Advertisement

Hyperglycemia and RBCs: too sweet to survive

  • Ahmad Mamoun Rajab
  • Khawaja Husnain Haider
Review Article
  • 35 Downloads

Abstract

Sustained untreated hyperglycemia is associated with complications at molecular, cellular, and organ levels in the body that ultimately lead to comorbidities including cardiovascular-related pathologies, neuropathies, nephropathies, blindness, limb amputations, etc. Mature RBCs are unique in their structure and function; being without cellular organelles including nucleus and mitochondria, they are highly sensitive and responsive to the molecular changes in their microenvironment in general and elevated glucose in particular. They lack the ability to synthesize new proteins, replenish its enzyme-based antioxidant machinery, and replace any cellular components in the event of oxidative damage. Although they are dependent on glycolytic processing of glucose for their energy requirements, sustained exposure to hyperglycemia significantly impacts their structure as well as function and leads to early aging of the circulating RBCs with shortened lifespan. Loss of deformability due to hyperglycemia prohibits them to reversibly change their shape and squeeze through the microvasculature, a hallmark of RBC functionality for nutrient and gaseous exchanges. This mini-review of literature signifies the effect of hyperglycemia on RBCs in terms of eryptosis, lipid peroxidation in the cell membrane to compromise membrane integrity which significantly alters its deformity and coaguability, and adherence to endothelial surface leading loss of functionality and life-span.

Keywords

Clinical Diabetes Erythrocyte, glycolysis, hyperglycemia RBCs 

Abbreviations

AGEs

Advanced glycation end products

Arg-P

Arg-pyrimidine

CEL

Carboxyethyllysine

CML

Carboxymethylysine

CP450

Cytochrome P-450

FAAD

Fas-associated death domain

FasL

Fas ligand

GLUT1

Glucose transporter 1

GLUT4

Glucose transporter 4

HSCs

Hematopoietic stem cells

LDH

Lactate dehydrogenase

MDA

Malonyldialdehyde

MCV

Mean corpuscular volume

Na+/K+-ATPase

Na+/K+ adenosine triphosphatase (ATPase)

ROS

Reactive oxygen species

RBCs

Red blood cells

WHO

World Health Organization

Notes

Acknowledgements

We thank SRC for supporting this student research project.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.

Research involving human participants and/or animals

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

Not applicable.

