Acta Diabetologica

, Volume 55, Issue 12, pp 1283–1293 | Cite as

Prevalence of vitamin B12 deficiency in South Indians with different grades of glucose tolerance

  • Ramamoorthy Jayashri
  • Ulagamathesan Venkatesan
  • Menon Rohan
  • Kuppan Gokulakrishnan
  • Coimbatore Subramanian Shanthi Rani
  • Mohan Deepa
  • Ranjit Mohan Anjana
  • Viswanathan Mohan
  • Rajendra PradeepaEmail author
Original Article



To determine the prevalence of vitamin B12 deficiency in an urban south Indian population in individuals with different grades of glucose tolerance.


A total of 1500 individuals [900 normal glucose tolerance (NGT), 300 prediabetes and 300 type 2 diabetes (T2DM)] who were not on vitamin B12 supplementation were randomly selected from the Chennai Urban Rural Epidemiological Study (CURES) follow-up study. Anthropometric, clinical and biochemical investigations, which included vitamin B12, insulin, homocysteine, HbA1c and serum lipids, were measured. Vitamin B12 ≤ 191 pg/ml was defined as absolute vitamin B12 deficiency and vitamin B12 > 191 pg/ml and ≤ 350 pg/ml as borderline deficiency.


The mean levels of vitamin B12 significantly decreased with increasing degrees of glucose tolerance (NGT 444 ± 368; prediabetes 409 ± 246; T2DM 389 ± 211 pg/ml, p = 0.021). The prevalence of absolute vitamin B12 deficiency was 14.9% while 37.6% had borderline deficiency. The prevalence of absolute vitamin B12 deficiency was significantly higher among individuals with T2DM (18.7%) followed by prediabetes (15%) and NGT(13.7%) [p for trend = 0.05]. The prevalence of vitamin B12 significantly increased with age (p < 0.05) and in those with abdominal obesity (p < 0.001). Men and vegetarians had twice the risk of vitamin B12 deficiency compared to women and non-vegetarians, respectively. Among individuals with NGT, prediabetes and T2DM, vitamin B12 negatively correlated with homocysteine.


This study reports that the levels of vitamin B12 decreased with increasing severity of glucose tolerance.


Vitamin B12 Diabetes Glucose tolerance Prevalence South Indians 



The authors acknowledge the Research Society for the Study of Diabetes in India (RSSDI) for the financial support for the study through their research grant (Project No: RSSDI/HQ/Grants/2014/250). We also thank the participants for their cooperation.

Compliance with ethical standards

Conflict of interest

All authors have no relevant conflict of interest to disclose.

Ethical standard statement

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all patients for being included in the study which has done according to the ethical standards and in keeping with Helsinki Declaration of 2008 (ICH GCP).


