Authors : Dr. M. Naga Pradeep; Dr. A. Nanda Gopal Reddy; Dr. S. Dimple

Volume/Issue : Volume 10 - 2025, Issue 1 - January

Google Scholar : https://tinyurl.com/bdtwn7yh

Scribd : https://tinyurl.com/2ucnhzp8

DOI : https://doi.org/10.5281/zenodo.14769398

Abstract : Background: Iron deficiency anemia (IDA) is the most prevalent nutritional anemia globally, affecting approximately 30% of the population. It has significant health implications, particularly in developing countries. Hemoglobin A1c (HbA1c) is a critical marker for assessing glycemic control and is used in diagnosing diabetes.  Objective: This study aims to evaluate the influence of iron deficiency anemia on HbA1c levels in non-diabetic and pre-diabetic individuals, assessing changes in HbA1c levels pre and post-correction of iron deficiency.  Methods: A prospective interventional study was conducted over 18 months at Katuri Medical College and Hospital. The study included 200 participants (100 with IDA and 100 controls). Various hematological parameters, including HbA1c, were measured before and after iron supplementation.  Results: The study found that participants with IDA had significantly lower HbA1c levels before treatment (4.60 ± 0.31%) compared to post-correction levels (5.80 ± 0.31%). The results indicated a statistically significant increase in HbA1c levels following the correction of iron deficiency, aligning closely with control group levels.  Conclusion: The findings suggest that iron deficiency anemia significantly affects HbA1c levels, which can lead to misdiagnosis of diabetes. It is crucial to consider iron status when interpreting HbA1c results in clinical practice, particularly in populations with a high prevalence of anemia. Further research is recommended to explore the relationship between IDA and glycemic control in larger cohorts.

References :

1. GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age- sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: A systematic analysis for the Global Burden of Disease Study 2013. Lancet, 2015; 385(9963): 117–71.
2. Bloomgarden ZT: A1C: Recommendations, debates, and questions. Diabetes Care, 2009; 32: e141–47.
3. Nadelson J, Satapathy SK, Nair S: Glycated hemoglobin levels in patients with decompensated cirrhosis. Int J Endocrinol, 2016; 2016: 8390210.
4. American Diabetes Association (ADA): Diagnosis and classification of dia betes mellitus. Diabetes Care, 2009; 32(Suppl. 1: S62–67.
5. Attard SM, Herring AH, Wang H et al: Implications of iron deficiency/ane mia on the classification of diabetes using HbA1c. Nutr Diabetes, 2015; 5: e166.
6. Lippi G, Targher G: A laboratory standpoint on the role of hemoglobin A1c for the diagnosis of diabetes in childhood: More doubts than certainties? Pediatr Diabetes, 2011; 12: 183–86.
7. Kim C, Bullard KM, Herman WH, Beckles GL: Association between iron de ficiency and A1C Levels among adults without diabetes in the National Health and Nutrition Examination Survey, 1999–2006. Diabetes Care, 2010; 33: 780–85.
8. Merono T, Dauteuille C, Tetzlaff W et al: Oxidative stress, HDL functional ity and effects of intravenous iron administration in women with iron de ficiency anemia. Clin Nutr, 2017; 36: 552–5.
9. International Expert Committee: International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care, 2009; 32: 1327–34.
10. American Diabetes Association: Diagnosis and classification of diabetes mellitus. Diabetes Care, 2013; 36(Suppl. 1): S67–74.
11. American Diabetes Association: Diagnosis and classification of diabetes mellitus. Diabetes Care, 2014; 37(Suppl. 1): S81–90.
12. Sehrawat T, Jindal A, Kohli P et al: Utility and limitations of glycated hemo globin (HbA1c) in patients with liver cirrhosis as compared with oral glucose tolerance test for diagnosis of diabetes. Diabetes Ther, 2018; 9: 243–51.
13. National Glycohemoglobin Standardization Program (NGSP). Factors that interfere with HbA1c test results. 2015; Available at [URL]: http://www. ngsp.org/factors.asp.
14. English E, Idris I, Smith G et al: The effect of anaemia and abnormalities of erythrocyte indices on HbA1c analysis: A systematic review. Diabetologia, 2015; 58: 1409–21.
15. Hanas R, John G: International HBA1c Consensus Committee. 2010 consen sus statement
16. on the worldwide standardization of the hemoglobin A1C measurement. Diabetes Care, 2010; 33: 1903–4.
