Nonfasting serum glucose and insulin concentrations and the risk of stroke

Background and Purpose-Type 2 diabetes is an established risk factor for st roke, but the relations between asymptomatic hyperglycemia, hyperinsulinemi a, and stroke incidence remain uncertain. We have examined the relationship between established diabetes, nonfasting serum glucose and serum insulin c oncentrations, and subsequent risk of stroke. Methods-We performed a prospective study of 7735 men aged 40 to 59 years dr awn from general practices in 24 British towns. Men with missing serum gluc ose values (n=50) and men on insulin injection (n=36) were excluded, leavin g 7649 men available for analysis. Baseline nonfasting serum was analyzed f or insulin with a specific enzyme-linked immunosorbent assay method in 18 o f the 24 towns (n=5663 men). Results-During the mean follow-up period of 16.8 years, there were 347 stro ke cases (fatal and nonfatal) in the 7649 men. Men who developed diabetes d uring follow-up (n=320) and men with established type 2 diabetes at screeni ng (n=98) both showed significantly increased risk of stroke, even after ad justment for cardiovascular risk factors, including blood pressure (adjuste d relative risk [RR], 2.27; 95% CT, 1.23 to 4.20; RR, 2.07; 95% CI, 1.44 to 2.98, respectively). In men with no diagnosed diabetes at screening (n=755 1), risk of stroke was increased significantly only in the top 2.5% of the nonfasting glucose distribution (greater than or equal to 8.2 mmol/L), and this persisted even after adjustment for cardiovascular risk factors, inclu ding hypertension (RR, 1.86; 95% CI, 1.11 to 3.13). Exclusion of the 320 me n who developed diabetes during follow-up attenuated this risk so that it w as no longer significant (RR, 1.56; 95% CI, 0.83 to 2.91), In the 5567 men with insulin measurements and no diagnosis of diabetes at screening, a J-sh aped relationship was seen between nonfasting insulin and risk of stroke. R isk was significantly raised in the first quintile and in the fourth quinti le and above compared with the second quintile, with all findings of margin al significance. Part of the increased risk at higher levels of insulin was due to men who developed diabetes in the follow-up period. Conclusions-This study confirms the importance of established type 2 diabet es as an independent risk factor for stroke. The increased risk of stroke s een in hyperglycemic subjects and those with elevated serum insulin levels at screening reflected to some extent the high proportion of men who subseq uently developed diabetes.