TCF7L2 Genetic Variants Do Not Influence Insulin Sensitivity or Secretion Indices in Autoantibody-Positive Individuals at Risk for Type 1 Diabetes.

Autor: Redondo MJ; Texas Children's Hospital, Baylor College of Medicine, Houston, TX redondo@bcm.edu., Warnock MV; University of South Florida, Tampa, FL., Libman IM; University of Pittsburgh, Pittsburgh, PA., Bocchino LE; University of South Florida, Tampa, FL.; Jaeb Center for Health Research, Tampa, FL., Cuthbertson D; University of South Florida, Tampa, FL., Geyer S; University of South Florida, Tampa, FL.; Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN., Pugliese A; University of Miami, Miami, FL., Steck AK; Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO., Evans-Molina C; Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine, Indianapolis, IN., Becker D; University of Pittsburgh, Pittsburgh, PA., Sosenko JM; Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL., Bacha F; Texas Children's Hospital, Baylor College of Medicine, Houston, TX.; Children's Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, Houston, TX.
Jazyk: angličtina
Zdroj: Diabetes care [Diabetes Care] 2021 Sep; Vol. 44 (9), pp. 2039-2044. Date of Electronic Publication: 2021 Jul 29.
DOI: 10.2337/dc21-0531
Abstrakt: Objective: We aimed to test whether type 2 diabetes (T2D)-associated TCF7L2 genetic variants affect insulin sensitivity or secretion in autoantibody-positive relatives at risk for type 1 diabetes (T1D).
Research Design and Methods: We studied autoantibody-positive TrialNet Pathway to Prevention study participants ( N = 1,061) (mean age 16.3 years) with TCF7L2 single nucleotide polymorphism (SNP) information and baseline oral glucose tolerance test (OGTT) to calculate indices of insulin sensitivity and secretion. With Bonferroni correction for multiple comparisons, P values < 0.0086 were considered statistically significant.
Results: None, one, and two T2D-linked TCF7L2 alleles were present in 48.1%, 43.9%, and 8.0% of the participants, respectively. Insulin sensitivity (as reflected by 1/fasting insulin [1/I F ]) decreased with increasing BMI z score and was lower in Hispanics. Insulin secretion (as measured by 30-min C-peptide index) positively correlated with age and BMI z score. Oral disposition index was negatively correlated with age, BMI z score, and Hispanic ethnicity. None of the indices were associated with TCF7L2 SNPs. In multivariable analysis models with age, BMI z score, ethnicity, sex, and TCF7L2 alleles as independent variables, C-peptide index increased with age, while BMI z score was associated with higher insulin secretion (C-peptide index), lower insulin sensitivity (1/I F ), and lower disposition index; there was no significant effect of TCF7L2 SNPs on any of these indices. When restricting the analyses to participants with a normal OGTT ( n = 743; 70%), the results were similar.
Conclusions: In nondiabetic autoantibody-positive individuals, TCF7L2 SNPs were not related to insulin sensitivity or secretion indices after accounting for BMI z score, age, sex, and ethnicity.
(© 2021 by the American Diabetes Association.)
Databáze: MEDLINE
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