston, Lenita Hanson, Lindsay Harrison, Israel Hartman, John Heitner, Srini Hejeebu, Paul Hermany, Carlos Hernandez-Cassis, Horacio Hidalgo, Alexander Higgins, Hassan Ibrahim, Shahram Jacobs, David Johnson, Parag Joshi, Steven Kaster, Daniel Kellum, Christopher Kim, Ellen Kim, William Kirby, Albert Knouse, Steven Kulback, Mariananda Kumar, Tulsidas Kuruvanka, Ajay Labroo, William Lasswell, John Lentz, Thomas Lenzmeier, David Lewis, Zhaoping Li, Michael Lillestol, Raymond Little, Richard Lorraine, Cecilia McKeown-Biagas, Robert McNeill, Anand Mehta, Alan Miller, Joseph Moran, Emily Morawski, Venkatesh Nadar, Thomas O'Connor, Alberto Odio, Reginald Parker, Rajesh Patel, Lawrence Phillips, George Raad, Aref Rahman, Marina Raikhel, Ajit Raisinghani, Raj Rajan, Neda Rasouli, Frank Rauzi, Kathryn Rohr, Hal Roseman, Sergio Rovner, Fadi Saba, Richard Sachson, Alex Schabauer, Ricky Schneider, Timothy Schuchard, John Sensenbrenner, Yshay Shlesinger, Narendra Singh, Kanagaratnam Sivalingam, Larry Stonesifer, Daniel Storey, David Suh, Mohammed Tahir, Anjanette Tan, Marilyn Tan, Alain Taylon, Maitreya Thakkar, Devjit Tripathy, Gabriel Uwaifo, Amarnath Vedere, Chandra Venugopal, Anthony Vo, Michelle Welch, James Welker, Alexander White, John Willis, Alan Wynne, Shahram Yazdani, Anne Rosenberg, Lauren Price, Kristina Sigmon, Yuliya Lokhngina, Weibing Xing, Robert Overton, Murray Stewart, Janet Stead, Alistair Lindsay, Vickas Patel, Jorge Ross, Joseph Soffer, Shruti Daga, Margaret Sowell, Prashant Patel, Louisa Garvey, Jessica Ackert, Sybil Abraham, Mary Beth Sabol, Desma Altobelli, JuYoung Ha, Mangesh Kulkarni, Matthew Somerville, Drusilla Noronha, Ed Casson, Eddie Zang, Chamandeep Sandhu, Rakesh Kumar, David Chen, Lin Taft, Rajivkumar Patel, June Ye, Jennifer Shannon, Tim Wilson, Charleen Babi, Diane Miller, Karl Thorpe, Rachael Russell, Georgina Bull, Belinda Hereghty, Eva Fernandez-Salazar, Troy Longley, Jill Donaldson, Marie Jarosz, Karen Murphy, Patricia Adams, Peter Smith, Rachel James, Jackie Richards, Sangeeta Sedani, Denise Althouse, David Watson, Jamie Lorimer, Steven Lauder, Ron Schultheis, Terese Womer, Ella Wraight, Wenyan Li, Emma Price-Olsen, Anthony Watson, Aoife Kelly, Patricia McLaughlin, John Fleming, Jessica Schubert, Debra Schleiden, Tara Harris, Rahul Prakash, Jody Breneman, Sameer Deshpande, Aarti Saswadkar, Aditi Kumari, Aditi Shitut, Amruta Raorane, Anisha Karmalkar, Ankita Mhambrey, Archana Bhosale, Ashok Vaphare, Ashwini P Patil, Chaitali Khandelwal, Fayaz Shaik, Madhumitha Nadar, Mounika Karka, Neha Kadgaonkar, Nikita Gupta, Nutan Aher, Omkar Potnis, Pallavi Naicker, Rakesh Shinde, Richa Sharma, Rupali Godse, Sheetal Solanki, Shruti Sahu, Snehal Dumbre, Somesh Kumar, Suradnya Patil, Trisha Mandal, Hernandez, Adrian F, Green, Jennifer B, Janmohamed, Salim, D'Agostino, Ralph B, Granger, Christopher B, Jones, Nigel P, Leiter, Lawrence A, Rosenberg, Anne E, Sigmon, Kristina N, Somerville, Matthew C, Thorpe, Karl M, Mcmurray, John J V, Del Prato, Stefano, Mcmurray, John J. V., D'Agostino, Ralph B., Granger, Christopher B., Hernandez, Adrian F., Leiter, Lawrence A., Califf, Robert M, Holman, Rury, Demets, David, Riddle, Matthew, Goodman, Shaun, Mcguire, Darren, Alexander, Karen, Devore, Adam, Melloni, Chiara, Patel, Chetan, Kong, David, Bloomfield, Gerald, Roe, Matthew, Tricoci, Pierluigi, Harrison, Rob, Lopes, Renato, Mathews, Robin, Mehta, Rajendra, Schuyler Jones, William, Vemulapalli, Sreekanth, Povsic, Thoma, Eapen, Zubin, Dombrowski, Keith, Kolls, Brad, Jordan, Dedrick, Ambrosy, Andrew, Greene, Stephen, Mandawat, Aditya, Shavadia, Jay, Cooper, Lauren, Sharma, Abhinav, Guimaraes, Patricia, Friedman, Daniel, Wilson, Matt, Endsley, Patricia, Gentry, Tracy, Collier, Jeannie, Perez, Kathleen, James, Kourtnei, Roush, Jennifer, Pope, Connie, Howell, Christina, Johnson, Megan, Bailey, Matt, Cole, Joanna, Akers, Teresa, Vandyne, Beth, Thomas, Betsy, Rich, Jenny, Bartone, Susan, Beaulieu, Gail, Brown, Kim, Chau, Tuan, Christian, Tamra, Coker, Rebecca, Greene, Deb, Haddock, Trevorlyn, Jenkins, Wendy, Haque, Ghazala, Marquess, Marsha, Pesarchick, Jean, Rethaford, Renee, Stone, Allegra, Al Kawas, Fira, Anderson, Michelle, Enns, Robert, Sinay, Isaac, Mathieu, Chantal, Yordanov, Victor, Hramiak, Irene, Haluzik, Martin, Galatius, Søren, Guerci, Bruno, Nauck, Michael, Migdalis, Ilia, Tan, Choon Beng Kathryn, Kocsis, Gyozo, Giaccari, Andrea, Lee, Moon Kyu, Muñoz, Ernesto German Cardona, Cornel, Jan, Birkeland, Kare, Pinto, Miguel, Tirador, Louie, Olesinska-Mader, Martyna, Shestakova, Marina, Distiller, Larry, Lopez-Sendon, Jose, Eliasson, Bjorn, Chiang, Chern-En, Srimahachota, Suphot, Mankovsky, Bori, Bethel, M Angelyn, Dungan, Kathleen, Kosiborod, Mikhail, Alvarisqueta, Andre, Baldovino, Jorge, Besada, Diego, Calella, Pedro, Cantero, Maria Cecilia, Castaño, Patricia, Chertkoff, Alejandro, Cuadrado, Jesu, De Loredo, Lui, Dominguez, Andrea, Español, Maria Vanesa, Finkelstein, Hernan, Frechtel, Gustavo, Fretes, Jose, Garrido Santos, Natalia, Gonzalez, Joaquin, Litvak, Marco, Loureyro, Juan, Maffei, Laura, Maldonado, Natacha, Mohr Gasparini, Diego, Orio, Silvia, Perez Manghi, Federico, Rodriguez Papini, Nelson, Sala, Jorgelina, Schygiel, Pablo, Sposetti, Georgina, Ulla, Maria, Verra, Fernando, Zabalua, Silvina, Zaidman, Cesar, Crenier, Laurent, Debroye, Corinne, Duyck, Franci, Scheen, André, Van Gaal, Luc, Vercammen, Chri, Damyanova, Velichka, Dimitrov, Stefan, Kovacheva, Snezhina, Lozanov, Lachezar, Margaritov, Viktor, Mihaylova-Shumkova, Rositsa, Nikolaeva, Antoaneta, Stoyanova, Zhasmina, Akhras, Ronald, Beaudry, Yve, Bedard, Jacque, Berlingieri, Joseph, Chehayeb, Raja, Cheung, Stephen, Conway, Jame, Cusson, Jean, Della Siega, Anthony, Dumas, Richard, Dzongowski, Peter, Ferguson, Murdo, Gaudet, Daniel, Grondin, Francoi, Gupta, Anil, Gupta, Milan, Halperin, Frank, Houle, Pierre-Alain, Jones, Michael, Kouz, Simon, Kovacs, Christopher, Landry, Daniel, Lonn, Eva, O'Mahony, William, Peterson, Sean, Reich, Denni, Rosenbloom, Alan, St-Maurice, Francoi, Tugwell, Barna, Vizel, Saul, Woo, Vincent, Brychta, Toma, Cech, Vladimir, Dvorakova, Eva, Edelsberger, Toma, Halciakova, Katarina, Krizova, Jarmila, Lastuvka, Jiri, Piperek, Martin, Prymkova, Vera, Raclavska, Lea, Silhova, Elena, Urbanek, Robin, Vrkoc, Jan, Andersen, Ulla, Brønnum-Schou, Jen, Hove, Jen, Jensen, Jan Skov, Kober, Lar, Kristiansen, Ole Peter, Lund, Per, Melchior, Thoma, Nyvad, Ole, Schou, Morten, Boye, Alain, Cadinot, Didier, Gouet, Didier, Henry, Patrick, Kessler, Laurence, Lalau, Jean-Daniel, Petit, Catherine, Thuan, Jean-Francoi, Voinot, Christel, Vouillarmet, Julien, Axthelm, Christoph, Berger, Dirk, Bieler, Tasso, Birkenfeld, Andrea, Bott, Jochen, Busch, Klau, Caca, Karel, Chevts, Julia, Donaubauer, Torsten, Erlinger, Rudolf, Funke, Klau, Grosskopf, Josef, Hagenow, Andrea, Hamann, Monika, Hartard, Manfred, Heymer, Peter, Huppertz, Wolfgang, Illies, Gabriele, Jacob, Stephan, Jung, Thoma, Kahrmann, Gerd, Kast, Petra, Kellerer, Monika, Kempe, Hans-Peter, Khariouzov, Andrei, Klausmann, Gerhard, Klein, Christiane, Kleinecke-Pohl, Uwe, Kleinertz, Klau, Koch, Thorsten, Kosch, Christine, Lorra, Babette, Luedemann, Joerg, Luttermann, Matthia, Maxeiner, Stephan, Milek, Karsten, Moelle, Andrea, Neumann, Gerhard, Nischik, Ruth, Oehrig-Pohl, Edith, Plassmann, Georg, Pohlmeier, Lar, Proepper, Felix, Regner, Stefan, Rieker, Werner, Rose, Ludger, Samer, Holger, Sauter, Joachim, Schaper, Frank, Schiffer, Clemen, Schmidt, Juergen, Scholz, Bernd-M., Schulze, Joerg, Segner, Alexander, Seufert, Jochen, Sigal, Helena, Steindorf, Joerg, Stockhausen, Juergen, Stuebler, Petra, Taeschner, Heidrun, Tews, Dietrich, Tschoepe, Diethelm, Wilhelm, Karl, Zeller-Stefan, Helga, Avramidis, Iakovo, Bousboulas, Stavro, Bristianou, Magdalini, Dimitriadis, Georgio, Elisaf, Mose, Kotsa, Kalliopi, Melidonis, Andrea, Mitrakou, Asimina, Pagkalos, Emmanouil, Papanas, Nikolao, Pappas, Angelo, Sampanis, Christo, Tentolouris, Nikolao, Tsapas, Apostolo, Tzatzagou, Glykeria, Ozaki, Risa, Hajdú, Csaba, Harcsa, Eleonóra, Konyves, Laszlo, Mucsi, Jáno, Pauker, Zsolt, Petró, Gizella, Plés, Zsolt, Revesz, Katalin, Sándor, Vangel, Vass, Viktor, Avogaro, Angelo, Boemi, Massimo, Bonadonna, Riccardo, Consoli, Agostino, De Cosmo, Salvatore, Di Bartolo, Paolo, Dotta, Francesco, Frontoni, Simona, Galetta, Marianna, Gambineri, Alessandra, Gazzaruso, Carmine, Giorgino, Francesco, Lauro, Davide, Orsi, Emanuela, Paolisso, Giuseppe, Perriello, Gabriele, Piatti, Piermarco, Pontiroli, Antonio, Ponzani, Paola, Rivellese, Angela Albarosa, Sesti, Giorgio, Tonolo, Giancarlo, Trevisan, Roberto, Ahn, Chul Woo, Baik, Sei-Hyun, Cha, Bong-Soo, Chung, Choon-Hee, Jang, Hak Chul, Kim, Chong-Jin, Kim, Hye Soon, Kim, In Joo, Lee, Eun Young, Lee, Hyoung Woo, Lee, Kwan-Woo, Moon, Keon-Woong, Namgung, June, Park, Kyong Soo, Yoo, Soon Jib, Yu, Jaemyung, Llamas, Edmundo-Alfredo Bayram, Cervantes-Escárcega, Jose-Lui, Flota-Cervera, Luis Fernando, González-González, José Gerardo, Pascoe-Gonzalez, Sara, Pelayo-Orozco, Emilia Susana, Ramirez-Diaz, Santiago-Paulino, Saldana-Mendoza, Arturo, Jerjes-Díaz, Carlos