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Impaired Vascular Reactivity in African-American Patients with Type 2 Diabetes Mellitus and Microalbuminuria or Proteinuria Despite Angiotensin-Converting Enzyme Inhibitor Therapy

Department of Medicine (A.J., S.A., V.F.), Section of Endocrinology, Tulane University Medical Center, New Orleans, Louisiana 70112-2699; Huey P. Long Medical Center (S.N.), Pineville, Louisiana 71361; and Brigham and Women’s Hospital (M.P.), Boston, Massachusetts 02115

Address all correspondence and requests for reprints to: Vivian A. Fonseca, M.D., Professor of Medicine and Pharmacology, Tullis Tulane Alumni Chair in Diabetes, Chief, Section of Endocrinology, Tulane University Medical Center, SL-53, 1430 Tulane Avenue, New Orleans, Louisiana 70112-2699. E-mail: vfonseca{at}tulane.edu.

Background: Microalbuminuria, an early indicator of diabetic nephropathy that reflects other vascular abnormalities, usually improves or resolves with angiotensin-converting enzyme inhibitor (ACEI) therapy. Persistent microalbuminuria despite ACEI therapy may be associated with poor prognosis for cardiovascular disease and mortality. African-Americans are reported to respond less well to ACEI and are at increased risk of disease progression.

Methods and Results: We compared flow-mediated dilatation (FMD) and nitroglycerine-dependent dilatation (NDD) in African-American diabetic subjects with persistent microalbuminuria (n = 35) despite ACEI therapy and those in whom microalbuminuria had resolved (n = 15). The two groups were not statistically different in terms of blood pressure, age, sex, lipids, and hemoglobin A1c. FMD was reduced in the microalbuminuria group, compared with subjects without microalbuminuria (4.2 vs. 11.4%; P < 0.0001). Similarly, NDD was reduced in the microalbuminuria group, compared with subjects without microalbuminuria (10.8 vs.16.6%; P = 0.011). The FMD in African-American patients with persistent microalbuminuria was also significantly lower than in clinically similar Caucasian patients whose microalbuminuria had persisted despite ACEI therapy (4.2 vs. 7.5%; P = 0.03). On multiple regression analysis, persistent microalbuminuria is the only predictor of abnormal endothelial function in these patients.

Conclusions: Our study clearly demonstrates that African-American type 2 diabetic subjects with persistent microalbuminuria have severely impaired FMD and NDD, compared with matched patients who had microalbuminuria that was eliminated by ACEI. This may explain the poor prognosis for cardiovascular disease in patients who have persistent microalbuminuria. Alternative strategies for reducing microalbuminuria in high-risk patients who do not respond adequately to ACEI therapy such as African-Americans are needed.

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