Higher Baseline HbA1c Research Articles

Temporal patterns in overweight and obesity in Type 1 diabetes.

Time trends in overweight and obesity in the general population have been well documented; however, temporal patterns in Type 1 diabetes (T1DM) have not been thoroughly investigated. We therefore assessed temporal patterns in overweight and obesity and predictors of weight change in 589 individuals from the Pittsburgh Epidemiology of Diabetes Complications Study, a cohort of childhood-onset T1DM. Participants were first seen in 1986-1988, when mean age and diabetes duration were 29 and 20 years, respectively, and biennially thereafter for 18 years. Overweight was defined as 25.0<or=body mass index (BMI)<30.0 kg/m2. Obesity was defined as BMI>or=30.0 kg/m2. At baseline, the prevalence of overweight and obesity were 28.6% and 3.4%, respectively. After 18 years' follow-up, the prevalence of overweight increased by 47% while the prevalence of obesity increased sevenfold. Seven per cent were on intensive insulin therapy (>or=3 insulin injections per day or on insulin pump) at baseline; by 2004-2007, this was 82%. Predictors of weight change were a higher baseline HbA1c, symptomatic autonomic neuropathy (inversely), overt nephropathy (inversely), and going onto intensive insulin therapy during follow-up. These data demonstrate dramatic weight gain in T1DM and underscore the complexity of weight change in this disease.

Temporal Patterns in Overweight and Obesity in Type 1 Diabetes

Diabet. Med. 27, 398–404 (2010) Abstract Aims Time trends in overweight and obesity in the general population have been well documented; however, temporal patterns in Type 1 diabetes (T1DM) have not been thoroughly investigated. We therefore assessed temporal patterns in overweight and obesity and predictors of weight change in 589 individuals from the Pittsburgh Epidemiology of Diabetes Complications Study, a cohort of childhood-onset T1DM. Methods Participants were first seen in 1986–1988, when mean age and diabetes duration were 29 and 20 years, respectively, and biennially thereafter for 18 years. Overweight was defined as 25.0 ≤ body mass index (BMI) < 30.0 kg/m2. Obesity was defined as BMI ≥ 30.0 kg/m2. Results At baseline, the prevalence of overweight and obesity were 28.6% and 3.4%, respectively. After 18 years’ follow-up, the prevalence of overweight increased by 47% while the prevalence of obesity increased sevenfold. Seven per cent were on intensive insulin therapy (≥ 3 insulin injections per day or on insulin pump) at baseline; by 2004–2007, this was 82%. Predictors of weight change were a higher baseline HbA1c, symptomatic autonomic neuropathy (inversely), overt nephropathy (inversely), and going onto intensive insulin therapy during follow-up. Conclusions These data demonstrate dramatic weight gain in T1DM and underscore the complexity of weight change in this disease.

Efficacy and safety of biphasic insulin aspart 70/30 versus exenatide in subjects with type 2 diabetes failing to achieve glycemic control with metformin and a sulfonylurea

ABSTRACTObjective: To compare safety and efficacy of biphasic insulin aspart 70/30 (BIAsp 30) with exenatide in subjects with type 2 diabetes mellitus (T2DM) not achieving glycemic targets with metformin and sulfonylurea in a randomized, open-label, 24-week trial.Research design and methods: Subjects (N = 372, T2DM > 6 months, age ≥ 18 and ≤ 80 years, HbA1c ≥ 8%, insulin naive not achieving glycaemic targets, receiving metformin and sulfonylurea) were randomized 1: 1: 1 to receive either BIAsp 30 QD (12 U before supper); BIAsp 30 BID (12 U divided equally between pre-breakfast and pre-supper); or exenatide (5 µg BID for 4 weeks and 10 µg BID thereafter). Efficacy (HbA1c, fasting plasma glucose [FPG]) and safety (adverse events and hypoglycemic episodes) were assessed.Results: Glycemic control achieved with both BIAsp 30 BID and BIAsp 30 QD was superior to that with exenatide (BIAsp 30 BID-exenatide: HbA1c difference −0.91% [95% CI: −1.23 to −0.59%] and BIAsp 30 QD-exenatide: difference: −0.67% [95% CI: −0.99 to −0.34%]). At the end of the study, more subjects achieved HbA1c < 7% and ≤ 6.5% in the BIAsp 30 BID group than in the exenatide group (HbA1c < 7%: 37% vs. 20%, p = 0.0060; HbA1c ≤ 6.5%: 25% vs. 8%, p = 0.0004, respectively). Combined hypoglycemic episodes (major, minor, symptoms only) were reported by 56%, 61%, and 29% of the subjects in the BIAsp 30 QD, BIAsp 30 BID, and exenatide groups, respectively. Weight gain was observed in the BIAsp 30 group (BIAsp 30 QD: 2.85 kg, BIAsp 30 BID: 4.08 kg) and weight loss was observed in the exenatide group (−1.96 kg). Nausea or vomiting was responsible for discontinuation of seven subjects in the exenatide group and one subject in the BIAsp 30 BID group.Conclusions: Significantly more T2DM patients (poorly controlled with combination metformin/sulfonylurea) achieved glycemic goals when treated with BIAsp 30 than with exenatide. The high baseline HbA1c values (∼10.2%) and the long duration of diabetes (∼9 years) suggests that some subjects may have been in an advanced stage of their diabetes and may not have had sufficient β-cell function for a GLP-1 mimetic to be effective. The insulin-treated groups had more minor hypoglycemic events and weight gain but less gastrointestinal side-effects. In summary, BIAsp 30 was more efficacious in helping patients with high baseline HbA1c achieve glycemic goals.Clinical trial registration: www.clinicaltrials.gov, NCT00097877

