Type 2 Diabetes and Risk of Rupture of Saccular Intracranial Aneurysm in Eastern Finland

OBJECTIVE

Type 2 diabetes is a risk factor for other forms of stroke, but its association with subarachnoid hemorrhage (SAH) from ruptured saccular intracranial aneurysm (sIA) has remained unclear.

RESEARCH DESIGN AND METHODS

Kuopio Intracranial Aneurysm Database (www.uef.fi/ns) includes all ruptured and unruptured sIA cases from a defined catchment population in eastern Finland since 1980. We compared the age-adjusted incidences of type 2 diabetes in 1,058 ruptured and 484 unruptured sIA patients during 1994–2008, using the national registry of prescribed medicine purchases.

RESULTS

Of the 1,058 ruptured sIA patients, 43% were males and 57% females, with a median age at rupture of 51 and 56 years, respectively. From 1994 to 2008 or until death, 9% had been prescribed antidiabetes medication (ADM) with a median starting age of 58 years for males and 66 years for females. Of the 484 unruptured sIA patients, 44% were males and 56% females, with a median age at the diagnosis of 53 and 55 years, respectively, and 9% had used ADM, with a median starting age of 61 years for males and 66 years for females. The incidence of type 2 diabetes was highest in the age-group 60–70 years, with no significant differences between the ruptured and unruptured sIA patients.

CONCLUSIONS

Our study suggests that type 2 diabetes does not increase the risk of rupture of sIA, which is by far the most frequent cause of nontraumatic SAH.Aneurysmal subarachnoid hemorrhage (SAH) is a devastating form of stroke that affects primarily the working-age population (1). In ~95% of cases, SAH is caused by the rupture of a saccular intracranial aneurysm (sIA) at the fork of intracranial extracerebral arteries in contrast to their infrequent fusiform, mycotic, and traumatic aneurysms. Some 2% of the general population develops sIAs (2–3) during life, but most do not rupture, as the general annual incidence of SAH is 4–7 per 100,000 (4–5). The sIA disease is a complex trait, affected by genomic (6–8) and acquired risk factors (3), the mechanisms of which in the formation, progress, and rupture of sIA pouches are poorly understood. Risk factors include age, female sex, smoking, hypertension, and excess drinking (3), and at least 10% of ruptured sIA patients have a family history (9–12). In a genome-wide association study, susceptibility loci at 2q33.1, 8q11.23, and 9p21.3 have been identified in Finnish subjects (7).Type 2 diabetes is a complex trait affecting the arterial wall through several different mechanisms (13–16). Type 2 diabetes is a well-established risk factor for brain infarction and may predispose to intracerebral hemorrhage (17–19). Instead, the association between type 2 diabetes and sIA disease has remained unclear. Three recent studies (20–22) and our present review of the literature suggest that diabetes is a protecting factor for rupture of sIA (Fig. 1A) (23–29). Both type 2 diabetes and sIA disease are associated with the 9p21.3 locus (6–8,30,31), although not with the same LD block, but they do not seem to share other loci in genome-wide association studies.

Table 1

Previous studies on the association of diabetes and intracranial aneurysm disease* since 2001Open in a separate windowOpen in a separate windowFigure 1A: Review of the literature of the association of diabetes and SAH in case-control studies published 2001–2012. The horizontal lines represent the 95% CIs of the OR or risk ratios (RRs). The size of the black box indicates the relative effect on the final fixed-effect estimate. The x-axis is logarithmic. B: Incidence of type 2 diabetes in 1,058 ruptured (aneurysmal SAH) and 484 unruptured sIA patients by age-group and 95% CIs.Kuopio Intracranial Aneurysm Database (www.uef.fi/ns) contains all cases of unruptured and ruptured sIAs admitted to the Kuopio University Hospital (KUH) from a defined eastern Finnish catchment population since 1980 (11,12). We have studied the phenotype (11), familial form (2,9), risk factors (32), outcome (12,33), concomitant diseases (12), and genomics of sporadic and familial sIA disease (6–8,34). Here, we investigated retrospectively whether type 2 diabetes predisposes to sIA rupture by comparing 1,058 ruptured sIA patients with 484 unruptured sIA patients with first diagnosis between 1995 and 2007. In this study, we tested the hypothesis that arterial long-term effects of type 2 diabetes predispose to the rupture of the sIA wall rather than the formation of the sIA pouch. We also performed a review of the literature of the published cohorts to summarize the previous data on the association of type 2 diabetes and sIA disease.