Skip to main content
SpringerLink
Log in

Vitamin B12 insufficiency is associated with increased risk of gestational diabetes mellitus: a systematic review and meta-analysis

  • Meta-Analysis
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose

Vitamin B12 deficiency has been associated with a plethora of metabolic abnormalities, such as hyperhomocysteinaemia, insulin resistance and defective synthesis of neurotransmitters and fatty acids. Inconsistency exists as to whether vitamin B12 deficiency is also associated with increased risk of gestational diabetes mellitus (GDM). The purpose of this study was to systematically review and meta-analyze the existing evidence for this association.

Methods

A comprehensive search was conducted in PubMed, Scopus and Cochrane Central up to April 30, 2019. Data are expressed as odds ratio (OR) with 95% confidence interval (CI). The I2 index was employed for heterogeneity.

Results

Six studies (n = 1810 pregnant women, 309 GDM cases) fulfilled the eligibility criteria for qualitative and two studies for quantitative analysis. In five studies providing data on vitamin B12 concentrations for both groups, women with GDM had lower vitamin B12 levels when compared with non-GDM women. Women with vitamin B12 deficiency were at higher risk for developing GDM when compared with those who were vitamin B12 sufficient: OR 1.81 (95% CI, 1.25–2.63, I2: 0%). Due to the small number of studies, the role of potential confounders could not be safely estimated.

Conclusions

Vitamin B12 deficiency seems to be associated with increased risk of GDM. More studies are needed to further strengthen this finding and to clarify possible pathogenetic mechanisms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. M.B. Landon, S.G. Gabbe, Gestational diabetes mellitus. Obstet. Gynecol. 118(6), 1379–1393 (2011). https://doi.org/10.1097/AOG.0b013e31823974e2

    Article  PubMed  Google Scholar 

  2. S.A. Paschou, P. Anagnostis, B.H.R. Wolffenbuttel, D.G. Goulis, The need for precision medicine in gestational diabetes mellitus. Maturitas 118, 74–75 (2018). https://doi.org/10.1016/j.maturitas.2018.07.003

    Article  PubMed  Google Scholar 

  3. I.J. Halperin, D.S. Feig, The role of lifestyle interventions in the prevention of gestational diabetes. Curr. Diabetes Rep. 14(1), 452 (2014). https://doi.org/10.1007/s11892-013-0452-2

    Article  Google Scholar 

  4. C.A. Crowther, J.E. Hiller, J.R. Moss, A.J. McPhee, W.S. Jeffries, J.S. Robinson, Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. New Engl. J. Med. 352(24), 2477–2486 (2005). https://doi.org/10.1056/NEJMoa042973

    Article  CAS  PubMed  Google Scholar 

  5. M.T. Mursleen, S. Riaz, Implication of homocysteine in diabetes and impact of folate and vitamin B12 in diabetic population. Diabetes Metab. Syndr.: Clin. Res. Rev. 11, S141–S146 (2017). https://doi.org/10.1016/j.dsx.2016.12.023

    Article  Google Scholar 

  6. M.C. Pflipsen, R.C. Oh, A. Saguil, D.A. Seehusen, D. Seaquist, R. Topolski, The prevalence of vitamin B(12) deficiency in patients with type 2 diabetes: a cross-sectional study. J. Am. Board Fam. Med. 22(5), 528–534 (2009). https://doi.org/10.3122/jabfm.2009.05.090044

    Article  PubMed  Google Scholar 

  7. Q. Liu, S. Li, H. Quan, J. Li, Vitamin B12 status in metformin treated patients: systematic review. PLoS ONE 9(6), e100379–e100379 (2014). https://doi.org/10.1371/journal.pone.0100379

    Article  PubMed  PubMed Central  Google Scholar 

  8. M. Nervo, A. Lubini, F.V. Raimundo, G.A. Faulhaber, C. Leite, L.M. Fischer, T.W. Furlanetto, Vitamin B12 in metformin-treated diabetic patients: a cross-sectional study in Brazil. Rev. da Assoc. Med. Bras. (1992) 57(1), 46–49 (2011)

