Abstract
ObjectivesAdult subjects with untreated, lifetime, isolated GH deficiency (IGHD) due to a homozygous GHRH receptor gene mutation (MUT/MUT) residing in Itabaianinha, Brazil, present with lower BMI, higher prevalence of impaired glucose tolerance (IGT), increased insulin sensitivity (IS), and reduced β-cell function (βCF) when compared with non-BMI-matched homozygous normal controls. However, the prevalence of diabetes mellitus (DM) in this cohort is unknown. Comparing their IS and βCF with BMI-matched individuals heterozygous for the same mutation (MUT/N) may be useful to elucidate the role of the GH–IGF1 axis in IS and βCF. The purposes of this work were to verify the prevalence of IGT and DM in adult MUT/MUT subjects from this kindred and to compare IS and βCF in MUT/MUT and MUT/N.DesignCross-sectional study.MethodsWe studied most (51) of the living IGHD adults of this kindred who are GH naive. The oral glucose tolerance test (OGTT) could be performed in 34 subjects, fasting glucose was measured in 15, while two had a previous diagnosis of DM. The OGTT results of 24 MUT/MUT subjects were compared with those of 25 BMI-matched MUT/N subjects. IS was assessed by homeostatic model assessment of insulin resistance (HOMA–IR), quantitative IS check index, and oral glucose IS index for 2 and 3 h. βCF was assayed by HOMA-β, insulinogenic index, and the area under the curve of insulin:glucose ratio.ResultsThe prevalence of DM and IGT in IGHD was 15.68 and 38.23% respectively. IS was increased and βCF was reduced in MUT/MUT in comparison with MUT/N.ConclusionsLifetime, untreated IGHD increases IS, impairs βCF, and does not provide protection from diabetes.
Highlights
GH regulates b-cell function and insulin sensitivity (IS) both directly and via complex interactions with its principal mediator, insulin-like growth factor 1 (IGF1) [1].While GH reduces IS, IGF1 increases it
We have previously described a large extended kindred with congenital isolated GH deficiency (GHD) (IGHD) due to the c.57C1GOA mutation in the GHRH receptor (GHRHR) gene (GHRHR), who reside in Itabaianinha county in northeast Brazil [9]
The prevalence of diabetes mellitus (DM) we have observed was similar to that of DM in two population studies in Brazil (12.1 and 13.5%), the prevalence of impaired glucose tolerance (IGT) is even higher than that reported in these studies (5 and 7.7% respectively) [16, 17]
Summary
GH regulates b-cell function (bCF) and insulin sensitivity (IS) both directly and via complex interactions with its principal mediator, insulin-like growth factor 1 (IGF1) [1]. While GH reduces IS, IGF1 increases it. 2 : 113 muscle [2]. At least in animal models, IGF1 has an important role in the development of b-cell mass [3, 4, 5]. Genetic forms of GH resistance or GH deficiency (GHD) may be useful to clarify the role of the GH–IGF1 axis in regulating insulin secretion and action in humans
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