Eating behavior and allelic variants of the leptin receptor gene in patients with type 2 diabetes: single center cross-sectional study

   Aim. The aim of this study was to analyze eating behavior and leptin receptor (LEPR) gene in patients with type 2 diabetes mellitus (T2D).
   Materials and methods. 83 patients with T2D (62 women, 21 men) aged 59.0 ± 9.9 years and 134 people without clinical and laboratory signs of diabetes mellitus (105 women, 29 men) aged 55.0 ± 10.2 years were examined. Bulimia nervosa was excluded in all the patients. Eating behavior was assessed using Dutch Eating Behavior Questionnaire, V.A. Losenkov’s
Impulsivity Questionnaire. Genotyping of the LEPR gene rs1137100 marker was performed using polymerase chain reaction. The Mann-Whitney U-test and Pearson chi-square were used to compare the values of the variables; ROC-analysis was performed.
   Results. The emotional eating was more pronounced in T2D group (4.9 (4.1; 5.2) vs 3.1 (2.8; 3.8), p < 0.0001), but the restrained (2.8 (2.6; 3.6) vs 3.3 (2.6; 4.2), p < 0.0001) and external eating was less pronounced (3.3 (3.0; 3.8) vs 3.8 (3.3; 4.4), p < 0.0001), T2D patients were also less impulsive (47 (38; 66) vs 61 (54.5; 70), p < 0.0001). These differences for emotional eating are confirmed in both subgroup of excess body weight and in subgroups of all degrees of obesity. The best predictive model of T2D was obtained for emotional eating with a cut-off point 4.1 scores: sensitivity 74.7 %, specificity 79.1 %, AUROC = 0.777; 95 % confidence interval: 0.715–0.830, p < 0.0001. The distribution of genotypes by the polymorphic marker rs1137100 of the LEPR gene was similar in both groups. Restrictive eating was lower in patients with GG genotype compared to AA and GA (1.77 ± 0.52 vs 2.94 ± 0.08, p < 0.01).
   Conclusion. Рatients with T2D are characterized by emotional eating behavior. The association of the polymorphic locus rs1137100 of the LEPR gene with restrained eating behavior in T2D suggests the presence of genetic factors for the formation of eating patterns.

1. Michaud A., Vainik U., Garcia-Garcia I., et al. Overlapping neural endophenotypes in addiction and obesity. Front Endocrinol (Lausanne). 2017 Jun; 8: 127. doi: 10.3389/fendo.2017.00127. PMID: 28659866

2. Yengo L., Vedantam S., Marouli E., et al. A saturated map of common genetic variants associated with human height. Nature. 2022 Oct; 610 (7933): 704–712. doi: 10.1038/s41586-022-05275-y. Epub 2022 Oct 12. PMID: 36224396

3. Hübel C., Leppä V., Breen G., et al. Rigor and reproducibility in genetic research on eating disorders. Int J Eat Disord. 2018 Jul; 51 (7): 593–607. doi: 10.1002/eat.22896. Epub 2018 Sep 8. PMID: 30194862

4. Hudson J. I., Javaras K. N., Pope H. G. Jr. The challenges of metabolic syndrome in eating disorders. Psychiatr Ann. 2020 Aug; 50 (8): 346–350. doi: 10.3928/00485713-20200713-02. Epub 2020 Jul 13. PMID: 34421139

5. Nieto-Martínez R., González-Rivas J. P., Medina-Inojosa J. R., et al. Are eating disorders risk factors for type 2 diabetes? A systematic review and meta-analysis. Curr Diab Rep. 2017 Nov 22; 17 (12): 138. doi: 10.1007/s11892-017-0949-1. PMID: 29168047

6. Avzaletdinova D. S., Morugova T. V., Sharipova L. F., et al. Eating behavior in patients with type 2 diabetes and melanocortin receptor gene polymorphism. Russian Medical Inquiry. 2020; 4 (6): 318–323 (In Russian). doi: 10.32364/2587-6821-2020-4-6-318-323. EDN: FNNIWH

7. Cao X., Huo P., Li W., et al. Interactions among moderate / severe periodontitis, ADIPOQ-rs1501299, and LEPR-rs1137100 polymorphisms on the risk of type 2 diabetes in a Chinese population. Arch Oral Biol. 2019 Jul; 103: 26–32. doi: 10.1016/j.archoralbio.2019.05.014. Epub 2019 May 17. PMID: 31128439

8. Bains V., Kaur H., Badaruddoza B. Association analysis of polymorphisms in LEP (rs7799039 and rs2167270) and LEPR (rs1137101) gene towards the development of type 2 diabetes in North Indian Punjabi population. Gene. 2020 Sep 5; 754: 144846. doi: 10.1016/j.gene.2020.144846. Epub 2020 Jun 5. PMID: 32512158

9. Abaturov A., Nikulina A. Obesity in children with leptin receptor gene polymorphisms. Acta Medica (Hradec Kralove). 2021 Sep; 64 (3): 158–164. doi: 10.14712/18059694.2021.27. PMID: 34779381

10. Obradovic M., Sudar-Milovanovic E., Soskic S., et al. Leptin and obesity: role and clinical implication. Front. Endocrinol. 2021 May 18; 12: 585887. doi: 10.3389/fendo.2021.585887. PMID: 34084149

11. Tu X., Yu C., Gao M., et al. LEPR gene polymorphism and plasma soluble leptin receptor levels are associated with polycystic ovary syndrome in Han Chinese women. Per Med. 2017 Jul; 14 (4): 299–307. doi: 10.2217/pme-2017-0016. Epub 2017 Jun 15. PMID: 29749830

12. Kochetova O .V., Avzaletdinova D. S., Sharipova L. F., et al. An analysis of the associations of polymorphic variants of the LEPR (rs1137100), LRP5 (rs3736228), and LPL (rs320) genes with the risk of developing type 2 diabetes mellitus. Russ J Genet. 2019; 55 (4): 495–503. doi: 10.1134/S1022795419040057. EDN: VVVVHG

13. Van Strien T. Causes of emotional eating and matched treatment of obesity. Current diabetes reports. 2018; 18(6): 35. doi: 10.1007/s11892-018-1000-x. PMID: 2969641

14. Shestakova M. V., Sklyanik I. A., Dedov I. I. Is it possible to achieve sustained remission or cure of type 2 diabetes mellitus in the 21^st century? Terapevticheskii Arkhiv. 2017; 89 (10): 4–11 (In Russian). doi: 10.17116/terarkh201789104-11. EDN: VVVVHG

15. Lopez-Cepero A., Frisard C. F., Lemon S. C., et al. Association of dysfunctional eating patterns and metabolic risk factors for cardiovascular disease among Latinos. J Acad Nutr Diet. 2018 May; 118 (5): 849–856. doi: 10.1016/j.jand.2017.06.007. Epub 2017 Aug 1. PMID: 28774505