LEP and diabetes mellitus: Despite equivalent weight loss post-RYGB, patients who fail to undergo remission of diabetes are hypoleptinemic when compared to those patients who do, as well as to lean controls [22].These lower levels of leptin in patients with sub-optimal diabetes response to RYGB suggest a neurohormonal role of leptin in mediating improvement in glucose metabolism In support of leptin’s role in RYGB, the full weight-reducing and gluco-regulatory effects of RYGB is melanocortin-4 receptor (MC4R)-dependent [23], a well-recognized mediator of many of leptin’s biological actions [24–30].