Association of Tumor Necrosis Factor Alpha, Interleukin 6, and C-Reactive Protein with the Risk of Developing Type 2 Diabetes: A Retrospective Cohort Study of Rural Thais

The linkage of obesity, inflammation, and type 2 diabetes mellitus (T2DM) has been extensively investigated for over a decade. However, the association between inflammatory biomarkers, including C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α), and T2DM is still inconsistent and limited. Thus, this study is aimed at elucidating the association between inflammatory marker levels and the risk of developing T2DM in many aspects. Among 296 subjects enrolled in 2013, 248 non-T2DM subjects who were completely reinvestigated in 2014 and 2015 were included in a 2-year retrospective analysis. Multivariate logistic regression was performed to evaluate the association of baseline inflammatory marker levels and variation with incidence of T2DM. After the 2-year follow-up, 18.6% of total subjects had developed T2DM. The risk of developing T2DM was significantly increased in subjects with a high level of baseline CRP (OR=4.02, 95% CI: 1.77-9.12, P=0.001), and a stronger impact was found with the combination of high CRP and IL-6 levels (OR=5.11, 95% CI: 1.27-20.49, P=0.021). One-year inflammatory marker variation analysis also revealed the significant association of elevated TNF-α and risk of developing T2DM (OR=4.88, 95% CI: 1.01-23.49, P=0.048). In conclusion, besides consideration of CRP levels alone, our findings suggested that IL-6 outstandingly plays a contributing role in T2DM progression and elevated TNF-α levels over time could be a potential predictor of T2DM.