The Haemolytic Changes During Progression of Pre-Diabetes to Type 2 Diabetes in a High-Fat High-Carbohydrate Diet-Induced Pre-Diabetic Rat Model


Authors

  • N.C. Mzimela School of Laboratory Medicine and Medical Science, College of Health Sciences, University of Kwa-Zulu Natal, Durban, South Africa
  • P.S. Ngubane School of Laboratory Medicine and Medical Science, College of Health Sciences, University of Kwa-Zulu Natal, Durban, South Africa
  • A. Khathi School of Laboratory Medicine and Medical Science, College of Health Sciences, University of Kwa-Zulu Natal, Durban, South Africa

DOI:

https://doi.org/10.3923/pjn.2021.55.63

Keywords:

Hemolysis, high-fat high-carbohydrate diet, pre-diabetes, pre-diabetic rat, type 2 diabetes, unhealthy diets

Abstract

Background and Objective: Reports show that type 2 diabetic (T2D) patients have changes in red blood cell (RBC) indices as well as decreased erythropoietin (EPO) levels and endothelial nitric oxide synthase (eNOS) activity. Some abnormalities have been reported to develop during the pre-diabetes stage. However, information on haemolytic changes during the progression of pre-diabetic stage has not yet been reported. Therefore, this study was sought to characterize the changes in RBC indices and concentration of eNOS and EPO in the pre-diabetic stage. Materials and Methods: Pre-diabetes was induced using a high-fat high-carbohydrate diet for 20 weeks. Rats were then divided into non-diabetic and prediabetic rats (n = 6 in each group). The pre-diabetes progressed to T2D over an additional 12-week experimental period. RBC indices were measured at the end of 20 and 32 week. Following sacrificed after 32 weeks, blood was collected for eNOS and EPO measurements. Results: The results showed significant increases in RBCs, hemoglobin (HGB), hematocrit (HCT) in the prediabetic group as compared to the non-prediabetic group. We further observed a significant decrease in white blood cell (WBC) concentration, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width (RDW) in the prediabetic group as compared to the non-prediabetic group. Conclusion: Changes in blood cells indices indicate various haemolytic changes in RBCs morphology during progression towards overt T2D. However, EPO upregulation indicates the production of new RBCs, while decrease in eNOS activity indicated decrease in bioavailability of nitric oxide (NO).

References

Graves, D.T. and R.A. Kayal, 2008. Diabetic complications and dysregulated innate immunity. Front. Biosci., 13: 1227-1239.

Taheri, E., M. Djalali, A. Saedisomeolia, A. Moghadam, A. Djazayeri and M. Qorbani, 2012. The relationship between the activates of antioxidant enzymes in red blood cells and body mass index in Iranian type 2 diabetes and healthy subjects. J. Dia. Meta. Diso., 11: 1-3.

Nada, A.M., 2015. Red cell distribution width in type 2 diabetic patients. Diabetes Metab. Syndr. Obesity: Targets Ther., 8: 525-533.

Viskupicova, J., D. Blaskovic, S. Galiniak, M. Soszyński, G. Bartosz, L. Horakova and I. Sadowska-Bartosz, 2015. Effect of high glucose concentrations on human erythrocytes in vitro. Redox Biol., 5: 381-387.

Jaman, M.S., M.S. Rahman, R.R. Swarna, J. Mahato, M.M. Miah and M. Ayshasiddeka, 2017. Diabetes and Red Blood Cell Parameters. Ann. Clin. Endocrinol. Metab., Vol. 2.

Salaza-Vazquez, B.Y., M. Intaglietta, M. Rodriguez-Moran and F. Guerrero-Romero, 2006. Blood pressure and hematocrit in diabetes and the role of endothelial responses in the variability of blood viscosity. Diabetes Care, 29: 1523-1588.

Borissoff, J.I., H.M.H. Spronk, S. Heeneman and H. ten Cate, 2009. Is thrombin a key player in the 'coagulation-atherogenesis' maze? Cardiovasc. Res., 82: 392-403.

