Gamma-Glutamyl Transferase Variability and Risk of Dementia in Diabetes Mellitus: A Nationwide Population-Based Study

Context: Gamma-glutamyl transferase (GGT) has been associated with oxidative stress and inflammatory reactions. Variability in various biomarkers has emerged as a new clinical indicator for diseases including neurodegenerative disorders. Objective: We investigated the association between GGT variability and dementia risk in patients with diabetes mellitus (DM). Design, Participants, and Methods: We used the Korean National Health Insurance Service datasets of Claims and Health Check-ups from 2004 to 2016. The risk of incident dementia (all-cause dementia, Alzheimer disease, vascular dementia) was analyzed by quartiles of GGT variability in ≥ 40-year-old DM individuals without baseline dementia. Results: During 6.12 years of follow-up, 37, 983 cases of dementia developed. In the fully adjusted model, the group with the highest quartile of GGT variability had a 19% increased risk of all-cause dementia when compared with the lowest quartile group (hazard ratio; 95% confidence interval): 1.19; 1.16-1.22, with a small effect size (Cohen d's = 0.14). Compared with the group with low baseline GGT level and the lowest quartiles of its variability, the group with high baseline GGT level and the highest quartile of its variability increased 27% of all-cause dementia. A 1 SD increment in the GGT variability was associated with a 3% increased risk of all-cause dementia. Subgroup analysis showed a more prominent association between increased GGT variability and dementia risk in men and < 60-year-old individuals (P for interaction ≤ .001). Conclusions: In subjects with DM, high variability of GGT increased the risk of dementia independently of other factors, including baseline GGT levels.