Sánchez, Torres-Colores, Jose Juan, Vidrio-Velázquez, Maricela, Villagordoa-Mesa, Juan, Beijerbacht, Hugo Peter, Groutars, Reginald G. E. J., Hoek, Boudewijn A, Hoogslag, Pieter A. M., Kooy, Adriaan, Kragten, Johannes A., Lieverse, Aloysius G., Swart, Hendrik P., Viergever, Eric P., Ahlqvist, Jørn, Cooper, John, Gulseth, Hanne, Guttormsen, Gaute, Wium, Cecilie, Arbañil, Hugo, Calderon, Jorge, Camacho, Lui, Espinoza, Augusto Dextre, Garrido, Elizabeth, Luna, Alejandro, Manrique, Helard, Revoredo, Frederick Massucco, Gonzales, Rolando Varga, Rincon, Luis Zapata, Zubiate, Carlo, Ebo, Geraldine, Morales-Palomares, Ellen, Arciszewska, Malgorzata, Banach, Marek, Bijata-Bronisz, Renata, Derezinski, Tadeusz, Gadzinski, Waldemar, Gajek, Jacek, Klodawska, Katarzyna, Krzyzagorska, Ewa, Madej, Andrzej, Miekus, Pawel, Opiela, Jaroslaw, Romanczuk, Piotr, Siegel, Anna, Skokowska, Ewa, Stankiewicz, Andrzej, Stasinska, Teresa, Trznadel-Morawska, Iwona, Witek, Robert, Aksentyev, Sergey, Bondar, Irina, Demidova, Irina, Dreval, Alexander, Ershova, Olga, Galstyan, Gagik, Garganeeva, Alla, Izmozherova, Nadezhda, Karetnikova, Victoria, Kharakhulakh, Marina, Khokhlov, Aleksandr, Kobalava, Zhanna, Koshelskaya, Olga, Kosmacheva, Elena, Kostin, Vladimir, Koziolova, Natalia, Kuzin, Anatoly, Lesnov, Victor, Lysenko, Tatyana, Markov, Valentin, Mayorov, Alexander, Moiseev, Sergey, Myasoedova, Svetlana, Petunina, Nina, Rebrov, Andrey, Ruyatkina, Ludmila, Samoylova, Julia, Sazonova, Olga, Shilkina, Natalia, Sokolova, Nadezhda, Vasilevskaya, Olga, Verbovaya, Nelli, Vishneva, Elena, Vorobyev, Sergey, Vorokhobina, Natalya, Zanozina, Olga, Zhdanova, Elena, Zykova, Tatyana, Burgess, Lesley, Coetzee, Kathleen, Dawood, Saleem, Lombard, Landman, Makotoko, Ellen, Moodley, Rajendran, Oosthuysen, Wessel, Sarvan, Mohamed, Calvo Gómez, Carlo, Cano Rodríguez, Isidoro, Castro Conde, Almudena, Cequier Fillat, Angel, Cuatrecasas Cambra, Guillem, de Álvaro Moreno, Fernando, De Teresa Parreño, Lui, Delgado Lista, Javier, Domínguez Escribano, José Ramón, Durán García, Santiago, Elvira González, Javier, Fernández Rodríguez, José María, Goday Arno, Alberto, Gomez Huelgas, Ricardo, González Juanatey, José Ramón, Hernandez Mijares, Antonio, Jiménez Díaz, Víctor Alfonso, Jodar Gimeno, Esteban, Lucas Morante, Tomá, Marazuela, Monica, Martell Claros, Nieve, Mauricio Puente, Didac, Mena Ribas, Elena, Merino Torres, Juan Francisco, Mezquita Raya, Pedro, Nubiola Calonge, Andreu, Ordoñez Sánchez, Xavier, Pascual Izuel, Jose Maria, Perea Castilla, Verónica, Pérez Pérez, Antonio, Perez Soto, Isabel, Quesada Charneco, Miguel, Quesada Simón, Angustia, Redón Mas, Josep, Rego Iraeta, Antonia, Rodriguez Alvarez, Maria, Rodríguez Rodríguez, Irene, Sabán Ruiz, José, Soto González, Alfonso, Tinahones Madueno, Francisco, Trescoli Serrano, Carlo, Ulied Armiñana, Angel, Bachus, Erasmu, Berndtsson Blom, Katarina, Eliasson, Ken, Koskinen, Pekka, Larnefeldt, Han, Lif-Tiberg, Cornelia, Linderfalk, Carina, Lund, Gustav, Lundman, Pia, Moris, Linda, Olsson, Åke, Salmonsson, Staffan, Sanmartin Berglund, Johan, Sjöberg, Folke, Söderberg, Stefan, Torstensson, Ingemar, Chen, Jung-Fu, Tien, Kai Jen, Tseng, Shih-Ting, Tu, Shih-Te, Wang, Chih-Yuan, Wang, Ji-Hung, Phrommintikul, Arintaya, Yamwong, Sukit, Jintapakorn, Woravut, Hutayanon, Pisit, Sansanayudh, Nakarin, Bazhan, Larysa, Fushtey, Ivan, Grachova, Mariya, Katerenchuk, Vitaliy, Korpachev, Vadym, Kravchun, Nonna, Larin, Oleksandr, Mykhalchyshyn, Galyna, Myshanych, Halyna, Oleksyk, Olga, Orlenko, Valeriia, Pashkovska, Nataliia, Pertseva, Nataliia, Petrosyan, Olena, Smirnov, Ivan, Vlasenko, Maryna, Zlova, Tetiana, Aye, Myint, Baksi, Arun, Balasubramani, Mathangi, Beboso, Ronnie, Blagden, Mark, Bundy, Charle, Cookson, Tobia, Copland, Allan, Emslie-Smith, Alistair, Green, Fiona, Gunstone, Anthony, Issa, Basil, Jackson-Voyzey, Ewart, Johnson, Andrew, Maclean, Malcolm, Mcknight, John, Muzulu, Solomon, O'Connell, Ian, Oyesile, Babatunde, Patterson, Catherine, Pearson, Ewan, Philip, Sam, Smith, Paul, Sukumaran, Usha, Abbas, Jalal, Aggarwala, Gaurav, Akhter, Faiq, Andersen, Jame, Anglade, Moise, Argoud, George, Ariani, Mehrdad, Ashdji, Reswan, Bakhtari, Ladan, Banerjee, Subhash, Bartlett, Andrew, Baum, Howard, Bays, Harold, Beasley, Richard, Belfort de Aguiar, Renata, Benjamin, Sabrina, Bhagwat, Ravi, Bhargava, Anuj, Bode, Bruce, Bratcher, Christina, Briskin, Toby, Brockmyre, Andrew, Broughton, Raymond, Brown, Judith, Budhraja, Madhusudan, Cannon, Kevin, Carr, Jewell, Cathcart, Harold, Cavale, Arvind, Chaykin, Loui, Cheung, Deanna, Childress, Richard, Cohen, Allan, Condit, Jonathan, Cooksey, Erin, Cornett, George Mitchell, Dauber, Ira, Davila, William, De Armas, Lui, Dean, Juliu, Detweiler, Robert, Diaz, Ernesto, Di Giovanna, Michael, Dor, Isaac, Drummond, Waymon, Eagerton, Donald, Earl, John, Eaton, Charle, Ellison, Howard, Farris, Neil, Fiel, Thoma, Firek, Anthony, First, Brian, Forgosh, Le, French, William, Gandy, Winston, Garcia, Ronald, Gill, Santosh, Gordon, Murray, Guice, Michael, Gummadi, Siva, Hackenyos, Jonathan, Hairston, Kristen, Hanson, Lenita, Harrison, Lindsay, Hartman, Israel, Heitner, John, Hejeebu, Srini, Hermany, Paul, Hernandez-Cassis, Carlo, Hidalgo, Horacio, Higgins, Alexander, Ibrahim, Hassan, Jacobs, Shahram, Johnson, David, Joshi, Parag, Kaster, Steven, Kellum, Daniel, Kim, Christopher, Kim, Ellen, Kirby, William, Knouse, Albert, Kulback, Steven, Kumar, Mariananda, Kuruvanka, Tulsida, Labroo, Ajay, Lasswell, William, Lentz, John, Lenzmeier, Thoma, Lewis, David, Li, Zhaoping, Lillestol, Michael, Little, Raymond, Lorraine, Richard, McKeown-Biagas, Cecilia, Mcneill, Robert, Mehta, Anand, Miller, Alan, Moran, Joseph, Morawski, Emily, Nadar, Venkatesh, O'Connor, Thoma, Odio, Alberto, Parker, Reginald, Patel, Rajesh, Phillips, Lawrence, Raad, George, Rahman, Aref, Raikhel, Marina, Raisinghani, Ajit, Rajan, Raj, Rasouli, Neda, Rauzi, Frank, Rohr, Kathryn, Roseman, Hal, Rovner, Sergio, Saba, Fadi, Sachson, Richard, Schabauer, Alex, Schneider, Ricky, Schuchard, Timothy, Sensenbrenner, John, Shlesinger, Yshay, Singh, Narendra, Sivalingam, Kanagaratnam, Stonesifer, Larry, Storey, Daniel, Suh, David, Tahir, Mohammed, Tan, Anjanette, Tan, Marilyn, Taylon, Alain, Thakkar, Maitreya, Tripathy, Devjit, Uwaifo, Gabriel, Vedere, Amarnath, Venugopal, Chandra, Vo, Anthony, Welch, Michelle, Welker, Jame, White, Alexander, Willis, John, Wynne, Alan, Yazdani, Shahram, Rosenberg, Anne, Price, Lauren, Sigmon, Kristina, Lokhngina, Yuliya, Xing, Weibing, Overton, Robert, Stewart, Murray, Stead, Janet, Lindsay, Alistair, Patel, Vicka, Ross, Jorge, Soffer, Joseph, Daga, Shruti, Sowell, Margaret, Patel, Prashant, Garvey, Louisa, Ackert, Jessica, Abraham, Sybil, Sabol, Mary Beth, Altobelli, Desma, Ha, Juyoung, Kulkarni, Mangesh, Somerville, Matthew, Noronha, Drusilla, Casson, Ed, Zang, Eddie, Sandhu, Chamandeep, Kumar, Rakesh, Chen, David, Taft, Lin, Patel, Rajivkumar, Ye, June, Shannon, Jennifer, Wilson, Tim, Babi, Charleen, Miller, Diane, Thorpe, Karl, Russell, Rachael, Bull, Georgina, Hereghty, Belinda, Fernandez-Salazar, Eva, Longley, Troy, Donaldson, Jill, Jarosz, Marie, Murphy, Karen, Adams, Patricia, Smith, Peter, James, Rachel, Richards, Jackie, Sedani, Sangeeta, Althouse, Denise, Watson, David, Lorimer, Jamie, Lauder, Steven, Schultheis, Ron, Womer, Terese, Wraight, Ella, Li, Wenyan, Price-Olsen, Emma, Watson, Anthony, Kelly, Aoife, Mclaughlin, Patricia, Fleming, John, Schubert, Jessica, Schleiden, Debra, Harris, Tara, Prakash, Rahul, Breneman, Jody, Deshpande, Sameer, Saswadkar, Aarti, Kumari, Aditi, Shitut, Aditi, Raorane, Amruta, Karmalkar, Anisha, Mhambrey, Ankita, Bhosale, Archana, Vaphare, Ashok, Patil, Ashwini P, Khandelwal, Chaitali, Shaik, Fayaz, Nadar, Madhumitha, Karka, Mounika, Kadgaonkar, Neha, Gupta, Nikita, Aher, Nutan, Potnis, Omkar, Naicker, Pallavi, Shinde, Rakesh, Sharma, Richa, Godse, Rupali, Solanki, Sheetal, Sahu, Shruti, Dumbre, Snehal, Kumar, Somesh, Patil, Suradnya, Mandal, Trisha, McMurray, John J V, McMurray, John J.V., DeMets, David, McGuire, Darren, Groutars, Reginald G.E.J., Hoogslag, Pieter A.M., McKnight, John, McNeill, Robert, Ha, JuYoung, McLaughlin, Patricia, Hernandez, A. F., Green, J. B., Janmohamed, S., D'Agostino, R. B., Granger, C. B., Jones, N. P., Leiter, L. A., Rosenberg, A. E., Sigmon, K. N., Somerville, M. C., Thorpe, K. M., Mcmurray, J. J. V., Del Prato, S., Califf, R. M., Holman, R., Demets, D., Riddle, M., Goodman, S., Mcguire, D., Alexander, K., Devore, A., Melloni, C., Patel, C., Kong, D., Bloomfield, G., Roe, M., Tricoci, P., Harrison, R., Lopes, R., Mathews, R., Mehta, R., Schuyler Jones, W., Vemulapalli, S., Povsic, T., Eapen, Z., Dombrowski, K., Kolls, B., Jordan, D., Ambrosy, A., Greene, S., Mandawat, A., Shavadia, J., Cooper, L., Sharma, A., Guimaraes, P., Friedman, D., Wilson, M., Endsley, P., Gentry, T., Collier, J., Perez, K., James, K., Roush, J., Pope, C., Howell, C., Johnson, M., Bailey, M., Cole, J., Akers, T., Vandyne, B., Thomas, B., Rich, J., Bartone, S., Beaulieu, G., Brown, K., Chau, T., Christian, T., Coker, R., Greene, D., Haddock, T., Jenkins, W., Haque, G., Marquess, M., Pesarchick, J., Rethaford, R., Stone, A., Al Kawas, F., Anderson, M., Enns, R., Sinay, I., Mathieu, C., Yordanov, V., Hramiak, I., Haluzik, M., Galatius, S., Guerci, B., Nauck, M., Migdalis, I., Tan, C. B. K., Kocsis, G., Giaccari, A., Lee, M. K., Munoz, E. G. C., Cornel, J., Birkeland, K., Pinto, M., Tirador, L., Olesinska-Mader, M., Shestakova, M., Distiller, L., Lopez-Sendon, J., Eliasson, B., Chiang, C. -E., Srimahachota, S., Mankovsky, B., Bethel, M. A., Dungan, K., Kosiborod, M., Alvarisqueta, A., Baldovino, J., Besada, D., Calella, P., Cantero, M. C., Castano, P., Chertkoff, A., Cuadrado, J., De Loredo, L., Dominguez, A., Espanol, M. 