Natural Progression of Diabetic Peripheral Neuropathy in the Zenarestat Study Population

• Published in: Diabetes care Vol. 27; no. 5; pp. 1153 - 1159
• Main Authors: BROWN, Mark J, BIRD, Shawn J, WATLING, Sharon, KALETA, Hong, HAYES, Lee, ECKERT, Stephen, FOYT, Howard L
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01-05-2004
• Subjects: Aldehyde Reductase - antagonists & inhibitors; Biological and medical sciences; Clinical trials; Development and progression; Diabetes; Diabetes Mellitus, Type 1 - physiopathology; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Diabetic neuropathies; Diabetic Neuropathies - physiopathology; Disease Progression; Drug therapy; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Enzyme Inhibitors - therapeutic use; Female; Humans; Male; Median Nerve - physiopathology; Medical sciences; Medical screening; Middle Aged; Motor Neurons - physiology; Neural Conduction - physiology; Neurological disorders; Neurons, Afferent - physiology; Sensation - physiology; Sural Nerve - physiopathology; Time Factors; United States; Endocrinopathy; Human; Nervous system diseases; Enzyme; Diabetes mellitus; Aldehyde reductase; Enzyme inhibitor; Zenarestat; Peripheral nerve disease; Oxidoreductases; Peripheral neuropathy
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/diacare.27.5.1153

Natural Progression of Diabetic Peripheral Neuropathy in the Zenarestat Study Population
Mark J. Brown , MD 1 ,
Shawn J. Bird , MD 1 ,
Sharon Watling , PHARMD 2 ,
Hong Kaleta , MS 2 ,
Lee Hayes , BSC 2 ,
Stephen Eckert , PHD 2 and
Howard L. Foyt , MD, PHD 2
1 Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
2 Pfizer Global Research and Development, Ann Arbor Laboratories, Ann Arbor, Michigan
Address correspondence and reprint requests to Sharon Watling, PharmD, Clinical Development/Metabolism, Pfizer Global Research
and Development, Ann Arbor Laboratories, 2800 Plymouth Rd., Ann Arbor, MI 48105. E-mail: sharon.watling{at}pfizer.com
Abstract
OBJECTIVE —The aim of this study was to report the baseline and natural progression of diabetic peripheral neuropathy over 12 months
in a large mild-to-moderate neuropathy population.
RESEARCH DESIGN AND METHODS —Patients from a multicentered trial of zenarestat, an aldose reductase inhibitor, had serial measures of neurologic function,
including nerve conduction studies (NCSs), quantitative sensory testing (QST), and clinical neuropathy rating scores at baseline
and at 12 months. Baseline population descriptors and changes in neurologic function in placebo-treated patients were analyzed.
RESULTS —Sural sensory velocity ( P = 0.0008 [95% CI −1.04 to −0.27]), median sensory amplitude ( P = 0.0021 [−1.3 to −0.29]), median distal motor latency ( P = 0.002 [0.09–0.28]), cool thermal QST ( P = 0.0005 [0.27–0.94]), and Michigan Neuropathy Screening Instrument results ( P = 0.0087 [0.04–0.30]) declined significantly from baseline in the placebo population. NCS changes from baseline were independent
of baseline HbA 1c stratification.
CONCLUSIONS —The neurologic decline over 12 months is evident when measured by NCS and cool thermal QST. Other measures (vibration QST,
neuropathy rating scores, monofilament examination) are insensitive to changes over 12 months in a mild-to-moderate affected
population of this size.
ARI, aldose reductase inhibitor
CRCC, Central Reading and Coordinating Center
DPN, diabetic peripheral neuropathy
MDNS, Michigan Diabetes Neuropathy Score
MNSI, Michigan Neuropathy Screening Instrument
NCS, nerve conduction study
PNSS, Penn Neuropathy Symptom Scale
QST, quantitative sensory testing
Footnotes
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
Accepted January 25, 2004.
Received September 27, 2003.
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