Double Trouble

Studies Point to Links Between COPD and IR

The link between insulin resistance (IR) and Chronic Obstructive Pulmonary Disease (COPD) has been studied for years in humans and is now being seen in horses. When COPD horses are starting to move gingerly over rocks in the driveway and when IR horses are puffing like freight trains just standing in the field, we see firsthand that these are systemic and not just local tissue diseases. Farriers report that COPD horses have poor hoof quality, white line disease, and laminitis signs and foot pain. Owners are doing all they can with good management of IR, but their horses continue to be footsore or are experiencing breathing issues now.  These two diseases have created a co-morbidity that churns each other into COPD, making IR worse and IR making COPD worse.

Items to cover:

  • Why inflammation of both diseases is effecting the entire body – not just feet in IR or just lungs in COPD
  • Thyroid dysfunction/suboptimal levels make both COPD and IR worse
  • Why muscle loss in both IR and COPD advances the disease progress in both
  • Why COPD treatments with clenbuterol can further increase IR
  • Blood flow problems in both COPD and IR 

 It’s not just local, it’s all over the body

Both IR and COPD are systemic diseases – they affect multiple organs and muscles. In both IR and COPD, inflammatory mediators are showing in the whole body. Specific mediators such as IL-1, IL-6, TNF and free radicals are well documented to be common to both diseases, so inflammation in the lungs will go on to attack hoof laminae and inflammation from fat in IR attacks lung tissue.

In addition, oxidative stress in the diseases will create a depletion of antioxidants such as vitamin E. Vitamin E is proven to help lung tissue protection, and if it’s depleted not just from COPD but also IR inflammation, the tissues get damaged, quicker and harder.

Thyroid Problems created by both IR and COPD

Thyroid dysfunction is frequently detected in chronic diseases. In COPD, studies show that TSH hormone decreases (TSH is the hormone in the brain that goes to the thyroid gland to trigger thyroid hormone release), that T3 thyroid hormone also decreases. The inflammatory mediators of COPD alter body systems in lung, brain, and muscle, leading to alterations in thyroid hormone levels in the bloodstream. The more severe the COPD is, the more the impairment of the thyroid glands ability. This leads to suboptimal thyroid levels – run at the far low end of the range. In COPD, veterinary testing of thyroid function needs to be increased to ensure proper health and management.

There are other conditions/treatments associated with COPD to further increase thyroid problems

1. Glucocorticoids (steroid inhalers, prednisone tablets, dexamethasone)

These often are given for COPD, but they have negative effects, such as

• [OU2] Decreasing TSH hormone from the brain, which leads to thyroid hormone dropping.

  1. Increasing blood glucose (hyperglycemia), which leads to increased prevalence of lung infections in COPD. The airway sugar levels increase and opportunistic bacteria grow.
  2. Breaking down of muscle (steroid myopathy), which increases IR, and damages breathing muscles
  3. Weakening the immune system, which leads to increased infections that take up more airspace and make COPD worse. Also, in bacterial infections, IR increases.
  4. Creating higher glucose levels, thereby increasing  IR levels

A hallmark of COPD is that with time, the amounts of steroids used in the past does not help anymore, so greater and greater amounts are needed. This is called “non-responsiveness” to steroids. Eventually, even high amounts are ineffective. Horse owners see this problem often in COPD horses.

Although the steroids don’t help breathing, the negative effects grow with increased doses: more lung infections, more muscle loss, lower thyroid levels and higher IR.

Cushing Disease further advances COPD in several ways:

  1. Dopamine agonists like pergolide also decrease TSH hormone, which lowers thyroid hormone. Lower thyroid hormone does not allow breathing muscles on skeletal muscle to operate normally. COPD is not just mucus accumulation in the lungs/fibrosis—it also affects the horse’s ability to take deep breaths and exhale normally.
  2. Most Cushing horses are also IR—lower thyroid levels means lower insulin sensitivity, which in turn means higher blood insulin levels that can lead to laminitis.
  3. Cushing horses are also thin due to high ACTH, which breaks down muscle. Muscle is the biggest user of insulin, so less muscle means higher insulin and more IR.
  4. Cushing horses have what is normal in all normal older horses, “sarcopenia,” muscle loss due to aging. Again, as muscle amount decreases, IR levels will increase. This is why IR is also common in older and thin animals—not just in overweight horses and people.
  5. Cushings can lead to higher blood glucose levels (hyperglycemia), which leads to increased frequency of lung infections.

