Insulin Resistance

Insulin Resistance In Horses

What is Insulin?

Striker, of Peirson, Florida, licks his lips for HEIRO™.

A.   Insulin is a hormone produced by an organ in the abdomen called the Pancreas. Using a Quarter Horse for reference, the Pancreas is about two feet behind the girth of the saddle on the right side and weighs approximately ¾ of a pound.

About 98% of the Pancreas produces enzymes to break down food in the gut and only 2% make hormones such as Insulin. Hormones are chemicals produced by one type of tissue that are transported to target tissues that have special receptors for the hormone; once the hormone and the receptor connect, the hormone will facilitate reactions inside the target cell.

B.   Horse Insulin has many jobs and many targets. Insulin has direct action on all cells in the body (except the brain), and helps in carbohydrate, protein, and fat breakdown products entering the cells.

Insulin’s main job involves carbohydrate metabolism.  Insulin release from the Pancreas is triggered by rising levels of carbohydrate in the bloodstream. The carbohydrate that causes this Insulin outflow is called Glucose. As Glucose levels rise, Insulin levels will rise and when Glucose levels go down, less Insulin is released from the Pancreas and hence Insulin levels go down.

There are several ways for Glucose levels to go up, but by far, the biggest rise comes after your horse eats. In hay and grass, carbohydrates are the main type of nutrient, with protein second, and fat the third type. In magazines, carbohydrates are often referred to as “sugars” or “starches”.

Starches are actually long chains of thousands of Glucose molecules linked together. As your horse chews, he is starting the process of breaking down starch to release the simple sugar unit of Glucose. Saliva enzymes, stomach acid, and small intestine enzymes further breakdown starch into individual Glucose molecules. Once these Glucose units get into the small intestine, they are absorbed out of the digestive tract and into the bloodstream. After a meal, large quantities of Glucose pour into the bloodstream. Blood Glucose levels are now rising. In literature, blood Glucose is often referred to as the “blood sugar”. This high level of Glucose circulates to the Pancreas and will trigger the Pancreas to release Insulin into the bloodstream. Now we understand Insulin’s source and what causes it to go up and down, which leads us to what it does.

C. Equine Insulin Resistance in horses is the correct term to use when they get pathologically high levels of Insulin. There are many other terms that have been used in the past that are inaccurate or confusing such as:

  • Metabolic Syndrome – this requires high resting Glucose levels which most horses do not get and requires central obesity which horses do not get.
  • Pseudo Cushings and Peripheral Cushings – horses get Insulin Resistance by itself with no Cushings at all in many cases, so trying to attach Cushings to this syndrome is not accurate. Many Cushings horses can develop Insulin Resistance but not all of them do.
  • Horse Diabetes -  most horses do not have elevated blood Glucose levels in Insulin Resistance. bluestarClick here to see more information on Horse Diabetes.
  • Hyperinsulinemia – this is inaccurate because horses and people elevate Insulin levels many times a day after a meal which is normal. The correct term, developed by Dr. Reilly, is Equine Pathological Hyperinsulinemia with Insulin Resistance being one of the causes.

D. Horse Insulin is crucial in promoting Glucose in the bloodstream to move into cells. Glucose is the major fuel used by cells for energy. Again, Insulin has many target tissues but the most important are muscle, fatty tissue, and the liver. How Insulin gets Glucose into cells is much like a lock and key. On the muscle cell, for example, are thousands of receptors waiting for Insulin to arrive. The receptor is the lock and Insulin is the key. When the key fits the lock, it allows Glucose to enter the cell. As Glucose goes from the bloodstream into the cell, the blood Glucose level will drop and hence the output of Insulin from the Pancreas will drop.Glucose transport into muscle and fatty tissue goes up 5-20 times in the presence of Insulin. This fact highlights how important Insulin’s action is in obtaining energy for the cell.

E. Regarding fatty tissue which is another target tissue for Insulin:

  1. Horse Insulin promotes Glucose into fat cells which help in fat synthesis
  2. Simultaneously, Insulin promotes enzymes that help increase fat synthesis
  3. At the same time, Insulin inhibits another type of enzyme that normally breaks down fat

This is a “triple-barrel shotgun effect” — all of which promote fat. This action by Insulin is normal in your horse but you can already hear warning bells if things go wrong. Too much Insulin means too much fat and that puts weight on your horse.

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What is Horse Insulin Resistance?

A. The Definition: Inability to respond to and use Insulin the body produces because Insulin is not functioning properly;higher Insulin levels are needed to achieve the same effect.

There is an abnormally high amount of Insulin circulating for long periods of time that leads to diseases such as Laminitis. Normally, we know the usual level of Insulin throughout the day and know that after a grain meal, the Insulin level will go up 3-4 times the regular level due to Insulin responding to Glucose pouring into the bloodstream. The short-term high level of Insulin is normal Hyperinsulinemia and lasts only a few hours.

In Horse Insulin Resistance, the base level of Insulin is about 3 times higher, so there is a constant elevation during the day. When an Insulin Resistance horse has a grain meal, there is a pathological Hyperinsulinemia that sees the level of Insulin go up 30, 40, 50, and over 100 times usual levels, and can remain elevated much longer than normal.

According to the American Diabetes Association, people with Insulin Resistance and Diabetes have a 7-12 year decreased life span. In a horse, that translates to losing 2.5 to 4.5 years of life.

B. What is causing the condition?

Basically, the key and lock system is broken. There are several ways this occurs and they can occur separately, or combine to do multiple damage.

