Intranasal insulin enhanced resting-state functional connectivity of hippocampal
regions in type 2 diabetes.
Author(s): Zhang H(1), Hao Y(1), Manor B(2), Novak P(3), Milberg W(4), Zhang J(5), Fang
J(5), Novak V(6).
Affiliation(s): Author information:
(1)Academy for Advanced Interdisciplinary Studies, Peking University, Beijing,
China. (2)Academy for Advanced Interdisciplinary Studies, Peking University,
Beijing, China Division of Gerontology, Beth Israel Deaconess Medical Center,
Harvard Medical School, Boston, MA. (3)Department of Neurology, University of
Massachusetts Medical School, Worcester, MA. (4)New England Geriatric Research
Education and Clinical Center-Boston Division, VA Boston Healthcare, and
Department of Psychiatry, Harvard Medical School, Boston, MA. (5)Academy for
Advanced Interdisciplinary Studies, Peking University, Beijing, China College of
Engineering, Peking University, Beijing, China. (6)Department of Neurology, Beth
Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
vnovak@bidmc.harvard.edu.
Publication date & source: 2015, Diabetes. , 64(3):1025-34
Type 2 diabetes mellitus (T2DM) alters brain function and manifests as brain
atrophy. Intranasal insulin has emerged as a promising intervention for treatment
of cognitive impairment. We evaluated the acute effects of intranasal insulin on
resting-state brain functional connectivity in older adults with T2DM. This
proof-of-concept, randomized, double-blind, placebo-controlled study evaluated
the effects of a single 40 IU dose of insulin or saline in 14 diabetic and 14
control subjects. Resting-state functional connectivity between the hippocampal
region and default mode network (DMN) was quantified using functional MRI (fMRI)
at 3Tesla. Following insulin administration, diabetic patients demonstrated
increased resting-state connectivity between the hippocampal regions and the
medial frontal cortex (MFC) as compared with placebo (cluster size: right, P =
0.03) and other DMN regions. On placebo, the diabetes group had lower
connectivity between the hippocampal region and the MFC as compared with control
subjects (cluster size: right, P = 0.02), but on insulin, MFC connectivity was
similar to control subjects. Resting-state connectivity correlated with cognitive
performance. A single dose of intranasal insulin increases resting-state
functional connectivity between the hippocampal regions and multiple DMN regions
in older adults with T2DM. Intranasal insulin administration may modify
functional connectivity among brain regions regulating memory and complex
cognitive behaviors.
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