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Krentz AJ, Ellis SH, Hardman M, et al. Metabolic effects of aldose reductase inhibition in diabetic man. Diabetes Res. 1992;19(1):41-8
Krentz, A. J., Ellis, S. H., Hardman, M., & Nattrass, M. (1992). Metabolic effects of aldose reductase inhibition in diabetic man. Diabetes research (Edinburgh, Scotland), 19(1), 41-8.
Krentz, A J, et al. "Metabolic effects of aldose reductase inhibition in diabetic man." Diabetes research (Edinburgh, Scotland) vol. 19,1 (1992): 41-8.
Krentz AJ, Ellis SH, Hardman M, Nattrass M. Metabolic effects of aldose reductase inhibition in diabetic man. Diabetes Res. 1992 Jan;19(1):41-8. PMID: 1468186.
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Diabetes Res. 1992 Jan;19(1):41-8.

Metabolic effects of aldose reductase inhibition in diabetic man.

Diabetes research (Edinburgh, Scotland)

A J Krentz, S H Ellis, M Hardman, M Nattrass

Affiliations

  1. Diabetic Clinic, General Hospital, Birmingham, UK.

PMID: 1468186

Abstract

The metabolic effects of 52 weeks treatment with the aldose reductase inhibitor ponalrestat were examined in 32 diabetic patients (16 insulin treated) in a randomized, double-blind, placebo-controlled clinical trial. Twelve hour metabolic profiles were performed on two separate occasions in each patient (a) during a single-blind placebo run-in period and (b) after 52 weeks treatment with either ponalrestat 600 mg/day or matching placebo. No effects attributable to ponalrestat were evident in glucose, pyruvate, or alanine metabolism. A significant overall treatment effect was observed for lactate concentration (ponalrestat vs. placebo 12 h least square mean at 52 weeks: 1.35 vs. 1.65 mmol/l, p = 0.024). For glycerol (p = 0.018), non-esterified fatty acids (p = 0.003) and total ketone bodies (p = 0.045) there was evidence for a variation of treatment with time between the insulin treated and non-insulin treated patients, although no statistically significant overall treatment effects were observed for any metabolite. Fasting total ketone body concentration at 52 weeks was significantly elevated in the insulin-treated patients receiving ponalrestat (antilog LS mean: 0.12 vs. 0.01 mmol/l, p = 0.01). In conclusion, ponalrestat has no effect on glucose metabolism in diabetic patients. A potentially beneficial effect on lactate metabolism was accompanied by a minor ketogenic effect in insulin-treated patients.

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