Effects of a single bout of interval hypoxia on cardiorespiratory control and blood glucose in patients with type 2 diabetes

Tobias Duennwald, Hannes Gatterer, Per-Henrik Groop, Martin Burtscher, Luciano Bernardi, Tobias Duennwald, Hannes Gatterer, Per-Henrik Groop, Martin Burtscher, Luciano Bernardi

Abstract

Objective: Hypoxia may cause functional autonomic imbalance in diabetes. Intermittent hypoxia (IH), a technique improving the adaptation to hypoxia, might improve cardiorespiratory reflexes and, ultimately, blood glucose concentrations in patients with type 2 diabetes. We tested whether a single bout of IH could initiate a long-lasting response potentially leading to better adaptation to hypoxia.

Research design and methods: In 14 patients with type 2 diabetes without autonomic complications, we measured blood pressure, heart rate, oxygen saturation, chemoreflex (hypoxic and hypercapnic ventilatory responses, ventilatory recruitment threshold), and baroreflex sensitivity before, immediately after, and 3 and 6 h after a 1-h single bout of IH (6-min breathing of 13% oxygen mixture 5 times each separated by 6-min recovery). The measurements were repeated on a placebo day (at least 1 week apart, in random sequence) when subjects were only breathing room air (single-blind protocol).

Results: IH significantly increased hypercapnic ventilatory responses and reduced ventilatory recruitment threshold, and increased oxygen saturation and blood pressures, whereas increases in heart rate variability and baroreflex sensitivity were not significant. Blood glucose significantly decreased after IH. No such changes were observed during the placebo day, except an increase in oxygen saturation. Some of the effects lasted 3 h after IH, and some even persisted until 6 h after IH.

Conclusions: A single bout of IH induced an initial adaptation to hypoxia, with improvement in cardiorespiratory reflexes and reduction in blood glucose. Patients with type 2 diabetes could potentially benefit from the application of a full (>2 weeks) IH intervention.

Figures

Figure 1
Figure 1
Plot shows changes in HCVR (top panel), VRT-CO2 (middle panel), and HVR (bottom panel) immediately after 1 h of IH or placebo exposure (n = 14). *Significant differences (P < 0.05, paired t test) from baseline (t1) to postintervention (t2). Bold lines show mean values ± SEM.
Figure 2
Figure 2
Blood glucose changes over time on the hypoxia day (continuous line) and the placebo day (dotted line). Measurements were performed at baseline (t1), immediately after (t2), 3 h after (t3), and 6 h after (t4) the hypoxic or placebo exposure (n = 14). Standardized meal was taken after t2 on both days. A: Comparing blood glucose levels with t1 of the same day. B: Comparing Δ (t − t1) IH vs. Δ (t − t1) placebo day. Data are presented as means ± SEM.

