Serum concentrations of insulin-like growth factors (IGFs), IGF binding proteins 1 and 3 and growth hormone binding protein in obese women and the effects of growth hormone administration: A double-blind, placebo-controlled study

Obesity is associated with suppressed growth hormone (GH) concentrations but relatively little is known about insulin-like growth factors(IGFs) and binding proteins for GH and IGFs (GHBP and IGFBPs) and the modulatory effect of GH administration. In a double-blind, crossover design we studied the impact of 5 weeks of placebo or GH administration (0.03 mg · kg^-1 body wt · day^-1) in nine obese women (mean±SEM: age 30.4 ± 2.4 years: body mass index 37.0 ± 2.8 kg/m²) on IGF-I, IGF-II, IGFBP-1 and -3 and GHBP. Serum IGF-I (μg/l) levels were subnormal and increased significantly following GH (117 ± 16 (placebo) vs 434 ± 33 (GH) vs 198 ± 15 (control (p < 0.01)). By contrast, serum IGF-II (μg/l) levels were in the normal range and remained unchanged (608 ± 20 (placebo) vs 647 ± 40 (GH) (NS)). Serum IGFBP-3 was in the normal range and increased significantly during GH treatment, although relatively less than IGF-I, such that the molar ratio between IGF-I and IGFBP-3 increased with GH treatment, whereas the ratio between IGF-I + IGF- II and IGFBP-3 remained unchanged. Serum IGFBP-1 was low in the placebo situation but became further and almost completely suppressed during GH treatment. During a 2-h hyperinsulinemic, euglycemic glucose clamp. IGFBP-1 decreased in the placebo study and remained suppressed during GH. Serum GHBP (nmol/l) levels were elevated substantially compared to non-obese controls (p < 0.001) and did not change during GH treatment (2.37 ± 0.36 (placebo) vs 2.21 ± 0.25 (GH) vs 0.80 ± 0.19 (control)). In conclusion, obese subjects have low total IGF-I levels but may exhibit relatively increased free IGF-I levels due to the suppression of IGFBP-1. This presumed elevation in free IGF-I in obesity may explain the normal levels of IGFBP-3 and IGF-II, which contrasts with classic GH deficiency. Furthermore, obese subjects are responsive to exogenous GH in terms of total IGF-I generation and normalization of the ratio between IGF-I and IGFBP-3. Finally, obesity is associated with marked elevations in GHBP levels that were unaffected by 5 weeks of GH administration.