TY - JOUR
T1 - Insulin Secretion Defect in Children and Adolescents with Obesity
T2 - Clinical and Molecular Genetic Characterization
AU - Enders-Seidlitz, Helena
AU - Raile, Klemens
AU - Gong, Maolian
AU - Galler, Angela
AU - Kuehnen, Peter
AU - Wiegand, Susanna
N1 - Publisher Copyright:
© 2024 Helena Enders-Seidlitz et al.
PY - 2024
Y1 - 2024
N2 - 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, glucose+insulin) 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 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 on 12 patients. We found five monogenetic defects (ABCC8 (n=3), GCK (n=1), and GLI2/PTF1A (n=1)). 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.
AB - 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, glucose+insulin) 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 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 on 12 patients. We found five monogenetic defects (ABCC8 (n=3), GCK (n=1), and GLI2/PTF1A (n=1)). 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.
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U2 - 10.1155/2024/5558634
DO - 10.1155/2024/5558634
M3 - Article
C2 - 38550917
AN - SCOPUS:85189270443
SN - 2314-6745
VL - 2024
JO - Journal of Diabetes Research
JF - Journal of Diabetes Research
M1 - 5558634
ER -