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


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.
Johnson
Brian F
BF
Pfizer Research, Groton, Connecticut, USA.
Nesto
Richard W
RW
Pfeifer
Michael A
MA
Slater
William R
WR
Vinik
Aaron I
AI
Chyun
Deborah A
DA
Law
Gordon
G
Wackers
Frans J Th
FJ
Young
Lawrence H
LH
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D052160:Benzothiazoles; D002302:Cardiac Output; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000503:physiopathology*; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005080:Exercise Test; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006329:Heart Conduction System / Q000503:physiopathology; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D010793:Phthalazines / Q000627:therapeutic use*; D010919:Placebos; D013318:Stroke Volume; D013844:Thiazoles / Q000627:therapeutic use*; D016277:Ventricular Function, Left
D052160:Benzothiazoles; D004791:Enzyme Inhibitors; D010793:Phthalazines; D010919:Placebos; D013844:Thiazoles; C067172:zopolrestat; D000449:Aldehyde Reductase