At the NO Laminitis Conference last year I spent several hours talking about what insulin related laminitis is not. A paper just published in The Veterinary Journal (Patterson-Kane et al) called Paradigm shifts in understanding equine laminitis does the same thing.
Laminitis has always been incompletely understood. We have assembled a list of causes/triggers but did not really understand the mechanism behind the damage to the laminae.
One theory was that it was vascular. Compromised blood flow caused cellular damage or death. Others focused on infiltration by white blood cells and the inflammatory reaction. Most recently bacterial toxins gaining access to the body after damage to the lining of the hind gut was proposed as the triggering event. The toxins activate enzymes called MMPs which then break down the basement membrane, a tissue that forms a bond between the secondary dermal and epidermal laminae. These are factors involved in laminitis caused by plant toxins, bacterial infections (e.g. retained placenta, “bastard” Strangles) and hind gut overload with starch or inulin. However, it is now recognized that approximately 90% of laminitis cases are caused by endocrine disease – high insulin levels.
Hyperinsulinemia is seen in Equine Metabolic Syndrome (EMS) and pituitary pars intermedia dysfunction (PPID), aka Cushing’s disease complicated by insulin resistance. With such a high percentage of cases being caused by hyperinsulinemia, it becomes extremely important to understand both how to control insulin levels and exactly how insulin causes damage to the laminae if we are going to effectively prevent and treat this type of laminitis.
Controlling insulin involves medication if the horse has PPID, as much exercise as possible and a diet where everything the horse eats has less than 10% simple carbohydrates – sugar (ESC) and starch. Fructan is not a sugar and does not enter into that 10% total.
As for the mechanisms underlying the damage to laminae, the logical place to start looking for those is to go back to what is known about other forms of laminitis. Studies have now found that with hormonal laminitis there is no activation of MMP enzymes or basement membrane destruction, no evidence of inflammation as an early event. These are important findings because they explain why NSAID drugs like phenylbutazone typically have little effect on the pain of hormonal laminitis. Anti-inflammatories don’t “treat” anything when there is no inflammation.
One theory was that insulin resistance deprives the laminae of needed glucose but this was soon shown to be incorrect because these cells do not rely on insulin for glucose uptake. A current hypothesis being investigated is that the high insulin levels interfere with normal cellular reactions to IGF-1 (insulin-like growth factor 1) because IGF-1 cellular receptors can also be triggered by insulin, albeit much more weakly than by IGF-1. There is some evidence so far that IGF-1 activity is disrupted in hormonal laminitis but much more needs to be done to determine the consequences and whether this is actually a cause or just a reaction to tissue damage.
The one abnormality that is well documented is high levels of endothelin-1, the most potent vasoconstricting substance in the body. This is also a feature of human insulin resistance and type 2 diabetes, and explains the circulatory problems these people have. It also explains why many hyperinsulinemic horses experience hoof pain with exposure to cold and why treatments designed to increase nitric oxide, a vasodilator, are often very helpful with hormonal laminitis pain.
We have a lot more to learn. The first step is letting go of old information on other causes of laminitis because they simply don’t apply here.
Eleanor Kellon, VMD