Response to Letter by Brainin et al
We appreciate the comments by Brainin et al concerning our recent article on dynamic of hyperglycemia and its impact on outcome after acute ischemic stroke.1
The study of Matz et al2 revealed a substantial part of stroke patients with undiagnosed disorder of glucose metabolism. This finding is clinically important and supplement to our results. The finding could also imply a misclassification of diabetics into the nondiabetics in our study, and in clinical routine in general. In our study, the potential association between persistent hyperglycemia and the stroke outcome was not significant, probably due to the insufficient statistical power. If the assumption of misclassification of diabetes is appropriate, an overestimation of the risks of hyperglycemia in the nondiabetics could be induced, because the deteriorating effect of unrecognized impaired glucose metabolism has not been taken into account.
The natural course of glucose in acute stroke is not well studied. To define a course, the timing, the level, and the dynamic of hyperglycemia have to be considered. These parameters and their causes and impacts should be evaluated in future research. To determine the impact of impaired glucose metabolism, serial glucose measurements should be performed also in clinical routine. Furthermore, distinction between a clinically relevant level change and numeric variation of measurements is crucial in assessment of prognostic value of hyperglycemia.
The duration of hyperglycemia and its prognostic value is less well understood. It is possible that the pattern of change in the acute phase, especially the first few hours to days after the stroke onset, will be more important in the early development of ischemic brain injury, and therefore clinically relevant although longstanding undiagnosed diabetes undoubtedly has a deleterious effect on brain arterial tree and its autoregulation capacity. The plasma glucose level began to decline within the first 8 hours in the patients administered with a saline lotion.3 In the study of Matz et al, 2 glucose measurements, each in the 1st and 2nd week after the stroke, were used to classify the patterns of disturbances in glucose metabolism. It would be interesting to know whether the glucose dynamic in the acute phase was associated with the outcome of Matz and coworkers’ patients.
We acknowledged the consideration of Brainin et al that our results were based on a post hoc analysis and therefore subject to bias. Furthermore, patients in clinical trials are selected and may not represent ordinary patients treated in clinical routine. Regarding the timing of glucose course after stroke, the first measurement in our study was derived in a relative short window due to the study design of the ECASS-II, while many studies suffer from the uncertain time of the blood sample collection related to the stroke onset.
Yong M, Kaste M. Dynamic of hyperglycemia as a predictor of stroke outcome in the ECASS-II trial. Stroke. 2008; 39: 2749–2755.
Matz K, Keresztes K, Tatschl C, Nowotny M, Dachenhausen A, Brainin M, Tuomilehto J. Disorders of glucose metabolism in acute stroke patients: an underrecognized problem. Diabetes Care. 2006; 29: 792–797.
Gray CS, Hildreth AJ, Alberti GKMM, O'Connell JE; on behalf of the GIST Collaboration. Poststroke hyperglycemia: natural history and immediate management. Stroke. 2004; 35: 122–126.