17. World Health Organization (WHO): Worldwide prevalence of anae mia 1993–2005. 2008.
18. Available     at            [URL]:   https://apps.who.int/iris/bitstream/ handle/10665/43894/9789241596657_eng.pdf.
19. Algarin C, Nelson CA, Peirano P et al: Iron-deficiency anemia in infancy and poorer cognitive inhibitory control at age 10 years. Dev Med Child Neurol, 2013; 55: 453–58.
20. Lukowski AF, Koss M, Burden MJ et al: Iron deficiency in infancy and neu rocognitive functioning at 19 years: Evidence of long-term deficits in ex ecutive function and recognition mem.
21. Mojs E, Stanislawska-Kubiak M, Wojciak RW et al: Reduced iron parame ters and cognitive processes in children and adolescents with DM1 com pared to those with standard parameters. J Investig Med.
22. Soliman AT, De Sanctis V, Yassin M, Soliman N: Iron deficiency anemia and glucose metabolism. Acta Biomed, 2017; 88: 112–18.
23. Ahmad J, Rafat D: HbA1c and iron deficiency: A review. Diabetes Metab Syndr, 2013; 7: 118–22.
24. Cavagnolli G, Pimentel AL, Freitas PA et al: Factors affecting A1C in non-di abetic individuals: Review and meta-analysis. Clin Chim Acta, 2015; 445: 107–14.
25. Grossman A, Gafter-Gvili A, Schmilovitz-Weiss H et al: Association of gly cated hemoglobin with hemoglobin levels in elderly nondiabetic subjects. Eur J Intern Med, 2016; 36: 32–35.
26. Akkermans MD, Mieke Houdijk ECA, Bakker B et al: Iron status and its as sociation with HbA1c levels in Dutch children with diabetes mellitus type 1. Eur J Pediatr, 2018; 177: 603– 10.
27. Christy AL, Manjrekar PA, Babu RP et al: Influence of iron deficiency ane mia on hemoglobin A1c levels in diabetic individuals with controlled plas ma glucose levels. Iran Biomed J, 2014; 18: 88–93.
28. Simmons D, Hlaing T: Interpretation of HbA1c: Association with mean cell volume and haemoglobin concentration. Diabet Med, 2014; 31: 1387–92.
29. Hardikar PS, Joshi SM, Bhat DS et al: Spuriously high prevalence of pre diabetes diagnosed by HbA(1c) in young indians partly explained by he matological factors and iron deficiency anemia. Diabetes Care, 2012; 35: 797–802.
30. Gallagher EJ, Le Roith D, Bloomgarden Z: Review of hemoglobin A(1c) in the management of diabetes. J Diabetes, 2009; 1: 9–17.
31. Ford ES, Cowie CC, Li C et al: Iron-deficiency anemia, non-iron-deficiency      anemia and HbA1c among adults in the US. J Diabetes, 2011; 3: 67–73.
32. Coban E, Ozdogan M, Timuragaoglu A: Effect of iron deficiency anemia on the levels of hemoglobin A1c in nondiabetic patients. Acta Haematol, 2004; 112: 126–28.
33. Brooks AP, Metcalfe J, Day JL, Edwards MS: Iron deficiency and glycosylat ed haemoglobin Lancet, 1980; 2: 141.
34. Koga M, Morita S, Saito H et al: Association of erythrocyte indices with glycated haemoglobin in pre-menopausal women. Diabet Med, 2007; 24: 843–47.
35. El-Agouza I, Abu Shahla A, Sirdah M: The effect of iron deficiency anaemia on the levels of haemoglobin subtypes: Possible consequences for clinical diagnosis. Clin Lab Haematol, 2002; 24: 285–89.
36. Wu X, Ding X, Dai J et al: [Changes of glycosylated hemoglobin in various anemia diseases.] Modern Diagnosis and Treatment, 1991; 2: 228–30 [in Chinese.
37. O’Keeffe DT, Maraka S, Rizza RA: HbA1c in the evaluation of diabetes mel litus. JAMA, 2016; 315: 605–6.
38. Xia D, McShine R, Berg AH: Misleading hemoglobin A1c levels in a patient with paroxysmal nocturnal hemoglobinuria. Am J Clin Pathol, 2014; 142: 261–65.
39. Silva JF, Pimentel AL, Camargo JL. Effect of iron deficiency anaemia on HbA1c levels is dependent on the degree of anaemia. Clinical biochemistry. 2016 Jan 1;49(1-2):117-20.
40. Ditzel J, Kjaergaard JJ: Haemoglobin AIc concentrations after initial insulin treatment for newly discovered diabetes. Br Med J, 1978; 1: 741–42.
41. Rajagopal L, Ganapathy S, Arunachalam S et al: Does iron deficiency anae mia and its severity influence HbA1C level in non diabetics? An analysis of 150 cases. J Clin Diagn Res, 2017; 11: EC13–15.
