Metabolic Syndrome Components and Their Response to Lifestyle and Metformin Interventions are Associated with Differences in Diabetes Risk in Persons with Impaired Glucose Tolerance

Aims: To determine the association of metabolic syndrome (MetS) and its components with diabetes risk in participants with impaired glucose tolerance (IGT), and whether interventionrelated changes in MetS lead to differences in diabetes incidence. Methods: We used the NCEP/ATP III revised MetS definition at baseline and interventionrelated 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%CI) for diabetes in those with MetS (versus 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, favorable changes in WC (placebo and lifestyle) and HDLc (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 hyperglycemia, the most predictive factors for diabetes were baseline hypertriglyceridemia and both baseline and lifestyle-associated changes in waist circumference. Targeting these cardiometabolic risk factors may help to assess the benefits of interventions that reduce diabetes incidence.