INS and obesity due to melanocortin 4 receptor deficiency: The strengths of our study include: use of the “gold standard” in measurement of insulin sensitivity, i.e., the hyperinsulinemic-euglycemic clamp; analysis of AT and muscle gene expression in a human study with a large group of participants and the examination of an apparently healthy study population, which allowed us to assess early events in the development of obesity-related insulin resistance, without the confounding effects of hyperglycemia, morbid obesity and other diseases.