References

  1. 1.
    World Health Organization. WHO global report on diabetes 2016. http://www.who.int/diabetes/global-report/.
  2. 2.
    Forbes JM, Cooper ME. Mechanisms of diabetic complications. Physiol Rev. 2013;93:137–88.CrossRefPubMedGoogle Scholar
  3. 3.
    Lee PG, Halter JB. The pathophysiology of hyperglycemia in older adults: clinical considerations. Diabetes Care. 2017;40(4):444–52.  https://doi.org/10.2337/dc16-1732.CrossRefPubMedGoogle Scholar
  4. 4.
    Sheetz MJ, King GL. Molecular understanding of hyperglycemia’s adverse effects for diabetic complications. JAMA. 2002;288(20):2579–88.  https://doi.org/10.1001/jama.288.20.2579.CrossRefPubMedGoogle Scholar
  5. 5.
    Kaneto H, Katakami N, Matsuhisa M, Matsuoka T. Role of reactive oxygen species in the progression of type 2 diabetes and atherosclerosis. Mediat Inflamm. 2010;2010:453892. 11 pagesCrossRefGoogle Scholar
  6. 6.
    Robertson RP, Harmon J, Takahasi H. Glucose toxicity in β-cells: type 2 diabetes, good radicals gone bad, and the glutathione connection. Diabetes. 2003;52(3):581–7.  https://doi.org/10.2337/diabetes.52.3.581.CrossRefPubMedGoogle Scholar
  7. 7.
    Leney SE, Tavare JM. The molecular basis of insulin-stimulated glucose uptake: signalling, trafficking and p2otential drug targets. J Endocrinol. 2009;203(1):1–18.  https://doi.org/10.1677/JOE-09-0037.CrossRefPubMedGoogle Scholar
  8. 8.
    Ebeling P, Koistinen HA, Koivisto VA. Hypothesis: Insulin-independent glucose transport regulates insulin sensitivity. FEBS Lett. 1998;436(3):301–3.  https://doi.org/10.1016/S0014-5793(98)01149-1.CrossRefPubMedGoogle Scholar
  9. 9.
    Campos C. Chronic hyperglycemia and glucose toxicity: pathology and clinical sequelae. Postgrad Med. 2012;124(6):90–7.  https://doi.org/10.3810/pgm.2012.11.2615.CrossRefPubMedGoogle Scholar
  10. 10.
    Arias CF, Arias CF. How do red blood cells know when to die? R Soc Open Sci. 2017;4(4):160850.  https://doi.org/10.1098/rsos.160850.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Adamson JW. Regulation of red blood cell production. Am J Med. 1996;101(2):4S–6S.  https://doi.org/10.1016/S0002-9343(96)00160-X.CrossRefPubMedGoogle Scholar
  12. 12.
    Burrilla DR, Verneta A, Collinsa JJ, Silvera PA, Waya JC. Targeted erythropoietin selectively stimulates red blood cell expansion in vivo. PNAS. 2016;113(19):5245–50.  https://doi.org/10.1073/pnas.1525388113.CrossRefGoogle Scholar
  13. 13.
    Pries AR, Secomb TW, Gaehtgens P. Biophysical aspects of blood flow in the microvasculature. Cardiovasc Res. 1996;32(4):654–67.  https://doi.org/10.1016/S0008-6363(96)00065-X.CrossRefPubMedGoogle Scholar
  14. 14.
    Kholoussi N, Helwa I, Amara F. Red blood cells surface morphology in diabetic ketoacidosis. Middle East J Appl Sci. 2012;2(1):51–7.Google Scholar
  15. 15.
    Jain SK. Hyperglycemia can cause membrane lipid peroxidation and osmotic fragility in human red blood cells. J Biol Chem. 1989;264(35):21340–5.PubMedGoogle Scholar
  16. 16.
    Lutz HU, Bogdanova A. Mechanisms tagging senescent red blood cells for clearance in healthy humans. Front Physiol. 2013;4:387. Pages 1–15CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    van Wijk R, van Solinge WW. The energy-less red blood cell is lost: erythrocyte enzyme abnormalities of glycolysis. Blood. 2005;106(13):4034–42.  https://doi.org/10.1182/blood-2005-04-1622.CrossRefPubMedGoogle Scholar
  18. 18.
    Valentine WN, Paglia DE. The primary cause of hemolysis in enzymopathies of anaerobic glycolysis: a viewpoint. Blood Cells. 1980;6(4):819–29.PubMedGoogle Scholar
  19. 19.
