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1. 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

2. 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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3. Islamic fasting: cardiovascular disease perspective

Author

Hifza Naz, Rakhshan Haider, Haroon Rashid, Zargham Ul Haq, Jahanzeb Malik, Syed Muhammad Jawad Zaidi, Uzma Ishaq, Roberto Trevisan, Naz, H, Haider, R, Rashid, H, Ul Haq, Z, Malik, J, Zaidi, S, Ishaq, U, and Trevisan, R

Subjects
ramadan fasting, Percutaneous Coronary Intervention, Cardiovascular Diseases, intermittent fasting, Internal Medicine, Diabetes Mellitus, Humans, heart failure, General Medicine, Fasting, Cardiology and Cardiovascular Medicine, Islam, ischemic heart disease
Abstract

Introduction: Ramadan is a month of obligatory fasting observed by the majority of 2 billion Muslims living around the globe. The guidelines for ‘risk-free’ fasting exist for chronic diseases, including diabetes mellitus, but recommendations for cardiovascular disease (CVD) patients are deficient due to the paucity of literature. Areas Covered: Databases were screened to find relevant studies for an evidence-based consensus regarding the risk stratification and management of CVD. Using practical guidelines of the European Society of Cardiology (ESC), we categorized patients into low-, moderate-, and high-risk categories and proposed a pre-Ramadan checklist for the assessment of cardiac patients before fasting. Regular moderate-intensity exercise is recommended for most cardiac patients, which has been demonstrated to provide an anti-inflammatory and antioxidant effect that improves immune function. Expert opinion: In Ramadan, many physiological changes occur during fasting, which brings about a balanced metabolic homeostasis of the body. In addition, Ramadan fasting is a nonpharmacologic means of decreasing CV risk factors. As Islam exempts Muslims from fasting if they are unwell; therefore, patients with the acute coronary syndrome (ACS), advanced heart failure (HF), recent percutaneous coronary intervention (PCI), or cardiac surgery should avoid fasting.

Published
2022

4. Resilience in pregnant women with pre-gestational diabetes during COVID-19 pandemic: the experience of the Papa Giovanni XXIII Hospital in Bergamo, Italy

Author

Maria Simonetta Spada, Alessandro Roberto Dodesini, Roberto Trevisan, Anna Caffi, Dodesini, A, Caffi, A, Spada, M, and Trevisan, R

Subjects
medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Endocrinology, Diabetes and Metabolism, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), MEDLINE, diabetes, pregnancy, COVID-19, General Medicine, medicine.disease, Endocrinology, Family medicine, Diabetes mellitus, Pandemic, Internal Medicine, medicine, Psychology, Resilience (network), Letter to the Editor, Pre-Gestational Diabetes
Published
2020
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5. 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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6. 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

7. 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

8. 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

9. 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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10. 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