Meta-analysis of health behavior change interventions in type 1 diabetes.

To meta-analyze research testing interventions to improve health behaviors including exercise among adults with type 1 diabetes. Multiple literature-searching strategies identified published and unpublished studies reporting glycated hemoglobin outcomes. Fixed- and random-effects meta-analyses included moderator effects. Data were synthesized across 1435 subjects. The overall effect size was 0.26. This translates into a reduction of 0.33 in mean HbA1c levels between treatment (8.47%) and control (8.80%) groups. Effect sizes were larger with more females, lower body mass index, higher baseline HbA1c, and interventions targeting multiple behaviors. Behavior change interventions improve metabolic control in type 1 diabetes.

Effectiveness of comprehensive diabetes care program in Taiwanese with type 2 diabetes

Objective To assess continuing diabetic education in Taiwan, we evaluated the impact of comprehensive diabetes care program for Taiwanese people with type 2 diabetes. Methods 211 diabetic patients were enrolled and followed up for 1 year at Kaohsiung Medical University Hospital. Patients were provided comprehensive care and their medications were not changed. Clinical and biophysical variables were collected and assessed at 0, 3, 6, 9, 12 months. Results Metabolic control had improved significantly by 1 year: fasting plasma glucose (164.6 ± 60.4 vs. 137 ± 37.5 mg/dl, p < 0.001); total serum cholesterol (198.7 ± 38.8 vs. 187.2 ± 43.1 mg/dl, p < 0.001); high-density lipoproteins cholesterol (43.2 ± 10.2 vs. 46.2 ± 11.7 mg/dl, p < 0.001); low-density lipoproteins cholesterol (121.1 ± 32.9 vs. 113.1 ± 29.6 mg/dl, p < 0.005). In the male group, HbA1c level fell from 8.16 ± 1.99% to 7.61 ± 1.31% and 7.72 ± 1.40% after 9 months and 1 year, respectively, p < 0.05. There were also significant improvements in female group after 6 months and 9 months (7.89 ± 1.62% after 6 months; 7.94 ± 1.66% after 9 months vs. 8.22 ± 1.70% at baseline). The change of HbA1c level was significant in male patients, patients whose duration of disease was shorter and in those with higher baseline HbA1c levels after multi-variable and age-adjusted analysis. Conclusion The comprehensive diabetes care program effectively improved glycemic and cholesterol control. The patients who were more likely to achieve better glycemic control were male, had diabetes for shorter periods of time and had high baseline HbA1c levels. Therefore, diabetic education should be offered to patients as close to the time of diagnosis as possible.

Endothelial dysfunction and low‐grade inflammation and the progression of retinopathy in Type 2 diabetes

