Search

Basal-bolus therapy (BBT) refers to the combination of a long-acting basal insulin with a rapid-acting insulin at mealtimes. Basal insulin glargine 100 U/mL and prandial insulin lispro have been available for many years and there is a substantial evidence base to support the efficacy and safety of these agents when they are used in BBT or basal-plus therapy for patients with type 1 or type 2 diabetes mellitus (T1DM, T2DM). With the growing availability of alternative insulins for use in such regimens, it seems timely to review the data regarding BBT with insulin glargine 100 U/mL and insulin lispro. In patients with T1DM, BBT with insulin glargine plus insulin lispro provides similar or better glycemic control and leads to less nocturnal hypoglycemia compared to BBT using human insulin as the basal and/or prandial component, and generally provides similar glycemic control and rates of severe hypoglycemia to those achieved with insulin lispro administered by continuous subcutaneous insulin infusion (CSII). Studies evaluating BBT with insulin glargine plus insulin lispro in patients with T2DM also demonstrate the efficacy and safety of these insulins. Available data suggest that BBT with insulin glargine and insulin lispro provides similar levels of efficacy and safety in pediatric and adult populations with T1DM and in adult patients and those aged more than 65 years with T2DM. These insulin preparations also appear to be safe and effective for controlling T2DM in people of different ethnicities and in patients with T1DM or T2DM and comorbidities., Funding: Eli Lilly and Company.

Introduction: The aim of the study was to evaluate whether the reduction in glycated hemoglobin (HbA1c) observed in clinical trials with liraglutide in type 2 diabetes (T2D) could be attained in routine clinical practice., Methods: ReaL was a multicenter, non-interventional, observational, retrospective, longitudinal study on the effectiveness of liraglutide, a human glucagon-like peptide-1 analog, in individuals with T2D treated in daily practice in Italy. Between 26 March and 16 November 2015, data were taken from clinical records of patients aged ≥ 18 years with treatment follow-up data of up to 24 months and who received their first prescription of liraglutide in 2011., Results: A total of 1723 patients were included in the analysis. At baseline, mean age was 58.9 years, duration of diabetes was 9.6 years, and HbA1c was 8.3%. At 12 months, 36.1% of patients were prescribed the maximum 1.8 mg dose; 43.5% [95% confidence interval (CI): 40.9; 46.2] of patients attained the primary outcome of a reduction in HbA1c of ≥ 1% point at 12 months. At 24 months, 40.9% (95% CI 38.1; 43.7) of patients had attained the HbA1c target of ≤ 7%. Additionally, body weight significantly decreased by 3.4 kg (95% CI - 3.6; - 3.1, p < 0.0001)., Conclusion: In this observational study conducted in routine clinical practice for up to 2 years, treatment with liraglutide improved HbA1c and reduced body weight in a similar fashion to that observed under randomized clinical trial conditions. The data support the use of liraglutide as an effective treatment for T2D in clinical practice., Funding: Novo Nordisk S.p.A., Trial Registration: ClinicalTrials.gov identifier, NCT02255266.

