Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Carbohydrates, glycemic index and diabetes mellitus

Plasma 25-hydroxyvitamin D and risk of metabolic syndrome: an ancillary analysis in the Diabetes Prevention Program

European Journal of Clinical Nutrition volume 68, pages 376–383 (2014)Cite this article

Subjects

Abstract

Background/Objectives:

Low blood levels of 25-hydroxyvitamin D (25OHD) have been associated with cardiometabolic disease but results are inconsistent. The objective of the study was to investigate the association of 25OHD with metabolic syndrome in a population at increased risk for diabetes.

Subjects/Methods:

Using baseline data from the placebo and lifestyle intervention arms of the Diabetes Prevention Program (N=2000), multivariable logistic regression models were used to estimate the odds of prevalent metabolic syndrome and each of its individual components across 25OHD tertiles. Multivariable linear regression was used to estimate the adjusted mean difference of insulin secretion and sensitivity across the same 25OHD tertiles. In participants free of metabolic syndrome at baseline (N=546), incident metabolic syndrome in the first 2 years of follow-up was assessed using discrete-time proportional hazards regression to test its association with 25OHD concentration.

Results:

After multivariate adjustment, participants in the highest tertile of 25OHD had lower odds of prevalent metabolic syndrome (odds ratio=0.62; 95% confidence interval (CI)=0.45–0.84), smaller waist circumference, higher high-density lipoprotein and lower fasting plasma glucose compared with participants in the lowest tertile of 25OHD. Higher plasma 25OHD concentration was associated with greater insulin sensitivity and lower insulin secretion. After multivariate adjustment, there was a nonsignificant lower risk of metabolic syndrome in the highest tertile of 25OHD (hazard ratio=0.79; 95% CI=0.48–1.32) compared with the lowest tertile.

Conclusions:

In a population at increased risk for diabetes, higher plasma 25OHD concentration was inversely associated with prevalent metabolic syndrome and nonsignificantly with incident metabolic syndrome.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Dobnig H, Pilz S, Scharnagl H, Renner W, Seelhorst U, Wellnitz B et al. Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Arch Intern Med 2008; 168: 1340–1349.

    Article  CAS  Google Scholar 

  2. Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation 2008; 117: 503–511.

    Article  CAS  Google Scholar 

  3. Lu L, Yu Z, Pan A, Hu FB, Franco OH, Li H et al. Plasma 25-hydroxyvitamin D concentration and metabolic syndrome among middle-aged and elderly Chinese individuals. Diabetes Care 2009; 32: 1278–1283.

    Article  CAS  Google Scholar 

  4. Beydoun MA, Boueiz A, Shroff MR, Beydoun HA, Wang Y, Zonderman AB . Associations among 25-hydroxyvitamin D, diet quality, and metabolic disturbance differ by adiposity in adults in the United States. J Clin Endocrinol Metab 2010; 95: 3814–3827.

    Article  CAS  Google Scholar 

  5. Kayaniyil S, Vieth R, Harris SB, Retnakaran R, Knight JA, Gerstein HC et al. Association of 25(OH)D and PTH with metabolic syndrome and its traditional and nontraditional components. J Clin Endocrinol Metab 2011; 96: 168–175.

    Article  CAS  Google Scholar 

  6. Ganji V, Zhang X, Shaikh N, Tangpricha V . Serum 25-hydroxyvitamin D concentrations are associated with prevalence of metabolic syndrome and various cardiometabolic risk factors in US children and adolescents based on assay-adjusted serum 25-hydroxyvitamin D data from NHANES 2001-2006. Am J Clin Nutr 2011; 94: 225–233.

    Article  CAS  Google Scholar 

  7. Lee DM, Rutter MK, O'Neill TW, Boonen S, Vanderschueren D, Bouillon R et al. Vitamin D, parathyroid hormone and the metabolic syndrome in middle-aged and older European men. Eur J Endocrinol 2009; 161: 947–954.

    Article  CAS  Google Scholar 

  8. He JL, Scragg RK . Vitamin D, parathyroid hormone, and blood pressure in the National Health and Nutrition Examination Surveys. Am J Hypertens 2011; 24: 911–917.

    Article  CAS  Google Scholar 

  9. Ford ES, Ajani UA, McGuire LC, Liu S . Concentrations of serum vitamin D and the metabolic syndrome among U.S. adults. Diabetes Care 2005; 28: 1228–1230.

    Article  CAS  Google Scholar 

  10. Botella-Carretero JI, Alvarez-Blasco F, Villafruela JJ, Balsa JA, Vazquez C, Escobar-Morreale HF . Vitamin D deficiency is associated with the metabolic syndrome in morbid obesity. Clin Nutr 2007; 26: 573–580.

