Cardiac abnormalities in diabetic patients with neuropathy: Effects of aldose reductase inhibitor administration

Brian F. Johnson, Richard W. Nesto, Michael A. Pfeifer, William R. Slater, Aaron I. Vinik, Deborah A. Chyun, Gordon Law, Frans J.Th Wackers, Lawrence H. Young

Research output: Contribution to journalArticlepeer-review


OBJECTIVE - The goal of this study was to determine whether treatment with an aldose reductase inhibitor (ARI) has beneficial effects on asymptomatic cardiac abnormalities in diabetic patients with neuropathy. RESEARCH DESIGN AND METHODS - Diabetic subjects with neuropathy (n = 81) with either a low diastolic peak filling rate or impaired augmentation of left ventricular (LV) ejection fraction (LVEF) during maximal bicycle exercise were identified by gated radionuclide ventriculography. Coronary artery disease, left ventricular hypertrophy, and valvular heart disease were excluded by clinical evaluation, myocardial perfusion imaging, and echocardiography. Subjects were randomized to receive blinded treatment with either the placebo or the ARI zopolrestat 500 or 1,000 mg daily for 1 year. RESULTS - After 1 year of ARI treatment, there were increases in resting LVEF (P < 0.02), cardiac output (P < 0.03), LV stroke volume (P < 0.004), and exercise LVEF (P < 0.001). In placebo-treated subjects, there were decreases in exercise cardiac output (P < 0.03), stroke volume (P < 0.02), and end diastolic volume (P < 0.04). Exercise LVEF increased with ARI treatment independent of blood pressure, insulin use, or the presence of baseline abnormal heart rate variability. There was no change in resting diastolic filling rates in either group. CONCLUSIONS - Diabetic patients with neuropathy have LV abnormalities that can be stabilized and partially reversed by ARI treatment.

Original languageEnglish (US)
Pages (from-to)448-454
Number of pages7
JournalDiabetes Care
Issue number2
StatePublished - Feb 2004

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing


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