  1. 1.
    Miller A, Korem M, Almog R, Galboiz Y (2005) Vitamin B12, demyelination, remyelination and repair in multiple sclerosis. J NeurolSci 233:93–97Google Scholar
  2. 2.
    Oh R, Brown D (2003) Vitamin B12 deficiency. Am Fam Physician 67:979–986PubMedGoogle Scholar
  3. 3.
    Savage DG, Lindenbaum J, Stabler SP, Allen RH (1994) Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamin and folate deficiencies. Am J Med 96:239–246CrossRefGoogle Scholar
  4. 4.
    Klee GG, (2000)Cobalamin and folate evaluation; measurement of methylmalonic acid and homocysteinevs vitamin B12 and folate. Clin Chem 46:1277–1283Google Scholar
  5. 5.
    Yajnik CS, Deshpande SS, Lubree HG, et al (2006) Vitamin B12 deficiency and hyperhomocysteinemia in rural and urban Indians. J Assoc Physicians India 54:775–782PubMedGoogle Scholar
  6. 6.
    Misra A, Vikram NK, Pandey RM et al (2002) Hyperhomocysteinemia, and low intakes of folic acid and vitamin B12 in urban North India. Eur J Nutr 41:68–77CrossRefGoogle Scholar
  7. 7.
    Pflipsen M, Oh R, Saguil A, Seehusen D, Topolski R (2009) The prevalence of vitamin B12 deficiency in patients with type 2 diabetes: a cross-sectional study. J Am Board Fam Med 22:528–534CrossRefGoogle Scholar
  8. 8.
    Akabwai GP, Kibirige D, Mugenyi L et al (2016) Vitamin B12 deficiency among adult diabetic patients in Uganda: relation to glycaemic control and haemoglobin concentration. J Diabetes Metab Disord 15:26CrossRefGoogle Scholar
  9. 9.
    Shailendra D, Rizwan K, Narayan KMV, Prabhakaran D, Nikhil T, Reddy PS (2003) Prevalence of vitamin B12 deficiency among individuals with type 2 diabetes mellitus in a South Indian rural community. Int J Basics Clin Pharmacol. CrossRefGoogle Scholar
  10. 10.
    Adaikalakoteswari A, Jayashri R, Sukumar N et al (2014) Vitamin B12 deficiency is associated with adverse lipid profile in Europeans and Indians with type 2 diabetes. Cardiovasc Diabetol. 13:129Google Scholar
  11. 11.
    van Guldener C, Nanayakkara PW, Stehouwer CD (2003) Homocysteine and blood pressure. Curr Hypertens Rep 5:26–31CrossRefGoogle Scholar
  12. 12.
    Sudchada P, Saokaew S, Sridetch S et al (2012) Effect of folic acid supplementation on plasma total homocysteine levels and glycemic control in patients with type 2 diabetes: a systematic review and meta-analysis. Diabetes Res Clin Pract 98:151–158CrossRefGoogle Scholar
  13. 13.
    Agullo-Ortuno MT, Albaladejo MD, Parra S et al (2002) Plasmatic homocysteine concentration and its relationship with complications associated to diabetes mellitus. Clin Chim Acta 326:105–112CrossRefGoogle Scholar
  14. 14.
    Chambers JC, Obeid OA, Refsum H et al (2000) Plasma homocysteine concentrations and risk of coronaryheart disease in UK Indian Asian and European men. Lancet 355:523–527CrossRefGoogle Scholar
  15. 15.
    Enas EA, Garg A, Davidson MA, Nair VM, Huet BA, Yusuf S (1996) Coronary heart disease and its risk factors in first-generation immigrant Asian Indians to the United States of America. Indian Heart J 48:343–353PubMedGoogle Scholar
  16. 16.
    Anjana RM, Shanthi Rani CS, Deepa M et al (2015) Incidence of diabetes and prediabetes and predictors of progression among Asian Indians: 10-year follow-up of the Chennai Urban rural epidemiology study (CURES). Diabetes Care 38:1441–1448CrossRefGoogle Scholar
  17. 17.
    Deepa M, Pradeepa R, Rema M et al (2003) The Chennai urban rural epidemiology study (CURES)- study design and methodology (urban component). J Assoc Physicians India 51:863–870PubMedGoogle Scholar
  18. 18.
    Rothman KJ (1986) Modern epidemiology. Little, Brown and Company, BostonGoogle Scholar
  19. 19.
    Naik S, Joglekar C, Bhat D et al (2011) Marked gender difference in plasma total homocysteine concentrations in Indian adults with low vitamin B12. Int J Vitam Nutr Res 81:306–316CrossRefGoogle Scholar
  20. 20.
    Harrison GG, Buskirk ER, Lindsay Carter ER et al. Skinfold thickness and measurement technique. In: Lohman TG, Roche AF, Martorell R (eds) Anthropometric standardization reference manual. Human Kinetics Books, Champaign, 55–70Google Scholar