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Z., Zubiate, C., Ebo, G., Morales-Palomares, E., Arciszewska, M., Banach, M., Bijata-Bronisz, R., Derezinski, T., Gadzinski, W., Gajek, J., Klodawska, K., Krzyzagorska, E., Madej, A., Miekus, P., Opiela, J., Romanczuk, P., Siegel, A., Skokowska, E., Stankiewicz, A., Stasinska, T., Trznadel-Morawska, I., Witek, R., Aksentyev, S., Bondar, I., Demidova, I., Dreval, A., Ershova, O., Galstyan, G., Garganeeva, A., Izmozherova, N., Karetnikova, V., Kharakhulakh, M., Khokhlov, A., Kobalava, Z., Koshelskaya, O., Kosmacheva, E., Kostin, V., Koziolova, N., Kuzin, A., Lesnov, V., Lysenko, T., Markov, V., Mayorov, A., Moiseev, S., Myasoedova, S., Petunina, N., Rebrov, A., Ruyatkina, L., Samoylova, J., Sazonova, O., Shilkina, N., Sokolova, N., Vasilevskaya, O., Verbovaya, N., Vishneva, E., Vorobyev, S., Vorokhobina, N., Zanozina, O., Zhdanova, E., Zykova, T., Burgess, L., Coetzee, K., Dawood, S., Lombard, L., Makotoko, E., Moodley, R., Oosthuysen, W., Sarvan, M., Calvo Gomez, C., Cano Rodriguez, I., Castro Conde, A., Cequier Fillat, A., Cuatrecasas Cambra, G., de Alvaro Moreno, F., De Teresa Parreno, L., Delgado Lista, J., Dominguez Escribano, J. 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B., Altobelli, D., Ha, J., Kulkarni, M., Noronha, D., Casson, E., Zang, E., Sandhu, C., Kumar, R., Chen, D., Taft, L., Ye, J., Shannon, J., Wilson, T., Babi, C., Miller, D., Russell, R., Bull, G., Hereghty, B., Fernandez-Salazar, E., Longley, T., Donaldson, J., Jarosz, M., Murphy, K., Adams, P., James, R., Richards, J., Sedani, S., Althouse, D., Watson, D., Lorimer, J., Lauder, S., Schultheis, R., Womer, T., Wraight, E., Li, W., Price-Olsen, E., Watson, A., Kelly, A., Mclaughlin, P., Fleming, J., Schubert, J., Schleiden, D., Harris, T., Prakash, R., Breneman, J., Deshpande, S., Saswadkar, A., Kumari, A., Shitut, A., Raorane, A., Karmalkar, A., Mhambrey, A., Bhosale, A., Vaphare, A., Patil, A. 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Banach, M, Bijata-Bronisz, R, Derezinski, T, Gadzinski, W, Gajek, J, Klodawska, K, Krzyzagorska, E, Madej, A, Miekus, P, Opiela, J, Romanczuk, P, Siegel, A, Skokowska, E, Stankiewicz, A, Stasinska, T, Trznadel-Morawska, I, Witek, R, Aksentyev, S, Bondar, I, Demidova, I, Dreval, A, Ershova, O, Galstyan, G, Garganeeva, A, Izmozherova, N, Karetnikova, V, Kharakhulakh, M, Khokhlov, A, Kobalava, Z, Koshelskaya, O, Kosmacheva, E, Kostin, V, Koziolova, N, Kuzin, A, Lesnov, V, Lysenko, T, Markov, V, Mayorov, A, Moiseev, S, Myasoedova, S, Petunina, N, Rebrov, A, Ruyatkina, L, Samoylova, J, Sazonova, O, Shilkina, N, Sokolova, N, Vasilevskaya, O, Verbovaya, N, Vishneva, E, Vorobyev, S, Vorokhobina, N, Zanozina, O, Zhdanova, E, Zykova, T, Burgess, L, Coetzee, K, Dawood, S, Lombard, L, Makotoko, E, Moodley, R, Oosthuysen, W, Sarvan, M, Calvo Gomez, C, Cano Rodriguez, I, Castro Conde, A, Cequier Fillat, A, Cuatrecasas Cambra, G, de Alvaro Moreno, F, De Teresa Parreno, L, Delgado Lista, J, Dominguez Escribano, J, Duran Garcia, S, Elvira Gonzalez, J, Fernandez Rodriguez, J, Goday Arno, A, Gomez Huelgas, R, Gonzalez Juanatey, J, Hernandez Mijares, A, Jimenez Diaz, V, Jodar Gimeno, E, Lucas Morante, T, Marazuela, M, Martell Claros, N, Mauricio Puente, D, Mena Ribas, E, Merino Torres, J, Mezquita Raya, P, Nubiola Calonge, A, Ordonez Sanchez, X, Pascual Izuel, J, Perea Castilla, V, Perez Perez, A, Perez Soto, I, Quesada Charneco, M, Quesada Simon, A, Redon Mas, J, Rego Iraeta, A, Rodriguez Alvarez, M, Rodriguez Rodriguez, I, Saban Ruiz, J, Soto Gonzalez, A, Tinahones Madueno, F, Trescoli Serrano, C, Ulied Arminana, A, Bachus, E, Berndtsson Blom, K, Eliasson, K, Koskinen, P, Larnefeldt, H, Lif-Tiberg, C, Linderfalk, C, Lund, G, Lundman, P, Moris, L, Olsson, A, Salmonsson, S, Sanmartin Berglund, J, Sjoberg, F, Soderberg, S, Torstensson, I, Chen, J, Tien, K, Tseng, S, Tu, S, Wang, C, Wang, J, Phrommintikul, A, Yamwong, S, Jintapakorn, W, Hutayanon, P, Sansanayudh, N, Bazhan, L, Fushtey, I, Grachova, M, Katerenchuk, V, Korpachev, V, Kravchun, N, Larin, O, Mykhalchyshyn, G, Myshanych, H, Oleksyk, O, Orlenko, V, Pashkovska, N, Pertseva, N, Petrosyan, O, Smirnov, I, Vlasenko, M, Zlova, T, Aye, M, Baksi, A, Balasubramani, M, Beboso, R, Blagden, M, Bundy, C, Cookson, T, Copland, A, Emslie-Smith, A, Green, F, Gunstone, A, Issa, B, Jackson-Voyzey, E, Johnson, A, Maclean, M, Mcknight, J, Muzulu, S, O'Connell, I, Oyesile, B, Patterson, C, Pearson, E, Philip, S, Smith, P, Sukumaran, U, Abbas, J, Aggarwala, G, Akhter, F, Andersen, J, Anglade, M, Argoud, G, Ariani, M, Ashdji, R, Bakhtari, L, Banerjee, S, Bartlett, A, Baum, H, Bays, H, Beasley, R, Belfort de Aguiar, R, Benjamin, S, Bhagwat, R, Bhargava, A, Bode, B, Bratcher, C, Briskin, T, Brockmyre, A, Broughton, R, Brown, J, Budhraja, M, Cannon, K, Carr, J, Cathcart, H, Cavale, A, Chaykin, L, Cheung, D, Childress, R, Cohen, A, Condit, J, Cooksey, E, Cornett, G, Dauber, I, Davila, W, De Armas, L, Dean, J, Detweiler, R, Diaz, E, Di Giovanna, M, Dor, I, Drummond, W, Eagerton, D, Earl, J, Eaton, C, Ellison, H, Farris, N, Fiel, T, Firek, A, First, B, Forgosh, L, French, W, Gandy, W, Garcia, R, Gill, S, Gordon, M, Guice, M, Gummadi, S, Hackenyos, J, Hairston, K, Hanson, L, Harrison, L, Hartman, I, Heitner, J, Hejeebu, S, Hermany, P, Hernandez-Cassis, C, Hidalgo, H, Higgins, A, Ibrahim, H, Jacobs, S, Johnson, D, Joshi, P, Kaster, S, Kellum, D, Kim, E, Kirby, W, Knouse, A, Kulback, S, Kumar, M, Kuruvanka, T, Labroo, A, Lasswell, W, Lentz, J, Lenzmeier, T, Lewis, D, Li, Z, Lillestol, M, Little, R, Lorraine, R, McKeown-Biagas, C, Mcneill, R, Mehta, A, Miller, A, Moran, J, Morawski, E, Nadar, V, O'Connor, T, Odio, A, Parker, R, Patel, R, Phillips, L, Raad, G, Rahman, A, Raikhel, M, Raisinghani, A, Rajan, R, Rasouli, N, Rauzi, F, Rohr, K, Roseman, H, Rovner, S, Saba, F, Sachson, R, Schabauer, A, Schneider, R, Schuchard, T, Sensenbrenner, J, Shlesinger, Y, Singh, N, Sivalingam, K, Stonesifer, L, Storey, D, Suh, D, Tahir, M, Tan, A, Tan, M, Taylon, A, Thakkar, M, Tripathy, D, Uwaifo, G, Vedere, A, Venugopal, C, Vo, A, Welch, M, Welker, J, White, A, Willis, J, Wynne, A, Yazdani, S, Price, L, Lokhngina, Y, Xing, W, Overton, R, Stewart, M, Stead, J, Lindsay, A, Patel, V, Ross, J, Soffer, J, Daga, S, Sowell, M, Patel, P, Garvey, L, Ackert, J, Abraham, S, Sabol, M, Altobelli, D, Ha, J, Kulkarni, M, Noronha, D, Casson, E, Zang, E, Sandhu, C, Kumar, R, Chen, D, Taft, L, Ye, J, Shannon, J, Wilson, T, Babi, C, Miller, D, Russell, R, Bull, G, Hereghty, B, Fernandez-Salazar, E, Longley, T, Donaldson, J, Jarosz, M, Murphy, K, Adams, P, James, R, Richards, J, Sedani, S, Althouse, D, Watson, D, Lorimer, J, Lauder, S, Schultheis, R, Womer, T, Wraight, E, Li, W, Price-Olsen, E, Watson, A, Kelly, A, Mclaughlin, P, Fleming, J, Schubert, J, Schleiden, D, Harris, T, Prakash, R, Breneman, J, Deshpande, S, Saswadkar, A, Kumari, A, Shitut, A, Raorane, A, Karmalkar, A, Mhambrey, A, Bhosale, A, Vaphare, A, Patil, A, Khandelwal, C, Shaik, F, Nadar, M, Karka, M, Kadgaonkar, N, Gupta, N, Aher, N, Potnis, O, Naicker, P, Shinde, R, Sharma, R, Godse, R, Solanki, S, Sahu, S, Dumbre, S, Kumar, S, Patil, S, and Mandal, T
Subjects: Male, Placebo-controlled study, Myocardial Infarction, alanine aminotransferase, albiglutide, bilirubin, placebo, antidiabetic agent, glucagon like peptide 1, rGLP-1 protein, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Glucagon-Like Peptide 1, Cardiovascular Disease, Medicine(all), education.field_of_study, Subcutaneous, Medicine (all), albigutide, Hazard ratio, General Medicine, Middle Aged, Albiglutide, Stroke, Treatment Outcome, Tolerability, Cardiovascular Diseases, Female, type 2 diabetes, Type 2, Human, Adult, medicine.medical_specialty, Injections, Subcutaneous, Population, 030209 endocrinology & metabolism, Placebo, Injections, Subcutaneou, Drug Administration Schedule, Injections, 03 medical and health sciences, Double-Blind Method, Internal medicine, Diabetes Mellitus, medicine, Humans, Hypoglycemic Agents, education, Aged, Diabetes Mellitus, Type 2, Hypoglycemic Agent, business.industry, Semaglutide, Settore MED/13 - ENDOCRINOLOGIA, Harmony, business
Abstract: Background: \ud Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke.\ud \ud Methods: \ud We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515.\ud \ud Findings: \ud Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p
Published: 2018