11. 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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12. 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, Zhang, Peng, Ai, Jianhua, Ma, Yuxiu, Li, Hongguang, Zheng, Minxiang, Lei, Zhaohui, Mo, Nanwei, Tong, Jinluo, Cheng, Youping, Dong, Xudong, Xu, Qinkai, Chen, Tianjun, Guan, Gang, Long, Changying, Xing, Ling, Li, Yinghong, Liu, Hao, Zhang, Ling, Zhong, Zhonghe, Li, Longyi, Zeng, Jiali, Wei, Hanqing, Cai, Tianfeng, Wu, Weiping, Lu, Ning, Xu, Yibing, Lu, Dejun, Chen, Ruifang, Bu, Jiansong, Shen, Junwu, Dong, Zhiquan, Zhao, Fei, Xiong, Fangfang, Jiang, Jinkui, Yang, Jian, Kuang, Guoyuan, Lu, Lihua, Wang, Yanlin, Zhang, Shuifu, Tang, Weiying, Guo, Jian, Liu, Sheng, Jiang, Fang, Yi, Yuming, Du, Zhuxing, Sun, Yuantao, Liu, Liyong, Zhong, Dongmei, Li, Hongmei, Li, Chuanming, Hao, Feixia, Shen, Jianqin, Wang, Jingmei, Li, Dora, Molina, Carlos, Cure, Jaime, Ibarra, Gustavo, Aroca, Hernán, Yupanqui, Eric, Hernández, Mónica, López, Gregorio, Sánchez, Germán, Barreto, Edgar, Arcos, Miguel, Urina, William, Kattah, Carlos, Durán, Clara, Arango, Julian, Coronel, Guillermo, Blanco, Mónica, Terront, Gustavo, Guzmán, Luis, García, Carlos, Jaramillo, Manuel, Liévano, Diego, Benitez, Tatiana, Cárdenas, Iván, Villegas, Sandra, Barrera, Nicolás, Jaramillo, Rodrigo, Botero, Nelly Beltrán López, Freddy, Trujillo, Martin, Prazny, Jitka Hasalova Zapletalova, Libor, Okenka, Dino, Alferi, Tomas, Edelsberger, Pavel, Tomanek, Jiri, Brezina, Olga, Hola, Jana, Houdova, Petr, Bucek, David, Karasek, Sarka, Kopecka, Richard, Kovar, Michal, Brada, Lucie, Hornova, Eva, Krcova, Hana, Lubanda, Vlasta, Kutejova, Jiri, Kuchar, Helena, Hrmova, Jiri, Pumprla, Magdalena, Mokrejsova, Drahomira, Gulakova, Ivo, Matyasek, Thilo, Krüger, Hermann, Haller, Thorsten, Koch, Ludger, Rose, Diethelm, Tschöpe, Lutz, Stemler, Volker, Schettler, Andreas, Pfützner, Karl, Derwahl, Thomas, Horacek, Helena, Sigal, Heidrun, Täschner, Ingolf, Schiefke, Andreas, Hagenow, Andreas, Birkenfeld, Christoph, Axthelm, Christoph, Wanner, Klaus, Busch, Heike, Schlichthaar, Christoph, Hasslacher, Stefan, Degenhardt, Markus van der Giet, Georg, Strack, Norbert, Schöll, Bernhard, R Winkelmann, Lars, Rump, Ruth, Nischik, Bernd, Schröppel, Thomas, Giebel, Achim, Ulmer, Andrea, Rinke, Christel, Contzen, Wolfgang, Jungmair, Nicole, Toursarkissian, Christof, Kloos, Joachim, Müller, Thomas, Schürholz, Hermann, Braun, Frank, Pistrosch, Per, Poulsen, Claus, Juhl, Joan, Nielsen, Jesper, Bech, Ole, Rasmussen, Peter, Rossing, Jens, Faber, Thure, Krarup, Morten, Lindhardt, Ulrik Pedersen-Bjergaard Pedersen-Bjergaard, Karoline, Schousboe, Jørgen, Hangaard, Sten, Madsbad, Gunnar, Gislason, Grzegorz Jaroslaw Pacyk, Olga González Albarrán, Carlos Sánchez Juan, José Julián Segura de la Morena, Secundino Cigarrán Guldris, Francisco Martínez Deben, José María Pascual Izuel, Julio Pascual Santos, Francesca, Calero, Alfonso, Soto, Manuel Polaina Rusillo, Josep, Redón, Josep, Galcerán, Juan, Mediavilla, Mª Dolores Martínez Esteban, Alfredo, Michán, Fernando de Álvaro, Javier Escalada San Martín, Josep Cruzado Garrit, Cristina, Castro, Fernando Cereto Castro, Rafael Santamaría Olmo, Esteban, Poch, Judith, Martins, Julio Hernández Jaras, Meritxell, Ibernón, Daniel, Seron, Hanane, Bouarich, Maribel, Troya, Jorma, Strand, Ilkka, Kantola, Sakari, Nieminen, Arvo, Koistinen, Kristiina, Kananen, Sakari, Sulosaari, Mikko, Honkasalo, Pirkko, Korsoff, Tuomo, Nieminen, Karita, Sadeharju, Kari, Humaloja, Jorma, Lahtela, Philippe, Zaoui, Jean-Pierre, Fauvel, Ronan, Roussel, Didier, Gouet, Pierre, Serusclat, Sylvaine, Clavel, Bruno, Guerci, Bruno, Verges, Olivier, Moranne, Arnaud, Monier, Alexandre, Klein, François, Chantrel, Yannick LE Meur, Rafik, Mesbah, Bertrand, Cariou, Dominique, Guerrot, Karim, Gallouj, Kieran, Mccafferty, Arutchelvam, Vijayaraman, Yuk-Ki, Wong, Dhanya, Kalathil, Sam, Rice, Sui Phi Kon, Hassan, Kahal, Cuong, Dang, Fahmy, Hanna, Christina, Kyriakidou, Imrozia, Arif, Anne, Kilvert, Pauline, Swift, Ioannis, Stefanidis, Ploumis, Passadakis, Aikaterini, Papagianni, Erifili, Hatziagelaki, Dorothea, Papadopoulou, Ioannis, Boletis, Ioanna, Makriniotou, Theodora, Kounadi, Ioannis, Ioannidis, Paul, Lee, Ching Wan Ronald Ma, Vincent, Yeung, Tai Pang Ip, Ebrahim, Noori, Julianna, Kiss, Eleonora, Harcsa, Albert, Szocs, Szilard, Vasas, Krisztina, Wudi, Robert, Kirschner, Dora, Bajcsi, Beata, Lamboy, Botond, Literati-Nagy, Gabor, Nyirati, Gizella, Petro, Karoly, Schneider, Katalin, Keltai, Akos, Kalina, Peter, Danos, Szilvia, Kazup, Zsolt, Zilahi, Judit, Simon, Laszlo, Kovacs, Marianna, Zsom, Margit, Mileder, Laszlo, Nagy, Yoram, Yagil, Julio, Wainstein, Ofri, Mosenzon, Rosane Abramof Ness, Sydney Ben Chetrit, Faiad, Adawi, Idit, Liberty, Ehud, Grossman, Mazen, Elias, Zaher, Armaly, Evgeny, Farber, Assy, Nimer, Amir, Bashkin, Gil, Chernin, Shai, Efrati, Doron, Schwartz, Noa Berar Yanay, Mariela, Glandt, Robert, Zukermann, Majdi, Halabi, Shaul, Atar, Mahmud, Darawsha, Norberto, Perico, Gaetano La Manna, Giovanni Giorgio Battaglia, Domenico, Santoro, Piermarco, Piatti, Bonora, Enzo, Davide Carlo Maggi, Paolo, Calabrò, Roberto, Cimino, Roberto, Trevisan, Paolo, Fiorina, Antonio, Pisani, Antonello, Pani, Gennaro, Santorelli, Carlo Antonio Bossi, Giancarlo, Tonolo, Enrico, Fiaccadori, Anna Maria Veronelli, Michele, Emdin, Paola, Ponzani, Maria Cristina Gregorini, Franco Luigi Cavalot, Carlo Bruno Giorda, Taro, Shibasaki, Akihiro, Hamasaki, Takashi, Nomiyama, Sunao, Matsubayashi, Junji, Shinoda, Kazunari, Matsumoto, Hideo, Kanehara, Yoshihide, Hirohata, Masayo, Yamada, Jun, Nakazawa, Yoshimitsu, Yamasaki, Mikihiro, Nakayama, Ryuichi, Furuya, Osamu, Ebisui, Satsuki, Kawasaki, Daishiro, Yamada, Masayuki, Noritake, Tamayo, Ishiko, Nobuhiro, Sasaki, Daisuke, Suzuki, Asami, Tanaka, Miyuki, Kubota, Hideo, Araki, Hiroshi, Ohashi, Takeshi, Osonoi, Kazuo, Yamagata, Naruhiro, Fujita, Daisuke, Kanda, Seiichi, Tanaka, Junko, Koide, Masao, Ishii, Takayuki, Ogiwara, Masaaki, Suzuki, Taiji, Sekigami, Takayuki, Higashi, Yuko, Yambe, Yoshiro, Kusano, Hidetoshi, Kikuchi, Hiroaki, Miyaoka, Kiyoe, Kato, Masayuki, Kashima, Fumiko, Yamakawa, Shuji, Horinouchi, Hirofumi, Imoto, Hiroshi, Sobajima, Hidetoshi, Kanai, Naoki, Matsuoka, Hirotaka, Shibata, Akemi, Inagaki, Toshiyuki, Sugiura, Toru, Sugiyama, Hidekatsu, Yanai, Yoshiyuki, Hamamoto, Masahiro, Hatazaki, Terumasa, Hayashi, Kunihisa, Kobayashi, Satoshi, Murao, Makoto, Ujihara, Kazuya, Sugitatsu, Katsunori, Kawamitsu, Ken, Yamakawa, Izumi, Tsunematsu, Fumi, Kikuchi, Hideaki, Jinnouchi, Tetsuyuki, Yasuda, Hajime, Maeda, Yasuto, Matsuo, Hideki, Okamoto, Takeshi, Katsuki, Ken, Yajima, Takeshi, Morita, Masayuki, Inagaki, Wooje, Lee, Jungoo, Kang, Cheol Young Park, Hyesoon, Kim, Singon, Kim, Youcheol, Hwang, Injoo, Kim, Jaehyeon, Kim, Young Min Cho, Byungwan, Lee, Choonhee, Chung, Soo, Lim, Jae Myung Yu, Dovile, Kriauciuniene, Antanas, Navickas, Audrone, Velaviciene, Egle, Urbanaviciene, Gediminas, Urbonas, Jurate, Lasiene, Lina, Radzeviciene, Ron, Gansevoort, Adriaan, Kooy, G Lieverse, A, L Penne, E, Ruud J, M van Leendert, M van Buren, H 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, Madrzejewski, Tomasz, Stompor, Jose, Guia, Amalia, Pereira, Pedro, Melo, Cristina, Roque, Francisco, Rosario, Fernando Teixeira, E Costa, Fernando, Nolasco, Edgar, Almeida, Pedro, Matos, Cesar, Esteves, Rui, Carvalho, Ilidio, Brandao, Susana, Heitor, Ana Vila Lobos, Rosa, Ballesteros, Gil, Silva, Carlos, Barreto, Ana, Silva, Natalya, Vorokhobina, Alexander, Sherenkov, Ivan, Gordeev, Olga, Semenova, Sergey, Levashov, Vyacheslav, Marasaev, Ruslan, Sardinov, Vadim, Klimontov, Vitaliy, Baranov, Nadezhda, Verlan, Albert, Galyavich, Arkadiy, Demko, Zhanna, Kobalava, Elena, Zakharova, Lyudmila, Kvitkova, Oleg, Solovev, Elena, Smolyarchuk, Larisa, Zhukova, Elena, Zhdanova, Andrey, Babkin, Galina, Nechaeva, Olga, Barbarash, Elena, Rechkova, Roman, Libis, Elena, Kosmacheva, Tatyana, Rodionova, Irina, Ipatko, Alexander, Dreval, Nina, Petunina, Elena, Chernyavskaya, Alsu, Zalevskaya, Yuriy, Khalimov, Tatyana, Zykova, Anton, Edin, Ashot, Mkrtumyan, Shamil, Palyutin, Vyacheslav, Mareev, Leonid, Strongin, Olga, Ukhanova, Mikhail, Antsiferov, Davyd, Yakhontov, Leonid, Pimenov, Natalya, Koziolova, Konstantin, Nikolaev, Imad, Merai, Olga, Zanozina, Leyla, Gaysina, Mikhail, Arkhipov, Natalia, Malykh, Oksana, Rymar, Vladimir, Martynenko, Sofya, Malyutina, Polina, Ermakova, Marina, Kalashnikova, Bengt-Olov, Tengmark, Carl-Johan, Lindholm, Dan, Curiac, Ken, Eliasson, Erik, Rein-Hedin, Gregor, Guron, Inga, Soveri, Annette, Bruchfeld, Jonas, Spaak, Malin, Frank, Magnus, Löndahl, Hans, Larnefeldt, Margareta, Hellgren, Olof, Hellberg, Yong Mong Bee, Chee Fang Sum, Ru San Tan, Piyamitr, Sritara, Chaicharn, Deerochanawong, Chatlert, Pongchaiyakul, Natapong, Kosachunhanan, Bancha, Satirapoj, Ahmet, Temizhan, Ibrahim, Gul, Ramazan, Sari, Aytekin, Oguz, Mustafa, Tigen, Huseyin, Yilmaz, Ozer, Badak, Oner, Ozdogan, Talat, Tavli, Necmi, Eren, Murat, Cayli, Sedat, Ustundag, Yavuz, Yenicerioglu, Ismail, Kocyigit, Abdulbaki, Kumbasar, Idris, Sahin, Lee-Ming, Chuang, Ju-Ying, Jiang, Chien-Te, Lee, Der-Cherng, Tarng, Shih-Te, Tu, Mai-Szu, Wu, Ming-Ju, Wu, Chiz-Tzung, Chang, Cheng-Chieh, Hung, Liubov, Sokolova, Borys, Mankovsky, Dmytro, Kogut, Viktoriia, Chernikova, Kateryna, Malyar, Nonna, Kravchun, Volodymyr, Botsyurko, Vitaliy, Maslyanko, Liliya, Martynyuk, Oleksandr, Serhiyenko, Vasyl, Stryzhak, Halyna, Myshanych, Oleksandra, Donets, Iryna, Bondarets, Maryna, Vlasenko, Nataliia, Pertseva, Mariia, Grachova, Ivan, Smirnov, Larysa, Pererva, Ivan, Fushtey, Julia, Komisarenko, Anna, Isayeva, Carl, Meisner, Bobby, Khan, Louis, Maletz, Bradley, Dixon, Ahmed, Arif, Timothy, Jackson, Mirela, Ponduchi, Mahfouz El Shahawy, Salil, Nadkarni, Daniel, Urbach, Jorge, Paoli-Bruno, Henry, Lora, Umar, Farooq, Steven, Zeig, Lance, Rudolph, Nabil, Andrawis, William, Kaye, Jill, Meyer, Khalid, Bashir, Glenn, Heigerick, James, Smelser, Javier Ricardo Colomar, David, Scott, Brian, First, Stuart, Handelsman, Jose, Bautista, Rajesh, Patel, Stephen, Minton, Juan, Frias, Luis, Ramos-Gonez, John, Bertsch, Ali, Iranmanesh, Vivian, Fonseca, Michael, Yuryev, Larry, Popeil, Jose, Cardona, Sanjeev, Saxena, Santosh, Sharma, Edgar, Gonzalez, Richard, Solomon, Muhammad, Khan, Ahmed, Awad, David, Fitz-Patrick, Douglas, Linfert, David, Grant, Susan, Brian, Leon, Fogelfeld, Rafael, Canadas, Pablo, Pergola, Joseph, Soufer, Rakesh, Patel, Shujauddin, Valika, Jonathan, Winston, Allison, D, Maria, Caramori, Stanley, Koch, Anjay, Rastogi, Jonathan, Bornfreund, Michael, Rocco, Maxine, Hamilton, Luis, Garcia-Mayol, Peter, Weissman, Suzanne, Oparil, Gary, Ruoff, Kyaw, Soe, Gary, Korff, Robert, Busch, Alexander, Lurie, Israel, Hartman, Garfield, Samuels, Derek, Lejeune, Visal, Numrungroad, Stephen, Brietzke, Zeid, Kayali, Harold, Szerlip, Steven, Barag, Gilberto, Seco, Damaris, Vega, Osvaldo, Brusco, Camil, Kreit, Humberto, Cruz, Bharat, Mocherla, Sharma, Prabhakar, George, Fadda, Martin, Valdes, Eugene, Soroka, Ramin, Berenji, Sreedhara, Alla, Shweta, Bansal, Odugbesan, A, Karlton, Pettis, Masoud, Azizad, 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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13. 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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14. 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

