Alternatively, some studies were conducted to demonstrate the effect of TNF-α neutralization on insulin sensitivity in patients with type 2 diabetes: most of them indicated no appreciable effect of TNF-α neutralization on insulin sensitivity [65–67].The basis for this controversy is unclear but may relate to patient populations studied or length of clinical trials; all these studies potentially did not allow sufficient time for normalization of the metabolic derangements. In fact more recently, a long-term study conducted in obese subjects with glucose alterations and subclinical inflammation treated with etanercept, TNF-α antagonist, found an improved fasting glucose, increased ratio of high molecular weight (HMW) adiponectin to total adiponectin, and decreased soluble intracellular adhesion molecule-1 (sICAM) [68].