INS and obesity due to melanocortin 4 receptor deficiency: Studies on rs659366 have demonstrated associations between the A allele and enhanced adipose tissue mRNA expression and decreased risk of obesity [17], increased energy expenditure [20], reduced beta cell function and higher risk of T2DM [14], lower insulin secretion [15], decreased lipid oxidation [16], increased preclinical atherosclerosis in women [21], and increased coronary heart disease risk [18].