Longitudinal glycemic variation linked to increased mortality risk
medwireNews: Long-term variation in fasting blood glucose (FBG) may be associated with an increased risk for all-cause mortality, but not cardiovascular disease (CVD) events, in people with no history of diabetes, US researchers report.
They say: “Our data highlight the importance of achieving normal and consistent glycemic levels for improving clinical outcomes.”
The analysis, which appears in Diabetes Care, included 4982 individuals with and without diabetes who were participating in the ALLHAT study and had FBG measurements at baseline, and at 24 and 48 months.
In the following 5 years there were 305 CVD events, including 189 cases of coronary heart disease, 45 strokes, and 81 cases of heart failure, as well as 154 deaths. The main causes of death were cancer (n=36), other non-CVD causes (n=36), and coronary heart disease (n=35).
Justin Echouffo-Tcheugui (Johns Hopkins School of Medicine, Baltimore, Maryland, USA) and colleagues found that people with the highest levels of visit-to-visit variability in FBG had a significantly higher risk for all-cause mortality than those with the lowest variability.
Specifically, individuals in the highest quartile of standard deviation (SD) of FBG (≥26.4 mg/dL) had a significant 2.2-fold higher risk for death than those in the lowest quartile of SD (<5.5 mg/dL), after adjustment for multiple potential confounders including mean glucose levels.
Similar results were observed for other measures of visit-to-visit variability including variability independent of the mean (VIM; hazard ratio [HR]=1.9) and coefficient of variation (HR=2.0), but there was no significant association between variation in FBG and risk for CVD events.
When the researchers separated the cohort into those with (n=3224) and without (n=1758) diabetes, they found no significant associations between the measures of FBG variability and either CVD events or all-cause mortality among patients with diabetes.
They suggest this may be because of “the use of diabetes medications in this subgroup that may have blunted glycemic variability, as well as the possible underestimation of the number of diabetes cases.”
They add: “It is also possible that long-term glycemic variability matters more among those without diabetes, and among those with diabetes short-term variability is a predictor of outcomes.”
Indeed, in the group without diabetes, being in the highest quartile of SD, VIM, and coefficient of variation was associated with a significantly higher risk for death than being in the lowest quartile, at HRs of 2.7, 2.5, and 3.1, respectively.
Echouffo-Tcheugui and co-authors caution that the observational nature of the study prevents them from establishing causality, while the limited age range of the participants (≥55 years) “restricts the generalizability” of their findings.
They add that “[f]uture studies are needed to further elucidate the mechanisms underlying high level of glycemic variability (which could ultimately inform a more efficacious approach to treating hyperglycemia) and to determine whether decreasing long-term glycemic variability would be associated with reduced risk of mortality.”
By Laura Cowen
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