GH Receptor Deficiency in Ecuadorian Adults Is Associated With Obesity and Enhanced Insulin Sensitivity

J Clin Endocrinol Metab. 2015 Jul;100(7):2589-96. doi: 10.1210/jc.2015-1678. Epub 2015 May 18.


Context: Ecuadorian subjects with GH receptor deficiency (GHRD) have not developed diabetes, despite obesity.

Objective: We sought to determine the metabolic associations for this phenomenon.

Design: 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.

Setting: Clinical Research Institute in Quito, Ecuador.

Subjects: 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.

Results: 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.

Main outcome measures: Measures of insulin sensitivity, adipocytokines, and energy metabolites.

Conclusions: 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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines / blood
  • Adult
  • Body Mass Index
  • Carbohydrate Metabolism
  • Case-Control Studies
  • Ecuador / epidemiology
  • Female
  • Humans
  • Insulin Resistance*
  • Laron Syndrome / complications*
  • Laron Syndrome / epidemiology
  • Laron Syndrome / metabolism*
  • Lipids / blood
  • Male
  • Middle Aged
  • Obesity / complications*
  • Obesity / epidemiology
  • Obesity / metabolism*
  • Young Adult


  • Adipokines
  • Lipids