Cardiac Abnormalities in Diabetic Patients With Neuropathy

Effects of aldose reductase inhibitor administration

  1. Brian F. Johnson, MD1,
  2. Richard W. Nesto, MD2,
  3. Michael A. Pfeifer, MD3,
  4. William R. Slater, MD, FACC4,
  5. Aaron I. Vinik, MD5,
  6. Deborah A. Chyun, RN, PHD6,
  7. Gordon Law, PHD1,
  8. Frans J.Th. Wackers, MD7 and
  9. Lawrence H. Young, MD7
  1. 1Pfizer Research, Groton, Connecticut
  2. 2Department of Cardiovascular Medicine, Lahey Clinic, Burlington, Massachusetts
  3. 3Department of Internal Medicine (Endocrinology and Metabolism), East Carolina Medical School, Greenville, North Carolina
  4. 4Department of Internal Medicine (Cardiology), New York University Medical School, New York, New York
  5. 5Strelitz Diabetes Institute, Eastern Virginia Medical School, Norfolk, Virginia
  6. 6Yale University School of Nursing, New Haven, Connecticut
  7. 7Department of Internal Medicine (Cardiovascular Medicine), Yale University School of Medicine, New Haven, Connecticut
  1. Address correspondence and reprint requests to Lawrence H. Young, MD, Yale University School of Medicine, 333 Cedar Street, FMP 3, New Haven, CT 06520. E-mail: lawrence.young{at}yale.edu

Abstract

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.

Footnotes

  • B.J. holds stock in Pfizer and was employed by Pfizer Research until retirement in February 2002. G.L. holds stock in and is employed by Pfizer Research.

    A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    • Accepted October 20, 2003.
    • Received May 15, 2003.
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  1. doi: 10.2337/diacare.27.2.448 Diabetes Care February 2004 vol. 27 no. 2 448-454
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