Tumor necrosis factor-α (TNF-α), a proinflammatory cytokine, plays a prominent role in obesity-associated insulin resistance and β-cell dysfunction (1) and, therefore, in the development of diabetes. An association between obesity and elevated TNF-α levels and, furthermore, the substantial decline of TNF-α levels with the simultaneous restoration of insulin sensitivity during weight loss was reported by Dandona et al. (2). Recently, we found evidence that prolonged administration of anti–TNF-α antibody is able to improve insulin sensitivity in insulin-resistant subjects (3); this finding has been confirmed by Kiortsis et al. (4).

Here, we report a case demonstrating the relapse of diabetes in a former type 2 diabetic patient after an interruption of prolonged treatment for psoriatic arthritis with infliximab, an anti–TNF-α antibody. The improvement in insulin sensitivity of this patient has been reported along with post hoc evidence that chronic administration of infliximab improves insulin resistance in a small sample of patients with inflammatory joint diseases (3).

The patient, a 33-year-old male with a BMI of 22.4 kg/m2, had been treated with infliximab continuously until April 2003. From April 2003 to October 2003, infliximab was stopped due to remission of psoriatic arthritis. Readministration of infliximab was started again in October 2003 because of increased disease activity. In the interval without infliximab treatment, we observed a significant increase of fasting capillary blood glucose (monitored by self measurement) from a mean of 4.93 ± 0.18 mmol/l in the preinterruption period to 6.77 ± 0.26 mmol/l in the infliximab-free period (Fig. 1). Interestingly, there was a prompt decrease of fasting blood glucose (mean 4.86 ± 0.41 mmol/l, P > 0.001 by repeated-measures ANOVA) after 3 months of readministration of infliximab. Infliximab has been administrated in 8-week intervals, and until present, the patient has had stable fasting blood glucose in the nondiabetic range.

Our case strongly supports the hypothesis that chronic TNF-α blockade impacts glucose metabolism. First, the patient’s diabetes disappeared during the chronic administration of infliximab due to active psoriatic arthritis, and then he redeveloped diabetes at the infliximab-free interval. After the readministration of the anti–TNF-α antibody, fasting blood glucose was normalized again.

Further prospective studies are strongly needed to investigate the effects of an anti–TNF-α antibody on insulin sensitivity and β-cell function in insulin resistant or diabetic patients.

Greenberg AS, McDaniel ML: Identifying the links between obesity, insulin resistance and beta-cell function: potential role of adipocyte-derived cytokines in the pathogenesis of type 2 diabetes.
Eur J Clin Invest
32(Suppl. 3)
Dandona P, Weinstock R, Thusu K, Abdel-Rahman E, Aljada A, Wadden T: Tumor necrosis factor-α in sera of obese patients: fall with weight loss.
J Clin Endocrinol Metab
Yazdani-Biuki B, Stelzl H, Brezinschek HP, Hermann J, Mueller T, Krippl P, Graninger W, Wascher TC: Improvement of insulin sensitivity in insulin resistant subjects during prolonged treatment with the anti-TNF-α antibody infliximab (Letter).
Eur J Clin Invest
Kiortsis DN, Mavridis AK, Vasakos S, Nikas SN, Drosos AA: Effects of infliximab treatment on insulin resistance in patients with rheumatoid arthritis and ankylosing spondylitis.
Ann Rheum Dis