MC4R and type 2 diabetes mellitus: However, in an exome sequencing study of 6760 Pima Indians, mutations decreasing MC4R activity were detected and these individuals with MC4R defects had increased T2D risk, partially independent of BMI in childhood (BMI-adjusted hazard rate ratio = 3.3, 95 % CI = 1.2–9.2, p = 0.03).