Sir, Insulin resistance (IR) is an important component in the pathophysiology of type-II diabetes, hypertension, hyperlipidaemia and finally cardiovascular disease with both genetic and environmental factors contributing to its development. Tumour necrosis factor alpha (TNF-α), a proinflammatory cytokine, may play a prominent role in obesity associated IR as well as β-cell dysfunction [1]. Elevated expression of TNF-α in obese insulin resistant rodents and humans was observed along with the indication of elevated plasma TNF-α in some studies. TNF-α has tissue specific effects on glucose homeostasis and is known to impair insulin receptor signalling experimentally. Furthermore, cytokines that activate (NF)-kB (a nuclear transcription factor closely involved into regulation of cellular inflammatory response), such as TNF-α, are thought to be a common denominator for βcell apoptosis in type 1 and type 2 diabetes [2]. In addition, it has been suggested that TNF-α is a powerful regulator of adipose tissue [3]. Neutralizing TNF-α in obese fa/fa-rats has shown increased insulin sensitivity [4]. So far, in humans two studies failed to demonstrate an effect of acute administration of either a chimeric anti-TNF-α antibody [5] or a recombinant soluble human TNF-α receptor [6] on insulin sensitivity in obese or type-II diabetic subjects. Prolonged administration of anti–TNF-α antibody is used in the treatment of chronic inflammatory diseases such as rheumatic diseases [7] or Crohn’s disease [8]. Here we report observational findings of chronic treatment with infliximab (a chimeric anti-TNF-α antibody) on insulin sensitivity as assessed by the homeostasis model assessment (HOMA: fasting plasma glucose (mmol L− 1)× fasting serum insulin (mU L− 1) divided by 225 [9]), in such patients. Our index case, a 31 years old male with a body-mass-index (BMI) of 31· 2 kg m− 2 was diagnosed with type-II diabetes in November 1999 with an HbA1c of 9· 2%. The patient lost weight within 8 months to a BMI of 22· 4 kg m− 2 and was treated with insulin (approx. 28 IU per day). As a result stable, good glycaemic control (fasting blood glucose: 6· 05 mmol L− 1) in the absence of hypoglycaemia could be reached and maintained till 2001. In January 2001 treatment with infliximab (5 mg kg− 1) every 8 weeks, was started due to refractory psoriatic arthritis. At this time point he exhibited an unexpectedly severe insulin resistance with a HOMA of 36· 98 despite maintenance of normal body weight (In healthy subjects the median HOMA is about 1· 4 whereas only 10% of them exhibit a HOMA between 4· 5 and 20). After 4–5 months, the patient noticed a decline in insulin requirements and the occurrence of hypoglycaemia. In October 2001, after a severe hypoglycaemic episode, the patient stopped insulin treatment. In July 2002, still on infliximab treatment glucose status was reevaluated. Fasting plasma glucose was 5· 17 mmol L− 1 and 2-h after challenge with 75 g glucose 10· 56 mmol L− 1 were observed indicating the presence of impaired glucose tolerance instead of insulin requiring diabetes. The respective serum insulin was 32· 8 mU L− 1 and 96· 4 mU L− 1, HbA1c was 5· 4%. Today the patient is still without insulin therapy. This observation prompted us to evaluate insulin sensitivity retrospectively, using the HOMA, in samples stored from patients treated with infliximab after obtaining informed consent (Fig. 1).

Interestingly, with exception of our lean index patient, only the most obese patients (patients 3 and 5), available for analysis (Table 1), showed a pronounced insulin resistance at baseline and improved substantially. In contrast, the other patients (patients 2 and 4) with a lower BMI were …