Metformin monotherapy downregulates diabetes-associated inflammatory status and impacts on mortality

Tizazu, A. M. et al. (2019) Metformin monotherapy downregulates diabetes-associated inflammatory status and impacts on mortality. Frontiers in Physiology, 10, 572. (doi: 10.3389/fphys.2019.00572)

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Aging is the main risk factor for developing diabetes and other age-related diseases. One of the most common features of age-related comorbidities is the presence of low-grade chronic inflammation. This is also the case of metabolic syndrome and diabetes. At the subclinical level, a pro-inflammatory phenotype was shown to be associated with Type-2 diabetes mellitus (T2DM). This low to mid-grade inflammation is also present in elderly individuals and has been termed inflammaging. Whether inflammation is a component of aging or exclusively associated with age-related diseases in not entirely known. We used clinical data and biological readouts in a group of individuals stratified by age, diabetes status and comorbidities to investigate this aspect. While aging is the main predisposing factor for several diseases there is a concomitant increased level of pro-inflammatory cytokines. DM patients show an increased level of sTNFRll, sICAM-1, and TIMP-1 when compared to Healthy, Non-DM and Pre-DM individuals. These inflammatory molecules are also associated with insulin resistance and metabolic syndrome in Non-DM and pre-DM individuals. We also show that metformin monotherapy was associated with significantly lower levels of inflammatory molecules, like TNF, sTNFRI and sTNFRII, when compared to other monotherapies. Longitudinal follow up indicates a higher proportion of death occurs in individuals taking other monotherapies compared to metformin monotherapy. Together our finding shows that chronic inflammation is present in healthy elderly individuals and exacerbated with diabetes patients. Likewise, metformin could help target age-related chronic inflammation in general, and reduce the predisposition to comorbidities and mortality.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Combet Aspray, Professor Emilie
Authors: Tizazu, A. M., NYUNT, S. Z., Cexus, O., Suku, K., Mok, E., Xian, C. H., Chong, J., Tan, C., How, W., Hubert, S., Combet, E., Fulop, T., Ng, T. P., and Larbi, A.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Frontiers in Physiology
Publisher:Frontiers Media
ISSN (Online):1664-042X
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Frontiers in Physiology 10:572
Publisher Policy:Reproduced under a Creative Commons License

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