Effects of Intensive Glucose Lowering in Type 2 Diabetes

Background—Epidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes. We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors. Methods—In this randomized study, 10,251 patients (mean age, 62.2 years) with a median glycated hemoglobin level of 8.1% were assigned to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level from 7.0 to 7.9%). Of these patients, 38% were women, and 35% had had a previous cardiovascular event. The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The finding higher mortality in the intensive-therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up. Results—At 1 year, stable median glycated hemoglobin levels of 6.4% and 7.5% were achieved in the intensive-therapy group and the standard-therapy group, respectively. During follow-up, the primary outcome occurred in 352 patients in the intensive-therapy group, as compared with 371 in the standard-therapy group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P = 0.16). At the same time, 257 patients in the intensive-therapy group died, as compared with 203 patients in the standard-therapy group (hazard ratio, 1.22; 95% CI, 1.01 to 1.46; P = 0.04). Hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group (P<0.001). Conclusions—As compared with standard therapy, the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events. These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.

Glycemic Effects of Once-a-Day Rapid-Acting Insulin Analogue Addition on a Basal Insulin Analogue in Korean Subjects with Poorly Controlled Type 2 Diabetes Mellitus

BackgroundThe present study investigates the efficacy in glycemic control by adding once-a-day glulisine to glargine as a basal plus regimen and factors influencing glycemic control with the basal plus regimen in Korean subjects with type 2 diabetes.MethodsIn the present retrospective study, subjects previously treated with the basal plus regimens for at least 6 months were reviewed. Changes in glycemic profiles and clinical parameters were evaluated.ResultsA total of 87 subjects were ultimately enrolled in this study. At baseline, mean glycated hemoglobin (A1c) and glycated albumin were 8.5% (8.0% to 9.6%) and 25.2±7.6%, respectively. After treatment with the basal plus regimen, patients had significant reductions of A1c at 6 months (0.8±0.1%, P<0.001) and their postprandial glucose levels were decreased by 48.7±10.3 mg/dL (P<0.001). Multiple logistic regression showed old age (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.02 to 1.55), high initial A1c (OR, 22.21; 95% CI, 2.44 to 201.78), and lower amounts of glargine (OR, 0.85; 95% CI, 0.76 to 0.99), and glimepiride (OR, 0.23; 95% CI, 0.06 to 0.93) at baseline were independently associated with good responders whose A1c reduction was more than 0.5%.ConclusionThe authors suggest a basal plus regimen may be effective in reducing glucose levels of subjects with old age, high initial A1c, and patients on low doses of glimepiride and glargine. Despite the use of high doses of hypoglycemic agents, elderly patients with poorly-controlled diabetes are preferred for early initiation of the basal plus regimen

Building capacity for rigorous controlled trials in autism: the importance of measuring treatment adherence

Research groups across Europe have been networking to share information and ideas about research on preschool children with autism. The paper describes preliminary work to develop capacity for future multi-site randomized controlled trials of early intervention, with a specific focus on the need to measure treatment adherence where parents deliver therapy. The paper includes a review of randomized and controlled studies of parent-mediated early intervention from two sources, a recent Cochrane Collaboration review and a mapping of European early intervention studies in autism published since 2002. The data extracted focused on methods for describing parent adherence, that is, how and to what extent parents carry out the strategies taught them by therapists. Less than half of the 32 studies reviewed included any measure of parent adherence. Only seven included a direct assessment method. The challenges of developing pan-European early intervention evaluation studies are discussed, including choice of intervention model and of important outcomes, the need for translation of measurement tools and achievement of joint training to reliability of assessors. Measurement of parent-child interaction style and of adherence to strategies taught need further study

Comparison of Vildagliptin-Metformin and Glimepiride-Metformin Treatments in Type 2 Diabetic Patients

BackgroundThe present study investigated the efficacy and safety of vildagliptin-metformin treatment compared to those of glimepiride-metformin treatment for type 2 diabetes.MethodsIn a randomized, open-label, comparative study, 106 patients with type 2 diabetes were enrolled. The primary endpoint was a reduction in HbA1c from baseline and secondary endpoints included fasting plasma glucose (FPG) or 2-hour postprandial glucose (2h-PPG) reduction from baseline, as well as HbA1c responder rate and HbA1c reduction according to baseline HbA1c category.ResultsComparable HbA1c reduction was observed with a mean±standard deviation change from baseline to the 32-week endpoint of -0.94±1.15% in the vildagliptin group and -1.00±1.32% in the glimepiride group. A similar reduction in 2h-PPG (vildagliptin group 3.53±4.11 mmol/L vs. the glimepiride group 3.72±4.17 mmol/L) was demonstrated, and the decrements in FPG (vildagliptin group 1.54±2.41 mmol/L vs. glimepiride group 2.16±2.51 mmol/L) were not different between groups. The proportion of patients who achieved an HbA1c less than 7% at week 32 was 50.1% in the vildagliptin group and 56.0% in the glimepiride group. An average body weight gain of 2.53±1.21 kg in the glimepiride group was observed in contrast with the 0.23±0.69 kg weight gain noted in the vildagliptin group. A 10-fold lower incidence of hypoglycemia was demonstrated in the vildagliptin group, in addition to an absence of severe hypoglycemia.ConclusionVildagliptin-metformin treatment provided blood glucose control efficacy comparable to that of glimepiride-metformin treatment and resulted in better adverse event profiles with lower risks of hypoglycemia and weight gain