    Article  CAS  Google Scholar 

  11. Hypponen E, Boucher BJ, Berry DJ, Power C . 25-Hydroxyvitamin D, IGF-1, and metabolic syndrome at 45 years of age: a cross-sectional study in the 1958 British Birth Cohort. Diabetes 2008; 57: 298–305.

    Article  CAS  Google Scholar 

  12. Reis JP, von Muhlen D, Kritz-Silverstein D, Wingard DL, Barrett-Connor E . Vitamin D, parathyroid hormone levels, and the prevalence of metabolic syndrome in community-dwelling older adults. Diabetes Care 2007; 30: 1549–1555.

    Article  CAS  Google Scholar 

  13. Hjelmesaeth J, Hofso D, Aasheim ET, Jenssen T, Moan J, Hager H et al. Parathyroid hormone, but not vitamin D, is associated with the metabolic syndrome in morbidly obese women and men: a cross-sectional study. Cardiovasc Diabetol 2009; 8: 7.

    Article  Google Scholar 

  14. McGill AT, Stewart JM, Lithander FE, Strik CM, Poppitt SD . Relationships of low serum vitamin D3 with anthropometry and markers of the metabolic syndrome and diabetes in overweight and obesity. Nutr J 2008; 7: 4.

    Article  Google Scholar 

  15. Rueda S, Fernandez-Fernandez C, Romero F, Martinez de Osaba J, Vidal J . Vitamin D, PTH, and the metabolic syndrome in severely obese subjects. Obes Surg 2008; 18: 151–154.

    Article  Google Scholar 

  16. Bell NH, Greene A, Epstein S, Oexmann MJ, Shaw S, Shary J . Evidence for alteration of the vitamin D-endocrine system in blacks. J Clin Invest 1985; 76: 470–473.

    Article  CAS  Google Scholar 

  17. The Diabetes Prevention Program. Design and methods for a clinical trial in the prevention of type 2 diabetes. Diabetes Care 1999; 22: 623–634.

    Article  Google Scholar 

  18. Hankinson SE, London SJ, Chute CG, Barbieri RL, Jones L, Kaplan LA et al. Effect of transport conditions on the stability of biochemical markers in blood. Clin Chem 1989; 35: 2313–2316.

    CAS  PubMed  Google Scholar 

  19. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005; 112: 2735–2752.

    Article  Google Scholar 

  20. Phillips DI, Clark PM, Hales CN, Osmond C . Understanding oral glucose tolerance: comparison of glucose or insulin measurements during the oral glucose tolerance test with specific measurements of insulin resistance and insulin secretion. Diabet Med 1994; 11: 286–292.

    Article  CAS  Google Scholar 

  21. Hanson RL, Pratley RE, Bogardus C, Narayan KM, Roumain JM, Imperatore G et al. Evaluation of simple indices of insulin sensitivity and insulin secretion for use in epidemiologic studies. Am J Epidemiol 2000; 151: 190–198.

    Article  CAS  Google Scholar 

  22. Kitabchi AE, Temprosa M, Knowler WC, Kahn SE, Fowler SE, Haffner SM et al. Role of insulin secretion and sensitivity in the evolution of type 2 diabetes in the diabetes prevention program: effects of lifestyle intervention and metformin. Diabetes 2005; 54: 2404–2414.

    Article  Google Scholar 

  23. Utzschneider KM, Prigeon RL, Faulenbach MV, Tong J, Carr DB, Boyko EJ et al. Oral disposition index predicts the development of future diabetes above and beyond fasting and 2-h glucose levels. Diabetes Care 2009; 32: 335–341.

    Article  CAS  Google Scholar 

  24. Kriska AM, Caspersen CJ . Introduction to a collection of physical activity questionnaires. Med Sci Sports Exerc 1997; 29 (Suppl), S5–S9.

    Article  Google Scholar 

  25. Mayer-Davis EJ, Sparks KC, Hirst K, Costacou T, Lovejoy JC, Regensteiner JG et al. Dietary intake in the diabetes prevention program cohort: baseline and 1-year post randomization. Ann Epidemiol 2004; 14: 763–772.

    Article  Google Scholar 

  26. Orchard TJ, Temprosa M, Goldberg R, Haffner S, Ratner R, Marcovina S et al. The effect of metformin and intensive lifestyle intervention on the metabolic syndrome: the Diabetes Prevention Program randomized trial. Ann Int Med 2005; 142: 611–619.

