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Another Microvascular Complication of Type 1 Diabetes?

Nonaneurysmal subarachnoid hemorrhage (SAH) appears to be a distinct microvascular complication of type 1 diabetes….

Miikka Korja, MD, PhD, associate professor in neurosurgery at Helsinki University Central Hospital, and colleagues, examined data from the nationwide Finnish Diabetic Nephropathy (FinnDiane) study, and demonstrated that SAH is usually caused by the rupture of a cerebrovascular aneurysm. In such cases, it is considered a macrovascular lesion because the intracranial vessels involved are fairly large, at 1 mm or greater.

Dr. Korja, who is also affiliated with Macquarie University, New South Wales, Australia, added that, nonaneurysmal SAH can be due to trauma, but other causes are not known. This new study sheds some light: "According to our study, it appears likely that nonaneurysmal SAH is a microvascular disease, which means that it is a disease of small intracranial arteries." "We have identified for the first time that type 1 diabetes patients have exceptionally high incidence of ‘microvascular SAHs,’ if we may say so. After this primary finding, we can hopefully study in the future the specific risk factors for this subtype of stroke," he said.

From the FinnDiane study cohort of 4083 patients with type 1 diabetes, a total of 15 were identified who had a confirmed primary SAH, giving a crude rate of 40.9 per 100,000 person-years. Of those, 10 (27.3 per 100,000 person-years) were nonaneurysmal based on cerebral angiographic studies that did not show intracranial aneurysms. None of the nonaneurysmal SAHs was fatal.

Only 1 aneurysmal SAH could be confirmed, giving a crude incidence rate of 2.7 per 100,000. However, the other 4 had died within 24 hours after the SAH and did not have angiographic studies performed, but it is likely that they had aneurysms. Assuming that to be the case, the crude incidence of aneurysmal SAH would be 13.6/100,000, the authors note.

By comparison, in the general Finnish population the incidence of SAH is 35 per 100,000 person-years for those aged 25 years and older. The incidence of nonaneurysmal SAH is globally unknown, but it is believed that 5% to 15% of all SAHs are of nonaneurysmal origin.

A comparison of baseline characteristics of the 10 type 1 diabetes patients with nonaneurysmal SAH with those of the 4068 type 1 diabetes patients without revealed that the nonaneurysmal SAH patients were slightly older (47.0 vs 36.8 years, P < .001) and were more likely to use antihypertensives (70% vs 38%, P = .037), to have severe diabetic retinopathy (60% vs 34%, P = .077), and to be current smokers (50% vs 24%, P = .057).

There were no significant differences between those with and without nonaneurysmal SAH in the age of type 1 diabetes onset, body mass index, blood pressure, cholesterol or triglyceride levels, HbA1c, use of any medication other than antihypertensives, or the prevalence of coronary heart disease or diabetic nephropathy.

Dr. Korja explained that, the small numbers might explain the lack of association with glycemic control. "Finding any associations with such a small number of SAH cases is almost impossible. Given that type 1 diabetes and especially SAH are relatively rare diseases, a much larger cohort of type 1 diabetes patients with SAH is needed for adequate association studies. From this point of view, we are not surprised at the insignificant role of HbA1c in SAH."

In age- and sex-adjusted univariate analysis, current smoking significantly increased both the risks for nonaneurysmal SAH (hazard ratio, 4.82) and for all SAH (5.12), with P = .003.

"If more similar evidence to ours is presented in the future, ‘nontraumatic/spontaneous’ nonaneurysmal SAH can perhaps be classified as ‘microvascular SAH,’ which suggests that the etiology lies in small arteries. Then, future studies can focus on this enigmatic disease from perhaps a slightly different point of view," Dr. Korja said.

And from a clinical perspective, these new findings might point to stroke prevention. "All stroke subtypes have differing risk factors, and therefore none of the stroke subtypes can be prevented without knowing the contributing factors… By knowing these specific risk factors, we can probably enhance stroke prevention in type 1 diabetes."

In all, he said, "This is a primary finding, which hopefully encourages clinicians and research people to focus on this stroke subtype in type 1 diabetes, too."

Diabetes Care. Published online July 22, 2013. Abstract