Insulin resistance

Insulin resistance can lead to life-threatening health problems. What does insulin do and how do issues develop?

 

 

How does it normally work?

When a healthy horse eats, the sugars and carbohydrates are absorbed in the small intestine. They are transformed into glucose, which is an energy source for tissues. Because of this, glucose levels in the blood go up after a meal. In response, insulin goes up as well, which opens channels that can transport the glucose into the tissues, where it’s either used or stored. When the glucose is taken up by the tissues, the levels in the blood go down to a normal baseline. The body realizes this and brings insulin levels down, so that the channels close again. This is how the body makes sure that there’s always a certain amount of glucose in the blood to feed the brain and other tissues.

 

What is insulin resistance?

Insulin dysregulation” is a term that describes insulin resistance, and/or excessive insulin responses to glucose and/or fasting hyperinsulinaemia.

When a horse has “insulin resistance”, this means that the channels don’t open as well anymore in response to insulin. So, when a horse eats, the glucose level goes up, the insulin level goes up as it normally would, but only a couple channels open. Not enough glucose can be transported into the tissues, so the glucose level in the blood stays higher than what it should normally be.

In an effort to correct the situation, the body then releases even more insulin. This opens some more channels. This process keeps going until enough glucose has gone into the tissues and the basic glucose level in the blood is restored. Horses with insulin resistance often don’t clear the insulin out of the blood as well either so levels stay higher for longer than usual.

With “excessive insulin responses to glucose” the amount of insulin that’s released when glucose goes up is too high from the very start. Horses can be genetically predisposed to this condition (see EMS).

“Fasting hyperinsulinaemia“ describes the situation where the horse has an increased insulin baseline, so this is not in response to food but a consequence of an overactive pancreas.

 

How does a horse get insulin dysregulation?

There are a few things that can lead to insulin problems. An important cause is being overweight. When the horse gains too much weight, it makes more fat cells and those cells grow bigger. At some point, the blood supply through the fat tissue can’t nurture all those expanded fat cells well enough anymore and the cells become “stressed”. They start to give off inflammatory mediators (TNFa, IL-1 and IL-6) and mediators called “adipokines” (Leptine, Adiponectine and Resistine). These substances all lead to reduced sensitivity of the glucose channels to insulin (insulin resistance).

A certain amount of fatty tissue in the body is normal and healthy, but when this becomes too much the body enters what we call a “pro-inflammatory state”. As you can imagine, this has more negative effects than just causing insulin resistance and laminitis.

In a healthy horse, after insulin has done its job it should go down again. This happens because the liver takes insulin out of the blood and breaks it down. However, the liver has been programmed to store fat and when there’s too much, the liver can become so fatty that it can’t function properly anymore. The liver doesn’t clear the insulin out of the blood as quickly and insulin lingers around for too long. The channels then become desensitized to it, so next time they don’t respond as well (more insulin resistance).

Another group of horses that are often obese and are at risk of developing laminitis are horses with Equine Metabolic Syndrome (EMS). These horses are often known as “easy keepers”. They have a genetic prediposition that makes them prone to developing a range of endocrine and metabolic abnormalities, such as insulin dysregulation, hyperleptinaemia, a tendency to lay down fat tissue and hypertriglyceridaemia. These abnormalities are all risk factors for laminitis. The difference between EMS which has a genetic background and horses that have just become overweight due to a mismatch in caloric intake and output, is that lean horses can also have EMS. In these cases, insulin dysregulation and laminitis occurs in ponies with a normal appearance.

So, overweight and EMS can lead to insulin dysregulation. What else should we be looking out for? Pituitary Pars Intermedia Dysfunction (PPID), previously known as Cushing’s, can cause insulin resistance and laminitis. This is a benign growth of the pituitary in the brain, which causes an over-production of hormones that have a wide range of effects such as:

  • changes in attitude/lethargy
  • long/curly hair coat
  • delayed hair coat shedding
  • loss of (topline) muscle mass
  • abnormal sweating
  • regional fat depositions (cresty neck, fat above the eyes, etc)
  • infertility
  • laminitis and/or recurrent sole abscesses
  • decreased athletic performance
  • rounded abdomen
  • excessive thirst and / or urination
  • recurrent infections
  • blindness
  • tendon laxity
 

PPID occurs more often in older horses, but has occasionally been found in younger horses (5 years). Research shows that it happens in about 20% of horses over 15 years of age. It can be diagnosed in the blood before clinical signs appear, which can be helpful because the first clinical sign can be laminitis. Laminitis is such a debilitating disease that it can have grave consequences for performance and welfare, that we prefer testing and treating PPID before it happens.