    Article  Google Scholar 

  9. K.W. Liu, L.K. Dai, W. Jean, Metformin-related vitamin B12 deficiency. Age Ageing 35(2), 200–201 (2006). https://doi.org/10.1093/ageing/afj042

    Article  CAS  PubMed  Google Scholar 

  10. D.S. Bell, Metformin-induced vitamin B12 deficiency presenting as a peripheral neuropathy. South. Med. J. 103(3), 265–267 (2010). https://doi.org/10.1097/SMJ.0b013e3181ce0e4d

    Article  PubMed  Google Scholar 

  11. A.A. Kumthekar, H.V. Gidwani, A.B. Kumthekar, Metformin associated B12 deficiency. J. Assoc. Physicians India 60, 58–60 (2012)

    PubMed  Google Scholar 

  12. N. Sukumar, H. Venkataraman, S. Wilson, I. Goljan, S. Selvamoni, V. Patel, P. Saravanan, Vitamin B12 status among pregnant women in the UK and its association with obesity and gestational diabetes. Nutrients 8(12) (2016). https://doi.org/10.3390/nu8120768

    Article  Google Scholar 

  13. G.V. Krishnaveni, J.C. Hill, S.R. Veena, D.S. Bhat, A.K. Wills, C.L. Karat, C.S. Yajnik, C.H. Fall, Low plasma vitamin B12 in pregnancy is associated with gestational ‘diabesity’ and later diabetes. Diabetologia 52(11), 2350–2358 (2009). https://doi.org/10.1007/s00125-009-1499-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. E. Tarim, T. Bagis, E. Kilicdag, S. Erkanli, E. Aslan, N. Sezgin, E. Kuscu, Elevated plasma homocysteine levels in gestational diabetes mellitus. Acta Obstet. et. Gynecol. Scand. 83(6), 543–547 (2004). https://doi.org/10.1111/j.0001-6349.2004.00540.x

    Article  Google Scholar 

  15. M.A. Guven, M. Kilinc, C. Batukan, H.C. Ekerbicer, T. Aksu, Elevated second trimester serum homocysteine levels in women with gestational diabetes mellitus. Arch. Gynecol. Obstet. 274(6), 333–337 (2006). https://doi.org/10.1007/s00404-006-0191-6

    Article  CAS  PubMed  Google Scholar 

  16. G. Seghieri, M.C. Breschi, R. Anichini, A. De Bellis, L. Alviggi, I. Maida, F. Franconi, Serum homocysteine levels are increased in women with gestational diabetes mellitus. Metab.: Clin. Exp. 52(6), 720–723 (2003)

    Article  CAS  Google Scholar 

  17. B. Idzior-Walus, K. Cyganek, K. Sztefko, G. Seghieri, M.C. Breschi, M. Walus-Miarka, E. Kawalec, M. Seretny, J. Sieradzki, Total plasma homocysteine correlates in women with gestational diabetes. Arch. Gynecol. Obstet. 278(4), 309–313 (2008). https://doi.org/10.1007/s00404-008-0571-1

    Article  CAS  PubMed  Google Scholar 

  18. M.W. Carpenter, D.R. Coustan, Criteria for screening tests for gestational diabetes. Am. J. Obstet. Gynecol. 144(7), 768–773 (1982)

    Article  CAS  Google Scholar 

  19. World Health Organization, Definition and Diagnosis of Diabetes Mellitus and Intermediate Hyperglycemia: A Report of WHO/IDF Consultation (World Health Organization, Geneva, 2006)

  20. American Diabetes Association, Clinical practice recommendations 2001. Diabetes Care 24(Suppl 1), S1–133 (2001)

    Google Scholar 

  21. S. Finer, P. Saravanan, G. Hitman, C. Yajnik, The role of the one-carbon cycle in the developmental origins of Type 2 diabetes and obesity. Diabet. Med. 31(3), 263–272 (2014). https://doi.org/10.1111/dme.12390

