HYPERINSULINISM AND CEREBRAL MICROANGIOPATHY

Background and Purpose High insulin levels are a recognized risk facto r for atherosclerosis. Microvascular endothelium is more susceptible t o metabolic and mitogenic effects of insulin than large-vessel endothe lium. Besides their atherogenic effect, high insulin levels impair fib rinolysis by enhancing plasminogen activator inhibitor-1. We undertook this study to evaluate the hypothesis that elevated serum insulin and C-peptide levels are related to cerebral small-vessel disease rather than large-vessel pathology. Methods One hundred ninety-four consecuti ve patients presenting with symptomatic cerebrovascular disease were a ssigned to three subgroups that were differentiated by clinical presen tations, brain imaging studies, and extracranial as well as transcrani al vascular ultrasound findings: (1) patients with lacunes (n=20), (2) patients with subcortical arteriosclerotic encephalopathy (n=35), and (3) patients with strokes due to large-vessel disease (n=99). Patient s who had suffered a cryptogenic (n=9) or cardioembolic (n=16) stroke or who showed characteristics of the microangiopathy and macroangiopat hy groups (n=15) were not further evaluated. Thirty patients without m anifestations of cerebrovascular disease were also examined. Fasting b lood glucose, insulin, and C-peptide levels were determined in all sub jects. Results There were no significant differences in age or sex amo ng the three groups and control patients. Insulin levels were signific antly higher in the lacunar group compared with the subcortical arteri osclerotic encephalopathy group, the macroangiopathy group, and the co ntrol patients (median [interquartile range]: 103.8 [198.6], 72.0 [103 .2], 66.0 [57.0], and 52.2 [57.0] pmol/L, respectively; all P<.05, Man n-Whitney test). There was a statistically significant difference in i nsulin concentrations between the microangiopathy group (subcortical a rteriosclerotic encephalopathy and lacunes) and the macroangiopathy an d control groups (81.0 [110.4], 66.0 [57.0], and 55.2 [57.0] pmol/L, r espectively; all P<.05, Mann-Whitney). The same was true for the distr ibution of C-peptide levels and to a minor extent blood glucose values , but these differences failed to reach statistical significance. Conc lusions Elevated insulin levels potentially represent a pathogenetic f actor in the development of cerebral small-vessel disease, predominant ly in patients presenting with lacunes. Whether this is due solely to atherosclerotic changes of the small penetrating arteries or whether c hanges in hemorheology are operative as well remains to be evaluated.