42. Nakatani R, Murata T, Usui T et al: Importance of the average glucose level and estimated glycated hemoglobin in a diabetic patient with hereditary hemolytic anemia and liver cirrhosis. Intern Med, 2018; 57: 537–43.
43. Sacks DB, Arnold M, Bakris GL et al: Executive summary: Guidelines and recommendations for laboratory analysis in the diagnosis and manage ment of diabetes mellitus. Clin Chem, 2011; 57: 793–98.
44. Bry L, Chen PC, Sacks DB: Effects of hemoglobin variants and chemically modified derivatives on assays for glycohemoglobin. Clin Chem, 2001; 47: 153–63.
45. Szymezak J, Lavalard E, Martin M et al: Carbamylated hemoglobin remains a critical issue in HbA1c measurements. Clin Chem Lab Med, 2009; 47: 612–13.
46. Sinha N, Mishra TK, Singh T, Gupta N: Effect of iron deficiency anemia on hemoglobin A1c levels. Ann Lab Med, 2012; 32: 17–22.
47. Otabe S, Nakayama H, Ohki T et al: Haemoglobin variants may cause sig nificant differences in haemoglobin A1c as measured by high-performance liquid chromatography and enzymatic methods in diabetic patients: A cross sectional study. Ann Clin Biochem, 2017; 54: 432–37.
48. Lacy ME, Wellenius GA, Sumner AE et al: Association of sickle cell trait with hemoglobin A1c in African Americans. JAMA, 2017; 317: 507–15.
49. Rohlfing C, Hanson S, Weykamp C et al: Effects of hemoglobin C, D, E and S traits on measurements of hemoglobin A1c by twelve methods. Clin Chim Acta, 2016; 455: 80–83.
50. Lee BS, Jayathilaka GD, Huang JS et al: Analyses of in vitro nonenzymat ic glycation of normal and variant hemoglobins by MALDI-TOF mass spec trometry. J Biomol Tech, 2011; 22: 90–94.
51. Higgins T, Stewart D, Boehr E: Challenges in HbA1c analysis and reporting: An interesting case illustrating the many pitfalls. Clin Biochem, 2008; 41: 1104–6.
52. Little RR, Rohlfing CL: The long and winding road to optimal HbA1c mea surement. Clin Chim Acta, 2013; 418: 63–71.
53. Koga M, Kurebayashi S, Murai J et al: Degree of discrepancy between HbA1c and glycemia in variant hemoglobin is smaller when HbA1c is measured by new-type Arkray HPLC compared with old-type HPLC. Clin Biochem, 2014; 47: 123–25.
54. World Health Organization (WHO) Guidelines Approved by the Guidelines Review Committee. Use of Glycated Haemoglobin (HbA1c) in the Diagnosis of Diabetes Mellitus: Abbreviated Report of a WHO Consultation. Geneva: World Health Organization; 2011. Available from [URL]: https://www.ncbi. nlm.nih.gov/books/NBK304267/.
55. Gould BJ, Davie SJ, Yudkin JS: Investigation of the mechanism underlying the variability of glycated haemoglobin in non-diabetic subjects not relat ed to glycaemia. Clin Chim Acta, 1997; 260: 49–64.
56. Zhang Y, Li Y, Zheng F: [Effects of iron deficiency on blood lipids and liver lipid peroxidation in rats.] Chinese Chronic Disease Prevention and Control, 2011; 19: 577–78.
57. Zaka-Ur-Rab Z, Adnan M et al: Effect of oral iron on markers of oxidative stress and antioxidant status in children with iron deficiency anaemia. J Clin Diagn Res, 2016; 10: SC13–19.
58. Sundaram RC, Selvaraj N, Vijayan G et al: Increased plasma malondial dehyde and fructosamine in iron deficiency anemia: effect of treatment. Biomed Pharmacother, 2007; 61: 682–85.
59. Jain SK, Palmer M: The effect of oxygen radicals metabolites and vitamin E on glycosylation of proteins. Free Radic Biol Med, 1997; 22: 593–96.
60. Jain SK: Glutathione and glucose-6-phosphate dehydrogenase deficiency can increase protein glycosylation. Free Radic Biol Med, 1998; 24: 197–201.
61. Silva JF, Pimentel AL, Camargo JL: Effect of iron deficiency anaemia on HbA1c levels is dependent on the degree of anaemia. Clin Biochem, 2016; 49: 117–20.
62. Sinha N, Mishra TK, Singh T, Gupta N. Effect of iron deficiency anemia on hemoglobin A1c levels. Annals of laboratory medicine. 2012 Jan 1;32(1):17-22.
