Association between hematological parameters, serum retinol, and glycemic indices in diabetes mellitus: a preliminary case–control study

Background: The global prevalence of type 2 diabetes mellitus (T2DM) is on the rise. Hyperglycemia, free radical damage, and inflammation are commonly implicated as the etiopathological factors of diabetes mellitus. This preliminary study aims to investigate the association of the disease with serum retinol and hematological parameters and compare these parameters with non-diabetic controls.
Methods: The biophysical profiles of 85 subjects with diabetes and the same number of healthy controls were recorded using standard techniques. Biochemical and hematological investigations were carried out. The data are expressed as median with interquartile range (IQR) values. Mann–Whitney U-test was conducted to assess the difference between the two groups.
Results: There were a significant increase in median values of glycated hemoglobin (HbA1c), fasting blood glucose (FPG), and white blood cells (WBC) and a significant decrease in median values of monocytes in subjects with T2DM as compared to controls. There was a significant negative correlation between eosinophils and FPG in subjects with T2DM. In healthy controls, there was a significant positive correlation between serum retinol, certain hematological parameters, and HbA1c; and there was a significant negative correlation between WBC and FPG. The T2DM group had a significant negative correlation between eosinophil count and FBG.
Conclusion: Our study shows that serum retinol levels are not reflective of oxidative stress, but a routine WBC and differential count can shed light on the chronic inflammatory status. These results help with the formulation of targeted treatment to delay progression of the disease and prevent its complications.
Relevance for Patients: Vitamin A plays a pivotal role safeguarding the immunity and eye health for diabetic patients, but serum retinol estimation is not reflective of inflammatory or glycemic control status in diabetic patients. They would benefit from a hematocrit test.
[1] Roglic G, World Health Organization, editors. Global Report on Diabetes. Geneva, Switzerland: World Health Organization; 2016. p. 86. doi: 10.4103/2468-8827.184853
[2] India State-Level Disease Burden Initiative Cancer Collaborators. The Burden of Cancers and their Variations across the States of India: The Global Burden of Disease Study 1990-2016. Lancet Oncol 2018;19:1289-306.
[3] Powers AC, Niswender KD, Evans-Molina C. Diabetes Mellitus: Diagnosis, Classification, and Pathophysiology. In: Jameson JL, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J, editors. Harrison’s Principles of Internal Medicine. 20th ed. New York: McGraw-Hill Education; 2018. Available from: https://accessmedicine. mhmedical.com/content.aspx?aid=1156520865 [Last accessed on 2021 May 11].
[4] Muranyi M, Li PA. Hyperglycemia Increases Superoxide Production in the CA1 Pyramidal Neurons After Global Cerebral Ischemia. Neurosci Lett 2006;393:119-21. doi: 10.1016/j.neulet.2005.09.079
[5] Neri S, Bruno CM, Raciti C, D’Angelo G, D’Amico R, Cristaldi R. Alteration of Oxide Reductive and Haemostatic Factors in Type 2 Diabetics. J Intern Med 1994;236:495-500. doi: 10.1111/j.1365-2796.1994.tb00835.x
[6] Ott C, Jacobs K, Haucke E, Navarrete Santos A, Grune T, Simm A. Role of Advanced Glycation End Products in Cellular Signaling. Redox Biol 2014;2:411-29. doi: 10.1016/j.redox.2013.12.016
[7] Jabeen F, Rizvi HA, Aziz F, Wasti AZ. Hyperglycemic Induced Variations in Hematological Indices in Type 2 Diabetics. IJAR 2013;1:322-34.
[8] Edge R, McGarvey DJ, Truscott TG. The Carotenoids as Anti-oxidants - a Review. J Photochem Photobiol B 1997;41:189-200. doi: 10.1016/S1011-1344(97)00092-4
[9] Twig G, Afek A, Shamiss A, Derazne E, Tzur D, Gordon B, et al. White Blood Cells Count and Incidence of Type 2 Diabetes in Young Men. Diabetes Care 2013;36:276-82. doi: 10.2337/dc11-2298
[10] Palella E, Cimino R, Pullano SA, Fiorillo AS, Gulletta E, Brunetti A, et al. Laboratory Parameters of Hemostasis, Adhesion Molecules, and Inflammation in Type 2 Diabetes Mellitus: Correlation with Glycemic Control. Int J Environ Res Public Health 2020;17:300. doi: 10.3390/ijerph17010300
[11] Balmer JE, Blomhoff R. Gene Expression Regulation by Retinoic Acid. J Lipid Res 2002;43:1773-808. doi: 10.1194/jlr.r100015-jlr200
[12] Iqbal S, Naseem I. Role of Vitamin A in Type 2 Diabetes Mellitus Biology: Effects of Intervention Therapy in a Deficient State. Nutrition 2015;31:901-7. doi: 10.1016/j.nut.2014.12.014
[13] Basualdo CG, Wein EE, Basu TK. Vitamin A (retinol) Status of First Nation Adults with Non-insulin-dependent Diabetes Mellitus. J Am Coll Nutr 1997;16:39-45. doi: 10.1080/07315724.1997.10718647
[14] Reunanen A, Knekt P, Aaran RK, Aromaa A. Serum Antioxidants and Risk of Non-insulin Dependent Diabetes Mellitus. Eur J Clin Nutr 1998;52:89-93. doi: 10.1038/sj.ejcn.1600519
[15] Abahusain MA, Wright J, Dickerson JW, de Vol EB. Retinol, Alpha-tocopherol and Carotenoids in Diabetes. Eur J Clin Nutr 1999;53:630-5. doi: 10.1038/sj.ejcn.1600825
[16] Zhang C, Li K, Zhang J, Kuang X, Liu C, Deng Q, et al. Relationship between Retinol and Risk of Diabetic Retinopathy: A Case-control Study. Asia Pac J Clin Nutr 2019;28:607-13. doi: 10.6133/apjcn.201909_28(3).0021
[17] Viroonudomphol D, Pongpaew P, Tungtrongchitr R, Changbumrung S, Tungtrongchitr A, Phonrat B, et al. The Relationships between Anthropometric Measurements, Serum Vitamin A and E Concentrations and Lipid Profiles in Overweight and Obese Subjects. Asia Pac J Clin Nutr 2003;12:73-9.
