Horm Metab Res 2018; 50(01): 56-64
DOI: 10.1055/s-0043-122144
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Serum Vitamin D Status, Vitamin D Receptor Polymorphism, and Glucose Homeostasis in Healthy Subjects

Otto Mayer
1   2nd Department of Internal Medicine, Medical Faculty of Charles University and University Hospital, Pilsen, Czech Republic
2   Biomedical Center, Medical Faculty of Charles University, Pilsen, Czech Republic
,
Jitka Seidlerová
1   2nd Department of Internal Medicine, Medical Faculty of Charles University and University Hospital, Pilsen, Czech Republic
2   Biomedical Center, Medical Faculty of Charles University, Pilsen, Czech Republic
,
Václava Černá
2   Biomedical Center, Medical Faculty of Charles University, Pilsen, Czech Republic
3   Department of Biology, Medical Faculty of Charles University, Pilsen, Czech Republic
,
Alena Kučerová
2   Biomedical Center, Medical Faculty of Charles University, Pilsen, Czech Republic
3   Department of Biology, Medical Faculty of Charles University, Pilsen, Czech Republic
,
Petra Karnosová
1   2nd Department of Internal Medicine, Medical Faculty of Charles University and University Hospital, Pilsen, Czech Republic
,
Markéta Hronová
1   2nd Department of Internal Medicine, Medical Faculty of Charles University and University Hospital, Pilsen, Czech Republic
,
Peter Wohlfahrt
4   Centre for Cardiovascular Prevention of the First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic
,
Radka Fuchsová
5   Department of Immunodiagnostics, University Hospital, Pilsen, Czech Republic
,
Jan Filipovský
1   2nd Department of Internal Medicine, Medical Faculty of Charles University and University Hospital, Pilsen, Czech Republic
2   Biomedical Center, Medical Faculty of Charles University, Pilsen, Czech Republic
,
Renata Cífková
4   Centre for Cardiovascular Prevention of the First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic
,
Ondřej Topolčan
5   Department of Immunodiagnostics, University Hospital, Pilsen, Czech Republic
,
Martin Pešta
2   Biomedical Center, Medical Faculty of Charles University, Pilsen, Czech Republic
3   Department of Biology, Medical Faculty of Charles University, Pilsen, Czech Republic
› Author Affiliations
Further Information

Publication History

received 14 September 2017

accepted 18 October 2017

Publication Date:
28 November 2017 (online)

Abstract

Low vitamin D status has been frequently associated with impaired glucose metabolism. We examined associations between 25-hydroxyvitamin D (25-OH-D) and several parameters of glucose homeostasis in virtually healthy subjects, and explored possible interaction with vitamin D receptor (VDR) polymorphism. Nondiabetic subjects without chronic medication or any known significant manifest disease were selected from large general-population based population survey. Insulin sensitivity and β cell secretion were calculated by homeostasis model assessment (HOMA) and soluble isoform of receptor for advanced glycation end-products (sRAGE) using commercial ELISA. Subjects were also genotyped for rs2228570 polymorphism of VDR. After adjustment for potential confounders, we observed a significant relationship between 25-OH-D and fasting glycemia (β coefficient=–5.904; p=0.002) or insulin sensitivity (β=0.042; p=0.001), but not with β cell secretion or sRAGE. We found also an interaction with VDR polymorphism. Subjects with low 25-OH-D and AA genotype had significantly lower insulin sensitivity than those with GG genotype plus highest 25-OH-D concentrations (107.3% vs. 183.9%, p=0.021). In conclusion, low vitamin D status was in virtually healthy subjects associated with decreased insulin sensitivity, namely in those with GG genotype of rs2228570 VDR polymorphism.

