Augmented effect of short-term pulsatile versus continuous insulin delivery on lipid metabolism but similar effect on whole-body glucose metabolism in obese subjects.

The present study was designed to examine the effect of pulsatile versus continuous insulin delivery on glucose and lipid metabolism in insulin-resistant subjects. Six obese women (body mass index, 40.0 +/- 2.8 kg/m2) underwent a euglycemic glucose clamp (plasma glucose, 90 mg/dL) twice. In random order, insulin was infused intravenously for 375 minutes either at a constant rate (0.4 mU/kg/min) or in a pulsatile manner (2.4 mU/kg/min for 2 minutes followed by an off interval of 10 minutes). Endogenous insulin release was suppressed by infusion of somatostatin (250 micrograms/h). Mean circulating insulin concentrations were similar during the two protocols (pulsatile v continuous infusion, 60 +/- 10 v 56 +/- 9 mU/L), but pulsatile infusion was accompanied by oscillations with an amplitude of 120 mU/L. After 6 hours of pulsatile versus continuous insulin, isotopically determined total glucose disposal (3-3H-glucose) and hepatic glucose production (HGP) were comparable (pulsatile v continuous, 2.80 +/- 0.56 v 2.82 +/- 0.51 and 0.37 +/- 0.14 v 0.32 +/- 0.17 mg/kg/min). However, the rate of glucose oxidation (indirect calorimetry) was augmented (P < .05), whereas lipid oxidation tended to be diminished (.10 > P > .05) following pulsatile infusion. In addition, blood glycerol was more suppressed with pulsatile (31 +/- 9 nmol/L) than with continuous infusion (36 +/- 10 nmol/L, P < .05), whereas blood lactate, alanine, and 3-hydroxybutyrate were similar in the two infusion protocols.(ABSTRACT TRUNCATED AT 250 WORDS)