    Mazzanti L, Faloia E, Rabini RA, Staffolani R, Kantar A, Fiorini R, et al. Diabetes mellitus induces red blood cell plasma membrane alterations possibly affecting the aging process. Clin Biochem. 1992;25(1):41–6.  https://doi.org/10.1016/0009-9120(92)80044-H.CrossRefPubMedGoogle Scholar
  20. 20.
    Cohen RM, Franco RS, Joiner C. Is poor glycemic control associated with reduced red blood cell lifespan? Diabetes Care. 2004;27(4):1013–4.  https://doi.org/10.2337/diacare.27.4.1013.CrossRefPubMedGoogle Scholar
  21. 21.
    Huang Z, Liu Y, Mao Y, Chen W, Xiao Z, Yu Y. Relationship between glycated haemoglobin concentration and erythrocyte survival in type 2 diabetes mellitus determined by a modified carbon monoxide breath test. J Breath Res. 2017;  https://doi.org/10.1088/1752-7163/aa9081.
  22. 22.
    Carruthers A, DeZutter J, Ganguly A, Devaskar SU. Will the original glucose transporter isoform please stand up! Am J Physiol Endocrinol Metab. 2009;297(4):E836–48.  https://doi.org/10.1152/ajpendo.00496.2009.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Montel-Hagen A, Kinet S, Manel N, et al. Erythrocyte Glut1 triggers dehydroascorbic acid uptake in mammals unable to synthesize vitamin C. Cell. 2008;132:1039–48.CrossRefPubMedGoogle Scholar
  24. 24.
    Montel-Hagen A, Blanc L, Boyer-Clavel M, Jacquet C, Vidal M, Sitbon M, et al. The Glut1 and Glut4 glucose transporters are differentially expressed during perinatal and postnatal erythropoiesis. Blood. 2008;112:4729–38.CrossRefPubMedGoogle Scholar
  25. 25.
    Vrhovac I, Breljak D, Sabolic I. Glucose transporters in the mammalian blood cells. Period Biol. 2014;116(2):131–8.Google Scholar
  26. 26.
    Zhang J-Z, Ismail-Beigi F. Activation of GLUT1 glucose transporter in human erythrocytes. Arch Biochem Biophys. 1998;365(1):86–92.CrossRefGoogle Scholar
  27. 27.
    Hajjawi OS. Glucose transport in human red blood cells. Am J Biomed Life Sci. 2013;1(3):44–52.CrossRefGoogle Scholar
  28. 28.
    Mueckler M, Thorens B. The SLC2 (GLUT) family of membrane transporters. Mol Asp Med. 2013;34(2-3):121–38.  https://doi.org/10.1016/j.mam.2012.07.001.CrossRefGoogle Scholar
  29. 29.
    Hu X-J, Peng F, Zhou H-Q, Zhang Z-H, Cheng W-Y, Feng H-F. The abnormality of glucose transporter in the erythrocyte membrane of Chinese type 2 diabetic patients. Biochim Biophys Acta. 2000;1466(1-2):306–14.  https://doi.org/10.1016/S0005-2736(00)00175-9.CrossRefPubMedGoogle Scholar
  30. 30.
    Lang KS, Lang PA, Bauer C, Duranton C, Wieder T, Huber SM, et al. Mechanisms of suicidal erythrocyte death. Cell Physiol Biochem. 2005;15(5):195–202.  https://doi.org/10.1159/000086406.CrossRefPubMedGoogle Scholar
  31. 31.
    Fırat U, Kaya S, Çim A, Büyükbayram H, Gökalp O, Dal MS, et al. Increased caspase-3 immunoreactivity of erythrocytes in stz diabetic rats. Exp Diabetes Res. 2012;2012:316384.  https://doi.org/10.1155/2012/316384.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Mandal D, Mazumder A, Das P, Kundu M, Basu J. Fas-, caspase 8-, and caspase 3-dependent signaling regulates the activity of the aminophospholipid translocase and phosphatidylserine externalization in human erythrocytes. J Biol Chem. 2005;280(47):39460–7.  https://doi.org/10.1074/jbc.M506928200.CrossRefPubMedGoogle Scholar
  33. 33.
    Ghashghaeinia M, Cluitmans JCA, Akel A, Dreischer P, Toulany M, Köberle M, et al. The impact of erythrocyte age on eryptosis. Br J Haematol. 2012;157(5):606–14.  https://doi.org/10.1111/j.1365-2141.2012.09100.x.CrossRefPubMedGoogle Scholar
  34. 34.
