Metabolic Syndrome and Prediabetes Fail to Detect a High Prevalence of Early Insulin Resistance—The PREMIER Study

The PREMIER Study was a multi-center randomized controlled trial of lifestyle interventions in 810 nondiabetic subjects with elevated blood pressure. At baseline, one half of the cohort met the criteria for metabolic syndrome (MetS) and one third met the fasting glucose criterion for prediabetes (PreD). The purpose of the current analysis of PREMIER data was to quantify the sensitivity of the MetS criteria and cut points for detecting hyperinsulinemia and insulin resistance, defined here as fasting insulin ≥ 12 μIU/mL based on prior calibration against the euglycemic clamp. Insulin showed statistically significant bivariate correlations with 4 of the 5 MetS criteria in decreasing order of strength: waist circumference, fasting glucose, HDL-cholesterol and fasting triglycerides. By contrast, systolic and diastolic blood pressure, and total- and LDL-cholesterol did not correlate with fasting insulin. Logistic regression revealed that each MetS criterion, except blood pressure, had an independent contribution to hyperinsulinemia, even after correcting for age, race and gender. Receiver operator characteristic curves showed that the harmonized MetS cut points were non-optimal for detecting hyperinsulinemia. Specifically, the fasting triglyceride and glucose cut points were too high, while those for waist circumference were too low. Using the criteria for MetS and hyperinsulinemia, the subjects were divided into four metabolic subtypes. The subtype with hyperinsulinemia but not MetS represented 14.7% (95% CI 12.4-17.5) of the cohort. The prevalence of individuals with hyperinsulinemia that did not meet the criteria for MetS or PreD was surprisingly high at 12.7% (95% CI 10.3-15.1). This subtype is an important target for early intervention and diabetes prevention, but was not detected in this population using the current criteria for MetS or PreD. New screening strategies and metabolic health measures are needed to improve outcomes for diabetes prevention.