Background and aims

We investigated the interrelationship of rs7903146-T in TCF7L2 with measures of glucose metabolism and measures of adiposity.

Methods and results

This cross-sectional analysis was conducted in 5744 middle-aged participants (mean (standard deviation [SD]) age is 55.9 (6.0) years) from the Netherlands Epidemiology of Obesity (NEO) Study. Associations between rs7903146-T and Type 2 diabetes mellitus (T2D) were assessed with logistic regression. Additive (per-allele) associations with measures of glucose metabolism (e.g., fasting insulin) and adiposity (e.g., body mass index [BMI]) were examined with multivariable linear regression. In the total study population, rs7903146-T was associated with a higher risk of T2D (additive odds ratio: 1.42; 95% confidence interval: 1.17; 1.72), and specifically with T2D treated with insulin analogs (2.31 [1.19; 4.46]). After exclusion of participants treated with glucose-lowering medication, rs7903146-T was associated with lower mean insulin concentration (additive mean difference: -0.07 SD [-0.14; 0.00]), but not with higher mean glucose concentration (0.03 SD [-0.01; 0.07]). Furthermore, rs7903146-T was associated with, among other measures of adiposity, a lower mean BMI (-0.04 SD [-0.09; -0.00]), and a lower mean total body fat (-0.04 SD [-0.08; -0.00]). The association between rs7903146-T and T2D increased after adjustment for BMI (odds ratio: 1.51 [1.24; 1.86]); the association between rs7903146-T and fasting insulin diminished after adjustment (-0.05 SD [-0.11; 0.02]).

Conclusion

rs7903146-T is associated with a decreased insulin concentration and increased risk of T2D with opposing effects of adjustment for adiposity.

Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.