To study whether microalbuminuria, endothelial dysfunction and low-grade inflammation are associated with the presence and progression of diabetic retinopathy. Patients with Type 2 diabetes (n = 328) attending a diabetes clinic were followed for 10 years and examined annually during the last 7 years. Retinopathy was assessed after pupillary dilatation by direct ophthalmoscopy (baseline) and two-field 60 degrees fundus photography (follow-up). Urinary albumin excretion, and markers of endothelial function (von Willebrand factor, tissue-type plasminogen activator, soluble E-selectin (sE-selectin), and soluble vascular cell adhesion molecule 1) and inflammatory activity (C-reactive protein and fibrinogen) were determined. The prevalence of retinopathy was 33.8%. The median diabetes duration at baseline was 7 years (interquartile range 2-12 years). The highest tertiles of baseline urinary albumin excretion and glycated haemoglobin (HbA(1c)) were associated with prevalent retinopathy: odds ratio (OR) 95% confidence interval (CI) 2.80 (1.44-5.46) and 2.19 (1.11-4.32), respectively. Progression of retinopathy occurred in 188 patients. The second and third tertiles of baseline sE-selectin were associated with progression of retinopathy [1.44 (1.04-2.01) and 1.61 (1.19-2.18)] but not independently of HbA(1c). None of the other markers was significantly associated with the presence or progression of retinopathy. High baseline HbA(1c) was significantly associated with progression of retinopathy: 1.65 (1.21-2.25). In this population of patients with Type 2 diabetes who attended a diabetes clinic, there was some evidence for a role of endothelial dysfunction in the progression of retinopathy. We could not demonstrate a role for low-grade inflammation. Our study emphasizes the importance of glycaemic control in the development and progression of retinopathy.

Vildagliptin in Drug-naïve Patients with Type 2 Diabetes: A 24-Week, Double-blind, Randomized, Placebo-controlled, Multiple-dose Study

This 24-week double-blind, randomized, multicenter, placebo-controlled, parallel-group study was performed in 632 drug-naïve patients with type 2 diabetes to assess efficacy and tolerability of vildagliptin (50 mg qd, 50 mg bid, or 100 mg qd). HbA1c decreased modestly in patients receiving placebo (Delta=-0.3+/-0.1%) and to a significantly greater extent in patients receiving vildagliptin 50 mg qd (Delta=-0.8+/-0 .1%), 50 mg bid (Delta=-0.8+/-0.1%), or 100 mg qd (Delta=-0.9+/-0.1%, p<0.01 for all groups VS. placebo) from an average baseline of 8.4%. In patients diagnosed >or=3 months before enrollment, HbA1c increased with placebo (Delta=+0.2+/-0.2%) and between-treatment differences (vildagliptin-placebo) were -0.8+/-0.2% (p<0.001), -0.7+/-0.2% (p=0.003), and -0.9+/-0.2% (p<0.001) with vildagliptin 50 mg qd, 50 mg bid, and 100 mg qd, respectively. There was no apparent dose-response in the overall population; however, in patients with high baseline HbA1c, there were greater reductions with either 100 mg dose regimen (Delta=-1.3+/-0.2% and -1.4+/-0.2%) compared to 50 mg qd (Delta=-0.8+/-0.1%). Body weight decreased modestly in all groups (by 0.3 to 1.8 kg). The incidence of adverse events was similar across all groups and <or=1.2% of patients in any treatment group reported mild hypoglycemia. In conclusion, vildagliptin monotherapy decreases HbA1c in drug-naïve patients without weight gain and is well tolerated with minimal hypoglycemia.

A method to predict the metabolic effects of changes in insulin treatment in subgroups of a large population based patient cohort

This case-control study was designed to analyse predictors of the effects on HbA1c levels in 4001 type 1 and type 2 diabetic patients after changing their insulin treatment. Patients from 15 outpatient diabetic clinics were treated with basal insulin and multiple injections of short-acting insulin. The effects on HbA1c of changing from NPH insulin to insulin glargine as basal insulin were studied, compared to patients continuing with NPH insulin. The following possible predictors were examined with multiple regression analysis: age, sex, type and duration of diabetes, smoking, metformin use, insulin requirement, number of basal doses per day, BMI and HbA1c at baseline. The difference between the two regression functions yielded the effect of switching treatment to insulin glargine compared to continuing with NPH insulin. Male gender, low BMI and high baseline HbA1c levels were significant predictors for a greater decrease in HbA1c when changing to insulin glargine. For example, for men with a BMI of 25 and an HbA1c of 8.0%, there was a calculated mean benefit in HbA1c of 0.26 percentage points by changing to insulin glargine, whereas women with a BMI 30 had no benefit of such a change. Thus, changing to insulin glargine had best effect in male patients with low BMI. This is one of the first studies designed to find responders to insulin treatment. Analyses of predictors may prove useful in order to tailor insulin treatment in diabetic patients in clinical practice. The clinical effects need to be confirmed in other studies and randomised controlled trials.