 
  • References

  • 1 Jain SK, Micinski D, Huning L, Kahlon G, Bass PF, Levine SN. Vitamin D and L-cysteine levels correlate positively with GSH and negatively with insulin resistance levels in the blood of type 2 diabetic patients. Eur J Clin Nutr 2014; 68: 1148-1153
  • 2 Esteghamati A, Aryan Z, Nakhjavani M. Vitamin D deficiency is associated with insulin resistance in nondiabetics and reduced insulin production in type 2 diabetics. Horm Metab Res 2015; 47: 273-279
  • 3 Dutta D, Maisnam I, Shrivastava A, Sinha A, Ghosh S, Mukhopadhyay P, Mukhopadhyay S, Chowdhury S. Serum Vitamin-D predicts insulin resistance in individuals with prediabetes. Indian J Med Res 2013; 138: 853-860
  • 4 Song Y, Wang L, Pittas AG, Del Gobbo LC, Zhang C, Manson JE, Hu FB. Blood 25-hydroxy vitamin D levels and incident type 2 diabetes: A meta-analysis of prospective studies. Diabetes Care 2013; 36: 1422-1428
  • 5 Maestro B, Dávila N, Carranza MC, Calle C. Identification of a Vitamin D response element in the human insulin receptor gene promoter. J Steroid Biochem Mol Biol 2003; 84: 223-230
  • 6 Park S, Kim dS, Kang S. Vitamin D deficiency impairs glucose-stimulated insulin secretion and increases insulin resistance by reducing PPAR-g expression in nonobese Type 2 diabetic rats. J Nutr Biochem 2016; 27: 257-265
  • 7 Chen S, Villalta SA, Agrawal DK. FOXO1 Mediates Vitamin D Deficiency-Induced Insulin Resistance in Skeletal Muscle. J Bone Miner Res 2016; 31: 585-595
  • 8 Ashraf AP, Huisingh C, Alvarez JA, Wang X, Gower BA. Insulin resistance indices are inversely associated with vitamin D binding protein concentrations. J Clin Endocrinol Metab 2014; 99: 178-183
  • 9 Miraglia del Giudice E, Grandone A, Cirillo G, Capristo C, Marzuillo P, Di Sessa A, Umano GR, Ruggiero L, Perrone L. Bioavailable Vitamin D in Obese children: The role of insulin resistance. J Clin Endocrinol Metab 2015; 100: 3949-3955
  • 10 Sugden JA, Davies JI, Witham MD, Morris AD, Struthers AD. Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low vitamin D levels. Diabet Med 2008; 25: 320-325
  • 11 Dutta D, Mondal SA, Choudhuri S, Maisnam I, Hasanoor Reza AH, Bhattacharya B, Chowdhury S, Mukhopadhyay S. Vitamin-D supplementation in prediabetes reduced progression to type 2 diabetes and was associated with decreased insulin resistance and systemic inflammation: An open label randomized prospective study from Eastern India. Diabetes Res Clin Pract 2014; 103: e18-e23
  • 12 Cardus A, Panizo S, Encinas M, Dolcet X, Gallego C, Aldea M, Fernandez E, Valdivielso JM. 1,25-dihydroxyvitamin D3 regulates VEGF production through a vitamin D response element in the VEGF promoter. Atherosclerosis 2009; 204: 85-89
  • 13 Forman JP, Williams JS, Fisher ND. Plasma 25-hydroxyvitamin D and regulation of the renin-angiotensin system in humans. Hypertension 2010; 55: 1283-1288
  • 14 Mayer Jr. O, Filipovsky J, Seidlerova J, Vanek J, Dolejsova M, Vrzalova J, Cifkova R. The association between low 25-hydroxyvitamin D and increased aortic stiffness. J Hum Hypertens 2012; 26: 650-655
  • 15 Saijo T, Ito M, Takeda E, Huq AH, Naito E, Yokota I, Sone T, Pike JW, Kuroda Y. A unique mutation in the vitamin D receptor gene in three Japanese patients with vitamin D-dependent rickets type II: Utility of single-strand conformation polymorphism analysis for heterozygous carrier detection. Am J Hum Genet 1991; 49: 668-673
  • 16 Yu F, Cui LL, Li X, Wang CJ, Ba Y, Wang L, Li J, Li C, Dai LP, Li WJ. The genetic polymorphisms in vitamin D receptor and the risk of type 2 diabetes mellitus: An updated meta-analysis. Asia Pac J Clin Nutr 2016; 25: 614-624
