Blood Pressure Variability is Better Associated with Acute Relative Hyperglycemia Than the Heart Rate Variability in Healthy Young Adults

Abstract

Background Deranged cardiovascular autonomic functions are well-reported complications of diabetes mellitus, where chronic hyperglycemia is an important factor. The role of acute relative hyperglycemia on cardiovascular autonomic functions, particularly on blood pressure variability in healthy subjects, has been rarely explored. Therefore, this study aimed to examine the effect of acute relative hyperglycemia on cardiovascular autonomic functions in healthy young adults.

Methods Beat-to-beat blood pressure and electrocardiogram were recorded to assess the heart rate variability and blood pressure variability in 42 young, healthy subjects during fasting and relative hyperglycemic states. Recorded cardiovascular parameters were analyzed in time and frequency domains. Correlations among analyzed parameters of cardiovascular autonomic variabilities were explored during fasting and relative hyperglycemic state.

Results A few of the systolic, mean, and diastolic blood-pressure-variability parameters were significantly altered during acute relative hyperglycemia when compared to the fasting state. However, no significant changes were observed in any of the heart-rate-variability parameters. Also, novel significant correlations were found among many of the parameters of cardiovascular autonomic variabilities during fasting and relative hyperglycemic states.

Conclusions The blood pressure variability is affected significantly during acute relative hyperglycemia in healthy young adults; however, the heart rate variability does not show such changes. Also, many blood pressure variability parameters show significant correlations with heart rate variability and baroreflex sensitivity. It may be hypothesized that although the variabilities in heart rate and blood pressure assess cardiovascular autonomic functions, blood pressure variability is a better indicator of cardiovascular autonomic effects of acute relative hyperglycemia.

