Defining insulin resistance from hyperinsulinemic-euglycemic clamps
Charmaine S Tam, Wenting Xie, William D Johnson, William T Cefalu, Leanne M Redman, Eric Ravussin, Charmaine S Tam, Wenting Xie, William D Johnson, William T Cefalu, Leanne M Redman, Eric Ravussin
Abstract
Objective: This study was designed to determine a cutoff point for identifying insulin resistance from hyperinsulinemic-euglycemic clamp studies performed at 120 mU/m(2)·min in a white population and to generate equations from routinely measured clinic and blood variables for predicting clamp-derived glucose disposal rate (GDR), i.e., insulin sensitivity.
Research design and methods: We assembled data from hyperinsulinemic-euglycemic clamps (120 mU/m(2)·min insulin dose) performed at the Pennington Biomedical Research Center between 2001 and 2011. Subjects were divided into subjects with diabetes (n = 51) and subjects without diabetes (n = 116) by self-report and/or fasting glucose ≥126 mg/dL.
Results: We found that 75% of individuals with a GDR <5.6 mg/kg fat-free mass (FFM) + 17.7·min were truly insulin resistant. Cutoff values for GDRs normalized for body weight, body surface area, or FFM were 4.9 mg/kg·min, 212.2 mg/m(2)·min, and 7.3 mg/kgFFM·min, respectively. Next, we used classification tree models to predict GDR from routinely measured clinical and biochemical variables. We found that individual insulin resistance could be estimated with good sensitivity (89%) and specificity (67%) from the homeostasis model assessment of insulin resistance (HOMA-IR) >5.9 or 2.8< HOMA-IR <5.9 with HDL <51 mg/dL.
Conclusions: We developed a cutoff for defining insulin resistance from hyperinsulinemic-euglycemic clamps. Moreover, we now provide classification trees for predicting insulin resistance from routinely measured clinical and biochemical markers. These findings extend the clamp from a research tool to providing a clinically meaningful message for participants in research studies, potentially providing greater opportunity for earlier recognition of insulin resistance.
Figures
References
- DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 1979;237:E214–E223
- Lillioja S, Bogardus C. Obesity and insulin resistance: lessons learned from the Pima Indians. Diabetes Metab Rev 1988;4:517–540
- Bergman RN, Finegood DT, Ader M. Assessment of insulin sensitivity in vivo. Endocr Rev 1985;6:45–86
- Stern SE, Williams K, Ferrannini E, DeFronzo RA, Bogardus C, Stern MP. Identification of individuals with insulin resistance using routine clinical measurements. Diabetes 2005;54:333–339
- Stull AJ, Cash KC, Johnson WD, Champagne CM, Cefalu WT. Bioactives in blueberries improve insulin sensitivity in obese, insulin-resistant men and women. J Nutr 2010;140:1764–1768
- Plaisance EP, Greenway FL, Boudreau A, et al. Dietary methionine restriction increases fat oxidation in obese adults with metabolic syndrome. J Clin Endocrinol Metab 2011;96:E836–E840
- Cefalu WT, Rood J, Pinsonat P, et al. Characterization of the metabolic and physiologic response to chromium supplementation in subjects with type 2 diabetes mellitus. Metabolism 2010;59:755–762
- Du Bois D, Du Bois EF. A formula to estimate the approximate surface area if height and weight be known. 1916. Nutrition 1989;5:303–311; discussion 312–313
- Bewick V, Cheek L, Ball J. Statistics review 13: receiver operating characteristic curves. Crit Care 2004;8:508–512
- Bradley AP. The use of the area under the ROC curve in the evalution of machine learning algorithms. Pattern Recognit 1997;30:1145–1159
- Hastie T, Tibshirani R, Friedman J. Tree-based models. In The Elements of Statistical Learning, Second Edition Springer, New York, 2008, p. 305–316
- Breiman L, Friedman JH, Olshen RA, Stone CJ. Classification and Regression Trees. Belmont, CA, Wadsworth International Group, 1984
- Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412–419
- Olefsky JM. Lilly lecture 1980. Insulin resistance and insulin action. An in vitro and in vivo perspective. Diabetes 1981;30:148–162
- DeFronzo RA: Pathogenesis of type 2 diabetes mellitus. Med Clin North Am 88:787–835, ix, 2004
Source: PubMed