title: Longitudinal association of glycemia and microalbuminuria: the Framingham Offspring Study.
abstract: OBJECTIVE
  To assess current and long-term associations of glycemia with microalbuminuria, a marker of generalized endothelial injury.
  
  
  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 > or = 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.
authors.affiliation: General Medicine Division and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. jmeigs@partners.org
authors.forename: James B
authors.initials: JB
authors.lastname: Meigs
authors.forename: Ralph B
authors.initials: RB
authors.lastname: D'Agostino
authors.forename: David M
authors.initials: DM
authors.lastname: Nathan
authors.forename: Nader
authors.initials: N
authors.lastname: Rifai
authors.forename: Peter W F
authors.initials: PW
authors.lastname: Wilson
mesh_terms: D000368:Aged; D000419:Albuminuria; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D005215:Fasting; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008875:Middle Aged; D018579:Patient Selection; D012307:Risk Factors; D012727:Sex Characteristics
chemical_list: D001786:Blood Glucose