Although rare, true hypothyroidism with no COPD will lead to muscle impairment in studies. “Hypothyroid myopathy.” So COPD is creating thyroid problems and that only furthers worsening of COPD signs—it makes itself worse. In a study, hypothyroidism “significantly reduced pulmonary function tests.”

Nerve repair and regeneration —  Recent studies have shown that by bathing damaged nerves in thyroid hormone, they get a large increase in healing. As nerves are damaged in the feet of laminitic horses, you can imagine the importance of proper thyroid levels in order to regain foot comfort. If a horse is struggling to catch its breath just to stand in a field, you can see why proper nerve communication with breathing muscle is needed.

Evidence of Similar Muscle Loss Symptoms in Both IR and COPD Patients

  1. In humans studies  it’s “demonstrated that greater IR in COPD patients compared to normal patients” – several studies
  2. There are insulin receptors within lung tissue that influence lung structure and function. If in high levels, insulin in the lungs promotes mast cell degradation, leading to narrowing of airways and further airway problems. When insulin aerosol is inhaled in lungs, cell fibrosis of lung tissue and reduction in airway function is seen.
  3. Muscle loss occurs in both IR and COPD. In IR, muscle mass decreased as more fat cells move in and release inflammatory mediators. IR also lessens blood flow to muscle so it gets less oxygen and nutrients. Muscle wasting starts to occur. If respiratory muscles targeted, that means reduced breathing ability. In COPD, less oxygen goes to muscle and that will reduce muscle mass. Muscle is the biggest user of insulin in circulation, so if there’s less muscle present, then there’s more insulin in circulation.

In both IR and COPD, thyroid problems further muscle problems

Clenbuterol bronchodilator – what owners and your veterinarian need to know.

There are cases of horses on this medicine for 30+ days developing laminitis—why?

Clenbuterol has a short time limit for effectiveness if used daily – by day 10+, it doesn’t regulate and has little to no bronchodilator effect, but it has a huge effect on insulin in animals.

A study in 2007  showed that clenbuterol increased insulin levels in horses. Another study found that clenbuterol increased blood glucose 174 percent and insulin a huge 379 percent over control groups. High blood sugar leads to more lung infections and higher insulin leads to less blood flow to tissues. If this drug issued, it need only be used for a few days and then should be discontinued, as it effects multiple systems, not just the airway.

Blood Flow Problems with COPD and IR

COPD

  1. Hypoxia results in lower amounts of oxygen distributed to tissues. This will affect not only the lung tissue itself but also laminae in feet, creating more inflammation, thus damaging muscle, which will then increase symptoms of IR.
  2. Changes in the blood vessels themselves reduce blood flow so less oxygen and fewer nutrients flow to the tissue, which can increase inflammation, and increases both COPD and IR symptoms. In one study of severe COPD, in only 6 months there was a 10 percent decrease in blood flow.

IR  

  1. High insulin creates vasoconstriction, which again causes fewer nutrients and oxygen flow to tissues. This is an important reason to lower insulin to help in the healing of laminitic tissues.
  2. Pain in IR laminitis. Insulin increases in all animals when they experience pain, beyond just the pre-existing metabolic insulin problems. This pain is not just heartbreaking to owners, it’s actually making the problem worse. Higher “pain insulin” means more loss of blood flow.

Learn to Recognize the Link Between COPD and IR and Treat Simultaneously

COPD horses will struggle to breathe if they are already IR prior to COPD onset or become IR due to COPD. If an IR horse is genetically predisposed to becoming COPD later in life, then the pre-existing IR will become worse as COPD presents. Proper management of both conditions at the same time is key. Excellent IR diet control will not benefit the horse if its COPD is not addressed. In horses with breathing problems with COPD, medications need to be carefully controlled to help avoid intensifying IR.

And remember, COPD is a trigger for increasing IR, which can lead to foot pain and laminitis.

Finally, high insulin levels in IR will lead to worsening airway problems. Owners, farriers, and veterinarians alike need to be aware and understand this strong link so that measures are taken to avoid having to react to crisis events.

About Frank K. Reilly 

Frank K. Reilly is the senior doctor of Equine Medical and Surgical Associates INC, in West Chester, PA. He has been in equine practice for 30 years and has worked on six world-record racehorses. He is a mentor of the AUMA, AAEP, and on the Board of Trustees of the AAPF Professional Farrier Group. Dr. Reilly lectures at multiple events throughout the USA on equine COPD/asthma, insulin problems, Cushings, summer eczema, and vitamin E deficiencies. He can be reached at www.equimedsurg.com