Integrated cardio-respiratory control: Insight in diabetes - Bernardi and Bianchi (2016)

Key Points

  • Neuropathy (nerve damage) in diabetics might actually be autonomic dysfunction

  • Autonomic imbalance is partially functional and therefore reversible

  • Therapies focusing on autonomic balance (e.g., slow breathing) might prevent and/or reverse diabetic complications

The Breathing Diabetic Summary

When I was ~13 years old, I got an insulin pump. It was miraculous.  I could give myself insulin anytime I wanted, without taking shots.  Today, a child diagnosed with type 1 diabetes might receive a pump and a continuous glucose monitor, which they monitor through their iPhone.  Diabetes care has come a long way.

Because of that, many tests used to diagnose neuropathy (nerve damage) are not as relevant.  Even with poor control by today’s standards, we are much better off than we used to be.  Yet, diabetic complications are still rampant.  The authors of this paper suggest that subclinical autonomic dysfunction is the root of the problem.  In fact, subclinical autonomic problems are associated with increased illness and are predictive of other, more serious diabetic complications (e.g., eye problems).

What’s more, issues typically classified as “diabetic neuropathy” might not be nerve damage at all.  What if, instead, they are the first signs of autonomic dysfunction?  This is a huge difference, which can be seen in the name itself: dysfunction.  Nerve “damage” implies that the damage is done.  Autonomic “dysfunction” implies that something is not functioning correctly.  Maybe it can be reversed

Which brings me to the main hypothesis of this paper.  The autonomic tests used to reveal “nerve loss” also can be explained by over-activation of the sympathetic nervous system and under-activation of the parasympathetic nervous system.  This opens new treatment opportunities aimed at restoring proper autonomic balance rather than treating nerve damage.

But to start, we have to thoroughly assess autonomic function.  How do we do that?  As the title of this paper suggests, by examining integrated cardio-respiratory control.  There are two main components to this: baroreflexes and chemoreflexes.

We have discussed baroreflexes at length in other summaries.  As a quick recap, the baroreflexes help control blood pressure.  They respond to changes in blood pressure with rapid changes in sympathetic (or parasympathetic) activation to increase (or decrease) heart rate, which equalizes blood pressure.

Chemoreflexes primarily respond to changes in carbon dioxide and oxygen to regulate breathing.  However, the baro- and chemoreflexes do not work independently. 

Let’s imagine your chemoreflexes sense high levels of carbon dioxide.  This will stimulate a breathing response that activates the sympathetic nervous system, which will temporarily increase heart rate and blood pressure.  The baroreflexes will then respond, sending signals to increase parasympathetic firing to reduce heart rate and blood pressure. It’s a dynamic, bi-directional relationship that keeps our cardiovascular and respiratory systems in balance.

However, this balance is often disrupted in disease states.  If one loses cardiovascular control (that is, their baroreflexes are suppressed), this stimulates increased breathing due to sympathetic activation, which then modifies the chemoreflexes.  With many disease states, this can reset the balance point: the baroreflexes can get used to higher sympathetic activation and higher blood pressure.  Over time, this will lead to many complications.

How might this play out in diabetes?  We know from previous papers that mild tissue hypoxia is prevalent in diabetes.  This would trigger a chemoreflex response and stimulate the sympathetic nervous system.  To compensate, the baroreflexes would then be activated.  If our blood sugars continue to decline over time, the tissue hypoxia would not improve, and this vicious cycle would continue.

However, if this was caught early enough it might be correctable.  Because these problems are largely functional, we could potentially reverse them before they develop into more severe diabetic complications.  The authors suggest that the two main ways to do this are physical exercise and slow breathing.

The study shares a table comparing the short and long-term effects of both slow breathing and physical exercise on many outcomes that are crucial to cardio-respiratory control.  In the short-term, slow breathing has positive effects in almost every category (for example, suppressing sympathetic activation, increasing heart rate variability, etc.).  We need more studies to understand the long-term positive effects of slow breathing; however, we know from the few that have been published that sustained practice of slow breathing can enhance heart rate variability and reduce resting respiratory rate, thus helping restore cardio-respiratory balance.

Overall, this was a pivotal paper for diabetes care. What they presented is rather remarkable: What is typically considered “neuropathy” might actually be autonomic dysfunction. And if so, it is reversible. The two easiest ways to achieve this reversal are slow breathing and physical exercise. Focusing on integrated cardio-respiratory health provides a new outlook on preventing diabetic complications and restoring health to the diabetic population.

Abstract from Paper

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.

Journal Reference:

Bernardi, L. and L. Bianchi (2016), Integrated cardio-respiratory control: Insight in diabetes, Current Diabetes Reports, 16: 107, DOI 10.1007/s11892-016-0804-9.