    Lang E, Lang F. Triggers, inhibitors, mechanisms, and significance of eryptosis: the suicidal erythrocyte death. BioMed Res Int. 2015;2015:513518. 16 pagesCrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Awasthi S, Gayathiri SK, Ramya R, Duraichelvan R, Dhason A, Saraswathi NT. Advanced glycation-modified human serum albumin evokes alterations in membrane and eryptosis in erythrocytes. Appl Biochem Biotechnol. 2015;177(5):1013–24.  https://doi.org/10.1007/s12010-015-1793-x.CrossRefPubMedGoogle Scholar
  36. 36.
    Maellaro E, Leoncini S, Moretti D, BelloItalo BD, Claudio T, De Felice C, et al. Erythrocyte caspase-3 activation and oxidative imbalance in erythrocytes and in plasma of type 2 diabetic patients. Acta Diabetol. 2013;50(4):489–95.  https://doi.org/10.1007/s00592-011-0274-0.CrossRefPubMedGoogle Scholar
  37. 37.
    Mohandas N, Gallagher PG. Red cell membrane: past, present, and future. Blood. 2008;112(10):3939–48.  https://doi.org/10.1182/blood-2008-07-161166.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Himbert S, Alsop RJ, Rose M, Hertz L, Dhaliwal A, Moran-Mirabal JM, et al. The molecular structure of human red blood cell membranes from highly oriented, solid supported multi-lamellar membranes. Sci Rep. 2017;7:39661.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Lieberman M, Marks A, Peet A, Chansk M. Marks’ Basic Medical Biochemistry. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2012. p. 805–26.Google Scholar
  40. 40.
    Campanella ME, Chu H, Low PS. Assembly and regulation of a glycolytic enzyme complex on the human erythrocyte membrane. PNAS. 2005;102(7):2402–7.  https://doi.org/10.1073/pnas.0409741102.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Ferru E, Giger K, Pantaleo A, Campanella E, Grey J, Ritchie K, et al. Regulation of membrane-cytoskeletal interactions by tyrosine phosphorylation of erythrocyte band 3. Blood. 2011;117(22):5998–6006.  https://doi.org/10.1182/blood-2010-11-317024.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Cluitmans J, Gevi F, Siciliano A, Matte A, Leal J, De Franceschi L, et al. Red blood cell homeostasis: pharmacological interventions to explore biochemical, morphological and mechanical properties. Front Mol Biosci. 2016;3:10.  https://doi.org/10.3389/fmolb.2016.00010.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Dzik WH. The air we breathe: three vital respiratory gases and the red blood cell: oxygen, nitric oxide, and carbon dioxide. Transfusion. 2011;51(4):676–85.  https://doi.org/10.1111/j.1537-2995.2011.03114.x.CrossRefPubMedGoogle Scholar
  44. 44.
    Morse EE, Kalache G, Wermino FG, Stockwell R. Increased electronic mean corpuscular volume induced by marked hyperglycemia. Ann Clin Lab Sci. 1981;11(2):184–7.PubMedGoogle Scholar
  45. 45.
    Nagai R, Deemer EK, Brock JW, Thorpe SR, Baynes JW. Effect of glucose concentration on formation of AGEs in erythrocytes in vitro. Ann New York Acad Sci. 2005;1043(1):146–50.  https://doi.org/10.1196/annals.1333.018.CrossRefGoogle Scholar
  46. 46.
    Reshamwala S, Patil N. Biochemical changes in erythrocyte membrane in uncontrolled type 2 diabetes mellitus. Indian J Biochem Biophys. 2005;42(4):250–3.PubMedGoogle Scholar
  47. 47.
    Jameson J, Fauci A, Kasper D, Hauser S, Longo D, Jameson J, et al. Harrison’s principles of internal medicine. 19th ed. New York: McGraw-Hill, Medical Publishers; 2015. p. 2423–30.Google Scholar
  48. 48.
    Jain SK, McVie R, Duett J, Herbst JJ. Erythrocyte membrane lipid peroxidation and glycosylated hemoglobin in diabetes. Diabetes. 1989;38(12):1539–43.  https://doi.org/10.2337/diab.38.12.1539.CrossRefPubMedGoogle Scholar
  49. 49.