Egan, K., F.N. Ainle and D. Kenny, 2016. Platelets, Atherothrombosis, and Atherosclerosis. PeerJ Preprints.

Mazzone, T., A. Chait and J. Plutzky, 2008. Cardiovascular disease risk in type 2 diabetes mellitus: Insights from mechanistic studies. Lancet, 371: 1800-1809.

Sharif, A., S. Younus, K. Baig and N.H. Ali, 2014. Prevalence and risk of anemia in type-2 diabetic patients. Health, 6: 1415-1419.

Mzimela, N.C., P.S. Ngubane and A. Khathi, 2019. The Changes in Immune Cell Concentration during the Progression of Pre-diabetes to Type 2 Diabetes in a High-Fat High-Carbohydrate Diet-Induced Pre-Diabetic Rat Model. Autoimmunity, 52: 27-36.

Khathi, A., M. Luvuno and M. Mabandla, 2018. Voluntary Ingestion of a High-Fat High-Carbohydrate Diet: A Model for Prediabetes. PONTE Int. Sci. Res. J., Vol. 74.

Gamede, M., L. Mabuza, P. Ngubane and A. Khathi, 2018. The Effects of Plant-Derived Oleanolic Acid on Selected Parameters of Glucose Homeostasis in a Diet-Induced Pre-Diabetic Rat Model. Molecules, Vol. 23, No. 4.

Gamede, M., L. Mabuza, P. Ngubane and A. Khathi, 2019. Plant-Derived Oleanolic Acid (OA) Ameliorates Risk Factors of Cardiovascular Diseases in a Diet-Induced Pre-Diabetic Rat Model: Effects on Selected Cardiovascular Risk Factors. Molecules, Vol. 24.

Khathi, A., M. Luvuno and M. Mabandla, 2019. Diet-Induced Prediabetes: Effects on Oxidative Stress and Inflammatory Biomarkers as Agents for Vascular Complications in Renal Function. PONTE Int. Sci. Res. J., Vol. 75.

Mabuza, L.P., M.W. Gamede, S. Maikoo, I.N. Booysen, P.S. Ngubane and A. Khathi, 2019. Cardioprotective effects of a ruthenium (II) schiff base complex in diet-induced prediabetic rats. Diabetes, Metab. Syndr. Obesity: Targets Ther., 12: 217-223.

Malandrino, N., W.C. Wu, T.H. Taveira, H.B. Whitlatch and R.J. Smith, 2011. Association between red blood cell distribution width and macrovascular and microvascular complications in diabetes. Diabetologia, 55: 226-235.

American Diabetes Association, 2010. Diagnosis and classification of diabetes mellitus. Diabetes Care, 33: S62-S69.

WHO., 2016. Global Report on Diabetes. WHO Press, Geneva, Switzerland, ISBN: 9789241565257, Pages: 86.

Grundy, S.M., 2012. Pre-diabetes, metabolic syndrome, and cardiovascular risk. J. Am. Coll. Cardiol., 59: 635-643.

Jabeen, F., H.A. Rizvi and A. Subhan, 2012. Effect of hyperglycemia on superoxide dismutase defense system and erythrocyte indices in diabetic patients. Pak. J. Biochem. Mol. Biol., 45: 85-89.

Kim, J., H. Lee and S. Shin, 2015. Advances in the measurement of red blood cell deformability: A brief review. J. Cell. Biotechnol., 1: 63-79.

Bunn, H.F., 2013. Erythropoietin. Cold Spring Harbor Perspect. Med., Vol. 3.

Marsden, J.T., 2006. Erythropoietin - measurement and clinical applications. Ann. Clin. Biochem.: Int. J. Lab. Med., 43: 97-104.

Souma, T., N. Suzuki and M. Yamamoto, 2015. Renal Erythropoietin-Producing Cells in Health and Disease. Front. Physiol., Vol. 6.

Souma, T., M. Nezu, D. Nakano, S. Yamazaki and I. Hirano et al., 2015. Erythropoietin synthesis in renal myofibroblasts is restored by activation of hypoxia signaling. J. Am. Soc. Nephrology, 27: 428-438.

