Low-Grade Inflammation as a Unifying Mechanism in Chronic Internal Medicine: Diabetes at the Center of Cardiometabolic Disease

Authors

DOI:

https://doi.org/10.64784/125

Keywords:

low-grade inflammation, type 2 diabetes mellitus, insulin resistance, chronic disease, cardiometabolic risk, metabolic syndrome, atherosclerosis, internal medicine

Abstract

Low-grade inflammation has emerged as a central biological mechanism linking multiple chronic conditions commonly encountered in internal medicine. Increasing evidence indicates that metabolic and cardiovascular diseases are not isolated entities, but interconnected manifestations of a shared immunometabolic dysfunction. In this context, type 2 diabetes mellitus occupies a pivotal role, functioning both as a consequence and a driver of chronic inflammatory activation. This narrative review synthesizes experimental, epidemiological, and clinical evidence to analyze low-grade inflammation as a cross-cutting mechanism underlying chronic disease, with particular emphasis on its relationship with insulin resistance, metabolic dysregulation, and cardiovascular risk. The findings demonstrate a progressive increase in inflammatory burden across the metabolic continuum, a close association between inflammation and insulin resistance, and a consistent convergence between inflammatory activity and cardiovascular risk. These patterns are preserved across different population contexts, supporting the global relevance of inflammation-centered models of chronic disease. Conceptualizing diabetes as an immunometabolic disorder within this framework offers an integrative perspective that may enhance clinical reasoning, prevention strategies, and medical education in internal medicine.

References

[1] S. Calder et al., “Low-grade inflammation, metabolic disease and clinical outcomes,” Clinical Science, vol. 133, no. 1, pp. 1–15, 2019, doi: 10.1042/CS20180415.

[2] P. Dandona, A. Aljada, and A. Bandyopadhyay, “Inflammation: The link between insulin resistance, obesity, and diabetes,” Trends in Immunology, vol. 25, no. 1, pp. 4–7, 2004, doi: 10.1016/j.it.2003.10.013.

[3] M. Donath and S. E. Shoelson, “Type 2 diabetes as an inflammatory disease,” Nature Reviews Immunology, vol. 11, no. 2, pp. 98–107, 2011, doi: 10.1038/nri2925.

[4] M. Y. Donath, “Targeting inflammation in the treatment of type 2 diabetes,” Diabetes, Obesity and Metabolism, vol. 15, Suppl 3, pp. 193–196, 2013, doi: 10.1111/dom.12172.

[5] K. Esser, N. Paquot, and A. J. Scheen, “Anti-inflammatory agents to treat or prevent type 2 diabetes,” Expert Opinion on Investigational Drugs, vol. 24, no. 2, pp. 283–307, 2015, doi: 10.1517/13543784.2015.997709.

[6] M. Esser et al., “Inflammation as a link between metabolic and cardiovascular disease,” Cardiovascular Research, vol. 110, no. 2, pp. 200–212, 2016, doi: 10.1093/cvr/cvw106.

[7] E. Ferrannini et al., “Insulin resistance, inflammation, and the metabolic syndrome,” Circulation, vol. 113, no. 13, pp. 1528–1534, 2006, doi: 10.1161/CIRCULATIONAHA.105.539650.

[8] A. Festa et al., “Chronic subclinical inflammation as part of the insulin resistance syndrome,” Circulation, vol. 102, no. 1, pp. 42–47, 2000, doi: 10.1161/01.CIR.102.1.42.

[9] J. E. Hall et al., “Obesity-induced inflammation and insulin resistance,” Endocrine Reviews, vol. 36, no. 1, pp. 1–31, 2015, doi: 10.1210/er.2014-1065.

[10] C. Herder et al., “Inflammation markers and risk of type 2 diabetes,” Diabetes Care, vol. 32, Suppl 2, pp. S210–S216, 2009, doi: 10.2337/dc09-S214.

[11] G. S. Hotamisligil, “Inflammation and metabolic disorders,” Nature, vol. 444, no. 7121, pp. 860–867, 2006, doi: 10.1038/nature05485.

[12] M. Kolb and T. Mandrup-Poulsen, “The global diabetes epidemic as a consequence of lifestyle-induced low-grade inflammation,” Diabetologia, vol. 53, no. 1, pp. 10–20, 2010, doi: 10.1007/s00125-009-1573-7.

[13] P. Libby, G. K. Hansson, and P. M. Ridker, “Inflammation and atherosclerosis,” Journal of the American College of Cardiology, vol. 70, no. 18, pp. 2293–2300, 2017, doi: 10.1016/j.jacc.2017.09.009.

[14] J. C. Pickup, “Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes,” Diabetes Care, vol. 27, no. 3, pp. 813–823, 2004, doi: 10.2337/diacare.27.3.813.

[15] M. Pradhan et al., “C-reactive protein, interleukin-6, and risk of developing type 2 diabetes,” JAMA, vol. 286, no. 3, pp. 327–334, 2001, doi: 10.1001/jama.286.3.327.

[16] P. M. Ridker et al., “Inflammation, C-reactive protein, and diabetes risk,” Circulation, vol. 107, no. 3, pp. 391–397, 2003, doi: 10.1161/01.CIR.0000052939.59093.45.

[17] P. Ridker et al., “Antiinflammatory therapy with canakinumab and incident diabetes,” New England Journal of Medicine, vol. 377, no. 12, pp. 1119–1131, 2017, doi: 10.1056/NEJMoa1707914.

[18] S. E. Shoelson, J. Lee, and A. B. Goldfine, “Inflammation and insulin resistance,” Journal of Clinical Investigation, vol. 116, no. 7, pp. 1793–1801, 2006, doi: 10.1172/JCI29069.

[19] I. Tabas and C. K. Glass, “Anti-inflammatory therapy in chronic disease,” Science, vol. 339, no. 6116, pp. 166–172, 2013, doi: 10.1126/science.1230720.

[20] C. Wellen and G. Hotamisligil, “Inflammation, stress, and diabetes,” Journal of Clinical Investigation, vol. 115, no. 5, pp. 1111–1119, 2005, doi: 10.1172/JCI25102.

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Published

2026-01-31

How to Cite

[1]
Maribel Villaseñor Landeros, Trans., “Low-Grade Inflammation as a Unifying Mechanism in Chronic Internal Medicine: Diabetes at the Center of Cardiometabolic Disease”, TheSci, vol. 3, no. 1, Jan. 2026, doi: 10.64784/125.