title: GH Receptor Deficiency in Ecuadorian Adults Is Associated With Obesity and Enhanced Insulin Sensitivity.
abstract: BACKGROUND
  Ecuadorian subjects with GH receptor deficiency (GHRD) have not developed diabetes, despite obesity.
  
  
  OBJECTIVE
  We sought to determine the metabolic associations for this phenomenon.
  
  
  METHODS
  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.
  
  
  METHODS
  Clinical Research Institute in Quito, Ecuador.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: 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.
authors.forename: Jaime
authors.initials: J
authors.lastname: Guevara-Aguirre
authors.affiliation: 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.
authors.forename: Arlan L
authors.initials: AL
authors.lastname: Rosenbloom
authors.affiliation: 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.
authors.forename: Priya
authors.initials: P
authors.lastname: Balasubramanian
authors.affiliation: 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.
authors.forename: Enrique
authors.initials: E
authors.lastname: Teran
authors.affiliation: 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.
authors.forename: Marco
authors.initials: M
authors.lastname: Guevara-Aguirre
authors.affiliation: 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.
authors.forename: Carolina
authors.initials: C
authors.lastname: Guevara
authors.affiliation: 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.
authors.forename: Patricio
authors.initials: P
authors.lastname: Procel
authors.affiliation: 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.
authors.forename: Irene
authors.initials: I
authors.lastname: Alfaras
authors.affiliation: 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.
authors.forename: Rafael
authors.initials: R
authors.lastname: De Cabo
authors.affiliation: 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.
authors.forename: Stefano
authors.initials: S
authors.lastname: Di Biase
authors.affiliation: 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.
authors.forename: Luis
authors.initials: L
authors.lastname: Narvaez
authors.affiliation: 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.
authors.forename: Jannette
authors.initials: J
authors.lastname: Saavedra
authors.affiliation: 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.
authors.forename: Valter D
authors.initials: VD
authors.lastname: Longo
mesh_terms: D054392:Adipokines / Q000097:blood; D000328:Adult; D015992:Body Mass Index; D050260:Carbohydrate Metabolism; D016022:Case-Control Studies; D004484:Ecuador / Q000453:epidemiology; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D046150:Laron Syndrome / Q000150:complications* / Q000453:epidemiology / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000453:epidemiology / Q000378:metabolism*; D055815:Young Adult
chemical_list: D054392:Adipokines; D008055:Lipids