15. 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. V., Finkelstein, H., Frechtel, G., Fretes, J., Garrido Santos, N., Gonzalez, J., Litvak, M., Loureyro, J., Maffei, L., Maldonado, N., Mohr Gasparini, D., Orio, S., Perez Manghi, F., Rodriguez Papini, N., Sala, J., Schygiel, P., Sposetti, G., Ulla, M., Verra, F., Zabalua, S., Zaidman, C., Crenier, L., Debroye, C., Duyck, F., Scheen, A., Van Gaal, L., Vercammen, C., Damyanova, V., Dimitrov, S., Kovacheva, S., Lozanov, L., Margaritov, V., Mihaylova-Shumkova, R., Nikolaeva, A., Stoyanova, Z., Akhras, R., Beaudry, Y., Bedard, J., Berlingieri, J., Chehayeb, R., Cheung, S., Conway, J., Cusson, J., Della Siega, A., Dumas, R., Dzongowski, P., Ferguson, M., Gaudet, D., Grondin, F., Gupta, A., Gupta, M., Halperin, F., Houle, P. -A., Jones, M., Kouz, S., Kovacs, C., Landry, D., Lonn, E., O'Mahony, W., Peterson, S., Reich, D., Rosenbloom, A., St-Maurice, F., Tugwell, B., Vizel, S., Woo, V., Brychta, T., Cech, V., Dvorakova, E., Edelsberger, T., Halciakova, K., Krizova, J., Lastuvka, J., Piperek, M., Prymkova, V., Raclavska, L., Silhova, E., Urbanek, R., Vrkoc, J., Andersen, U., Bronnum-Schou, J., Hove, J., Jensen, J. 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R., Duran Garcia, S., Elvira Gonzalez, J., Fernandez Rodriguez, J. M., Goday Arno, A., Gomez Huelgas, R., Gonzalez Juanatey, J. R., Hernandez Mijares, A., Jimenez Diaz, V. A., Jodar Gimeno, E., Lucas Morante, T., Marazuela, M., Martell Claros, N., Mauricio Puente, D., Mena Ribas, E., Merino Torres, J. F., Mezquita Raya, P., Nubiola Calonge, A., Ordonez Sanchez, X., Pascual Izuel, J. M., 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. -F., Tien, K. J., Tseng, S. -T., Tu, S. -T., Wang, C. -Y., Wang, J. -H., 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. M., 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, C., 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. 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. P., 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., Mandal, T., Skin function and permeability, Dermatology, Hernandez, A, Green, J, Janmohamed, S, D'Agostino, R, Granger, C, Jones, N, Leiter, L, Rosenberg, A, Sigmon, K, Somerville, M, Thorpe, K, Mcmurray, J, Del Prato, S, Califf, R, 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, 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F, Scheen, A, Van Gaal, L, Vercammen, C, Damyanova, V, Dimitrov, S, Kovacheva, S, Lozanov, L, Margaritov, V, Mihaylova-Shumkova, R, Nikolaeva, A, Stoyanova, Z, Akhras, R, Beaudry, Y, Bedard, J, Berlingieri, J, Chehayeb, R, Cheung, S, Conway, J, Cusson, J, Della Siega, A, Dumas, R, Dzongowski, P, Ferguson, M, Gaudet, D, Grondin, F, Gupta, A, Gupta, M, Halperin, F, Houle, P, Jones, M, Kouz, S, Kovacs, C, Landry, D, Lonn, E, O'Mahony, W, Peterson, S, Reich, D, Rosenbloom, A, St-Maurice, F, Tugwell, B, Vizel, S, Woo, V, Brychta, T, Cech, V, Dvorakova, E, Edelsberger, T, Halciakova, K, Krizova, J, Lastuvka, J, Piperek, M, Prymkova, V, Raclavska, L, Silhova, E, Urbanek, R, Vrkoc, J, Andersen, U, Bronnum-Schou, J, Hove, J, Jensen, J, Kober, L, Kristiansen, O, Lund, P, Melchior, T, Nyvad, O, Schou, M, Boye, A, Cadinot, D, Gouet, D, Henry, P, Kessler, L, Lalau, J, Petit, C, Thuan, J, Voinot, C, Vouillarmet, J, Axthelm, C, Berger, D, Bieler, T, Birkenfeld, A, Bott, J, Busch, K, Caca, K, Chevts, J, Donaubauer, T, Erlinger, R, Funke, K, Grosskopf, J, Hagenow, A, Hamann, M, Hartard, M, Heymer, P, Huppertz, W, Illies, G, Jacob, S, Jung, T, Kahrmann, G, Kast, P, Kellerer, M, Kempe, H, Khariouzov, A, Klausmann, G, Klein, C, Kleinecke-Pohl, U, Kleinertz, K, Koch, T, Kosch, C, Lorra, B, Luedemann, J, Luttermann, M, Maxeiner, S, Milek, K, Moelle, A, Neumann, G, Nischik, R, Oehrig-Pohl, E, Plassmann, G, Pohlmeier, L, Proepper, F, Regner, S, Rieker, W, Rose, L, Samer, H, Sauter, J, Schaper, F, Schiffer, C, Schmidt, J, Scholz, B, Schulze, J, Segner, A, Seufert, J, Sigal, H, Steindorf, J, Stockhausen, J, Stuebler, P, Taeschner, H, Tews, D, Tschoepe, D, Wilhelm, K, Zeller-Stefan, H, Avramidis, I, Bousboulas, S, Bristianou, M, Dimitriadis, G, Elisaf, M, Kotsa, K, Melidonis, A, Mitrakou, A, Pagkalos, E, Papanas, N, Pappas, A, Sampanis, C, Tentolouris, N, Tsapas, A, Tzatzagou, G, Ozaki, R, Hajdu, C, Harcsa, E, Konyves, L, Mucsi, J, Pauker, Z, Petro, G, Ples, Z, Revesz, K, Sandor, V, Vass, V, Avogaro, A, Boemi, M, Bonadonna, R, Consoli, A, De Cosmo, S, Di Bartolo, P, Dotta, F, Frontoni, S, Galetta, M, Gambineri, A, Gazzaruso, C, Giorgino, F, Lauro, D, Orsi, E, Paolisso, G, Perriello, G, Piatti, P, Pontiroli, A, Ponzani, P, Rivellese, A, Sesti, G, Tonolo, G, Trevisan, R, Ahn, C, Baik, S, Cha, B, Chung, C, Jang, H, Kim, C, Kim, H, Kim, I, Lee, E, Lee, H, Lee, K, Moon, K, Namgung, J, Park, K, Yoo, S, Yu, J, Llamas, E, Cervantes-Escarcega, J, Flota-Cervera, L, Gonzalez-Gonzalez, J, Pascoe-Gonzalez, S, Pelayo-Orozco, E, Ramirez-Diaz, S, Saldana-Mendoza, A, Jerjes-Diaz, C, Torres-Colores, J, Vidrio-Velazquez, M, Villagordoa-Mesa, J, Beijerbacht, H, Groutars, R, Hoek, B, Hoogslag, P, Kooy, A, Kragten, J, Lieverse, A, Swart, H, Viergever, E, Ahlqvist, J, Cooper, J, Gulseth, H, Guttormsen, G, Wium, C, Arbanil, H, Calderon, J, Camacho, L, Espinoza, A, Garrido, E, Luna, A, Manrique, H, Revoredo, F, Gonzales, R, Rincon, L, 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, 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

16. 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

17. 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

18. 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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19. 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. ≥. 55/≤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

20. 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

21. 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

22. 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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23. 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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24. 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

25. 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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26. 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

27. 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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28. [Not Available]

Author

Matteo Marco, Riva, Marisa, Santini, Daniela, Borleri, Roberto, Trevisan, and Giovanni, Mosconi

Subjects
Adult, Automobile Driving, Young Adult, Adolescent, Construction Industry, Diabetes Mellitus, Prevalence, Humans, Shift Work Schedule, Middle Aged, Child, Occupational Health, Aged
Abstract

Diabetes is a disease with high social impact and it is important to consider how work may be influenced by it or whether work itself may promote or accelerate its course.The objective was to investigate the prevalence of diabetes in four critical categories of workers. The survey involved construction workers, truck drivers, bus drivers and shift workers in the manufacturing sector.In the years 2012-14 we investigated 2034 males workers, through personal history, physical examination, laboratory tests. The subjects with fasting glucose125 mg/dl underwent a second control and haemoglobin A1c determination. Positive cases were referred to specialist control. Expected prevalence and standardized prevalence ratio (SPR) were calculated using official data regarding diabetes prevalence in Italy.The prevalence of diabetes in 608 truck drivers was 4.4% (expected 2.6%, SPR 1.69, IC95% 1.08 to 2.31); in 860 construction workers 1.9% (expected 2.1%, SPR 0.90, IC95% 0.48 to 1.33); in 378 bus drivers 2.6% (expected 3.5%, SPR 0.74, IC95% 0.29 to 1.20); in 188 shift workers 3.2% (expected 2.1%, SPR 1.52, IC95% 0.33 to 2.71). In the age range 35-59 years the prevalence in 467 truck drivers was 5.1% (expected 2.4%, SPR 2.13, IC 95% 1.29 to 2.96).Diabetes was confirmed to be highly prevalent at working ages. The study highlighted an increased diabetes prevalence among truck drivers, whereas other jobs might represent protective factors; this hypothesis, however, needs further investigation.

Published
2015

29. 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

30. Hypertriglyceridemia Is Independently Associated with Renal, but Not Retinal Complications in Subjects with Type 2 Diabetes: A Cross-Sectional Analysis of the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study

Author

Giuseppe Penno, Anna Solini, Giacomo Zoppini, Cecilia Fondelli, Roberto Trevisan, Monica Vedovato, Gabriella Gruden, Olga Lamacchia, Antonio E Pontiroli, Maura Arosio, Emanuela Orsi, Giuseppe Pugliese, Renal Insufficiency And Cardiovascular Events (RIACE) Study Group, Penno, G, Solini, A, Zoppini, G, Fondelli, C, Trevisan, R, Vedovato, M, Gruden, G, Lamacchia, O, Pontiroli, A, Arosio, M, Orsi, E, and Pugliese, G

Subjects
Male, Genetics and Molecular Biology (all), Complications, lcsh:Medicine, Type 2 diabetes, urologic and male genital diseases, Gastroenterology, Biochemistry, hydroxymethylglutaryl coenzyme A reductase inhibitor, Odds Ratio, Diabetic Nephropathies, Renal Insufficiency, lcsh:Science, Hypertriglyceridemia, Multidisciplinary, Medicine (all), creatinine, Italy, Female, medicine.symptom, triacylglycerol, Retinopathy, Glomerular Filtration Rate, Research Article, medicine.medical_specialty, Statin, medicine.drug_class, Renal function, Diabetes mellitus, Internal medicine, medicine, Albuminuria, Humans, Agricultural and Biological Sciences (all), Biochemistry, Genetics and Molecular Biology (all), Renal Insufficiency, Chronic, business.industry, lcsh:R, medicine.disease, Hypertriglyceridemia, Complications, Type 2 Diabetes, Endocrinology, Cross-Sectional Studies, Diabetes Mellitus, Type 2, albumin excretion rate, type 2 diabetes, chronic kidney disease, egfr, diabetic retinopathy, Type 2 Diabetes, creatinine, triacylglycerol, albuminuria, lcsh:Q, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, Kidney disease
Abstract

