Jay Shah, MD

Saxena A, Anderson CS, Wang X, Sato S, Arima H, Chan E, et al. Prognostic Significance of Hyperglycemia in Acute Intracerebral Hemorrhage: The INTERACT2 Study. Stroke. 2016

Known prognostic factors of intracerebral hemorrhage (ICH) are hematoma volume and clinical severity. Hyperglycemia is associated with adverse outcomes in various medical conditions but its impact on ICH is relatively unknown. In this study, the authors seek to quantify risk associations of hyperglycemia and diabetes in patients that participated in the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). This study evaluated intense versus standard blood pressure control in ICH patients. Blood glucose level and history of diabetes was recorded at enrollment. Primary outcome was death or major disability. Secondary outcomes included serious adverse events such as neurological deterioration. 

1348 (51%) patients had hyperglycemia and 292 (11%) had diabetes. After adjusting for confounding factors, hyperglycemic patients were significantly more often female, had greater cortical hematomas, higher systolic blood pressure and larger hematomas with intraventricular extension. There was a continuous relationship between baseline glucose level and death or disability (OR 1.29). Hyperglycemic patients had significantly greater frequency of early neurologic deterioration but there was no difference in hematoma expansion. 

This study shows that elevated glucose levels and diabetes are associated with worse outcomes. An interesting element to these results indicate that the adverse outcomes are specific to the effects of hyperglycemia rather than simply a history of diabetes which impacted outcomes by increased cardiovascular event risk. While hyperglycemia and diabetes are certainly related, this suggests that adequate control of diabetes, and this lower blood glucose levels, may negate the potential risk of adverse outcomes following ICH. However, it is important to realize that INTERACT2 was not powered to evaluate hyperglycemia and therefore a causal relationship between hyperglycemia and outcomes cannot necessarily be established. Nonetheless, the study does elucidate a potential relationship and determining the pathophysiological mechanism remains an important biological query. Animal studies suggest that hyperglycemia plays a role in free radical generation which in turn disrupts blood-brain barrier and enhances edema. A possible limitation of this study is that hyperglycemia is based on a single time point and future studies should address effect of persistent hyperglycemia on outcomes. Ultimately, a trial designed to specifically control hyperglycemia should elucidate further this relationship and whether intervention improves outcomes.