INS and obesity due to melanocortin 4 receptor deficiency: Design problems include open label studies[22,30,35,39]; some studies including subjects with different disorders s e.g. type 1 and type 2 patients[30,34]; type 2 subjects remaining on drugs that affect insulin secretion or insulin action[35,39,47]; inadequate control of confounders such as hyperglycemia and obesity that affect insulin action[22]; and failure to address the role of chromium levels on the measured parameters.