  21. 21.
    Sudha V, Radhika G, Sathya RM, Ganesan A, Mohan V (2006) Reproducibility and validity of an interviewer-administered semi-quantitative food frequency questionnaire to assess dietary intake of urban adults in southern India. Int J Food Sci Nutr 57:481–493CrossRefGoogle Scholar
  22. 22.
    Willett WC (1998) Nutritional epidemiology, 2nd edn. Oxford University Press, New YorkCrossRefGoogle Scholar
  23. 23.
    Alberti KG, Zimmet PZ (1998) Definition diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus, provisional report of a WHO consultation. Diabet Med 15:539–553CrossRefGoogle Scholar
  24. 24.
    Howard AJ, Kulkarni O, Lekwuwa G, Emsley HC (2010) Rapidly progressive polyneuropathy due to dry beriberi in a man: a case report. J Med Case Rep 4:409CrossRefGoogle Scholar
  25. 25.
    Carmel R, Green R, Rosenblatt DS, Watkins D (2003) Update on cobalamin, folate, and homocysteine. Hematol Am Soc Hematol Educ Program 2003:62–81CrossRefGoogle Scholar
  26. 26.
    Stabler SP, Allen RH (2004) Megaloblasticanemias. In: Cecil RL, Goldman L, Ausiello DA (eds) Cecil textbook of medicine. 22nd ed, Pa Saunders, Philadelphia, 1050–1057Google Scholar
  27. 27.
    Kang SS (1996) Treatment of hyperhomocysteinemia: physiological basis. J Nutr 126:1273S–1275SCrossRefGoogle Scholar
  28. 28.
    World Health Organization (2000) Redefining obesity and its treatment. Regional office for the western pacific of the. In: World health organization, international association for the study of obesity and international obesity task force. Health Communications Australia Pty Limited, St Leonards, 22–29 pGoogle Scholar
  29. 29.
    Chobanian AV, Bakris GL, Black HR et al (2003) National heart, lung, and blood institute joint national committee on prevention, detection, evaluation, and treatment of high blood pressure; national high blood pressure education program coordinating committee. The seventh report of the joint national committee on prevention, detection, evaluation and treatment of high blood pressure (JNC-7). JAMA 289:2560–2572CrossRefGoogle Scholar
  30. 30.
    Early Treatment of Diabetic Retinopathy Study Research Group: Grading diabetic retinopathy from stereoscopic colour fundus photographs—an extension of the modified Airlie House classification (1991). ETDRS report number 10. Ophthalmology 98:786–806Google Scholar
  31. 31.
    Pradeepa R, Rema M, Vignesh J, Deepa M, Deepa R, Mohan V (2008) Prevalence and risk factors for diabetic neuropathy in an urban south Indian population: the Chennai Urban rural epidemiology study (CURES-55). Diabet Med 25:407–412CrossRefGoogle Scholar
  32. 32.
    Varghese A, Deepa R, Rema M, Mohan V (2001) Prevalence of microalbuminuria in type 2 diabetes mellitus at a diabetes centre in Southern India. Postgraduate Med J 77:399–402CrossRefGoogle Scholar
  33. 33.
    Rose GA, Blackburn H, GillumRF et al (1982) Cardiovascular survey methods. In: Minnesota code for resting electrocardiograms, 2nd Ed, Minnesota Code, p 124–143Google Scholar
  34. 34.
    Rooke TW, Hirsch AT, Misra S et al.(2011). Society for cardiovascular angiography and interventions; society of interventional radiology; society for vascular medicine; society for vascular surgery. 2011 ACCF/AHA focused update of the guideline for the management of patients with peripheral artery disease (updating the 2005 guideline): a report of the American college of cardiology foundation/ American heart association task force on practice guidelines. J Am Coll Cardiol 58: 2020–2045CrossRefGoogle Scholar
  35. 35.
    Liu X (2012) Classification accuracy and cut point selection. Stat Med 31(23):2676–2686CrossRefGoogle Scholar
  36. 36.
    Valdés-Ramos R, Ana Laura G-L, Elina M-CB, Donají B-AA (2015) Vitamins and type 2 diabetes mellitus. Endocr Metab Immune Disord Drug Targets 15:54–63CrossRefGoogle Scholar
  37. 37.
    Ko SH, Ko SH, Ahn YB et al. (2014) Association of vitamin B12 deficiency and metformin use in patients with type 2 diabetes. J Korean Med Sci 29:965–972CrossRefGoogle Scholar
