Impairment of Erythrocyte Deformability Observed in Type 2 Diabetic Patients with Clustering Diabetic Complications

Main Article Content

Takeshi Arita
Taku Yokoyama
Shohei Moriyama
Mitsuhiro Fukata
Kei Irie
Toru Maruyama
Takehiko Fujino
Koichi Akashi

Abstract

Aims: Hemorheologic and microvascular dysfunction are interdependent in type 2 diabetic patients. However, exact mechanisms explaining this interaction remains unclear. This study aimed to investigate the impairment of erythrocyte deformability under concurrent recording of electrocardiogram (ECG), since heart-rate-corrected QT interval (QTc interval) prolongation reflects autonomic and microvascular dysfunction in diabetic patients.

Methodology: The erythrocyte deformability was investigated on the day of digital ECG recording in diabetic (n = 215) and control (n = 88) groups of outpatients using specific filtration technique. Significant contributors to the erythrocyte deformability were analyzed by multivariate analysis. Results: Difference of mean erythrocyte deformability in the diabetic vs. control group did not reach the statistical significance, but the difference was significant in comparison of diabetic smokers vs. non-smokers and of diabetic patients with vs. without diabetic complications. Impaired diabetic erythrocyte deformability was dependent mostly on the glycated hemoglobin (HbA1c), and negative correlation between QTc interval and the deformability was marginal.

Conclusions: Erythrocyte deformability was not necessarily impaired in diabetic patients under the intensive antidiabetic medication. However, this deformability was impaired in diabetic smokers and diabetic patients with clustering of complications. Future studies are required for hemorheologic and microvascular interaction leading to the impaired diabetic microcirculation.

Keywords:
Deformability, diabetes, erythrocytes, microcirculation.

Article Details

How to Cite
Arita, T., Yokoyama, T., Moriyama, S., Fukata, M., Irie, K., Maruyama, T., Fujino, T., & Akashi, K. (2020). Impairment of Erythrocyte Deformability Observed in Type 2 Diabetic Patients with Clustering Diabetic Complications. Cardiology and Angiology: An International Journal, 9(1), 27-37. https://doi.org/10.9734/ca/2020/v9i130127
Section
Original Research Article

References

Cuschieri S. Type 2 diabetes – An unresolved disease across centuries contributing to a public health emergency. Diabetes Metab Syndr. 2019;13:450-3.

Caimi G, Presti RL. Techniques to evaluate erythrocyte deformability in diabetes mellitus. Acta Diabetol. 2004;41: 99-103.

Loyola-Leyva A, Loyola-Rodríguez JP, Atzori M, González FJ. Morphological changes in erythrocytes of people with type 2 diabetes mellitus evaluated with atomic force microscopy: A brief review. Micron. 2018;105:11-7.

Tsukada K, Sekizuka E, Oshio C, Minamitani H. Direct measurement of erythrocyte deformabality in diabetes mellitus with a transient microchannel capillary model and high-speed video camera system. Microvasc Res. 2001;61: 231-9.

Moon JS, Kim JH, Kim JH, Park IR, Lee JH, Kim HJ, et al. Impaired RBC deformability is associated with diabetic retinopathy in patients with type 2 diabetes. Diabetes Metab. 2016;42:448-52.

Ejima J, Ijichi T, Ohnishi Y, Maruyama T, Kaji Y, Kanaya S, et al. Relationship of high-density lipoprotein cholesterol and red blood cell filterability: Cross-sectional study of healthy subjects. Clin Hemorheol Microcirc. 2000;22:1-7.

Ariyoshi K, Maruyama T, Odashiro K, Akashi K, Fujino T, Uyesaka N. Impaired erythrocyte filterability of spontaneously hypertensive rats: Investigation by nickel mesh filtration technique. Circ J. 2010;74: 129-36.

Yokoyama A. Prognostic significance of QT prolongation and autonomic nervous dysfunction in alcoholics with diabetes mellitus. Keio J Med. 1993;42:141-8.

Ohta Y, Tsuchihashi T, Onaka U, Hasegawa E. Clustering of cardiovascular risk factors and blood pressure control status in hypertensive patients. Intern Med. 2010;49:1483-7.

Saito K, Kokawa Y, Fukata M, Odashiro K, Maruyama T, Akashi K, et al. Impaired deformability of erythrocytes in diabetic rat and human: Investigation by the nickel-mesh-filtration technique. J Biorheol. 2011; 25:18-26.

Haustein KO, Krause J, Haustein H, Rasmussen T, Cort N. Effects of cigarette smoking or nicotine replacement on cardiovascular risk factors and parameters of haemorheology. J Intern Med. 2002; 252:130-9.

