A commentary on 10 years of aldose reductase inhibition for limited joint mobility in diabetes.
This investigation examines the clinical response to long-term treatment of the diabetic syndrome of limited joint mobility (LJM) using an aldose reductase inhibitor (ARI) in comparison to historical controls, and proposes a potential role of aldose reductase (AR) genotype and expression in the clinical response to ARI. Clinical parameters, including quantitative hand movement and electromyogram, were followed over a decade of continuous ARI treatment with sorbinil (400 mg/day) in two patients with insulin-dependent diabetes mellitus (IDDM) and severe compromising LJM, and compared to the published 10-year prospective investigation of untreated IDDM diabetic patients with LJM. Both subjects were homozygous for the Z-2 AR allele (A-C)23 that has been linked with microvascular complications of DM. Cellular AR mRNA/beta-actin ratios for both treated patients while on ARI therapy were approximately one-half the value observed in untreated patients with the complications of nephropathy or neuropathy. This is the longest reported experience of ARI intervention for any diabetic complication, documenting sustained correction of LJM, lack of side effects, and a potential molecular basis for the therapeutic response.
Eaton
R P
RP
Department of Medicine, University of New Mexico School of Medicine, Albuquerque 87131, USA.
Sibbitt
W L
WL
Shah
V O
VO
Dorin
R I
RI
Zager
P G
PG
Bicknell
J M
JM
D000199:Actins / Q000235:genetics; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000188:drug therapy; D018900:Dinucleotide Repeats; D004576:Electromyography; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015870:Gene Expression; D005838:Genotype; D006225:Hand / Q000503:physiopathology; D018737:Hand Strength; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D048289:Imidazolidines; D007592:Joint Diseases / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D013577:Syndrome
D000199:Actins; D004791:Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; D012333:RNA, Messenger; D000449:Aldehyde Reductase; C026411:sorbinil