Blood rheological and electrical properties and relationships with the microvascular tone regulation in patients with diabetes mellitus type 2

Aim. The study aims to evaluate impairment of the rheological and electrical properties of blood, plasma viscosity and blood conductivity in patients with type 2 diabetes mellitus (T2DM) in comparison with the data of the control group of healthy individuals. It also aims to investigate the changes of the skin blood flow responses to cold stress in T2DM patients through wavelet analysis of the peripheral skin temperature pulsations and to estimate their relationships with the blood viscosity and blood conductivity parameters, obtained from the simulation of experimental data with mathematical equations.

Materials and methods. The whole blood viscosity was measured by Contraves LS30 viscometer (Switzerland) at a steady flow in 9 healthy individuals and in 13 patients with type 2 diabetes mellitus. Time variation of whole blood conductivity σ under transient flow at rectangular and trapezium shaped Couette viscometric flow and under electric field of 2 kHz was determined. The amplitudes of the skin temperature pulsations (ASTP) were monitored by «Microtest» device («FM-Diagnostics», Russia). To analyze the temperature fluctuations, wavelet transformation analysis of the low amplitude oscillations of skin temperature in accordance with myogenic (0.05–0.14 Hz), neurogenic (0.02–0.05 Hz), and endothelial (0.0095–0.02 Hz) control mechanisms of the vascular tone (WAST method) was applied.

Results. Blood viscosity was increased in the T2DM patients’ group, while blood conductivity decreased in comparison to controls. Two sigmoidal equations were applied to describe the kinetics of blood conductivity. Both models include conductivity indices (σ₁ , σ₂ , σ₃ ) and time indices too. The Pearson correlations between these parameters and the ASTP in the frequency ranges, corresponding to the myogenic, neurogenic and endothelial mechanisms of the microcirculation tone regulation were analyzed. The correlation analysis revealed good ASTP–(σ₁ , σ₂ , σ₃ ) relationships in the neurogenic range 3 minutes after the cold test, while the ASTP–(σ₁ , σ₂ , σ₃ ) correlation in the myogenic frequency range before the cold test was negative (r<–0.8, p<0.5).

Conclusion. The results complement the studies of the microvascular regulatory mechanisms and endothelial dysfunction in patients with type 2 diabetes mellitus, as well as their relationships with the rheological and electrical properties of blood.

1. Velcheva I, Stoyneva Z, Antonova N, Damianov P, Kostova V, Dimitrova V. Skin hemodynamics and temperature oscillations in diabetic patients. Relation to blood rheology. J. Clin. Hemorheology and Microcirculation. 2013;167. Doi: 10.3233/CH-131750.

2. Velcheva I, Damianov P, Mantarova S, Antonova N. Cold pressor test: Effects on cardiac autonomic control and cerebral hemodynamic response in patients with diabetes mellitus type 2. Series on Biomechanics, 2012;27(1–2):64–69. ISSN:1313-2458.

3. Allen J, Howell K. Microvascular imaging: techniques and opportunities for clinical physiological measurements. Physiol Meas. 2014;(35):91–141. Doi: 10.1088/0967-3334/35/7/R91.

4. Kvandal P, Landsverk A, Bernjak A, Stefanovska A, Kvernmo D, Kirkebøen A. Low-frequency oscillations of the laser Doppler perfusion signal in human skin. Microvasc Res. 2006;72(3):120–127. Doi: 10.1016/j.mvr.2006.05.006.

5. Shusterman V, Anderson P, Barnea O. Spontaneous skin temperature oscillations in normal human subjects. Am J Physiol. 1997;(273):1173–1181.

6. Podtaev S, Morozov M, Frick P. Wavelet-based correlations of skin temperature and blood flow oscillations. Cardiovasc Eng. 2008;8(3):185–189. Doi: 10.1007/s10558-008-9055-y.

7. Isii Y, Matsukawa K, Tsuchimochi H, Nakamoto T. Icewater hand immersion causes a reflex decrease in skin temperature in the contralateral hand, J Physiol Sci. 2007;57(4):241– 248. Doi: 10.2170/physiolsci.RP007707.

8. Smirnova E, Podtaev S, Mizeva I, Loran E. Assessment of endothelial dysfunction in patients with impaired glucose tolerance during a cold pressor test. Diab Vasc Dis Res. 2013; 10(6):489–497. Doi: 10.1177/1479164113494881

9. Kostova V, Antonova N, Chaushev N, Velcheva I, Ivanov I. Oscillations in skin temperature after cold test in patients with type 2 diabetes mellitus and rheological properties of the blood, J Series on Biomechanics. 2015;29(1):11–16.

10. Antonova N, Tsiberkin K, Podtaev S, Paskova V, Velcheva I, Chaushev N. Comparative study between microvascular tone regulation and rheological properties of blood in patients with type 2 diabetes mellitus. Clinical Hemorheology and Microcirculation. 2016;64(4):837–844. Doi: 0.3233/CH-168000,837-844.

11. Antonova N, Riha P, Ivanov I. Time dependent variation of human blood conductivity as a method for an estimation of RBC aggregation. Clinical Hemorheology and Microcirculation. 2008;(39):69–78.

12. Kaliviotis E, Ivanov I, Antonova N, Yianneskis M. Erythrocyte aggregation at non-steady flow conditions: A comparison of characteristics measured with electrorheology and image analysis. Clinical Hemorheology and Microcirculation. 2010;44(1):43–54. Doi: 10.3233/CH-2009-1251.

13. Roitman E, Firsov N, Dementyeva M, Samsonova N, Plyushch M, Vorobieva N. Terms, concepts and approaches to the study of blood rheology in the clinic. Thrombosis, Hemostasis and Rheology. 2000;3(3):5–12. (In Russ.)

14. Dintenfass L. Red cell rigidity, «Tk» and filtration. Clinical Hemorheology. 1985;(5):241–244.

15. Paskova V, Antonova N, Ivanov I, Velcheva I, Chaushev N. Rheological and electrical behaviour of blood in patients with diabetes mellitus type 2. Series on Biomechanics. 2019;33(1):51–58.

16. Antonova N. Methods in hemorheology and their clinical applications. Clinical Hemorheology and Microcirculation. 2016;(64):509–515. Doi: 10.3233/CH-168001.

17. Frick P, Grossmann A, Tchamitchian P. Wavelet analysis of signals with gaps, J Math Physcs. 1998;(39):4091–4107. Doi: 10.1063/1.532485.

18. Zilberman-Kravits D, Harman-Boehm I, Shuster T, Meyerstein N. Increased red cell aggregation is correlated with HbA1C and lipid levels in type 1 but not type 2 diabetes. Clinical Hemorheology and Microcirculation. 2006; 35(4):463–471.

19. Desouky O. Rheological and electrical behavior of diabetes mellitus, Romanian J. Biophys. 2009;19(4):239–250.

20. Kruchinina MV, Gromov AA, Generalov VM, Kruchinin VN. Possible differential diagnosis of the degrees of rheological disturbances in patients with type 2 diabetes mellitus by dielectrophoresis of erythrocytes, J. Pers. Med. 2020;(10):60. Doi: 10.3390/jpm10030060.