Association between FokI Vitamin D Receptor Gene Polymorphism and Visceral Obesity in Patients with Type 2 Diabetes: A Single-Blinded Randomised Clinical Trial
Abstract
Background: Role of genetic variants on the effect of vitamin D on adiposity measures is still unclear. This study aimed to investigate the effect of vitamin D on visceral adiposity using intake of vitamin D fortified doogh.
Methods: This was a single-blinded randomised clinical trial which seventy type 2 diabetic Iranian subjects were randomly allocated to two groups of receiving plain Doogh (PD; n 32, containing 170 mg Ca and no vitamin D/250 ml) or vitamin D3-fortified Doogh (FD; n 38, containing 170 mg Ca and 12•5 μg/250 ml) twice a day for 3 months. Serum 25-hydroxyvitamin D (25(OH)D, anthropometric measures, body composition, glycaemic status and visceral obesity indicators assessed twice before and after the intervention. Genotyping was conducted for FokI single nucleotide polymorphisms (SNPs) of the VDR gene by polymerase chain reaction.
Results: Serum 25(OH)D (P<0.001) was increased in FD compared to PD and waist circumference (P= 0.022), fat mass (P<0.001), visceral adipose tissue (P<0.001), and trunk fat (P<0.001) were decreased after 3-month intervention. Analysis of FOK-1 genotyping was showed significant change for 25(OH)D (P=0.03), FSG (P=0.036), HbA1c (P=0.003), waist circumference (P=0.045), waist: hip ratio (P=0.04), fat mass (P=0.016), visceral adipose tissue (P=0.024), and Truncal fat (P=0.004) after Tukey’s post hoc analysis.
Conclusion: In conclusion, FD compared to PD could increase serum 25(OH)D and improve glyceamic, anthropometric, and visceral obesity indicators. Moreover, significant differences was seen between FOK-1 (FF, Ff, and ff) genotypic groups for 25(OH)D, FSG, HbA1c, waist circumference, waist: hip ratio, fat mass, visceral adipose tissue, and Truncal fat
1. Safar HA, Chehadeh SEH, Abdel-Wareth L, Haq A, Jelinek HF, ElGhazali G, et al. Vitamin D receptor gene polymorphisms among Emirati patients with type 2 diabetes mellitus. J Steroid Biochem Mol Biol. 2018; 175:119-124.
2. Kriska AM, LaPorte RE, Patrick SL, Kuller LH, Orchard TJ. The association of physical activity and diabetic complications in individuals with insulin-dependent diabetes mellitus: the Epidemiology of Diabetes Complications Study--VII. J Clin Epidemiol. 1991;44(11):1207-14.
3. Traversy G, Chaput JP. Alcohol Consumption and Obesity: An Update. Curr Obes Rep. 2015;4(1):122-30.
4. Saha SK, Panwar R, Kumar A, Pal S, Ahuja V, Dash NR, et al. Early colectomy in steroid-refractory acute severe ulcerative colitis improves operative outcome. Int J Colorectal Dis. 2018;33(1):79-82.
5. Van Leiden HA, Dekker JM, Moll AC, Nijpels G, Heine RJ, Bouter LM, et al. Blood pressure, lipids, and obesity are associated with retinopathy: the hoorn study. Diabetes care. 2002;25(8):1320-5.
6. DeFronzo RA. Pathogenesis of type 2 diabetes mellitus. Med Clin North Am. 2004;88(4):787-835.
7. Molarius A, Seidell J. Selection of anthropometric indicators for classification of abdominal fatness—a critical review. Int J Obes Relat Metab Disord. 1998;22(8):719-27.
8. Allison DB, Kaprio J, Korkeila M, Koskenvuo M, Neale MC, Hayakawa K. The heritability of body mass index among an international sample of monozygotic twins reared apart. Int J Obes Relat Metab Disord. 1996;20(6):501-6.
9. Dennis KE. Postmenopausal women and the health consequences of obesity. J Obstet Gynecol Neonatal Nurs. 2007;36(5):511-7.