Old age is another cause of insulin dysregulation. Recent research compared insulin responses in healthy young and heathy senior horses. Results confirm that even healthy older horses can have an increased insulin response compared to younger horses. This means that as a horse ages, a decrease in insulin sensitivity is likely to occur. This explains why some horses develop laminitis as they age, while they are not overweight, don’t have PPID and have not ever been known to have EMS.

 

What are the consequences of insulin dysregulation?

Insulin dysregulation results in higher than normal insulin levels one way or another. Research has shown that when healthy horses are put on IV fluids with higher levels of insulin, horses consistently develop laminitis.

The horse's foot has a very extensive network of capillary blood vessels.

The integrity of this vascular network is of paramount importance to the foot’s health. Increased insulin levels damage the vascular network and cause little blood clots. This causes blood circulation problems in the foot. The result is oxygen shortage, which causes damage and inflammation of the foot and its lamini.

Laminitis” means inflammation of the lamini. The lamini are what attach the internal foot to the hoof. The lamini interlock to hold things tightly together. When the lamini become inflamed, the swelling in this area pushes these interlocked lamini apart, which weakens the attachment. The pressue in the foot builds up which causes pain. When the attachments are weakened, there’s a risk of the internal structures being displaced inside the hoof. The deep digital flexor tendon pulls the toe tip of the hoofbone backward, which causes it to rotate. The hoofbone can also sink within the hoof. These two things are also very painful and have significant consequences for the horse. It is therefore important that horses with an acute episode of laminitis are not walked to reduce the effect of the deep digital flexor tendon, and that they get immediate veterinary care to reduce the inflammation of the lamini.

Insulin dysregulation causes increased insulin levels. Insulin has anabolic effects on fat metabolism, which means that horses acquire fat tissue more easily. As we’ve mentioned before, when the fat portion in the body increases too much the body enters what we call a “pro-inflammatory state”. This means that the body is not in good health and becomes prone to inflammation.

 

How can we diagnose?

We can test for PPID by taking a blood sample.

To test for insulin resistance, Totally Vets offers an internationally acknowledged in-feed oral glucose test. The horse is first fasted for 6 hours (a 6-hour break from eating food). We then feed the horse a calculated dose of dextrose and chaff and then take a blood sample 2 hours later to measure the insulin response in the blood.

 

How can we treat or resolve the issue?

Treatment depends on what the cause of insulin dysregulation is. If a horse has PPID we can treat the horse with Prascend. If a horse is overweight we can help you put together a plan involving a an exercise plan and a diet that’s low in calories but supplies enough fibre, protein, vitamins and minerals. If a horse has EMS it will need to be managed from different perspectives. All horses that have insulin resistance or an excessive insulin responses to glucose will need to be on low sugar/carbohydrate diets and have their portions managed.

By keeping the glucose response to each meal low, the insulin response stays lower. This requires feeding less than 0.3grams of sugars/carbohydrates per kg of bodyweight per meal. If you need to feed your horse more than that, divide the feed into several meals. We can help you determine portion size by measuring your horse's body weight and calculating the sugar/carbohydrate content of the feed you use.

If you’re worried about laminitis, PPID or your horse being overweight, please give us a call.

 

Resources:
Franklin N, Tadros EM. (2013) Insulin dysregulation. Equine Veterinary Journal 12169
https://thehorse.com/116414/insulin-resistance-not-just-for-old-cushings-horses/
https://thehorse.com/157653/study-even-healthy-old-horses-have-increased-insulin-responses/
Rapson JL, Schott II HC, Nielsen BD, McCutcheon LJ, Harris PA, and Geor R.J. (2018) Effects of age and diet on glucose and insulin dynamics in the horse. Equine Vet J.
Jacob SI, Geor RJ, Weber PSD, Harris PA, and McCue ME. (2018) Effect of age and dietary carbohydrate profiles on glucose and insulin dynamics in horses. Equine Vet J. 50: 249 – 254.
Asplin KE, Sillence MN, Pollitt CC, McGowan CM. (2007) Induction of laminitis by prolonged hyperinsulinaemia in clinically normal ponies. Vet J. 174(3): 530 - 5.

 

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