Although dramatic progress has been made in our understanding of the role of inflammation in obesity-associated insulin resistance, clinical trials targeting inflammatory mediators of obesity and T2DM (such as TNF-α and IL-1β) to improve glycemic control in T2DM have shown limited benefits [25,59], indicating that there must be other factors contributing to decreased insulin sensitivity. This evidence concerns the gene IL1B and obesity due to melanocortin 4 receptor deficiency.