Rapid deterioration of insulin secretion in obese adolescents preceding the onset of type 2 diabetes
| Autor: | Ron L. Prigeon, Patricia M. Herbers, Deborah A. Elder, Jessica G. Woo, David A. D'Alessio, Lindsey Hornung |
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| Rok vydání: | 2014 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Pediatric Obesity Time Factors Adolescent medicine.medical_treatment Type 2 diabetes Article Insulin resistance Internal medicine Diabetes mellitus Insulin-Secreting Cells Glucose Intolerance Insulin Secretion medicine Humans Insulin Child Chromatography High Pressure Liquid Proinsulin Glycated Hemoglobin business.industry medicine.disease Endocrinology Diabetes Mellitus Type 2 Pediatrics Perinatology and Child Health Cohort Homeostatic model assessment Female Insulin Resistance business Body mass index Follow-Up Studies |
| Zdroj: | The Journal of pediatrics. 166(3) |
| ISSN: | 1097-6833 |
| Popis: | Objective To identify pathophysiologic changes that lead to the onset of type 2 diabetes (T2DM) in adolescents. Study design Obese adolescents with normal glucose tolerance (n = 41) were studied longitudinally over the course of 4 years with serial measure of the acute insulin response to glucose (AIR g ) as well as proinsulin (PI) concentrations. Insulin resistance was estimated with the homeostatic model assessment of insulin resistance (HOMA-IR), the disposition index (DI) computed as AIR g × 1/HOMA-IR, and intravenous glucose tolerance estimated as the glucose disappearance constant. Results Four adolescents developed diabetes mellitus (DM) during the study, and the rest of the cohort remained nondiabetic. Baseline PI exceeded the IQR of the nondiabetic group in 3 of 4 subjects with DM, and all had >85% reduction from baseline AIR g , and DI, within 6 months of diagnosis. All the subjects with DM gained weight over the course of the study, but these changes paralleled those for the nondiabetic group. HOMA-IR increased substantially in 1 of the subjects with DM at the time of diagnosis but was comparable with baseline in the other 3. The DI and glucose disappearance constant of the subjects with DM was less than the 10th percentile of the nondiabetic group before and after diagnosis. Conclusion Conversion from normal glucose tolerance to T2DM in adolescents can occur rapidly, and the onset of T2DM is heralded by a substantial decrease in AIR g and DI, as well as increased release of PI. These results support loss of β-cell function as the proximate step in the development of T2DM in this age group. |
| Databáze: | OpenAIRE |
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