Eating Behavior, Low-Frequency Functional Mutations in the Melanocortin-4 Receptor (MC4R) Gene, and Outcomes of Bariatric Operations: A 6-Year Prospective Study
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OBJECTIVE: Data on the effects of eating behavior and genetics on outcomes of gastrointestinal surgery for diabesity have been sparse, often flawed, and controversial. We aimed to assess long-term outcomes of bariatric operations in patients characterized for eating behavior and rare mutations in the melanocortin-4 receptor (MC4R) gene, which is strongly implicated in energy balance. RESEARCH DESIGN AND METHODS: Between 1996 and 2005, 1,264 severely obese Swiss patients underwent current laparoscopic adjustable gastric banding, gastroduodenal bypass, or a hybrid operation. Of these, 872 patients were followed for a minimum of 6 years and were screened for MC4R mutations. Using regression models, we studied relationships between eating behavior and MC4R mutations and postoperative weight loss, complications, and reoperations after 6 years. RESULTS: At baseline, rare functional MC4R mutation carriers exhibited a significantly higher prevalence of binge eating disorder (BED) or loss-of-control eating independent of age, sex, and BMI. Six years after bariatric surgery, the mutation carriers had more major complications than wild-type subjects independent of age, baseline BMI, sex, operation type, and weight loss. Furthermore, high baseline BMI, male sex, BED, and functional MC4R mutations were independent predictors of higher reoperation rates. CONCLUSIONS: Sequencing of MC4R and eating typology, combined with stratification for sex and baseline BMI, might significantly improve patient allocation to banding or bypass operations for diabesity as well as reduce both complication and reoperation rates.
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