Ayush Agarwal, MD, DM, DNB

Qureshi AI, Huang W, Lobanova I, Chandrasekaran PN, Hanley DF, Hsu CY, Martin RH, Steiner T, Suarez JI, Yamamoto H, Toyoda K. Effect of Moderate and Severe Persistent Hyperglycemia on Outcomes in Patients With Intracerebral Hemorrhage. Stroke. 2021.

The optimal management of hyperglycaemia in ICH continues to be a grey area with precise guidelines yet to be framed. This multi centric study sought to answer this query and evaluated the effect of persistent hyperglycaemia on the 90-day functional outcome (mRS) in patients with ICH, enrolled within 4.5 hours of symptom onset with hematomas<60ml and GCS>5. Moderate hyperglycaemia was defined as serum glucose concentrations between 140-180mg/dl and severe hyperglycaemia as beyond 180mg/dl. Blood sugar monitoring was done for 3 days (upon admission and successively at 24, 48 and 72 hours). 

The study found that moderate and severe persistent hyperglycaemia was associated with statistically significant worse outcomes (higher 90-day death or disability). These were mirrored in non-diabetic patients with ICH. However, statistical significance was not attained in the previously diagnosed diabetic group. The calculated risk was adjusted for Glasgow coma scale score, hematoma volume, intraventricular hemorrhage, hypertension, hyperlipidemia and cigarette smoking to rule out potential bias and confounding. No glycemic association with hematoma expansion was found.

Acute hyperglycaemia, therefore, was notoriously more harmful in ICH when compared to chronic hyperglycaemia. The possible explanation might be that ICH induces catecholamine, cortisol and growth hormone surges leading to increased gluconeogenesis and reduced peripheral action of insulin leading to hyperglycaemia. These increased serum glucose leads to eventual disproportionately high lactate/pyruvate ratio and oxidative stress leading to formation of reactive oxygen species and inflammation, causing further neuronal damage. The same pathway is at play in chronic hyperglycaemia as well. However, chronically increased serum glucose levels likely lead to preferential down regulation of glucose transporters decreasing the glucose transport to the brain and therefore subsequent inflammation as well.

It is also worth mentioning that intensive systolic blood pressure reduction was associated with lesser hematoma expansion in normoglycemic but not hyperglycaemic patients. This further reinstates the need for good control of these reversible risk factors.

The most important message might be hidden in this finding, i.e., the need for re-evaluation of the cut-off targets for defining hyperglycaemia in stroke patients. This study used a cut-off of 140mg/dl in accordance with the American Diabetic Association and American Association of Clinical Endocrinologist guidelines. However, the traditional one recommended in neurology is 180mg/dl.