Validation of insulin sensitivity surrogate indices and prediction of clinical outcomes in individuals with and without impaired renal function.
As chronic kidney disease (CKD) progresses with abnormalities in glucose and insulin metabolism, commonly used insulin sensitivity indices (ISIs) may not be applicable in individuals with CKD. Here we sought to validate surrogate ISIs against the glucose disposal rate by the gold-standard hyperinsulinemic euglycemic glucose clamp (HEGC) technique in 1074 elderly men of similar age (70 years) of whom 495 had and 579 did not have CKD (estimated glomerular filtration rate (eGFR) under 60 ml/min per 1.73 m(2) (median eGFR of 46 ml/min per 1.73 m(2))). All ISIs provided satisfactory (weighted κ over 0.6) estimates of the glucose disposal rate in patients with CKD. ISIs derived from oral glucose tolerance tests (OGTTs) agreed better with HEGC than those from fasting samples (higher predictive accuracy). Regardless of CKD strata, all ISIs allowed satisfactory clinical discrimination between the presence and absence of insulin resistance (glucose disposal rate under 4 mg/kg/min). We also assessed the ability of both HEGC and ISIs to predict all-cause and cardiovascular mortality during a 10-year follow-up. Neither HEGC nor ISIs independently predicted mortality. Adjustment for renal function did not materially change these associations. Thus, ISIs can be applied in individuals with moderately impaired renal function for diagnostic purposes. For research matters, OGTT-derived ISIs may be preferred. Our data do not support the hypothesis of kidney function mediating insulin sensitivity (IS)-associated outcomes nor a role for IS as a predictor of mortality.
Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden.
Ting
T
Jia
1] Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden [2] Division of Nephrology, Peking University Shenzhen Hospital, Peking University, Shenzhen, China.
Xiaoyan
X
Huang
Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden.
Abdul R
AR
Qureshi
1] Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden [2] Division of Renal Medicine, Peking Union Medical College Hospital, Beijing, China.
Hong
H
Xu
1] Department of Public Health and Caring Sciences, Section of Geriatrics, Uppsala University, Uppsala, Sweden [2] School of Health and Social Studies, Dalarna University, Falun, Sweden.
Johan
J
Ärnlöv
Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden.
Bengt
B
Lindholm
Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
Tommy
T
Cederholm
Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden.
Peter
P
Stenvinkel
Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
Ulf
U
Risérus
1] Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden [2] Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Juan J
JJ
Carrero
D000368:Aged; D018450:Disease Progression; D005919:Glomerular Filtration Rate; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D011379:Prognosis; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis / Q000378:metabolism*