Objectives: The preferred countermeasure to avoid exercise-related hypoglycemia was investigated in a group of patients with type 1 diabetes participating in a stressful event, a 24×1-hour relay marathon. The carbohydrates actually consumed were compared to those estimated for each patient by applying a customizable algorithm, Exercise Carbohydrates Requirement Estimating Software (ECRES), based on patient's usual therapy and diet and on the exercise characteristics., Methods: Glycemia was tested at the start, middle and end of the races. Usual therapies and diets and the adopted countermeasures were recorded in detail., Results: We studied 19 patients who walked/ran 10.4±2.8 km with a heart rate of 167±11 beats per minute. Of the 19 patients, 7 patients reduced the administered insulin (premeal bolus or basal infusion rate). Glycemia fell by the end of the races (p=0.006; median -1.8 mmol⋅L -1 ; interquartile range -0.4 mmol⋅L -1 to -5.3 mmol⋅L -1 ), despite 9 patients being hyperglycemic at the start. Of the patients, 14 concluded the race with glycemia on target, and 4 patients were hyperglycemic. Amounts of carbohydrates actually consumed (median 30 g; interquartile range 0 g to 71 g) were not significantly different from those estimated by ECRES (median 38 g; interquartile range 24 g to 68 g), the 2 quantities being significantly related (R=0.64; p=0.003). ECRES estimated lower carbohydrate levels (-13 g) than the amounts actually consumed by the 4 patients who concluded their exercises with hyperglycemia., Conclusions: Patients preferred to consume extra carbohydrates to avoid the possible exercise-induced hypoglycemia. ECRES would provide satisfactory estimates of the carbohydrate requirements, even for a stressful condition, and almost equal to the quantities consumed following medical advice., (Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Aims: The main objective of this study was to estimate the incidence rate and prevalence of pediatric type 1 diabetes mellitus (T1DM; population 0-18 years of age) in the northeastern Italian region Friuli Venezia Giulia and to characterize the subjects affected by the disease., Methods: This was a retrospective population-based study conducted through the individual-level linkage of several health administrative databases of the Friuli Venezia Giulia region. The incidence rate and prevalence were calculated in the population 0-18 years of age. Using the Mid-p exact method, 95 % confidence intervals for rates were calculated., Results: The incidence rate of pediatric T1DM in the years 2010-2013 was 15.8 new cases/100,000 person-years, peaking in the age class 10-14 years. The rate has increased substantially as compared with the previous regional estimate that dated back to 1993. We observed a seasonal pattern both in the date of birth of the incident cases and in the date of onset of the disease. In the region in 2013, there were 294 prevalent cases (15.1/10,000 inhabitants). Most of them had at least one glycated hemoglobin test in the year. More than 15 % had co-existing autoimmune comorbidities., Conclusions: The incidence rate of pediatric T1DM in Friuli Venezia Giulia has increased in the last years, and the disease is a relevant public health issue in the region.

Objective: Recent studies have demonstrated that Ang1-7 has anti-inflammatory effects. Since the formation of Ang1-7 is significantly altered in the setting of diabetes, here we aimed to evaluate whether Ang1-7 infusion could ameliorate diabetes-induced leukocyte recruitment., Methods: Wild-type male Wistar rats were randomly allocated to the following groups: control + saline, control + Ang1-7, diabetes + saline, diabetes + Ang1-7. Diabetes was induced by streptozotocin. Saline and Ang1-7 (576 μg/kg/day) were injected intraperitoneally daily. After 4 weeks leukocyte trafficking was studied in vivo by intravital microscopy in the mesenteric bed, where the expression of pro-oxidative, proinflammatory, and profibrotic molecules was also assessed. In parallel in vitro studies, HUVEC were grown in 5 mM, 22 mM, 30 mM, 40 mM, 50 mM, and 75 mM glucose media for 48 h, 72 h and 6 days and were treated either with placebo, or with Ang1-7, or with Ang1-7 and its inhibitor A779 in order to evaluate the expression of ICAM-1 and VCAM-1. We further studied leukocytes recruitment in vitro by evaluating PMN-HUVEC adhesion., Results: Ang1-7 prevented in vivo diabetes-induced leukocyte adhesion and extravasation, and it significantly reduced vascular hypertrophy and the other molecular changes due to diabetes. Ang 1-7 prevented also in vitro the hyperglycemia-induced increase of ICAM-1 and VCAM-1 as well as the hyperglycemia-induced PMN adhesion. A779 inhibited Ang 1-7 effects., Conclusions: Ang1-7 significantly reduced diabetes-induced leukocyte recruitment both in vivo and in vitro. These findings emphasize the potential utility of ACE2/Ang1-7/Mas repletion as a strategy to reduce diabetes-induced atherosclerosis., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: Quality of care monitoring is a key strategy for health policy. In Italy, the AMD Annals continuous monitoring and quality improvement initiative has been in place since 2006. Results after 8 years are now available., Research Design and Methods: Quality of diabetes care indicators during the years 2004-2011 were extracted from electronic medical records of 300 diabetes clinics. From 200,000 to 500,000 patients with type 2 diabetes were analyzed per year. Six process indicators, eight intermediate outcome indicators, seven indicators of treatment intensity/appropriateness, and a quality of care summary score (Q score) were evaluated. Previous studies documented that the risk of developing a new cardiovascular event was 80 % higher in patients with a Q score <15 and 20 % higher in those with a score between 15 and 25, as compared to those with a score >25., Results: The proportion of patients with HbA1c ≤7 %, LDL cholesterol <100 mg/dl, and blood pressure ≥140/90 mmHg increased by 4.8, 21.9, and 10.0 %, respectively. Process and treatment intensity/appropriateness indicators consistently improved. The proportion of patients with a Q score <15 decreased from 13.5 to 6.5 %, while those with a Q score >25 increased from 22.9 to 38.5 %., Conclusions: AMD Annals document the progress in quality of diabetes care. Longitudinal improvements in Q score can translate into less cardiovascular events, with evident clinical and economic implications. AMD Annals represent a physician-led effort not requiring allocation of extra-economic resources, which is easy to implement and deeply rooted in routine clinical practice. They are a potential case model for other healthcare systems.

