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

¹From Harvard Medical School and the General Medicine Division, Department of Medicine, Massachusetts General Hospital, Boston, MA
²The Manchester Diabetes Centre, Manchester Royal Infirmary and The Division of Cardiovascular and Endocrine Sciences, University of Manchester, UK
³Department of Biostatistics, Boston University School of Public Health, Boston, MA
⁴Department of Mathematics, Statistics, and Consulting Unit, Boston University, Boston, MA
⁵the National Heart, Lung, and Blood Institute's Framingham (Mass) Heart Study
⁶Emory University School of Medicine, Atlanta, GA

jmeigs{at}partners.org

ABSTRACT

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

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.

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.

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.

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