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Lookup NU author(s): Martina Magistri, Professor Vijay KunadianORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© The Author(s) 2026. Up to 40–60% of patients undergoing coronary angiography because of angina and/or evidence of inducible ischaemia on non-invasive stress testing are diagnosed with ischaemia and non-obstructive coronary artery disease (INOCA). The pathogenesis of this condition is primarily attributed to two mechanisms: coronary microvascular dysfunction (CMD) and coronary vasospasm. Notably, ischaemic heart disease is the leading cause of death in patients with type 2 diabetes mellitus (T2DM). Insulin resistance (IR), affecting 10–25% of the general adult population, plays a major role in the pathophysiology of T2DM, but can precede diabetes by years. IR is recognised as a major cardiovascular risk factor, involved in endothelial dysfunction and inflammation, two key processes leading to CMD and vasomotor dysfunction. Hyperinsulinaemia, dysglycaemia, and oxidative stress contribute to this complex relationship, yet the connection between IR, CMD and coronary vasospasm remains incompletely defined. Moreover, IR may represent a target for tailored therapies aimed at improving microvascular function and alleviating symptom burden. Although a few studies have investigated this relationship, the molecular mechanisms by which multiple pathways lead to different INOCA endotypes remain incompletely defined. The aim of this review is to summarise current evidence linking IR, CMD and coronary vasospasm, with emphasis on pathophysiological mechanisms and diagnostic approaches, and to highlight future research directions in this clinical setting.
Author(s): Magistri M, Portolan L, Trevisanello A, Tosi F, Locatelli A, Piana S, Rubinelli M, Molinaroli E, Mantovani A, Ribichini F, Kunadian V, Bonadonna R, Scarsini R
Publication type: Review
Publication status: Published
Journal: Cardiovascular Diabetology
Year: 2026
Volume: 25
Online publication date: 20/01/2026
Acceptance date: 29/12/2025
ISSN (print): elec-tronic
ISSN (electronic): 1475-2840
Publisher: BioMed Central Ltd
URL: https://doi.org/10.1186/s12933-025-03068-x
DOI: 10.1186/s12933-025-03068-x
PubMed id: 41559641
Data Access Statement: No datasets were generated or analysed during the current study.