  38. 38.
    Hermann L, Nilsson B, Wettre S (2004) Vitamin B12 status of patients treated with metformin: a cross-sectional cohort study. Br J Diabetes Vasc Dis 4:401CrossRefGoogle Scholar
  39. 39.
    Kumthekar A, Gidwani H, Kumthekar A (2012) Metformin associated B12 deficiency. J Assoc Physicians India 60:58–59PubMedGoogle Scholar
  40. 40.
    Reynolds E (2006) Vitamin B12, folic acid, and the nervous system. Lancet Neurol 5:949–960CrossRefGoogle Scholar
  41. 41.
    Aaron S, Kumar S, Vijayan J, Jacob J, Alexander M, Gnanamuthu C (2005) Clinical and laboratory features and response to treatment in patients presenting with vitamin B12 deficiency-related neurological syndromes. Neurol India 53(1):55–8 (discussion 59) CrossRefGoogle Scholar
  42. 42.
    Looker HC, Fagot-Campagna A, Gunter EW et al. (2007) Homocysteine and vitamin B(12) concentrations and mortality rates in type 2 diabetes. Diabetes Metab Res Rev 23:193–201CrossRefGoogle Scholar
  43. 43.
    Satyanarayana A, Balakrishna N, Pitla S et al (2011) Status of B-vitamins and homocysteine in diabetic retinopathy: association with vitamin-B12 deficiency and hyperhomocysteinemia. PLoS One 6:e26747CrossRefGoogle Scholar
  44. 44.
    Fotiou P, Raptis A, Apergis G, Dimitriadis G, Vergados I, Theodossiadis P (2014) Vitamin status as a determinant of serum homocysteine concentration in type 2 diabetic retinopathy. J Diabetes Res. 2014:807209CrossRefGoogle Scholar
  45. 45.
    Refsum H, Yajnik CS, Gadkari M et al. (2001) Hyperhomocysteinemia and elevated methylmalonic acid indicate a high prevalence of cobalamin deficiency in Asian Indians. Am J Clin Nutr 74:233–241CrossRefGoogle Scholar
  46. 46.
    Sivaprasad M, Shalini T, Balakrishna N et al. (2016) Status of vitamin B12 and folate among the Urban adult population in South India. Ann Nutr Metab 68:94–102CrossRefGoogle Scholar
  47. 47.
    Shobha V, Tareya S, Singh R, Shetty P, Unni US, Srinivasan K, Kurpad AV (2011) Vitamin B12 deficiency and levels of metabolites in an apparently normal urban south Indian elderly population. Indian J Med Res 134:432–439PubMedPubMedCentralGoogle Scholar
  48. 48.
    Henry OR, Benghuzzi H, Taylor HA Jr, Tucci M, Butler K et al (2012) Suppression of homocysteine levels by vitamin B12 and folates: age and gender dependency in the Jackson Heart Study. Am J Med Sci 344:110–115CrossRefGoogle Scholar
  49. 49.
    Moore E, Pasco J, Mander A et al. (2014) The prevalence of vitamin B12 deficiency in a random sample from the Australian population. J Investigational Biochem 3:95–100CrossRefGoogle Scholar
  50. 50.
    Fakhrzadeh H, Ghotbi S, Pourebrahim R et al (2006) Total plasma homocysteine, folate, and vitamin b12 status in healthy Iranian adults: the Tehran homocysteine survey (2003–2004)/a cross-sectional population based study. BMC Public Health 6:29–36CrossRefGoogle Scholar
  51. 51.
    Mehta BM, Rege DV, Satoskar RS (1964) Serum vitamin B12 and folic acid activity in lactovegetarian and non vegetarian healthy adult Indians. Am J Clin Nutr 15:77–84CrossRefGoogle Scholar
  52. 52.
    Huang YC, Chang SJ, Chiu YT, Chang HH, Cheng CH. The status of plasmahomocysteine and related B-vitamins in healthy young vegetarians and nonvegetarians. Eur J Nutr. R2:84–90CrossRefGoogle Scholar
  53. 53.
    Allen LH (2008) Causes of vitamin B12 and folate deficiency. Food Nutr Bull. 29(2_suppl1): S20-S34Google Scholar
  54. 54.
    Global Poultry Trends (2012) Chicken consumption steady in oceania, rising in Africa 2012. Accessed 3 Sept 2018
  55. 55.
    Herrmann W, Schorr H, Obeid R, Geisel J (2003) Vitamin B-12 status, particularly holotranscobalamin II and methylmalonic acid concentrations, and hyperhomocysteinemia in vegetarians. Am J Clin Nutr 78:131–136CrossRefGoogle Scholar
  56. 56.
    Koebnick C, Hoffmann I, Dagnelie PC et al. (2004) Long-term ovo-lacto vegetarian diet impairs vitamin B-12 status in pregnant women. J Nutr 134:3319–3326CrossRefGoogle Scholar
  57. 57.
