Chronic Kidney Disease, Insulin Resistance, and Incident Diabetes in Older Adults

Background and objectives Insulin resistance is a complication of advanced CKD. Insulin resistance is less well characterized in earlier stages of CKD. The response of the pancreatic beta cell, effects on glucose tolerance, and risk of diabetes are not clear. Design, setting, participants, & measurements The Cardiovascular Health Study included 4680 adults without baseline diabetes. The Chronic Kidney Disease Epidemiology Collaboration creatinine equation was used to obtain the estimated GFR (eGFR). Insulin resistance was evaluated as fasting insulin concentration. The insulin sensitivity index, beta cell function, and glucose tolerance were assessed by oral glucose tolerance testing. Incident diabetes was defined as fasting glucose >= 126 mg/dl, nonfasting glucose >= 200 mg/dl, or use of glucose-lowering medications. Results Mean age was 72.5 years (range, 65-98 years). Mean eGFR was 72.2 (SD 17.1) ml/min per 1.73 m(2). After adjustment, each 10 ml/min per 1.73 m(2) lower eGFR was associated with a 2.2% higher fasting insulin concentration (95% confidence interval [CI], 1.4%, 2.9%; P<0.001) and a 1.1% lower insulin sensitivity index (95% Cl, 0.03%, 2.2%; P=0.04). Surprisingly, eGFR was associated with an augmented beta cell function index (P<0.001), lower 2-hour glucose concentration (P=0.002), and decreased risk of glucose intolerance (P=0.006). Over a median 12 years' follow-up, 437 participants (9.3%) developed diabetes. eGFR was not associated with the risk of incident diabetes. Conclusions Among older adults, lower eGFR was associated with insulin resistance. However, with lower eGFR, beta cell function was appropriately augmented and risks of impaired glucose tolerance and incident diabetes were not increased. Clin J Am Soc Nephrol 7: 588-594, 2012. doi: 10.2215/CJN.11861111