    Article  CAS  Google Scholar 

  27. Eckel RH, Grundy SM, Zimmet PZ . The metabolic syndrome. Lancet 2005; 365: 1415–1428.

    Article  CAS  Google Scholar 

  28. Maestro B, Molero S, Bajo S, Davila N, Calle C . Transcriptional activation of the human insulin receptor gene by 1,25-dihydroxyvitamin D(3). Cell Biochem Funct 2002; 20: 227–232.

    Article  CAS  Google Scholar 

  29. Dunlop TW, Vaisanen S, Frank C, Molnar F, Sinkkonen L, Carlberg C . The human peroxisome proliferator-activated receptor delta gene is a primary target of 1alpha,25-dihydroxyvitamin D3 and its nuclear receptor. J Mol Biol 2005; 349: 248–260.

    Article  CAS  Google Scholar 

  30. Kadowaki S, Norman AW . Dietary vitamin D is essential for normal insulin secretion from the perfused rat pancreas. J Clin Invest 1984; 73: 759–766.

    Article  CAS  Google Scholar 

  31. Tanaka Y, Seino Y, Ishida M, Yamaoka K, Yabuuchi H, Ishida H et al. Effect of vitamin D3 on the pancreatic secretion of insulin and somatostatin. Acta Endocrinol (Copenh) 1984; 105: 528–533.

    Article  CAS  Google Scholar 

  32. Cade C, Norman AW . Vitamin D3 improves impaired glucose tolerance and insulin secretion in the vitamin D-deficient rat in vivo. Endocrinology 1986; 119: 84–90.

    Article  CAS  Google Scholar 

  33. Johnson JA, Grande JP, Roche PC, Kumar R . Immunohistochemical localization of the 1,25(OH)2D3 receptor and calbindin D28k in human and rat pancreas. Am J Physiol 1994; 267 (3 Pt 1), E356–E360.

    CAS  PubMed  Google Scholar 

  34. Bland R, Markovic D, Hills CE, Hughes SV, Chan SL, Squires PE et al. Expression of 25-hydroxyvitamin D3-1alpha-hydroxylase in pancreatic islets. J Steroid Biochem Mol Biol 2004; 89-90: 121–125.

    Article  CAS  Google Scholar 

  35. Sergeev IN, Rhoten WB . 1,25-Dihydroxyvitamin D3 evokes oscillations of intracellular calcium in a pancreatic beta-cell line. Endocrinology 1995; 136: 2852–2861.

    Article  CAS  Google Scholar 

  36. Reis JP, von Muhlen D, Miller 3rd ER . Relation of 25-hydroxyvitamin D and parathyroid hormone levels with metabolic syndrome among US adults. Eur J Endocrinol 2008; 159: 41–48.

    Article  CAS  Google Scholar 

  37. Kim MK, Il Kang M, Won OhK, Kwon HS, Lee JH, Lee WC et al. The association of serum vitamin D level with presence of metabolic syndrome and hypertension in middle-aged Korean subjects. Clin Endocrinol (Oxf) 2010; 73: 330–338.

    Article  CAS  Google Scholar 

  38. Kayaniyil S, Vieth R, Retnakaran R, Knight JA, Qi Y, Gerstein HC et al. Association of vitamin D with insulin resistance and beta-cell dysfunction in subjects at risk for type 2 diabetes. Diabetes Care 2010; 33: 1379–1381.

    Article  Google Scholar 

  39. Chacko SA, Song Y, Manson JE, Van Horn L, Eaton C, Martin LW et al. Serum 25-hydroxyvitamin D concentrations in relation to cardiometabolic risk factors and metabolic syndrome in postmenopausal women. Am J Clin Nutr 2011; 94: 209–217.

    Article  CAS  Google Scholar 

  40. Forouhi NG, Luan J, Cooper A, Boucher BJ, Wareham NJ . Baseline serum 25-hydroxy vitamin d is predictive of future glycemic status and insulin resistance: the Medical Research Council Ely Prospective Study 1990-2000. Diabetes 2008; 57: 2619–2625.

    Article  CAS  Google Scholar 

  41. Gagnon C, Lu ZX, Magliano DJ, Dunstan DW, Shaw JE, Zimmet PZ et al. 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 2012; 97: 1953–1961.

    Article  CAS  Google Scholar 

  42. Harris SS . Does vitamin D deficiency contribute to increased rates of cardiovascular disease and type 2 diabetes in African Americans? Am J Clin Nutr 2011; 93: 1175S–1178SS.

    Article  Google Scholar 

  43. Liu E, Meigs JB, Pittas AG, McKeown NM, Economos CD, Booth SL et al. Plasma 25-hydroxyvitamin d is associated with markers of the insulin resistant phenotype in nondiabetic adults. J Nutr 2009; 139: 329–334.