Exenatide compared with long-acting insulin to achieve glycaemic control with minimal weight gain in patients with type 2 diabetes: results of the Helping Evaluate Exenatide in patients with diabetes compared with Long-Acting insulin (HEELA) study

Aim: The Helping Evaluate Exenatide in overweight patients with diabetes compared with Long-Acting insulin (HEELA) study was designed to examine whether the glucagon-like peptide-1 (GLP-1) receptor agonist, exenatide, could improve HbA1c (≤7.4%) with minimal weight gain (≤1 kg) compared with insulin glargine

Increasing Trend in the Number of Severe Hypoglycemia Patients in Korea

BackgroundTo investigate whether the number of subjects with severe hypoglycemia who are brought to a hospital emergency department is increasing and to identify whether there have been changes in the demographic and clinical characteristics of those subjects.MethodsWe analyzed data from the Emergency Departments of two general hospitals in Seoul, Korea. We included data from all adult subjects with type 2 diabetes who presented to an emergency department with severe hypoglycemia between January 1, 2004 and December 30, 2009.ResultsA total of 740 cases of severe hypoglycemia were identified. The mean subject age was 69±12 years, mean duration of diabetes was 13.8±9.3 years, and 53.2% of subjects were receiving insulin therapy. We observed a sharp rise in the number of cases between 2006 and 2007. Stages 3-5 chronic kidney disease was diagnosed in 31.5% of subjects, and low C-peptide levels (<0.6 ng/mL) were found in 25.5%. The mean subject age, duration of diabetes, HbA1c level, and renal and insulin secretory function values did not change significantly during the study period. The proportion of glimepiride use increased, while use of gliclazide decreased among sulfonylurea users. Use of insulin analogues increased, while use of NPH/RI decreased among insulin users.ConclusionWe identified a sharp increase in the number of subjects with severe hypoglycemia presenting to an emergency room since 2006. The clinical characteristics of these subjects did not change markedly during the study period. Nationwide studies are warranted to further clarify this epidemic of severe hypoglycemia

Hotline update of clinical trials and registries presented at the American College of Cardiology Congress 2010: ACCORD, INVEST, NAVIGATOR, RACE II, SORT OUT III, CSP-474, DOSE, ASPIRE and more

This article gives an overview on a number of novel clinical trials in the field of cardiovascular medicine, which were presented during the Late Breaking Clinical Trial Sessions at the 59th annual meeting of the American College of Cardiology in Atlanta, USA, from 14th March to 16th March 2010. The data were presented by leading experts in the field with relevant positions in the trials. These comprehensive summaries should provide the readers with the most recent data on diagnostic and therapeutic developments in cardiovascular medicine similar as previously reported (Schirmer SH, van der Laan AM, Bohm M, Mahfoud F in Clin Res Cardiol 98:691–699, 2009; Maier LS, Schirmer SH, Walenta K, Jacobshagen C, Bohm M in Clin Res Cardiol 98:413–419, 2009)

Association between insulin-induced weight change and CVD mortality: Evidence from a historic cohort study of 18,814 patients in UK primary care.

BACKGROUND: This study explores the association of insulin-induced weight (wt) gain on cardiovascular outcomes and mortality among patients with type 2 diabetes (T2D) following insulin initiation using real-world data. METHODS: A historical cohort study was performed in 18,814 adults with insulin-treated T2D derived from the UK The Health Improvement Network database. Based on the average weight change of 5 kg, 1 year postinsulin initiation, patients were grouped into 5 categories (>5 kg wt loss; 1.0-5.0 kg wt loss; no wt change; 1.0-5.0 kg wt gain; >5.0 kg wt gain) and followed-up for 5 years. Cox proportional hazard models and Kaplan-Meier estimators were fitted to estimate the hazards of a 3-point composite of nonfatal myocardial infarction, stroke, and all-cause mortality between categories. RESULTS: The median age was 62.8 (IQR: 52.3-71.8) years, HbA1c : 8.6% (IQR: 7.4-9.8) and mean BMI: 31.8 (6.5) kg/m2 . The 5 year probability of survival differed significantly within the wt-change categories (log-rank test P value = .0005). Only 1963 composite events occurred. Compared with the weight-neutral group, the risk of composite events was 31% greater in the >5 kg wt-loss group (aHR: 1.31; 95% CI: 1.02, 1.68), the same in the 1.0 to 5.0 kg wt-gain category, but nonsignificantly increased in the 1.0 to 5.0 kg wt loss (15%) and >5.0 kg wt gain (13%) categories, respectively. In the obese subgroup, this risk was 50% (aHR: 1.50, 95% CI: 1.08-2.08) more in the >5 kg weight-loss group compared with the weight-neutral group. CONCLUSION: Insulin-induced weight gain did not translate to adverse cardiovascular outcomes and mortality in patients with T2D. These data provide reassurance on the cardiovascular safety of insulin patients with T2D