Long-term clinical effects of epalrestat, an aldose reductase inhibitor, on progression of diabetic neuropathy and other microvascular complications: multivariate epidemiological analysis based on patient background factors and severity of diabetic neuropathy

• Published in: Diabetic medicine Vol. 29; no. 12; pp. 1529 - 1533
• Main Authors: Hotta, N., Kawamori, R., Fukuda, M., Shigeta, Y.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.2012; Blackwell; Wiley Subscription Services, Inc
• Subjects: Aged; Aged, 80 and over; Aldehyde Reductase - antagonists & inhibitors; Asian Continental Ancestry Group; Biological and medical sciences; Blood Glucose - drug effects; Cost-Benefit Analysis; Diabetes; Diabetes. Impaired glucose tolerance; Diabetic Neuropathies - blood; Diabetic Neuropathies - drug therapy; Diabetic Neuropathies - physiopathology; Diabetic neuropathy; Diabetic retinopathy; Diabetic Retinopathy - blood; Diabetic Retinopathy - drug therapy; Diabetic Retinopathy - physiopathology; Disease Progression; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Enzyme Inhibitors - pharmacology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Glycated Hemoglobin A; Humans; Male; Medical sciences; Middle Aged; Multivariate Analysis; Neural Conduction - drug effects; Rhodanine - analogs & derivatives; Rhodanine - pharmacology; Severity of Illness Index; Thiazolidines - pharmacology; Time Factors; Treatment Outcome; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Endocrinopathy; Epalrestat; Prognosis; Cardiovascular disease; Neuropathy; Multivariate analysis; Epidemiology; Vascular disease; Evolution; Nutritional status; Public health; Human; Obesity; Nervous system diseases; Nutrition; Enzyme; Diabetes mellitus; Nutrition disorder; Enzyme inhibitor; Patient; Metabolic diseases; Severity; Long term; Microangiopathy; Aldehyde reductase; Oxidoreductases; Antecedent; Endocrinology
• ISSN: 0742-3071; 1464-5491; 1464-5491
• DOI: 10.1111/j.1464-5491.2012.03684.x

Diabet. Med. 29, 1529–1533 (2012) Aims  The goal of the study was to evaluate the efficacy of epalrestat, an aldose reductase inhibitor, on diabetic retinopathy and diabetic nephropathy, based on analysis of the results of the Aldose Reductase Inhibitor–Diabetes Complications Trial, a 3‐year multicentre comparative clinical trial of conventional therapy (control group) and epalrestat therapy (epalrestat group) in Japanese patients with mild diabetic neuropathy. Methods  The subjects of the study were patients enrolled in the Aldose Reductase Inhibitor–Diabetes Complications Trial for whom data for major patient characteristics, severity of diabetic neuropathy at the end of the study and time‐courses of diabetic retinopathy and diabetic nephropathy were available (57 and 52 patients from the control and epalrestat groups, respectively). Progression of diabetic retinopathy/nephropathy (a primary endpoint) in relation to major patient characteristics, severity of diabetic neuropathy at the end of the study (assessed from the mean of z‐scores in four neurological function tests) and epalrestat treatment were analysed using univariate analysis and multiple logistic regression analysis. Results  Progression of diabetic retinopathy/nephropathy was significantly inhibited in the epalrestat group compared with the control group (odds ratio = 0.323, P = 0.014) and was dependent on the severity of diabetic neuropathy at the end of the study (odds ratio = 2.131, P = 0.025). Conclusions  Epalrestat prevented progression of diabetic neuropathy and retinopathy/nephropathy. The effect on diabetic retinopathy/nephropathy may have occurred indirectly because of the prevention of progression of diabetic neuropathy, in addition to the inhibitory action of epalrestat on aldose reductase.