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Impact of Degree of Obesity on Surrogate Estimates of Insulin Resistance

Department of Medicine, Stanford University School of Medicine, Stanford, California

Address correspondence and reprint requests to Gerald M. Reaven, MD, Division of Cardiovascular Medicine, Falk CVRC, Stanford Medical Center, 300 Pasteur Dr., Stanford, CA 94305-5406. E-mail: greaven{at}cvmed.stanford.edu

OBJECTIVE—To evaluate the role of adiposity in the relationship between specific and surrogate estimates of insulin-mediated glucose uptake (IMGU) in a large nondiabetic population.

RESEARCH DESIGN AND METHODS—Healthy volunteers were classified by BMI into normal weight (<25.0 kg/m², n = 208), overweight (25.0–29.9 kg/m², n = 168), and obese (30.0 kg/m², n = 109) groups. We then assessed how differences in BMI affect the correlation between steady-state plasma glucose (SSPG) concentration at the end of a 180-min infusion of octreotide, glucose, and insulin (a specific measure of IMGU) and five surrogate estimates: fasting plasma glucose, fasting plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and area under the curve for insulin in response to oral glucose (I-AUC).

RESULTS—Correlation coefficients (r values) between SSPG and surrogate measures of IMGU were all significant (P < 0.05), but the magnitude varied between BMI groups: normal weight: fasting plasma glucose 0.20, fasting plasma insulin 0.33, HOMA-IR 0.36, QUICKI –0.33, and I-AUC 0.69; overweight: fasting plasma glucose 0.19, fasting plasma insulin 0.55, HOMA-IR 0.55, QUICKI –0.54, and I-AUC 0.72; and obese: fasting plasma glucose 0.40, fasting plasma insulin 0.56, HOMA-IR 0.60, QUICKI –0.61, and I-AUC 0.69.

CONCLUSIONS—The relationship between direct and surrogate estimates of IMGU varies with BMI, with the weakest correlations seen in the normal-weight group and the strongest in the obese group. In general, I-AUC is the most useful surrogate estimate of IMGU in all weight groups. Fasting plasma insulin, HOMA-IR, and QUICKI provide comparable information about IMGU. Surrogate estimates of IMGU based on fasting insulin and glucose account for no more than 13% of the variability in insulin action in the normal-weight group, 30% in the overweight group, and 37% in the obese group.

Abbreviations: HOMA-IR, homeostasis model assessment of insulin resistance • I-AUC, area under the curve for insulin in response to oral glucose • IMGU, insulin-mediated glucose uptake • IST, insulin suppression test • QUICKI, quantitative insulin sensitivity check index • SSPG, steady-state plasma glucose

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