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Validation of Steady-State Insulin Sensitivity Indices in Chronic Kidney Disease

¹ Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania, Philadelphia, Pennsylvania
² Renal Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
³ University of Pennsylvania General Clinical Research Center, Philadelphia, Pennsylvania

Address correspondence and reprint requests to Michael Crutchlow, MD, Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania School of Medicine, Room 778, Clinical Research Building, 415 Curie Blvd., Philadelphia, PA 19104. E-mail: mcrutchl{at}mail.med.upenn.edu

OBJECTIVE— Insulin resistance may contribute to cardiovascular disease and the progression of renal insufficiency in patients with chronic kidney disease (CKD). However, feasible methods for estimating insulin sensitivity in large-population CKD studies have not been validated. The purpose of this study was to attempt to validate several commonly used steady-state insulin sensitivity (SI-SS) indices in a CKD population.

RESEARCH DESIGN AND METHODS— Twenty-seven subjects with estimated glomerular filtration rate (eGFR) ranging from 70 to <10 ml/min per 1.73m² (median eGFR = 48) underwent a frequently sampled intravenous glucose tolerance test (FSIVGTT) on a single occasion. Correlations were obtained between the minimal model-derived insulin sensitivity parameter from the FSIVGTT (SI-FSIVGTT) and seven SI-SS indices derived from fasting insulin and glucose data obtained just before the FSIVGTT.

RESULTS— Each of the seven steady-state indices was significantly correlated with SI-FSIVGTT. For indices obtained using the mean of four fasting insulin and glucose values over 15 min, Pearson correlation coefficients (|r|) ranged from 0.51 to 0.87 (P < 0.01 for each). For indices using single fasting insulin and glucose values, |r| ranged from 0.51 to 0.72 (P < 0.01 for each). By both the four and one time point approaches, 1/I₀ had the highest correlation with SI-FSIVGTT. The correlation with SI-FSIVGTT did not change significantly according to eGFR level for any of the SI-SS indices.

CONCLUSIONS— SI-SS indices are valid surrogates for SI-FSIVGTT in the CKD population. Their use will expand the range of testable hypotheses in CKD cohort studies.

Abbreviations: CKD, chronic kidney disease • CVD, cardiovascular disease • eGFR, estimated glomerular filtration rate • FSIVGTT, frequently sampled intravenous glucose tolerance test • HOMA, homeostasis model assessment • IR-HOMA, homeostasis model assessment of insulin resistance • SI-clamp, insulin sensitivity estimation from hyperinsulinemic-euglycemic clamp • SI-FSIVGTT, insulin sensitivity estimation from FSIVGTT • SI-SS, steady-state insulin sensitivity

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