Chirantan Banerjee, MD

Hägg S, Thorn LM, Forsblom CM, Gordin D, Saraheimo M, Tolonen N, et al. Different Risk Factor Profiles for Ischemic and Hemorrhagic Stroke in Type 1 Diabetes Mellitus. Stroke. 2014

Risk factor epidemiology is the crux of cerebrovascular prevention. It guides us towards appropriate targets to ameliorate future strokes. Prospective cohort studies, albeit expensive, are one of the most effective ways to learn the most about stroke epidemiology in a population, as they give us the ability to ask varied questions within the same study framework. The Finnish Diabetic Nephropathy Study (FinnDiane) was founded to uncover the risk factors and mechanisms of diabetic micro and macro-vascular complications, with a focus on type 1 diabetes, and has previously reported associations between diabetic nephropathy as well as severe diabetic retinopathy and stroke.

In this issue of Stroke, Hagg et al attempt to identify and compare risk factors for stroke and its subtypes in the FinnDiane multicenter observational cohort. 4083 stroke free participants with type 1 diabetes were enrolled at baseline, and data on clinical as well as laboratory variables was collected. Outcome was ascertained by questionnaires, death certificates, and the Finnish National Hospital Discharge Register, and confirmed by medical records, neuroimaging. There were 149 incident strokes, with more than usual proportion of hemorrhage (30%) and lacunar (55% of ischemic) strokes. Diabetic nephropathy and higher systolic blood pressure were associated with both ischemic and hemorrhagic strokes. Although longer duration of diabetes, higher HbA1c, insulin resistance and history of smoking were associated with ischemic stroke, they were not associated with hemorrhagic stroke. Lower BMI was independently associated with hemorrhagic strokes. Sex, waist circumference, metabolic syndrome, triglycerides, LDL and HDL cholesterol were not associated with either stroke.

Several thoughts come to mind with these novel findings. The fact that higher systolic blood pressure is associated with stroke despite adjusting for nephropathy, hints that not all of the effect of high SBP on stroke risk is mediated by nephropathy in these patients. Also, the fact that metabolic syndrome, sex, triglycerides, as well as LDL and HDL cholesterol were not associated with any stroke suggest that the pathophysiology of stroke in Type 1 diabetics may be distinct from those in Type 2 diabetes patients. 

Although an association between glycemic control and microvascular complications has been demonstrated previously, there had been conflicting evidence with regard to macrovascular complications. This study found HbA1C levels to be independently associated with ischemic stroke in Type 1 diabetes patients. With regards to lower BMI being associated with hemorrhagic stroke, some of the effect may be driven by the fact that most of the hemorrhagic stroke patients had diabetic nephropathy, which has been associated with cachexia and platelet dysfunction. 

The study has several weaknesses. The findings cannot be generalized to Type 2 diabetes patients or the general stroke at risk population. Outcome assessment was based on questionnaires and the national register, where silent strokes would be missed, thus biasing towards null. Also, including subarachnoid hemorrhages in the composite hemorrhagic stroke outcome may be a confounder as the etiology of SAH is disparate from intraparenchymal hemorrhage.

Despite having a restricted cohort with a specific phenotype, this study generates several pathophysiological hypotheses, and stresses on the need for further inquiry into modifiable risk factors in diabetic patients. As stroke clinicians, we should tailor our preventative efforts to each patient!”