Impact of <i>TCF7L2</i> rs7903146 on clinical presentation and risk of complications in patients with type 2 diabetes
Aleksander L. Hansen, Mette K. Andersen, Leonie Mieke Engelhard, Charlotte Brøns, Torben Hansen, Jens Steen Nielsen, Peter Vestergaard, Kurt Højlund, Niels Jessen, Michael Hecht Olsen, Reimar W. Thomsen, Allan Vaag
Abstract
AIMS: TCF7L2 rs7903146 is the most impactful single genetic risk variant for type 2 diabetes. However, its role on disease progression, complications and mortality among people with type 2 diabetes at diagnosis remains unclear. MATERIALS AND METHODS: We assessed the per allele impact of the rs7903146 T-allele on clinical characteristics and complication risk in 9231 individuals with type 2 diabetes at diagnosis and over a 10-year follow-up period. Log-binomial and robust Poisson regression analyses were used to estimate prevalence ratios for clinical characteristics and macro- and microvascular complications at diabetes onset, while Cox regression was applied to estimate the risk of complications post-diagnosis. Analyses were adjusted for sex, calendar year at birth, age at enrollment and diabetes duration. RESULTS: (95% CI: 0.4, 0.8) lower BMI, 1.4 cm (95% CI: 1.0, 1.8) smaller waist circumference, 5.6% (95% CI: 4.2, 7.0) lower insulin secretion and 5.0% (95% CI: 3.3, 6.7) higher insulin sensitivity. Over 10 years, the per T-allele impact was associated with lower risks for major adverse cardiovascular events (0.87 [95% CI 0.79, 0.95]), myocardial infarction (0.82 [95% CI: 0.72, 0.93]) and heart failure (0.85 [95% CI 0.73, 1.00]), with no significant impact on microvascular complications. CONCLUSIONS: The TCF7L2 variant is associated with less obesity, lower insulin secretion and higher insulin action at diabetes onset, and decreased risk of cardiovascular events following type 2 diabetes onset.