29. An adalimumab-induced late-onset immune reconstitution inflammatory syndrome treated with adalimumab

Author: Marco Confalonieri, Nicola Di Meo, Giovanni Damiani, Chiara Torregiani, Roberto Trevisan, Metka Kodric, Giusto Trevisan, Confalonieri, Marco, DI MEO, Nicola, Damiani, Giovanni, Torregiani, Chiara, Trevisan, Roberto, Kodric, Metka, and Trevisan, Giusto
Subjects: business.industry, Late onset, Dermatology, pulmonary tuberculosi, medicine.disease, immune reconstitution inflammatory syndrome, Infectious Diseases, Immune reconstitution inflammatory syndrome, adalimumab, Immunology, medicine, Adalimumab, pulmonary tuberculosis, business, medicine.drug
Abstract: Immune reconstitution inflammatory syndrome (IRIS) is a violent inflammatory response in a patient previously immunosuppressed that discontinued this status and develops a paradoxical clinical deterioration, not explainable with drug-toxicity or opportunistic infection. We describe the case of a 59-year-old non-smoking man, treated for arthropathic psoriasis with adalimumab for 16 months who developed severe IRIS and pulmonary tuberculosis. The reintroduction of the TNF-blocker agent was effective.
Published: 2018

30. Defining the contribution of chronic kidney disease to all-cause mortality in patients with type 2 diabetes. the renal insufficiency and cardiovascular events (RIACE) italian multicenter study

Author: Giuseppe Pugliese, Cecilia Fondelli, Monica Vedovato, Emanuela Orsi, Enzo Bonora, Gianpaolo Zerbini, Franco Cavalot, Luigi Laviola, Roberto Trevisan, Giuseppe Penno, Antonio Nicolucci, Anna Solini, Penno, G, Solini, A, Bonora, E, Orsi, E, Fondelli, C, Zerbini, G, Trevisan, R, Vedovato, M, Cavalot, F, Laviola, L, Nicolucci, A, and Pugliese, G
Subjects: Male, Endocrinology, Diabetes and Metabolism, Longitudinal Studie, Type 2 diabetes, urologic and male genital diseases, Type 2 diabete, Cohort Studies, 0302 clinical medicine, Cause of Death, 80 and over, Prevalence, Diabetic Nephropathies, Renal Insufficiency, 030212 general & internal medicine, Longitudinal Studies, clomerular filtration rate, Chronic, Cardiovascular risk factors, Cause of death, Aged, 80 and over, aardiovascular risk factors, Absolute risk reduction, General Medicine, Middle Aged, Italy, albuminuria, all-cause mortality, chronic kidney disease, type 2 diabetes, internal Medicine, endocrinology, diabetes and Metabolism, endocrinology, Female, medicine.symptom, Type 2, Human, Cohort study, Glomerular Filtration Rate, Adult, medicine.medical_specialty, Diabetic Angiopathie, Renal function, 030209 endocrinology & metabolism, Cardiovascular risk factor, diabetes and Metabolism, 03 medical and health sciences, Albuminuria, All-cause mortality, Chronic kidney disease, Glomerular filtration rate, Aged, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Humans, Renal Insufficiency, Chronic, Diabetes mellitus, Internal medicine, Diabetes Mellitus, medicine, MED/13 - ENDOCRINOLOGIA, business.industry, medicine.disease, MED/14 - NEFROLOGIA, Diabetic Nephropathie, Cohort Studie, business, Kidney disease
Abstract: Aims: To define the contribution of chronic kidney disease (CKD) to excess mortality in patients with type 2 diabetes and identify the baseline variables associated with all-cause death in those with and without CKD using the RECursive Partitioning and Amalgamation (RECPAM) method. Methods: This observational, longitudinal, cohort study enrolled 15,773 consecutive non-dialytic patients with type 2 diabetes in 19 Diabetes Clinics throughout Italy in 2006–2008. Based on the presence of albuminuria ≥ 30 mg day−1 and/or estimated glomerular filtration rate (eGFR) < 60 mL min−1·1.73 m−2 at baseline, patients were classified as having or not CKD. Vital status was verified on October 31, 2015 for 99.26% of patients. Results: Mortality increased with increasing albuminuria and eGFR category. Excess risk versus the general population was maximal in patients aged < 55 years in the worse albuminuria or eGFR category. Conversely, in subjects aged ≥ 75 years with albuminuria < 10 mg day−1 or eGFR ≥ 75 mL min−1·1.73 m−2, excess mortality was no longer detectable. At RECPAM analysis, the main correlates of death in the whole cohort were albuminuria > 44 mg day−1, prevalent CVD, and eGFR < ~ 75 mL min−1·1.73 m−2; gender, prevalent CVD, and higher albuminuria in the normoalbuminuric range, in patients without CKD; and CVD, eGFR ~ < 50 mL min−1·1.73 m−2, and albuminuria > 53 mg day−1, in those with CKD. Conclusions: CKD is a major contributor to excess mortality in type 2 diabetes, conferring a very high risk in younger patients and fully accounting for excess risk in the older ones. Higher albuminuria and lower eGFR, even in the normal range, identify individuals with increased mortality risk. Trial registration ClinicalTrials.gov (NCT00715481; https://clinicaltrials.gov/ct2/show/NCT00715481).
Published: 2018

31. Haemoglobin A1c variability is a strong, independent predictor of all-cause mortality in patients with type 2 diabetes

Author: Roberto Trevisan, Cecilia Fondelli, Antonio Nicolucci, Monica Vedovato, Enzo Bonora, Susanna Morano, Emanuela Orsi, Anna Solini, Giuseppe Penno, Gabriella Gruden, Giuseppe Pugliese, Franco Cavalot, Orsi, E, Solini, A, Bonora, E, Fondelli, C, Trevisan, R, Vedovato, M, Cavalot, F, Gruden, G, Morano, S, Nicolucci, A, Penno, G, and Pugliese, G
Subjects: Male, cardiovascular risk factors, Glycated Hemoglobin A, endocrine system diseases, Diabetic Cardiomyopathies, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, Kidney, Cohort Studies, 0302 clinical medicine, Endocrinology, Risk Factors, Prevalence, cardiovascular risk factor, Diabetic Nephropathies, Prospective Studies, Renal Insufficiency, Prospective cohort study, Confounding, Middle Aged, all-cause mortality, complications, HbA1c, type 2 diabetes, variability, Aged, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Follow-Up Studies, Glomerular Filtration Rate, Humans, Hyperglycemia, Hypoglycemia, Italy, Mortality, Quartile, Type 2, Cohort study, Coefficient of variation, Renal function, 030209 endocrinology & metabolism, complication, HbA1c variability, 03 medical and health sciences, Diabetes mellitus, Internal Medicine, medicine, Diabetes Mellitus, MED/13 - ENDOCRINOLOGIA, Glycated Hemoglobin, type 2 diabete, business.industry, nutritional and metabolic diseases, medicine.disease, business, Demography
Abstract: Aims To evaluate various measures of haemoglobin (Hb) A1c variability, compared with average HbA1c, as independent predictors of mortality. Materials and methods The Renal Insufficiency And Cardiovascular Events Italian multicentre study enroled 15 733 patients with type 2 diabetes from 19 diabetes clinics during 2006-2008. A total of 3 to 5 HbA1c measures, obtained during the 2-year period before enrolment, were available from 9 centres (8290 patients) and were used to calculate average HbA1c (HbA1c -MEAN) and HbA1c variability, measured as intra-individual standard deviation (HbA1c-SD), SD adjusted for the number of HbA1c assessments (HbA1c-AdjSD) and coefficient of variation (HbA1c-CV), that is, the HbA1c-SD to HbA1c-MEAN ratio. Vital status on October 31, 2015 was retrieved for 8252 patients (99.5%). Results The measures of HbA1c variability increased according to quartiles of HbA1c-MEAN and vice versa. HbA1c-MEAN and measures of HbA1c variability were associated with all-cause mortality; however, the strength of association of HbA1c-MEAN was lower than that of HbA1c -SD, HbA1c-CV or HbA1c-AdjSD, and disappeared after adjusting for confounders and any of the measures of HbA1c variability. Mortality increased with quartiles of HbA1c-MEAN, HbA1c -SD, HbA1c-CV and HbA1c-AdjSD, but only the association with HbA1c variability measures remained after adjustment for confounders and/or each other measure. In the fully adjusted model, mortality risk was lower for HbA1c-SD below the median and higher for HbA1c-SD above the median, regardless of whether HbA1c-MEAN was below or above the median. Conclusions HbA1c variability is a strong, independent predictor of all-cause mortality in type 2 diabetes and appears to be even more powerful than average HbA1c in predicting mortality.
Published: 2018

