Treat & reverse the root cause of diabetic complications (tissue hypoxia) with slow breathing

Key Points

• Type-1 diabetics exhibit lower resting oxygen saturation, lower cardiovascular control, reduced hypoxic chemoreflexes, and enhanced hypercapnic chemoreflexes

• The root cause of these problems is resting tissue hypoxia, which causes over-activation of the sympathetic nervous system and autonomic and cardiovascular dysfunction

• Autonomic imbalance in diabetes is largely functional, and therefore reversible

The Breathing Diabetic Summary

This is a follow-on to our previous paper on cardio-respiratory control in diabetes.  This paper, however, is a clinical study rather than a literature review.

Previous studies have shown respiratory problems in diabetics.  Previous studies also have shown cardiovascular dysfunction in diabetics.  However, no studies simultaneously examined both of these factors in an integrated fashion.  Thus, the aim of this study was to comprehensively examine cardio-respiratory function in type-1 diabetics.

The key measurements from this paper were resting oxygen saturation, baroreflex sensitivity (BRS; a marker of cardiovascular and autonomic control), and both hypoxic and hypercapnic chemoreflexes (markers of respiratory control). 

Their hypothesis: If the BRS and chemoreflexes were suppressed in diabetics, this would indicate nerve damage was present.  However, if cardiovascular function was suppressed, while chemoreflexes were enhanced, this would indicate autonomic imbalance that has a functional cause.  In this latter case, therapies aimed at restoring cardio-respiratory control (for example, slow breathing) could help prevent diabetic complications.

The study had 46 patients with type-1 diabetes and 103 age-matched control subjects.  The participants went through a variety of tests to evaluate baroreflex functioning and chemoreflexes.  For example, to measure the patients’ hypercapnic chemoreflex, oxygen was kept constant while CO2 was gradually increased.  The chemoreflex can then be measured as the slope of the relationship between minute ventilation and change in CO2 (or oxygen in the case of the hypoxic chemoreflex).  A large change in minute ventilation for a small change in CO2 would represent an enhanced hypercapnic chemoreflex.

Interestingly, the results showed that although diabetics displayed larger breathing volumes than controls, they had slightly higher CO2 levels and reduced oxygen saturation.  However, they did have an enhanced hypercapnic chemoreflex, meaning they could not tolerate changes in CO2 as well as controls.  And, somewhat surprisingly, they had a reduced hypoxic chemoreflex, meaning they could tolerate lower oxygen levels without increasing their breathing as much as controls.

The diabetics also exhibited a lower resting oxygen saturation. This is fascinating because the lower resting oxygen saturation implies a significantly reduced partial pressure of oxygen (due to the oxyhemoglobin dissociation curve). This would result in tissue hypoxia. What’s more, they cite a paper (which is now near the top of my reading list) that shows that a high HbA1c also reduces tissue oxygenation by increasing oxygen’s affinity to hemoglobin (shifting the dissociation curve to the left). 

The authors suggest that their results can be interpreted as follows: Resting tissue hypoxia, combined with a suppressed hypoxic chemoreflex, leads to an enhanced compensatory hypercapnic chemoreflex and chronic activation of the sympathetic nervous system.  This, in turn, leads to a suppression of the cardiovascular system (reduced BRS and reduced heart rate variability).  It’s a vicious cycle.

However, this is actually great news.  Their results suggest that diabetic autonomic imbalance is largely functional and not related to nerve damage.  (Remember, both the cardiovascular reflexes and the chemoreflexes would have been suppressed with nerve damage).  In fact, the authors suggest that this imbalance likely leads to nerve damage rather than being the result of it. Therefore, therapies targeting cardio-respiratory control could help reverse/prevent diabetic complications.

Finally, the authors suggest that breathing control and physical exercise could be two such therapies to restore cardio-respiratory function.  We know that slow breathing has many therapeutic benefits for the cardiovascular, autonomic, and respiratory systems.  And, we know that slow, light breathing increases CO2 and increases tissue oxygenation (due to the Bohr effect).  Now, we know that these positive benefits have the potential to stop or reverse diabetic complications. 

Abstract from Paper

BACKGROUND: Cardiovascular (baroreflex) and respiratory (chemoreflex) control mechanisms were studied separately in diabetes, but their reciprocal interaction (well known for diseases like heart failure) had never been comprehensively assessed. We hypothesized that prevalent autonomic neuropathy would depress both reflexes, whereas prevalent autonomic imbalance through sympathetic activation would depress the baroreflex but enhance the chemoreflexes.