    Allen LH (2008) Causes of B12 and folate deficiency. Food Nutr Bull 29:S20–S35CrossRefGoogle Scholar
  58. 58.
    Dhopeswarkar GA, Trivedi JC, Kulkarni BS, Satoskar RS, Lewis RD (1956) The effect of vegetarianism and antibiotics upon proteins and vitamin B-12 in the blood. Br J Nutr 10:105–110CrossRefGoogle Scholar
  59. 59.
    Naik S, Bhide V, Babhulkar A et al. (2013) Daily milk intake improves vitamin B-12 status in young vegetarian Indians: an intervention trial. Nutr J 12:136CrossRefGoogle Scholar
  60. 60.
    Baltaci D, Kutlucan A, Turker Y et al. (2013) Association of vitamin B12 with obesity, overweight, insulin resistance and metabolic syndrome, and body fat composition; primary care-based study. Med Glas (Zenica) 10:203–210Google Scholar
  61. 61.
    Kimmons JE, Blanck HM, Tohill BC, Zhang J, Khan LK (2006) Associations between body mass index and the prevalence of low micronutrient levels among US adults. Med Gen Med. 8:59Google Scholar
  62. 62.
    Narang M, Singh M, Dange S (2016) Serum homocysteine, vitamin B12 and folic acid levels in patients with metabolic syndrome. J Assoc Physicians India 64:22–26PubMedGoogle Scholar
  63. 63.
    Reinstatler L, Qi Y, Williamson R, Garn J, Oakley-Jr G (2012) Association of biochemical B12 deficiency with metformin therapy and vitamin B12 supplements. The national health and nutrition examination survey, 1999–2006. Diabetes Care. 35:327–333CrossRefGoogle Scholar
  64. 64.
    DeFronzo R, Goodman A (1995) Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The multicenter metformin study group. N Engl J Med 333:541–549CrossRefGoogle Scholar
  65. 65.
    Tavares Bello C, Capitão RM, Sequeira Duarte J, Azinheira J, Vasconcelos C(2017) Vitamin B12 deficiency in type 2 diabetes mellitus. Acta Med Port. 30719–726Google Scholar
  66. 66.
    Huang T, Ren J, Huang J, Li D(2013). Association of homocysteine with type 2 diabetes: a meta-analysis implementing Mendelian randomization approach. BMC Genomics. 14:867CrossRefGoogle Scholar
  67. 67.
    Gilfix BM((2005) Vitamin B12 and homocysteine. CMAJ 173:1360CrossRefGoogle Scholar
  68. 68.
    Platt DE, Hariri E, Salameh P et al. (2017) Type II diabetes mellitus and hyperhomocysteinemia: a complex interaction. Diabetol Metab Syndr. 9:19CrossRefGoogle Scholar
  69. 69.
    Head KA((2006) Peripheral neuropathy: pathogenic mechanisms and alternative therapies. Altern Med Rev. 11:294–329PubMedGoogle Scholar
  70. 70.
    Satyanarayana A, Balakrishna N, Pitla S et al. (2011) Status of B-vitamins and homocysteine in diabetic retinopathy: association with vitamin-B12 deficiency and hyperhomocysteinemia. Malaga G. ed. PLoS One 6:e26747CrossRefGoogle Scholar
  71. 71.
    Shargorodsky M, Boaz M, Pasternak S et al. (2009) Serum homocysteine, folate, vitamin B12 levels and arterial stiffness in diabetic patients: which of them is really important in atherogenesis? Diabetes Metab Res Rev 25:70–75CrossRefGoogle Scholar
  72. 72.
    Bherwani S, Ahirwar AK, Saumya AS et al. (2017) The study of association of Vitamin B(12) deficiency in type 2 diabetes mellitus with and without diabetic nephropathy in North Indian population. Diabetes Metab Syndr 11(Suppl 1):S365–S368CrossRefGoogle Scholar
  73. 73.
    Wu F, Jing Y, Tang X et al. (2017) Anemia: an independent risk factor of diabetic peripheral neuropathy in type 2 diabetic patients. Acta Diabetol 54(10):925–931CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2018

Authors and Affiliations

  • Ramamoorthy Jayashri
    • 1
  • Ulagamathesan Venkatesan
    • 1
  • Menon Rohan
    • 1
  • Kuppan Gokulakrishnan
    • 1
  • Coimbatore Subramanian Shanthi Rani
    • 1
  • Mohan Deepa
    • 1
  • Ranjit Mohan Anjana
    • 1
  • Viswanathan Mohan
    • 1
  • Rajendra Pradeepa
    • 1
    Email author
  1. 1.Madras Diabetes Research Foundation, Dr. Mohan’s Diabetes Specialities CentreWHO Collaborating Centre for Non-communicable Diseases Prevention and Control, ICMR Centre for Advanced Research on DiabetesChennaiIndia

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