New measure of insulin sensitivity predicts cardiovascular disease better than HOMA estimated insulin resistance

Abstract

Context: Accurate assessment of insulin sensitivity may better identify individuals at increased risk of cardio-metabolic diseases.

Objectives: To examine whether a combination of anthropometric, biochemical and imaging measures can better estimate insulin sensitivity index (ISI) and provide improved prediction of cardio-metabolic risk, in comparison to HOMA-IR.

Design and participants: Healthy male volunteers (96 Chinese, 80 Malay, 77 Indian), 21 to 40 years, body mass index 18-30 kg/m(2). Predicted ISI (ISI-cal) was generated using 45 randomly selected Chinese through stepwise multiple linear regression, and validated in the rest using non-parametric correlation (Kendall's tau τ). In an independent longitudinal cohort, ISI-cal and HOMA-IR were compared for prediction of diabetes and cardiovascular disease (CVD), using ROC curves.

Setting: The study was conducted in a university academic medical centre.

Outcome measures: ISI measured by hyperinsulinemic euglycemic glucose clamp, along with anthropometric measurements, biochemical assessment and imaging; incident diabetes and CVD.

Results: A combination of fasting insulin, serum triglycerides and waist-to-hip ratio (WHR) provided the best estimate of clamp-derived ISI (adjusted R(2) 0.58 versus 0.32 HOMA-IR). In an independent cohort, ROC areas under the curve were 0.77±0.02 ISI-cal versus 0.76±0.02 HOMA-IR (p>0.05) for incident diabetes, and 0.74±0.03 ISI-cal versus 0.61±0.03 HOMA-IR (p<0.001) for incident CVD. ISI-cal also had greater sensitivity than defined metabolic syndrome in predicting CVD, with a four-fold increase in the risk of CVD independent of metabolic syndrome.

Conclusions: Triglycerides and WHR, combined with fasting insulin levels, provide a better estimate of current insulin resistance state and improved identification of individuals with future risk of CVD, compared to HOMA-IR. This may be useful for estimating insulin sensitivity and cardio-metabolic risk in clinical and epidemiological settings.

Figure 1. Comparison of ISI-cal with HOMA-IR in validation group from the SAMS study.

N = 208; P = 0.024 HOMA-IR – homeostatic model of insulin resistance, ISI-cal – calculated insulin sensitivity, SAMS – Singapore Adult Metabolism study.