Bariatric Surgery Improves Glycemia But Not Obesity in a Family with Inactive Melanocortin 4 Receptor Signaling

Abstract

We conducted an observational long-term study with a median follow-up of 102 months on the outcomes of bariatric surgery in a family that carries a deleterious mutation in the melanocortin 4 receptor (MC4R) gene. In homozygous patients, bariatric surgery led to transient weight-loss and improvements in associated comorbidities, but in the long-term did not resolve morbid obesity: median presurgical/final body mass index 71.2/64.3 kg/m2. Glycemia however was improved despite regaining: median presurgical/final fasting blood glucose 218/101 mg/dL. Heterozygous patients responded normally to bariatric surgery. This unique case series, the largest and longest of its kind, demonstrates that bariatric surgery is dependent on MC4R signaling for sustained weight-loss, but its anti-diabetic effect is also independent of weight-loss. Bariatric surgery provides temporary relief in comorbidities for super-obese patients, may improve long-term glycemic control, and should be considered as a metabolic treatment for such genetic cases.