Intranasal insulin enhances resting-state functional connectivity in Type 2 Diabetes

• Published in: PloS one Vol. 20; no. 5; p. e0324029
• Main Authors: Zhang, Zongpai, Novak, Vera, Novak, Peter, Mantzoros, Christos, Ngo, Long, Lioutas, Vasileios, Dai, Weiying
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.05.2025; Public Library of Science (PLoS)
• Subjects: Administration, Intranasal; Adult; Aged; Basal ganglia; Biology and Life Sciences; Blood levels; Cognition; Cognition & reasoning; Cognition - drug effects; Cognitive ability; COVID-19; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - physiopathology; Dosage and administration; Drug therapy; Executive function; Fasting; FDA approval; Female; Functional magnetic resonance imaging; Gait; Ganglia; Glucose; Glycated Hemoglobin - metabolism; Glycosylated hemoglobin; Health aspects; Hemoglobin; Hippocampus - drug effects; Hippocampus - physiopathology; Humans; Hypotheses; Hypothesis testing; Image acquisition; Insulin; Insulin - administration & dosage; Insulin - therapeutic use; Insulin Resistance; Intranasal medication; Magnetic Resonance Imaging; Male; Measurement; Medicine and Health Sciences; Memory; Middle Aged; Older people; Patient outcomes; Placebos; Prefrontal Cortex - drug effects; Prefrontal Cortex - physiopathology; Research and Analysis Methods; Rest; Tissues; Type 2 diabetes; Walking; United States; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0324029

Type 2 diabetes mellitus (T2DM) affects cognition and resting-state functional connectivity (rsFC). Intranasal insulin (INI) has emerged as a potential treatment for T2DM-related cognitive decline. We aimed to evaluate the effect of INI treatment on rsFC with medio-prefrontal (mPFC) and left/right hippocampus (lHPC/rHPC), and their relationship with the cognition, hemoglobin A1c (HbA1c), and homeostatic model assessment of insulin resistance (HOMA-IR) and walking speed. An MRI sub-study of the MemAID trial was conducted, involving a 24-week treatment with either intranasal insulin or placebo. Blood oxygen level-dependent (BOLD) functional MRI (fMRI) images were acquired on eighteen DM subjects at baseline and eleven DM subjects (eight DM-INI patients and three DM-Placebo) at the end-of-treatment. Compared to DM-Placebo treated subjects, DM-INI patients showed increased mPFC-postcentral rsFC, lHPC-frontal rsFC, lHPC-postcentral rsFC, rHPC-frontal rsFC, and lHPC-mPFC rsFC (p < 0.05). The decreased HOMA-IR, which was observed in the MemAID trial, was associated with increased mPFC-basal ganglia rsFC (p < 0.05). This sub-study provides insights into potential mechanisms of INI effects on rsFC that require validation in a larger trial.