Background: This study aimed at investigating the effects of genetic angiotensin-converting enzyme (ACE) 2 deficiency on glucose homeostasis in the pancreas and skeletal muscle and their reversibility following ACE inhibition., Procedures: ACE2-knockout and C57bl6J mice were placed on a standard diet (SD) or a high-fat diet (HFD) for 12 weeks. An additional group of ACE2-knockout mice was fed a SD and treated with the ACE inhibitor, perindopril (2 mg kg(-1)day(-1)). Glucose and insulin tolerance tests, indirect calorimetry measurements and EchoMRI were performed. Non-esterfied 'free' fatty acid oxidation rate in skeletal muscle was calculated by measuring the palmitate oxidation rate. β-cell mass was determined by immunostaining. Insulin, collectrin, glucose transporter protein, and peroxisome proliferator-activated receptor-γ expression were analysed by RT-PCR. Markers of mithocondrial biogenesis/content were also evaluated., Main Findings: ACE2-knockout mice showed a β-cell defect associated with low insulin and collectrin levels and reduced compensatory hypertrophy in response to a HFD, which were not reversed by perindopril. On the other hand, ACE2 deficiency shifted energy metabolism towards glucose utilization, as it increased the respiratory exchange ratio, reduced palmitate oxidation and PCG-1α expression in the skeletal muscle, where it up-regulated glucose transport proteins. Treatment of ACE2-knockout mice with perindopril reversed the skeletal muscle changes, suggesting that these were dependent on Angiotensin II (Ang II)., Principal Conclusions: ACE2-knockout mice display a β-cell defect, which does not seem to be dependent on Ang II but may reflect the collectrin-like action of ACE2. This defect seemed to be compensated by the fact that ACE2-knockout mice shifted their energy consumption towards glucose utilisation via Ang II., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Patients with metabolic syndrome (MetS) have high cardiovascular event rates. The additional effect of MetS on left ventricular (LV) systolic function in patients with type 2 diabetes mellitus (T2DM) is unknown. We studied the relation between MetS and LV systolic function in T2DM patients without coronary artery disease (CAD). Clinical and echocardiographic data from 331 T2DM patients were analyzed. Prevalence of MetS was assessed based on NCEP ATPIII definition. Stress-corrected midwall shortening (sc-MS) and mitral annular peak systolic velocity (S') were analyzed as indexes of circumferential and longitudinal shortening, respectively. Sc-MS was impaired if <89 %, S' if <8.5 cm/s (10th percentile of healthy controls). MetS was diagnosed in 172 patients. Sc-MS and S' were similar in T2DM patients with and without MetS (91 ± 14 vs 92 ± 15 %; 9.8 ± 2.0 vs 9.5 ± 2.1 cm/s, respectively; p = ns) but significantly reduced comparing to controls (102 ± 11 % and 10.8 cm/s; p < 0.0001). Impairment of sc-MS and S' were detected in 37 vs 40 % and in 29 vs 32 % of T2DM patients with and without MetS (p = ns), respectively. LV systolic function measured as sc-MS and S' is frequently impaired in T2DM patients without CAD; however, the coexistence of MetS is not associated with more severe LV systolic dysfunction. Further pathological mechanisms have to be considered to explain the negative prognostic impact of MetS in T2DM patients.

