Strategies to Modulate Insulin Concentrations

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Written By Dr. Kris Hiney

Much recent research in the horse industry has centered on fluctuations in insulin concentrations under a variety of conditions and the effects on the health of the horse.  Many horse owners are aware that traditional feeding practices which rely on a larger proportion of concentrate feeding may result in prolonged insulin secretion by the pancreas.  In young horses, it is thought that prolonged elevations in insulin may lead to cartilage abnormalities, promoting epiphysitis and osteochondrosis.  High starch diets are linked to behavioral issues such as more excitable or reactive horses;  and certain typing up disorders such as polysaccharide storage myopathy and recurrent exertional rhabdomylosis. Finally, high concentrate diets can certainly contribute to the development of insulin resistance and laminitis. As a result of this information, many  current horse feeds are now designed to minimize insulin fluctuations in the horse.  These feeds are typically low in traditional cereal grains such as corn and oats, may be higher in fat and fiber, or may be processed differently.   All of these techniques are designed to either minimize or slow the absorption of glucose out of the small intestine, and thus lower the need of the pancreas to secrete insulin to regulate blood glucose.  But what if switching feeds or eliminating concentrate is simply is not enough?  Are there other options available to the horse owner which can potentially help regulate insulin and glucose in their horses?
One of the concerns for owners of insulin resistant horses is the frequent bouts of laminitis which occur if the horse is allowed access to pasture high in fructans.   Owners of these horses need to monitor their horses grazing carefully.  In order to avoid plants with high fructan content owners are advised against allowing access to pasture during the afternoon (when photosynthesis is at its peak rate), the spring, late fall or when grasses are stressed.  Further, warm season grasses offer a lower fructan concentration than cool season species of grasses and make better grazing choices for insulin resistant horses.

But why are fructans such a concern?

One of the theories addressing the laminitis inducing effect of high fructan content in plants is that fructans when consumed by the horse ,create changes in the bacterial population of the hindgut.  They undergo rapid fermentation, can alter pH of the gut and may result in bacterial endotoxin release.  However, this explanation does little to explain why insulin resistant horses in particular are so sensitive to fructans.  It may be that fructans trigger an increase in insulin itself that creates alterations to the vasculature of the hoof and the accompanying painful syndrome.   Insulin, while typically thought of as having a primary role in glucose disposal, has tremendous effects on the vasculature.  Insulin can act as both a vasodilator, or a vasoconstrictor.   Insulin resistance has been repeatedly been shown to cause cardiovascular dysfunction in many other species.  However, this role has not been fully explored in the equine.

In attempt to explore this issue, researchers conducted a trial examining changes in insulin and glucose in horses allowed access to pasture during two different eight hour periods.  Horses were allowed to graze between 7 am and 3 pm or between 12:30 pm and 10:30 pm.   In this experiment, nonstructural carbohydrate content of the grass varied from 13.5% to 19.1% from 8 am to 10 pm.  The study did find a detectable, though not large, increase in insulin, in the horses fed during the afternoon grazing period when NSC values were there highest.   While the number of horses used in the study was small, and the grazing period did overlap, this study does indicate that the concentration of insulin in the horse may be sensitive to fructan content of grasses. The horses used in this study were also not insulin resistant horses.   Insulin resistant horses  may have differed in their insulinemic response to the feeding schedules.  However, this study may offer information as to why bouts of laminitis are triggered in the insulin resistant horse exposed to the wrong type of grasses.

While we know that insulin resistant horses need to be stringently maintained on low soluble carbohydrate diets, other horses may benefit by paying attention to how we feed them.    While simply avoiding feeding grain may be an easy solution to avoiding insulin and glucose fluctuations, some horses  may require a diet higher in concentrates to meet their energy needs.  A common sense approach is to divide the horse’s meals into several smaller meals.  This is certainly an effective strategy in lowering glucose and insulin response.  However, one approach rather than running out to the barn multiple times per day to split up your horse’s meals, is to use a feeding system designed to slow down the horse’s consumption rate.  Researchers interested in this technique attempted to slow feed intake by adding grids to feed buckets, small hard balls or soaking the feed completely in water.   Using physical obstructions to feeding did prove to be successful  in increasing total feeding time, while adding water did little to alter consumption rate.  The best technique to lower insulin response was to add bocci balls to the bucket so that the horses had to move the balls around to gain access to the feed.  This idea has been elaborated to produce commercial feeding balls, which trickle out small amounts of concentrate as the horse rolls it about.  This also provides the added benefit of increasing the mental stimulation of the horse simultaneously!

