New Measure of Insulin Sensitivity Predicts Cardiovascular Disease Better than HOMA Estimated Insulin Resistance

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.

Lithium or Valproate Adjunctive Therapy to Second-generation Antipsychotics and Metabolic Variables in Patients With Schizophrenia or Schizoaffective Disorder

“…HOMA-IR, which is a computation based on fasting insulin and glucose values, represents the most common surrogate measure of insulin resistance. 39 It has a moderate correlation with insulin sensitivity, which is likely why it was not statistically significant in our study. We also found that participants taking adjunctive lithium or valproate had higher average body mass index of approximately 3.28 units (kg/m 2 ) compared with those not taking lithium or valproate, although this relationship did not reach statistical significance.…”

The Evidence for Saturated Fat and for Sugar Related to Coronary Heart Disease

“…Regardless of diabetes status, degree of insulin resistance is associated with future CV events 125, 126 and severity of MI. 127 An elevated insulin response to sugar (an oral glucose load) has been found in patients with atherosclerosis of the peripheral, cerebral, and coronary arteries, 128, 129 and insulin levels following a glucose challenge have been independently associated with MI occurrence 130 and CHD mortality.…”

Added Fructose

“…3 Insulin resistance is associated with hyperinsulinemia, a condition that may promote abdominal-fat storage, increased triglyceride levels, and other metabolic disturbances 4 dall part of a broader metabolic syndrome 5 that is sometimes referred to as insulin-resistance syndrome. Markers of insulin resistance predict future cardiovascular (CV) risk, 6,7 with hyperinsulinemia being an independent risk factor for coronary heart disease. 8,9 Individuals with insulin-resistant (ie, type 2) diabetes have a life expectancy 5 to 10 years shorter than those unaffected by the disease, with much of the difference due to CV causes.…”