Background/objective: Left ventricular (LV) circumferential or longitudinal shortening may be impaired in patients with type 2 diabetes mellitus (DM). In the present study, patients with type 2 DM without myocardial ischemia and combined impairment of circumferential and longitudinal (C+L) shortening were studied to assess the prevalence and factors associated with this condition., Methods: Data from 386 patients with type 2 DM enrolled in the SHORTening of midWall and longitudinAl left Ventricular fibers in diabEtes study were analyzed. One hundred twenty healthy subjects were used to define C+L dysfunction. Stress-corrected midwall shortening and mitral annular peak systolic velocity were considered as indexes of C+L shortening and classified as low if <89% and <8.5 cm/s, respectively (10th percentiles of controls)., Results: Combined C+L dysfunction was detected in 66 patients (17%). The variables associated with this condition were lower glomerular filtration rate (OR 0.98 [95% CI 0.96 to 0.99], greater LV mass (OR 1.05 [95% CI 1.02 to 1.08]), high pulmonary artery wedge pressure (OR 1.23 [95% CI 1.04 to 1.44]) and mitral annular calcifications (OR 3.35 [95% CI 1.71 to 6.55]). Considering the entire population, the relationship between stress-corrected midwall shortening and peak systolic velocity was poor (r=0.20), and the model was linear. The relationship was considerably closer and nonlinear in patients with combined C+L dysfunction (r=0.61; P<0.001), having the best fit by cubic function., Conclusions: Combined C+L dysfunction was present in one-sixth of patients with type 2 DM without myocardial ischemia. This condition was associated with reduced renal function, worse hemodynamic status and structural LV abnormalities, and may be considered a preclinical risk factor for heart failure.

Background & Aims: The development and/or progression of metabolic syndrome (MetS) in overweight and obese individuals have been associated to low-grade inflammation, but few studies have simultaneously analyzed the circulating levels of several cytokines., Methods: In this pilot study, a group of 27 cytokines and growth factors was analyzed in the serum of obese patients (n=40) diagnosed for MetS in comparison with sex- and age-matched control subjects without MetS (n=53) by using a multiplex immunoassay. Release of cytokines was measured in culture supernatants of human primary endothelial cells, THP-1 macrophagic cells and HuH-7 hepatoma cells upon exposure to a high fat mixture., Results: While the majority of cytokines did not show significant differences between the investigated groups, the circulating levels of CXCL10/IP-10 and IL-6 were higher in the MetS group versus overweight control group. In contrast, PDGF-BB serum levels were significantly decreased in MetS patients. The in vitro addition of a high fat mixture increased the release of IL-6 and/or CXCL10/IP-10 in the culture supernatant of human primary endothelial cells and THP-1 macrophagic cells, while the same mixture significantly decreased the release of PDGF-BB by human THP-1 macrophagic and HuH-7 hepatoma cells., Conclusions: The current demonstration that MetS is associated with decrease of the pro-fibrotic PDGF cytokine is a completely novel finding, which adds complexity to the interplay between inflammation and fibrosis in patients affected by MetS., (Copyright © 2012. Published by Elsevier Ltd.)

