Guevara-Aguirre Jaime, Rosenbloom Arlan L, Balasubramanian Priya, Teran Enrique, Guevara-Aguirre Marco, Guevara Carolina, Procel Patricio, Alfaras Irene, De Cabo Rafael, Di Biase Stefano, Narvaez Luis, Saavedra Jannette, Longo Valter D
Universidad San Francisco de Quito (J.G.-A., E.T.), Quito, Ecuador; Instituto de Endocrinologia, Metabolismo y Repróduccion (J.G.-A., A.L.R., M.G.-A., C.G., P.P., L.N., J.S.), Quito Ecuador; University of Florida College of Medicine (A.L.R.), Gainesville, Florida 32608; Davis School of Gerontology (P.B., S.D.B., V.D.L.), University of Southern California, Los Angeles, California 90089; Experimental Gerontology Section (I.A., R.D.C.), Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224; and Longevity Institute (V.D.L.), University of Southern California, Los Angeles, California 90089.
J Clin Endocrinol Metab. 2015 Jul;100(7):2589-96. doi: 10.1210/jc.2015-1678. Epub 2015 May 18.
Ecuadorian subjects with GH receptor deficiency (GHRD) have not developed diabetes, despite obesity.
We sought to determine the metabolic associations for this phenomenon.
Four studies were carried out: 1) glucose, lipid, adipocytokine concentrations; 2) metabolomics evaluation; 3) metabolic responses to a high-calorie meal; and 4) oral glucose tolerance tests.
Clinical Research Institute in Quito, Ecuador.
Adults homozygous for the E180 splice mutation of the GH receptor (GHRD) were matched for age, gender, and body mass index with unaffected control relatives (C) as follows: study 1, 27 GHRD and 35 C; study 2, 10 GHRD and 10 C; study 3, seven GHRD and 11 C; and study 4, seven GHRD and seven C.
Although GHRD subjects had greater mean percentage body fat than controls, their fasting insulin, 2-hour blood glucose, and triglyceride levels were lower. The indicator of insulin sensitivity, homeostasis model of assessment 2%S, was greater (P < .0001), and the indicator of insulin resistance, homeostasis model of assessment 2-IR, was lower (P = .0025). Metabolomic differences between GHRD and control subjects were consistent with their differing insulin sensitivity, including postprandial decreases of branched-chain amino acids that were more pronounced in controls. High molecular weight and total adiponectin concentrations were greater in GHRD (P = .0004 and P = .0128, respectively), and leptin levels were lower (P = .02). Although approximately 65% the weight of controls, GHRD subjects consumed an identical high-calorie meal; nonetheless, their mean glucose concentrations were lower, with mean insulin levels one-third those of controls. Results of the 2-hour oral glucose tolerance test were similar.
Measures of insulin sensitivity, adipocytokines, and energy metabolites.
Without GH counter-regulation, GHRD is associated with insulin efficiency and obesity. Lower leptin levels, despite higher percentage body fat, suggest that obesity-associated leptin resistance is GH dependent. Elevated adiponectin levels not correlated with percentage body fat indicate that GH signaling is necessary for their typical suppression with obesity.
患有生长激素受体缺乏症（GHRD）的厄瓜多尔受试者尽管肥胖但并未患糖尿病。
我们试图确定这一现象的代谢关联。
进行了四项研究：1）葡萄糖、脂质、脂肪细胞因子浓度；2）代谢组学评估；3）对高热量餐的代谢反应；4）口服葡萄糖耐量试验。
厄瓜多尔基多的临床研究所。
生长激素受体E180剪接突变纯合子的成年人（GHRD）在年龄、性别和体重指数方面与未受影响的对照亲属（C）相匹配，具体如下：研究1，27名GHRD和35名C；研究2，10名GHRD和10名C；研究3，7名GHRD和11名C；研究4，7名GHRD和7名C。
尽管GHRD受试者的平均体脂百分比高于对照组，但其空腹胰岛素、2小时血糖和甘油三酯水平较低。胰岛素敏感性指标，即稳态模型评估2%S更高（P <.0001），胰岛素抵抗指标，即稳态模型评估2-IR更低（P =.0025）。GHRD和对照受试者之间的代谢组学差异与其不同的胰岛素敏感性一致，包括支链氨基酸的餐后降低在对照组中更明显。GHRD中高分子量和总脂联素浓度更高（分别为P =.0004和P =.0128），瘦素水平更低（P =.02）。尽管GHRD受试者的体重约为对照组的65%，但他们摄入了相同的高热量餐；尽管如此，他们的平均葡萄糖浓度更低，平均胰岛素水平仅为对照组的三分之一。2小时口服葡萄糖耐量试验的结果相似。
胰岛素敏感性、脂肪细胞因子和能量代谢物的指标。
在没有生长激素反调节的情况下，GHRD与胰岛素效率和肥胖有关。尽管体脂百分比更高，但瘦素水平更低，这表明肥胖相关的瘦素抵抗是生长激素依赖性的。脂联素水平升高与体脂百分比无关，表明生长激素信号传导对于其在肥胖时的典型抑制是必要的。