36: Primary and secondary prevention of obesity in older female adolescents attending a reproductive health clinic: A missed opportunity to intervene

the risk of developing life-threatening complications. In chronic illnesses, degree of control can be influenced by quality of life, self-efficacy, and disease management. This study investigates the factors affecting these parameters among adolescents with type 1 DM, including gender-specific differences. Methods: Data were obtained from 47 subjects with type 1 DM, age 12-21 years, enrolled in a clinical trial assessing factors affecting glycemic control. Inclusion criteria included baseline HbA1c 7.5% and 12.0% and duration of diabetes 1 year. Subjects completed the following: Diabetes Quality of Life, a three subscale instrument assessing disease satisfaction, impact, and worries; Diabetes Self-Efficacy, a two subscale instrument used to assess subjective personal ability to control diabetes; Diabetes Expectancy, a measure of how well subjects expect to manage their diabetes over the next three months; and Diabetes Attitudes and Knowledge, a four subscale instrument assessing attitudes, knowledge, beliefs, and healthy/unhealthy weight behaviors. Subjects also completed the Diabetes Self-Management interview. Statistical analyses included linear multiple regression analysis and Cronbach’s coefficient alpha. Results: At baseline, mean age was 16.0 years ([12-21], SD 2.2); 18 subjects (38.3%) were female; 41 subjects (87.2%) were white; mean duration of diabetes was 7.2 years ([1.2-18.3], SD 4.2); and mean HbA1c was 9.6% ([7.5-11.8%], SD 1.2). Diabetes Quality of Life subscales (all 0.80) showed that females reported greater diabetes dissatisfaction (p 0.01) and worry (p 0.10). Worry was associated with age (p 0.05). Females had significantly lower scores (p 0.05) in both Diabetes Self-Efficacy subscales (both 0.80). Duration of diabetes was associated with greater self-efficacy (p 0.05). Females had significantly poorer Diabetes Expectancy scores (p 0.05). Analysis of Diabetes Attitudes and Knowledge subscales (all 0.70) revealed that females were more likely to engage in healthy weight control behaviors (p 0.01) and trended towards significance for unhealthy weight control behaviors (p 0.11). Higher baseline HbA1c was related to unhealthy weight control behaviors (p 0.01). The Diabetes Self-Management interview revealed that females were more likely to report delaying, missing, or altering their insulin doses (p 0.05). Conclusions: Females with type 1 DM report poorer diabetesrelated quality of life, self-efficacy, and diabetes management expectancy, and greater misuse of insulin. These data demonstrate gender-specific correlates of glycemic control and support the need for specific attention to weight management, particularly among young women with type 1 DM. Sources of Support: Roche Diagnostics, Indianapolis, IN; HRSA/ MCHB T71M8.

The effects of orlistat in patients with diabetes: improvement in glycaemic control and weight loss

ABSTRACTObjective: In addition to direct weight reduction, there may be other benefits of obesity treatment including improved insulin sensitivity. The purpose of this study was to characterise concomitant diabetes drug use and the related costs in patients with diabetes treated with orlistat (Xenical) in the first 6 months of treatment.* Xenical is a trade name of Roche Pharmaceuticals, Basle, SwitzerlandMethods: One hundred overweight patients with diabetes and a body mass index (BMI) ≥ 28 kg/m2 were enrolled in a structured UK hospital-based weight management clinic and treated with orlistat plus behavioural interventions. Among other measures, weight, glucose control (HbA1c) and drug treatments were recorded. Subjects were followed-up for a maximum of 24 months at intervals of 1–3 months, with a maximum treatment period of 24 months.Results: The majority of subjects (91%) had type 2 diabetes. They had a mean age of 55 years and 55% were women. For patients followed up at 6 months, their mean BMI at baseline was 39.5 kg/m2 with a mean HbA1c of 7.6%. The mean weight loss at 6 months was 7.1 kg ( p < 0.001). Despite a significant average absolute HbA1c reduction of 0.62% ( p < 0.001), the most notable gains were made by those with the highest baseline HbA1c values (a mean relative reduction of 20% for those above the 75th percentile). There were 50 patients treated with insulin at baseline and 47 at 6 months. Of those treated with insulin, the mean dose was 130 units at baseline and 90 units at 6 months ( p < 0.001). Twenty patients (44.4%) initially treated with oral hypoglycaemic agents alone reduced their dose after 6 months (not significant). Despite marked improvement in insulin sensitivity (baseline mean, 1.24 units/kg; 6 month mean, 0.90 units/kg [p < 0.001]) there was no correlation with BMI change. The average cost of diabetes treatment at baseline was £1.16 per day and £0.83 at 6 months ( p < 0.001). Age was the only independent predictor for insulin dose reduction.Conclusions: Orlistat appears to reduce the need for concomitant diabetes medication irrespective of weight loss, a reduction that is likely to represent a large cost offset for orlistat treatment.