Diabetes mellitus has become increasingly prevalent in recent years, the most dramatic increase being observed in younger women. Diabetes is a multiplier of cardiovascular risk and decreases life expectancy more in women than in men. Diabetic women are less likely to achieve therapeutic targets for cardiovascular risk factors and to be optimally treated. They present more often with atypical symptoms that cause delays in timely recognition and management of cardiovascular disease. Diabetes is an independent risk factor for heart failure and is associated with a worse outcome in women than in men affected by heart failure. Despite the high prevalence of early asymptomatic ventricular dysfunction in diabetics observed in the DYDA and SHORTWAVE studies, female gender was neither a protective nor predisposing factor to ventricular dysfunction or heart failure. Among 1129 outpatients with heart failure, data from the Cardiovascular Epidemiologic Observatory of Trieste show a prevalence of diabetes of 39% in men and 28% in women. In this ongoing epidemiological study, a significantly better prognosis was observed in female than in male diabetics, whereas diabetic and non-diabetic women showed comparable mortality and hospital admission rates. These findings underscore the impact and effectiveness of strict follow-up and management in the high-risk female diabetic population.

Cardiovascular complications are the leading cause of death in diabetes. Over the past decade a number of studies have addressed the underlying mechanisms. Derangements of endothelial function, also referred to as endothelial dysfunction, have emerged to be the crucial early step in the development of atherosclerosis and are also involved in plaque progression and clinical emergence. Endothelial dysfunction is a condition of impaired endothelium-dependent vasodilation and most important of "endothelial activation", characterized by a proinflammatory, proliferative, and procoagulatory milieu that promotes initiation and complications of atherogenesis. A synergistic cross-talk among the conventional cardiovascular risk factors associated with diabetes contributes to disruption of endothelial integrity and accelerated atherosclerosis. This review will focus on the multifactorial nature of endothelial dysfunction in diabetes, the relationship between endothelial dysfunction, conventional cardiovascular risk factors and atherosclerosis, and the therapeutic options to improve endothelial function.

Cardiovascular disease (CVD) is the major cause of morbidity and mortality in patients with diabetes mellitus (DM). The pathophysiology of CVD in diabetes involves traditional and novel cardiac risk factors, including hypertension, dyslipidemia, smoking, genetic factors, hyperglycemia, insulin resistance/hyperinsulinemia, metabolic abnormalities, oxidative/glycoxidative stress, inflammation, endothelial dysfunction, a procoagulant state and myocardial fibrosis. Specific vascular, myopathic and neuropathic alterations have been suggested to be responsible for the excessive cardiovascular morbidity and mortality in diabetes. These alterations manifest themselves clinically as coronary heart disease, congestive heart failure and/or sudden cardiac death. In order to contain the emerging epidemic of CVD in DM, diabetic patients should ideally have excellent glycemic control, a low normal blood pressure and low levels of low-density lipoprotein cholesterol, and be taking an angiotensin-converting enzyme inhibitor and aspirin, which may go some way to containing the emerging epidemic of CVD in DM.

Diabetic nephropathy is now the leading cause of end-stage renal disease in the Western world. Renal disease develops secondary to long-standing hyperglycemia and hemodynamic alterations, which activate a common pathway that ultimately leads to the renal damage. Current strategies to treat diabetic nephropathy include optimization of glycemic control and treatment of glomerular and systemic hypertension. Although these strategies can slow the progression of proteinuria and decline in renal function, diabetic nephropathy remains a huge clinical problem. It is anticipated that future treatment modalities for preventing and treating diabetic nephropathy will involve drugs that modulate common pathogenetic pathways, possibly acting to inhibit both metabolic and hemodynamically induced forms of renal injury. These include inhibitors of growth factor and cytokine release or action, and inhibitors of intracellular second messengers. Although most of these agents have only been investigated in vitro, in animal experiments, or in relatively short-term human studies, these studies suggest that therapeutic strategies which involve a multifactorial approach may be more successful in the treatment of diabetic kidney disease than drugs which influence only one pathway.