    Pani LN, Korenda L, Meigs JB, Driver C, Chamany S, Fox CS, et al. Effect of aging on A1C levels in individuals without diabetes. Evidence from the Framingham Offspring Study and the National Health and Nutrition Examination Survey 2001–2004. Diabetes Care. 2008;31(10):1991–6.  https://doi.org/10.2337/dc08-0577.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Jain SK, Levinea SN, Duetta J, Hollie B. Elevated lipid peroxidation levels in red blood cells of streptozotocin-treated diabetic rats. Metabolism. 1990;39(9):971–5.  https://doi.org/10.1016/0026-0495(90)90310-9.CrossRefPubMedGoogle Scholar
  51. 51.
    Viskupicova J, Blaskovic D, Galiniak S, Soszyński M, Bartosz G, Horakova L, et al. Effect of high glucose concentrations on human erythrocytes in vitro. Redox Biol. 2015;5:381–7.  https://doi.org/10.1016/j.redox.2015.06.011.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Dianzani M, Barrera G. Pathology and physiology of lipid peroxidation and its carbonyl products. In: Álvarez S, Evelson P, editors. Free Radical Pathophysiology. Kerala: Transworld Research Network; 2008. p. 19–38. ISBN: 978-81-7895-311-3.Google Scholar
  53. 53.
    Blisard KS, Mieyal JJ. Characterization of the aniline hydroxylase activity of erythrocytes. J Biol Chem. 1979;254:5104–10.PubMedGoogle Scholar
  54. 54.
    Starke DW, Blisard KS, Mieyal JJ. Substrate specificity of the monooxygenase activity of hemoglobin. Mol Pharrnacol. 1984;25:467–75.Google Scholar
  55. 55.
    Edwards CJ, Fuller J. Oxidative stress in erythrocytes. Comp Haematol Int. 1996;6(1):24–31.  https://doi.org/10.1007/BF00368098.CrossRefGoogle Scholar
  56. 56.
    Mohanty JG, Nagababu E, Rifkind JM. Red blood cell oxidative stress impairs oxygen delivery and induces red blood cell aging. Front Physiol. 2014;5:84.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Pandey KB, Rizvi SI. Biomarkers of oxidative stress in red blood cells. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2011;155(2):131–6.  https://doi.org/10.5507/bp.2011.027.CrossRefPubMedGoogle Scholar
  58. 58.
    Varashree BS, Bhat GP. Correlation of lipid peroxidation with glycated hemoglobin levels in diabetes mellitus. Online J Health Allied Sci. 2011;10(2):11.Google Scholar
  59. 59.
    Jain SK, Mohandas N, Clark M, Shohet SB. The effect of malonyldialdehyde, a product of lipid peroxidation, on the deformability, dehydration, and 51-Cr-survival of erythrocytes. Br J Haematol. 1983;53(2):247–55.  https://doi.org/10.1111/j.1365-2141.1983.tb02018.x.CrossRefPubMedGoogle Scholar
  60. 60.
    Rodrigo R, Bächler JP, Araya J, Prat H, Passalacqua W. Relationship between (Na+K)-ATPase activity, lipid peroxidation and fatty acid profile in erythrocytes of hypertensive and normotensive subjects. Mol Cell Biochem. 2007;303(1-2):73–81.  https://doi.org/10.1007/s11010-007-9457-y.CrossRefPubMedGoogle Scholar
  61. 61.
    Cazzola R, Rondanelli M, Russo-Volpe S, Ferrari E, Cestaro B. Decreased membrane fluidity and altered susceptibility to peroxidation and lipid composition in overweight and obese female erythrocytes. J Lipid Res. 2004;45(10):1846–51.  https://doi.org/10.1194/jlr.M300509-JLR200.CrossRefPubMedGoogle Scholar
  62. 62.
    Bravi MC, Armiento A, Laurenti O, Cassone-Faldetta M, De Luca O, Moretti A, et al. Insulin decreases intracellular oxidative stress in patients with type 2 diabetes mellitus. Metabolism. 2006;55(5):691–5.  https://doi.org/10.1016/j.metabol.2006.01.003.CrossRefPubMedGoogle Scholar
  63. 63.
    Sompong W, Cheng H, Adisakwattana S. Protective effects of ferulic acid on high glucose-induced protein glycation, lipid peroxidation, and membrane ion pump activity in human erythrocytes. PLoS One. 2015;10(6):e0129495.  https://doi.org/10.1371/journal.pone.0129495.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Iannello S, Milazzo P, Belfiore F. Animal and human tissue Na, K-ATPase in obesity and diabetes: a new proposed enzyme regulation. Am J Med Sci. 2007;333:1–9.CrossRefPubMedGoogle Scholar