[18] Parthiban A, Vijayalingam S, Shanmugasundaram KR, Mohan R. Oxidative Stress and the Development of Diabetic Complications--Antioxidants and Lipid Peroxidation in Erythrocytes and Cell Membrane. Cell Biol Int 1995;19:987-93. doi: 10.1006/cbir.1995.1040
[19] Yang Q, Graham TE, Mody N, Preitner F, Peroni OD, Zabolotny JM, et al. Serum Retinol Binding Protein 4 Contributes to Insulin Resistance in Obesity and Type 2 Diabetes. Nature 2005;436:356-62. doi: 10.1038/nature03711
[20] Bobbert T, Raila J, Schwarz F, Mai K, Henze A, Pfeiffer AF, et al. Relation between Retinol, Retinol-Binding Protein 4, Transthyretin and carotid Intima Media Thickness. Atherosclerosis 2010;213:549-51. doi: 10.1016/j.atherosclerosis.2010.07.063
[21] Kuo TY, Wu CZ, Lu CH, Lin JD, Liang YJ, Hsieh CH, et al. Relationships between White Blood Cell Count and Insulin Resistance, Glucose Effectiveness, and First- and Second-Phase Insulin Secretion in Young Adults. Medicine (Baltimore) 2020;99:e22215. doi: 10.1097/MD.0000000000022215
[22] Vozarova B, Weyer C, Lindsay RS, Pratley RE, Bogardus C, Tataranni PA. High White Blood Cell Count is Associated with a Worsening of Insulin Sensitivity and Predicts the Development of Type 2 Diabetes. Diabetes 2002;51:455-61. doi: 10.2337/diabetes.51.2.455
[23] Ford ES. Leukocyte Count, Erythrocyte Sedimentation Rate, and Diabetes Incidence in a National Sample of US Adults. Am J Epidemiol 2002;155:57-64. doi: 10.1093/aje/155.1.57
[24] Tong PC, Lee KF, So WY, Ng MH, Chan WB, Lo MK, et al. White Blood Cell Count is Associated with Macro- and Microvascular Complications in Chinese Patients with Type 2 Diabetes. Diabetes Care 2004;27:216-22. doi: 10.2337/diacare.27.1.216
[25] Chung FM, Tsai JC, Chang DM, Shin SJ, Lee YJ. Peripheral Total and differential Leukocyte Count in Diabetic Nephropathy: The Relationship of Plasma Leptin to Leukocytosis. Diabetes Care 2005;28:1710-7. doi: 10.2337/diacare.28.7.1710
[26] Gkrania-Klotsas E, Ye Z, Cooper AJ, Sharp SJ, Luben R, Biggs ML, et al. Differential White Blood Cell Count and Type 2 Diabetes: Systematic Review and Meta-analysis of Cross-sectional and Prospective Studies. PLoS One 2010;5:e13405. doi: 10.1371/journal.pone.0013405
[27] Moradi S, Kerman SR, Rohani F, Salari F. Association between Diabetes Complications and Leukocyte Counts in Iranian Patients. J Inflamm Res 2012;5:7-11.
[28] Chen Y, Yan SS, Colgan J, Zhang HP, Luban J, Schmidt AM, et al. Blockade of Late Stages of Autoimmune Diabetes by Inhibition of the Receptor for Advanced Glycation End Products. J Immunol 2004;173:1399-405.
[29] Lorenzo C, Hanley AJ, Haffner SM. Differential White Cell Count and Incident Type 2 Diabetes: The Insulin Resistance Atherosclerosis Study. Diabetologia 2014;57:83-92. doi: 10.1007/s00125-013-3080-0
[30] Zhang H, Yang Z, Zhang W, Niu Y, Li X, Qin L, et al. White Blood Cell Subtypes and Risk of Type 2 Diabetes. J Diabetes Complications 2017;31:31-7. doi: 10.1016/j.jdiacomp.2016.10.029
[31] Sulochana S, Viswanath A, Gautaman S. Correlation of Haematological Parameters such as Haemoglobin, Total and differential Leucocyte Count, Platelet Count, Mean Platelet Volume, Platelet Distribution width in Relation to Glycated Haemoglobin in Type 2 Diabetes Mellitus. Int J Pharm Biol Sci 2017;8:527-31. doi: 10.22376/ijpbs.2017.8.2.b527-531
[32] Huang ZS, Wang CH, Yip PK, Yang CY, Lee TK. In Hypercholesterolemia, Lower Peripheral Monocyte Count is Unique among the Major Predictors of Atherosclerosis. Arterioscler Thromb Vasc Biol 1996;16:256-61. doi: 10.1161/01.atv.16.2.256
[33] Bhutto AR, Abbasi A, Abro AH. Correlation of Hemoglobin A1c with Red Cell width Distribution and Other Parameters of Red Blood Cells in Type II Diabetes Mellitus. Cureus 2019;11:e5533. doi: 10.7759/cureus.5533
[34] Wen Y. High Red Blood Cell Distribution width is Closely Associated with Risk of Carotid Artery Atherosclerosis in Patients with Hypertension. Exp Clin Cardiol 2010;15:37-40.