Glucose variability and the risks of stroke, myocardial infarction, and all-cause mortality in individuals with diabetes: retrospective cohort study

Abstract

Background Previous research regarding long-term glucose variability over several years which is an emerging indicator of glycemic control in diabetes showed several limitations. We investigated whether variability in long-term fasting plasma glucose (FG) can predict the development of stroke, myocardial infarction (MI), and all-cause mortality in patients with diabetes. Methods This is a retrospective cohort study using the data provided by the Korean National Health Insurance Corporation. A total of 624,237 Koreans ≥ 20 years old with diabetes who had undergone health examinations at least twice from 2005 to 2008 and simultaneously more than once from 2009 to 2010 (baseline) without previous histories of stroke or MI. As a parameter of variability of FG, variability independent of mean (VIM) was calculated using FG levels measured at least three times during the 5 years until the baseline. Study endpoints were incident stroke, MI, and all-cause mortality through December 31, 2017. Results During follow-up, 25,038 cases of stroke, 15,832 cases of MI, and 44,716 deaths were identified. As the quartile of FG VIM increased, the risk of clinical outcomes serially increased after adjustment for confounding factors including duration and medications of diabetes and the mean FG. Adjusted hazard ratios (95% confidence intervals) of FG VIM quartile 4 compared with quartile 1 were 1.20 (1.16–1.24), 1.20 (1.15–1.25), and 1.32 (1.29–1.36) for stroke, MI and all-cause mortality, respectively. The impact of FG variability was higher in the elderly and those with a longer duration of diabetes and lower FG levels. Conclusions In diabetes, long-term glucose variability showed a dose–response relationship with the risk of stroke, MI, and all-cause mortality in this nationwide observational study.

Comprehensive elaboration of glycemic variability in diabetic macrovascular and microvascular complications

“…Moreover, Coronary Artery Risk Development in Young Adults (CARDIA) study suggested that higher long-term FPG variability assessed by CV during young adulthood before the onset of diabetes was associated with incident diabetes, macrovascular events and mortality [ 53 ]. Recently, Lee et al showed that long-term FPG variability calculated by VIM was correlated with the risk of stroke, myocardial infarction, and all-cause mortality in patients with diabetes [ 54 ]. More importantly, the impact of FPG variability was higher in the elderly and those with a longer duration of diabetes and lower FPG levels.…”

Ranolazine Improves Glycemic Variability and Endothelial Function in Patients with Diabetes and Chronic Coronary Syndromes: Results from an Experimental Study

“…Conversely, short-term glycemic variability (GV) includes an overall measure of intraday and between-day glucose fluctuations. Interestingly, GV demonstrated to add significant information, on top of HbA1c values, for the prediction of micro-and macrovascular complications, hypoglycemic episodes, and all-cause mortality in T2D patients [7][8][9][10]. Currently, no study has specifically investigated the effects of ranolazine on short-term GV.…”

Visit-to-visit fasting blood glucose variability and lifetime risk of cardiovascular disease: a prospective study

“…Previous studies have suggested an adverse effect of high FBG variability on CVD in high risk populations, such as patients with diabetes or acute coronary syndrome [ 8 – 10 ]. However, whether high FBG variability can increase the risk of CVD in the general population remains uncertain.…”

“…As an integral component of glucose homoeostasis, measuring FBG variability may be an essential addition to the use of FBG in clinical practice, and may contribute to identifying those at high risk of CVD [ 7 ]. A growing body of studies suggest that visit-to-visit FBG variability is an independent predictor of CVD events in patients with diabetes or with acute coronary syndrome [ 8 – 11 ], while evidence on the association between visit-to-visit FBG variability and CVD in the general population is limited [ 12 – 14 ]. Moreover, previous studies primarily estimated the short-term relative risk of CVD, which may not provide a comprehensive assessment for the overall burden of FBG variability on CVD [ 15 ].…”