  65. 65.
    Srivatsan R, Das S, Gadde R, Manoj-Kumar K, Taduri S, Rao N. Antioxidants and lipid peroxidation status in diabetic patients with and without complications. Arch Iran Med. 2009;12:121–7.PubMedGoogle Scholar
  66. 66.
    Nans A, Mohandas N, Stokes DL. Native ultrastructure of the red cell cytoskeleton by cryo-electron tomography. Biophys J. 2011;101(10):2341–50.  https://doi.org/10.1016/j.bpj.2011.09.050.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Li J, Lykotrafit G, Dao M, Suresh S. Cytoskeletal dynamics of human erythrocyte. PNAS. 2007;104(12):4937–42.  https://doi.org/10.1073/pnas.0700257104.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Simmons D. Increased red cell count in diabetes and pre-diabetes. Diabetes Res Clin Pract. 2010;90(3):e50–3.  https://doi.org/10.1016/j.diabres.2010.07.005.CrossRefPubMedGoogle Scholar
  69. 69.
    Babu N, Singh M. Influence of hyperglycemia on aggregation, deformability and shape parameters of erythrocytes. Clin Hemorheol Microcirc. 2004;31:273–80.PubMedGoogle Scholar
  70. 70.
    van Buys A, van Rooy M-J, Soma P, Papendorp DV, Lipinski B, Pretorius E. Changes in red blood cell membrane structure in type 2 diabetes: a scanning electron and atomic force microscopy study. Cardiovasc Diabetol. 2013;12(1):25.  https://doi.org/10.1186/1475-2840-12-25.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Agrawal R, Smart T, Nobre-Cardoso J, Richards C, Bhatnagar R, Tufail A, et al. Assessment of red blood cell deformability in type 2 diabetes mellitus and diabetic retinopathy by dual optical tweezers stretching technique. Sci Rep. 2016;6(1):15873.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Elshennawy ATM. Effect of gestational diabetes on gross morphology, histology and histochemistry of human placenta. Endocrinol Metab Syndr. 2016;5:1.Google Scholar
  73. 73.
    Kamana KC, Shakya S, Zhang H. Gestational diabetes mellitus and macrosomia: a literature review. Ann Nutr Metab. 2015;66(suppl 2):14–20.Google Scholar
  74. 74.
    Gioia S, Cerekja A, Larciprete G, Vallone C, Demaliaj E, Evangelista MT, et al. Gestational diabetes: is it linked to platelets hyperactivity? Platelets. 2009;20(2):140–1.  https://doi.org/10.1080/09537100802630062.CrossRefPubMedGoogle Scholar
  75. 75.
    Min Y, Ghebremeskel K, Lowy C, Thomas B, Crawford MA. Adverse effect of obesity on red cell membrane arachidonic and docosahexaenoic acids in gestational diabetes. Diabetologia. 2004;47(1):75–81.  https://doi.org/10.1007/s00125-003-1275-5.CrossRefPubMedGoogle Scholar
  76. 76.
    Min Y, Nam J-H, Ghebremeskel K, Kim A, Crawford M. A distinctive fatty acid profile in circulating lipids of Korean gestational diabetics: a pilot study. Diabetes Res Clin Pract. 2006;73(2):178–83.  https://doi.org/10.1016/j.diabres.2006.01.003.CrossRefPubMedGoogle Scholar
  77. 77.
    Taschereau-Charron A, Da Silva MS, Bilodeau J-F, Morisset A-S, Julien P, Rudkowska I. Alterations of fatty acid profiles in gestational diabetes and influence of the diet. Maturitas. 2017;99:98–104.  https://doi.org/10.1016/j.maturitas.2017.01.014.CrossRefPubMedGoogle Scholar
  78. 78.
    Moretti N, Rabini RA, Nanetti L, Grechi G, Curzi MC, Cester N, et al. Sialic acid content in erythrocyte membranes from pregnant women affected by gestational diabetes. Metabolism. 2002;51(5):605–8.  https://doi.org/10.1053/meta.2002.32015.CrossRefPubMedGoogle Scholar

Copyright information

© Research Society for Study of Diabetes in India 2018

Authors and Affiliations

  1. 1.Sulaiman AlRajhi CollegesAl BukairiyahKingdom of Saudi Arabia

Personalised recommendations