Risk of type 2 diabetes among individuals with high and low glomerular filtration rates

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.

Fig. 1

Relationship between the 5 year risk of type 2 diabetes and GFR modelled by a smooth function. a Probability of incident diabetes adjusted for age, sex, race/ethnicity, clinic location, BMI, systolic blood pressure (SBP), antihypertensive treatment, history of diabetes in first-degree relatives, insulin sensitivity index, acute insulin response and ACR, and levels of triacylglycerols, HDL-cholesterol, PAI-1 and fasting and 2 h glucose. The OR has a reference level GFR of 80 ml min⁻¹ 1.73 m⁻². b The 5 year cumulative probability for a hypothetical individual with a relevant set of values for the confounders. The participant modelled is a 65 year old Hispanic man at the San Antonio clinic with the following risk factors: SBP 140 mmHg, BMI 30 kg/m², fasting glucose 6.66 mmol/l and 2 h glucose 6.66 mmol/l. All other risk factors are at the study averages