Cardiovascular Complications Over 5 Years and Their Association With Survival in the GERODIAB Cohort of Elderly French Patients With Type 2 Diabetes.

OBJECTIVE: The GERODIAB study is a multicenter prospective observational study performed over 5 years in French patients aged 70 years or above with type 2 diabetes. This report deals with their cardiovascular complications and their relationship with survival. RESEARCH DESIGN AND METHODS: Consecutive patients (n = 987, median age = 77 years) were included from 56 diabetes centers over 1 year. Individual characteristics, history and complications of diabetes, geriatric factors, and clinical and biological parameters were recorded. Survival was analyzed using the Kaplan-Meier method and proportional hazards regression models. RESULTS: The frequency of cardiovascular complications increased from 47% at inclusion to 67% at 5 years. The most frequent complications were coronary heart disease (increasing from 30% to 41%) and vascular disease of the lower limbs (25% to 35%) and of the cerebral vessels (15% to 26%). Heart failure was less common, but its frequency doubled during the follow-up (9% to 20%). It was strongly associated with poor survival (P < 0.0001), as was vascular disease of the lower limbs (P = 0.0004), whereas coronary heart disease (P = 0.0056) and vascular disease of cerebral vessels (P = 0.026) had mild associations. Amputation (P < 0.0001) and foot wounds (P < 0.0001) were strongly associated with survival. In multivariate models, heart failure was the strongest predictor of poor survival (hazard ratio [HR] 1.96 [95% CI 1.45-2.64]; P < 0.0001). It remained significant when other factors were considered simultaneously (HR 1.92 [95% CI 1.43-2.58]; P < 0.0001). CONCLUSIONS: Cardiovascular complications are associated with poor survival in elderly patients with type 2 diabetes, especially heart failure.

An Effective Intervention for Diabetic Lipohypertrophy: Results of a Randomized, Controlled, Prospective Multicenter Study in France.

BACKGROUND: Lipohypertrophy (LH) is highly prevalent and is potentially harmful to insulin-injecting patients. METHODS: In this study, we assessed the impact of injection technique (IT) education, including use of a 4-mm pen needle on insulin-treated patients with clinically observed LH in a randomized, controlled, prospective multicenter study in France with follow-up of 6 months. Intensive education and between-visit reinforcement were given to the intervention group. Control patients received similar messages at study outset. RESULTS: A total of 123 patients were recruited (age 52.1 ± 15.7 years; men 70.7%; body mass index >30 kg/m2: 34.2%; type 1: 53.7%; years with diabetes mellitus: 18.1 ± 10.5), of which 109 patients were included in the final analysis. The intervention group (n = 53) showed a significant decrease of total daily dose of insulin (average at baseline: 54.1 IU) at 3 months (T-3) and 6 months (T-6), reaching just over 5 IU versus baseline (P = 0.035). Corresponding, although not significant, decreases occurred in controls (n = 56); between-group differences were not significant. There were significant decreases in HbA1c (up to 0.5%) at T-3 and T-6 in both groups, with no significant differences between groups. A significant number of intervention patients improved their IT habits; about half achieved ideal IT habits by T-3 versus a quarter of control patients. By T-6, 2/3 of intervention patients achieved either ideal or acceptable IT habits, while only 1/3 of control patients did. CONCLUSIONS: Our intervention was effective in both study arms, however, to a greater degree and more rapidly in the intervention group. Widespread application of this intervention could be highly cost-effective.

Glucose Variability: Comparison of Different Indices During Continuous Glucose Monitoring in Diabetic Patients.

BACKGROUND: Glucose variability has been suspected to be a major factor of diabetic complications. Several indices have been proposed for measuring glucose variability, but their interest remains discussed. Our aim was to compare different indices. METHODS: Glucose variability was studied in 150 insulin-treated diabetic patients (46% men, 42% type 1 diabetes, age 52 ± 11 years) using a continuous glucose monitoring system (668 ± 564 glucose values; mean glucose value 173 ± 38 mg/dL). Results from the mean, the median, different indices (SD, MAGE, MAG, glucose fluctuation index (GFI), and percentages of low [<60 mg/dL] and high [>180 mg/dL] glucose values), and ratios (CV = SD/m, MAGE/m, MAG/m, and GCF = GFI/m) were compared using Pearson linear correlations and a multivariate principal component analysis (PCA). RESULTS: CV, MAGE/m (ns), GCF and GFI (P < .05), MAG and MAG/m (P < .01) were not strongly correlated with the mean. The percentage of high glucose values was mainly correlated with indices. The percentage of low glucose values was mainly correlated with ratios. PCA showed 3 main axes; the first was associated with descriptive data (mean, SD, CV, MAGE, MAGE/m, and percentage of high glucose values); the second with ratios MAG/m and GCF and with the percentage of low glucose values; and the third with MAG, GFI, and the percentage of high glucose values. CONCLUSIONS: Indices and ratios provide complementary pieces of information associated with high and low glucose values, respectively. The pairs MAG+MAG/m and GFI+GCF appear to be the most reliable markers of glucose variability in diabetic patients.

