Lack of evidence for improvement in long-term glycemic control by pulsatile insulin infusion in streptozocin-induced diabetic baboon

Abstract

To assess the potential therapeutic use of pulsatile intravenous insulin delivery, five streptozocin-induced diabetic baboons were treated with alternate 3- to 6-wk periods of pulsatile and continuous insulin infusion. Time-averaged insulin concentrations were matched during two pulsatile administration periods (P1 and P2) and an intervening period of continuous insulin administration (C). There were no significant differences among the overall means of four daily glucose determinations performed during the three periods (P1, 5.7 +/- 1 mM; C, 5.6 +/- 0.9 mM; P2, 5.3 +/- 0.9 mM); the mean M value, a measure of the stability of glycemic control (P1, 4 +/- 1.7; C, 3.9 +/- 1.8; P2, 3.6 +/- 1.5); the percentage of glucose values less than 2.8 mM (P1, 13 +/- 8.5%; C, 14 +/- 12%; P2, 13 +/- 9.1%); or the glycosylated hemoglobin levels determined at the end of the P1 and C (7.5 +/- 3.4 and 6.5 +/- 1.8%, respectively [all values are means +/- SD]). Fasting hepatic glucose production was suppressed to a similar degree during pulsatile and continuous insulin infusion (P1, 23 +/- 3 mumol.kg-1.min-1; C, 24 +/- 8 mumol.kg-1.min-1). Arterial glucagon levels were similar during pulsatile and continuous insulin infusion, both in the fasting state (84 +/- 29 and 84 +/- 31 ng/L, respectively) and postprandially (30 +/- 14 and 27 +/- 12 ng/L, respectively). Pulsatile insulin infusion failed to entrain a corresponding glucagon secretory rhythm. These data suggest that the metabolic consequences of long-term pulsatile and continuous insulin infusion in an animal model of human non-insulin-dependent diabetes are comparable.