32. Effects of a low glycemic index high in fiber diet on blood glucose in women with gestational diabetes

Author: Veronica Donadoni, Luisa Patanè, Alessandro Roberto Dodesini, Roberto Trevisan, Ottavia Colombo, Silvia Galliani, Fiorenzo Cortinovis, Elena Ciriello, Dodesini, A, Donadoni, V, Ciriello, E, Colombo, O, Patane, L, Galliani, S, Cortinovis, F, and Trevisan, R
Subjects: Blood Glucose, medicine.medical_specialty, First line, 030209 endocrinology & metabolism, Low glycemic index, MELLITUS, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Internal medicine, Diabetes mellitus, Dietary Carbohydrates, Humans, Medicine, 030212 general & internal medicine, METAANALYSIS, Therapeutic strategy, business.industry, Obstetrics and Gynecology, medicine.disease, Diet, Gestational diabetes, Diabetes, Gestational, Endocrinology, Glycemic index, Diabetes Mellitus, Type 2, Glycemic Index, Pediatrics, Perinatology and Child Health, Gestation, Female, business
Abstract: Diet is the first line and the main therapeutic strategy in the treatment of gestational diabetes (GDM) with the primary objective to achieve normal blood glucose levels while promoting adequate ma...
Published: 2019
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33. Strategy to identify subjects with diabetes mellitus more suitable for selective echocardiographic screening: The DAVID-Berg study

Author: Alessandra Fontana, Gianfranco Parati, Paola Ferrari, Mihai Gheorghiade, Attilio Iacovoni, Paolo Canova, Aurelia Grosu, Alice Calabrese, Roberto Trevisan, Michele Senni, Stephen J. Greene, Renata De Maria, Mauro Gori, Antonello Gavazzi, Giovanni Cioffi, Gori, M, Canova, P, Calabrese, A, Cioffi, G, Trevisan, R, De Maria, R, Grosu, A, Iacovoni, A, Fontana, A, Ferrari, P, Greene, S, Gheorghiade, M, Parati, G, Gavazzi, A, and Senni, M
Subjects: Male, medicine.medical_specialty, Clinical variables, 030209 endocrinology & metabolism, Disease, 030204 cardiovascular system & hematology, Long term follow-up, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Diabetes mellitus, Diabetes Mellitus, Medicine, Humans, Prospective Studies, Prospective cohort study, Aged, Aged, 80 and over, Heart Failure, Routine screening, business.industry, Mean age, Middle Aged, medicine.disease, Electrocardiogram, Echocardiography, Heart failure, NTproBNP, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Echocardiographic screening, Cohort study, Follow-Up Studies
Abstract: Background: Despite the burden of pre-clinical heart failure (HF) among diabetes mellitus (DM) patients, routine screening echocardiography is not currently recommended. We prospectively assessed risk prediction for HF/death of a screening strategy combining clinical data, electrocardiogram, NTproBNP, and echocardiogram, aiming to identify DM patients more suitable for selective echocardiography. Methods: Among 4047 screened subjects aged. â¥. 55/â¤80. years, the DAVID-Berg Study prospectively enrolled 623 outpatients with DM, or hypertension, or known cardiovascular disease but with no HF history/symptoms. The present analysis focuses on data obtained during a longitudinal follow-up of the 219 patients with DM. Results: Mean age was 68. years, 61% were men, and median DM duration was 4.9. years. During a median follow-up of 5.2. years, 50 subjects developed HF or died. A predictive model using clinical data demonstrated moderate predictive power, which significantly improved by adding electrocardiogram (C-statistic 0.75 versus 0.70; p
Published: 2017

34. Efficacy of pasireotide in controlling severe hypercortisolism until cardiac transplantation

Author: Claudia Vettori, Roberto Attanasio, Liana Cortesi, Daniela Gianola, Fulvio Sileo, Roberto Trevisan, Attanasio, R, Cortesi, L, Gianola, D, Vettori, C, Sileo, F, and Trevisan, R
Subjects: medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Urology, Cardiomyopathy, 030209 endocrinology & metabolism, Physical examination, pasireotide, Cushing syndrome, lcsh:Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Prednisone, Internal Medicine, medicine, Teriparatide, 030212 general & internal medicine, MED/13 - ENDOCRINOLOGIA, Dexamethasone, Heart transplantation, lcsh:RC648-665, medicine.diagnostic_test, business.industry, medicine.disease, Novel Treatment, Pasireotide, Transplantation, chemistry, business, medicine.drug
Abstract: Summary Cushing’s syndrome is associated with increased morbidity and mortality. Although surgery is the first-line treatment, drugs can still play a role as an ancillary treatment to be employed while waiting for surgery, after unsuccessful operation or in patients unsuitable for surgery. We were asked to evaluate a 32-year-old male waiting for cardiac transplantation. Idiopathic hypokinetic cardiomyopathy had been diagnosed since 6 years. He was on treatment with multiple drugs, had a pacemaker, an implantable cardioverter and an external device for the support of systolic function. Physical examination showed severely impaired general status, signs of hypercortisolism and multiple vertebral compression fractures. We administered teriparatide, and the few evaluable parameters supported the diagnosis of ACTH-dependent hypercortisolism: serum cortisol was 24.2 µg/dL in the morning and 20.3 µg/dL after overnight 1 mg dexamethasone, urinary free cortisol (UFC) was 258 µg/24 h and ACTH 125 pg/mL. Pituitary CT was negative. Pasireotide 300 µg bid was administered and uptitrated to 600 µg bid. Treatment was well tolerated, achieving dramatic improvement of clinical picture with progressive normalization of serum cortisol and ACTH levels as well as UFC. After 4 months, the patient underwent successful heart transplantation. Many complications ensued and were overcome. Pituitary MRI was negative. On pasireotide 300 µg bid and prednisone 2.5 mg/day (as part of immunosuppressive therapy), morning serum cortisol and ACTH were 15.6 µg/dL and 54 pg/mL respectively, UFC was 37 µg/24 h, fasting glucose: 107 mg/dL and HbA1c: 6.5%. In conclusion, primary treatment with pasireotide achieved remission of hypercortisolism, thus allowing the patient to undergo heart transplantation. Learning points: Untreated Cushing’s syndrome is associated with ominous prognosis. First-line treatment is surgery (at pituitary or adrenal, according to disease localization). A few drugs are available to treat hypercortisolism. Pasireotide is a multi-ligand somatostatin analog approved for treatment of hypercortisolism. Primary treatment with pasireotide was effective in a patient with severe Cushing’s syndrome, allowing him to undergo heart transplantation.
Published: 2017
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35. The Hyperfiltering Kidney in Diabetes

Author: Alessandro Roberto Dodesini, Roberto Trevisan, Trevisan, R, and Dodesini, A
Subjects: medicine.medical_specialty, Sodium, Hyperfiltration, Renal function, chemistry.chemical_element, 030209 endocrinology & metabolism, Disease, Diabetic nephropathy, 030204 cardiovascular system & hematology, Diabete, Kidney, 03 medical and health sciences, Intraglomerular pressure, 0302 clinical medicine, Sodium-Glucose Transporter 2, Internal medicine, Diabetes mellitus, medicine, Humans, Diabetic Nephropathies, MED/13 - ENDOCRINOLOGIA, Sodium-Glucose Transporter 2 Inhibitors, Reabsorption, business.industry, Sodium-Glucose Transporter 2 Inhibitor, medicine.disease, Renal glucose reabsorption, MED/14 - NEFROLOGIA, Endocrinology, medicine.anatomical_structure, chemistry, Diabetes Mellitus, Type 2, Diabetic Nephropathie, Disease Progression, business, Human, Glomerular Filtration Rate
Abstract: Hyperfiltering kidney is a typical feature of diabetes. Improvement observed with regard to glucose control and blood pressure control reduces the high glomerular filtration rate and may contribute to retard the appearance and the progression of diabetic renal disease. Although the mechanism of hyperfiltration is still unclear, there is mounting evidence that the increased reabsorption of glucose and sodium by sodium glucose transporter-2 (SGLT-2) is involved in this altered renal function. There is a possibility that SGLT-2 inhibition may correct hyperfiltration in diabetes, adding a new therapeutic approach to halt renal disease in patients with diabetes.
Published: 2017

36. Beneficial effect of lixisenatide after 76 weeks of treatment in patients with type 2 diabetes mellitus: A meta-analysis from the GetGoal programme

Author: Antonio Nicolucci, William Stager, Raffaele Napoli, Francesco Purrello, Fabio Broglio, Elena Nikonova, Roberto Trevisan, Edoardo Mannucci, Broglio, Fabio, Mannucci, Edoardo, Napoli, Raffaele, Nicolucci, Antonio, Purrello, Francesco, Nikonova, Elena, Stager, William, Trevisan, Roberto, Broglio, F, Mannucci, E, Napoli, R, Nicolucci, A, Purrello, F, Nikonova, E, Stager, W, and Trevisan, R
Subjects: Blood Glucose, Male, Glycated Hemoglobin A, Endocrinology, Diabetes and Metabolism, 030204 cardiovascular system & hematology, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, diabetes mellitus, GLP-1 RA, glycosylated, haemoglobin A, hypoglycaemia, lixisenatide, long-term efficacy, long-term safety, Internal Medicine, Endocrinology, Insulin, diabetes mellitu, Thiazolidinedione, Nausea, Middle Aged, Postprandial Period, Metformin, Sulfonylurea Compound, Diabetes and Metabolism, Postprandial, Peptide, Drug Therapy, Combination, Female, Human, medicine.drug, Adult, medicine.medical_specialty, Vomiting, 030209 endocrinology & metabolism, Hypoglycemia, Placebo, 03 medical and health sciences, Lixisenatide, Diabetes mellitus, Internal medicine, medicine, Humans, Hypoglycemic Agents, Adverse effect, Aged, Glycemic, Glycated Hemoglobin, Pioglitazone, Hypoglycemic Agent, business.industry, Body Weight, diabetes mellitus, GLP-1 RA, glycosylated, haemoglobin A, hypoglycaemia, lixisenatide, long-term efficacy, long-term safety, medicine.disease, Sulfonylurea Compounds, Diabetes Mellitus, Type 2, chemistry, Thiazolidinediones, Peptides, business
Abstract: Aims: To evaluate the long-term efficacy and safety of lixisenatide, a short-acting, prandial glucagon-like peptide-1 receptor agonists (GLP-1 RA) as add-on therapy in type 2 diabetes mellitus.Methods: A meta-analysis of 76-week results of 5 placebo-controlled clinical trials from the GetGoal programme was performed, including 3000 inadequately controlled adult diabetic patients where lixisenatide 20 mu g once-daily was administered in combination with metformin (GetGoal-M and GetGoal-F1), sulphonylurea +/- metformin (GetGoal-S), basal insulin +/- metformin (GetGoal-L) or pioglitazone +/- metformin (GetGoal-P).Results: A significant reduction in HbA1c at 76 weeks was observed in the intervention arm compared to placebo (LSM difference: -0.41%, 95% CI: -0.51, -0.32, P < .00001). Compared to placebo, lixisenatide induced a larger decrease in fasting plasma glucose (LSM difference -0.49 mmol/L, 95% CI -0.71, -0.27, P < .0001) and postprandial glucose excursion after a standard test meal (LSM difference -3.29 mmol/L, 95% CI -4.17, -2.42, P < .00001). A body-weight reduction was observed in the lixisenatide arm (LSM difference -0.40 kg, 95% CI: -0.8, -0.01, P = .05). The risk of hypoglycaemia was slightly higher with lixisenatide vs placebo (risk difference +0.02, 95% CI: 0, 0.04, P = .04). The most commonly observed non-severe adverse events were nausea and vomiting, which after week 16 and week 8, were steadily
Published: 2017

37. Assessment of the association between glycemic variability and diabetes-related complications in type 1 and type 2 diabetes