Medical treatments of elderly, French patients with type 2 diabetes: results at inclusion in the GERODIAB Cohort.

Prevalence of diabetes in the elderly increases, and half of the French diabetics are over the age of 75 years. The GERODIAB study is the first French multicentre, prospective, observational study designed to analyse over 5 years the influence of glycaemic control on morbidity-mortality in type 2 diabetics patients 70 years old and over. This study analysed the diabetic and geriatric factors associated with the treatment modalities, particularly insulin, at inclusion in the cohort. The cohort of 987 type 2 diabetics was divided into three groups according to the method of treatment. Slightly fewer than one-third of these patients (26.4%) were treated with insulin alone, 31% received insulin and oral antidiabetic drugs, and 42.7% oral antidiabetic drugs alone. The patients that received insulin alone were significantly older, had poorer glycaemic control (HbA1c = 7.9 ± 1.4, 7.8 ± 1.0 and 7.1 ± 1.2%, respectively; P < 0.001) and had greater alterations of glomerular filtration rate (GFR). HbA1c was below 6.5% in 15% of patients and 37.3% of patients had a GFR below 60 mL/min. The patients treated with insulin alone had significantly more hypoglycaemic episodes (respectively 53.3, 36.3 and 19.5%, P < 0.001), retinopathy, cardiovascular involvement and more specific geriatric complications, such as cognitive disorders (respectively 34.1, 31.4 and 23.6%, P = 0.006). In this specific population of elderly type 2 diabetic patients, diabetic and geriatric conditions significantly differed between the types of drug treatments. Considering low values of HbA1c and GFR, some patients seemed overtreated and other patients received inappropriate drugs.

Continuous glucose monitoring in hemodialyzed patients with type 2 diabetes: a multicenter pilot study.

AIMS: Hemodialyzed patients with diabetes face an increased cardiovascular risk. Optimal glycemic control can reduce morbidity and mortality, but it is difficult to achieve because of the alternation between dialysis and non-dialysis periods. This study evaluated the contribution of continuous glucose monitoring (CGM) to the management of insulin regimen. METHODS: In this pilot prospective multicenter study, we performed CGM (Navigator®, Abbott, Rungis, France) for a total of 54 hours at baseline and for a 3-month follow-up period in a group of 28 hemodialyzed patients with type 2 diabetes treated by a basal-bolus detemir plus aspart insulin regimen. Insulin therapy was adapted to the CGM values. HbA1c and CGM parameters collected over the 3-month treatment period were compared using MANOVA for repeated measures. RESULTS: After 3 months, HbA1c significantly decreased from 8.4 ± 1.0% (65 ± 1 mmol/mol) to 7.6 ± 1.0% (60 ± 11 mmol/mol; p < 0.01). Similarly, mean CGM glucose values significantly decreased from 9.9 ± 1.9 to 8.9 ± 2.1 mmol/L (p = 0.05). The frequency of glucose values > 10 mmol/L significantly decreased from 41.3 ± 21.9% to 30.1 ± 22.4% (p < 0.05), without a significant increase in the frequency of glucose values < 3.3 mmol/L. Insulin requirements significantly increased from 70 ± 51 IU/d to 82 ± 77 IU/d (p < 0.001), without significant changes in body weight. CONCLUSIONS: CGM-adapted insulin regimen improves glycemic control without increasing hypoglycemic events in hemodialyzed diabetic patients. CGM could be a useful tool for the management of insulin therapy in these patients. These results need to be confirmed by long-term studies with larger sample sizes.

Cardiovascular events and geriatric scale scores in elderly (70 years old and above) type 2 diabetic patients at inclusion in the GERODIAB cohort.

