Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

Insulin secretion defect in children and adolescents with obesity: clinical and molecular genetic characterization

[thumbnail of Original Article]
Preview
PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
956kB
[thumbnail of Supplementary Materials] MS Word (Supplementary Materials)
84kB

Item Type:Article
Title:Insulin secretion defect in children and adolescents with obesity: clinical and molecular genetic characterization
Creators Name:Enders-Seidlitz, H., Raile, K., Gong, M., Galler, A., Kuehnen, P. and Wiegand, S.
Abstract:INTRODUCTION: Childhood obesity is increasing worldwide and presents as a global health issue due to multiple metabolic comorbidities. About 1% of adolescents with obesity develop type 2 diabetes (T2D); however, little is known about the genetic and pathophysiological background at young age. The objective of this study was to assess the prevalence of impaired glucose regulation (IGR) in a large cohort of children and adolescents with obesity and to characterize insulin sensitivity and insulin secretion. We also wanted to investigate adolescents with insulin secretion disorder more closely and analyze possible candidate genes of diabetes in a subcohort. METHODS: We included children and adolescents with obesity who completed an oral glucose tolerance test (OGTT, ) in the outpatient clinic. We calculated Matsuda index, the area under the curve (AUC (Ins/Glu)), and an oral disposition index (ISSI-2) to estimate insulin resistance and beta-cell function. We identified patients with IGR and low insulin secretion (maximum insulin during  mU/l) and tested a subgroup using next generation sequencing to identify possible mutations in 103 candidate genes. RESULTS: The total group consisted of 903 children and adolescents with obesity. 4.5% showed impaired fasting glucose, 9.4% impaired glucose tolerance, and 1.2% T2D. Matsuda index and Total AUC (Ins/Glu) showed a hyperbolic relationship. Out of 39 patients with low insulin secretion, we performed genetic testing on 12 patients. We found five monogenetic defects (ABCC8 (), GCK (), and GLI2/PTF1A ()). CONCLUSION: Using surrogate parameters of beta-cell function and insulin resistance can help identify patients with insulin secretion disorder. A prevalence of 40% mutations of known diabetes genes in the subgroup with low insulin secretion suggests that at least 1.7% of patients with adolescent obesity have monogenic diabetes. A successful molecular genetic diagnosis can help to improve individual therapy.
Keywords:Blood Glucose, Glucose, Insulin, Insulin Resistance, Insulin Secretion, Molecular Biology, Pediatric Obesity, Type 2 Diabetes Mellitus
Source:Journal of Diabetes Research
ISSN:2314-6745
Publisher:Hindawi
Volume:2024
Page Range:5558634
Date:20 March 2024
Official Publication:https://doi.org/10.1155/2024/5558634
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library