Author: M. Brändle, J. Smith-Palmer, M. Orsini Federici, S. Liabat, W. Valentine, Roberto Trevisan, Smith-Palmer, J, Brandle, M, Trevisan, R, Federici, M, Liabat, S, and Valentine, W
Subjects: Blood Glucose, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Macrovascular complication, Coronary Artery Disease, Type 2 diabetes, Cochrane Library, Coronary artery disease, Endocrinology, Risk Factors, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Diabetic Nephropathies, Glycemic variability, Risk factor, Glycemic, Type 1 diabetes, Diabetic Retinopathy, business.industry, General Medicine, medicine.disease, Surgery, Oxidative Stress, Diabetes Mellitus, Type 1, Systematic review, Diabetes Mellitus, Type 2, Microvascular complication, Hyperglycemia, Female, business
Abstract: Chronic hyperglycemia is the main risk factor for the development of diabetes-related complications in both type 1 and type 2 diabetes, but it is thought that frequent or large glucose fluctuations may contribute independently to diabetes-related complications. A systematic literature review was performed using the PubMed, EMBASE and Cochrane Library databases with searches limited to studies published from June 2002 to March 2014, in English and including ≥50 patients. Twenty eight articles were included in the final review. Eighteen studies reported the association between glucose variability and diabetes-related complications exclusively in type 2 diabetes. A positive association between increased variability and microvascular complications and coronary artery disease was consistently reported. Associations between glucose variability and other macrovascular complications were inconsistent in type 2 diabetes. Seven studies examined the association between glucose variability and complications exclusively in type 1 diabetes. Increased glucose variability appears to play a minimal role in the development of micro- and macrovascular complications in type 1 diabetes. Consistent findings suggest that in type 2 diabetes glucose variability is associated with development of microvascular complications. The role of increased glucose variability in terms of microvascular and macrovascular complications in type 1 diabetes is less clear; more data in are needed.
Published: 2014
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38. Effect on blood pressure of combined inhibition of endothelin-converting enzyme and neutral endopeptidase with daglutril in patients with type 2 diabetes who have albuminuria: a randomised, crossover, double-blind, placebo-controlled trial

Author: Giuseppe Remuzzi, Flavio Gaspari, Aneliya Parvanova, Roberto Trevisan, Piero Ruggenenti, Ilian Iliev, Antonio Bossi, Irene M. van der Meer, Annalisa Perna, Ariela Benigni, Parvanova, A, van der Meer, I, Iliev, I, Perna, A, Gaspari, F, Trevisan, R, Bossi, A, Remuzzi, G, Benigni, A, and Ruggenenti, P
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Population, Urology, Placebo-controlled study, Blood Pressure, Type 2 diabetes, Endothelin-Converting Enzymes, Placebo, Endocrinology, Double-Blind Method, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Albuminuria, Aspartic Acid Endopeptidases, Humans, Prospective Studies, Enzyme Inhibitors, education, Aged, education.field_of_study, Cross-Over Studies, business.industry, Metalloendopeptidases, Benzazepines, Middle Aged, medicine.disease, Crossover study, Treatment Outcome, Blood pressure, Diabetes Mellitus, Type 2, Female, Neprilysin, albuminuria, blood pressure,type 2 diabetes, endothelin-converting enzyme and neutral endopeptidase inhibitor, medicine.symptom, business
Abstract: Summary Background Effective reduction of albuminuria and blood pressure in patients with type 2 diabetes who have nephropathy is seldom achieved with available treatments. We tested the effects of treatment of such patients with daglutril, a combined endothelin-converting enzyme and neutral endopeptidase inhibitor. Methods We did this randomised, crossover trial in two hospitals in Italy. Eligibility criteria were: age 18 years or older, urinary albumin excretion 20–999 μg/min, systolic blood pressure (BP) less than 140 mm Hg, and diastolic BP less than 90 mm Hg. Patients were randomly assigned (1:1) with a computer-generated randomised sequence to receive either daglutril (300 mg/day) then placebo for 8 weeks each or vice versa, with a 4-week washout period. Patients also took losartan throughout. Participants and investigators were masked to treatment allocation. The primary endpoint was 24-h urinary albumin excretion in the intention-to-treat population. Secondary endpoints were median office and ambulatory (24 h, daytime, and night-time) BP, renal haemodynamics and sieving function, and metabolic and laboratory test results. This study is registered with ClinicalTrials.gov, number NCT00160225. Findings We screened 58 patients, of whom 45 were enrolled (22 assigned to daglutril then placebo, 23 to placebo then daglutril; enrolment from May, 2005, to December, 2006) and 42 (20 vs 22) were included in the primary analysis. Daglutril did not significantly affect 24-h urinary albumin excretion compared with placebo (difference in change −7·6 μg/min, IQR −78·7 to 19·0; p=0·559). 34 patients had complete 24-h BP readings; compared with placebo, daglutril significantly reduced 24-h systolic (difference −5·2 mm Hg, SD 9·4; p=0·0013), diastolic (–2·5, 6·2; p=0·015), pulse (–3·0, 6·3; p=0·019), and mean (–3·1, 6·2; p=0·003) BP, as well as all night-time BP readings and daytime systolic, pulse, and mean BP, but not diastolic BP. Compared with placebo, daglutril also significantly reduced office systolic BP (–5·4, 15·4; p=0·028), but not diastolic (–1·8, 9·9; p=0·245), pulse (–3·1, 10·6; p=0·210), or mean (–2·1, 10·4; p=0·205) BP, and increased big endothelin serum concentration. Other secondary outcomes did not differ significantly between treatment periods. Three patients taking placebo and six patients taking daglutril had mild treatment-related adverse events—the most common was facial or peripheral oedema (in four patients taking daglutril). Interpretation Daglutril improved control of BP in hypertensive patients with type 2 diabetes and nephropathy and had an acceptable safety profile. Combined endothelin-converting enzyme and neutral endopeptidase inhibition could provide a new approach to hypertension in this high-risk population. Funding Solvay Pharmaceuticals.
Published: 2013
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39. ADAMTS13 Predicts Renal and Cardiovascular Events in Type 2 Diabetic Patients and Response to Therapy

Author: Piero Ruggenenti, Antonio Bossi, Erica Rurali, Carolina Haefliger, Roberto Trevisan, Marina Noris, Ilian Iliev, Sara Gastoldi, Giuseppe Remuzzi, Federica Banterla, Antonietta Chianca, Roberta Donadelli, Miriam Galbusera, Aneliya Parvanova, Giulia Gherardi, Rurali, E, Noris, M, Chianca, A, Donadelli, R, Banterla, F, Galbusera, M, Gherardi, G, Gastoldi, S, Parvanova, A, Iliev, I, Bossi, A, Haefliger, C, Trevisan, R, Remuzzi, G, and Ruggenenti, P
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, ADAMTS13 Protein, Angiotensin-Converting Enzyme Inhibitors, Diabetic angiopathy, Gastroenterology, Polymorphism, Single Nucleotide, Von Willebrand factor, Polymorphism (computer science), Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Humans, Diabetic Nephropathies, cardiovascular diseases, Original Research, type 2 diabete, Thrombospondin, biology, business.industry, diabetic nephropathy, Hazard ratio, Genetics/Genomes/Proteomics/Metabolomics, medicine.disease, ADAMTS13, ADAM Proteins, Endocrinology, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Predictive value of tests, biology.protein, Female, business, Diabetic Angiopathies
Abstract: In patients with diabetes, impaired ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) proteolysis of highly thrombogenic von Willebrand factor (VWF) multimers may accelerate renal and cardiovascular complications. Restoring physiological VWF handling might contribute to ACE inhibitors’ (ACEi) reno- and cardioprotective effects. To assess how Pro618Ala ADAMTS13 variants and related proteolytic activity interact with ACEi therapy in predicting renal and cardiovascular complications, we genotyped 1,163 normoalbuminuric type 2 diabetic patients from BErgamo NEphrologic DIabetes Complications Trial (BENEDICT). Interaction between Pro618Ala and ACEi was significant in predicting both renal and combined renal and cardiovascular events. The risk for renal or combined events versus reference Ala carriers on ACEi progressively increased from Pro/Pro homozygotes on ACEi (hazard ratio 2.80 [95% CI 0.849–9.216] and 1.58 [0.737–3.379], respectively) to Pro/Pro homozygotes on non-ACEi (4.77 [1.484–15.357] and 1.99 [0.944–4.187]) to Ala carriers on non-ACEi (8.50 [2.416–29.962] and 4.00 [1.739–9.207]). In a substudy, serum ADAMTS13 activity was significantly lower in Ala carriers than in Pro/Pro homozygotes and in case subjects with renal, cardiovascular, or combined events than in diabetic control subjects without events. ADAMTS13 activity significantly and negatively correlated with all outcomes. In patients with diabetes, ADAMTS13 618Ala variant associated with less proteolytic activity, higher risk of chronic complications, and better response to ACEi therapy. Screening for Pro618Ala polymorphism may help identify patients with diabetes at highest risk who may benefit the most from early reno- and cardioprotective therapy.
Published: 2013

40. Trialogue. Managing hyperglycaemia in internal medicine. Instructions for use: Consensus document of the Associazione Medici Diabetologi (AMD), Federazione delle Associazioni dei Dirigenti Ospedalieri Internisti (FADOI) and Società Italiana di Diabetologi

Author: Roberto Trevisan, Valeria Manicardi, and Giampietro Beltramello
Subjects: medicine.medical_specialty, business.industry, Hospitalized patients, lcsh:R, lcsh:Medicine, General Medicine, Hospitalized patient, Recommendations, After discharge, medicine.disease, Disease course, Multidisciplinary approach, Instructions for use, Internal medicine, Good clinical practice, Continuity of care, medicine, Hyperglycaemia, Insulin therapy, Medical emergency, Operational costs, business
Abstract: Hyperglycaemic patients admitted to hospital have worse clinical outcomes with higher operational costs than normoglycaemic patients. Identifying, defining and treating hyperglycaemia promptly and appropriately is essential during hospitalization; adequate “continuity of care” must be assured after discharge. This requires a multidisciplinary clinical collaboration between the internist and the diabetes team, which plays a central role in the treatment course and should be involved soon after patient admission to the hospital. This document aims to establish guidelines and recommendations for good clinical practice in managing hyperglycaemic Internal Medicine patients, with or without previous diagnosis of diabetes. The Associazione Medici Diabetologi (AMD), Federazione delle Associazioni dei Dirigenti Ospedalieri Internisti (FADOI) and Società Italiana di Diabetologia (SID) have decided to publish a document useful for internists in the management of hospitalised patients with hyperglycaemia. The Trialogue project, coordinated by the Board of Scientific experts from the three Scientific Societies, was initiated for this purpose. A questionnaire consisting of 16 multiple choice questions on the management of hyperglycaemia in hospital was answered by 660 physicians from over 250 internal medicine units distributed throughout Italy. Analysis of responses has yielded an overview of routine clinical practice and provided a wealth of ideas to better identify critical points in the treatment of hospitalized patients with hyperglycaemia. These recommendations were developed with the aim of providing mutually agreed practical guidance (instructions for use) that can be readily applied by healthcare professionals in routine clinical practice.
Published: 2013
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41. Inspiratory muscle training for diaphragm dysfunction after cardiac surgery

