Enhancement of Vasoreactivity and Cognition by Intranasal Insulin in Type 2 Diabetes

OBJECTIVE: To determine acute effects of intranasal insulin on regional cerebral perfusion and cognition in older adults with type 2 diabetes mellitus (DM). RESEARCH DESIGN AND METHODS: This was a proof-of-concept, randomized, double-blind, placebo-controlled intervention evaluating the effects of a single 40-IU dose of insulin or saline on vasoreactivity and cognition in 15 DM and 14 control subjects. Measurements included regional perfusion, vasodilatation to hypercapnia with 3-Tesla MRI, and neuropsychological evaluation. RESULTS: Intranasal insulin administration was well tolerated and did not affect systemic glucose levels. No serious adverse events were reported. Across all subjects, intranasal insulin improved visuospatial memory (P ≤ 0.05). In the DM group, an increase of perfusion after insulin administration was greater in the insular cortex compared with the control group (P = 0.0003). Cognitive performance after insulin administration was related to regional vasoreactivity. Improvements of visuospatial memory after insulin administration in the DM group (R(2)(adjusted) = 0.44, P = 0.0098) and in the verbal fluency test in the control group (R(2)(adjusted) = 0.64, P = 0.0087) were correlated with vasodilatation in the middle cerebral artery territory. CONCLUSIONS: Intranasal insulin administration appears safe, does not affect systemic glucose control, and may provide acute improvements of cognitive function in patients with type 2 DM, potentially through vasoreactivity mechanisms. Intranasal insulin-induced changes in cognitive function may be related to vasodilatation in the anterior brain regions, such as insular cortex that regulates attention-related task performance. Larger studies are warranted to identify long-term effects and predictors of positive cognitive response to intranasal insulin therapy.