    Article  CAS  Google Scholar 

  44. Scragg R, Sowers M, Bell C . Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the Third National Health and Nutrition Examination Survey. Diabetes Care 2004; 27: 2813–2818.

    Article  CAS  Google Scholar 

  45. Pinelli NR, Jaber LA, Brown MB, Herman WH . Serum 25-hydroxy vitamin d and insulin resistance, metabolic syndrome, and glucose intolerance among Arab Americans. Diabetes Care 2010; 33: 1373–1375.

    Article  CAS  Google Scholar 

  46. Gulseth HL, Gjelstad IM, Tierney AC, Lovegrove JA, Defoort C, Blaak EE et al. Serum vitamin D concentration does not predict insulin action or secretion in European subjects with the metabolic syndrome. Diabetes Care 2010; 33: 923–925.

    Article  CAS  Google Scholar 

  47. Pittas AG, Nelson J, Mitri J, Hillmann W, Garganta C, Nathan DM et al. Plasma 25-hydroxyvitamin D and progression to diabetes in patients at risk for diabetes: an ancillary analysis in the Diabetes Prevention Program. Diabetes Care 2012; 35: 565–573.

    Article  CAS  Google Scholar 

  48. Shoben AB, Kestenbaum B, Levin G, Hoofnagle AN, Psaty BM, Siscovick DS et al. Seasonal variation in 25-hydroxyvitamin d concentrations in the cardiovascular health study. Am J Epidemiol 2011; 174: 1363–1372.

    Article  Google Scholar 

Download references

Acknowledgements

We thank David Kent, MD MSc, Associate Professor of Medicine, Director of the Clinical and Translational Science MS/PhD Program at the Sackler School, for his valuable input into interpretation of the results. We also acknowledge the commitment and dedication of the DPP participants. A portion of the work was presented at the 2012 Endocrine Society meeting as an oral presentation, on 23 June 2012, in Houston, TX. This study was supported by research grants R01DK79003, U34DK091958 and U01DK098245 (to AGP) from the National Institute of Diabetes and Digestive and Kidney Disease, the Office Of The Director—National Institutes of Health, and the National Institutes of Health Office of Dietary Supplements; UL1RR025752 (to Tufts University) from the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health. The US Department of Agriculture Agreement 58-1950-9001 (to BDH); the Marilyn Fishman Grant for Diabetes Research (to JM) from the Endocrine Fellows Foundation; U01DK48489 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health to the DPP clinical centers and the Coordinating Center for the design and conduct of the DPP study. The Southwestern American Indian Centers were supported directly by the NIDDK, including its Intramural Research Program, and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, supported data collection at many of the clinical centers. Funding was also provided by the National Institute of Child Health and Human Development, the National Institute on Aging, the National Eye Institute, the National Heart Lung and Blood Institute, the Office of Research on Women’s Health, the National Center for Minority Health and Human Disease, the Centers for Disease Control and Prevention, the Indian Health Service, and the American Diabetes Association. Lipha (Merck-Sante) provided medication. LifeScan Inc., Merck-Medco Managed Care, Inc., and Merck and Co. donated materials, equipment or medicines for concomitant conditions. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the above listed institutions.

Author information

Authors and Affiliations

  1. Division of Endocrinology, Diabetes and Metabolism, Tufts Medical Center, Boston, MA, USA

    J Mitri, B Dawson-Hughes & A G Pittas

  2. Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, USA

    J Nelson & R Ruthazer

  3. Department of Clinical Genetics, Floating Hospital for Children at Tufts Medical Center, Boston, MA, USA

    C Garganta

  4. Diabetes Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    D M Nathan

  5. Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA, USA

    F B Hu

  6. Channing Laboratory, Brigham and Women’s Hospital, Boston, MA, USA

    F B Hu

  7. Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Bone Metabolism Laboratory, Tufts University, Boston, MA, USA

    B Dawson-Hughes

Authors
  1. J Mitri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J Nelson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R Ruthazer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C Garganta
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D M Nathan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. F B Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. B Dawson-Hughes
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A G Pittas
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

and the Diabetes Prevention Program Research Group

Corresponding author

Correspondence to J Mitri.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mitri, J., Nelson, J., Ruthazer, R. et al. Plasma 25-hydroxyvitamin D and risk of metabolic syndrome: an ancillary analysis in the Diabetes Prevention Program. Eur J Clin Nutr 68, 376–383 (2014). https://doi.org/10.1038/ejcn.2013.293

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ejcn.2013.293

Keywords

This article is cited by

Search

Advanced search

Quick links