  • 17 Bertoccini L, Sentinelli F, Leonetti F, Bailetti D, Capoccia D, Cimini FA, Barchetta I, Incani M, Lenzi A, Cossu E, Cavallo MG, Baroni MG. The vitamin D receptor functional variant rs2228570 (C>T) does not associate with type 2 diabetes mellitus. Endocr Res 2017; 1-5
  • 18 Chiu KC, Chuang LM, Yoon C. The vitamin D receptor polymorphism in the translation initiation codon is a risk factor for insulin resistance in glucose tolerant Caucasians. BMC Med Genet 2001; 2: 2
  • 19 Filus A, Trzmiel A, Kuliczkowska-Plaksej J, Tworowska U, Jedrzejuk D, Milewicz A, Medras M. Relationship between vitamin D receptor BsmI and FokI polymorphisms and anthropometric and biochemical parameters describing metabolic syndrome. Aging Male 2008; 11: 134-139
  • 20 Schleicher ED, Wagner E, Nerlich AG. Increased accumulation of the glycoxidation product N(epsilon)-(carboxymethyl)lysine in human tissues in diabetes and aging. J Clin Invest 1997; 99: 457-468
  • 21 Park L, Raman KG, Lee KJ, Lu Y, Ferran Jr. LJ, Chow WS, Stern D, Schmidt AM. Suppression of accelerated diabetic atherosclerosis by the soluble receptor for advanced glycation endproducts. Nat Med 1998; 4: 1025-1031
  • 22 Yamagishi S, Matsui T. Soluble form of a receptor for advanced glycation end products (sRAGE) as a biomarker. Front Biosci (Elite Ed) 2010; 2: 1184-1195
  • 23 Cífková R, Skodová Z, Bruthans J, Adámková V, Jozífová M, Galovcová M, Wohlfahrt P, Krajcoviechová A, Poledne R, Stávek P, Lánská V. Longitudinal trends in major cardiovascular risk factors in the Czech population between 1985 and 2007/8. Czech MONICA and Czech post-MONICA. Atherosclerosis 2010; 211: 676-681
  • 24 Kotseva K, Wood D, De Bacquer D, De Backer G, Ryden L, Jennings C, Gyberg V, Amouyel P, Bruthans J, Castro Conde A, Cifkova R, Deckers JW, De Sutter J, Dilic M, Dolzhenko M, Erglis A, Fras Z, Gaita D, Gotcheva N, Goudevenos J, Heuschmann P, Laucevicius A, Lehto S, Lovic D, Milicic D, Moore D, Nicolaides E, Oganov R, Pajak A, Pogosova N, Reiner Z, Stagmo M, Stork S, Tokgozoglu L, Vulic D. Eurospire Investigators. EUROASPIRE IV: A european society of cardiology survey on the lifestyle, risk factor and therapeutic management of coronary patients from 24 European countries. Eur J Prev Cardiol 2016; 23: 636-648
  • 25 Levy JC, Matthews DR, Hermans MP. Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care 1998; 21: 2191-2192
  • 26 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419
  • 27 Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999; 130: 461-470
  • 28 Perk J, De Backer G, Gohlke H, Graham I, Reiner Z, Verschuren M, Albus C, Benlian P, Boysen G, Cifkova R, Deaton C, Ebrahim S, Fisher M, Germano G, Hobbs R, Hoes A, Karadeniz S, Mezzani A, Prescott E, Ryden L, Scherer M, Syvänne M, Scholte op, Reimer WJ, Vrints C, Wood D, Zamorano JL, Zannad F. (EACPR) EAfCPaR, (CPG) ECfPG. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The fifth joint task force of the european society of cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts). Eur Heart J 2012 33: 1635-1701
  • 29 Vaccaro O, Riccardi G. Changing the definition of impaired fasting glucose: impact on the classification of individuals and risk definition. Diabetes Care 2005; 28: 1786-1788
  • 30 Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357: 266-281
  • 31 Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC. Prevention IDFTFoEa, Hational Heart Ln, and Blood Institute, Association AH, Federation WH, Society IA, Obesity IAftSo. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009; 120: 1640-1645
