The Effects of Carbohydrate, Unsaturated Fat, and Protein Intake on Measures of Insulin Sensitivity

Results from the OmniHeart Trial

  1. Edgar R. Miller III, PHD, MD1,2,3
  1. 1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
  3. 3Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland
  4. 4Division of Epidemiology, Statistics, and Prevention Research, Epidemiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland
  5. 5Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
  6. 6Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham and Womens’ Hospital, Boston, Massachusetts
  1. Corresponding author: Meghana D. Gadgil, mgadgil2{at}


OBJECTIVE Impaired insulin sensitivity increases the risk of cardiovascular disease. Although calorie restriction and weight loss increase insulin sensitivity, the effects of modifying macronutrient composition on insulin sensitivity are uncertain. The purpose of this study is to determine the effects on insulin sensitivity of a carbohydrate-rich diet (CARB; similar to the Dietary Approaches to Stop Hypertension [DASH] diet), a protein-rich diet (PROT; protein predominantly from plant sources), and an unsaturated fat–rich diet (UNSAT; predominantly monounsaturated).

RESEARCH DESIGN AND METHODS This study was a randomized, controlled, three-period, crossover feeding study. The study participants were 164 individuals with prehypertension or stage 1 hypertension without diabetes. Diets were administered for 6 weeks each, with a washout period between diets of 2–4 weeks. Weight was held constant throughout the study. For our primary outcome, we calculated the quantitative insulin sensitivity check index (QUICKI) using the end-of-period fasting serum glucose and insulin. QUICKI is a validated measure of insulin sensitivity. The primary analyses used generalized estimating equations.

RESULTS At baseline, mean (SD) BMI was 30.2 (6.1) kg/m2, and mean (SD) QUICKI was 0.35 (0.04). The UNSAT diet increased QUICKI by 0.005, more than the CARB diet (P = 0.04). PROT had no significant effect compared with CARB.

CONCLUSIONS A diet that partially replaces carbohydrate with unsaturated fat may improve insulin sensitivity in a population at risk for cardiovascular disease. Given the well-recognized challenges of sustaining weight loss, our results suggest an alternative approach for improving insulin sensitivity.


  • Received May 6, 2012.
  • Accepted October 31, 2012.


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  1. Diabetes Care vol. 36 no. 5 1132-1137
  1. All Versions of this Article:
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