Objective Atherogenic dyslipidemia seems to play a major role in microvascular complications and in residual microvascular risk after statin therapy, which reduces triglycerides up to 40%. We assessed whether raised TG levels are associated with an increased burden from microvascular complications in patients with type 2 diabetes. Methods Subjects from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study (n=15,773) were divided in 4 groups depending on whether they had plasma triglycerides below (NTG, 67.8%) or above (HTG, 32.2%) 1.7 mmol/L and were (42.4%) or not on (57.6%) statin therapy. Estimated GFR (eGFR) was calculated from serum creatinine, albuminuria was measured by immunonephelometry or immunoturbidimetry, and retinopathy was evaluated by fundus examination. Results HTG subjects, either with or without statin, had higher prevalence of albuminuria, reduced eGFR and chronic kidney disease (CKD), especially the albuminuric forms, but not of retinopathy, than NTG subjects. In contrast, cardiovascular disease and advanced DR were more prevalent in subjects on statin than in those not, independently of triglyceride levels. Logistic regression analysis confirmed that HTG, without or with statin, was independently associated with micro and macroalbuminuria, mildly to severely reduced eGFR, and all CKD phenotypes, but not with retinopathy. The adjusted odd ratios for CKD increased linearly for every 0.26 mmol/L increase (approximately one decile) in triglyceride levels. The increase was higher with increasing severity of albuminuria, eGFR loss and CKD phenotype as well as in subjects receiving than in those not receiving statin treatment. Conclusions Triglycerides are associated with CKD, but not retinopathy in subjects with type 2 diabetes, independently of statin treatment. These data point to a possible role of hypertriglyceridemia in the development of CKD, though it remains to be demonstrated that diabetic individuals might benefit from triglyceride reduction with statins and eventually with combination therapy with fibrates. Trial Registration www.ClinicalTrials.gov NCT00715481

Published
2015

31. Insulin Resistance and Microalbuminuria

Author

Giuseppe Remuzzi, Borislav D. Dimitrov, Piero Ruggenenti, Antonio Tiengo, Roberto Trevisan, Monica Vedovato, Ilian Iliev, and Aneliya Parvanova

Subjects
medicine.medical_specialty, Proteinuria, business.industry, Endocrinology, Diabetes and Metabolism, Urology, Case-control study, Type 2 diabetes, medicine.disease, Excretion, Endocrinology, Insulin resistance, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Microalbuminuria, Risk factor, medicine.symptom, business
Abstract

Microalbuminuria is a risk factor for renal and cardiovascular disease. A role for insulin resistance in the pathogenesis of microalbuminuria has been suggested but is still unproven. In this case-control, cross-sectional study, we compared glucose disposal rate (GDR), measured by hyperinsulinemic-euglycemic clamp, in 50 pairs of matched type 2 diabetic patients with micro- or normoalbuminuria (main study) and in 29 matched pairs of diabetic patients with macro- or microalbuminuria (substudy). In the main study, GDR was ∼25% lower in micro- than in normoalbuminuric patients (5.20 ± 1.91 vs. 6.86 ± 2.88 mg · kg−1 · min−1, P < 0.05) and was independently associated with microalbuminuria (P = 0.002), with each 1 mg · kg−1 · min−1 decrease predicting ∼40% increased prevalence (odds ratio 1.37 [95% CI 1.14–1.70]). Microalbuminuria was threefold more frequent in patients with GDR ≤7.50 ± 2.56 mg · kg−1 · min−1 than in those with higher GDR (60% vs. 20%, P < 0.005). In the substudy, GDR in macro- and microalbuminuric patients was comparable (5.52 ± 2.56 vs. 5.16 ± 1.61 mg · kg−1 · min−1) and independent of macroalbuminuria. GDR was significantly correlated with urinary albumin excretion rate in the main study (P = 0.004) but not in the substudy (P = 0.60). In type 2 diabetes, more severe insulin resistance is independently associated with microalbuminuria. Longitudinal studies are needed to clarify the role of insulin resistance in the pathogenesis of microalbuminuria and related complications.

Published
2006
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32. Insulin Resistance and Proliferative Retinopathy: A Cross-Sectional, Case-Control Study in 115 Patients with Type 2 Diabetes

Author

Piero Ruggenenti, Antonio Tiengo, Marco Filipponi, Roberto Trevisan, Giuseppe Remuzzi, Borislav D. Dimitrov, Ilian Iliev, Monica Vedovato, and Aneliya Parvanova

Subjects
Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, Type 2 diabetes, Biochemistry, Endocrinology, Insulin resistance, Internal medicine, Diabetes mellitus, Humans, Medicine, Aged, Glycated Hemoglobin, Diabetic Retinopathy, business.industry, Insulin, Biochemistry (medical), Case-control study, Diabetic retinopathy, Middle Aged, medicine.disease, Cross-Sectional Studies, Logistic Models, Diabetes Mellitus, Type 2, Case-Control Studies, Albuminuria, Female, Insulin Resistance, medicine.symptom, business, Retinopathy
Abstract

In this cross-sectional, case-control study we explored the association of proliferative diabetic retinopathy (PDR) with insulin resistance (IR) in type 2 diabetics with serum creatinine less than 2.0 mg/dl. For each PDR case, one reference case with background diabetic retinopathy (BDR) and two controls without retinopathy were identified. IR was evaluated by hyperinsulinemic euglycemic clamp; retinopathy was evaluated by indirect ophthalmoscopy and photography. Patients were matched by age, gender, and body mass index. PDR patients (n = 28) had higher IR and low-density lipoprotein cholesterol and triglyceride levels than BDR patients (n = 29), but comparable levels of glycosylated hemoglobin. Compared with patients without retinopathy (n = 58), those with PDR had higher IR, low-density lipoprotein cholesterol, and albuminuria (P < 0.05); those with BDR had higher glycosylated hemoglobin (P < 0.05), but comparable IR. At multivariate regression analysis, IR was the only independent marker of PDR among patients with retinopathy (P = 0.016). IR also retained its independent predictive value at multiple comparison among all groups (by Kruskal-Wallis test, P = 0.019). In type 2 diabetes, IR is an independent specific marker of proliferative retinopathy that may characterize patients at increased risk for blindness who may benefit most from early screening and therapeutic intervention. Longitudinal studies are needed to evaluate the role of IR in the pathogenesis of proliferative retinopathy.

Published
2004
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33. Nephroprotective Effect of Bosentan in Diabetic Rats

Author

Alessandro Cosenzi, Giuseppe Bellini, Roberto Trevisan, Annamaria Borri, Neva Milutinovic, E. Bernobich, Cosenzi, Alessandro, Bernobich, E, Trevisan, R, Milutinovic, N, Borri, A, and Bellini, G.

Subjects
Blood Glucose, Endothelin Receptor Antagonists, medicine.hormone, medicine.medical_specialty, Urinary system, Kidney, Rats, Inbred WKY, Diabetes Mellitus, Experimental, Endothelins, chemistry.chemical_compound, Transforming Growth Factor beta, Diabetes mellitus, Internal medicine, medicine, Animals, Diabetic Nephropathies, Pharmacology, Sulfonamides, Creatinine, business.industry, Kidney metabolism, Bosentan, medicine.disease, Fibronectins, Rats, Endocrinology, medicine.anatomical_structure, chemistry, Collagen, Cardiology and Cardiovascular Medicine, business, Endothelin receptor, medicine.drug
Abstract

Previous studies have suggested that endothelins could be involved in the pathogenesis of target organ damage in diabetes. The aim of this study was to evaluate the possible protective effect of Bosentan, an antagonist of endothelin receptor, on the kidney of diabetic rats. The study comprised a control group of 10 WKY rats and a group of 22 WKY rats in which diabetes was induced by streptozotocin i.v.; 10 rats were the control group. Diabetic rats received insulin and mean blood glucose was approximately mS 400 mg/dl throughout the study; they were divided into two groups: 11 rats received Bosentan 100 mg/kg/die by gastric gavage and 11 received vehicle for 1 month. Twenty-four hour urine collection was performed before and at the end of the study. Urinary protein excretion rate was expressed as microg urinary protein/mg urinary creatinine. The renal collagen I, fibronectin, and TGFbeta were evaluated by means of immunochemistry. The statistical analysis of the results demonstrates that Bosentan has prevented the increase in urinary protein excretion and that of renal immunoreactive collagen I, fibronectin, and TGFbeta induced by diabetes without reducing blood pressure. This study suggests a new clinical application for the antagonists of endothelin receptors.

Published
2003
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34. Early effects of diabetes on inducible nitric oxide synthase in the kidney

Author

Roberto Trevisan, E. Bernobich, M. Bonavita, L. Campanacci, Alessandro Cosenzi, Giuseppe Bellini, Cosenzi, Alessandro, Bernobich, E, Bonavita, M, Trevisan, R, Bellini, G, and Campanacci, L.

Subjects
Male, medicine.medical_specialty, Afferent arterioles, Nitric Oxide Synthase Type III, Endocrinology, Diabetes and Metabolism, Nitric Oxide Synthase Type II, Kidney, Rats, Inbred WKY, Diabetes Mellitus, Experimental, Nitric oxide, Excretion, chemistry.chemical_compound, Endocrinology, Reference Values, Diabetes mellitus, Internal medicine, Internal Medicine, Animals, Medicine, biology, business.industry, General Medicine, medicine.disease, Streptozotocin, Immunohistochemistry, Rats, Nitric oxide synthase, medicine.anatomical_structure, chemistry, biology.protein, Nitric Oxide Synthase, business, Glomerular hyperfiltration, medicine.drug
Abstract

NO may be responsible for the glomerular hyperfiltration observed in diabetic kidney by inducing vasodilation of the afferent arteriole. The aim of this study was to evaluate which isoform of nitric oxide synthase (NOS) is responsible for increased renal production of NO in diabetic kidney. Thirty male WKY rats were divided into 6 groups. Five rats were sacrificed immediately, five after 20 days. In the other rats, diabetes was induced by streptozotocin. The four diabetic groups were sacrificed respectively after 5, 10, 15 and 20 days. Urine excretion of NO metabolites was assayed; immunochemistry showed the presence of inducible (iNOS) and endothelial constitutive (ecNOS) synthases in the kidney. Urinary excretion of NO metabolites increased significantly in diabetic rats five days after the induction of diabetes and at the end of the study whereas it was unchanged in the control group. Renal ecNOS remained unchanged throughout the study in all rats whereas iNOS increased significantly in diabetic rats from the fifth day until the end of the study. The results demonstrate that iNOS is activated in the kidney of rats, soon after the induction of diabetes, thus suggesting its involvement in the increased production of NO observed immediately after the onset of diabetes.