63. MS: Iron deficiency and glycosylat ed haemoglobin A. Lancet, 1980; 2: 141.
64. Çetinkaya Altuntaş S, Evran M, Gürkan E, Sert M, Tetiker T. HbA1c level decreases in iron deficiency anemia. Wiener klinische Wochenschrift 2021;133:102–6.
65. Kalairajan S, AR M. A study on influence of iron deficiency anaemia over HbA1c levels. 2019;
66. Solomon A, Hussein M, Negash M, Ahmed A, Bekele F, Kahase D. Effect of iron deficiency anemia on HbA1c in diabetic patients at Tikur Anbessa specialized teaching hospital, Addis Ababa Ethiopia. BMC hematology 2019;19:1–5.
67. Renz PB, Hernandez MK, Camargo JL. Effect of iron supplementation on HbA1c levels in pregnant women with and without anaemia. Clinica Chimica Acta 2018;478:57–61.
68. Rao LV, Pratt GW, Bi C, Kroll MH. Large-scale retrospective analyses of the effect of iron deficiency anemia on hemoglobin A1c concentrations. Clinica Chimica Acta 2022;529:21–4.
69. Nasli-Esfahani E, Larijani B, Amini P, GHASEMABADI RG, Razmandeh R. Effect of treatment of iron deficiency anemia onhemoglobin A1c in type 2 diabetic patients. Turkish journal of medical sciences 2017;47(5):1441–6.
70. Sumathi K, Dilliraj G, Shanthi B, Selvi VK, Rani AJ. Correlation between iron deficiency anemia and HbA1C levels in type 2 diabetes mellitus. Int J Clin Biochem Res 2020;7(3):400– 2.
71. Aydın B, Özçelik S, Kilit TP, Eraslan S, Çelik M, Onbaşı K. Relationship between glycosylated hemoglobin and iron deficiency anemia: A common but overlooked problem. Primary Care Diabetes 2022;16(2):312–7.
72. Hameed HA. Effect of Iron Deficiency Anemia on HbA1c in Diabetic Patients in Salah al-Din Hospital, Iraq. Journal of Survey in Fisheries Sciences 2023;10(4S):1304–14.
73. Rajagopal L, Arunachalam S, Ganapathy S, Ramraj B, Raja V. A comparison of effect of Iron Deficiency Anemia on HbA1c levels in controlled diabetics and non-diabetics: A cross sectional analysis of 300 cases. Annals of Pathology and Laboratory Medicine 2017;4(02):212–8.
74. Narayanan S, Dash P, Mahajan P. Effect of total hemoglobin level on HbA1c value in type 2 diabetes mellitus patients. Bangladesh Journal of Medical Science 2020;19(1):110–3.
75. Jeyaprakash N, Sudha M. A study on influence of iron deficiency anemia over HbA1c levels.
76. International Archives of Integrated Medicine 2020;7(12).
77. Qureshi MD, Waqar S, Khan MI, Naseem L. Association between iron deficiency anemia and HBA1C level in diabetic patients with controlled plasma glucose levels. The Professional Medical Journal 2020;27(09):1849–54.
78. Vijaya Durairaj K. A Study on Influence of Iron Deficiency Anaemia over HbA1c Levels. 2017;
79. Intra J, Limonta G, Cappellini F, Bertona M, Brambilla P. Glycated haemoglobin and iron deficiency anaemia: a case‐control study. Practical Diabetes 2018;35(3):90–96a.
80. Mohamed AS, Mohamed EN, Abd El Halim AF, Metwally ESA. Effect of Iron Deficiency Anemia on HbA1c Levels in Non-Diabetic Individuals. The Egyptian Journal of Hospital Medicine 2021;82(1):74–9.
81. Porwal V, Malik A, Deshpande R, Salve C. The Impact of Iron Deficiency Anemia on HbA1c Levels in Non-Diabetic Patients.
82. Gharde C, Atkar CM, Tayade A, Kungar T. TO STUDY THE EFFECT OF IRON DEFICIENCY ANAEMIA ON HBA1C LEVELS IN NON DIABETICS AT TERTIARY CARE CENTRE OF CENTRAL INDIA A CROSS SECTIONAL STUDY. Int J Acad Med Pharm 2023;5(2):1446–50.
83. Kaltsum TI, Pusparini P. Poor Glycemic Control Correlates with Iron Deficiency Anemia in Type 2 Diabetes Mellitus. Althea Medical Journal 2023;10(2):99–103.
84. Sinha N, Mishra TK, Singh T, Gupta N. Effect of iron deficiency anemia on hemoglobin A1c levels. Ann Lab Med. 2012;32:17–22.