Author: Chiara Torregiani, Metka Kodric, Marco Confalonieri, Cinzia Longo, Roberto Trevisan, Fabiana Cantarutti, Rossella Cifaldi, Kodric, Metka, Trevisan, Roberto, Torregiani, Chiara, Cifaldi, Rossella, Longo, Cinzia, Cantarutti, Fabiana, and Confalonieri, Marco
Subjects: Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Respiratory Muscle, Endpoint Determination, medicine.medical_treatment, Diaphragm, Breathing Exercises, Statistics, Nonparametric, Pulmonary function testing, Inspiratory Capacity, Valve replacement, Surveys and Questionnaires, Activities of Daily Living, Humans, Surveys and Questionnaire, Cardiac Surgical Procedure, Medicine, Nonparametric, Lung volumes, Prospective Studies, Cardiac Surgical Procedures, Prospective cohort study, Aged, Respiratory Function Test, Analysis of Variance, COPD, Chi-Square Distribution, business.industry, Statistics, medicine.disease, Female, Fluoroscopy, Respiratory Function Tests, Respiratory Muscles, Cardiology and Cardiovascular Medicine, Surgery, Diaphragm (structural system), Cardiac surgery, Prospective Studie, Breathing Exercise, Anesthesia, business, Human
Abstract: OBJECTIVE: Diaphragm dysfunction is a complication of cardiac surgery with partial or absent spontaneous recovery in most cases. Surgical diaphragm plication represents the only option when symptoms persist. Because training improves functional nerve recovery after a nerve lesion, we hypothesized that early diaphragm muscle training may be beneficial. METHODS: A prospective, randomized at 2:1 ratio, controlled trial of diaphragm training using an adjustable pressure device (Threshold; Philips Respironics Inc, Murrysville, Pa) versus no training (sham device) was performed in patients with diaphragm paralysis after major cardiac surgery. This 1-year study recruited consecutive adult patients with sniff fluoroscopy-defined diaphragm paralysis after coronary bypass, valve replacement, or both. The outcome measures were diaphragm function recovery assessed by sniff fluoroscopy, maximum inspiratory and expiratory pressures, and lung function tests. RESULTS: A total of 69 patients were randomized. At 12 months, 52 patients completed the study assessments, 36 in the treatment group and 16 in the control group. Inspiratory muscle training produced a significant improvement of diaphragm mobility after 12 months (P < .001). Most patients in the training group (77.78%) experienced a partial improvement (41.67%) or achieved a complete improvement (36.11%) versus no improvement (87.5%) or partial recovery (12.5%) among controls. CONCLUSIONS: Inspiratory muscle training may improve inspiratory muscle strength and increases paralyzed diaphragm mobility.
Published: 2013
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42. Impact of substitution among generic drugs on persistence and adherence: A retrospective claims data study from 2 Local Healthcare Units in the Lombardy Region of Italy

Author: Claudio Mencacci, Alberico L. Catapano, Roberto Trevisan, Giorgio L Colombo, Alberto Margonato, Carlomaurizio Montecucco, Enrico Agabiti-Rosei, Colombo, G, Agabiti-Rosei, E, Margonato, A, Mencacci, C, Montecucco, C, Trevisan, R, Catapano, A, Colombo, G. L., Agabiti Rosei, E, Margonato, Alberto, Montecucco C., M, and Catapano, A. L.
Subjects: Male, Pediatrics, medicine.medical_specialty, Health Knowledge, Attitudes, Practice, Time Factors, Databases, Factual, Population, Comorbidity, 030204 cardiovascular system & hematology, Drug Substitution, Drug Prescriptions, Medication Adherence, 03 medical and health sciences, Insurance Claim Review, 0302 clinical medicine, Internal medicine, Generic drug, Health care, medicine, Internal Medicine, Drugs, Generic, Humans, 030212 general & internal medicine, Medical prescription, education, Aged, Retrospective Studies, Polypharmacy, Aged, 80 and over, education.field_of_study, business.industry, Age Factors, Drugs, Retrospective cohort study, General Medicine, Middle Aged, medicine.disease, Administrative databases, Italy, Adherence, Female, business, Cardiology and Cardiovascular Medicine, Administrative Claims, Healthcare, Compliance, Adherence, Administrative databases, Compliance, Drugs
Abstract: Background The use of generics, equivalent but less expensive drugs, is an important opportunity to reduce healthcare expenditure. Methods The purpose of this study was to investigate the effect of substitution between unbranded generics on persistence and adherence to therapy in two Italian Local Health Units (ASL) in real-world clinical practice in 5 therapeutic areas using tracing drugs. Substitution of generic drugs is any change in the name of the manufacturer of the generic drug. The therapeutic areas were: diabetes (metformin); hypertension (amlodipine); dyslipidemia (simvastatin); psychiatry (sertraline); cardiology (propafenone); osteoporosis (alendronate). The retrospective analysis was carried out on the administrative databases of two Local Healthcare Units (ASL – Azienda sanitaria locale Bergamo (BG) and Pavia (PV)) in the Lombardy Region of Italy. The correlation between persistence and adherence with the different cohorts of generic substitution frequency within each therapeutic area was then calculated. Results According to the inclusion criteria, 23,773 patients were evaluated. Patients were observed for a period of 36 months starting from the first drug delivery (index date). The median age of the overall population was above 61 years in all therapeutic areas. The generic drug substitution occurred in 61.5% of patients (BG: 57.6% and PV: 65.4% respectively); Hypertension was the therapeutic area with the highest percentage of patients with substitutions. Patients' adherence, evaluated by the Medical Possession Rate (MPR) and persistence to the treatment decreases with the increase in the frequency of generic substitutions. This observation was confirmed by a statistically significant negative correlation (p-value of
Published: 2016

43. Rate and Determinants of Association Between Advanced Retinopathy and Chronic Kidney Disease in Patients With Type 2 Diabetes

Author: Gabriella Gruden, Anna Solini, Luigi Laviola, Gianpaolo Zerbini, Susanna Morano, Giuseppe Pugliese, Giuseppe Penno, Giacomo Zoppini, Antonio Nicolucci, Roberto Trevisan, Emanuela Orsi, and Franco Cavalot
Subjects: Advanced and Specialized Nursing, medicine.medical_specialty, Type 1 diabetes, business.industry, Endocrinology, Diabetes and Metabolism, Renal function, Type 2 diabetes, urologic and male genital diseases, medicine.disease, female genital diseases and pregnancy complications, Nephropathy, Endocrinology, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Albuminuria, Microalbuminuria, medicine.symptom, business, Kidney disease
Abstract: OBJECTIVE To evaluate the rate and determinants of concordance between advanced diabetic retinopathy (DR) and chronic kidney disease (CKD), as assessed by both albuminuria and estimated glomerular filtration rate (eGFR), in the large cohort of the Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicenter study. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes (n = 15,773) visiting consecutively 19 hospital–based diabetes clinics in years 2007 and 2008 were examined. DR was assessed by dilated fundoscopy. CKD was defined based on albuminuria and eGFR. RESULTS CKD was present in 58.64% of subjects with advanced DR, whereas advanced DR was detectable only in 15.28% of individuals with any CKD and correlated with the albuminuric CKD phenotypes more than with the nonalbuminuric phenotype. Age, male sex, diabetes duration, hemoglobin A1c, hypertension, triglycerides, previous cardiovascular disease, and, inversely, HDL-cholesterol correlated independently with the presence of any CKD in individuals with advanced DR; correlates differed according to the presence of albuminuria, reduced eGFR, or both. Conversely, factors associated with the presence of advanced DR in subjects with any CKD were diabetes treatment, previous cardiovascular disease, albuminuria, and, inversely, smoking, eGFR, and age at diagnosis. CONCLUSIONS Concordance of CKD with advanced DR is low in subjects with type 2 diabetes, and CKD without advanced DR is more frequent than isolated advanced DR, at variance with type 1 diabetes. Factors independently associated with the presence of any CKD in individuals with advanced DR differ, at least in part, from those correlating with the presence of advanced DR in subjects with any CKD and by CKD phenotype.
Published: 2012
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44. Trialogue. La gestione dell’iperglicemia in area medica. Istruzioni per l’uso

Author: Giampietro Beltramello, Roberto Trevisan, and Valeria Manicardi
Subjects: Hospitalized patients, business.industry, Medicine, Continuity of care, General Medicine, business, Humanities
Abstract: Riassunto Il paziente iperglicemico ricoverato in ospedale va incontro a esiti clinici peggiori con costi gestionali piu elevati rispetto al paziente normoglicemico. E indispensabile individuare, definire e trattare tempestivamente e opportunamente l’iperglicemia durante il ricovero, ma anche garantire alla dimissione una adeguata “continuita di cura” dall’ospedale al territorio. E pertanto necessario avviare una collaborazione clinica multidisciplinare tra l’internista e il team diabetologico, che svolge un ruolo centrale nel percorso di cura e deve essere coinvolto fin dall’inizio. Il presente documento si propone di definire linee di indirizzo e raccomandazioni di buona pratica clinica sulla gestione del paziente che presenta iperglicemia, con o senza pregressa diagnosi di diabete, ospedalizzato in un reparto di Medicina Interna. L’Associazione Medici Diabetologi (AMD), la Federazione delle Associazioni dei Dirigenti Ospedalieri Internisti (FADOI) e la Societa Italiana di Diabetologia (SID) hanno deciso di condividere un documento capace di fornire all’internista utili indicazioni per la gestione del paziente ospedalizzato con iperglicemia. Nasce quindi il progetto Trialogue, coordinato da un Board Scientifico di esperti delle tre Societa Scientifiche. E stato predisposto un questionario costituito da 16 domande a risposta multipla sulla gestione dell’iperglicemia in ospedale a cui hanno risposto 660 medici operanti in oltre 250 Unita Operative di Medicina Interna distribuite sull’intero territorio nazionale. L’analisi delle risposte al questionario ha portato innanzitutto a una rilevazione della reale pratica clinica quotidiana e ha fornito molteplici spunti per meglio identificare i punti critici nel trattamento del paziente ospedalizzato con iperglicemia. Sono state quindi elaborate le seguenti raccomandazioni, con l’obiettivo di fornire indicazioni pratiche e condivise che possano trovare impiego immediato (Istruzioni per l’uso) nella pratica clinica con cui gli operatori sanitari si confrontano quotidianamente.
Published: 2012
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45. Carrier density and interfacial kinetics of mesoporous TiO2 in aqueous electrolyte determined by impedance spectroscopy

Author: Francisco Fabregat-Santiago, Antonio Guerrero, Roberto Trevisan, Sara G. Miralles, Sixto Gimenez, Juan Bisquert, Halina K. Dunn, Pau Rodenas, and Eva M. Barea
Subjects: Electron density, Aqueous solution, Titanium oxide, Chemistry, business.industry, General Chemical Engineering, Analytical chemistry, Impedance spectroscopy, Capacitance, Analytical Chemistry, Dielectric spectroscopy, Chemical energy, Semiconductor, Chemical physics, Transmission line, Electrochemistry, Water splitting, Porous semiconductors, business, Surface states
Abstract: Water splitting at a semiconductor/solution interface with the only input of sunlight to generate hydrogen is one of the most attractive strategies to produce and store chemical energy. In the present study we have investigated carrier dynamics and interfacial kinetics of mesoporous TiO 2 in an aqueous solution. The applicability of the transmission line model for mesoporous semiconductors has been validated to identify chemical capacitance, transport resistance and charge transfer resistance in this system by testing samples of different thicknesses in the dark and under illumination. We found that both transport resistance and chemical capacitance scale well with sample thickness, while charge transfer resistance scales with thickness when the FTO substrate is not exposed to the solution. Otherwise, there is a competition between charge transfer through TiO 2 and through the FTO substrate. Under illumination, the electron density is dominated by photogenerated carriers at biases below the open circuit potential, whereas at higher bias, the applied potential determines the electron density. Evidence of charge transfer via surface states has been experimentally observed and corroborated with a physical model, which explicitly includes charge transfer through a monoenergetic trap for electron and holes. This study may lay the basis for understanding more complex processes at anodic potentials on the TiO 2 /solution interface where water splitting reactions take place.
Published: 2012
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46. Diverging Association of Reduced Glomerular Filtration Rate and Albuminuria With Coronary and Noncoronary Events in Patients With Type 2 Diabetes

