Integrated Cardio-Respiratory Control: Insight in Diabetes
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Autonomic dysfunction is a frequent and relevant complication of diabetes mellitus, as it is associated with increased morbidity and mortality. In addition, it is today considered as predictive of the most severe diabetic complications, like nephropathy and retinopathy. The classical methods of screening are the cardiovascular reflex tests and were originally interpreted as evidence of nerve damage. A more modern approach, based on the integrated control of cardiovascular and respiratory function, reveals that these abnormalities are to a great extent functional, at least in the early stage of the disease, thus suggesting new potential interventions. Therefore, this review aims to go further investigating how the imbalance of the autonomic nervous system is altered and can be influenced in many chronic pathologies through a global view of cardio-respiratory and metabolic interactions and how the same mechanisms are applicable to diabetes.
KeywordsChemoreflex Baroreflex Heart rate variability Diabetic neuropathy Hypoxia Autonomic nervous system Cardio-respiratory interactions
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Conflict of Interest
Luciano Bernardi and Lucio Bianchi declare that they have no conflict of interest.
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This article does not contain any studies with human or animal subjects performed by any of the authors.
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- 4.Duvnjak L, Tomić M, Blaslov K, et al. Autonomic nervous system function assessed by conventional and spectral analysis might be useful in terms of predicting retinal deterioration in persons with type 1 diabetes mellitus. Diabetes Res Clin Pract. 2016;116:111–6. doi: 10.1016/j.diabres.2016.04.042.CrossRefPubMedGoogle Scholar
- 12.••Francis DA, Coats JS, Ponikowski P. Chemoreflex-baroreflex interactions in cardiovascular disease. In: Bradley TD, Floras JS, editors. Sleep apnea. Implication in cardiovascular and cerebrovascular disease. New York: Marcel Dekker; 2000. p. 261–83. Describes the reciprocal interaction between control of breathing and control of circulation.Google Scholar
- 17.•Bernardi L, De Barbieri G, Rosengård-Bärlund M, et al. New method to measure and improve consistency of baroreflex sensitivity values. Clin Auton Res. 2010;20(6):353–61. Describes a new method to measure baroreflex sensitivity and compare it with all other methods, showing that the new method has higher robustness and in agreement with the rest of methods.CrossRefPubMedGoogle Scholar
- 18.••Bernardi L, Spallone V, Stevens M, et al. Methods of investigation for cardiac autonomic dysfunction in human research studies. Toronto Consensus Panel on Diabetic Neuropathy. Diabetes Metab Res Rev. 2011;27(7):654–64. Review describing in critical terms the most relevant methods for research, with special emphasis to the misconceptions related to heart rate variability-based methods.CrossRefPubMedGoogle Scholar
- 22.••Rosengård-Bärlund M, Bernardi L, Fagerudd J, FinnDiane Study Group, et al. Early autonomic dysfunction in type 1 diabetes: a reversible disorder? Diabetologia. 2009;52(6):1164–72. doi: 10.1007/s00125-009-1340-9. Describes for the first time that autonomic dysfunction is potentially reversible.CrossRefPubMedGoogle Scholar
- 24.••La Rovere MT, Bigger Jr JT, Marcus FI, et al. Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) Investigators. Lancet. 1998;351(9101):478–84. One of the most important papers showing the prognostic power of baroreflex sensitivity in cardiac patients.CrossRefPubMedGoogle Scholar
- 25.•Johansson M, Gao SA, Friberg P, et al. Baroreflex effectiveness index and baroreflex sensitivity predict all-cause mortality and sudden death in hypertensive patients with chronic renal failure. J Hypertens. 2007;25(1):163–8. Another important paper showing the prognostic power of baroreflex sensitivity in hypertensive patients.CrossRefPubMedGoogle Scholar
- 26.•Gerritsen J, Dekker JM, TenVoorde BJ, et al. Impaired autonomic function is associated with increased mortality, especially in subjects with diabetes, hypertension, or a history of cardiovascular disease: the Hoorn Study. Diabetes Care. 2001;24(10):1793–8. This paper reports some information about the prognostic value of baroreflex sensitivity in diabetes.Google Scholar
- 28.••Piepoli MF, Coats AJ. The ‘skeletal muscle hypothesis in heart failure’ revised. Eur Heart J. 2013;34(7):486–8. doi: 10.1093/eurheartj/ehs463. Describes the “muscle hypothesis” in heart failure. In the paper, we describe how this seems to apply to diabetes as well.
