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Relations of vitamin D status, gender and type 2 diabetes in middle-aged Caucasians

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Abstract

Vitamin D (Vit D) deficiency may be linked to the development of obesity-associated complications such as insulin resistance and type 2 diabetes. We therefore evaluated the relationship of Vit D serum concentrations with metabolic parameters and type 2 diabetes in middle-aged Caucasian men and women. One thousand six hundred and thirty-one Caucasians (832 males, 58.8 ± 9.7 years; 799 females, 59.7 ± 10.7 years) were evaluated in a cross-sectional study. Vit D status was assessed by measuring the serum concentration of 25-hydroxyvitamin D3 [25(OH)D3]. Type 2 diabetes prevalence was ascertained by medical history, fasting plasma glucose concentrations, oral glucose tolerance testing and/or glycosylated hemoglobin. Men displayed higher crude or seasonally adjusted 25(OH)D3 serum concentrations than women (24.64 ± 10.98 vs. 22.88 ± 11.6 ng/ml; P < 0.001). Strong associations between body mass index (BMI) and 25(OH)D3 were observed in both genders (P < 0.001). Seasonally adjusted levels of 25(OH)D3 revealed stronger associations with type 2 diabetes in women than men (P < 0.001). However, adjustment for BMI and other confounding variables revealed an independent inverse association of 25(OH)D3 with diabetes only in women (P < 0.001), whereas the association was abrogated in men. Using a 15 ng/ml 25(OH)D3 cutoff for binary comparison, adjusted odds ratios for having newly diagnosed or known type 2 diabetes more than doubled (2.95 [95 % CI 1.37–4.89] and 3.26 [1.59–6.68], respectively), in women below the cutoff. We conclude that in women, but not in men, low 25(OH)D3 serum levels are independently associated with type 2 diabetes. These findings suggest sex-specific effects of Vit D in the pathogenesis of type 2 diabetes.

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References

  1. Holick MF (2007) Vitamin D deficiency. N Engl J Med 357(3):266–281. doi:10.1056/NEJMra070553

    Article  CAS  PubMed  Google Scholar 

  2. Holick MF, Chen TC (2008) Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr 87(4):1080S–1086S

    CAS  PubMed  Google Scholar 

  3. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) (2001) Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA 285(19):2486–2497

  4. Martini LA, Wood RJ (2006) Vitamin D status and the metabolic syndrome. Nutr Rev 64(11):479–486

    Article  PubMed  Google Scholar 

  5. Hypponen E, Power C (2006) Vitamin D status and glucose homeostasis in the 1958 British birth cohort: the role of obesity. Diabetes Care 29(10):2244–2246. doi:10.2337/dc06-0946

    Article  CAS  PubMed  Google Scholar 

  6. Kositsawat J, Freeman VL, Gerber BS, Geraci S (2010) Association of A1C levels with vitamin D status in U.S. adults: data from the national health and nutrition examination survey. Diabetes Care 33(6):1236–1238. doi:10.2337/dc09-2150

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Knekt P, Laaksonen M, Mattila C, Harkanen T, Marniemi J, Heliovaara M, Rissanen H, Montonen J, Reunanen A (2008) Serum vitamin D and subsequent occurrence of type 2 diabetes. Epidemiology 19(5):666–671. doi:10.1097/EDE.0b013e318176b8ad

    Article  PubMed  Google Scholar 

  8. Grimnes G, Emaus N, Joakimsen RM, Figenschau Y, Jenssen T, Njolstad I, Schirmer H, Jorde R (2010) Baseline serum 25-hydroxyvitamin D concentrations in the Tromso Study 1994–95 and risk of developing type 2 diabetes mellitus during 11 years of follow-up. Diabetic Med J Br Diabetic Assoc 27(10):1107–1115. doi:10.1111/j.1464-5491.2010.03092.x

    Article  CAS  Google Scholar 

  9. Parker J, Hashmi O, Dutton D, Mavrodaris A, Stranges S, Kandala NB, Clarke A, Franco OH (2010) Levels of vitamin D and cardiometabolic disorders: systematic review and meta-analysis. Maturitas 65(3):225–236. doi:10.1016/j.maturitas.2009.12.013

