Impact of Insulin Resistance on Risk of Type 2 Diabetes and Cardiovascular Disease in People with Metabolic Syndrome

Abstract

Abstract OBJECTIVE - Metabolic syndrome (MetS) increases risk for type 2 DM and CVD and may be associated with insulin resistance (IR).

Abstract RESEARCH DESIGN AND METHODS - We tested the hypothesis that MetS confers risk with or without concomitant IR among 2803 Framingham Offspring Study subjects followed up to 11 years for new DM (135 cases) or CVD (240). We classified subjects by presence of MetS (using ATP3, IDF, or EGIR criteria) and IR (HOMA-IR ≥75%ile) and used separate risk factor-adjusted proportional hazards models to estimate relative risks (RR) for DM or CVD using as referents those without IR, MetS, or without both.

Abstract RESULTS -- Fifty-six percent with ATP3, 52% with IDF, and 100% with EGIR MetS had IR. IR increased risk for DM (RR 2.6, 95% CI 1.7-4.0) and CVD (1.8, 1.4-2.3), as did MetS (DM: ATP3, 3.5, 2.2-5.6; IDF, 4.6, 2.7-7.7; EGIR, 3.3, 2.1-5.1; CVD: ATP3, 1.8, 1.4-2.3; IDF, 1.7, 1.3-2.3; EGIR, 2.1, 1.6-2.7). Relative to those without either Mets or IR, MetS and IR increased risk for DM (ATP3, 6.0, 3.3-10.8; IDF 6.9, 3.7-13.0) and CVD (ATP3, 2.3, 1.7-3.1; IDF 2.2, 1.6-3.0). Any MetS without IR increased risk for DM ∼3-fold (p<0.001); IDF MetS without IR (RR 1.6, p=0.01) but not ATP3 MetS without IR (RR 1.3, p=0.2) increased risk for CVD.

Abstract CONCLUSIONS - MetS increased risk for DM regardless of IR. ATP3 MetS may need IR to increase risk for CVD. The simultaneous presence of MetS and IR identify an especially high risk individual.