Author: Anna Solini, Francesco Andreozzi, Mauro Cignarelli, Maura Arosio, Roberto Trevisan, Cecilia Fondelli, Enzo Bonora, Giuseppe Pugliese, Monica Vedovato, Antonio Nicolucci, Emanuela Orsi, and Giuseppe Penno
Subjects: Male, medicine.medical_specialty, Cardiovascular and Metabolic Risk, Endocrinology, Diabetes and Metabolism, Renal function, Type 2 diabetes, Lower risk, urologic and male genital diseases, Cohort Studies, Risk Factors, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Albuminuria, Humans, Prospective Studies, Renal Insufficiency, Chronic, Original Research, Aged, Advanced and Specialized Nursing, business.industry, Odds ratio, Middle Aged, medicine.disease, female genital diseases and pregnancy complications, Endocrinology, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Cardiology, Regression Analysis, Microalbuminuria, Female, medicine.symptom, business, Kidney disease, Glomerular Filtration Rate
Abstract: OBJECTIVE Although a reduced estimated glomerular filtration rate (eGFR) was shown to be a powerful independent predictor of cardiovascular disease (CVD), other studies suggested that it confers a much lower risk than albuminuria alone, whereas the combination of the two abnormalities is associated with multiplicative risk. This study aimed at assessing the independent association of previous CVD events, either total or by vascular bed, with eGFR and albuminuria and chronic kidney disease (CKD) phenotypes. RESEARCH DESIGN AND METHODS This cross-sectional study evaluated 15,773 patients with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study in 19 outpatient diabetes clinics in years 2007–2008. Albuminuria was assessed by immunonephelometry or immunoturbidimetry. GFR was estimated by the simplified Modification of Diet in Renal Disease Study and the Chronic Kidney Disease-Epidemiology Collaboration equation. CKD was defined as an eGFR RESULTS CVD risk increased linearly with eGFR decline and albuminuria and became significant for values CONCLUSIONS These data, although cross-sectional, show that reduced eGFR, irrespective of albuminuria, is associated with significant CVD, particularly in the coronary district.
Published: 2011

47. Prolonged Physiologic Doses of Corticosteroids for the Treatment of Severe Community Acquired Pneumonia

Author: Chiara Torregiani, Pietro Geri, Fabio Giuseppe Vassallo, Marco Confalonieri, Rossella Cifaldi, Metka Kodric, Marco Biolo, and Roberto Trevisan
Subjects: Pulmonary and Respiratory Medicine, Pediatrics, medicine.medical_specialty, Community-acquired pneumonia, business.industry, medicine, medicine.disease, business
Published: 2009
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48. Association of the Q121 Variant of ENPP1 Gene With Decreased Kidney Function Among Patients With Type 2 Diabetes

Author: Salvatore, De Cosmo, Antonio, Minenna, Yuan-Yuan, Zhang, Ryan, Thompson, Robert, Thompson, Giuseppe, Miscio, Monica, Vedovato, Anna, Rauseo, Alois, Saller, Sandra, Mastroianno, Fabio, Pellegrini, Roberto, Trevisan, Paola, Fioretto, Alessandro, Doria, and Vincenzo, Trischitta
Subjects: Male, medicine.medical_specialty, gene polymorphism, Renal function, Type 2 diabetes, Polymorphism, Single Nucleotide, vascular diabetic complications, Article, chemistry.chemical_compound, Insulin resistance, insulin resistance, pc-1, Internal medicine, Diabetes mellitus, medicine, Albuminuria, Humans, Pyrophosphatases, Creatinine, Phosphoric Diester Hydrolases, business.industry, Odds ratio, Middle Aged, medicine.disease, Hemoglobin A, Endocrinology, Amino Acid Substitution, Diabetes Mellitus, Type 2, chemistry, Nephrology, Female, medicine.symptom, business, Glomerular Filtration Rate
Abstract: Background Insulin resistance has a role in diabetic kidney complications. The K121Q (lysine to glutamine substitution at amino acid 121, encoded by single-nucleotide polymorphism rs1044498) variant of the ectonucleotide pyrophosphatase/phosphodiesterase gene ( ENPP1) has been associated with insulin resistance and related vascular complications in patients with type 2 diabetes (T2D) in many, although not all, studies. This study investigated whether the ENPP1 Q121 variant modulates the risk of decreased glomerular filtration rate (GFR) in patients with T2D. Study Design Cross-sectional study. Setting & Participants 2 diabetes units from Italy (in Gargano and Padua) and 1 from the United States (Boston, MA) recruited a total of 1,392 patients with T2D. Predictor The ENPP1 Q121 variant. Measurements Estimated GFR from serum creatinine, urinary albumin excretion, blood pressure, hemoglobin A 1c , triglycerides, total cholesterol, and high-density lipoprotein cholesterol. Outcomes Decreased GFRs (ie, estimated GFR 2 ). Results In the Gargano and Boston populations, according to the dominant model of inheritance, Q121 carriers (ie, individual with either KQ or QQ alleles) had an increased risk of decreased GFR: odds ratios (ORs) of 1.69 (95% confidence interval [CI], 1.1 to 2.6) and 1.50 (95% CI, 1.0 to 2.2), respectively. In the Padua set, the association was in the same direction, but did not reach formal statistical significance (OR, 1.77; 95% CI, 0.7 to 4.5). When the 3 studies were pooled, Q121 carriers showed an increased risk of decreased GFR (OR, 1.58; 95% CI, 1.2 to 2.1; P = 0.002). Also, pooled mean differences in absolute GFRs were different across genotype groups, with Q121 carriers showing lower GFRs compared with KK individuals ( P = 0.04). Limitations P values not approaching a genome-wide level of significance. Conclusions Our data suggest that patients with T2D carrying the ENPP1 Q121 variant are at increased risk of decreased GFR.
Published: 2009
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49. Independent correlates of urinary albumin excretion within the normoalbuminuric range in patients with type 2 diabetes: The Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study

Author: Franco Cavalot, Giuseppe Penno, Anna Solini, Olga Lamacchia, Luigi Laviola, Cecilia Fondelli, Monica Vedovato, Giacomo Zoppini, Emanuela Orsi, Giuseppe Pugliese, Gabriella Gruden, Roberto Trevisan, Penno, G, Solini, A, Zoppini, G, Fondelli, C, Trevisan, R, Vedovato, M, Cavalot, F, Gruden, G, Lamacchia, O, Laviola, L, Orsi, E, and Pugliese, G
Subjects: albumin excretion rate, chronic kidney disease, diabetic retinopathy, type 2 diabetes, egfr, Male, Cross-sectional study, Diabetic Cardiomyopathies, Endocrinology, Diabetes and Metabolism, Blood Pressure, Type 2 diabetes, urologic and male genital diseases, Gastroenterology, Body Mass Index, Endocrinology, Diabetic retinopathy, Reference Values, Chronic kidney disease, eGFR, Diabetic Nephropathies, Albumin excretion rate, General Medicine, Middle Aged, Diabetes and Metabolism, Italy, Cohort, Female, medicine.symptom, Albumin excretion rate, Chronic kidney disease, Diabetic retinopathy, eGFR, Type 2 diabetes, medicine.medical_specialty, Diabetes Complications, Diabetes mellitus, Internal medicine, medicine, Internal Medicine, Albuminuria, Humans, Triglycerides, Aged, Glycated Hemoglobin, Albumin excretion rate, Chronic kidney disease, Diabetic retinopathy, Type 2 diabetes, eGFR, business.industry, Cholesterol, HDL, medicine.disease, Blood pressure, Cross-Sectional Studies, Diabetes Mellitus, Type 2, business, Body mass index
Abstract: Aims Within the normoalbuminuric range, low albuminuria (LA, 10-29 mg/24 h) is associated with higher adverse cardiovascular and renal outcomes than normal albuminuria (NA, < 10 mg/24 h). This cross-sectional analysis of the cohort from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study was aimed at assessing the independent correlates of LA versus NA in patients with type 2 diabetes. Methods This analysis involved 11,538 normoalbuminuric patients (73.2 % of the entire RIACE cohort): 6023 (52.2 %) with NA and 5515 (47.8 %) with LA. Binary logistic regression analysis with backward conditional variable selection was applied to assess the independent correlates of LA versus NA. Results Compared with NA subjects, LA patients were more frequently males, older and with family history of hypertension, had longer diabetes duration, lower HDL cholesterol, and higher haemoglobin (Hb) A(1c), triglycerides, and blood pressure (BP), use of anti-hyperglycaemic and anti-hypertensive drugs, and prevalence of metabolic syndrome, retinopathy, chronic kidney disease, any cardiovascular disease, myocardial infarction, and coronary and peripheral events. Men with LA were also more frequently current or former smokers and had higher body mass index, waist circumference, and non-HDL cholesterol. Independent correlates of LA were age (OR 1.018), family history of hypertension (OR 1.321), smoking status (former, OR 1.158; current, OR 1.237), HbA(1c) (OR 1.062), waist circumference (OR 1.050), triglycerides (OR 1.001), and diastolic BP (OR 1.014), together with use of anti-hyperglycaemic and anti-hypertensive agents. Conclusions Several risk factors are associated with increased albuminuria within the normoalbuminuric range. As most of these factors are potentially modifiable, treating them aggressively might reduce the excess risk associated with LA.
Published: 2015

50. Opening of a respiratory intermediate care unit in a general hospital: Impact on mortality and other outcomes

Author: Mario Santagiuliana, Maja Demsar, Cinzia Longo, Rossella Cifaldi, Marco Confalonieri, Mitja Jevnikar, Lucia Pelusi, Riccardo Pistelli, Luca Lattuada, Roberto Trevisan, Confalonieri, Marco, Trevisan, Roberto, Demsar, Maja, Lattuada, Luca, Longo, Cinzia, Cifaldi, Rossella, Jevnikar, Mitja, Santagiuliana, Mario, Pelusi, Lucia, and Pistelli, Riccardo
Subjects: Male, Acute exacerbation of chronic obstructive pulmonary disease, Intermediate Care Facilitie, Acute respiratory failure, Intermediate Care Facility, Pulmonary Disease, Chronic Obstructive, Community-acquired pneumonia, Cause of Death, Outcome Assessment, Health Care, Health care, Odds Ratio, Community-Acquired Infection, Hospital Mortality, Cause of death, Mortality rate, Middle Aged, Hospitals, Community-Acquired Infections, Respiratory intermediate care unit, Treatment Outcome, Female, France, Survival Analysi, Intermediate Care Facilities, Case-Control Studie, Respiratory Insufficiency, Human, Adult, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Chronic Obstructive, Mortality, Aged, Case-Control Studies, Confidence Intervals, Hospitals, General, Humans, Length of Stay, Outcome Assessment (Health Care), Pneumonia, Risk Assessment, Survival Analysis, Pulmonary Disease, medicine, Intensive care medicine, General, business.industry, Odds ratio, medicine.disease, business, Confidence Interval
Abstract: Background: Respiratory intermediate care units (RICUs) are specialized areas aimed at optimizing the cost-benefit ratio of care. No data exist about the impact of opening a RICU on hospital outcomes. Objectives: We wondered if opening a RICU may improve the outcomes of patients with acute respiratory failure (ARF), acute exacerbation of chronic obstructive pulmonary disease (AECOPD), or community-acquired pneumonia (CAP). Methods: We analyzed the discharge abstracts of 2,372 admissions to the RICU and internal medicine units (IMUs) for ARF, AECOPD, and CAP. The IMUs at the Hospital of Trieste comprise emergency and internal wards. In order to investigate the determinants of outcomes, a matched case-control study was performed using clinical records. Results: The in-hospital mortality rate was lower in the RICU vs. IMUs (5.4 vs. 19.1%, p = 0.0001). Statistical differences did not change when comparing the RICU with the emergency and internal wards. After adjusting for potential confounders, the risk of death for patients with CAP, AECOPD, or ARF was significantly higher in the IMUs than in the RICU (OR 6.90, 3.19, and 6.7, respectively, p < 0.04). Both the frequency of transfer to the ICU (6 vs. 12%, p = 0.0001, OR 0.38) and the hospital stay (9.3 vs. 12.1 days, p = 0.0001) were reduced in patients admitted to the RICU compared to those admitted to non-RICUs. Significant differences were found in care management concerning chest physiotherapy, mechanical ventilation, antibiotics, and corticosteroids. Conclusions: The opening of a RICU may be advantageous to reduce in-hospital mortality, the need for ICU admission, and the hospital stay of patients with AECOPD, CAP, and ARF. Better use of care resources contributed to better patient management in the RICU.
Published: 2015

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