Trained breathing-induced oxygenation acutely reverses cardiovascular autonomic dysfunction in patients with type 2 diabetes and renal disease - Esposito et al. (2016)

Key Points

  • Slow breathing and oxygen administration both significantly increased baroreflex sensitivity in type 2 diabetic patients

  • Similar improvements were observed in diabetic patients with or without diabetic kidney disease

  • Autonomic balance is restored by treating the root cause of dysfunction: tissue hypoxia

The Breathing Diabetic Summary

A 2011 study showed that slow breathing and oxygen administration could improve autonomic function in type 1 diabetics.  This was a radical breakthrough: it revealed that autonomic imbalance in diabetes is partially functional and, therefore, can be reversed.  In this current paper, the authors examine if the same is true for type 2 diabetics with or without diabetic kidney disease. If so, this would be another paradigm shift.  It would show that, even in diabetics with severe complications, autonomic imbalance is partially functional and, hence, reversible.

If you are a type 1 or type 2 diabetic, you have probably heard that your autonomic nervous system is compromised.  There are a lot of factors contributing to this, including chronic blood sugar fluctuations and their resulting emotional fluctuations, changes in blood circulation, accumulation of AGEs (advanced glycation end products), and inflammation.  One robust way to measure whether autonomic dysfunction is present is through the baroreflex sensitivity (BRS).  BRS measures your body’s ability to quickly adjust blood pressure to meet the current demands of your situation.  In general, diabetics have significantly lower BRS scores than non-diabetics.  Moreover, reduced BRS serves as a telltale sign of future complications.  Therefore, in this study BRS is used as a marker of autonomic function.

The study enrolled 26 diabetic patients, 12 of which had diabetic kidney disease, and 24 non-diabetic controls.  They had the participants lie down and breathe normally for 5 minutes followed by 2 minutes of slow breathing at 6 breaths/min.  Afterward, the patients repeated the procedure (5 min of rest followed by 2 min of slow breathing) while inhaling increased oxygen at 5 liters/min.

The results showed that the diabetics generally had lower oxygen saturation and BRS scores than the controls.  Slow breathing at 6 breaths/min increased oxygen saturation and significantly increased BRS in both the diabetic and control participants.  Moreover, slow breathing reduced by systolic and diastolic blood pressure in both groups.

When the procedure was repeated with added oxygen, similar results occurred: oxygen saturation increased and BRS scores rose.  Combining slow breathing with increased oxygen did not improve results further: slow breathing or oxygen administration alone were enough to achieve maximum improvements in BRS.  Finally, whereas slow breathing improved blood pressure, oxygen administration had no effect.

Encouragingly, the results were not different when comparing diabetics with our without kidney disease.  Both groups of patients showed similar improvements in oxygen saturation and BRS.  Thus, even in diabetics with extreme complications, slow breathing or oxygen administration have the capability to acutely reverse autonomic dysfunction.

Because the immediate effect of both slow breathing and oxygen administration was to increase blood oxygen saturation, the authors hypothesize that the improvements in autonomic function were secondary to tissue oxygenation.  That is, by increasing tissue oxygenation, we restore autonomic functioning.  Tissue hypoxia leads to chronic activation of the sympathetic nervous system and disrupted cardiovascular and respiratory control.  Thus, by increasing tissue oxygenation, we treat the root cause (tissue hypoxia), and restore autonomic balance.

Overall, this paper showed us three remarkable things. First, slow breathing can improve autonomic functioning in type 2 diabetics. Second, even when severe complications exist, such as kidney disease, autonomic function can still be restored with slow breathing. And third, autonomic function is restored by treating the root cause of the problem: tissue hypoxia. Moreover, their results (along with the results found here & here) indicate that autonomic dysfunction is not an expression of nerve damage. Rather, it is a reversible phenomenon that might indeed be the precursor to nerve damage. This is a paradigm-shifting view that opens new opportunities for treatment of autonomic imbalance in diabetics.

Abstract from Paper

AIMS: Cardiovascular autonomic dysfunction, evaluated as baroreflex sensitivity (BRS), could be acutely corrected by slow breathing or oxygen administration in patients with type 1 diabetes, thus suggesting a functional component of the disorder. We tested this hypothesis in patients with the type 2 diabetes with or without renal impairment.

METHODS: Twenty-six patients with type 2 diabetes (aged 61.0 ± 0.8 years, mean ± SEM; duration of diabetes 10.5 ± 2 years, BMI 29.9 ± 0.7 kg/m(2), GFR 68.1 ± 5.6 ml/min) and 24 healthy controls (aged 58.5 ± 1.0 years) were studied. BRS was obtained from recordings of RR interval and systolic blood pressure fluctuations during spontaneous and during slow, deep (6 breaths/min) controlled breathing in conditions of normoxia or hyperoxia (5 l/min oxygen).

RESULTS: During spontaneous breathing, diabetic patients had lower RR interval and lower BRS compared with the control subjects (7.1 ± 1.2 vs. 12.6 ± 2.0 ms/mmHg, p < 0.025). Deep breathing and oxygen administration significantly increased arterial saturation, reduced RR interval and increased BRS in both groups (to 9.6 ± 1.8 and 15.4 ± 2.4 ms/mmHg, respectively, p < 0.05, hyperoxia vs. normoxia). Twelve diabetic patients affected by chronic diabetic kidney disease (DKD) presented a significant improvement in the BRS during slow breathing and hyperoxia (p < 0.025 vs. spontaneous breathing during normoxia).

CONCLUSIONS: Autonomic dysfunction present in patients with type 2 diabetes can be partially reversed by slow breathing, suggesting a functional role of hypoxia, also in patients with DKD. Interventions known to relieve tissue hypoxia and improve autonomic function, like physical activity, may be useful in the prevention and management of complications in patients with diabetes.

Journal Reference:

Esposito P., Mereu R., De Barbieri G., Rampino T., Di Toro A., Groop P.H., Dal Canton A., and L. Bernardi (2016), Trained breathing-induced oxygenation acutely reverses cardiovascular autonomic dysfunction in patients with type 2 diabetes and renal disease, Acta Diabetologica, 53(2), 217 – 226, doi: 10.1007/s00592-015-0765-5.