    Article  CAS  PubMed  Google Scholar 

  10. Robinson JG, Manson JE, Larson J, Liu S, Song Y, Howard BV, Phillips L, Shikany JM, Allison M, Curb JD, Johnson KC, Watts N (2011) Lack of association between 25(OH)D levels and incident type 2 diabetes in older women. Diabetes Care 34(3):628–634. doi:10.2337/dc10-1632

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Pilz S, van den Hurk K, Nijpels G, Stehouwer CD, Van’t Riet E, Kienreich K, Tomaschitz A, Dekker JM (2012) Vitamin D status, incident diabetes and prospective changes in glucose metabolism in older subjects: the Hoorn study. Nutr Metab Cardiovasc Dis 22(10):883–889. doi:10.1016/j.numecd.2012.03.008

    Article  CAS  PubMed  Google Scholar 

  12. Rosenblum JL, Castro VM, Moore CE, Kaplan LM (2012) Calcium and vitamin D supplementation is associated with decreased abdominal visceral adipose tissue in overweight and obese adults. Am J Clin Nutr 95(1):101–108. doi:10.3945/ajcn.111.019489

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Song Y, Wang L, Pittas AG, Del Gobbo LC, Zhang C, Manson JE, Hu FB (2013) Blood 25-hydroxy vitamin D levels and incident type 2 diabetes: a meta-analysis of prospective studies. Diabetes Care 36(5):1422–1428. doi:10.2337/dc12-0962

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Lee BK, Park S, Kim Y (2012) Age- and gender-specific associations between low serum 25-hydroxyvitamin D level and type 2 diabetes in the Korean general population: analysis of 2008–2009 korean national health and nutrition examination survey data. Asia Pac J Clin Nutr 21(4):536–546

    CAS  PubMed  Google Scholar 

  15. Stadlmayr A, Aigner E, Steger B, Scharinger L, Lederer D, Mayr A, Strasser M, Brunner E, Heuberger A, Hohla F, Steinwendner J, Patsch W, Datz C (2011) Nonalcoholic fatty liver disease: an independent risk factor for colorectal neoplasia. J Intern Med 270(1):41–49. doi:10.1111/j.1365-2796.2011.02377.x

    Article  CAS  PubMed  Google Scholar 

  16. Craig CL, Marshall AL, Sjostrom M, Bauman AE, Booth ML, Ainsworth BE, Pratt M, Ekelund U, Yngve A, Sallis JF, Oja P (2003) International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc 35(8):1381–1395. doi:10.1249/01.MSS.0000078924.61453.FB

    Article  PubMed  Google Scholar 

  17. Hahne P, Krempler F, Schaap FG, Soyal SM, Hoffinger H, Miller K, Oberkofler H, Strobl W, Patsch W (2008) Determinants of plasma apolipoprotein A-V and APOA5 gene transcripts in humans. J Intern Med 264(5):452–462. doi:10.1111/j.1365-2796.2008.01987.x

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Gillett MJ (2009) International expert committee report on the role of the A1c assay in the diagnosis of diabetes: Diabetes Care 32(7):1327–1334 (Clin Biochem Rev Aust Assoc Clin Biochem 30(4):197–200)

  19. Niederseer D, Ledl-Kurkowski E, Kvita K, Patsch W, Dela F, Mueller E, Niebauer J (2011) Salzburg skiing for the elderly study: changes in cardiovascular risk factors through skiing in the elderly. Scand J Med Sci Sports 21(Suppl 1):47–55. doi:10.1111/j.1600-0838.2011.01341.x

    Article  PubMed  Google Scholar 

  20. Ding C, Gao D, Wilding J, Trayhurn P, Bing C (2012) Vitamin D signalling in adipose tissue. Br J Nutr 108(11):1915–1923. doi:10.1017/S0007114512003285