85. Intra J, Limonta G, Cappellini F, Bertona M, Brambilla P. Glycosylated hemoglobin in subjects affected by iron-deficiency anemia. Diabetes & Metabolism Journal. 2019 Aug;43(4):539.
86. Jeyaprakash N, Sudha M. A study on influence of iron deficiency anemia over HbA1c levels.
87. International Archives of Integrated Medicine. 2020 Dec 1;7(12).
88. Kumar CH, Nutakki G. A prospective study of effect of iron deficiency anemia on HbA1c levels in non-diabetics. International Archives of Integrated Medicine. 2017 Dec 1;4(12).
89. Mohamed AS, Mohamed EN, Abd El Halim AF, Metwally ES. Effect of iron deficiency anemia on HbA1c levels in non-diabetic individuals. The Egyptian Journal of Hospital Medicine. 2021 Jan 1;82(1):74-9.
90. Manisha G, Nitin S, Ranjana M et al. of glycosylated hemoglobin in Iron deficiency Anemia. Sch J App Med Sci., 4(2C): 532-5.
91. Sacks D, Arnold M, Bakris G et al. (2011): Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem., 57: 1–47.
92. Saudek C, Brick J (2009): The clinical use of hemoglobin A1c. J. Diabetes Sci Technol., 3: 629–634.
93. American Diabetes Association (2015): Classification and diagnosis of diabetes. Diabetes Care, 38(1): 8–16.
94. Madhu SV, Raj A, Gupta S, Giri S, Rusia U. Effect of iron deficiency anemia and iron supplementation on HbA1c levels: implications for diagnosis of prediabetes and diabetes mellitus in Asian Indians. Clin Chim Acta. 2017;468:225–229.
95. Solomon A, Hussein M, Negash M et al. of iron deficiency anemia on HbA1c in diabetic patients at Tikur Anbessa specialized teaching hospital, Addis Ababa Ethiopia. BMC Hematology, 19(1): 2-7.
96. Silva JF, Pimentel AL, Camargo JL. Effect of iron deficiency anemia on HbA1c levels is dependent on the degree of anemia. Clin Biochem. 2016;49:117–120.
97. Grossman A, Gafter-Gvili A, Schmilovitz-Weiss H, Koren-Morag N, Beloosesky Y, Weiss A. Association of glycated hemoglobin with hemoglobin levels in elderly nondiabetic subjects. Eur J Intern Med. 2016;36:32–35.
98. Selvaraj N, Bobby Z, Sathiyapriya V. Effect of lipid peroxides and antioxidants on glycation of hemoglobin: an in vitro study on human erythrocytes. Clin Chim Acta. 2006;366:190–195.
99. Zaka-Ur-Rab Z, Adnan M, Ahmad SM, Islam N. Effect of oral iron on markers of oxidative stress and antioxidant status in children with iron deficiency anemia. J Clin Diagn Res. 2016;10:SC13–SC19.
100. Del Rio D, Stewart AJ, Pellegrini N. A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis. 2005;15:316– 328.
101. Mitchell TR, Anderson D, Shepperd J. Iron deficiency, haemochromatosis, and glycosylated haemoglobin. Lancet. 1980;2:747.
102. van Heyningen C, Dalton RG. Glycosylated haemoglobin in iron-deficiency anaemia. Lancet.
103. 1985;1:874.
104. Brooks AP, Metcalfe J, Day JL, Edwards MS. Iron deficiency and glycosylated haemoglobin A. Lancet. 1980;2:141.
105. Sluiter WJ, van Essen LH, Reitsma WD, Doorenbos H. Glycosylated haemoglobin and iron deficiency. Lancet. 1980;2:531–532.
106. Gram-Hansen P, Eriksen J, Mourits-Andersen T, Olesen L. Glycosylated haemoglobin (HbA1c) in iron- and vitamin B12 deficiency. J Intern Med. 1990;227:133–136.
107. Rai KB, Pattabiraman TN. Glycosylated haemoglobin levels in iron deficiency anaemia. Indian J Med Res. 1986;83:234–236.
108. Christy AL, Manjrekar PA, Babu RP, Hegde A, Rukmini MS. Influence of iron deficiency anemia on hemoglobin A1c levels in diabetic individuals with controlled plasma glucose levels. Iranian biomedical journal. 2014 Apr;18(2):88.
109. Kim C, Bullard KM, Herman WH, Beckles GL. Association between iron deficiency and A1C Levels among adults without diabetes in the National Health and Nutrition Examination Survey, 1999–2006. Diabetes Care. 2010;33:780–785.