Published
2002
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35. Resistant hypertension in patients with type 2 diabetes: clinical correlates and association with complications

Author

Monica Vedovato, Emanuela Orsi, Maura Arosio, Marco Giorgio Baroni, Cecilia Fondelli, Anna Solini, Giuseppe Penno, Giuseppe Pugliese, Franco Cavalot, Olga Lamacchia, Roberto Trevisan, Giacomo Zoppini, Solini, A, Zoppini, G, Orsi, E, Fondelli, C, Trevisan, R, Vedovato, M, Cavalot, F, Lamacchia, O, Arosio, M, Baroni, M, Penno, G, and Pugliese, G

Subjects
Male, medicine.medical_specialty, Physiology, Renal function, Type 2 diabetes, Type 2 diabete, Cohort Studies, Diabetic retinopathy, Chronic kidney disease, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Prevalence, Albuminuria, Humans, Renal Insufficiency, Chronic, Antihypertensive Agents, Aged, cardiovascular disease, chronic kidney disease, diabetic retinopathy, resistant hypertension, type 2 diabetes, business.industry, Cardiovascular disease, medicine.disease, Resistant hypertension, Endocrinology, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Italy, Cardiovascular Diseases, Cohort, Hypertension, Female, medicine.symptom, Waist Circumference, Cardiology and Cardiovascular Medicine, business, Cohort study, Kidney disease, Retinopathy, Glomerular Filtration Rate
Abstract

Objective: The phenotype of resistant hypertension in patients with type 2 diabetes has been poorly characterized. This cross-sectional analysis of the large cohort from the Renal Insufficiency and Cardiovascular Events (RIACE) study was aimed at assessing the clinical correlates and association with complications of resistant hypertension in patients with type 2 diabetes. Methods: The RIACE study enrolled 15 773 patients consecutively visiting 19 diabetes clinics during the years 2007-2008. Resistant hypertension, defined as BP values not on target (i.e. >130/80 mmHg, respectively) with three antihypertensive agents, was detected in 2363 individuals (15% of the whole RIACE cohort, 17.4% of hypertensive individuals, and 21.2% of treated hypertensive patients). Patients without resistant hypertension [nonresistant hypertension (NRH)], that is on target with one (n = 1569), two (n = 1369), and three (n = 803) drugs, and individuals with uncontrolled hypertension, that is untreated or not on target with less than three drugs (n = 7440), served as controls. Results: As compared with NRH and uncontrolled hypertension patients, patients with resistant hypertension were older and more frequently women and had significantly higher waist circumference, albuminuria, and serum creatinine, and lower glomerular filtration rate. Prevalence values of chronic kidney disease and advanced retinopathy were significantly higher in resistant hypertension than in both nonresistant hypertension and uncontrolled hypertension individuals, whereas cardiovascular disease was more frequent in resistant hypertension versus uncontrolled hypertension, but not nonresistant hypertension patients, especially those on 2-3 drugs. Conclusions: Resistant hypertension is relatively common in patients with type 2 diabetes. In these individuals, age, female sex and waist circumference are independent correlates of resistant hypertension, which is strongly associated with microvascular (especially renal) disease, whereas relation with macrovascular complications is unclear.

Published
2014

36. [Multidisciplinary management of patients with acute coronary syndrome and diabetes mellitus: from antithrombotic therapy to treatment of hyperglycemia]

Author

Roberta, Rossini, Antonino, Cimino, Stefano, De Servi, Niccolò, Grieco, Corrado, Lettieri, Antonio, Mafrici, Giuseppe, Musumeci, Gianluca, Perseghin, Carlo, Sponzilli, Roberto, Trevisan, and Luigi Oltrona, Visconti

Subjects
Diabetes Complications, Clinical Trials as Topic, Early Diagnosis, Evidence-Based Medicine, Italy, Hyperglycemia, Diabetes Mellitus, Myocardial Revascularization, Prevalence, Humans, Interdisciplinary Communication, Acute Coronary Syndrome, Platelet Aggregation Inhibitors
Abstract

Patients with diabetes mellitus (DM) and acute coronary syndromes (ACS) present a significantly higher risk of developing ischemic complications as compared to nondiabetic patients. Multiple mechanisms contribute to DM patients' enhanced prothrombotic status, including impaired fibrinolysis and coagulation, as well as endothelial and platelet dysfunction. Therefore, antithrombotic agents generally, and antiplatelet agents in particular, represent a logical secondary preventive strategy to reduce the risk of recurrent ischemic events in DM patients with ACS. However, DM patients often show attenuated responses to antiplatelet therapies for ACS patients. DM patients benefit from early coronary angiography and revascularization. Although randomized clinical trials have demonstrated that surgical revascularization is associated with an improved prognosis compared to percutaneous coronary intervention, a tailored revascularization strategy should be provided for each patient. The type of revascularization should be decided on the basis of SYNTAX score, surgical risk profile, and feasibility of total arterial revascularization in case of surgery. An accurate diagnosis and prompt treatment of hyperglycemia should also be provided for all patients. The present multidisciplinary document provides practical recommendations regarding diagnosis of DM and the management of hyperglycemia, from the acute phase to discharge. It is aimed at favoring early detection of hyperglycemia and identification of diabetic patients so as to provide adequate glucose control.

Published
2014

37. Effects of Combined Ezetimibe and Simvastatin Therapy as Compared With Simvastatin Alone in Patients With Type 2 Diabetes

Author

Olimpia Diadei, Silvia Ferrari, Ilian Iliev, Giuseppe Remuzzi, Dario Cattaneo, Antonio Bossi, Piero Ruggenenti, Antonio Belviso, Bogdan Ene-Iordache, Aneliya Parvanova, Stefano Rota, and Roberto Trevisan

Subjects
Adult, Male, Simvastatin, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, Placebo, Gastroenterology, Young Adult, chemistry.chemical_compound, Double-Blind Method, Ezetimibe, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Humans, Aged, Apolipoproteins B, Original Research, Advanced and Specialized Nursing, biology, Cholesterol, business.industry, Anticholesteremic Agents, Clinical Care/Education/Nutrition/Psychosocial Research, Cholesterol, LDL, Middle Aged, medicine.disease, Endocrinology, Diabetes Mellitus, Type 2, chemistry, HMG-CoA reductase, biology.protein, Albuminuria, Azetidines, Drug Therapy, Combination, Female, lipids (amino acids, peptides, and proteins), medicine.symptom, business, medicine.drug, Lipoprotein
Abstract

OBJECTIVE To assess the effects of inhibited gastrointestinal cholesterol absorption in statin-treated dyslipidemic patients. RESEARCH DESIGN AND METHODS In a multicenter prospective randomized double-blind placebo-controlled trial, we primarily compared by ANCOVA the effect of 2-month ezetimibe (10 mg/day) or placebo therapy on LDL cholesterol serum levels in 108 type 2 diabetic patients with albuminuria 135 mg/dl despite simvastatin treatment (40 mg/day). RESULTS Unlike placebo, ezetimibe decreased LDL cholesterol from 99 ± 31 to 66 ± 22 mg/dl, total cholesterol from 162 ± 36 to 124 ± 30 mg/dl, and apolipoprotein B from 83 ± 22 to 64 ± 18 mg/dl (P < 0.0001 for all changes versus placebo). A total of 72 and 17% of patients on ezetimibe or placebo achieved LDL levels CONCLUSIONS Adding ezetimibe to simvastatin therapy helps to improve the pro-atherogenic lipoprotein profile in type 2 diabetic patients who fail to reach recommended lipid targets with statin therapy alone.

Published
2010

38. ACE, PAI-1, decorin and Werner helicase genes are not associated with the development of renal disease in European patients with Type 1 diabetes

Author

Monica Vedovato, Roberto Trevisan, S. De Cosmo, Vincenzo Trischitta, Donatella Colaizzo, Carmela Cisternino, Vittorio Tassi, M. Garrubba, G. Di Minno, P. Cavallo Perin, Simonetta Bacci, C Olivetti, S. Thomas, Maurizio Margaglione, G P Piras, L Zucaro, and Gc Viberti

Subjects
medicine.medical_specialty, Type 1 diabetes, biology, business.industry, Endocrinology, Diabetes and Metabolism, Angiotensin-converting enzyme, medicine.disease, Nephropathy, Diabetic nephropathy, Endocrinology, Polymorphism (computer science), Internal medicine, Diabetes mellitus, Internal Medicine, medicine, biology.protein, Albuminuria, Gene polymorphism, medicine.symptom, business
Abstract

Background Genetic factors are involved in the development of diabetic nephropathy in Type 1 diabetes. We have examined the association of four candidate genes, angiotensin converting enzyme (ACE): insertion/deletion (I/D) polymorphism, plasminogen activator inhibitor-1 (PAI-1): 4G/5G polymorphism, decorin: 179/183/185 polymorphism and Werner syndrome helicase: C/R polymorphism, with the presence of diabetic nephropathy in Type 1 diabetic patients. Methods 175 Type 1 diabetic patients with albuminuria (59 with microalbuminuria and 116 with macroalbuminuria) were compared with 136 Type 1 diabetic patients with normoalbuminuria and duration of disease longer than 15 years (meantSD: 25t8 years). 200 non-diabetic subjects were also studied as background population. Results We found no association in the polymorphism of the four genes examined between patients with and without diabetic nephropathy and the control subjects. Conclusions The genes studied are unlikely to be involved in the susceptibility to nephropathy in Type 1 diabetic patients. Copyright # 1999 John Wiley & Sons, Ltd.

Published
1999
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39. The epidemiology of diabetes mellitus

Author

A Tiengo, Roberto Trevisan, and Monica Vedovato

Subjects
medicine.medical_specialty, endocrine system diseases, medicine.medical_treatment, Population, Environment, Insulin resistance, Internal medicine, Diabetes mellitus, Diabetes Mellitus, Prevalence, Genetic predisposition, Humans, Medicine, Obesity, education, Transplantation, education.field_of_study, business.industry, Insulin, Incidence (epidemiology), nutritional and metabolic diseases, Family aggregation, medicine.disease, Europe, Diabetes Mellitus, Type 1, Endocrinology, Diabetes Mellitus, Type 2, Nephrology, Insulin Resistance, business
Abstract

Insulin-dependent diabetes mellitus (IDDM) develops predominantly in children and young adults, but may appear in all age groups. The incidence of IDDM differs greatly among populations, with Finland and Sardinia showing the greatest incidence rates (approximately 30-35% of cases annually per 100000 children up to age 14 years) and oriental populations showing the lowest rates. IDDM is diagnosed more frequently in the winter months. The major genetic susceptibility to IDDM is linked to the HLA complex on chromosome 6. These genetic backgrounds interact with environmental factors (possibly certain viruses, foods and climate) to initiate the immune-mediated process that leads to beta-cell destruction. Non-insulin dependent diabetes (NIDDM) is the most common form of diabetes. The prevalence of NIDDM varies enormously from population to population. The greatest rates have been found in Pima Indians. The major environmental factors identified as contributing to this form of diabetes are obesity and reduced physical activity. NIDDM shows strong familial aggregation in all populations and is clearly the result of an interaction between genetic susceptibility and environmental factors. Before NIDDM develops, insulin concentrations are high for the degree of glycaemia and of obesity, reflecting the presence of insulin resistance. As insulin resistance worsens, glucose levels increase, with the appearance of glucose intolerance and, finally, of NIDDM, when insulin response cannot compensate for insulin resistance.

