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CC BY 4.0 · TH Open 2026; 10: a27905251
DOI: 10.1055/a-2790-5251
Review Article

Diabetes, Protein Misfolding, and Heat Stress: Molecular Insights and Translational Perspectives

Authors

  • M. Marc Abreu

    1   Department of Clinical Sciences, BTT Medical Institute, Aventura, Florida, United States
    2   Department of Biomedical Engineering and Medical Physics, BTT Medical Institute, Aventura, Florida, United States

  • Victor Hugo Spitz

    3   Department of Medicine, Nova Southeastern University Medical School, Fort Lauderdale, Florida, United States

  • David M. Smadja 

    4   Université Paris Cité, Institut national de la santé et de la recherche médicale (INSERM), Paris Cardiovascular Research Center (PARCC), Paris, France
    5   Hematology Department, Assistance Publique–Hôpitaux de Paris (AP–HP), European Georges Pompidou Hospital, Paris, France
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Abstract

Diabetes mellitus (DM), particularly type 1 (T1D) and type 2 (T2D), is a growing global health burden with complex pathophysiology extending beyond glucose dysregulation. Both forms of diabetes involve cellular stress, chronic inflammation, and β-cell dysfunction. Heat shock proteins (HSPs), key mediators of protein homeostasis and immune modulation, are emerging as critical players in the progression and complications of diabetes. In T1D, HSPs act at the crossroads of β-cell stress and autoimmunity, while in T2D, their dysregulation contributes to insulin resistance and mitochondrial dysfunction. Misfolded proteins, particularly amylin aggregates, further drive β-cell apoptosis in T2D and may influence immune activation in T1D. Hyperthermia (HT) and passive heat therapy (hT) activate protective stress responses through HSP induction, mimicking some benefits of exercise and improving glycemic control, insulin sensitivity, and vascular health. Preclinical and early clinical studies suggest that thermal interventions could complement standard care, especially in patients unable to engage in regular physical activity. This review consolidates current evidence on the roles of HSPs, amylin misfolding, and hT in the pathogenesis of diabetes, with a particular emphasis on vascular and thrombotic complications and their therapeutic implications. Targeting these converging molecular pathways may offer new avenues for preserving β-cell function, mitigating metabolic complications, and enhancing diabetes management.

Keywords

cardiovascular disease - heat shock proteins - heat therapy - hyperthermia - mitochondrial dysfunction - diabetes mellitus - endothelial progenitor cells - thrombosis - amylin

Contributors' Statement

M.M.A.: Conceptualization, writing–review and editing. V.H.S.: Conceptualization, writing–review and editing. D.M.S.: Conceptualization, writing–original draft, writing–review and editing.




Publication History

Received: 15 October 2025

Accepted: 15 January 2026

Article published online:
09 February 2026

© 2026. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

Bibliographical Record
M. Marc Abreu, Victor Hugo Spitz, David M. Smadja. Diabetes, Protein Misfolding, and Heat Stress: Molecular Insights and Translational Perspectives. TH Open 2026; 10: a27905251.
DOI: 10.1055/a-2790-5251
 

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