    Article  CAS  PubMed  Google Scholar 

  21. Uberti F, Lattuada D, Morsanuto V, Nava U, Bolis G, Vacca G, Squarzanti DF, Cisari C, Molinari C (2013) Vitamin D protects human endothelial cells from oxidative stress through the autophagic and survival pathways. J Clin Endocrinol Metab. doi:10.1210/jc.2013-2103

  22. Cross HS, Bises G, Lechner D, Manhardt T, Kallay E (2005) The vitamin D endocrine system of the gut—its possible role in colorectal cancer prevention. J Steroid Biochem Mol Biol 97(1–2):121–128. doi:10.1016/j.jsbmb.2005.06.005

    Article  CAS  PubMed  Google Scholar 

  23. Clark SA, Stumpf WE, Sar M, DeLuca HF, Tanaka Y (1980) Target cells for 1,25 dihydroxyvitamin D3 in the pancreas. Cell Tissue Res 209(3):515–520

    Article  CAS  PubMed  Google Scholar 

  24. Brozek W, Manhardt T, Kallay E, Peterlik M, Cross HS (2012) Relative expression of vitamin D hydroxylases, CYP27B1 and CYP24A1, and of cyclooxygenase-2 and heterogeneity of human colorectal cancer in relation to age, gender, tumor location, and malignancy: results from factor and cluster analysis. Cancers 4(3):763–776. doi:10.3390/cancers4030763

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Gagnon C, Lu ZX, Magliano DJ, Dunstan DW, Shaw JE, Zimmet PZ, Sikaris K, Ebeling PR, Daly RM (2012) Low serum 25-hydroxyvitamin D is associated with increased risk of the development of the metabolic syndrome at five years: results from a national, population-based prospective study (The Australian diabetes, obesity and lifestyle study: AusDiab). J Clin Endocrinol Metab 97(6):1953–1961. doi:10.1210/jc.2011-3187

    Article  CAS  PubMed  Google Scholar 

  26. Heaney RP, French CB, Nguyen S, Ferreira M, Baggerly LL, Brunel L, Veugelers P (2013) A novel approach localizes the association of vitamin D status with insulin resistance to one region of the 25-hydroxyvitamin D continuum. Adv Nutr 4(3):303–310. doi:10.3945/an.113.003731

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Hurskainen AR, Virtanen JK, Tuomainen TP, Nurmi T, Voutilainen S (2012) Association of serum 25-hydroxyvitamin D with type 2 diabetes and markers of insulin resistance in a general older population in Finland. Diabetes Metab Res Rev 28(5):418–423. doi:10.1002/dmrr.2286

    Article  CAS  PubMed  Google Scholar 

  28. Dalgard C, Petersen MS, Weihe P, Grandjean P (2011) Vitamin D status in relation to glucose metabolism and type 2 diabetes in septuagenarians. Diabetes Care 34(6):1284–1288. doi:10.2337/dc10-2084

    Article  PubMed Central  PubMed  Google Scholar 

  29. Protiva P, Cross HS, Hopkins ME, Kallay E, Bises G, Dreyhaupt E, Augenlicht L, Lipkin M, Lesser M, Livote E, Holt PR (2009) Chemoprevention of colorectal neoplasia by estrogen: potential role of vitamin D activity. Cancer Prev Res (Phila) 2(1):43–51. doi:10.1158/1940-6207.CAPR-08-0103

    Article  CAS  Google Scholar 

  30. Barzi A, Lenz AM, Labonte MJ, Lenz HJ (2013) Molecular pathways: estrogen pathway in colorectal cancer. Clin Cancer Res Off J Am Assoc Cancer Res 19(21):5842–5848. doi:10.1158/1078-0432.CCR-13-0325

    Article  CAS  Google Scholar 

  31. Lechner D, Cross HS (2003) Phytoestrogens and 17beta-estradiol influence vitamin D metabolism and receptor expression-relevance for colon cancer prevention. Recent Results Cancer Res 164:379–391