A randomized, double-blind, placebo-controlled, clinical trial of the effects of pioglitazone on glycemic control and dyslipidemia in oral antihyperglycemic medication-naive patients with type 2 diabetes mellitus

Objective: The goal of this study was to compare the effects of 2 doses of pioglitazone hydrochloride (a thiazolidinedione insulin sensitizer) with placebo on glycated hemoglobin (HbA1c), insulin sensitivity, and lipid profiles in patients with type 2 diabetes mellitus who had suboptimal glycemic control and mild dyslipidemia.Methods: Patients with type 2 diabetes mellitus (HbA1c ≥6.5% and ≤9.8%) who had not previously received insulin or oral antihyperglycemic medications (OAMs) were randomized to treatment with placebo, pioglitazone 30 mg QD, or pioglitazone 45 mg QD in double-blind fashion for 16 weeks at 41 centers in Canada and Spain.Results: A total of 297 patients were randomized (99 in each group). Overall, 286 (96.3%) were white. Mean (SD) age was 58.4 (10.9) years (range, 24–85 years), mean (SD) body mass index was 31.4 (4.8) kg/m2, mean (SD) duration of type 2 diabetes mellitus was 20.0 (37.4) months, and 30.6% of patients were receiving medication for dyslipidemia. Treatment with pioglitazone 30 or 45 mg QD for 16 weeks reduced mean HbA1c by 0.8% and 0.9% from baseline, respectively (both P < 0.001 vs baseline and placebo). A reduction in HbA1c of 0.2% was observed in the placebo group (P = 0.025). In patients with medium (≥7% to <8%) or high (≥8% to ≤9.8%) baseline HbA1c, both doses of pioglitazone significantly reduced HbA1c (both P < 0.001 vs plcebo). Pioglitazone 30 and 45 mg significantly reduced fasting serum insulin versus placebo (P = 0.008 and P = 0.006, respectively) and increased insulin sensitivity by Homeostasis Model Assessment versus placebo (P = 0.039 and P = 0.001, respectively). Relative to placebo, pioglitazone 30 and 45 mg significantly increased high-density lipoprotein cholesterol (HDL-C [P = 0.028 and P < 0.001, respectively]) and lowered the atherogenic index of plasma (P = 0.018 and P < 0.001, respectively). Pioglitazone 45 mg also significantly reduced serum triglycerides, apolipoprotein B, and total cholesterol:HDL-C ratio versus placebo (P = 0.007, P = 0.015, and P = 0.005, respectively). Pioglitazone 30 and 45 mg were associated with a significant reduction in serum alanine aminotransferase relative to placebo (P = 0.036 and P = 0.005, respectively). Pioglitazone appeared to be safe and was well tolerated.Conclusions: In the present study, pioglitazone 30 and 45 mg produced significant improvements in HbA1c, insulin sensitivity, and lipid profile in OAM-naive patients with type 2 diabetes mellitus with suboptimal glycemic control and mild dyslipidemia.

Acknowledgement to reviewers

To evaluate predictors of outcomes associated with an inpatient diabetes education and discharge support program for hospitalized patients with poorly controlled diabetes (glycated hemoglobin [HbA1c]>9%).Patients participated in individualized diabetes education conducted by a certified diabetes educator (CDE) that included an exploration of barriers and goal setting during hospitalization with telephone follow-up and communication with primary providers at discharge. Predictors of HbA1c reduction, successful follow-up, and readmission were analyzed.There were 82 subjects, and 48% were insulin naïve. Patients with type 2 diabetes (T2D, n = 58) had a significant decrease in HbAlc at follow-up (-2.8%, P < .0001), while those with type 1 diabetes (T1D, n = 19) did not (+ 0.02%, P = .96). However, after adjustment for other factors, only increasing age, higher baseline HbA1c, earlier education, and initiation of basal insulin were significant predictors of reduction in HbA1c. Higher area level income and empowerment and earlier education were significant predictors of outpatient follow-up within 30 days. While 28% were admitted for severe hyperglycemia, only 1 patient was readmitted with severe hyperglycemia. Successful phone contact was 77% and 57% with and without the support of non-CDE assistants respectively, but all outcomes were similar.The study suggests that an individualized inpatient diabetes education and transition program is associated with a significant reduction in HbA1c that is dependent on baseline HbA1c, older age, initiation of insulin, and earlier enrollment. Additional interventions are needed to ensure better continuity of care. (Endocr Pract. 2014;20:1265-1273)