Keywords

beat-to-beat blood pressure - electrocardiogram - hyperglycemia - autonomic

• References

• 1 Williams SM, Eleftheriadou A, Alam U. et al. Cardiac autonomic neuropathy in obesity, the metabolic syndrome and prediabetes: A narrative review. Diabetes Ther Res Treat Educ Diabetes Relat Disord 2019; 10: 1995-2021
• 2 Williams S, Raheim SA, Khan MI. et al. Cardiac autonomic neuropathy in type 1 and 2 diabetes: Epidemiology, pathophysiology, and management. Clin Ther 2022; 44: 1394-1416
• 3 Katsiki N, Anagnostis P, Kotsa K. et al. Obesity, metabolic syndrome and the risk of microvascular complications in patients with diabetes mellitus. Curr Pharm Des 2019; 25: 2051-2059
• 4 Watkins LL, Surwit RS, Grossman P. et al. Is there a glycemic threshold for impaired autonomic control?. Diabetes Care 2000; 23: 826-830
• 5 Marfella R, Nappo F, Marfella MA. et al. Acute hyperglycemia and autonomic function. Diabetes Care 2001; 24: 2016-2017
• 6 Lefrandt JD, Mulder MC, Bosma E. et al. Inverse relationship between blood glucose and autonomic function in healthy subjects. Diabetes Care 2000; 23: 1862-1864
• 7 Gupta S, Sussman I, McArthur CS. et al. Endothelium-dependent inhibition of Na(+)-K+ ATPase activity in rabbit aorta by hyperglycemia. Possible role of endothelium-derived nitric oxide. J Clin Invest 1992; 90: 727-732
• 8 Lu S, Liao Z, Lu X. et al. Hyperglycemia acutely increases cytosolic reactive oxygen species via O-linked GlcNacylation and CaMKII activation in mouse ventricular myocytes. Circ Res 2020; 126: e80-e96
• 9 Chowdhary S, Vaile JC, Fletcher J. et al. Nitric oxide and cardiac autonomic control in humans. Hypertens Dallas Tex 1979 2000; 36: 264-269
• 10 Veves A, Akbari CM, Primavera J. et al. Endothelial dysfunction and the expression of endothelial nitric oxide synthetase in diabetic neuropathy, vascular disease, and foot ulceration. Diabetes 1998; 47: 457-463
• 11 Parati G, Saul JP, Di Rienzo M. et al. Spectral analysis of blood pressure and heart rate variability in evaluating cardiovascular regulation. A critical appraisal. Hypertens Dallas Tex 1979 1995; 25: 1276-1286
• 12 Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur Heart J 1996; 17: 354-381
• 13 Fournié C, Chouchou F, Dalleau G. et al. Heart rate variability biofeedback in chronic disease management: A systematic review. Complement Ther Med 2021; 60: 102750
• 14 Parati G, Ochoa JE, Bilo G. Blood pressure variability, cardiovascular risk, and risk for renal disease progression. Curr Hypertens Rep 2012; 14: 421-431
• 15 Parati G, Ochoa JE, Lombardi C. et al. Assessment and management of blood-pressure variability. Nat Rev Cardiol 2013; 10: 143-155
• 16 Stauss HM. Identification of blood pressure control mechanisms by power spectral analysis. Clin Exp Pharmacol Physiol 2007; 34: 362-368
• 17 Ranjan N, Prakash K, Malhotra AS. Effect of acute hyperglycemia on baroreflex sensitivity in healthy young adults. Folia Med Cracov 2022; 62: 111-122
• 18 Sakamoto M, Matsutani D, Kayama Y. Clinical implications of baroreflex sensitivity in type 2 diabetes. Int Heart J 2019; 60: 241-246
• 19 Samora M, Huo Y, McCuller RK. et al. Spontaneous baroreflex sensitivity is attenuated in male UCD-type 2 diabetes mellitus rats: A link between metabolic and autonomic dysfunction. Auton Neurosci Basic Clin 2023; 249: 103117
• 20 Freckmann G, Pleus S, Link M. et al. Accuracy evaluation of four blood glucose monitoring systems in unaltered blood samples in the low glycemic range and blood samples in the concentration range defined by ISO 15197. Diabetes Technol Ther 2015; 17: 625-634
• 21 Silva AFRD, Cruz RC, Albuquerque NLS. et al. Blood pressure variability in individuals with diabetes mellitus: A scoping review. Rev Bras Enferm 2022; 75: e20210804
• 22 Berkelaar M, Eekhoff EMW, Simonis-Bik AMC. et al. Effects of induced hyperinsulinaemia with and without hyperglycaemia on measures of cardiac vagal control. Diabetologia 2013; 56: 1436-1443
• 23 Bathula R, Hughes AD, Panerai R. et al. Indian Asians have poorer cardiovascular autonomic function than Europeans: this is due to greater hyperglycaemia and may contribute to their greater risk of heart disease. Diabetologia 2010; 53: 2120-2128
• 24 Indumathy J, Pal GK, Pal P. et al. Decreased baroreflex sensitivity is linked to sympathovagal imbalance, body fat mass and altered cardiometabolic profile in pre-obesity and obesity. Metabolism 2015; 64: 1704-1714
• 25 Young BE, Kaur J, Vranish JR. et al. Augmented resting beat-to-beat blood pressure variability in young, healthy, non-Hispanic black men. Exp Physiol 2020; 105: 1102-1110
• 26 Sabino-Carvalho JL, Jeong J, Sprick J. et al. Augmented resting beat-to-beat blood pressure variability in patients with chronic kidney disease. Clin Auton Res Off J Clin Auton Res Soc 2023; 33: 705-714
• 27 Vranish JR, Holwerda SW, Young BE. et al. Exaggerated vasoconstriction to spontaneous bursts of muscle sympathetic nerve activity in healthy young black men. Hypertens Dallas Tex 1979 2018; 71: 192-198
• 28 Brothers RM, Fadel PJ, Keller DM. Racial disparities in cardiovascular disease risk: Mechanisms of vascular dysfunction. Am J Physiol Heart Circ Physiol 2019; 317: H777-H789
• 29 Stein CM, Lang CC, Nelson R. et al. Vasodilation in black Americans: Attenuated nitric oxide-mediated responses. Clin Pharmacol Ther 1997; 62: 436-443
• 30 Parati G, Ochoa JE, Salvi P. et al. Prognostic value of blood pressure variability and average blood pressure levels in patients with hypertension and diabetes. Diabetes Care 2013; 36: S312-S324
• 31 Sethi BK, Baruah MP, Kumar AS. Blood pressure variability in patients with diabetes mellitus with hypertension: Treatment recommendations and role of amlodipine. J Assoc Physicians India 2017; 65: 67-71
• 32 Koval OM, Nguyen EK, Mittauer DJ. et al. Regulation of smooth muscle cell proliferation by mitochondrial Ca2+ in type 2 diabetes. Int J Mol Sci 2023; 24: 12897
• 33 Teixeira AL, Nardone M, Samora M. et al. Potentiation of GABAergic synaptic transmission by diazepam acutely increases resting beat-to-beat blood pressure variability in young adults. Am J Physiol Regul Integr Comp Physiol 2022; 322: R501-R510
• 34 Holwerda SW, Reynolds LJ, Restaino RM. et al. The influence of reduced insulin sensitivity via short-term reductions in physical activity on cardiac baroreflex sensitivity during acute hyperglycemia. J Appl Physiol Bethesda Md 1985 2015; 119: 1383-1392
• 35 Montano N, Ruscone TG, Porta A. et al. Power spectrum analysis of heart rate variability to assess the changes in sympathovagal balance during graded orthostatic tilt. Circulation 1994; 90: 1826-1831
• 36 Parati G, Mancia G, Di Rienzo M. et al Point: Cardiovascular variability is/is not an index of autonomic control of circulation. J Appl Physiol Bethesda Md 1985 2006; 101: 676-678 discussion 681–682