Higher gamma-glutamyltransferase (GGT) variability was found to be significantly associated with increased risk for dementia among patients with diabetes, according to study results published in The Journal of Clinical Endocrinology & Metabolism.
Serum GGT is a commonly used biomarker for hepatic or biliary disease that has also been associated with oxidative stress and atherosclerosis. Previous studies have reported increased GGT activity in patients with diabetes, and high levels of GGT were found to be associated with increased cardiovascular risk in this population.
The goal of the current study was to explore the use of GGT, and its variability, as a biomarker for dementia risk among patients with diabetes.
The researchers used data from the large-scale Korean National Health Insurance Service database from 2004 to 2016. They focused on patients 40 years of age and older with a known diagnosis of diabetes and classified them according to quartile of GGT variability. The prevalence of hypertension, dyslipidemia, myocardial infarction, stroke, and depression increased with increasing GGT variability.
Of 670,822 individuals with diabetes, 37,983 developed dementia during approximately 6 years of follow-up. Increasing quartiles of baseline GGT level were associated with increasing incidence of all-cause dementia (lowest quartile vs highest quartile: hazard ratio [HR], 1.10; 95% CI, 1.07-1.14), Alzheimer disease (HR, 1.07; 95% CI, 1.04-1.11), and vascular dementia (HR, 1.14; 95% CI, 1.05-1.24).
In a similar fashion, cumulative incidence of all-cause dementia, Alzheimer disease, and vascular dementia increased progressively with increasing quartiles of GGT variability. In the fully adjusted model, the highest vs lowest quartile of GGT variability was associated with a 23% increased risk for dementia (HR, 1.23; 95% CI, 1.19-1.26) with a relatively small effect size (Cohen’s d, 0.14). A single standard deviation increment of GGT variability was associated with a significant increase in the risk for all-cause dementia (HR, 1.03; 95% CI, 1.02-1.04), Alzheimer disease (HR, 1.03; 95% CI, 1.02-1.04), and vascular dementia (HR, 1.03; 95% CI, 1.02-1.05).
With a combination of baseline GGT level and quartile of GGT variability, the risk for all-cause dementia (HR, 1.27; 95% CI, 1.25-1.30) or Alzheimer disease (HR, 1.25; 95% CI, 1.23-1.28) was highest for individuals with a high baseline GGT concentration and GGT variability in the highest quartile. However, risk for vascular dementia was highest in patients with a low baseline GGT level and GGT variability in the highest quartile (HR, 1.28; 95% CI, 1.15-1.42).
For Alzheimer disease, these associations were more prominent in men and patients <60 years of age. For vascular dementia, they were more significant in men and patients with depression or longer duration of diabetes.
The study had several limitations, including possibly inaccurate diagnoses of diabetes and dementia, lack of data on severity of diabetes and dementia, and no consideration of the effect of the apolipoprotein E (ApoE) genotype.
“[T]his study demonstrated that higher GGT variability and basal GGT levels significantly increased the risk of developing dementia,” concluded the researchers.
Hong SH, Han K, Park S, et al. Gamma-glutamyl transferase variability and risk of dementia in diabetes mellitus: a nationwide population-based study [published online January 19, 2020]. J Clin Endocrinol Metab. doi:10.1210/clinem/dgaa019