  • 32 Chung SJ, Lee YA, Hong H, Kang MJ, Kwon HJ, Shin CH, Yang SW. Inverse relationship between vitamin D status and insulin resistance and the risk of impaired fasting glucose in Korean children and adolescents: The Korean National Health and Nutrition Examination Survey (KNHANES) 2009-2010. Public Health Nutr 2014; 17: 795-802
  • 33 Feng R, Li Y, Li G, Li Z, Zhang Y, Li Q, Sun C. Lower serum 25 (OH) D concentrations in type 1 diabetes: A meta-analysis. Diabetes Res Clin Pract 2015; 108: e71-e75
  • 34 Qin WH, Wang HX, Qiu JL, Huang XB, Huang Y, Wu NR, Liang HS. A meta-analysis of association of vitamin D receptor BsmI gene polymorphism with the risk of type 1 diabetes mellitus. J Recept Signal Transduct Res 2014; 34: 372-377
  • 35 Abbasi F, Blasey C, Feldman D, Caulfield MP, Hantash FM, Reaven GM. Low circulating 25-hydroxyvitamin D concentrations are associated with defects in insulin action and insulin secretion in persons with prediabetes. J Nutr 2015; 145: 714-719
  • 36 Mitchell DM, Leder BZ, Cagliero E, Mendoza N, Henao MP, Hayden DL, Finkelstein JS, Burnett-Bowie SA. Insulin secretion and sensitivity in healthy adults with low vitamin D are not affected by high-dose ergocalciferol administration: A randomized controlled trial. Am J Clin Nutr 2015; 102: 385-392
  • 37 Gagnon C, Daly RM, Carpentier A, Lu ZX, Shore-Lorenti C, Sikaris K, Jean S, Ebeling PR. Effects of combined calcium and vitamin D supplementation on insulin secretion, insulin sensitivity and b-cell function in multi-ethnic vitamin D-deficient adults at risk for type 2 diabetes: A pilot randomized, placebo-controlled trial. PLoS One 2014; 9: e109607
  • 38 Filus A, Trzmiel A, Kuliczkowska-Płaksej J, Tworowska U, Jedrzejuk D, Milewicz A, Medraś M. Relationship between vitamin D receptor BsmI and FokI polymorphisms and anthropometric and biochemical parameters describing metabolic syndrome. Aging Male 2008; 11: 134-139
  • 39 Jain R, von Hurst PR, Stonehouse W, Love DR, Higgins CM, Coad J. Association of vitamin D receptor gene polymorphisms with insulin resistance and response to vitamin D. Metabolism 2012; 61: 293-301
  • 40 George PS, Pearson ER, Witham MD. Effect of vitamin D supplementation on glycaemic control and insulin resistance: A systematic review and meta-analysis. Diabet Med 2012; 29: e142-e150
  • 41 de Boer IH, Tinker LF, Connelly S, Curb JD, Howard BV, Kestenbaum B, Larson JC, Manson JE, Margolis KL, Siscovick DS, Weiss NS. Calcium plus vitamin D supplementation and the risk of incident diabetes in the Women's Health Initiative. Diabetes Care 2008; 31: 701-707
  • 42 Seida JC, Mitri J, Colmers IN, Majumdar SR, Davidson MB, Edwards AL, Hanley DA, Pittas AG, Tjosvold L, Johnson JA. Clinical review: Effect of vitamin D3 supplementation on improving glucose homeostasis and preventing diabetes: A systematic review and meta-analysis. J Clin Endocrinol Metab 2014; 99: 3551-3560
  • 43 Sturmer M, Sebekova K, Fazeli G, Bahner U, Stab F, Heidland A. 25-hydroxyvitamin d and advanced glycation endproducts in healthy and hypertensive subjects: Are there interactions?. J Ren Nutr 2015; 25: 209-216
  • 44 Irani M, Minkoff H, Seifer DB, Merhi Z. Vitamin D increases serum levels of the soluble receptor for advanced glycation end products in women with PCOS. J Clin Endocrinol Metab 2014; 99: E886-E890
  • 45 Sung JY, Chung W, Kim AJ, Kim HS, Ro H, Chang JH, Lee HH, Jung JY. Calcitriol treatment increases serum levels of the soluble receptor of advanced glycation end products in hemodialysis patients with secondary hyperparathyroidism. Tohoku J Exp Med 2013; 230: 59-66