OBJECTIVE To analyze the relationships between cardiovascular complications and geriatric scale scores in French elderly (≥70 years of age) type 2 diabetic patients at inclusion in the GERODIAB cohort. RESEARCH DESIGN AND METHODS GERODIAB is the first French multicenter, prospective, observational survey designed to analyze the influence of glycemic control on morbidity/mortality in type 2 diabetic patients aged ≥70 years during a 5-year follow-up period. This study analyzed the relationships between classical macroangiopathic complications and geriatric scale scores in 987 patients at baseline, using bivariate and multivariate analyses. RESULTS Cardiac ischemia (31.2%) was significantly associated with impaired activities of daily living (ADL) scores (P < 0.001). Stepwise logistic regression included hypercholesterolemia, ADL, sex, and hypertension successively (70.3% concordance; P < 0.001). Heart failure (10.1%) was associated with impaired Mini Mental State Examination (MMSE), instrumental ADL (IADL) (P < 0.05), and ADL scores (P < 0.001). With the logistic model, waist circumference, age, and HDL cholesterol were significant factors (70.7% concordance; P < 0.001). Arterial disease of the lower limbs (25.6%) was associated with impaired IADL and ADL scores (P < 0.001). Significant factors using the logistic model were duration of diabetes, IADL score, hypertension, and sex (62.8% concordance; P < 0.001). Cerebral ischemia (15.8%) was associated with impaired MMSE, Mini Nutritional Assessment, ADL, and IADL scores (P < 0.01). IADL, sex, hypertension, and ADL were included in the logistic model successively (65.6% concordance; P < 0.001). CONCLUSIONS In this specific population, impaired geriatric scale scores were found to be associated with classical macrovascular complications, notably using multivariate analyses. This suggests the benefits of thorough screening and management of cognitive and functional decline in elderly type 2 diabetic patients.

Critical appraisal of the safety and efficacy of insulin detemir in glycemic control and cardiovascular risk management in diabetics.

Insulin detemir is an analog of human insulin designed to provide a long duration of basal insulin action. This is achieved by protracted absorption from the injection depot, which results in part from increased self-association of insulin detemir molecules and in part from reversible albumin binding. Subsequent albumin binding in the circulation is thought to buffer changes in the effects at target tissues that could otherwise arise from variability in absorption rate. In consequence, insulin detemir has shown a less variable pharmacodynamic profile than alternative basal insulins; this manifests as more consistent temporal glucose reduction profiles in repeat-clamp studies. In clinical trials, insulin detemir has been characterized by consistent risk reductions in hypoglycemia, as well as reduced weight gain in comparison with other basal insulins. Given some recent associations that have been made in prospective and epidemiologic studies between glucose variability and/or hypoglycemia and increased cardiovascular risk, and the long-known association between excess weight and cardiovascular risk, it is possible that the clinical profile of insulin detemir may carry prognostic value with regard to cardiovascular safety, although this is yet to be substantiated. There have also been some concerns raised recently over the use of insulin analogs and cancer risk, but available clinical data and the receptor interaction profile of insulin detemir suggest no excess in risk in comparison with human insulin therapy. Optimal approaches for the clinical use of insulin detemir have been emerging through an increasing clinical study base, and the analog is becoming established as a potentially valuable therapy option.

Comparison of once- versus twice-daily administration of insulin detemir, used with mealtime insulin aspart, in basal-bolus therapy for type 1 diabetes: assessment of detemir administration in a progressive treat-to-target trial (ADAPT).

OBJECTIVE: The purpose of this study was to compare effects of insulin detemir once daily versus twice a day in a basal-bolus insulin regimen. RESEARCH DESIGN AND METHODS: In this open-label, 7-month study, 520 patients with type 1 diabetes were randomly assigned to receive detemir once daily or twice daily with mealtime insulin aspart. Insulin doses were titrated over 1 month, with patients followed up over the subsequent 3 months. Thereafter, patients were able to switch from one regimen to the other, with an additional nonrandomized 3-month follow-up, to a total of 7 months. The primary end point was A1C at 4 months, with noninferiority defined as a difference <0.4% between groups. RESULTS: A1C at 4 months was 8.1 +/- 0.9 versus 8.0 +/- 1.0% with once- and twice-daily detemir, respectively, with an adjusted between-group difference of 0.12% (95% CI -0.01 to 0.25%), showing noninferiority for once-daily dosing. Similar results were found in the per protocol population. Improvement in A1C was similar in both groups (-0.4 +/- 0.8 vs. -0.5 +/- 0.8%; P = 0.09, NS) but with differences in the 7-point glucose profile. Detemir doses were lower (29 +/- 18 vs. 39 +/- 20 units/day, P < 0.001), but aspart doses were higher (34 +/- 17 vs. 26 +/- 14 IU/day, P < 0.001) with once-daily detemir. At 7 months, A1C decreased slightly in patients switched from once-daily to twice-daily administration (8.2 +/- 0.8 vs. 8.0 +/- 0.8%; P = 0.34, NS) in association with increased total insulin doses (P < 0.05), but A1C increased in those switched from twice-daily to once-daily administration (7.2 +/- 0.9 vs. 7.6 +/- 0.8%, P < 0.05) in association with decreased doses (P < 0.05). CONCLUSIONS: Although some individuals may benefit from twice-daily dosing, the most suitable routine starting schedule for detemir in a basal-bolus regimen for type 1 diabetes is once-daily injection.