Abstract

BackgroundPrevious 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.MethodsThis 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.ResultsDuring 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.ConclusionsIn 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.

Highlights

  • Previous research regarding long-term glucose variability over several years which is an emerging indicator of glycemic control in diabetes showed several limitations

  • As incident cardiovascular disease (CVD) and deaths associated with diabetes cannot be fully explained by increased HbA1c itself [2,3,4], more attention has been focused on non-traditional risk factors such as glucose variability (GV)

  • fasting plasma glucose (FG) variability independent of mean (VIM) quartile 4 had more males and current smokers and showed higher FG and triglyceride levels compared with quartile 1 (Table 1)

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Summary

Introduction

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. As incident cardiovascular disease (CVD) and deaths associated with diabetes cannot be fully explained by increased HbA1c itself [2,3,4], more attention has been focused on non-traditional risk factors such as glucose variability (GV). Long-term GV represents the visit-to-visit variability in fasting glucose (FG) estimated over months to years; compliance with medication; and deterioration of insulin secretion and resistance, which can be important issues [6]. Because GV could modify the correlation between time in range and estimated HbA1c, GV consideration was recommended when setting individualized goals for glycemic control [10]

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