دورية أكاديمية
Metabolic and Genetic Determinants of Glucose Shape After Oral Challenge in Obese Youths : A Longitudinal Study
| العنوان: | Metabolic and Genetic Determinants of Glucose Shape After Oral Challenge in Obese Youths : A Longitudinal Study |
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| المؤلفون: | Galderisi, Alfonso, Tricò, Domenico, Dalla Man, Chiara, Santoro, Nicola, Pierpont, Bridget, Groop, Leif, Cobelli, Claudio, Caprio, Sonia |
| المصدر: | The Journal of clinical endocrinology and metabolism; 105(2), no dgz207 (2020) ; ISSN: 1945-7197 |
| بيانات النشر: | Oxford University Press |
| سنة النشر: | 2020 |
| المجموعة: | Lund University Publications (LUP) |
| مصطلحات موضوعية: | Endocrinology and Diabetes, Pediatrics, pediatric obesity, prediabetes, TCF7L2, time to glucose peak |
| الوصف: | CONTEXT: The time-to-glucose-peak following the oral glucose tolerance test (OGTT) is a highly reproducible marker for diabetes risk. In obese youths, we lack evidence for the mechanisms underlying the effects of the TCF7L2 rs7903146 variant on glucose peak. METHODS: We analyzed the metabolic phenotype and the genotype for the TCF7L2 rs7903146 in 630 obese youths with normal (NGT) and impaired (IGT) glucose tolerance. Participants underwent a 3-hour, 9-point OGTT to estimate, using the oral minimal model, the disposition index (DI), the static (φstatic) and dynamic (φdynamic) components β-cell responsiveness and insulin sensitivity (SI). In a subgroup (n = 241) longitudinally followed for 2 years, we estimated the effect of time-to-glucose-peak on glucose tolerance change. RESULTS: Participants were grouped into early (<30 minutes) and late (≥30 minutes) glucose peakers. A delayed glucose peak was featured by a decline in φstatic (P < .001) in the absence of a difference in φdynamic. The prevalence of T-risk allele for TCF7L2 rs7903146 variant significantly increased in the late peak group. A lower DI was correlated with higher glucose concentration at 1 and 2 hours, whereas SI was inversely associated with 1-hour glucose. Glucose peak <30 minutes was protective toward worsening of glucose tolerance overtime (odds ratio 0.35 [0.15-0.82]; P = .015), with no subjects progressing to NGT or persisting IGT, in contrast to the 40% of progressor in those with late glucose peak. CONCLUSION: The prevalence of T-risk allele for the TCF7L2 rs7903146 prevailed in the late time-to-glucose peak group, which in turn is associated with impaired β-cell responsiveness to glucose (φ), thereby predisposing to prediabetes and diabetes in obese youths. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://lup.lub.lu.se/record/b555247f-ddf2-4a39-a5af-20e8e75c383cTest; http://dx.doi.org/10.1210/clinem/dgz207Test; scopus:85078266343; pmid:31972003 |
| DOI: | 10.1210/clinem/dgz207 |
| الإتاحة: | https://doi.org/10.1210/clinem/dgz207Test https://lup.lub.lu.se/record/b555247f-ddf2-4a39-a5af-20e8e75c383cTest |
| رقم الانضمام: | edsbas.4CB7CF1F |
| قاعدة البيانات: | BASE |
| DOI: | 10.1210/clinem/dgz207 |
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