Five weeks of insulin-like growth factor-I treatment does not alter glucose kinetics or insulin sensitivity during a hyperglycemic clamp in older women

Insulin sensitivity and the activity of the hypothalamic-growth hormone (GH)- insulin-like growth factor-I (IGF-I) axis both decline with age. Treatment with IGF-I increases insulin sensitivity in healthy young subjects. We hypothesized that increasing plasma IGF-I in postmenopausal women to levels characteristic of young women would enhance insulin sensitivity. To test the hypothesis, fasting glucose kinetics and insulin sensitivity were measured in 24 healthy, normoglycemic, postmenopausal women-before and after 5 weeks of treatment with either recombinant human (rh)IGF-I (15 mug/kg body weight/d twice daily) or placebo in a double-blind study. Diet energy content and composition were rigidly controlled to maintain energy balance. A hyperglycemic clamp..(8, mmol/L) coupled with stable isotope infusion ([6,6(2)H]glucose) was performed before and after treatment to assess whole-body insulin sensitivity; defined as the glucose rate of disappearance (Rd) or rate of infusion (GRIF) scaled to the steady-state insulin concentration (1). There were no differences in fasting glucose or insulin concentrations, glucose kinetics, or glucose oxidation after either treatment. During the clamps, steady-state insulin concentrations with placebo (pre = 151 +/- 28 pmol/L, post = 173 +/- 31 pmol/L) were slightly different than with IGF-I (pre 182 37 pmol/L, post = 163 33 pmol/L), but the variations were not significant. No significant changes in whole-body insulin sensitivity were observed after treatment with IGF-I, calculated as Rd/I (pre = 17.7 +/- 2.6 mug/kg/min/pmol/L, post = 19.3 +/- 2.0 mug/kg/min/pmol/L for IGF-I v pre = 24.2 +/- 2.5 mug/kg/min/pmol/L, post = 22.8 +/- 3.4 mug/kg/min/pmol/L for placebo) or as GRIF/I (pre 18.0 +/- 3.9 mug/kg/min/pmol/L, post = 22.3 +/- 3.5 mug/kg/min/pmol/L for IGF-1 v pre = 26.4 +/- 6.2 mug/kg/min/pmol/L, post 26.9 +/- 4.8 mug/kg/min/pmol/L for placebo). Baseline insulin sensitivity in women using hormone replacement therapy (HRT, n = 15) was similar to nonusers (n = 9), but HRT users derived a greater portion of energy expenditure from carbohydrate oxidation compared with nonusers. HRT use had no impact on the response to IGF-I. Overall, we observed subtle, but physiologically insignificant, variations after IGF-I treatment in the direction of enhanced insulin sensitivity. The data suggest that 5 weeks of low-dose rhIGF-I treatment has no material influence on whole-body insulin sensitivity in normoglycemic postmenopausal women. (C) 2003 Elsevier Inc. All rights reserved.