Diabetes Care 28 2436 2440 2005


Glycemic Status and Development of Kidney Disease
The Framingham Heart Study
Caroline S. Fox, MD, MPH1,2,3, Martin G. Larson, SCD1,4, Eric P. Leip, MS1,4, James B. Meigs, MD5, Peter W.F. Wilson, MD4 and Daniel Levy, MD1,3,4
1 National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, Massachusetts
2 Department of Endocrinology, Diabetes, and Hypertension, the Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
3 National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland
4 Boston University School of Medicine, Boston, Massachusetts
5 General Medicine Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

Address correspondence and reprint requests to Caroline S. Fox, MD, MPH, Framingham Heart Study, 73 Mt. Wayte Ave. Suite 2, Framingham, MA 01702. E-mail:


OBJECTIVE—Diabetes is a major risk factor for the development of kidney disease and is the leading cause of end-stage renal disease in the U.S. Whether pre-diabetes is associated with the development of kidney disease is unclear.

RESEARCH DESIGN AND METHODS—Subjects free of chronic kidney disease (CKD) were drawn from the Framingham Heart Study offspring cohort (1991–1995), given an oral glucose tolerance test, and followed for an average of 7 years for development of CKD (glomerular filtration rate [GFR] of <59 ml/min per 1.73 m2 in women and <64 ml/min per 1.73 m2 in men). Multivariable logistic regression models, adjusted for cardiovascular disease risk factors including age, sex, hypertension, smoking, BMI, total and HDL cholesterol levels, and prevalent myocardial infarction or congestive heart failure, were used to estimate the odds of patients developing kidney disease among glycemic categories.

RESULTS—Of 2,398 subjects (53% women; mean age 54 years), 63% were normoglycemic, 29% had impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), 3.4% were newly diabetic, and 4.6% had known diabetes. By glycemic category, mean GFR at follow-up was 87, 85, 82, and 78 ml/min per 1.73 m2, respectively. The fully adjusted odds of developing CKD were 0.98 (95% CI 0.67–1.45), 1.71 (95% CI 0.83–3.55), and 1.93 (95% CI 1.06–3.49) among those with IFG or IGT, newly diagnosed diabetes, or known diabetes, respectively, compared with those who were normoglycemic at baseline. Among participants without diabetes, metabolic syndrome was not associated with kidney disease at follow-up (odds ratio 1.46, P = 0.06).

CONCLUSIONS—Cardiovascular disease risk factors explain much of the relationship between prediabetes and the development of chronic kidney disease. Clinical trials are warranted to determine whether vascular risk factor modification can slow the decline of kidney function among those with pre-diabetes.


Abbreviations: CKD, chronic kidney disease • GFR, glomerular filtration rate • HOMA-IR, homeostasis model assessment of insulin resistance • IFG, impaired fasting glucose • IGT, impaired glucose tolerance • K/DOQI, National Kidney Foundation Kidney Disease Outcome Quality Initiative • NGT, normal glucose tolerance • NHANES, National Health and Nutrition Examination Survey