Long-term effects of lifestyle and metformin interventions in DPP on bone density.

In the Diabetes Prevention Program Outcome Study (DPPOS), a cohort at high risk of diabetes, randomization to intensive lifestyle intervention or metformin, both associated with weight loss, did not have long-term negative effects on BMD compared with the placebo group. Potential positive effects of metformin on bone warrant further investigation. INTRODUCTION: Randomization to lifestyle intervention (ILS) or metformin in the Diabetes Prevention Program (DPP) resulted in weight loss and reduced progression to diabetes. Weight loss is associated with reduced bone mineral density (BMD), but the long-term effects of these interventions on BMD are unknown. In the DPP Outcome Study (DPPOS), we determined if randomization to ILS or metformin, compared with placebo, was associated with differences in BMD approximately 16 years later. METHODS: Of 3234 DPP participants, 2779 continued in DPPOS and were offered ILS in group format. Those randomized to metformin were offered unmasked metformin. At DPPOS year 12, 1367 participants had dual-energy X-ray absorptiometry scans. BMD in metformin and ILS groups was compared to placebo using sex-specific linear regression models, adjusted for age, race/ethnicity, and weight and weight-bearing activity at DPP baseline. RESULTS: At DPPOS year 12, mean age was 66.5 (±9.5) years. Femoral neck BMD was similar in the ILS and placebo groups in men (difference = -0.021 g/cm2, 95%CI (-0.063, 0.021)) and in women (+0.014 g/cm2, 95%CI (-0.014, 0.042)). Femoral neck BMD was higher in the metformin compared to placebo group although not statistically different in men (+0.017 g/cm2, 95% CI (-0.023, 0.058)) and in women (+0.019 g/cm2, 95% CI (-0.009, 0.047)). Prevalence of osteoporosis was low and similar across treatment groups in men (0.9%; p=0.745) and women (2.4%; p=0.466). CONCLUSION: In a cohort at high risk of diabetes, lifestyle intervention or metformin did not appear to have long-term negative effects on BMD. Potential positive effects of metformin on bone warrant further research.

Blood thrombogenicity in type 2 diabetes mellitus patients is associated with glycemic control.

OBJECTIVES: This study was designed to determine whether blood thrombogenicity is related to chronic glycemic control in type 2 diabetes mellitus (T2DM). BACKGROUND: Type 2 diabetes mellitus is associated with accelerated atherosclerosis and a high rate of arterial thrombotic complications. Whether increased blood thrombogenicity is associated with glycemic control has not been properly tested. METHODS: Forty patients with T2DM with hemoglobin A1c (HbA1c) > or =7.5% were selected. Maintaining their current hypoglycemic therapies, patients were randomized into a conservative (diet modification plus placebo) or intensive (diet modification plus troglitazone) hypoglycemic regimen for three months. Blood thrombogenicity was measured at baseline and after three months with the Badimon ex vivo perfusion chamber and assessed as platelet-thrombus formation. The repeated measurements allowed every patient to be his/her own control. RESULTS: Patients in both groups (48% and 74% of the conservative and intensive groups, respectively) improved glucose control (HbA1c reduction > or =0.5%), showing a significant decrease in blood thrombogenicity. A significant positive correlation was observed between the reduction in thrombus formation and the reduction in HbA1c (r = 0.47, p < 0.01). The reduction in HbA1c achieved by both treatments was comparable. Patients without glycemic improvement showed no change in blood thrombogenicity. Improved glycemic control was the only significant predictor of a decrease in blood thrombogenicity. CONCLUSIONS: In T2DM, there is an association between improved glycemic control and blood thrombogenicity reduction. The effect of glycemic control on the thrombotic complications of T2DM patients deserves further investigation.

Detection and management of early diabetic nephropathy.

It has proven difficult to alter the progression of diabetic nephropathy once overt proteinuria is established. The presence of microalbuminuria reflects an early renal lesion that may be more amenable to therapeutic intervention. Dietary protein restriction, improved glycemic control, and aggressive treatment of high blood pressure all have shown beneficial effects in some patients. Angiotensin-converting enzyme inhibitor therapy may offer specific advantages in terms of its renal protective effects.