medwireNews: People with glycated hemoglobin (HbA1c) levels just below the diabetes diagnosis threshold have the greatest risk for major adverse cardiovascular events (MACE) and death, suggests a study of individuals in the upper normal glycemic range.
These findings “raise the question of whether medical treatment should be more aggressive and whether we should start treating cardiovascular risk factors even before the patients cross the diabetes threshold,” write Sam Kafai Yahyavi (Rigshospitalet, Copenhagen, Denmark) and co-authors in Diabetes Care.
Their registry-based study included 84,678 Danish people with no history of cardiovascular disease or diabetes who had a first measured HbA1c of 5.8% to 6.8% (40–51 mmol/mol) between 2011 and 2017.
The researchers report that, during 1 year of follow-up, the overall incidence of MACE, defined as nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes, was 0.94%.
However, the risk increased with increasing HbA1c levels, peaking at an HbA1c of 6.5% (48 mmol/mol).
Specifically, individuals with a first measured HbA1c of 6.2% to 6.3% (44–45 mmol/mol; n=8694) had a significant 1.35-fold higher risk for MACE than those with an HbA1c of 5.8% to 5.9% (40–41 mmol/mol; n=48,157), after adjustment for potential confounders.
This increased to a significant 1.91-fold higher risk among individuals with a baseline HbA1c of 6.4% to 6.5% (46–47 mmol/mol; n=3374). The standardized absolute risk for MACE in this group was 1.73% compared with 0.95% in the group with the lowest HbA1c levels.
The adjusted hazard ratios for MACE among individuals in the HbA1c 6.5% to 6.6% (48–49 mmol/mol; n=2047) and 6.7% to 6.8% (50–51 mmol/mol; n=1173) groups were a nonsignificant 1.14, and 1.63, respectively, when compared with the lowest HbA1c group.
A similar pattern was observed for all-cause mortality, with individuals in the HbA1c 6.4% to 6.5% group having the highest risk relative to those in the 5.8% to 5.9% group.
The investigators also looked at prescribed medications during the follow-up period and found that the proportions of participants who initiated glucose-lowering medications, statins, renin-angiotensin system inhibitors, and acetylsalicylic acid increased with increasing HbA1c.
The trend was particularly strong for glucose-lowering medications, rising from 2.75% of people in the HbA1c 6.2% to 6.3% group starting these drugs to 43.82% of those in the 6.7–6.8% group.
For statins, the corresponding proportions were 9.20% to 27.02%.
Yahyavi et al suggest that the lower risk for MACE among individuals with HbA1c levels of 6.5% and higher compared with those in the prediabetes group “is connected to the more aggressive treatment of cardiovascular risk factors initiated among patients with diagnosed diabetes as recommended in national guidelines compared with treatment of patients with prediabetes.”
“It is also possible that patients with diabetes are much more likely to receive self-management education and change lifestyle accordingly compared with subjects with prediabetes,” they add.
The researchers conclude that their data “support the hypothesis that treatment for cardiovascular risk factors should start before type 2 diabetes develops and suggest that more attention and potentially evidence-based guidelines are needed in the management of prediabetes with better monitoring of this patient group.”
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