10. Pourshahidi LK. Vitamin D and obesity: current perspectives and future directions. Proc Nutr Soc. 2015;74(2):115-24.
11. Pereira‐Santos M, Costa PR, Assis AM, Santos CA, Santos DB. Obesity and vitamin D deficiency: a systematic review and meta‐analysis. Obes Rev. 2015;16(4):341-9.
12. Vanlint S. Vitamin D and obesity. Nutrients. 2013;5(3):949-56.
13. Verstuyf A, Carmeliet G, Bouillon R, Mathieu C. Vitamin D: a pleiotropic hormone. Kidney Int. 2010;78(2):140-5.
14. Sun J. Vitamin D and mucosal immune function. Curr Opin Gastroenterol. 2010;26(6):591-5.
15. Palomer X, González‐Clemente J, Blanco‐Vaca F, Mauricio D. Role of vitamin D in the pathogenesis of type 2 diabetes mellitus. Diabetes Obes Metab. 2008;10(3):185-97.
16. Norman AW, Frankel JB, Heldt AM, Grodsky GM. Vitamin D deficiency inhibits pancreatic secretion of insulin. Science. 1980;209(4458):823-5.
17. Kumar S, Davies M, Zakaria Y, Mawer EB, Gordon C, Olukoga AO, et al. Improvement in glucose tolerance and beta-cell function in a patient with vitamin D deficiency during treatment with vitamin D. Postgrad Med J. 1994;70(824):440-3.
18. Filus A, Trzmiel A, Kuliczkowska-Płaksej J, Tworowska U, Jędrzejuk D, Milewicz A, et al. Relationship between vitamin D receptor BsmI and FokI polymorphisms and anthropometric and biochemical parameters describing metabolic syndrome. Aging Male. 2008;11(3):134-9.
19. Uitterlinden AG, Fang Y, van Meurs JB, Pols HA, van Leeuwen JP. Genetics and biology of vitamin D receptor polymorphisms. Gene. 2004;338(2):143-56.
20. Roth SM, Zmuda JM, Cauley JA, Shea PR, Ferrell RE. Vitamin D receptor genotype is associated with fat-free mass and sarcopenia in elderly men. J Gerontol A Biol Sci Med Sci. 2004;59(1):10-5.
21. Shab-Bidar S, Neyestani TR, Djazayery A. Efficacy of vitamin D3-fortified-yogurt drink on anthropometric, metabolic, inflammatory and oxidative stress biomarkers according to vitamin D receptor gene polymorphisms in type 2 diabetic patients: a study protocol for a randomized controlled clinical trial. BMC Endocr Disord. 2011; 11:12.
22. Shab-Bidar S, Neyestani TR, Djazayery A, Eshraghian M-R, Houshiarrad A, Gharavi Aa, et al. Regular consumption of vitamin D-fortified yogurt drink (Doogh) improved endothelial biomarkers in subjects with type 2 diabetes: a randomized double-blind clinical trial. BMC Med. 2011; 9:125.
23. Shab-Bidar S, Neyestani TR, Djazayery A. Vitamin D receptor Cdx-2-dependent response of central obesity to vitamin D intake in the subjects with type 2 diabetes: a randomised clinical trial. Br J Nutr. 2015;114(9):1375-84.
24. Slusher AL, McAllister MJ, Huang CJ. A therapeutic role for vitamin D on obesity-associated inflammation and weight-loss intervention. Inflamm Res. 2015;64(8):565-75.
25. Akiyama M, Okada Y, Kanai M, Takahashi A, Momozawa Y, Ikeda M, et al. Genome-wide association study identifies 112 new loci for body mass index in the Japanese population. Nat Genet. 2017;49(10):1458-1467.
26. Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. 2006;444(7121):840-6.
27. Liefaard MC, Ligthart S, Vitezova A, Hofman A, Uitterlinden AG, Kiefte-de Jong JC, et al. Vitamin D and C-reactive protein: a Mendelian randomization study. PLoS One. 2015;10(7):e0131740.
28. Blum M, Dolnikowski G, Seyoum E, Harris SS, Booth SL, Peterson J, et al. Vitamin D (3) in fat tissue. Endocrine. 2008;33(1):90-4.
