Divergent metabolic phenotypes in two genetic syndromes of low insulin secretion

Jaime Guevara-Aguirre*, Arlan L Rosenbloom, Alexandra Guevara, Mark A Atkinson, MacKenzie D Williams, Enrique Terán, Amanda L Posgai, Carolina Guevara, Verónica Rosado, Antonio W D Gavilanes, Clive H Wasserfall

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


AIMS: We examined the effect of growth hormone (GH) counter-regulation on carbohydrate metabolism in individuals with life-long diminished insulin secretion (DIS).

METHODS: Adults homozygous for the E180 splice site mutation of GHR [Laron syndrome (LS)], adults with a gain-of-function mutation in CDKN1c [Guevara-Rosenbloom syndrome (GRS)], and controls were evaluated for body composition, leptin, total and high molecular weight (HMW) adiponectin, insulin-like growth factor (IGF) axis molecules, and a 5-hour oral glucose tolerance test (OGTT), with measurements of glucose, insulin, glucagon, ghrelin, pancreatic polypeptide, gastric inhibitory peptide, glucagon-like peptide-1, peptide YY, and islet amyloid polypeptide (IAPP).

RESULTS: Both syndromic cohorts displayed DIS during OGTT. LS subjects had higher serum concentrations of total and HMW adiponectin, and lower levels of IGF-I, IGF-II, and IGF-Binding Protein-3 than individuals in other study groups. Furthermore, they displayed normal glycemic responses during OGTT with the lowest IAPP secretion. In contrast, individuals with GRS had higher levels of protein glycation, deficient glucose control during OGTT, and increased secretion of IAPP.

CONCLUSIONS: A distinct metabolic phenotype depending on GH counter-regulatory status, associates with diabetes development and excess glucose-induced IAPP secretion.

Original languageEnglish
Article number110228
Number of pages8
JournalDiabetes Research and Clinical Practice
Issue number1
Early online date19 Dec 2022
Publication statusPublished - 2023


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