A circadian rhythm-related MTNR1B genetic variant (rs10830963) modulates glucose metabolism and insulin resistance after body weight loss secondary to biliopancreatic diversion surgery

Objective: the rs10830963 SNP of the MTNR1B gene may be related with biochemical changes after weight loss induced by caloric restriction. We investigated the role of this SNP on biochemical parameters after biliopancreatic diversion (BPD) surgery in morbid obese subjects. Patients and methods: one hundred and fifty-four patients with morbid obesity, without diabetes mellitus type 2, were enrolled. Their biochemical and anthropometric parameters were recorded before the procedure and after one, two, and three years of follow-up. All subjects were genotyped (rs10830963) at baseline. Results: the decrease in fasting insulin levels seen after the first year (delta: -3.9 ± 1.2 mIU/L vs. -1.8 ± 1.1 mIU/L; p = 0.03), the second year (delta: -5.0 ± 0.3 mIU/L vs. -2.3 ± 0.2 mIU/L; p = 0.01) and the third year (delta: -5.1 ± 1.9 mIU/L vs. -2.8 ± 1.1 mIU/L; p = 0.02) was higher in non-G-allele carriers than in G-allele carriers. Additionally, the improvement of HOMA-IR levels at year one (delta: -0.7 ± 0.2 mIU/L vs. -0.2 ± 0.2 mIU/L; p = 0.03), year two (delta: -1.0 ± 0.3 mIU/L vs. -0.5 ± 0.2 mIU/L; p = 0.01) and year three (delta: -1.2 ± 0.3 mIU/L vs. -0.4 ± 0.2 mIU/L; p = 0.03) was also higher in non-G-allele carriers than in G-allele carriers. Finally, basal glucose levels after the first year (delta: -10.1 ± 2.4 mg/dL vs. -3.6 ± 1.8 mg/dL; p = 0.02), the second year (delta: -16.0 ± 2.3 mg/dL vs. -8.4 ± 2.2 mg/dL; p = 0.01) and the third year (delta: -17.4 ± 3.1 mg/dL vs. -8.8 ± 2.9 mg/dL; p = 0.03) were higher in non-G-allele carriers than in G-allele carriers, too. Improvements seen in comorbidities were similar in both genotype groups. Conclusion: our study showed an association of the rs10830963 MTNR1B polymorphism after massive weight loss with lower glucose response, insulin resistance, and fasting insulin levels in G-allele carriers.