We examined whether long-term gamma-glutamyl transferase (GGT) variability can predict cardiovascular disease (CVD) and mortality in individuals with diabetes. We included 698,937 Koreans diabetes patients older than 40 years without histories of CVD, chronic liver disease, or heavy alcoholics who received health exams supported by the Korean government more than once in 2009–2012 (baseline). We used Cox proportional analyses to estimate the risk of stroke, myocardial infarction (MI), and all-cause mortality until December 31, 2016, according to the quartiles of the average successive variability (ASV) of GGT measured during the five years before the baseline. A total 26,119, 15,103, and 39,982 cases of stroke, MI, and death, respectively, were found. GGT ASV quartile 4 had a significantly higher risk of stroke and all-cause mortality than quartile 1, with adjustment for risk factors, such as baseline glucose and GGT level, and comorbidities. Hazard ratios (95% confidence intervals) for GGT ASV quartile 4 were 1.06 (1.03–1.10) and 1.23 (1.20–1.27) for stroke and mortality, respectively. This significant association was shown consistently across the baseline GGT quartiles. GGT variability was related to the risk of stroke and all-cause mortality. The effect was most pronounced in all-cause mortality, irrespective of baseline GGT level.
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