29. Rafiq S, Jeppesen PB. Is hypovitaminosis D related to incidence of type 2 diabetes and high fasting glucose level in healthy subjects: a systematic review and meta-analysis of observational studies. Nutrients. 2018;10(1):59.
30. Rosenblum JL, Castro VM, Moore CE, Kaplan LM. Calcium and vitamin D supplementation is associated with decreased abdominal visceral adipose tissue in overweight and obese adults. Am J Clin Nutr. 2012;95(1):101-8.
31. McGill AT, Stewart JM, Lithander FE, Strik CM, Poppitt SD. Relationships of low serum vitamin D 3 with anthropometry and markers of the metabolic syndrome and diabetes in overweight and obesity. Nutr J. 2008; 7:4.
32. Cheng S, Massaro JM, Fox CS, Larson MG, Keyes MJ, McCabe EL, et al. Adiposity, cardiometabolic risk, and vitamin D status: the Framingham Heart Study. Diabetes. 2010;59(1):242-8.
33. Pou KM, Massaro JM, Hoffmann U, Lieb K, Vasan RS, O'donnell CJ, et al. Patterns of abdominal fat distribution: the Framingham Heart Study. Diabetes care. 2009;32(3):481-5.
34. Al-Rubeaan K, Siddiqui K, Saeb AT, Nazir N, Al-Naqeb D, Al-Qasim S. ACE I/D and MTHFR C677T polymorphisms are significantly associated with type 2 diabetes in Arab ethnicity: a meta-analysis. Gene. 2013;520(2):166-77.
35. Shea MK, Benjamin EJ, Dupuis J, Massaro JM, Jacques PF, D'Agostino Sr RB, et al. Genetic and non-genetic correlates of vitamins K and D. Eur J Clin Nutr. 2009;63(4):458-64.
36. Nosratabadi R, Arababadi MK, Salehabad VA, Shamsizadeh A, Mahmoodi M, Sayadi AR, et al. Polymorphisms within exon 9 but not intron 8 of the vitamin D receptor are associated with the nephropathic complication of type‐2 diabetes. Int J Immunogenet. 2010;37(6):493-7.
37. Speer G, Cseh K, Winkler G, Vargha P, Braun E, Takacs I, et al. Vitamin D and estrogen receptor gene polymorphisms in type 2 diabetes mellitus and in android type obesity. Eur J Endocrinol. 2001;144(4):385-9.
38. Walsh S, Ludlow AT, Metter EJ, Ferrucci L, Roth SM. Replication study of the vitamin D receptor (VDR) genotype association with skeletal muscle traits and sarcopenia. Aging Clin Exp Res. 2016;28(3):435-42.
39. Ochs-Balcom HM, Chennamaneni R, Millen AE, Shields PG, Marian C, Trevisan M, et al. Vitamin D receptor gene polymorphisms are associated with adiposity phenotypes. Am J Clin Nutr. 2011; 93(1):5-10.
2. Kriska AM, LaPorte RE, Patrick SL, Kuller LH, Orchard TJ. The association of physical activity and diabetic complications in individuals with insulin-dependent diabetes mellitus: the Epidemiology of Diabetes Complications Study--VII. J Clin Epidemiol. 1991;44(11):1207-14.
3. Traversy G, Chaput JP. Alcohol Consumption and Obesity: An Update. Curr Obes Rep. 2015;4(1):122-30.
4. Saha SK, Panwar R, Kumar A, Pal S, Ahuja V, Dash NR, et al. Early colectomy in steroid-refractory acute severe ulcerative colitis improves operative outcome. Int J Colorectal Dis. 2018;33(1):79-82.
5. Van Leiden HA, Dekker JM, Moll AC, Nijpels G, Heine RJ, Bouter LM, et al. Blood pressure, lipids, and obesity are associated with retinopathy: the hoorn study. Diabetes care. 2002;25(8):1320-5.
6. DeFronzo RA. Pathogenesis of type 2 diabetes mellitus. Med Clin North Am. 2004;88(4):787-835.
7. Molarius A, Seidell J. Selection of anthropometric indicators for classification of abdominal fatness—a critical review. Int J Obes Relat Metab Disord. 1998;22(8):719-27.
