DOI: 10.2337/dc07-0422
Clamp-like Index: a Novel, Highly Sensitive Insulin Sensitivity Index to Calculate Hyperinsulinemic Clamp Glucose Infusion Rates from Oral Glucose Tolerance Test in Nondiabetic Humans
1 Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Austria christian-heinz.anderwald{at}meduniwien.ac.at
ABSTRACT Objective.: Insulin resistance (IR), the underlying pathophysiological mechanism of the metabolic syndrome, could predict not only type-2 diabetes (T2DM) development, but also cardiovascular disease. Thus, precise IR measurement in individuals at risk for metabolic diseases would support clinical risk stratification. However, the "gold-standard" to measure IR, the hyperinsulinemic clamp-test, is too labor-intensive to be performed in large clinical studies/settings. Research Design and Methods.: Using plasma glucose and C-peptide concentrations from oral glucose tolerance tests (oGTTs), we developed the novel "clamp-like index" (CLIX) for insulin sensitivity calculation, and compared CLIX to clamp glucose infusion rates (100-120min) (GIR100-120min). We evaluated CLIX in eighty-nine nondiabetic subjects (f/m=58/31, aged:45±1years, BMI=27.5±0.8kg·m-2) who underwent frequently-sampled three-hour-(75g)-oGTTs and two-hour hyperinsulinemic-(40mU·min-1·m-2)-isoglycemic clamp-tests. Results.: CLIX, calculated as serum creatinine(x0.85 if male)/(mean AUCglucosexmean AUCC-peptide)x6600, highly correlated (r=0.670, p<10-12) with and was comparable to clamp GIRs100-120min. In subgroup analyses, GIRs100-120min were lower (p<0.005) in T2DM-offspring (OFF) (6.2±0.7 mg·min-1·kg-1) than in gender-, age- and BMI-matched subjects without T2DM family history (NOFF) (8.6±0.5 mg·min-1·kg-1), which was also reflected by CLIX (OFF:6.4±0.6 vs. NOFF:9.0±0.5, p<0.002). When compared to normal-weight subjects (GIR:8.8±0.4 mg·min-1·kg-1; CLIX:9.0±0.5), both GIRs100-120min and CLIX of obese (5.2±0.9 mg·min-1·kg-1; 5.7±0.9) and morbid obese (2.4±0.4 mg·min-1·kg-1; 3.3±0.5) humans were lower (each p<0.02). Conclusion:CLIX, a novel index obtained from plasma oGTT glucose and C-peptide levels and serum creatinine without inclusion of anthropometrical measures to calculate insulin sensitivity in nondiabetic humans, highly correlates with clamp GIRs and reveals even slight insulin sensitivity alterations over a broad BMI-range as sensitively as the hyperinsulinemic clamp-test.
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