Metformin Monotherapy Downregulates Diabetes-Associated Inflammatory Status and Impacts on Mortality

Frontiers in Physiology

卷:10

Anis Larbi¹  Anteneh Mehari Tizazu²  Tze Pin Ng³  Ma Shwe Zin Nyunt³  Emilie Combet⁴  Tamas Fulop⁵  Olivier Cexus⁶  Joni Chong⁶  Sandra Hubert⁶  Chin Hui Xian⁶  Koolarina Suku⁶  Wilson How⁶  Esther Mok⁶  Crystal Tan⁶ 

[1] Department of Biology, Faculty of Sciences, Tunis El Manar University, Tunis, Tunisia;

[2] Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore;

[3] Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore;

[4] Human Nutrition, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom;

[5] Research Center on Aging, Graduate Program in Immunology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC, Canada;

[6] Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore;

关键词: aging;    diabetes;    chronic inflammation;    metabolic syndrome;    insulin resistance;    metformin;   

DOI  :  10.3389/fphys.2019.00572

来源: DOAJ

【 摘 要 】

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 TNFα, 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.

【 授权许可】

Unknown