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Original Article
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Volume 348:2285-2293 June 5, 2003 Number 23
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Regression of Microalbuminuria in Type 1 Diabetes
Bruce A. Perkins, M.D., M.P.H., Linda H. Ficociello, M.Sc., Kristen H. Silva, B.A., Dianne M. Finkelstein, Ph.D., James H. Warram, M.D., Sc.D., and Andrzej S. Krolewski, M.D., Ph.D.

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ABSTRACT

Background In the present study, we aimed to determine the frequency of a significant reduction in urinary albumin excretion and factors affecting such reduction in patients with type 1 diabetes and microalbuminuria.

Methods The study included 386 patients with persistent microalbuminuria, indicated by repeated measurements of urinary albumin excretion (estimated on the basis of albumin-to-creatinine ratios) in the range of 30 to 299 µg per minute during an initial two-year evaluation period. Subsequent measurements during the next six years were grouped into two-year periods, averaged, and analyzed for regression of microalbuminuria, which was defined as a 50 percent reduction in urinary albumin excretion from one two-year period to the next.

Results Regression of microalbuminuria was frequent, with a six-year cumulative incidence of 58 percent (95 percent confidence interval, 52 to 64 percent). The use of angiotensin-converting–enzyme inhibitors was not associated with the regression of microalbuminuria. However, microalbuminuria of short duration, salutary levels of glycosylated hemoglobin (less than 8 percent), low systolic blood pressure (less than 115 mm Hg), and low levels of both cholesterol and triglycerides (less than 198 mg per deciliter [5.12 mmol per liter] and 145 mg per deciliter [1.64 mmol per liter], respectively) were independently associated with the regression of microalbuminuria. Patients with salutary levels of all modifiable factors had a hazard ratio for regression of 3.0 (95 percent confidence interval, 1.5 to 6.0), as compared with patients with no salutary levels of any modifiable factor.

Conclusions Frequent regression of microalbuminuria in patients with type 1 diabetes indicates that elevated urinary albumin excretion does not imply inexorably progressive nephropathy. Identification of the multiple determinants of the regression of microalbuminuria has implications for current theories about the mechanisms of early diabetic nephropathy.


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From the Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center (B.A.P., L.H.F., K.H.S., J.H.W., A.S.K.); the Department of Medicine, Harvard Medical School (B.A.P., D.M.F., A.S.K.); the Massachusetts General Hospital Biostatistics Center (D.M.F.); and the Harvard School of Public Health (D.M.F., J.H.W., A.S.K.) — all in Boston.

Address reprint requests to Dr. Krolewski at the Section on Genetics and Epidemiology, Joslin Diabetes Center, 1 Joslin Pl., Boston, MA 02215, or at andrzej.krolewski{at}joslin.harvard.edu.

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Related Letters:

Regression of Microalbuminuria in Type 1 Diabetes
Friedman A. N., Catena C., Novello M., Sechi L. A., Hohenadel D., Bode H., van der Woude F. J., Zerbini G., Perkins B. A., Warram J. H., Krolewski A. S.
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N Engl J Med 2003; 349:906-908, Aug 28, 2003. Correspondence

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