Biological Variation of Homeostasis Model Assessment-Derived Insulin Resistance in Type 2 Diabetes

Biological Variation of Homeostasis Model Assessment-Derived Insulin Resistance in Type 2 Diabetes Vijay Jayagopal , MRCP 1 , Eric S. Kilpatrick , MRCPATH 2 , Paul E. Jennings , FRCP 1 3 , David A. Hepburn , FRCP 1 and Stephen L. Atkin , FRCP 1 1 Department of Medicine, University of Hull, Hull, U.K 2 Department of Clinical Biochemistry, Hull Royal Infirmary, Hull, U.K 3 Department of Medicine, York District General Hospital, York, U.K Abstract OBJECTIVE —Individuals with type 2 diabetes are particularly vulnerable to cardiovascular disease. Insulin resistance is a major determinant of this increased risk and is a potential therapeutic target. This study was undertaken to establish the natural biological variation of insulin resistance in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS —The biological variation of insulin resistance was assessed by measuring insulin resistance at 4-day intervals on 10 consecutive occasions in 12 postmenopausal women with diet-controlled type 2 diabetes and in 11 weight- and age-matched postmenopausal women without type 2 diabetes. Insulin resistance was derived using the homeostasis model assessment for insulin resistance (HOMA-IR) method. RESULTS —The distribution of HOMA-IR was log Gaussian in the type 2 diabetic study group and Gaussian in the control group. The HOMA-IR in the type 2 diabetic group was significantly greater than that of the control group (mean ± SD: 4.33 ± 2.3 vs. 2.11 ± 0.79 units, P = 0.001). After accounting for analytical variation, the mean intraindividual variation was also substantially greater in the type 2 diabetic group than in the control group (mean 1.05 vs. 0.15, P = 0.001). Consequently, at any level of HOMA-IR, a subsequent sample must increase by >90% or decrease by >47% to be considered significantly different from the first. CONCLUSIONS —HOMA-IR is significantly greater and more variable for individuals with type 2 diabetes. Therefore, this inherent variability needs to be accounted for in studies evaluating therapeutic reduction of HOMA-IR in this group. HOMA-IR, homeostasis model assessment for insulin resistance Footnotes Address correspondence and reprint requests to Dr. V. Jayagopal, Michael White Centre for Diabetes and Endocrinology, Brocklehurst Building, Hull Royal Infirmary, 220-236 Anlaby Rd., Hull, HU3 2RW, U.K. E-mail: v.jaygopal{at}hull.ac.uk . Received for publication 7 February 2002 and accepted in revised form 22 July 2002. A table elsewhere in this issue