Preventive effects of octreotide (SMS 201-995) on diabetic ketogenesis during insulin withdrawal.
1. Exogenous somatostatin inhibits glucagon secretion and prevents ketoacidosis in diabetic patients, but has the therapeutic disadvantage of requiring continuous intravenous infusion to exhibit these effects. 2. Consequently, we examined the effect of subcutaneous administration of the long-acting somatostatin analogue octreotide (SMS 201-995) on early ketogenesis in diabetic ketoacidosis. On two separate occasions insulin was withdrawn over a period of 9 h from seven type I diabetic patients. On the second occasion the patients were given 50 micrograms octreotide s.c. before the insulin withdrawal and every 3 h during insulin withdrawal. 3. Differences in integrated free fatty acid responses (4706 +/- 1227 mumol l-1 h vs 3026 +/- 835 mumol l-1 h, AUC, P = NS) were not significant, but the peak increments of acetoacetate (1413 +/- 354 mumol l-1 vs 612 +/- 176 mumol l-1, P less than 0.05), beta-hydroxybutyrate (2180 +/- 475 mumol l-1 vs 922 +/- 246 mumol l-1, P less than 0.01) and the decrements in plasma bicarbonate (-8 +/- 1 mumol l-1 vs -4 +/- 1 mumol l-1, P less than 0.05) and pH (-0.07 +/- 0.01 vs -0.03 +/- 0.01, P less than 0.05) were significantly less with octreotide. 4. At the same time peak increments of glucagon were lower with octreotide treatment (329 +/- 206 pg ml-1 vs 39 +/- 30 pg ml-1, P less than 0.05). 5. We conclude that, despite accelerated lipolysis and provision of substrate for ketogenesis during insulin withdrawal, this somatostatin analogue significantly reduces ketogenesis resulting from insulin deprivation, probably secondary to decreasing glucagon secretion. This drug may be useful in short term prophylactic treatment of diabetic patients during periods of increased risk for ketoacidosis.
Diem
P
P
Department of Medicine, University of Bern, Switzerland.
Robertson
R P
RP
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy; D016883:Diabetic Ketoacidosis / Q000188:drug therapy / Q000517:prevention & control*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000097:blood; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D007657:Ketone Bodies / Q000097:blood; D015282:Octreotide / Q000627:therapeutic use*
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007657:Ketone Bodies; D005934:Glucagon; D015282:Octreotide