enprostil and Diabetes-Mellitus--Type-2

Enprostil, a dehydro-prostaglandin E2 analogue, has been tested as treatment for peptic ulcer. Its effect on blood glucose and lipid metabolism in Type 2 diabetes was assessed in a randomized, double-blind trial. Fifteen patients on sulphonylurea therapy received, in addition, enprostil 35 micrograms or placebo thrice daily for two weeks, with a 2-week wash-out before crossover. Data from 12 patients were analysed. After a 530 Cal test breakfast at the end of active treatment, plasma glucose rose from a fasting concentration similar to that after the last placebo dose (10.5 +/- 0.8 (+/- SE) and 10.6 +/- 1.1 mmol l-1 respectively) to 1, 2 and 3 h concentrations which were 1.5 to 2.1 mmol l-1 lower than on placebo (2 h concentration 14.6 +/- 0.9 vs 16.4 +/- 1.3 mmol l-1, p less than 0.05). Serum fructosamine concentrations at the end of active treatment and placebo were 3.66 +/- 0.22 and 3.78 +/- 0.24 respectively (p = 0.051). No changes in fasting or post-prandial insulin concentrations were observed. After 2 weeks of enprostil, fasting serum triglyceride (1.76 +/- 0.18 mmol l-1) and total cholesterol (6.27 +/- 0.29 mmol l-1) concentrations were lower than after placebo (2.14 +/- 0.25 and 7.35 +/- 0.46 mmol l-1, p = 0.031 and p = 0.002, respectively), the latter effect being primarily due to reduced LDL-cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Blood Glucose; Cholesterol; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Double-Blind Method; Eating; Enprostil; Female; Fructosamine; Gastric Inhibitory Polypeptide; Hexosamines; Humans; Insulin; Kinetics; Male; Middle Aged; Prostaglandins E, Synthetic; Triglycerides

Measurements of various aspects of glucose, insulin and lipid metabolism were made before and after the administration of enprostil (a synthetic dehydroprostaglandin E2) for one week to ten patients with non-insulin-dependent diabetes mellitus (NIDDM). Both fasting (P less than 0.01) and postprandial (P less than 0.001) plasma glucose concentrations were significantly lower after one week of enprostil, and 24 hour urinary glucose excretion was reduced from (mean +/- SEM) 47 +/- 14 to 25 +/- 9 g/day. There was no change in either fasting or postprandial insulin concentration, but the postprandial GIP response was also significantly reduced (P less than 0.001). In addition, there were significant reductions in postprandial plasma free fatty acid (P less than 0.05) and triglyceride (P less than 0.001) concentrations, associated with a modest fall in fasting plasma triglyceride (P less than 0.05) and cholesterol (P less than 0.07) concentrations when measured after one week of treatment with enprostil. These results raise the possibility that enprostil may be of some benefit in the treatment of patients with non-insulin-dependent diabetes.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Enprostil; Humans; Insulin; Lipids; Middle Aged; Prostaglandins E, Synthetic