Mortality benefit of tighter glycemic control may vary by diabetes duration, study finds

Mortality risk increased with worse glycemic control among patients who had had diabetes for less than five years, while a mean HbA1c level between 6.5% to 7.9% was associated with the lowest mortality risk in those who had had the disease longer.


Strict glycemic control may be associated with higher all-cause mortality in patients who have had type 2 diabetes for five years or more but with lower all-cause mortality in those diagnosed more recently, according to a recent study.

Researchers in Denmark used data from nationwide registries to examine primary care patients at least 65 years of age with type 2 diabetes whose HbA1c levels were measured three times in succession between 2005 and 2013. The primary exposure was the mean of these measurements, and follow-up started on the day of the third measurement. Median follow-up was 7.3 years. Individual mean HbA1c levels were categorized as lower than 6.5%, 6.5% to 6.9%, 7% to 7.9%, 8% to 8.9%, or 9% or greater. The researchers looked at the effect of glycemic control on risk for all-cause mortality adjusted for age, sex, concomitant medications, and age- and disease-related comorbid conditions. Study results were published Oct. 9 by Diabetes, Obesity and Metabolism.

Overall, 9,734 patients were included in the study, 6,072 with short diabetes duration (less than five years) and 3,662 with long diabetes duration (five years or more). Median age was 73.5 years, and 50.1% were men. A total of 3,320 patients died during follow-up, 1,578 with short diabetes duration and 1,742 with long diabetes duration. The researchers found that the effect of mean HbA1c level on all-cause mortality appeared to depend on diabetes duration (P<0.001 for the interaction). Risk for death increased with worse glycemic control among patients who had had diabetes for less than five years, while among patients who had had diabetes for five years or more, the study found a J-shaped association, with the lowest mortality risk associated with a mean HbA1c level between 6.5% to 7.9%. Both the lowest and highest categories of HbA1c level (<6.5% and ≥9%) were associated with higher risk for death in patients with longer diabetes duration (hazard ratios, 1.21 [95% CI, 1.07 to 1.27; P=0.002] and 1.60 [95% CI, 1.28 to 1.99; P<0.001], respectively). Risk patterns were similar for long and short diabetes duration when five-year absolute risks for all-cause mortality were calculated.

The researchers noted that their study was observational and could not prove a causal effect. In addition, data on patients' functional limitations and indications for HbA1c testing were not available. However, they concluded that risk for death among older patients with type 2 diabetes appears to vary according to HbA1c level and disease duration. “[O]ur results suggest that aiming for normoglycemic levels in those with short duration of diabetes may be beneficial, whereas for individuals with long diabetes duration, setting universal goals may be less straight-forward,” the authors wrote. “In these patients, additional important factors, such as frailty, life expectancy and patient preferences should be considered, to better provide patient-centered care that balances the pros and cons of tight glycemic control.”