8. Allison DB, Kaprio J, Korkeila M, Koskenvuo M, Neale MC, Hayakawa K. The heritability of body mass index among an international sample of monozygotic twins reared apart. Int J Obes Relat Metab Disord. 1996;20(6):501-6.
9. Dennis KE. Postmenopausal women and the health consequences of obesity. J Obstet Gynecol Neonatal Nurs. 2007;36(5):511-7.
10. Pourshahidi LK. Vitamin D and obesity: current perspectives and future directions. Proc Nutr Soc. 2015;74(2):115-24.
11. Pereira‐Santos M, Costa PR, Assis AM, Santos CA, Santos DB. Obesity and vitamin D deficiency: a systematic review and meta‐analysis. Obes Rev. 2015;16(4):341-9.
12. Vanlint S. Vitamin D and obesity. Nutrients. 2013;5(3):949-56.
13. Verstuyf A, Carmeliet G, Bouillon R, Mathieu C. Vitamin D: a pleiotropic hormone. Kidney Int. 2010;78(2):140-5.
14. Sun J. Vitamin D and mucosal immune function. Curr Opin Gastroenterol. 2010;26(6):591-5.
15. Palomer X, González‐Clemente J, Blanco‐Vaca F, Mauricio D. Role of vitamin D in the pathogenesis of type 2 diabetes mellitus. Diabetes Obes Metab. 2008;10(3):185-97.
16. Norman AW, Frankel JB, Heldt AM, Grodsky GM. Vitamin D deficiency inhibits pancreatic secretion of insulin. Science. 1980;209(4458):823-5.
17. Kumar S, Davies M, Zakaria Y, Mawer EB, Gordon C, Olukoga AO, et al. Improvement in glucose tolerance and beta-cell function in a patient with vitamin D deficiency during treatment with vitamin D. Postgrad Med J. 1994;70(824):440-3.
18. Filus A, Trzmiel A, Kuliczkowska-Płaksej J, Tworowska U, Jędrzejuk D, Milewicz A, et al. Relationship between vitamin D receptor BsmI and FokI polymorphisms and anthropometric and biochemical parameters describing metabolic syndrome. Aging Male. 2008;11(3):134-9.
19. Uitterlinden AG, Fang Y, van Meurs JB, Pols HA, van Leeuwen JP. Genetics and biology of vitamin D receptor polymorphisms. Gene. 2004;338(2):143-56.
20. Roth SM, Zmuda JM, Cauley JA, Shea PR, Ferrell RE. Vitamin D receptor genotype is associated with fat-free mass and sarcopenia in elderly men. J Gerontol A Biol Sci Med Sci. 2004;59(1):10-5.
21. Shab-Bidar S, Neyestani TR, Djazayery A. Efficacy of vitamin D3-fortified-yogurt drink on anthropometric, metabolic, inflammatory and oxidative stress biomarkers according to vitamin D receptor gene polymorphisms in type 2 diabetic patients: a study protocol for a randomized controlled clinical trial. BMC Endocr Disord. 2011; 11:12.
22. Shab-Bidar S, Neyestani TR, Djazayery A, Eshraghian M-R, Houshiarrad A, Gharavi Aa, et al. Regular consumption of vitamin D-fortified yogurt drink (Doogh) improved endothelial biomarkers in subjects with type 2 diabetes: a randomized double-blind clinical trial. BMC Med. 2011; 9:125.
23. Shab-Bidar S, Neyestani TR, Djazayery A. Vitamin D receptor Cdx-2-dependent response of central obesity to vitamin D intake in the subjects with type 2 diabetes: a randomised clinical trial. Br J Nutr. 2015;114(9):1375-84.
24. Slusher AL, McAllister MJ, Huang CJ. A therapeutic role for vitamin D on obesity-associated inflammation and weight-loss intervention. Inflamm Res. 2015;64(8):565-75.
