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Cumulative glycaemic exposure and cardiovascular risk

Greater HbA1c exposure, which reflects long-term glycaemic control, significantly increases the risk of CVD and mortality in type 2 diabetes.

This post hoc analysis of ACCORD (Action to Control Cardiovascular Risk in Diabetes) study data investigated the relationship between cumulative HbA1c exposure (defined as the area under the HbA1c–time curve) and cardiovascular outcomes in people with type 2 diabetes. Data from 9307 ACCORD participants were analysed.

After adjustment for covariables including demographics and other risk factors for cardiovascular disease (CVD), HbA1c exposure during the first year of the study was significantly associated with the primary composite outcome of cardiovascular mortality, non-fatal myocardial infarction or non-fatal stroke (hazard ratio [HR] 1.32). It was also associated with all-cause mortality (HR 1.33) and cardiovascular mortality (HR 1.45). Similar findings were observed when the exposure time was extended to 2 years.

Baseline HbA1c was also associated with the risk of the primary outcome (HR 1.19); however, HbA1c exposure remained significantly associated with all-cause and cardiovascular mortality even after adjusting for HbA1c at baseline or at month 4.

The ACCORD study was halted early due to increased risk of mortality in the intensive intervention group. In this analysis, cumulative HbA1c had a significantly stronger association with mortality in the intervention group than in the control group (P<0.05 for interaction). When grouping participants according to tertiles of baseline HbA1c and HbA1c exposure, those in the highest tertiles for both parameters had the greatest risk of the primary outcome compared to the lowest tertiles, with participants in the intensive treatment arm having significantly higher risk than controls (HR 2.19 vs 1.44).

The authors conclude that, notwithstanding the limitations of the post hoc design and the multiple statistical comparisons made, greater HbA1c exposure, which reflects long-term glycaemic control, significantly increases the risk of CVD and mortality in people with type 2 diabetes.

Click here to read the study in full.

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