Metabolic syndrome components and their response to lifestyle and metformin interventions are associated with differences in diabetes risk in persons with impaired glucose tolerance

Abstract

Aims: To determine the association of metabolic syndrome (MetS) and its components with diabetes risk in participants with impaired glucose tolerance (IGT), and whether intervention-related changes in MetS lead to differences in diabetes incidence.

Methods: We used the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III) revised MetS definition at baseline and intervention-related changes of its components to predict incident diabetes using Cox models in 3234 Diabetes Prevention Program (DPP) participants with IGT over an average follow-up of 3.2 years.

Results: In an intention-to-treat analysis, the demographic-adjusted hazard ratios (95% confidence interval) for diabetes in those with MetS (vs. no MetS) at baseline were 1.7 (1.3-2.3), 1.7 (1.2-2.3) and 2.0 (1.3-3.0) for placebo, metformin and lifestyle groups, respectively. Higher levels of fasting plasma glucose and triglycerides at baseline were independently associated with increased risk of diabetes. Greater waist circumference (WC) was associated with higher risk in placebo and lifestyle groups, but not in the metformin group. In a multivariate model, favourable changes in WC (placebo and lifestyle) and high-density lipoprotein cholesterol (placebo and metformin) contributed to reduced diabetes risk.

Conclusions: MetS and some of its components are associated with increased diabetes incidence in persons with IGT in a manner that differed according to DPP intervention. After hyperglycaemia, the most predictive factors for diabetes were baseline hypertriglyceridaemia and both baseline and lifestyle-associated changes in WC. Targeting these cardiometabolic risk factors may help to assess the benefits of interventions that reduce diabetes incidence.

Keywords: cardiometabolic risk; diabetes prevention; lifestyle; metformin.

Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Figures

Figure 1. Demographically adjusted hazard ratio (95%CI) for developing diabetes associated with baseline metabolic syndrome and components

All hazard ratios are adjusted for age randomized, sex, and race/ethnicity. Components with an asterisk (*) denote significant heterogeneity among the treatment groups. Metabolic syndrome components are defined as: High FPG, fasting plasma glucose ≥ 100 mg/dl; abdominal obesity, waist ≥ 102 cm in men and ≥ 88 cm in women; High TG, triglycerides ≥ 150 mg/dl or use of TG lowering medications; High BP, systolic/diastolic blood pressure ≥ 130/85 mmHg or use of antihypertensive medications; Low HDL-c, high density lipoprotein cholesterol<40mg/dl in men and <50 in women or use of lipid lowering medications.High TG and abdominal obesity is defined as TG ≥ 150 mg/dl and waist ≥ 102 cm in men (waist≥ 88 cm in women).

Figure 2. Hazard ratio (95% CI) for developing diabetes associated with cardio-metabolic risk factors as continuous variables

All hazard ratios are adjusted for age randomized, sex, and race/ethnicity and computed in increments to approximate 1 SD of the baseline component and of the changes from baseline. Components with an asterisk (*) denote significant heterogeneity among the treatment groups. Changes in components are computed as the average change from baseline up to, but not including, each visit when diabetes was diagnosed. To facilitate comparison across variables, hazard ratios