Insulin Secretion Defect in Children and Adolescents with Obesity: Clinical and Molecular Genetic Characterization
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 ob...
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| Format: | Article |
| Language: | English |
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Wiley
2024-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2024/5558634 |
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| author | Helena Enders-Seidlitz Klemens Raile Maolian Gong Angela Galler Peter Kuehnen Susanna Wiegand |
| author_facet | Helena Enders-Seidlitz Klemens Raile Maolian Gong Angela Galler Peter Kuehnen Susanna Wiegand |
| author_sort | Helena Enders-Seidlitz |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5d16c910a5a143a8a90461df4388028e |
| institution | OA Journals |
| issn | 2314-6753 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-5d16c910a5a143a8a90461df4388028e2025-08-20T02:05:02ZengWileyJournal of Diabetes Research2314-67532024-01-01202410.1155/2024/5558634Insulin Secretion Defect in Children and Adolescents with Obesity: Clinical and Molecular Genetic CharacterizationHelena Enders-Seidlitz0Klemens Raile1Maolian Gong2Angela Galler3Peter Kuehnen4Susanna Wiegand5Charité Universitätsmedizin BerlinVivantes KlinikumMax Delbrück Center for Molecular MedicineCharité Universitätsmedizin BerlinCharité Universitätsmedizin BerlinCharité Universitätsmedizin BerlinIntroduction. 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.http://dx.doi.org/10.1155/2024/5558634 |
| spellingShingle | Helena Enders-Seidlitz Klemens Raile Maolian Gong Angela Galler Peter Kuehnen Susanna Wiegand Insulin Secretion Defect in Children and Adolescents with Obesity: Clinical and Molecular Genetic Characterization Journal of Diabetes Research |
| title | Insulin Secretion Defect in Children and Adolescents with Obesity: Clinical and Molecular Genetic Characterization |
| title_full | Insulin Secretion Defect in Children and Adolescents with Obesity: Clinical and Molecular Genetic Characterization |
| title_fullStr | Insulin Secretion Defect in Children and Adolescents with Obesity: Clinical and Molecular Genetic Characterization |
| title_full_unstemmed | Insulin Secretion Defect in Children and Adolescents with Obesity: Clinical and Molecular Genetic Characterization |
| title_short | Insulin Secretion Defect in Children and Adolescents with Obesity: Clinical and Molecular Genetic Characterization |
| title_sort | insulin secretion defect in children and adolescents with obesity clinical and molecular genetic characterization |
| url | http://dx.doi.org/10.1155/2024/5558634 |
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