Glycemic Control and Risk of Cardiovascular Disease Hospitalization and All-Cause Mortality

Objectives This study sought to evaluate the relationship between glycemic control and cardiovascular disease (CVD) hospitalizations and all-cause mortality among patients with type 2 diabetes in a real-world setting. Background Clinical trials have not established that tight glycemic control reduces CVD events and may be associated with increased mortality. Observational studies of specific cohorts have reported increased risk of those outcomes at both high and low glycosylated hemoglobin (HbA1c) levels. Methods Using the mean of all HbA1c measures over a mean follow-up of 6 years, we created categories of HbA1c (<6.0%, 6.0% to 6.4%, 6.5% to 6.9%, 7.0% to 7.4%, 7.5% to 7.9%, 8.0% to 8.4%, 8.5% to 8.9%, and ≥ 9.0%) to estimate the risk of CVD hospitalization and all-cause mortality associated with glycemic control, adjusting for demographic and clinical characteristics among 26,673 members of Kaiser Permanente Northwest with type 2 diabetes. Results Compared with patients with mean HbA1c levels 7.0% to 7.4%, those with mean HbA1c levels <6.0% had a 68% increased risk of CVD hospitalization (hazard ratio [HR]: 1.68 [95% confidence interval (CI): 1.39 to 2.04], p < 0.001) after adjustment for demographic and clinical characteristics. Those with HbA1c levels 6.0% to 6.4% (HR: 1.18 [95% CI: 1.00 to 1.40], p = 0.048) and 6.5% to 6.9% (HR: 1.18 [95% CI: 1.02 to 1.37], p = 0.031) also had significantly higher risk relative to the reference group of 7.0% to 7.4%, as did patients with HbA1c levels 8.5% to 8.9% (HR: 1.55 [95% CI: 1.24 to 1.94], p < 0.001) and ≥ 9.0% (HR: 1.83 [95% CI: 1.50 to 2.22], p < 0.001). Risk of all-cause mortality was significantly greater than the reference group among HbA1c categories <6.0%, 6.0% to 6.4%, 6.5% to 6.9%, and ≥ 9.0%. Conclusions The relationship between mean HbA1c and CVD hospitalizations and all-cause mortality was U-shaped, with greater risk at both higher and lower HbA1c levels.