Enhancement of Vasoreactivity and Cognition by Intranasal Insulin in Type 2 Diabetes
- Vera Novak, MD PhD1,
- William Milberg, PhD2,
- Ying Hao, BS1,3,
- Medha Munshi, MD1,4,
- Peter Novak, MD PhD5,
- Andrew Galica, MA1,
- Bradley Manor, PhD1,
- Paula Roberson, PhD6,
- Suzanne Craft, PhD7 and
- Amir Abduljalil, PhD8
- 1Division of Gerontology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
- 2New England Geriatric, Research, Education and Clinical Center (GRECC)-Boston Division, VA Boston Healthcare; Department of Psychiatry, Harvard Medical School, Boston, MA, USA
- 3Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
- 4Joslin Diabetes Center, Boston MA, USA
- 5Department of Neurology, Univ. of Massachusetts Medical School, Worcester, MA, USA
- 6Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
- 7Division of Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA
- 8Department of Radiology, Ohio State University, Columbus, OH, USA
- Corresponding author: Vera Novak, email:
Objective To determine acute effects of intranasal insulin on regional cerebral perfusion and cognition in older adults with type 2 diabetes.
Research design and methods This was a proof-of-concept, randomized, double-blind, placebo-controlled intervention evaluating the effects of a single 40IU dose of insulin or saline on vasoreactivity and cognition in 15 diabetic and 14 control subjects. Measurements included regional perfusion, vasodilatation to hypercapnia at 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 diabetes group, an increase of perfusion after insulin administration was greater in the insular cortex as compared to the control group (p=0.0003). Cognitive performance following insulin administration was related to regional vasoreactivity. Improvements of visuospatial memory after insulin administration in the diabetes group (R2adj=0.44, p=0.0098) and of verbal fluency test in the control group (R2adj =0.64, p=0.0087) were correlated with vasodilatation in the middle cerebral artery territory.
Conclusions Intranasal insulin administration appears safe and does not affect systemic glucose control, and may provide acute improvements of cognitive function in patients with type 2 diabetes, 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.
- © 2013 by the American Diabetes Association.
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