Dichtel Laura E, Bjerre Mette, Schorr Melanie, Bredella Miriam A, Gerweck Anu V, Russell Brian M, Frystyk Jan, Miller Karen K
Neuroendocrine Unit, Massachusetts General Hospital/Harvard Medical School, Boston, MA, United States.
Medical Research Lab, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Growth Horm IGF Res. 2018 Jun;40:20-27. doi: 10.1016/j.ghir.2018.03.003. Epub 2018 Mar 10.
Overweight/obesity is characterized by decreased growth hormone (GH) secretion whereas circulating IGF-I levels are less severely reduced. Yet, the activity of the circulating IGF-system appears to be normal in overweight/obese subjects, as estimated by the ability of serum to activate the IGF-I receptor in vitro (bioactive IGF). We hypothesized that preservation of bioactive IGF in overweight/obese women is regulated by an insulin-mediated suppression of IGF-binding protein-1 (IGFBP-1) and IGFBP-2, and by suppression of IGFBP-3, mediated by low GH. We additionally hypothesized that increases in bioactive IGF would drive changes in body composition with low-dose GH administration.
Cross-sectional analysis and 3-month interim analysis of a 6-month randomized, placebo-controlled study of GH administration in 50 overweight/obese women without diabetes mellitus. Bioactive IGF (kinase receptor activation assay) and body composition (DXA) were measured.
Prior to treatment, IGFBP-3 (r = -0.33, p = 0.02), but neither IGFBP-1 nor IGFBP-2, associated inversely with bioactive IGF. In multivariate analysis, lower IGFBP-3 correlated with lower peak stimulated GH (r = 0.45, p = 0.05) and higher insulin sensitivity (r = -0.74, p = 0.003). GH administration resulted in an increase in mean serum IGF-I concentrations (144 ± 56 to 269 ± 66 μg/L, p < 0.0001) and bioactive IGF (1.29 ± 0.39 to 2.60 ± 1.12 μg/L, p < 0.0001). The treatment-related increase in bioactive IGF, but not total IGF-I concentration, predicted an increase in lean mass (r = 0.31, p = 0.03) and decrease in total adipose tissue/BMI (r = -0.43, p = 0.003).
Our data suggest that in overweight/obesity, insulin sensitivity and GH have opposing effects on IGF bioactivity through effects on IGFBP-3. Furthermore, increases in bioactive IGF, rather than IGF-I concentration, predicted GH administration-related body composition changes.
NCT00131378.
超重/肥胖的特征是生长激素（GH）分泌减少，而循环中的胰岛素样生长因子-I（IGF-I）水平降低程度较轻。然而，根据血清在体外激活IGF-I受体的能力（生物活性IGF）估计，超重/肥胖受试者循环IGF系统的活性似乎正常。我们假设超重/肥胖女性体内生物活性IGF的维持受胰岛素介导的IGF结合蛋白-1（IGFBP-1）和IGFBP-2抑制以及低GH介导的IGFBP-3抑制调控。我们还假设低剂量GH给药时，生物活性IGF的增加会促使身体成分发生变化。
对50名无糖尿病的超重/肥胖女性进行为期6个月的GH给药随机、安慰剂对照研究的横断面分析和3个月中期分析。测量生物活性IGF（激酶受体激活试验）和身体成分（双能X线吸收法）。
治疗前，IGFBP-3（r = -0.33，p = 0.02）与生物活性IGF呈负相关，而IGFBP-1和IGFBP-2与生物活性IGF无相关性。多变量分析显示，较低的IGFBP-3与较低的峰值刺激GH（r = 0.45，p =
