Diabetes is associated with increased risk for intracerebral hemorrhage (ICH), and this risk is directly associated with diabetes duration, according to study results published in Diabetes Care. Furthermore, there appears to be a J-shaped relationship between level of glycated hemoglobin (HbA1c) and ICH risk, suggesting that both poor and very intensive glycemic control might be associated with elevated risk.

While the association between diabetes and ischemic stroke is well known, previous studies have reported conflicting results regarding the association between diabetes and ICH. Abnormal fasting blood glucose concentrations were associated with increased ICH risk in patients both with and without diabetes, but sparse data are available regarding the association between HbA1c and the risk for ICH. The goal of this study was to examine the association between diabetes and glycemic control based on glycated hemoglobin levels and ICH risk.

The study was based on data from the Israeli Clalit Health Services database. The researchers focused on adult members age ≥40 who were alive in January 2010. They collected data from 297,486 patients with a preexisting diagnosis of diabetes and at least 1 test result for HbA1c and more than 1.1 million members without diabetes. The patients were followed until incidence of ICH, death, loss to follow-up, or end of follow-up period in December 2017.

The researchers reported that during mean follow-up of 7.3 years, 4170 patients were diagnosed with ICH (crude incidence ratio, 38.8/100,000 person-years), including 1614 patients with diabetes and 2556 patients without diabetes (crude hazard ratio [HR] in patients with diabetes, 2.69; 95% CI, 2.53-2.87). The association between diabetes and ICH remained significant following adjustment for disease risk score, a summary measure of disease probability (crude HR, 1.36; 95% CI, 1.27-1.45).

There was a direct association between the risk for ICH and diabetes duration. Compared with the group of patients without diabetes, the age- and sex-adjusted HRs were 1.53 (95% CI, 1.40-1.68) and 2.06 (95% CI, 1.91-2.21) for diabetes duration ≤5 years and >5 years, respectively, and the respective HRs adjusted for clinically relevant risk factors (eg, obesity, cardiovascular disease, smoking) were 1.33 (95% CI, 1.21-1.46) and 1.64 (95% CI, 1.51-1.78), respectively. The respective disease risk score-adjusted HRs were 1.23 (95% CI, 1.12-1.35) and 1.44 (95% CI, 1.34-1.56).

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The risk for ICH associated with diabetes was related to HbA1c in a non-linear J-shaped manner, as the lowest risk was observed in participants with HbA1c between 6.5% and 6.7% and in these patients the risk was similar to patients without diabetes. Compared with patients without diabetes, the risk for ICH was highest in patients with diabetes and HbA1c >9.3% (crude HR, 3.80; 95% CI, 3.31-4.37), but was also significantly increased in patients with HbA1c ≤6% (crude HR, 2.79; 95% CI, 2.41-3.22).

The study had some limitations, noted the investigators, including its retrospective nature, reliance solely on an administrative computerized database, and potential residual unmeasured confounders.

The researchers concluded that “[the] study suggests that diabetes is associated with increased risk [for] 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.”

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Reference

Saliba W, Barnett-Griness O, Gronich N, et al. Association of diabetes and glycated hemoglobin with the risk of intracerebral aemorrhage: a population-based cohort study [published online February 6, 2019]. Diabetes Care. doi:10.2337/dc18-2472