Abstract
ContextAccurate assessment of insulin sensitivity may better identify individuals at increased risk of cardio-metabolic diseases.ObjectivesTo 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 participantsHealthy male volunteers (96 Chinese, 80 Malay, 77 Indian), 21 to 40 years, body mass index 18−30 kg/m2. 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.SettingThe study was conducted in a university academic medical centre.Outcome measuresISI measured by hyperinsulinemic euglycemic glucose clamp, along with anthropometric measurements, biochemical assessment and imaging; incident diabetes and CVD.ResultsA combination of fasting insulin, serum triglycerides and waist-to-hip ratio (WHR) provided the best estimate of clamp-derived ISI (adjusted R2 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.ConclusionsTriglycerides 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.
Highlights
Insulin resistance, or reduced insulin sensitivity, is the key pathophysiologic defect in type 2 diabetes mellitus, metabolic syndrome and cardiovascular disease [1,2,3,4]
Triglycerides and waist-to-hip ratio (WHR), combined with fasting insulin levels, provide a better estimate of current insulin resistance state and improved identification of individuals with future risk of cardiovascular disease (CVD), compared to homeostatic model of insulin resistance (HOMA-IR). This may be useful for estimating insulin sensitivity and cardio-metabolic risk in clinical and epidemiological settings
We derive an estimate of insulin sensitivity based on anthropometric and routine biochemical parameters. We examine if this derived measure of insulin sensitivity offers any advantage over HOMA-IR in identifying individuals with insulin resistance and risk of future cardio-metabolic events
Summary
Reduced insulin sensitivity, is the key pathophysiologic defect in type 2 diabetes mellitus, metabolic syndrome and cardiovascular disease [1,2,3,4]. The ‘‘gold standard’’ method for the assessment of insulin sensitivity is the hyperinsulinemic euglycemic clamp. This method estimates insulin sensitivity directly by determining peripheral glucose disposal rate during the steady-state of hyperinsulinemia when blood glucose is maintained at euglycemic levels by an exogenous glucose infusion [5]. It is widely-accepted as the reference method, the euglycemic clamp is costly, labor- and time-consuming. This approach is usually confined to research settings and is not feasible in population studies
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