Published
1998
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40. Enhanced collagen synthesis in cultured skin fibroblasts from insulin-dependent diabetic patients with nephropathy

Author

Roberto Trevisan, Giancarlo Viberti, Jeannie Yip, Leda Sarika, and Lai Kuen Li

Subjects
Adult, Male, medicine.medical_specialty, Proline, Carbohydrate metabolism, Nephropathy, Extracellular matrix, Diabetic nephropathy, Internal medicine, Diabetes mellitus, medicine, Extracellular, Humans, Diabetic Nephropathies, Fibroblast, Cells, Cultured, Skin, business.industry, General Medicine, Fibroblasts, Middle Aged, medicine.disease, Culture Media, Kinetics, Diabetes Mellitus, Type 1, Glucose, medicine.anatomical_structure, Endocrinology, Nephrology, Case-Control Studies, Protein Biosynthesis, Female, Collagen, business
Abstract

Excessive production and deposition of extracellular matrix proteins are characteristic features of diabetic nephropathy. This study tests the hypothesis that cells from diabetic patients who develop nephropathy have a disturbance in collagen metabolism compared with cells from diabetic patients without complications. Kinetics of overall collagen metabolism and total protein synthesis were examined in serially passaged, subconfluent, quiescent skin fibroblasts cultured in either normal (5 mM) or high (25 mM) glucose concentrations from 14 insulin-dependent diabetic (IDDM) patients with nephropathy; 14 IDDM patients without nephropathy matched for age, diabetes duration, and body mass index; and 14 healthy subjects. Fibroblasts were incubated in the presence of 2 microCi/ml [3H]proline, and after labeling the incorporation of [3H]proline into total protein, collagen (collagenase-sensitive material), and noncollagen proteins (collagenase-resistant material) was determined at different time points. Collagen degradation was determined in pulse-chase experiments by following the residual collagen-bound radioactivity after incubation for 8 h with 10 microCi/ml [3H]proline. In high glucose concentrations (25 mM), overall collagen synthesis (measured as [3H]proline incorporation into extracellular and intracellular collagenase-sensitive material) was significantly greater in the patients with nephropathy (mean +/- SEM after a 24-h labeling period: 7189 +/- 671 dpm/10(6) cells) than in the patients without (4341 +/- 267 dpm/10(6) cells; P < 0.01) or healthy control subjects (3836 +/- 234 dpm/10(6) cells; P < 0.01). No significant differences were observed in noncollagen protein production or in collagen degradation rates among the three groups of subjects. In the presence of normal glucose concentrations (5 mM), collagen synthesis was lower in all groups studied, but the differences between IDDM patients with nephropathy and those without remained unaltered. These results suggest that long-term cultured fibroblasts derived from diabetic patients with nephropathy exhibit an abnormality in collagen metabolism. Cells from long-standing diabetic patients without nephropathy have normal collagen metabolism. The increased collagen synthesis is likely to be intrinsic to those diabetic patients susceptible to nephropathy and may play an important role in the sclerotic processes that occur in the kidneys, arteries, and heart.

Published
1997
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41. Age, renal dysfunction, cardiovascular disease, and antihyperglycemic treatment in type 2 diabetes mellitus: findings from the Renal Insufficiency and Cardiovascular Events Italian Multicenter Study

Author

Anna Solini, Roberto Trevisan, Susanna Morano, Ele Ferrannini, Cecilia Fondelli, Monica Vedovato, Emanuela Orsi, Enzo Bonora, Giuseppe Penno, Mauro Cignarelli, Giuseppe Pugliese, Franco Cavalot, Solini, A, Penno, G, Bonora, E, Fondelli, C, Orsi, E, Trevisan, R, Vedovato, M, Cavalot, F, Cignarelli, M, Morano, S, Ferrannini, E, and Pugliese, G

Subjects
Male, endocrine system diseases, age, glomerular filtration rate, albuminuria, cardiovascular disease, oral hypoglycemic agents, Health Behavior, Cohort Studies, Epidemiology, Diabetic Nephropathies, Age Factors, Middle Aged, Repaglinide, Metformin, Treatment Outcome, Italy, Cardiovascular Diseases, Disease Progression, Drug Therapy, Combination, Female, medicine.symptom, medicine.drug, Glomerular Filtration Rate, medicine.medical_specialty, oral hypoglycemic agent, Renal function, Internal medicine, Diabetes mellitus, medicine, Albuminuria, Humans, Hypoglycemic Agents, Life Style, Aged, business.industry, Type 2 Diabetes Mellitus, medicine.disease, Drug Utilization, Endocrinology, Diabetes Mellitus, Type 2, Kidney Failure, Chronic, Thiazolidinediones, Geriatrics and Gerontology, business, Diabetic Angiopathies, Kidney disease
Abstract

Objectives: To assess the distribution of antihyperglycemic treatments according to age and renal function and its relationship with cardiovascular disease in type 2 diabetes mellitus (T2DM). Design: Cross-sectional analysis. Setting: Nineteen hospital-based diabetes mellitus clinics in 2007 and 2008. Participants: Fifteen thousand seven hundred thirty-three individuals with T2DM from the Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study. Measurements: Current antihyperglycemic treatments were recorded. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Albuminuria was measured using immunonephelometry or immunoturbidimetry. Prevalence of major acute cardiovascular events was calculated according to age quartiles, treatments, and categories of eGFR (1 = ?90; 2 = 60�89; 3 = 30�59; and 4 =

Published
2013

42. Hemoglobin A1c variability as an independent correlate of cardiovascular disease in patients with type 2 diabetes: a cross-sectional analysis of the Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study

Author

Franco Cavalot, Giuseppe Pugliese, Cecilia Fondelli, Giuseppe Penno, Susanna Morano, Roberto Trevisan, Giacomo Zoppini, Olga Lamacchia, Gianpaolo Zerbini, Monica Vedovato, Emanuela Orsi, Anna Solini, Penno, G, Solini, A, Zoppini, G, Orsi, E, Fondelli, C, Zerbini, G, Morano, S, Cavalot, F, Lamacchia, O, Trevisan, R, Vedovato, M, and Pugliese, G

Subjects
hemoglobin a(1c), Male, medicine.medical_specialty, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Aged, Cardiovascular Diseases, Cohort Studies, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Diabetic Retinopathy, Female, Hemoglobin A, Glycosylated, Humans, Longitudinal Studies, Middle Aged, Risk Factors, Glycosylated, Renal function, Type 2 diabetes, Type 2 diabete, Nephropathy, Interquartile range, Diabetes mellitus, Internal medicine, Chronic kidney disease, Diabetes Mellitus, medicine, Retinopathy, retinopathy, hemoglobin a1c, type 2 diabetes, risk factors, chronic kidney disease, Original Investigation, Macrovascular disease, Glycated Hemoglobin, business.industry, nutritional and metabolic diseases, Hemoglobin A, medicine.disease, Risk factors, Hemoglobin A1c, Albuminuria, Risk factor, medicine.symptom, business, Cardiology and Cardiovascular Medicine, Type 2, Kidney disease
Abstract

Background Previous reports have clearly indicated a significant relationship between hemoglobin (Hb) A1c change from one visit to the next and microvascular complications, especially nephropathy (albuminuria and albuminuric chronic kidney disease, CKD). In contrast, data on macrovascular disease are less clear. This study was aimed at examining the association of HbA1c variability with cardiovascular disease (CVD) in the large cohort of subjects with type 2 diabetes from the Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study. Methods Serial (3–5) HbA1c values obtained during the 2-year period preceding recruitment, including that obtained at the enrolment, were available from 8,290 subjects from 9 centers (out of 15,773 patients from 19 centers). Average HbA1c and HbA1c variability were calculated as the intra-individual mean (HbA1c-MEAN) and standard deviation (HbA1c-SD), respectively, of 4.52±0.76 values. Prevalent CVD, total and by vascular bed, was assessed from medical history by recording previous documented major acute events. Diabetic retinopathy (DR) was assessed by dilated fundoscopy. CKD was defined based on albuminuria, as measured by immunonephelometry or immunoturbidimetry, and estimated glomerular filtration rate, as calculated from serum creatinine. Results HbA1c-MEAN, but not HbA1c-SD, was significantly higher (P1c-MEAN, and 0.47 (0.29-0.75) and 0.46 (0.28-0.73), respectively, for HbA1c-SD. Logistic regression analyses showed that HbA1c-MEAN, but not HbA1c-SD (and independent of it), was a significant correlate of any CVD. Similar findings were observed in subjects with versus those without any coronary or cerebrovascular event or myocardial infarction. Conversely, none of these measures were associated with stroke, whereas both correlated with any lower limb vascular event and HbA1c-SD alone with ulceration/gangrene. All these associations were independent of known CVD risk factors and microvascular complications (DR and CKD). Conclusions In patients with type 2 diabetes, HbA1c variability has not a major impact on macrovascular complications, at variance with average HbA1c, an opposite finding as compared with microvascular disease, and particularly nephropathy. Trial registration ClinicalTrials.Gov NCT00715481

Published
2013

43. Enhanced Effects of Insulin and Angiotensin II on Intracellular pH and Free Cytosolic Calcium in Fibroblasts from Microalbuminuric Patients with Non-Insulin-Dependent Diabetes Mellitus

Author

Roberto Trevisan, F Di Virgilio, M. Trevisan, M. R. Cipollina, Elena Duner, Romano Nosadini, Trevisan, R, Duner, E, Cipollina, M, Divirgilio, F, Trevisan, M, and Nosadini, R

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, Intracellular pH, Population, Cell Culture Techniques, Skin fibroblasts, chemistry.chemical_element, Calcium, Cytosol, insulin, angiotensin II, diabetes mellitus, Internal medicine, Diabetes mellitus, medicine, Non-insulin-dependent diabetes, Albuminuria, Humans, Insulin, education, Aged, Skin, education.field_of_study, business.industry, Angiotensin II, General Medicine, Fibroblasts, Hydrogen-Ion Concentration, Middle Aged, medicine.disease, Free cytosolic calcium, Endocrinology, Diabetes Mellitus, Type 2, chemistry, Microalbuminuria, Female, business, Cation transport
Abstract

