التفاصيل البيبلوغرافية
| العنوان: |
The rs7903146 Variant in the Gene Increases the Risk of Prediabetes/Type 2 Diabetes in Obese Adolescents by Impairing β-Cell Function and Hepatic Insulin Sensitivity. |
| المؤلفون: |
Cropano, Catrina, Santoro, Nicola, Groop, Leif, Man, Chiara Dalla, Cobelli, Claudio, Galderisi, Alfonso, Kursawe, Romy, Pierpont, Bridget, Goffredo, Martina, Caprio, Sonia, Dalla Man, Chiara |
| المصدر: |
Diabetes Care; Aug2017, Vol. 40 Issue 8, p1082-1089, 8p |
| مصطلحات موضوعية: |
PREDIABETIC state, TYPE 2 diabetes, ADOLESCENT obesity, GENETIC disorders, BCL-2 proteins, ALLELES, DISEASE susceptibility, GLUCOSE tolerance tests, INSULIN, INSULIN resistance, ISLANDS of Langerhans, LIVER, LONGITUDINAL method, CHILDHOOD obesity, POPULATION, PROTEINS, RESEARCH funding, BODY mass index, GLUCOSE intolerance |
| مستخلص: |
Objective: In this study, we aimed to explore the mechanism by which TCF7L2 rs7903146 risk allele confers susceptibility to impaired glucose tolerance (IGT) or type 2 diabetes (T2D) in obese adolescents.Research Design and Methods: The rs7903146 variant in the TCF7L2 gene was genotyped in a multiethnic cohort of 955 youths. All subjects underwent an oral glucose tolerance test with the use of the Oral Minimal Model to assess insulin secretion, and 33 subjects underwent a hyperinsulinemic-euglycemic clamp. In 307 subjects, a follow-up oral glucose tolerance test was repeated after 3.11 ± 2.36 years.Results: The TCF7L2 rs7903146 risk allele was associated with higher 2-h glucose levels in Caucasians (P = 0.006) and African Americans (P = 0.009), and a trend was seen also in Hispanics (P = 0.072). Also, the T allele was associated with decreased β-cell responsivity and IGT (P < 0.05). Suppression of endogenous hepatic glucose production was lower in subjects with the risk variant (P = 0.006). Finally, the odds of showing IGT/T2D at follow-up were higher in subjects carrying the minor allele (odds ratio 2.224; 95% CI 1.370-3.612; P = 0.0012).Conclusions: The rs7903146 variant in the TCF7L2 gene increases the risk of IGT/T2D in obese adolescents by impairing β-cell function, and hepatic insulin sensitivity predicts the development of IGT/T2D over time. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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