References

    1. Vinik AI, Erbas T. Recognizing and treating diabetic autonomic neuropathy. Cleve Clin J Med 2001;68:928–944
    1. Schönauer M, Thomas A, Morbach S, Niebauer J, Schönauer U, Thiele H. Cardiac autonomic diabetic neuropathy. Diab Vasc Dis Res 2008;5:336–344
    1. Bergner DW, Goldberger JJ. Diabetes mellitus and sudden cardiac death: what are the data? Cardiol J 2010;17:117–129
    1. Rosengård-Bärlund M, Bernardi L, Fagerudd J, et al. FinnDiane Study Group Early autonomic dysfunction in type 1 diabetes: a reversible disorder? Diabetologia 2009;52:1164–1172
    1. Boyko EJ, Ahroni JH, Stensel VL. Tissue oxygenation and skin blood flow in the diabetic foot: responses to cutaneous warming. Foot Ankle Int 2001;22:711–714
    1. Boulton AJ, Scarpello JH, Ward JD. Venous oxygenation in the diabetic neuropathic foot: evidence of arteriovenous shunting? Diabetologia 1982;22:6–8
    1. Solomon LR, Cohen K. Erythrocyte O2 transport and metabolism and effects of vitamin B6 therapy in type II diabetes mellitus. Diabetes 1989;38:881–886
    1. Wheatley CM, Baldi JC, Cassuto NA, Foxx-Lupo WT, Snyder EM. Glycemic control influences lung membrane diffusion and oxygen saturation in exercise-trained subjects with type 1 diabetes: alveolar-capillary membrane conductance in type 1 diabetes. Eur J Appl Physiol 2011;111:567–578
    1. Choudhury S, Taheri S. Obstructive sleep apnoea and type 2 diabetes: whose disease is it anyway? Practical Diabetes Int 2011;28:183–186
    1. Bernardi L, Rosengård-Bärlund M, Sandelin A, Mäkinen VP, Forsblom C, Groop PH, FinnDiane Study Group Short-term oxygen administration restores blunted baroreflex sensitivity in patients with type 1 diabetes. Diabetologia 2011;54:2164–2173
    1. Gordin D, Bernardi L, Rosengård-Bärlund M, et al. Oxygen increases arterial stiffness and blood pressure in patients with type 1 diabetes. Diabetologia 2011;54(Suppl. 1):493.
    1. Neubauer JA. Invited review: Physiological and pathophysiological responses to intermittent hypoxia. J Appl Physiol 2001;90:1593–1599
    1. Casas M, Casas H, Pagés T, et al. Intermittent hypobaric hypoxia induces altitude acclimation and improves the lactate threshold. Aviat Space Environ Med 2000;71:125–130
    1. Burtscher M, Pachinger O, Ehrenbourg I, et al. Intermittent hypoxia increases exercise tolerance in elderly men with and without coronary artery disease. Int J Cardiol 2004;96:247–254
    1. Tin’kov AN, Aksenov VA. Effects of intermittent hypobaric hypoxia on blood lipid concentrations in male coronary heart disease patients. High Alt Med Biol 2002;3:277–282
    1. Meerson F, Pozharov V, Minyailenko T. Superresistance against hypoxia after preliminary adaptation to repeated stress. J Appl Physiol 1994;76:1856–1861
    1. Haider T, Casucci G, Linser T, et al. Interval hypoxic training improves autonomic cardiovascular and respiratory control in patients with mild chronic obstructive pulmonary disease. J Hypertens 2009;27:1648–1654
    1. Nishimura M, Miyamoto K, Suzuki A, et al. Ventilatory and heart rate responses to hypoxia and hypercapnia in patients with diabetes mellitus. Thorax 1989;44:251–257
    1. Weisbrod CJ, Eastwood PR, O’Driscoll G, Green DJ. Abnormal ventilatry responses to hypoxia in Type 2 diabetes. Diabet Med 2005;22:563–568
    1. Montserrat JM, Cochrane GM, Wolf C, Picado C, Roca J, Agusti Vidal A. Ventilatory control in diabetes mellitus. Eur J Respir Dis 1985;67:112–117
    1. Tantucci C, Scionti L, Bottini P, et al. Influence of autonomic neuropathy of different severities on the hypercapnic drive to breathing in diabetic patients. Chest 1997;112:145–153
    1. Homma I, Kageyama S, Nagai T, Taniguchi I, Sakai T, Abé M. Chemosensitivity in patients with diabetic neuropathy. Clin Sci (Lond) 1981;61:599–603
    1. Pikkujämsä SM, Huikuri HV, Airaksinen KE, et al. Heart rate variability and baroreflex sensitivity in hypertensive subjects with and without metabolic features of insulin resistance syndrome. Am J Hypertens 1998;11:523–531
    1. Ziegler D, Laude D, Akila F, Elghozi JL. Time- and frequency-domain estimation of early diabetic cardiovascular autonomic neuropathy. Clin Auton Res 2001;11:369–376
    1. Thangarajah H, Yao D, Chang EI, et al. The molecular basis for impaired hypoxia-induced VEGF expression in diabetic tissues. Proc Natl Acad Sci USA 2009;106:13505–13510
    1. Bernardi L, Gabutti A, Porta C, Spicuzza L. Slow breathing reduces chemoreflex response to hypoxia and hypercapnia, and increases baroreflex sensitivity. J Hypertens 2001;19:2221–2229
    1. Bernardi L, Passino C, Serebrovskaya Z, Serebrovskaya T, Appenzeller O. Respiratory and cardiovascular adaptations to progressive hypoxia; effect of interval hypoxic training. Eur Heart J 2001;22:879–886
    1. Spicuzza L, Gabutti A, Porta C, Montano N, Bernardi L. Yoga and chemoreflex response to hypoxia and hypercapnia. Lancet 2000;356:1495–1496
    1. Laude D, Elghozi JL, Girard A, et al. Comparison of various techniques used to estimate spontaneous baroreflex sensitivity (the EuroBaVar study). Am J Physiol Regul Integr Comp Physiol 2004;286:R226–R231
    1. Bernardi L, De Barbieri G, Rosengård-Bärlund M, Mäkinen VP, Porta C, Groop PH. New method to measure and improve consistency of baroreflex sensitivity values. Clin Auton Res 2010;20:353–361
    1. Bertinieri G, di Rienzo M, Cavallazzi A, Ferrari AU, Pedotti A, Mancia G. A new approach to analysis of the arterial baroreflex. J Hypertens Suppl 1985;3:S79–S81
    1. Pagani M, Somers V, Furlan R, et al. Changes in autonomic regulation induced by physical training in mild hypertension. Hypertension 1988;12:600–610
    1. Pinna GD, Maestri R. Reliability of transfer function estimates in cardiovascular variability analysis. Med Biol Eng Comput 2001;39:338–347
    1. Samaja M, Crespi T, Guazzi M, Vandegriff KD. Oxygen transport in blood at high altitude: role of the hemoglobin-oxygen affinity and impact of the phenomena related to hemoglobin allosterism and red cell function. Eur J Appl Physiol 2003;90:351–359
    1. Bento CF, Pereira P. Regulation of hypoxia-inducible factor 1 and the loss of the cellular response to hypoxia in diabetes. Diabetologia 2011;54:1946–1956

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