1. Whether an alteration in cell membrane cation transport after exposure to insulin and angiotensin II (two important growth promoters that have been shown to be involved in the pathogenesis of atherosclerosis and hypertension) is present in cells from non-insulin-dependent diabetes patients with microalbuminuria, a known risk factor for cardiovascular and renal disease, is unknown. We therefore examined intracellular pH and calcium changes after acute exposure to insulin and angiotensin II in cultured skin fibroblasts from eight non-insulin-dependent diabetes patients with and eight others without microalbuminuria and from a group of seven matched, normal control subjects. 2. Cultured fibroblasts were loaded with 2′,7′-bis (2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester or fura 2-acetoxymethyl ester for continuous monitoring of intracellular pH and free calcium concentrations respectively. 3. In quiescent growth-arrested cells, both intracellular pH and free calcium concentrations were similar in the three groups of subjects. Acutely, insulin induced a gradual alkalinization in all groups of patients. The pH increase was significantly greater in non-insulin-dependent diabetes mellitus patients with microalbuminuria (ΔpH +0.24 ± 0.04 pH units) than in normoalbuminuric patients with non-insulin-dependent diabetes mellitus (0.08 ± 0.02; P < 0.01) and normal control subjects (0.05 ± 0.01; P < 0.01). Although the alkalinizing effect of angiotensin II was smaller than that obtained by insulin, intracellular pH increase after angiotensin addition was more pronounced in non-insulin-dependent diabetes mellitus patients with microalbuminuria (ΔpH ± 0.14 ± 0.04 pH units) than in those without (0.08 ± 0.02; P < 0.01) and in normal control subjects (0.02 ± 0.02; P < 0.01). That the increase in intracellular pH was mediated by the sodium—hydrogen antiport was demonstrated by its dependence on the presence of sodium in the medium and its inhibition by amiloride. Whereas insulin addition did not evoke any significant increase in intracellular free calcium levels in fibroblasts from the three groups studied, angiotensin II evoked a fast and transient rise in intracellular free calcium that was higher in fibroblasts from microalbuminuric patients with non-insulin-dependent diabetes mellitus than in cells from normoalbuminuric patients with non-insulin-dependent diabetes mellitus and control subjects. In the whole population of patients with non-insulin-dependent diabetes mellitus, the increase in intracellular pH after exposure to angiotensin II was positively correlated with intracellular free calcium increase (r = 0.53; P < 0.05), suggesting a possible role of intracellular free calcium levels in the activation of the sodium—hydrogen antiport. 4. In conclusion, we have described an association between increased agonist-induced responsiveness of sodium—hydrogen antiport activity and the presence of microalbuminuria in patients with non-insulin-dependent diabetes mellitus. This increased responsiveness, persisting in cultured fibroblasts after several passages in vitro, suggests that in vitro phenotypic characteristics of fibroblasts are likely to be genetically determined and to be, at least in part, independent of the degree of metabolic control in vivo.

Published
1996
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44. Effect of low-dose ramipril on microalbuminuria in normotensive or mild hypertensive non-insulin-dependent diabetic patients*

Author

Antonio Tiengo and Roberto Trevisan

Subjects
Ramipril, medicine.medical_specialty, Chemotherapy, endocrine system diseases, biology, business.industry, medicine.medical_treatment, Insulin, Urology, Angiotensin-converting enzyme, urologic and male genital diseases, medicine.disease, female genital diseases and pregnancy complications, Endocrinology, Blood pressure, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Albuminuria, biology.protein, Microalbuminuria, medicine.symptom, business, medicine.drug
Abstract

Microalbuminuria predicts early mortality and renal disease in non-insulin-dependent diabetic patients. In insulin-dependent diabetic patients, angiotensin converting enzyme inhibition decreases microalbuminuria and retards the progression of renal disease. The aim of this study was to evaluate the effect of low dose ramipril on albumin excretion rate (AER) and blood pressure in non-insulin-dependent diabetic patients with persistent microalbuminuria (AER > 20 P

Published
1995
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45. Glomerular hyperfiltration and renal disease progression in type 2 diabetes

Author

Alessandro Roberto Dodesini, Silvia Ferrari, Nicola Motterlini, Antonio Cannata, Piero Ruggenenti, Antonio Bossi, Esteban Porrini, Claudia Cella, Jelka Zaletel, Flavio Gaspari, Nadia Stucchi, Giuseppe Remuzzi, Ilian Iliev, Roberto Trevisan, Fabiola Carrara, Aneliya Parvanova, Ruggenenti, P, Porrini, E, Gaspari, F, Motterlini, N, Cannata, A, Carrara, F, Cella, C, Ferrari, S, Stucchi, N, Parvanova, A, Iliev, I, Dodesini, A, Trevisan, R, Bossi, A, Zaletel, J, and Remuzzi, G

Subjects
Blood Glucose, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Kidney Glomerulus, Urology, Renal function, Type 2 diabetes, Nephropathy, Cohort Studies, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Albuminuria, Humans, Diabetic Nephropathies, Aged, Advanced and Specialized Nursing, business.industry, Hazard ratio, Middle Aged, medicine.disease, Endocrinology, Diabetes Mellitus, Type 2, Diabetic Nephropathie, Microalbuminuria, Female, Cohort Studie, medicine.symptom, Kidney Glomerulu, business, Glomerular hyperfiltration, Human, Glomerular Filtration Rate
Abstract

OBJECTIVE To describe the prevalence and determinants of hyperfiltration (glomerular filtration rate [GFR] ≥120 mL/min/1.73 m2), GFR decline, and nephropathy onset or progression in type 2 diabetic patients with normo- or microalbuminuria. RESEARCH DESIGN AND METHODS We longitudinally studied 600 hypertensive type 2 diabetic patients with albuminuria RESULTS Over a median (range) follow-up of 4.0 (1.7–8.1) years, GFR declined by 3.37 (5.71–1.31) mL/min/1.73 m2 per year. GFR change was bimodal over time: a larger reduction at 6 months significantly predicted slower subsequent decline (coefficient: −0.0054; SE: 0.0009), particularly among hyperfiltering patients. A total of 90 subjects (15%) were hyperfiltering at inclusion, and 11 of 47 (23.4%) patients with persistent hyperfiltration progressed to micro- or macroalbuminuria versus 53 (10.6%) of the 502 who had their hyperfiltration ameliorated at 6 months or were nonhyperfiltering since inclusion (hazard ratio 2.16 [95% CI 1.13–4.14]). Amelioration of hyperfiltration was independent of baseline characteristics or ACE inhibition. It was significantly associated with improved BP and metabolic control, amelioration of GDR, and slower long-term GFR decline on follow-up. CONCLUSIONS Despite intensified treatment, patients with type 2 diabetes have a fast GFR decline. Hyperfiltration affects a subgroup of patients and may contribute to renal function loss and nephropathy onset or progression. Whether amelioration of hyperfiltration is renoprotective is worth investigating.

Published
2012

46. The GFR and GFR decline cannot be accurately estimated in type 2 diabetics

Author

Flavio Gaspari, Fabiola Carrara, Piero Ruggenenti, Esteban Porrini, Alejandro Jiménez Sosa, Roberto Trevisan, Claudia Cella, Nicola Motterlini, Nadia Stucchi, Antonio Bossi, Jelka Zaletel, Silvia Ferrari, Antonio Cannata, Aneliya Parvanova, Ilian Iliev, Giuseppe Remuzzi, Gaspari, F, Ruggenenti, P, Porrini, E, Motterlini, N, Cannata, A, Carrara, F, Sosa, A, Cella, C, Ferrari, S, Stucchi, N, Parvanova, A, Iliev, I, Trevisan, R, Bossi, A, Zaletel, J, and Remuzzi, G

Subjects
medicine.medical_specialty, Time Factors, Concordance, Iohexol, Slovenia, Urology, Renal function, Type 2 diabetes, Kidney, Models, Biological, chemistry.chemical_compound, Predictive Value of Tests, Diabetes mellitus, Internal medicine, medicine, gloerular hyperfiltration, type 2 diabetes, diabetic nephropathy, Humans, Diabetic Nephropathies, Aged, Randomized Controlled Trials as Topic, Aged, 80 and over, Creatinine, business.industry, Disease progression, Middle Aged, medicine.disease, Endocrinology, chemistry, Diabetes Mellitus, Type 2, Italy, Nephrology, Predictive value of tests, Disease Progression, business, Biomarkers, medicine.drug, Glomerular Filtration Rate
Abstract

There are no adequate studies that have formally tested the performance of different estimating formulas in patients with type 2 diabetes both with and without overt nephropathy. Here we evaluated the agreement between baseline GFRs, GFR changes at month 6, and long-term GFR decline measured by iohexol plasma clearance or estimated by 15 creatinine-based formulas in 600 type 2 diabetics followed for a median of 4.0 years. Ninety patients were hyperfiltering. The number of those identified by estimation formulas ranged from 0 to 24:58 were not identified by any formula. Baseline GFR was significantly underestimated and a 6-month GFR reduction was missed in hyperfiltering patients. Long-term GFR decline was also underestimated by all formulas in the whole study group and in hyper-, normo-, and hypofiltering patients considered separately. Five formulas generated positive slopes in hyperfiltering patients. Baseline concordance correlation coefficients and total deviation indexes ranged from 32.1% to 92.6% and from 0.21 to 0.53, respectively. Concordance correlation coefficients between estimated and measured long-term GFR decline ranged from -0.21 to 0.35. The agreement between estimated and measured values was also poor within each subgroup considered separately. Thus, our study questions the use of any estimation formula to identify hyperfiltering patients and monitor renal disease progression and response to treatment in type 2 diabetics without overt nephropathy.

Published
2012

47. Skin fibroblasts as a tool for identifying the risk of nephropathy in the type 1 diabetic population

Author

Roberto Trevisan, Lucia Puricelli, Renato Millioni, Elisabetta Iori, Paolo Tessari, Millioni, R, Puricelli, L, Iori, E, Trevisan, R, and Tessari, P

Subjects
Proteomics, medicine.medical_specialty, Sodium-Hydrogen Exchangers, Endocrinology, Diabetes and Metabolism, Population, Skin fibroblast, Diabetic nephropathy, Bioinformatics, Risk Assessment, Nephropathy, Endocrinology, Transforming Growth Factor beta, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Humans, Diabetic Nephropathies, Epigenetics, education, Cells, Cultured, Protein Kinase C, Cell Proliferation, Skin, education.field_of_study, Cultured skin, business.industry, Fibroblasts, medicine.disease, Pathophysiology, Diabetes Mellitus, Type 1, In vitro system, Hyperglycemia, Collagen, business
Abstract

Human fibroblasts in culture have been employed as an in vitro system to investigate some pathophysiological mechanisms of diabetes mellitus also associated with the development of diabetic nephropathy. In fact, there is increasing evidence that genetic factors either convey the risk of, or protect from, diabetic nephropathy and that the expression profiles and/or the behaviour of the cultured skin fibroblasts from type 1 diabetic patients could reflect these genetic influences. On the other hand, alterations could be attributable not only to changes in DNA sequence, but also to epigenetic factors. Our aim is to make a critical overview of the studies involving primary cultures of skin fibroblasts as tools to investigate the pathophysiology of diabetic nephropathy performed until now in this area. Cultured skin fibroblasts could be useful not only for the identification of patients at risk of developing diabetic renal disease, but also for a better understanding of the complex multifactorial mechanisms leading to the long-term complications in diabetes. Copyright © 2011 John Wiley & Sons, Ltd.

