Effects of long-term glycemic variability on incident cardiovascular disease and mortality in subjects without diabetes: A nationwide population-based study

Increased glycemic variability (GV) is an independent risk factor for cardiovascular complications in patients with diabetes. We evaluated the risk of future development of cardiovascular disease (CVD) and death according to GV in a general population without diabetes. We used the National Health Insurance Service, providing a population-based, nationwide database of Koreans. We included individuals without diabetes who underwent glucose measurement at least 3 times during 2002 to 2006. GV was calculated as standard deviation (SD) of fasting plasma glucose (FPG) levels. We observed development of CVD or all-cause death from 2007 to 2015, and also evaluated the mortality within 1 year after CVD. Among 3,211,319 people, we found 23,374 incident cases of myocardial infarction (MI), 27,705 cases of stroke, and 63,275 deaths during 8.3 years of follow-up. After multivariate adjustment, GV was found to be a significant predictor of MI, stroke and all-cause death for their highest quartile, with corresponding hazard ratios (HR) of 1.08 (95% confidence interval, CI 1.04–1.11), 1.09 (95% CI 1.06–1.13), and 1.12 (95% CI 1.10–1.15), respectively. The risk of death increased more in those who had both impaired fasting glucose and the highest quartile of GV (HR 1.24 [95% CI 1.21–1.28]). Moreover, early death rate after 1 year of CVD was higher in the highest quartile of GV compared to the lowest quartile (HR 1.21 [95% CI 1.03–1.41]). Long-term FPG variation was independently associated with CVD and mortality in a general population without diabetes.