INS and obesity due to melanocortin 4 receptor deficiency: Findings from the POUNDS lost trial revealed significant interplays between dietary protein intake and DNAm levels on changes in insulin and HOMA-IR at 6 months of nutritional intervention, where mean protein intake (15%E) was associated with a greater decrease in insulin and HOMA-IR in participants with overweight or obesity within the highest tertile of DNAm at the TXNIP gene, but not in those with a high protein (25%E) intake [9].