Abstract P437: Early Insulin Resistance Responds To Lifestyle Interventions: The Premier Study

Abstract

Introduction: Compensatory hyperinsulinemia (CH) is the metabolic response to early insulin resistance. Elevated blood insulin compensates for insulin resistance in tissues, maintaining normal fasting glucose and lipid levels. Therefore, CH is undetected by conventional screening tests for diabetes and cardiovascular risk. Our prior work showed that CH is prevalent in the U.S., especially in teenagers, young adults and Hispanic populations. Moreover, CH in young adults doubles the risk for diabetes later in life, independent of other known risk factors. The current study tested the hypothesis that markers of early insulin resistance improve with behavioral lifestyle interventions. Methods: The parent PREMIER study was a randomized controlled trial to evaluate the effect of lifestyle interventions on blood pressure. Many subjects also had insulin resistance, prediabetes (PreD) and/or metabolic syndrome (MetS). The interventions included increased physical activity, weight loss, reduced sodium and alcohol intake, and the DASH diet (Dietary Approaches to Stop Hypertension). A total of 810 subjects were randomized into three intervention arms: “established”, “established plus DASH” and “advice only”. Established refers to the above interventions, except for DASH. The subjects were 62% women and 34% African Americans; the mean age was 50.0±8.9 years. Inclusion criteria were age ≥25, elevated BP and BMI of 18.5-45.0 kg/m 2 . Exclusion criteria were diabetes, history of cardiovascular event, heart failure, cancer or psychiatric hospitalization within the last 2 years. Here, the analysis of covariance method was used to determine whether markers of insulin resistance at 6 months improved in the established or established plus DASH arms compared with the advice-only arm, after adjusting for baseline values. The results are reported as geometric means and 95% confidence intervals (CI). Results: Subjects in the lifestyle intervention arms showed reduced fasting insulin and increased insulin sensitivity compared with the advice-only arm. The mean fasting insulin levels after 6 months of the established and established plus DASH interventions were 9.8 μIU/mL (95% CI: 9.3, 10.3) and 10.1 (9.6, 10.7), respectively, compared with 12.0 (11.4, 12.6) for advice only. After excluding subjects with PreD and/or MetS at baseline, insulin levels for established and established plus DASH were 8.0 (7.3, 8.7) and 8.3 (7.3, 9.0), respectively, as compared with 9.8 (9.1, 10.6) for advice only. Likewise, HOMA2 %S increased to 101.2 (92.5, 110.6) and 93.3 (85.6, 101.8), respectively, compared with 79.0 (73.0, 85.5) in the advice-only arm. Conclusion: Markers of insulin resistance improved with the PREMIER lifestyle interventions, even in subjects who did not meet the clinical criteria for prediabetes or metabolic syndrome. Early screening and intervention may improve diabetes prevention outcomes.