25. Akiyama M, Okada Y, Kanai M, Takahashi A, Momozawa Y, Ikeda M, et al. Genome-wide association study identifies 112 new loci for body mass index in the Japanese population. Nat Genet. 2017;49(10):1458-1467.
26. Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. 2006;444(7121):840-6.
27. Liefaard MC, Ligthart S, Vitezova A, Hofman A, Uitterlinden AG, Kiefte-de Jong JC, et al. Vitamin D and C-reactive protein: a Mendelian randomization study. PLoS One. 2015;10(7):e0131740.
28. Blum M, Dolnikowski G, Seyoum E, Harris SS, Booth SL, Peterson J, et al. Vitamin D (3) in fat tissue. Endocrine. 2008;33(1):90-4.
29. Rafiq S, Jeppesen PB. Is hypovitaminosis D related to incidence of type 2 diabetes and high fasting glucose level in healthy subjects: a systematic review and meta-analysis of observational studies. Nutrients. 2018;10(1):59.
30. Rosenblum JL, Castro VM, Moore CE, Kaplan LM. Calcium and vitamin D supplementation is associated with decreased abdominal visceral adipose tissue in overweight and obese adults. Am J Clin Nutr. 2012;95(1):101-8.
31. McGill AT, Stewart JM, Lithander FE, Strik CM, Poppitt SD. Relationships of low serum vitamin D 3 with anthropometry and markers of the metabolic syndrome and diabetes in overweight and obesity. Nutr J. 2008; 7:4.
32. Cheng S, Massaro JM, Fox CS, Larson MG, Keyes MJ, McCabe EL, et al. Adiposity, cardiometabolic risk, and vitamin D status: the Framingham Heart Study. Diabetes. 2010;59(1):242-8.
33. Pou KM, Massaro JM, Hoffmann U, Lieb K, Vasan RS, O'donnell CJ, et al. Patterns of abdominal fat distribution: the Framingham Heart Study. Diabetes care. 2009;32(3):481-5.
34. Al-Rubeaan K, Siddiqui K, Saeb AT, Nazir N, Al-Naqeb D, Al-Qasim S. ACE I/D and MTHFR C677T polymorphisms are significantly associated with type 2 diabetes in Arab ethnicity: a meta-analysis. Gene. 2013;520(2):166-77.
35. Shea MK, Benjamin EJ, Dupuis J, Massaro JM, Jacques PF, D'Agostino Sr RB, et al. Genetic and non-genetic correlates of vitamins K and D. Eur J Clin Nutr. 2009;63(4):458-64.
36. Nosratabadi R, Arababadi MK, Salehabad VA, Shamsizadeh A, Mahmoodi M, Sayadi AR, et al. Polymorphisms within exon 9 but not intron 8 of the vitamin D receptor are associated with the nephropathic complication of type‐2 diabetes. Int J Immunogenet. 2010;37(6):493-7.
37. Speer G, Cseh K, Winkler G, Vargha P, Braun E, Takacs I, et al. Vitamin D and estrogen receptor gene polymorphisms in type 2 diabetes mellitus and in android type obesity. Eur J Endocrinol. 2001;144(4):385-9.
38. Walsh S, Ludlow AT, Metter EJ, Ferrucci L, Roth SM. Replication study of the vitamin D receptor (VDR) genotype association with skeletal muscle traits and sarcopenia. Aging Clin Exp Res. 2016;28(3):435-42.
39. Ochs-Balcom HM, Chennamaneni R, Millen AE, Shields PG, Marian C, Trevisan M, et al. Vitamin D receptor gene polymorphisms are associated with adiposity phenotypes. Am J Clin Nutr. 2011; 93(1):5-10.
| Files | ||
| Issue | Vol 4, No 4 (Autumn 2018) | |
| Section | Original Article(s) | |
| Keywords | ||
| Vitamin D Adiposity Visceral fat Type 2 diabetes Vitamin D receptor polymorphism | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Tangestani H, Shab-Bidar S. Association between FokI Vitamin D Receptor Gene Polymorphism and Visceral Obesity in Patients with Type 2 Diabetes: A Single-Blinded Randomised Clinical Trial. J Nutr Sci & Diet. 2018;4(4):132-138.