METHODS: In 46 type-1 diabetic subjects (7.0±0.9year duration) and 103 age-matched controls we measured the baroreflex (average of 7 methods), and the chemoreflexes, (hypercapnic: ventilation/carbon dioxide slope during hyperoxic progressive hypercapnia; hypoxic: ventilation/oxygen saturation slope during normocapnic progressive hypoxia). Autonomic dysfunction was evaluated by cardiovascular reflex tests.

RESULTS: Resting oxygen saturation and baroreflex sensitivity were reduced in the diabetic group, whereas the hypercapnic chemoreflex was significantly increased in the entire diabetic group. Despite lower oxygen saturation the hypoxic chemoreflex showed a trend toward a depression in the diabetic group.

CONCLUSION: Cardio-respiratory control imbalance is a common finding in early type 1 diabetes. A reduced sensitivity to hypoxia seems a primary factor leading to reflex sympathetic activation (enhanced hypercapnic chemoreflex and baroreflex depression), hence suggesting a functional origin of cardio-respiratory control imbalance in initial diabetes.

Journal Reference:

Bianchi L, Porta C, Rinaldi A, Gazzaruso C, Fratino P, DeCata P, Protti P, Paltro R, Bernardi L. Integrated cardiovascular/respiratory control in type 1 diabetes evidences functional imbalance: Possible role of hypoxia. Int J Cardiol. 2017;244:254 – 259.

Slow breathing improves blood sugar by reducing body’s endogenous production of glucose

Key Points

• Slow breathing lowers blood sugar by reducing the liver’s production of glucose

• Slow breathing increases insulin sensitivity

• Slow breathing might be a no-cost beneficial intervention for diabetics

Breathing Blueprint Summary

This is a follow on to the previous Wilson et al. (2013) paper that described how a relaxation breathing exercise improved glycemic response in healthy college-aged humans.  In this review, the authors examine key evidence showing that breathing can potentially improve glycemic response and insulin sensitivity.  

Let’s start with some statistics. Can you believe that in 2013, ~9.3% of Americans had diabetes?!?  That’s insane.  And, pharmacy costs added up to ~$18 billion!  Breathing might not cure diabetes, but it might help reduce the costs and negative side effects of diabetics by improving our insulin sensitivity and glycemic control. Which is exactly what this paper examined.

One mechanism they found that explains why slow, relaxation breathing lowers blood sugar is reduction in sympathetic nervous system activity.  In short, the liver generates glucose via a process called gluconeogenesis.  When the sympathetic nervous system is activated, it increases this process, increasing the body’s endogenous production of glucose.  Other stress hormones, such as adrenaline, also increase the liver’s production of glucose.  By breathing slowly, we shift out of this sympathetic state, reducing the amount of glucose produced by the liver and helping reduce our blood sugar.

They also examined several studies showing that slow breathing can restore insulin sensitivity.  There were no clear mechanisms as to how slow breathing improved insulin sensitivity, but the take-home point was that it does. We will have to wait on future studies to identify exactly what’s going on “under the hood.”

Overall, this review showed scientific evidence that breathing exercises can improve glycemic control and increase insulin sensitivity.  The glucose-lowering effect of slow breathing is likely due to reduced sympathetic activity and reduced glucose production by the liver.  The improved insulin sensitivity might also be related to this, but the precise mechanism is unknown.

In any case, I think it’s safe to say that practicing Principle 1 and Principle 2 is a good idea, especially for diabetics, to improve glycemic control and insulin sensitivity.

Abstract from Paper

This is the first review of the literature on the effects of slow breathing on glycemic regulation and insulin sensitivity. While many studies have investigated the effects of yoga on individuals with diabetes, few studies have specifically focusing on the isolation of slow breathing as the principle factor in their intervention. While it is difficult to separate the exercise-related effects of yoga, there is considerable evidence that a breathing intervention is capable of increasing insulin sensitivity and improving glycemic regulation. This appears to be true both acutely and chronically in healthy individuals and those with diabetes. Yoga pranayama and the slow breathing practices that are fundamental to yoga represent a relatively low-cost and under-utilized intervention for individuals with conditions related to altered glycemic regulation and insulin sensitivity. More studies should focus on pranayama and slow breathing maneuvers to better clarify the role of respiratory modulation on glucose metabolism and insulin response.

Journal Reference:

Wilson T, Kelly KL, Baker SE. Review: Can yoga breathing exercises improve glycemic response and insulin sensitivity?. J Yoga Phys Ther. 2017;7(2). DOI: 10.4172/2157-7595.1000270.