Synergistic interactions among metabolic syndrome components and homeostasis model assessment of insulin resistance in a middle-aged general population over time.

Abstract

Insulin resistance is considered a hallmark feature of the metabolic syndrome, but how metabolic syndrome components and insulin resistance measures interact over time is unclear. The homeostasis model assessment of insulin resistance (HOMA-IR) is a static index of insulin resistance typically used in epidemiological studies. We explored how HOMA-IR is affected by clustering metabolic syndrome components over time in a population of middle-aged, healthy subjects. A total of 1757 subjects aged 41.3±7.5 years (39% males) free from diabetes at baseline were followed-up for a median of 5.7 years. At baseline and at the end of observation, we determined metabolic syndrome components and HOMA-IR. Cross-sectionally, HOMA-IR was synergistically increased by clustering of at least two to three metabolic syndrome components as determined at baseline and at study end by departure from additivity. Some combinations of metabolic syndrome components were associated with a significant synergic increase in HOMA-IR, and some combinations of two components entailed a synergistic risk of developing metabolic syndrome. Over time, the average change in HOMA-IR was more than additively affected by change in the number of metabolic syndrome components. Baseline HOMA-IR values were predictive of incident metabolic syndrome independent from age, sex, and each metabolic syndrome component. We show synergistic interaction between clustering metabolic syndrome components and insulin resistance, estimated by HOMA-IR, cross-sectionally and over time. This more than additive effect explains the incremental value of HOMA-IR in predicting metabolic risk.