    Article  CAS  PubMed  Google Scholar 

  32. Atteritano M, Marini H, Minutoli L, Polito F, Bitto A, Altavilla D, Mazzaferro S, D’Anna R, Cannata ML, Gaudio A, Frisina A, Frisina N, Corrado F, Cancellieri F, Lubrano C, Bonaiuto M, Adamo EB, Squadrito F (2007) Effects of the phytoestrogen genistein on some predictors of cardiovascular risk in osteopenic, postmenopausal women: a two-year randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 92(8):3068–3075. doi:10.1210/jc.2006-2295

    Article  CAS  PubMed  Google Scholar 

  33. Somjen D, Weisman Y, Kohen F, Gayer B, Limor R, Sharon O, Jaccard N, Knoll E, Stern N (2005) 25-Hydroxyvitamin D3-1alpha-hydroxylase is expressed in human vascular smooth muscle cells and is upregulated by parathyroid hormone and estrogenic compounds. Circulation 111(13):1666–1671. doi:10.1161/01.CIR.0000160353.27927.70

    Article  CAS  PubMed  Google Scholar 

  34. Yao S, Ambrosone CB (2013) Associations between vitamin D deficiency and risk of aggressive breast cancer in African-American women. J Steroid Biochem Mol Biol 136:337–341. doi:10.1016/j.jsbmb.2012.09.010

    Article  CAS  PubMed  Google Scholar 

  35. Laporta E, Welsh J (2013) Modeling vitamin D actions in triple negative/basal-like breast cancer. J Steroid Biochem Mol Biol. doi:10.1016/j.jsbmb.2013.10.022

    PubMed  Google Scholar 

  36. Chiu KC, Chu A, Go VL, Saad MF (2004) Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr 79(5):820–825

    CAS  PubMed  Google Scholar 

  37. Deleskog A, Hilding A, Brismar K, Hamsten A, Efendic S, Ostenson CG (2012) Low serum 25-hydroxyvitamin D level predicts progression to type 2 diabetes in individuals with prediabetes but not with normal glucose tolerance. Diabetologia 55(6):1668–1678. doi:10.1007/s00125-012-2529-x

    Article  CAS  PubMed  Google Scholar 

  38. Voorham QJ, Rondagh EJ, Knol DL, van Engeland M, Carvalho B, Meijer GA, Sanduleanu S (2013) Tracking the molecular features of nonpolypoid colorectal neoplasms: a systematic review and meta-analysis. Am J Gastroenterol 108(7):1042–1056. doi:10.1038/ajg.2013.126

    Article  CAS  PubMed  Google Scholar 

  39. Lee K (2013) Body composition and vitamin D status: the Korea National Health And Nutrition Examination Survey IV (KNHANES IV). J Hum Nutr Diet Off J Br Dietetic Assoc 26(Suppl 1):105–113. doi:10.1111/jhn.12047

    Article  Google Scholar 

  40. Bolland MJ, Grey AB, Ames RW, Mason BH, Horne AM, Gamble GD, Reid IR (2007) The effects of seasonal variation of 25-hydroxyvitamin D and fat mass on a diagnosis of vitamin D sufficiency. Am J Clin Nutr 86(4):959–964

    CAS  PubMed  Google Scholar 

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Acknowledgments

We gratefully acknowledge laboratory technical support by Elke Albrecht, Monika Ratkowitsch, Carmen Winkler, Oberndorf Hospital; Angela Eich, First Department of Medicine, Paracelsus Medical University Salzburg; Silke Winkler, Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Germany and support from SPAR Austria to Christian Datz is gratefully acknowledged.

Conflicts of interest

None of the authors have any potential conflicts of interest to declare with regard to this investigation.

Human and animal rights

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.

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Informed consent was obtained from all patients for being included in the study.

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Correspondence to Christian Datz.

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Managed by Massimo Porta.

Wolfgang Patsch and Christian Datz have contributed equally to this manuscript.

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Stadlmayr, A., Aigner, E., Huber-Schönauer, U. et al. Relations of vitamin D status, gender and type 2 diabetes in middle-aged Caucasians. Acta Diabetol 52, 39–46 (2015). https://doi.org/10.1007/s00592-014-0596-9

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  • DOI: https://doi.org/10.1007/s00592-014-0596-9

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