Can Anti-TNF Therapies Treat Insulin Resistance and Type 2 Diabetes?

Antagonism of tumor necrosis factor-alpha (TNF-alpha) may be a good treatment strategy to counter the deleterious effects of TNF-alpha on the development of insulin resistance and the pathogenesis of type 2 diabetes (T2D), according to a review in the Journal of Cellular Biochemistry by Muhammad Sajid Hamid Akash, PhD, and colleagues.

The review describes the fact that TNF-alpha, one of the most significant pro-inflammatory mediators, induces inflammation in vital organs and has been shown, along with other pro-inflammatory mediators, to become abnormally high in insulin-resistant and T2D experimental animal models and patients. TNF-alpha is interdependently involved in inducing tissue-specific inflammation that may lead to the development of insulin resistance and T2D, and its increased production in adipose tissues is also thought to be related to the obesity-associated insulin resistance that leads to the development of T2D. In addition, TNF-alpha has been shown to impair the beta-cells of pancreatic islet cells, the review notes.

Research has been conducted into anti—TNF-alpha (anti-TNF) treatment strategies in animal models to assess their ability to neutralize TNF-alpha and counter the development of insulin resistance. Some clinical studies of anti-TNF treatment strategies have also been conducted, including one published in Cutis in 2016 by Nawaf Al-Mutairi, MD, and Dalia Shabaan, MD, which showed a beneficial effect of anti-TNF agents on insulin resistance and insulin sensitivity in patients with both psoriasis and T2D.

The authors of the Cutis article note that psoriasis is known to be associated with an increased incidence of insulin resistance and T2D, and it is thought that psoriasis predisposes patients to insulin resistance and may put them at risk for developing T2D.

In their study of 35 psoriasis patients in Kuwait, patients were treated with the anti-TNF agents etanercept, adalimumab, or infliximab for 24 weeks. The study group (patients who received anti-TNF drugs) showed significant improvements in glycemic control as assessed by levels of fasting plasma glucose (FPG) and hemoglobin A1C (HbA1c) at the end of the study, with no significant differences between patients taking any of the 3 anti-TNF medications.

However, patients in the control group showed no significant changes in FPG and HbA1C. The improvement in glycemic control between the control group and the treatment group taking anti-TNF medications was significant. The authors concluded that the results of their study may support a hypothesis that long-term use of anti-TNF agents reduces the mechanisms involved in the development of T2D in patients with psoriasis, and may in turn decrease the coronary artery disease risk in these patients.

Additional large, prospective, multi-center studies are needed to further analyze the effects of anti-TNF antibodies on insulin sensitivity and beta-cell function in insulin-resistant or diabetic patients with psoriasis.