Association of Diabetes and Glycated Hemoglobin With the Risk of Intracerebral Hemorrhage: A Population-Based Cohort Study

Abstract

OBJECTIVE To examine the association of diabetes and glycated hemoglobin (HbA1c) with the risk of intracerebral hemorrhage (ICH) in a large population-based cohort. RESEARCH DESIGN AND METHODS The computerized database of the largest health care provider in Israel was used to identify adult members aged 40 years or older and alive at 1 January 2010 (297,486 with diabetes and 1,167,585 without diabetes). The cohort was followed until 31 December 2017 for incidence of ICH. Multivariable Cox proportional hazards regression models, adjusted for baseline disease risk score, were applied to estimate the hazard ratio (HR) of ICH. RESULTS Overall 4,170 ICH cases occurred during 10,730,915 person-years of follow-up. Diabetes was independently associated with increased ICH risk, with hazard ratio (HR) 1.36 (95% CI 1.27–1.45), and increased with longer diabetes duration: 1.23 (1.12–1.35) and 1.44 (1.34–1.56) for diabetes duration ≤5 years and >5 years, respectively. The increased ICH risk associated with diabetes was more pronounced in patients ≤60 years old (Pinteraction <0.001). Among patients with diabetes, HbA1c had a nonlinear J-shaped relationship with ICH (P for nonlinearity = 0.0186). Compared to the fourth HbA1c decile, 6.5–6.7% (48–50 mmol/mol), the HR for ICH was 1.27 (1.01–1.59) and 2.19 (1.75–2.73) in the lowest HbA1c decile, ≤6.0% (≤42 mmol/mol), and highest HbA1c decile, >9.3% (>78 mmol/mol), respectively. CONCLUSIONS Diabetes is associated with increased risk of ICH that is directly associated with diabetes duration. ICH and HbA1c appear to have a J-shaped relationship, suggesting that both poor control as well as extreme intensive diabetes control might be associated with increased risk.