Ways to cause Pathological Hyperinsulinemia:

  1. The receptor (the lock) on the target cell is directly damaged. Insulin comes along (the key) and can not make a Lock and Key connection. With no connection, Glucose can not enter the cell and is essentially shut out. Blood Glucose levels do not drop and are now artificially elevated, so the Pancreas pours out more and more Insulin to correct the problem. There are lots of keys with not enough working locks. Result: higher than normal levels of Insulin.
  2. The number of receptors on the cell is lower than normal. Again, the same result as above: higher than normal levels of Insulin. The receptors work, but there is just not enough to get Glucose quickly into the cells.
  3. Insulin’s normal action is directly inhibited. The keys do not work right even in target cells that are normal. Again, this means Glucose is not getting into the cells and the Pancreas keeps pouring out more and more Insulin in an attempt to overcome the problem.

The final result that the target cells are resisting to work normally with Insulin (hence the name Insulin Resistance) which causes the Pancreas to try to overcome the resistance by pouring out more and more Insulin. In Insulin Resistance, this higher and higher level of pathological Hyperinsulinemia is able to still push Glucose into the cells and maintain normal blood Glucose (blood sugar) levels.

C. What conditions are breaking the lock and key system in my horse?

If your horse is overweight at an early age, they can have 3 times the number of fat cells as a regular horse. Some fat cells release toxins that interfere with Insulin’s action at the target cell.

1. Toxins from fat cells.

  1. If your horse is overweight: Fat, itself, is increased with high levels of Insulin and it turns around to interfere with Insulin which leads to more Insulin. This leads to a vicious merry-go-round.
  2. Most Insulin Resistance horses are overweight. A recent University of Virginia/Maryland report estimates 50% of the horse population is overweight and 20% are obese (Obese is over 20% beyond ideal weight). In addition, if a horse is obese, about 1/3rd of them will have Insulin Resistance.

2. Insulin

Insulin at very high levels starts to interfere with other Insulin’s ability to get to receptors. The keys are breaking each other. This is “negative cooperatively”. *A recent study from Australia showed that injecting high Insulin into a normal horse caused Laminitis within 2 days. High Insulin and Laminitis are cause and effect.

Dr. Reilly is the “Ask the Vet” expert on Equine Insulin Resistance for the AAEP.

3. Does My Horse Have Horse Diabetes?

No.  Horses do not get Diabetes like people.

Equine Insulin Resistance is mistakenly called Horse Diabetes, Horse Pre-Diabetes, Horse Early Stage Diabetes, or Horse Type 2 Diabetes – for years and it created confusion.  Horses and people can both get Insulin Resistance, but horses do not go to the next step of Diabetes.  In people, they can advance on to Diabetes if Insulin Resistance is not controlled.

In Insulin Resistance: Blood Insulin is high but Blood Glucose (Blood Sugar) is normal for both horses and people.  In people, Early Stage Type 2 Diabetes occurs if Insulin Resistance is not controlled: Blood Insulin is High, Blood Glucose is also high.  Horses do not get this type of Diabetes.  In people, if Early Stage Type 2 Diabetes is not controlled, the Pancreas cells “burn out” and can’t make Insulin any more, so Blood Sugar goes super high and Insulin shots are required.  This is called Late Stage Diabetes.  Again, horses do not get this type of Diabetes.

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Blood Insulin

Blood Glucose

Horse and Human in Insulin Resistance

High

Normal

Human Early Stage Diabetes

High

High

Human Late Stage Diabetes

Low

Sky High

Rarely in horses, Glucose values can be elevated such as in Equine Cushings, extreme infections, or high fevers.  If the horse is already having Equine Insulin Resistance with high Insulin, then will see high Insulin and High Glucose. This is not true Horse Diabetes but an overlapping of diseases.  Once the horse is treated, Glucose levels will drop back down to normal.

4. Cushings Disease

Cushings disease can lead to Insulin Resistance in several different ways. The horse can have Cushings and Insulin Resistance at the same time. Why?

  1. High ACTH levels in Cushings can directly interfere with Insulin’s action. ACTH is damaging the keys.
  2. High ACTH levels lead to Cortisol abnormalities. Cortisol is responsible for increasing blood Glucose levels by causing stored sugars in muscle/liver to be released. The higher levels of Glucose trigger more and more Insulin.
  3. Cortisol, like ACTH, can directly interfere with Insulin’s action. More keys are damaged. This is why it is smart to test the ACTH level and the Insulin level of a Cushings horse on a regular basis. Your Cushings horse could have normal Insulin and later become an Insulin Resistance horse on top of Cushings in a large number of cases. You are treating it with Pergolide but not treating the Insulin Resistance and wonder why they have Laminitis still— now you know why!

5. Stress

Mental/Physical— surgery, infections, shipping… Increased Epinephrine causes increased ACTH, increased Cortisol, leading to more Insulin Resistance.

  1. Increased Cortisol will interfere with sleep, so more stress.
  2. Increased Cortisol will depress immune system leading to more infections that lead to higher Insulin levels.
  3. Increased Cortisol breaks down muscle which results in muscle weakness— often see in Cushings horses -skinny with fat pads.
  4. Increased Cortisol decreases muscle synthesis.

6. New study via Dr. Reilly – “Insulin Resistance – New Triggers”. More research results pending.

Genetic lock- diet/exercise is not controlling Insulin.
Owners have tried multiple management techniques but the horse is still foot sore, has repeat Laminitis, can’t be turned out on grass, and stays big on little food.  Also the horse is a candidate for future problems and the owner would like to avoid a problem instead of waiting for the problem to occur. These are the horses the HEIRO program can help.