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

**Authors:** Zongpai Zhang, Vera Novak, Peter Novak, Christos Mantzoros, Long Ngo, Vasileios Lioutas, Weiying Dai

PMC · DOI: 10.1371/journal.pone.0324029 · 2025-05-20

## TL;DR

Intranasal insulin improves brain connectivity in people with Type 2 Diabetes, potentially helping with cognitive issues.

## Contribution

The study shows that intranasal insulin increases specific resting-state functional connectivity patterns in Type 2 Diabetes patients.

## Key findings

- INI treatment increased mPFC-postcentral rsFC and hippocampal-frontal connectivity in Type 2 Diabetes patients.
- Reduced insulin resistance was linked to improved mPFC-basal ganglia connectivity.
- Results suggest INI may enhance brain connectivity related to cognition in T2DM.

## Abstract

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.

## Linked entities

- **Chemicals:** insulin (PubChem CID 70678557)
- **Diseases:** Type 2 Diabetes (MONDO:0005148), Type 2 Diabetes mellitus (MONDO:0005148), T2DM (MONDO:0005148)

## Full-text entities

- **Genes:** INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}
- **Diseases:** T2DM (MESH:D003924), cognitive decline (MESH:D003072), insulin resistance (MESH:D007333), DM (MESH:D009223)
- **Chemicals:** MemAID (-), oxygen (MESH:D010100)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

10 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12091882/full.md

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Source: https://tomesphere.com/paper/PMC12091882