Metformin in Prevention of Type 2 Diabetes.

Identification and treatment of individuals with prediabetes is crucial. Effective interventional strategies are key to reducing the diabetes risk at the population level. Lifestyle intervention is found to be more effective but more expensive. Evidence of potential benefits from pharmacotherapy is accumulating. The choice of a pharmacologic intervention to reduce the progression of type 2 diabetes (T2DM) in high risk individuals must consider the balance between the benefit to risk ratio. A meta-analysis of the results of the three important studies has shown that metformin used for up to three years decrease the likelihood of progression to diabetes. Metformin showed greater beneficial effect in people with higher baseline Body Mass Index (BMI) and higher Fasting Plasma Glucose (FPG) than in leaner prediabetic counterparts with low FPG concentrations. Besides diabetes risk reduction, the drug has also proved to be cancer and cardio-protective. The National Institute for Clinical Excellence, UK has recommended the use of metformin in prevention of T2DM in adults at high risk on failure to adhere to lifestyle changes. In view of the long standing safety and tolerability, metformin could be prescribed to people who are unable to comply with lifestyle advice.

Adiponectin, leptin, interleukin-6 and HbA1c in the prediction of incident type 2 diabetes: A nested case-control study in Asian Indian men with impaired glucose tolerance.

AIMS: The aims of this study were: (1) to assess the association of adiponectin, leptin and interleukin-6 (IL-6) with incidence of type 2 diabetes (T2DM) in Asian Indian men with impaired glucose tolerance (IGT) and (2) to evaluate the additional contribution of these with the well-established glycaemic marker HbA1c. METHODS: This is an ancillary analyses of a nested case-control study derived from a prospective, prevention trial in India. All the participants had IGT at baseline. For this subanalysis a total of 147 (T2DM: 71; nondiabetic: 76) participants were selected based on the final glycemic outcomes. Association of these selected adipokines with T2DM were assessed using logistic regression analyses. Clinical usefulness of adding adipokine markers with HbA1c on prediction of T2DM was assessed using the area under the curve (AUC) of the receiver operating characteristics. RESULTS: Baseline levels of adiponectin were lower and the levels of IL-6 were higher in T2DM cases when compared with non-diabetic cases (P<0.05). Levels of leptin were similar in both groups. In fully adjusted models, adiponectin (odds ratio (OR): 0.55 [95%CI: 0.33-0.91]; P=0.019) and IL-6 (OR: 2.27 [95%CI: 1.40-3.691]; P=0.001) were associated with diabetes. Addition of adiponectin to HbA1c improved the AUC (ΔAUC: 0.0619; P=0.0251), whereas addition of IL-6 did not improve the predictive power of HbA1c alone. CONCLUSIONS: Adiponectin and IL-6 are independently associated with incident diabetes. However, they are unlikely to serve as simple tools to predict future risk of diabetes but may have a role in understanding the pathogenesis.

Early improvement predicts reduced risk of incident diabetes and improved cardiovascular risk in prediabetic Asian Indian men participating in a 2-year lifestyle intervention program.

OBJECTIVE: Objectives of this ancillary analysis of a prospective, prevention study among Asian Indians with impaired glucose tolerance (IGT) were a) to quantify the reduction in incident diabetes at 24 months in participants who achieved normal glucose tolerance (NGT) at 6 months (NGT-6 m) compared with the other participants, b) the factors influencing the reversal to NGT at the end of the study at 24 months (NGT-24 m), and c) to assess changes in cardiometabolic risk factors in different categories of dysglycemia at 24 months. RESEARCH DESIGN AND METHODS: Data from a 2-year primary prevention trial were used. Effect of reversion to NGT-6 m on incidence of type 2 diabetes mellitus (T2DM) was analyzed using the Cox proportional hazards model. Predictive variables for reversal to NGT were identified using multiple logistic regression analysis. Changes in cardiometabolic risk factors were estimated according to the final glycemic status using fixed-effect, mixed-linear regression modeling. RESULTS: The risk of T2DM in 2 years was lower by 75% in NGT-6 m group (hazard ratio 0.25 [95% CI 0.12-0.52]). Predictive variables for reversal to NGT-24 m were good baseline ß-cell function (odds ratio [OR] 2.79 [95% CI 2.30-3.40]) and its further improvement (OR 5.70 [95% CI 4.58-7.08]), and NGT-6 m (OR 2.10 [95% CI 1.14-3.83]). BMI decreased in those who reverted to NGT. Deterioration to T2DM was associated with an increase in the levels of cardiometabolic risk factors. CONCLUSIONS: Early reversion to NGT by lifestyle intervention in prediabetic men was associated with a significant reduction in subsequent incidence of diabetes. Good baseline ß-cell function and its further improvement and NGT-6 m were associated with reversion to NGT-24 months. Reversion to NGT was associated with modest improvements, whereas conversion to T2DM was associated with significant worsening of the cardiometabolic risk profile.