Associations of Common Genetic Variants With Age-Related Changes in Fasting and Postload Glucose Evidence From 18 Years of Follow-Up of the Whitehall II Cohort

摘要

Objective-in the general, nondiabetic population, fasting glucose increases only slightly over time, whereas 2-h postload glucose shows a much steeper age-related rise. The reasons underlying these different age trajectories are unknown. We investigated whether common genetic variants associated with fasting and 2-h glucose contribute to age-related changes of these traits. Research design and methods-we studied 5,196 nondiabetic participants of the whitehall ii cohort (aged 40-78 years) attending up to four 5-yearly oral glucose tolerance tests. A genetic score was calculated separately for fasting and 2-h glucose, including 16 and 5 single nucleotide polymorphisms, respectively. Longitudinal modeling with age centered at 55 years was used to study the effects of each genotype and genetic score on fasting and 2-h glucose and their interactions with age, adjusting for sex and time-varying bmi. Results-the fasting glucose genetic score was significantly associated with fasting glucose with a 0.029 mmol/l (95% ci 0.023-0.034) difference (p = 2.76 × 10~(-21)) per genetic score point, an association that remained constant over time (age interaction p = 0.17). Two-hour glucose levels differed by 0.076 mmol/l (0.047-0.105) per genetic score point (p = 3.1 × 10~(-7)); notably, this effect became stronger with increasing age by 0.006 mmol/l (0.003-0.009) per genetic score point per year (age interaction p = 3.0 x 10~(-5)), resulting in diverging age trajectories by genetic score. Conclusions-common genetic variants contribute to the age-related rise of 2-h glucose levels, whereas associations of variants for fasting glucose are constant over time, in line with stable age trajectories of fasting glucose. Diabetes 60:1617-1623, 2011