Abstract
AIMS/HYPOTHESIS: Metabolic abnormalities frequently develop prior to the diagnosis of type 2 diabetes and chronic kidney disease. However, it is not known whether GFR predicts the onset of type 2 diabetes. METHODS: Incident diabetes was ascertained in the Insulin Resistance Atherosclerosis Study (IRAS) (n = 864; age 40-69 years; median follow-up 5.2 years [4.5-6.6 years]; 141 incident cases of diabetes). GFR was estimated by the Modification of Diet in Renal Disease equation. We assessed the relationship between GFR and incident diabetes by logistic regression analysis. Results were adjusted for age, sex, ethnicity, clinic location, BMI, systolic blood pressure, antihypertensive treatment, family history of diabetes, insulin sensitivity and secretion, albumin to creatinine ratio, and levels of triacylglycerols, HDL-cholesterol, plasminogen activator inhibitor-1, and fasting and 2 h glucose. RESULTS: The relationship between GFR and incident diabetes was not linear. This relationship was statistically significant (p = 0.039) using a restricted cubic polynomial spline for GFR as a regression modelling strategy. Participants were stratified by GFR quintiles. Mean values for GFR from the first to the fifth quintile were 60.8, 71.6, 79.8, 88.2 and 109.0 ml min(-1) 1.73 m(-2). Relative to the fourth quintile, the odds ratios of incident diabetes for the first, second, third and fifth quintiles were 2.32 (95% CI 1.06-5.05), 1.76 (95% CI 0.80-3.88), 1.26 (95% CI 0.56-2.84) and 2.59 (95% CI 1.18-5.65), respectively. CONCLUSIONS/INTERPRETATION: Individuals in the upper and lower ranges of GFR are at increased risk of future diabetes. GFR and type 2 diabetes may share common pathogenic mechanisms.