    Article  CAS  PubMed  Google Scholar 

  22. A. Adaikalakoteswari, R. Jayashri, N. Sukumar, H. Venkataraman, R. Pradeepa, K. Gokulakrishnan, R.M. Anjana, P.G. McTernan, G. Tripathi, V. Patel, S. Kumar, V. Mohan, P. Saravanan, Vitamin B12 deficiency is associated with adverse lipid profile in Europeans and Indians with type 2 diabetes. Cardiovasc. Diabetol. 13, 129 (2014). https://doi.org/10.1186/s12933-014-0129-4

    Article  PubMed  PubMed Central  Google Scholar 

  23. A. Adaikalakoteswari, M. Vatish, M.T. Alam, S. Ott, S. Kumar, P. Saravanan, Low vitamin B12 in pregnancy is associated with adipose-derived circulating miRs targeting PPARgamma and insulin resistance. J. Clin. Endocrinol. Metab. 102(11), 4200–4209 (2017). https://doi.org/10.1210/jc.2017-01155

    Article  PubMed  Google Scholar 

  24. J.B. Meigs, P.F. Jacques, J. Selhub, D.E. Singer, D.M. Nathan, N. Rifai, R.B. D’Agostino Sr., P.W. Wilson, Fasting plasma homocysteine levels in the insulin resistance syndrome: the Framingham offspring study. Diabetes Care 24(8), 1403–1410 (2001)

    Article  CAS  Google Scholar 

  25. M.A. Kothekar, Homocysteine in cardiovascular disease: a culprit or an innocent bystander? Indian J. Med. Sci. 61(6), 361–371 (2007)

    Article  Google Scholar 

  26. S. Taneja, N. Bhandari, T.A. Strand, H. Sommerfelt, H. Refsum, P.M. Ueland, J. Schneede, R. Bahl, M.K. Bhan, Cobalamin and folate status in infants and young children in a low-to-middle income community in India. Am. J. Clin. Nutr. 86(5), 1302–1309 (2007). https://doi.org/10.1093/ajcn/86.5.1302

    Article  CAS  PubMed  Google Scholar 

  27. V. Fonseca, M. Keebler, A. Dicker-Brown, C. Desouza, L.A. Poirier, S.N. Murthy, D.B. McNamara, The effect of troglitazone on plasma homocysteine, hepatic and red blood cell S-adenosyl methionine, and S-adenosyl homocysteine and enzymes in homocysteine metabolism in Zucker rats. Metab.: Clin. Exp. 51(6), 783–786 (2002)

    Article  CAS  Google Scholar 

  28. M.C. Walker, G.N. Smith, S.L. Perkins, E.J. Keely, P.R. Garner, Changes in homocysteine levels during normal pregnancy. Am. J. Obstet. Gynecol. 180(3 Pt 1), 660–664 (1999)

    Article  CAS  Google Scholar 

  29. G.M. Reaven, Role of insulin resistance in human disease (syndrome X): an expanded definition. Annu. Rev. Med. 44, 121–131 (1993). https://doi.org/10.1146/annurev.me.44.020193.001005

    Article  CAS  PubMed  Google Scholar 

  30. G. Paolisso, A. Gambardella, M.R. Tagliamonte, F. Saccomanno, T. Salvatore, P. Gualdiero, M.V. D’Onofrio, B.V. Howard, Does free fatty acid infusion impair insulin action also through an increase in oxidative stress? J. Clin. Endocrinol. Metab. 81(12), 4244–4248 (1996). https://doi.org/10.1210/jcem.81.12.8954022

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. First Department of Internal Medicine, General Hospital of Volos, Volos, Greece

    Eleni Kouroglou

  2. Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynaecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Panagiotis Anagnostis

  3. Department of Obstetrics and Gynaecology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece

    Alexandros Daponte

  4. Department of Endocrinology and Metabolic Diseases, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece

    Alexandra Bargiota

Authors
  1. Eleni Kouroglou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Panagiotis Anagnostis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alexandros Daponte
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alexandra Bargiota
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eleni Kouroglou.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kouroglou, E., Anagnostis, P., Daponte, A. et al. Vitamin B12 insufficiency is associated with increased risk of gestational diabetes mellitus: a systematic review and meta-analysis. Endocrine 66, 149–156 (2019). https://doi.org/10.1007/s12020-019-02053-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-019-02053-1

Keywords

Search

Navigation