title: Metabolic effects of aldose reductase inhibition in diabetic man.
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.
authors: Diabetic Clinic, General Hospital, Birmingham, UK.
authors: A J
authors: AJ
authors: Krentz
authors: S H
authors: SH
authors: Ellis
authors: M
authors: M
authors: Hardman
authors: M
authors: M
authors: Nattrass
mesh_terms: D000409:Alanine / Q000097:blood; D000449:Aldehyde Reductase / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D003929:Diabetic Neuropathies / Q000097:blood* / Q000188:drug therapy*; D004311:Double-Blind Method; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005990:Glycerol / Q000097:blood; D006801:Humans; D007657:Ketone Bodies / Q000097:blood; D007773:Lactates / Q000097:blood; D008297:Male; D008875:Middle Aged; D011773:Pyruvates / Q000097:blood
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007657:Ketone Bodies; D007773:Lactates; D011773:Pyruvates; D000449:Aldehyde Reductase; D000409:Alanine; D005990:Glycerol