Evidence map›Paper›PMID 39529444›Full record

ArticleDiabetes, obesity & metabolism2025

Targeting the cholinergic anti-inflammatory pathway for type 2 diabetes prevention: A retrospective cohort study.

Joseph Magagnoli, Tammy H Cummings, James W Hardin, Jayakrishna Ambati, S Scott Sutton

Abstract read
In one paragraph

Article in Diabetes, obesity & metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Joseph MagagnoliDorn Research Institute, Columbia VA Health Care System, Columbia, South Carolina, USA.ORCID 0000-0002-8568-0097
Tammy H CummingsDorn Research Institute, Columbia VA Health Care System, Columbia, South Carolina, USA.
James W HardinDorn Research Institute, Columbia VA Health Care System, Columbia, South Carolina, USA.
Jayakrishna AmbatiCenter for Advanced Vision Science, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
S Scott SuttonDorn Research Institute, Columbia VA Health Care System, Columbia, South Carolina, USA.

Funding

Visual system and cognitive biology in normal animals versus in an animal model of Alzheimer's disease with or without diabetes treated with solo or dual inflammasome inhibitorsR01EY031039 · NEI · UNIVERSITY OF VIRGINIA · PI AMBATI, JAYAKRISHNA, GELFAND, BRADLEY DAVID · 2020 to 2024
$3.2M
Defining the role of SINE retrotransposons and inflammasome activation in Alzheimer's diseaseR01AG078892 · NIA · UNIVERSITY OF VIRGINIA · PI Jayakrishna Ambati, Bradley David Gelfand · 2022 to 2026
$3.1M
Non-canonical inflammasome in activation in RPE degenerationR01EY029799 · NEI · UNIVERSITY OF VIRGINIA · PI AMBATI, JAYAKRISHNA · 2019 to 2022
$2.7M
Knowledge discovery and machine learning to elucidate the mechanisms of HIV activity and interaction with substance use disorderR01DA054992 · NIDA · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI SAFRO, ILYA, SHTUTMAN, MICHAEL · 2021 to 2025
$2.1M
NIH HHS R01AG078892NIH HHS R01AG082108NIH HHS R01DA054992NIH HHS R01EY029799NIH HHS R01EY031039
6 · The paper itself

Abstract

backgroundChronic inflammation is a key factor in type 2 diabetes mellitus (T2DM) development. The cholinergic anti-inflammatory pathway (CAP) reduces inflammation by activating α7 nicotinic acetylcholine receptors (α7nAChRs) on macrophages, suppressing proinflammatory cytokines. Acetylcholinesterase inhibitors (AChEis), primarily used for Alzheimer's disease (AD), may exert anti-inflammatory effects through the CAP. One AChEi, galantamine, also directly agonizes α7nAChRs, potentially enhancing its anti-inflammatory properties.

objectiveThis study aimed to investigate the association between AChEi use, particularly galantamine, and T2DM risk in AD patients.

methodsWe conducted a retrospective analysis of Veterans Health Administration (VA) data, examining early- and late-onset AD patients receiving galantamine or other AD medications. Propensity score matching was used to balance groups and minimize confounding. Cox proportional hazard models assessed T2DM risk for galantamine, other AChEis and memantine.

resultsA total of 40 065 AD patients were included in the study. Among early-onset AD patients, galantamine use significantly reduced T2DM risk (hazard ratio [HR] = 0.80, 95% confidence interval [CI]: 0.66-0.98). Memantine also showed a protective effect (HR = 0.82, 95% CI: 0.69-1) in this group. Neither galantamine nor memantine influenced T2DM risk in late-onset AD. Other AD medications showed no association with T2DM risk.

conclusionGalantamine use was associated with a lower risk of T2DM in early-onset AD patients, potentially due to enhanced anti-inflammatory effects through both AChE inhibition and direct α7nAChR agonism. Memantine also demonstrated a protective effect. These findings suggest potential new applications for existing AD medications in T2DM prevention, particularly in early-onset AD patients. Further research, including randomized controlled trials with diverse populations, is needed to confirm these results and the underlying mechanisms.

Indexed as

alpha7 Nicotinic Acetylcholine ReceptorAlzheimer DiseaseCholinesterase InhibitorsDiabetes Mellitus, Type 2GalantamineAgedAged, 80 and overAnti-Inflammatory AgentsFemaleHumansInflammationMaleMemantineMiddle AgedRetrospective StudiesUnited Statesalpha7 Nicotinic Acetylcholine ReceptorAnti-Inflammatory AgentsCholinesterase InhibitorsGalantamineMemantinedatabase researcheffectivenesspharmacoepidemiologytype 2 diabetes

Identifiers

PMID39529444
PMCPMC11701198

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.