Endocrine Abstracts

Background: 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 background in 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 analysed possible candidate genes of diabetes in a subcohort.

Methods: We included children and adolescents with obesity who completed an oral glucose tolerance test (OGTT, glucose + insulin) in 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 beta cell function (maximum insulin during OGTT <200 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 in 12 patients. We found 5 monogenetic defects (ABCC8 (n=3), GCK (n=1), GLI2/PTF1A (n=1)).

Conclusion: Using surrogate parameters of beta-cell function and insulin resistance can help to identify patients with insulin secretion disorder. The prevalence of 40% mutations of known diabetes genes in the subgroup with low beta-cell function suggests a minimum of about 1.7% monogenic T2D in a cohort of adolescents with obesity. A successful molecular genetic diagnosis can help to improve the individual therapy.