Barbieri, J., P.C. Fontela, E.R. Winkelmann, C.E.P. Zimmermann, Y.P. Sandri, E.K.V. Mallet and M.N. Frizzo, 2015. Anemia in Patients With Type 2 Diabetes Mellitus. Anemia.

Magri, C.J. and S. Fava, 2013. Red blood cell distribution width and diabetes-associated complications. Diabetes Metab. Syndr.: Clin. Res. Rev., 8: 13-17.

Calderón-Salinas, J.V., E.G. Muñoz-Reyes, J.F. Guerrero-Romero, M. Rodríguez-Morán, R.L. Bracho-Riquelme, M.A. Carrera-Gracia and M.A. Quintanar-Escorza, 2011. Eryptosis and oxidative damage in type 2 diabetic Mellitus patients with chronic kidney disease. Mol. Cell. Biochem., 357: 171-179.

Brown, C.D., H.S. Ghali, Z. Zhao, L.L. Thomas and E.L.I.A. Friedman, 2004. Association of reduced red blood cell deformability and diabetic nephropathy. Kidney Int., 67: 295-300.

Kristiansen, O.P. and T. Mandrup-Poulsen, 2005. Interleukin-6 and diabetes: The good, the bad, or the indifferent? Diabetes, 54: S114-S124.

Moon, J.S., J.H. Kim, J.H. Kim, I.R. Park and J.H. Lee et al., 2016. Impaired rbc deformability is associated with diabetic retinopathy in patients with type 2 diabetes. Diabetes Metab., 42: 448-452.

Chong-Martinez, B., T.A. Buchanan, R.B. Wenby and H.J. Meiselman, 2003. Decreased red blood cell aggregation subsequent to improved glycaemic control in type 2 diabetes mellitus. Diabetic Med., 20: 301-306.

Badimon, L. and G. Vilahur, 2014. Thrombosis formation on atherosclerotic lesions and plaque rupture. J. Internal Med., 276: 618-632.

Gutierrez, M., M.B. Fish, A.W. Golinski and O. Eniola-Adefeso, 2018. Presence of rigid red blood cells in blood flow interferes with the vascular wall adhesion of leukocytes. Langmuir, 34: 2363-2372.

Natali, A., E. Toschi, S. Baldeweg, A. Casolaro and S. Baldi et al., 2005. Haematocrit, type 2 diabetes, and endothelium-dependent vasodilatation of resistance vessels. Eur. Heart J., 26: 464-471.

Kita, T., N. Kume, M. Minami, K. Hayashida and T. Murayama et al., 2001. Role of oxidized LDL in atherosclerosis. Ann. N. Y. Acad. Sci., 947: 199-206.

Blake, G.J. and P.M. Ridker, 2002. Inflammatory bio-markers and cardiovascular risk prediction. J. Internal Med., 252: 283-294.

Frostegard, J., 2013. Immunity, Atherosclerosis and Cardiovascular Disease. BMC Med., Vol. 11.

Bizjak, D.A., C. Brinkmann, W. Bloch and M. Grau, 2015. Increase in Red Blood Cell-Nitric Oxide Synthase Dependent Nitric Oxide Production During Red Blood Cell Aging in Health and Disease: A Study on Age Dependent Changes of Rheologic and Enzymatic Properties in Red Blood Cells. PLOS ONE, Vol. 10.

Biadgo, B., M. Melku, S.M. Abebe and M. Abebe, 2016. Hematological indices and their correlation with fasting blood glucose level and anthropometric measurements in type 2 diabetes mellitus patients in Gondar, Northwest Ethiopia. Diabetes Metab. Syndr. Obesity: Targets Ther., 9: 91-99.

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Published

11.08.2021

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Research Article

How to Cite

Mzimela, N., Ngubane, P., & Khathi, A. (2021). The Haemolytic Changes During Progression of Pre-Diabetes to Type 2 Diabetes in a High-Fat High-Carbohydrate Diet-Induced Pre-Diabetic Rat Model. Pakistan Journal of Nutrition, 20(2), 55–63. https://doi.org/10.3923/pjn.2021.55.63