Glycemic variability within normal glucose range tied to poor outcomes
medwireNews: Among individuals without diabetes, high variability in glycated hemoglobin (HbA1c) levels is associated with an elevated risk for major adverse cardiovascular events (MACE) and mortality, researchers report.
The study included 6756 Danish primary care patients aged a median of approximately 65 years with no history of diabetes or cardiovascular disease who had three consecutive annual HbA1c measurements below 6.5% (48 mmol/mol).
Over a median follow-up of 6.3 years, 996 patients experienced the composite outcome of MACE (myocardial infarction, unstable angina pectoris, ischemic stroke, peripheral vascular disease, or cardiovascular death), while 856 patients died, and 1267 developed type 2 diabetes.
Jonas Nielsen (University Hospital of Copenhagen, Denmark) and colleagues demonstrated that patients with a greater degree of HbA1c variability – measured as the standard deviation (SD) of the residuals from a linear regression analysis of the three HbA1c measurements – were at higher risk for MACE than those with less HbA1c variability, with each SD increase conferring a significant 9% increased risk after adjustment for traditional cardiovascular risk factors including age, sex, and hypertension.
Similarly, each SD increase in HbA1c variability was associated with a significant 13% increase in the risk for all-cause mortality, but the researchers note that “the effect of trend [in HbA1c levels] on the hazard of all-cause mortality also depended on index HbA1c.”
For example, decreasing HbA1c levels over time were associated with a significant 92% increased risk for mortality compared with stable HbA1c levels among patients with low index HbA1c (<5.3% [34 mmol/mol]). This compared with a significant 54% increased risk for decreasing levels among those with moderate index HbA1c (5.3–5.7% [34–39 mmol/mol]), and a nonsignificant 3% increased risk among individuals with a high index HbA1c (>5.7% [39 mmol/mol]). Patients with increasing HbA1c levels over time did not have a significantly elevated mortality risk relative to those with stable levels regardless of index HbA1c category.
Nielsen and team note that there was no significant association between total HbA1c variability and incident type 2 diabetes risk over the follow-up period, but increasing versus stable HbA1c was associated with a significantly elevated risk, and decreasing versus stable HbA1c was associated with a significantly lower risk.
Taken together, these findings indicate that “glycemic variability may contain valuable prognostic information for the outcomes of MACE and mortality, even in individuals with HbA1c levels within normal range,” write the researchers in Diabetes Care.
They add that “future long-term studies are needed to examine whether strategies to reduce variability in HbA1c can effectively reduce risk of cardiovascular disease in subjects with HbA1c within the normal range.”
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