Chronic kidney disease, insulin resistance, and incident diabetes in older adults.

Pham H, Robinson-Cohen C, Biggs ML, Ix JH, Mukamal KJ, Fried LF, Kestenbaum B, Siscovick DS, de Boer IH
Clin J Am Soc Nephrol. 2012 7 (4): 588-94

PMID: 22383749 · PMCID: PMC3315343 · DOI:10.2215/CJN.11861111

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 β 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, β 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% CI, 0.03%, 2.2%; P=0.04). Surprisingly, eGFR was associated with an augmented β 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, β cell function was appropriately augmented and risks of impaired glucose tolerance and incident diabetes were not increased.

MeSH Terms (25)

Aged Aged, 80 and over Age Factors Biomarkers Chronic Disease Creatinine Diabetes Mellitus Female Glomerular Filtration Rate Glucose Tolerance Test Health Surveys Humans Hypoglycemic Agents Incidence Insulin Insulin-Secreting Cells Insulin Resistance Kidney Kidney Diseases Linear Models Male Proportional Hazards Models Risk Assessment Risk Factors United States

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