Citation: Garmes, H.M.; Castillo, A.R.; Monte Alegre, S.; de Souza, A.L.; Atala, Y.B.; Zantut-Wittmann, D.E. Childhood-Onset GH Deficiency versus Adult-Onset GH Deficiency: Relevant Differences Regarding Insulin Sensitivity. Metabolites 2022, 12, 1251. https://doi.org/10.3390/ metabo12121251 Academic Editor: Jose Donato, Jr. Received: 30 October 2022 Accepted: 7 December 2022 Published: 11 December 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). metabolites H OH OH Article Childhood-Onset GH Deficiency versus Adult-Onset GH Deficiency: Relevant Differences Regarding Insulin Sensitivity Heraldo Mendes Garmes 1, *, Alejandro Rosell Castillo 1 , Sarah Monte Alegre 2 , Aglecio Luiz de Souza 2 , Yeelen Ballesteros Atala 1 and Denise Engelbrecht Zantut-Wittmann 1 1 Endocrinology Division, Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Campinas 13083-852, SP, Brazil 2 Internal Medicine Division, Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Campinas 13083-852, SP, Brazil * Correspondence: heraldmg@unicamp.br Abstract: The results of the studies on the pattern of insulin sensitivity (IS) are contradictory in patients with GH deficiency (GHD); however, the interference of the GHD onset stage, childhood or adulthood in the IS has not been assessed by euglycemic hyperinsulinemic clamp (EHC), a gold- standard method for the assessment of insulin sensitivity. In a prospective cross-sectional study, we assessed IS and body composition in 17 adults with hypopituitarism without GH replacement, ten with childhood-onset (COGHD) and seven with adulthood-onset (AOGHD) and compared them to paired control groups. COGHD presented higher IS (p = 0.0395) and a similar percentage of fat mass (PFM) to AOGHD. COGHD showed higher IS than the control group (0.0235), despite a higher PFM (0.0022). No differences were found between AODGH and the control group. In AOGHD and the control group, IS was negatively correlated with PFM (rs: −0.8214, p = 0.0234 and rs: −0.3639, p < 0.0344), while this correlation was not observed with COGHD (rs: −0.1152, p = 0.7514). Despite the higher PFM, patients with COGHD were more sensitive to insulin than paired healthy individuals, while patients with AOGHD showed similar IS compared to controls. The lack of GH early in life could modify the metabolic characteristics of tissues related to the glucose metabolism, inducing beneficial effects on IS that persist into adulthood. Thus, the glycometabolic findings in patients with COGHD seems to be not applicable to AOGHD. Keywords: childhood-onset GH deficiency; euglycemic hyperinsulinemic clamp; insulin sensitivity; fat mass 1. Introduction Growth hormone deficiency (GHD) is known to cause changes in body composition (BC), such as an increased fatty mass and decreased lean mass [1]. GH is a counter- regulatory hormone of the action of insulin and therefore, changes in glucose metabolism have been associated with GHD, such as hypoglycemia, especially in children [2]. Although the increase in fat mass found in these patients could justify a decrease in insulin sensitivity (IS) [3], the results of the studies on the pattern of insulin sensitivity are contradictory in patients with GHD [4]. Some authors have demonstrated a decrease in IS in patients with GHD [3,5], but other studies have even shown an increase [6,7]. Otherwise, studies in animals with extended longevity have shown greater IS in models with decreased prenatal GH action, despite an increased in percentage of fat mass (PFM) [4,8]. These results are similar to those found in most populations with a congenital decrease of GH action, as in patients with a mutation of the GHRH receptor gene and patients with Laron syndrome [9,10]. Many factors have been reported to explain these contradictory aspects about IS in GHD, such as the etiology of GHD and the influence of other hormone replacement thera- pies in patients with hypopituitarism [11,12]. Another important element is the method Metabolites 2022, 12, 1251. https://doi.org/10.3390/metabo12121251 https://www.mdpi.com/journal/metabolites