Odashiro K, Maruyama T, Yokoyama T, Nakamura H, Fukata M, Yasuda S, et al. Impaired erythrocyte deformability in patients with coronary risk factors: Significance of nonvalvular atrial fibrillation. J Atr Fibrillation. 2013;6:939.
DOI: 10.4022/jafib.939

Odashiro K, Saito K, Arita T, Maruyama T, Fujino T, Akashi K. Impaired deformability of circulating erythrocytes obtained from nondiabetic hypertensive patients: Investigation by a nickel mesh filtration technique. Clin Hypertens. 2015;21:17.
DOI: 10.1186/s40885-015-0030-9

Mohandas N, Chasis JA. Red cell deformability, membrane material properties and shape: Regulation by transmembrane, skeletal and cytosolic proteins and lipids. Semin Hematol. 1993; 30:171-92.

Hiruma H. Noguchi CT, Uyesaka N, Schechter AN, Rodgers GP. Contributions of sickle hemoglobin polymer and sickle cell membranes to impaired filterability. Am J Physiol. 1995;268:H2003-8.

Rajeswari P, Natarajan R, Nadler JL, Kumar D, Kalra VK. Glucose induces lipid peroxidation and inactivation of membrane-associated ion-transport enzymes in human erythrocytes In vivo and In vitro. J Cell Physiol. 1991;149:100-9.

Ye S, Ruan P, Yong J, Shen H, Liao Z, Dong X. The impact of the HbA1c level of type 2 diabetics on the structure of hemoglobin. Sci Rep. 2016;6:33352.
DOI: 10.1038/srep33352

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 carbon monoxide breath test. J Breath Res. 2018;12: 026004.
DOI: 10.1088/1752-7163/aa9081

Uyesaka N, Hasegawa S, Ishioka N, Ishioka R, Shio H, Schechter AN. Effects of superoxide anions on red cell deformability and membrane proteins. Biorheology. 1992;29:217-29.

Iwata H, Ukeda H, Maruyama T, Fujino T, Sawamura M. Effect of carbonyl compounds on red blood cells deformability. Biochem Biophys Res Comm. 2004;321:700-6.

Okamoto K, Maruyama T, Kaji Y, Harada M, Mawatari S, Fujino T, et al. Verapamil prevents impairment in filterability of human erythrocytes exposed to oxidative stress. Jpn J Physiol. 2004;54:39-46.

Robson R, Kundur AR, Singh I. Oxidative stress biomarkers in type 2 diabetes mellitus for assessment of cardiovascular disease risk. Diabetes Metab Syndr. 2018; 12:455-62.

Thakur P, Kumar A, Kumar A. Targeting oxidative stress through antioxidants in diabetes mellitus. J Drug Target. 2018;26: 766-76.

Linderkamp O, Ruef P, Zilow EP, Hoffmann GF. Impaired deformability of erythrocytes and neutrophils in children with newly diagnosed insulin-dependent diabetes mellitus. Diabetologia. 1999;42: 865-9.

Forst T, Weber MM, Löbig M, Lehmann U, Müller J, Hohberg C, et al. Pioglitazone in addition to metformin improves erythrocyte deformability in patients with type 2 diabetes mellitus. Clin Sci (Lond). 2010; 119:345-51.

Shin S, Ku YH, Ho JX, Kim YK, Suh JS, Singh M. Progressive impairment of erythrocyte deformability as indicator of microangiopathy in type 2 diabetes mellitus. Clin Hemorheol Microcirc. 2007; 36:253-61.

Kobayashi S, Nagao M, Asai A, Fukuda I, Oikawa S, Sugihara H. Severity and multiplicity of microvascular complications are associated with QT interval prolongation in patients with type 2 diabetes. J Diabetes Investig. 2018;9:946-51.

Ma T, Cai J, Zhu YS, Chu XF, Wang Y, Shi GP, et al. Association between a frailty index based on common laboratory tests and QTc prolongation in older adults. Clin Interv Aging. 2018;13:797-804.

Indik JH, Nair V, Rafikov R, Nyotowidjojo IS, Bisla J, Kansal M, et al. Associations of prolonged QTc in sickle cell disease. PLoS One. 2016;11:e0164526.

Sara JD, Lennon RJ, Ackerman MJ, Friedman PA, Noseworthy PA, Lerman A. Coronary microvascular dysfunction is associated with baseline QTc prolongation amongst patients with chest pain and non-obstructive coronary artery disease. J Electrocardiol. 2016;49:87- 93.

Ninkovic VM, Ninkovic SM, Miloradovic V, Stanojevic D, Babic M, Giga V, et al. Prevalence and risk factors for prolonged QT interval and QT dispersion in patients with type 2 diabetes. Acta Diabetol. 2016; 53:737-44.

Chung JH, Lee KE, Park JW, Shin ES. Coronary microvascular disease and clinical prognosis in deferred lesions: The index of microcirculatory resistance. Clin Hemorheol Microcirc. 2019;71:137- 40.

Maruyama T, Arita T, Moriyama K, Irie K, Yokoyama T, Fukata M, Odashiro K, Akashi K, Fujino T. Impairment of erythrocyte deformability observed in type 2 diabetic patients with clustering diabetic complication. The 27th Congress of the Internat Soc Thromb Haemostat Melbourne; 2019.