Tumor Necrosis Factor Inhibitors May Improve Glycemic Control in Patients Rheumatoid Arthritis and Concomitant Type 2 Diabetes Mellitus

Abhijeet Danve*, Shivtej Sehra, Divya jaykumar and Supriya Kulkarni

Tumor Necrosis Factor Inhibitors May Improve Glycemic Control in Patients Rheumatoid
Arthritis and Concomitant Type 2 Diabetes Mellitus

Insulin resistance is a key feature of obesity, metabolic syndrome, and Type 2 Diabetes
Mellitus (T2DM). Inflammation and insulin resistance are closely linked with each other. I.
Tumor necrosis factor-α (TNF-α) has been found to impair the insulin sensitivity and promote
insulin resistance through multiple actions on the insulin sensitive tissues.

Inflammatory cytokines such as TNF, Interleukin (IL)-6, IL-1 and IL-8 may inhibit insulin signaling.
Hotamisligil et al2 did the pioneering work in 1993 confirming the link between TNF-α and insulin resistance in mice. Animal studies have confirmed that the TNF-α interferes with phosphorylation
cascades of the insulin receptor beta subunit and insulin receptor substrate-1, thereby altering the transmembrane signaling that is essential for insulin action in various insulin sensitive tissues.

Also TNF-α causes depletion of GLUT 4, the insulin sensitive glucose transporter
in adipocytes and muscles. A intravenous administration of a recombinant TNF-α receptor
antibody resulted in improvement in insulin sensitivity and dramatic reductions in plasma insulin, glucose, and non-esterified fatty acid levels in obese, as compared with lean rats.

These findings suggested that TNF-α inhibitors (TNFi) could be used for the treatment
of T2DM. But initial two human clinical trials of anti TNF-α antibodies for treatment T2DM
failed to show statistically significant improvement in insulin sensitivity.

These studies however had few limitations; they had short duration of treatment,
small number of patients and were underpowered.

Osteol Rheumatol Open J. 2016; 1(1): 17-19. doi: 10.17140/ORHOJ-1-106