Abstract
CONTEXT: It is unclear whether the pattern of GH delivery to peripheral tissues has important effects. OBJECTIVE: The aim of the study was to compare the effects of pulsatile vs. continuous administration of GH upon metabolic and IGF-I parameters in obese subjects. SETTING: The study was conducted at the General Clinical Research Center at the University of Michigan Medical Center. PARTICIPANTS: Four men and five women with abdominal obesity (body mass index, 33 +/- 3 kg/m(2); body fat, 40 +/- 3%) participated in the study. INTERVENTION: GH (0.5 mg/m(2) . d) was given iv for 3 d as: 1) continuous infusion (C); and 2) pulsatile boluses (P) (15% of the dose at 0700, 1300, and 1800 h and 55% at 2400 h). These trials were preceded by a basal period (B) when subjects received normal saline. MAIN OUTCOME MEASURES: Rate of lipolysis and hepatic glucose production were evaluated using stable isotope tracer techniques. The composite index of insulin sensitivity (Matsuda index) was assessed using oral glucose tolerance test. RESULTS: The increase in plasma IGF-I concentrations was greater (P < 0.05) with continuous GH infusion (211 +/- 31, 423 +/- 38, and 309 +/- 34 microg/liter for B, C, and P, respectively). Muscle IGF-I mRNA was significantly increased (P < 0.05) only after the continuous GH infusion (1.2 +/- 0.4, 4.4 +/- 1.3, and 2.3 +/- 0.6 arbitrary units, for B, C, and P, respectively). Only pulsatile GH augmented the rate of lipolysis (4.1 +/- 0.3, 4.8 +/- 0.7, and 7.1 +/- 1.1 mumol/kg . min for B, C, and P, respectively). GH had no effect on hepatic glucose production, but both modes of GH administration were equally effective in impairing insulin sensitivity. CONCLUSION: These findings indicate that, in obese subjects, discrete components of GH secretory pattern may differentially affect IGF-I generation and lipolytic responses.