- 32.••Ponikowski P, Francis DP, Piepoli MF, et al. Enhanced ventilatory response to exercise in patients with chronic heart failure and preserved exercise tolerance: marker of abnormal cardiorespiratory reflex control and predictor of poor prognosis. Circulation. 2001;103(7):967–72. Describes the prognostic significance of chemoreflex abnormalities.CrossRefPubMedGoogle Scholar
- 41.Somers VK, Mark AL, Zavala DC, et al. Contrasting effects of hypoxia and hypercapnia on ventilation and sympathetic activity in humans. J Appl Physiol (1985). 1989;67(5):2101–6.Google Scholar
- 43.•Ponikowski P, Chua TP, Piepoli M, et al. Augmented peripheral chemosensitivity as a potential input to baroreflex impairment and autonomic imbalance in chronic heart failure. Circulation. 1997;96(8):2586–94. Describes the reciprocal interaction between chemoreflexes and baroreflexes in heart failure.CrossRefPubMedGoogle Scholar
- 62.••Bernardi L, Rosengård-Bärlund M, Sandelin A, FinnDiane Study Group, et al. Short-term oxygen administration restores blunted baroreflex sensitivity in patients with type 1 diabetes. Diabetologia. 2011;54(8):2164–73. This paper shows that the parasympathetic reduction results from functional impairment in type 1 diabetes, since it was corrected by oxygen administration, and that hypoxia could be the cause for it.Google Scholar
- 63.•Esposito P, Mereu R, De Barbieri G et al. Trained breathing-induced oxygenation acutely reverses cardiovascular autonomic dysfunction in patients with type 2 diabetes and renal disease. Acta Diabetol. 2015. This paper shows similar results as the previous, in type 2 diabetes also with renal impairment.Google Scholar
- 67.Bianchi L, Porta C, A. Rinaldi et al. Integrated cardiovascular/respiratory control in type 1 diabetes. Accepted abstract, EASD 2015 StockholmGoogle Scholar
- 71.••Bento CF, Pereira P. Regulation of hypoxia-inducible factor 1 and the loss of the cellular response to hypoxia in diabetes. Diabetologia. 2011;54(8):1946–56. This review describes the role of hypoxia-inducible factor in diabetes.Google Scholar
- 72.Bernardi L, Porta C, Spicuzza L, et al. Slow breathing increases arterial baroreflex sensitivity in patients with chronic heart failure. Circulation. 2002;105(2):143–5.Google Scholar
- 73.Joseph CN, Porta C, Casucci G, et al. Slow breathing improves arterial baroreflex sensitivity and decreases blood pressure in essential hypertension. Hypertension. 2005;46(4):714–8.Google Scholar
- 74.Goso Y, Asanoi H, Ishise H, et al. Respiratory modulation of muscle sympathetic nerve activity in patients with chronic heart failure. Circulation. 2001;104(4):418–23.Google Scholar
- 75.Bianchi L, Bernardi L, Ghelardi R et al. Accepted abstract, EASD Munich 2016Google Scholar
- 76.Vimercati C, Qanud K, Ilsar I, et al. Acute vagal stimulation attenuates cardiac metabolic response to β-adrenergic stress. J Physiol. 2012;590(23):6065–74. doi: 10.1113/jphysiol.2012.241943.
- 77.Gupta RC, Imai M, Jiang AJ, et al. Chronic therapy with selective electric vagus nerve stimulation normalizes plasma concentration of tissue necrosis factor-α, interleukin- 6 and B- type natriuretic peptide in dogs with heart failure. J Am Coll Cardiol. 2006;47:77A.Google Scholar
- 78.Kong SS, Liu JJ, Yu XJ, et al. Protection against ischemia-induced oxidative stress conferred by vagal stimulation in the rat heart: involvement of the AMPK-PKC pathway. Int J Mol Sci. 2012;13(11):14311–25. doi: 10.3390/ijms131114311.
- 79.Hegde SV, Adhikari P, Kotian S, et al. Effect of 3-month yoga on oxidative stress in type 2 diabetes with or without complications: a controlled clinical trial. Diabetes Care. 2011;34(10):2208–10. doi: 10.2337/dc10-2430.
- 80.Gordon L, Morrison EY, McGrowder D, et al. Effect of yoga and traditional physical exercise on hormones and percentage insulin binding receptor in patients with type 2 diabetes. Am J Biochem Biotechnol. 2008;4(1):35–42. doi: 10.3844/ajbbsp.2008.35.42.
- 81.Duennwald T, Gatterer H, Groop PH, et al. Effects of a single bout of interval hypoxia on cardiorespiratory control and blood glucose in patients with type 2 diabetes. Diabetes Care. 2013;36(8):2183–9.Google Scholar
- 82.Xiao H, Gu Z, Wang G, et al. The possible mechanisms underlying the impairment of HIF-1α pathway signaling in hyperglycemia and the beneficial effects of certain therapies. Int J Med Sci. 2013;10(10):1412–21.Google Scholar