Published
2012

48. Type 2 diabetes mellitus is associated with faster degeneration of bioprosthetic valve: results from a propensity score-matched Italian multicenter study

Author

Roberto, Lorusso, Sandro, Gelsomino, Fabiana, Lucà, Giuseppe, De Cicco, Giuseppe, Billè, Rocco, Carella, Emmanuel, Villa, Emanuel, Villa, Gianni, Troise, Mario, Viganò, Carlo, Banfi, Carmine, Gazzaruso, Pier, Gagliardotto, Lorenzo, Menicanti, Francesco, Formica, Giovanni, Paolini, Stefano, Benussi, Ottavio, Alfieri, Matteo, Pastore, Sandro, Ferrarese, Giovanni, Mariscalco, Germano, Di Credico, Cristian, Leva, Claudio, Russo, Aldo, Cannata, Roberto, Trevisan, Ugolino, Livi, Roberto, Scrofani, Carlo, Antona, Andrea, Sala, Gian Franco, Gensini, Jos, Maessen, Andrea, Giustina, Lorusso, R, Gelsomino, S, Lucà, F, De Cicco, G, Billè, G, Carella, R, Villa, E, Troise, G, Viganò, M, Banfi, C, Gazzaruso, C, Gagliardotto, P, Menicanti, L, Formica, F, Paolini, G, Benussi, S, Alfieri, O, Pastore, M, Ferrarese, S, Mariscalco, G, Di Credico, G, Leva, C, Russo, C, Cannata, A, Trevisan, R, Livi, U, Scrofani, R, Antona, C, Sala, A, Gensini, G, Maessen, J, Giustina, A, Luca', F, Bille', G, Vigano', M, Alfieri, Ottavio, Gensini, Gf, Giustina, Andrea, RS: CARIM - R2.12 - Surgical intervention, CTC, and MUMC+: MA Cardiothoracale Chirurgie (3)

Subjects
Male, medicine.medical_specialty, Glycated Hemoglobin A, type 2 diabetes mellitus, Heart Valve Diseases, Diabetes, aortic valve replacement, bioprosthetic valve, Type 2 diabetes, Bioprosthesis Diabetes Mellitus Follow-Up Studies Hyperglycemia Prosthesis Failure Risk Factors, Postoperative Complications, Predictive Value of Tests, Risk Factors, Physiology (medical), Internal medicine, Diabetes mellitus, Diabetes Mellitus, Medicine, Humans, Aged, Bioprosthesis, Diabetes Mellitus, Type 2, Female, Follow-Up Studies, Heart Valve Prosthesis, Hyperglycemia, Incidence, Intensive Care Units, Italy, Multivariate Analysis, Prosthesis Failure, Glycated Hemoglobin, business.industry, Mortality rate, Incidence (epidemiology), Type 2 Diabetes Mellitus, medicine.disease, Confidence interval, Surgery, MED/23 - CHIRURGIA CARDIACA, Predictive value of tests, heart valve surgery, Propensity score matching, Cardiology and Cardiovascular Medicine, business, prosthetic heart valves, Type 2
Abstract

Background— The present study was aimed at determining the impact of type 2 diabetes mellitus (DM) on postoperative bioprosthetic structural valve degeneration. Methods and Results— Twelve Italian centers participated in the study. Patient data refer to bioprosthetic implantations performed from November 1988 to December 2009, which resulted in 6184 patients (mean age 71.3±5.4 years, 60.1% male) being enrolled. Of these patients, 1731 (27.9%) had type 2 DM. The propensity score–matching algorithm successfully matched 1113 patients with type 2 DM with the same number of no-DM patients. The postmatching standard differences were less than 0.1 for each of the covariates, and 64.2% of DM patients were matched. The early (30 days) mortality rate was 7.8% (n=87) versus 2.9% (n=33) in patients with or without type 2 DM ( P P Conclusions— Patients with type 2 DM undergoing bioprosthetic valve implantation are at high risk of early and long-term mortality, as well as of structural valve degeneration.

Published
2011

49. Effects of verapamil added-on trandolapril therapy in hypertensive type 2 diabetes patients with microalbuminuria: the BENEDICT-B randomized trial

Author

Piero, Ruggenenti, Anna, Fassi, Aneliya Parvanova, Ilieva, Ilian Petrov, Iliev, Carlos, Chiurchiu, Nadia, Rubis, Giulia, Gherardi, Bogdan, Ene-Iordache, Flavio, Gaspari, Annalisa, Perna, Paolo, Cravedi, Antonio, Bossi, Roberto, Trevisan, Nicola, Motterlini, Giuseppe, Remuzzi, G C, Viberti, Ruggenenti, P, Fassi, A, Ilieva, A, Iliev, I, Chiurchiu, C, Rubis, N, Gherardi, G, Ene-Iordache, B, Gaspari, F, Perna, A, Cravedi, P, Bossi, A, Trevisan, R, Motterlini, N, and Remuzzi, G

Subjects
Trandolapril, Male, medicine.medical_specialty, Indoles, microalbuminuria, Physiology, Urology, Angiotensin-Converting Enzyme Inhibitors, Type 2 diabetes, normoalbuminuria, Double-Blind Method, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Albuminuria, Humans, Prospective Studies, Antihypertensive Agents, Aged, nephroprotection, type 2 diabete, Proteinuria, business.industry, Hazard ratio, Middle Aged, medicine.disease, Calcium Channel Blockers, cardiovascular event, Endocrinology, Treatment Outcome, Diabetes Mellitus, Type 2, Verapamil, macroalbuminuria, Cardiovascular Diseases, cardioprotection, ACE inhibitor, Hypertension, regression, Microalbuminuria, Female, progression, medicine.symptom, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract

Objectives: To address whether nondihydropyridine calcium-channel blocker added-on angiotensin-converting-enzyme inhibitor therapy ameliorates albuminuria and cardiovascular outcomes in type 2 diabetes patients. Design: The Bergamo Nephrologic Diabetes Complications Trial-B was a multicentre, prospective, double-blind, parallel-group trial comparing renal and cardiovascular outcomes in 281 hypertensive type 2 diabetes patients with microalbuminuria randomized to at least 2-year VeraTran (verapamil/trandolapril 180 mg/2 mg daily) or trandolapril (2 mg daily, identical image) treatment. Main outcome was persistent macroalbuminuria (albuminuria >200 μg/min in two consecutive visits). Treatment targets were SBP/DBP less than 120/80 mmHg and HbA1C less than 7%. Results: Over a median follow-up of 4.5 years, 18 patients (13%) on VeraTran vs. 15 (10.5%) on trandolapril [unadjusted hazard ratio (95% confidence interval [CI]) 1.07 (0.54-2.12), P = 0.852] progressed to macroalbuminuria, respectively; 62 (44.9%) vs. 71 (49.7%) [0.80 (0.57-1.12), P = 0.198] regressed to normoalbuminuria (urinary albumin excretion

Published
2011

50. Na+/H+ Antiport Activity and Cell Growth in Cultured Skin Fibroblasts of IDDM Patients With Nephropathy

Author

Roberto Trevisan, Giancarlo Viberti, James D. Walker, Lai K. Li, Kenneth Earle, T Tariq, Jeanne Messent, Trevisan, R, Li, L, Messent, J, Tariq, T, Earle, K, Walker, J, and Viberti, G

Subjects
Adult, Male, medicine.medical_specialty, Sodium-Hydrogen Exchangers, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Antiporter, Stimulation, Sodium-Hydrogen Antiporter, Lithium, Middle Age, Nephropathy, Amiloride, Reference Values, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Extracellular, Humans, Diabetic Nephropathies, Reference Value, Support, Non-U.S. Gov't, Fibroblast, Cells, Cultured, Ion transporter, Skin, Kinetic, Analysis of Variance, Chemistry, Sodium, Fibroblasts, Middle Aged, Hydrogen-Ion Concentration, medicine.disease, Kinetics, Sodium–hydrogen antiporter, Diabetes Mellitus, Type 1, medicine.anatomical_structure, Endocrinology, Diabetic Nephropathie, Female, Carrier Proteins, Carrier Protein, Diabetes Mellitus, Insulin-Dependent, Cell Division, Human
Abstract

IDDM patients with incipient and overt nephropathy have been found to exhibit an overactivity of RBC sodium-lithium countertransport. To explore the physiological relevance of this finding, we measured the activity of Na+/H+ antiport in serially passaged cultured skin fibroblasts from IDDM patients with and without nephropathy and from normal, nondiabetic control subjects. Na+/H+ antiport activity (measured as the rate of amiloride-sensitive Na+ influx at pH1 = 6.4, extracellular pH = 8.0, and [Na+] = 1 mM) was elevated significantly in IDDM patients with nephropathy compared with IDDM patients without nephropathy and nondiabetic control subjects (13.35 ± 3.8 vs. 8.54 ± 2.0 vs. 7.33 ± 2.3 nmol Na+ · mg protein−1 · min−1; P < 0.006 and P < 0.001, respectively). A kinetic analysis of Na+/H+ antiport activity showed that the raised activity in IDDM patients with nephropathy was caused by an increased Vmax for extracellular Na+. Km values were similar in the three groups. pH-stimulated amiloride-sensitive Na+ influx also was higher under baseline conditions and after serum stimulation in cells from IDDM patients with nephropathy. pHI values were significantly higher, both during active proliferation and after 10-min exposure to serum, in cells from IDDM patients with nephropathy, compared with IDDM patients without nephropathy and nondiabetic control subjects. Serum-stimulated incorporation of [3H]thymidine into DNA was greater in IDDM patients with nephropathy than in the other two groups (35.7 ± 18.9- vs. 17.4 ± 7.5- vs. 11.9 ± 8.7-fold stimulation above baseline; P < 0.01 for both). These data from cultured skin fibroblasts suggest that intrinsic abnormalities in cell function, independent of the metabolic disturbances of diabetes, are characteristic of IDDM patients who develop nephropathy.

Published
1992
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