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Longitudinal Association of Glycemia and Microalbuminuria

The Framingham Offspring Study

¹ General Medicine Division and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
² Department of Mathematics, Statistics, and Consulting Unit, Boston University, Boston, Massachusetts
³ Diabetes Unit and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
⁴ Children’s Hospital Medical Center and Harvard Medical School, Boston, Massachusetts
⁵ Framingham Heart Study, Boston University School of Medicine, Framingham, Massachusetts

OBJECTIVE—To assess current and long-term associations of glycemia with microalbuminuria, a marker of generalized endothelial injury.

RESEARCH DESIGN AND METHODS—We measured clinical characteristics, fasting plasma glucose, and the urinary albumin-to-creatinine ratio (UACR) in 1,311 men and 1,518 women attending the sixth examination cycle (1995–1998) of the Framingham Offspring Study. After excluding participants with diabetes or cardiovascular disease (CVD) at the baseline examination (1971–1974), we used fasting glucose measured at baseline, examination 6, and at least two additional examinations from 1974 to 1995 in regression models to predict risk for microalbuminuria (UACR 30 mg/g) associated with baseline, current, and 24-year time-integrated glycemia.

RESULTS—Microalbuminuria was present in 9.5% of men and 13.4% of women. Among men, age-adjusted odds ratios (95% CI) for microalbuminuria associated with each 0.28 mmol/l (5 mg/dl) increase in baseline, current, and time-integrated glucose levels were 1.12 (1.00–1.16), 1.08 (1.05–1.10), and 1.16 (1.11–1.21), respectively. These effects persisted after adjustment for systolic blood pressure and other confounders. Higher glucose levels also predicted incident diabetes and CVD. Mean time-integrated glucose levels were highest among men who developed both CVD and microalbuminuria (SE 6.82 ± 0.16 mmol/l), intermediate among men with either condition (6.03 ± 0.65 mmol/l), and lowest among men with neither condition (5.49 ± 0.02 mmol/l; P < 0.001 for all pairwise comparisons). We observed similar associations in women.

CONCLUSIONS—Long-term hyperglycemia and subdiabetic glycemia increase risk for microalbuminuria. Microalbuminuria, type 2 diabetes, and CVD seem to arise together over the course of decades, consistent with the hypothesis that they share a common antecedent.

Abbreviations: CVD, cardiovascular disease • UACR, urinary albumin-to-creatinine ratio

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