An interesting new theory is that perhaps the stress we expose our horses to may contribute to elevated insulin levels.  Chronic stress does increase cortisol concentrations which may have inhibitory effects on insulin, thus creating a greater need for insulin secretion, or in essence an insulin resistant horse.  In humans, stress and high cortisol can result in insulin resistance and a shift in the deposition of fat in the body. Perhaps stress in horses may also be contributing to insulin resistance and why we see regional adiposity in these animals.  In an initial foray into stress evaluation in horses, researchers examined whether different feeding schedules resulted in an elevation in cortisol.  However, in this study feeding schedules were not a sufficient stressor to elicit any dramatic increase in cortisol.   It is interesting that equine researchers are starting to look in new directions to solve the puzzle of insulin resistance in the horse.  While at this time, the effect of stress on cortisol and thus insulin in the horse is just a theory, maybe it wouldn’t hurt us to avoid stressing our horses unnecessarily!

Much about insulin resistance and developing best practices still remains unknown.

For example, in a study in which pregnant mares were fed high concentrate diets and gained rapidly in body condition in the last trimester of pregnancy, foals from the grain fed mares were actually more sensitive to insulin and had lower resting blood glucose. This does indicate that fetal programming, or the in utero environment can have long lasting effects on the offspring, but not what management protocols may be best are unknown.  While we have learned much about insulin resistance in horses, so much remains unknown. We often have to look at studies in other species and try to extrapolate this information to our management practices.  So over all, the willingness to try new methods and incorporate new information may be our best option.  Continue to monitor grazing tightly in insulin resistant horses, get creative when feeding grain, and don’t stress your horse!

Keys to Preventing Laminitis

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Written By Dr. Kris Hiney

In previous articles we have discussed some of the key strategies in preventing laminitis in the equine.  Many of these have centered on grazing strategies which limit the horse’s access to pastures high in fructan content.  Remember that fructans are carbohydrates which are enzymatically unable to be digested in the small intestine of the horse.  These fructans pass into the hindgut of the horse where they are fermented by the microbial population, specifically gram positive bacteria. The production of certain organic acids and amines enhance the permeability of the gut wall allowing these and other endotoxins to enter the bloodstream of the horse and ultimately effect  the circulation to the digit.  However, it is not practical to simply right off all horses’ ability to graze.  Rather, we should try and identify those individuals which may have a susceptibility to fructan content in the grass.  With this month’s article, we will try to identify which individuals may be at risk, and other strategies that may be employed to reduce your horse’s risk.

While the outward appearance of your horse may give you an indication to whether they are susceptible to laminitis (See Carbohydrates III: Metabolic Syndrome), there may be more to it than just which horses are overweight.  There certainly appears to be a genetic link to laminitis, with pony breeds leading the list of susceptible horses.  Their comparatively thrifty genotype may make their utilization of carbohydrates and insulin sensitivity differ from breeds which typically do not possess these characteristics. For example, thoroughbreds, which typically have the reputation for being “harder keepers” do not experience the same rate of laminitis.  However, the lifestyle and management of thoroughbreds may differ significantly enough to partially explain the decreased incidence of laminitis.  Even within ponies, there does appear to be a decided link to genetics.  In a study examining the pedigrees of an inbred herd of ponies, 37% of these ponies had experienced laminitic episodes.  Of those, half had at least one parent which had also experienced laminitis.  Even in controlled research trials which attempt to examine the effects of various carbohydrate loads on horses, wide variability exists between individuals. This leads to the supposition that individual variation, thus genetics, is at play.  Thus, if you aware of your horse’s pedigree and know of relatives which have experienced laminitis, you might want to manage your own horse more carefully.  Perhaps some day the genes which make a horse more susceptible to laminitis will be identified, and we can use genetic tests in developing management protocols.

As mentioned previously, development of obesity and insulin resistance certainly predisposes the horse to laminitis.  One theory behind the development of laminitis in the insulin resistant horse is the glucose deprivation model.  When a horse becomes insulin resistant, more and more insulin release is needed to elicit a normal tissue response.  In essence, the tissues become “desensitized” to insulin.  One of the key roles of insulin in the body is to allow cellular uptake of glucose.  Due to the polarity of glucose, it cannot freely enter the cell without the presence of specialized protein transporters. Glut 4 is a protein transporter which is located internally in the cell until insulin binds to the cell membrane.  Binding of insulin to the receptor causes a cascade of intracellular reactions to occur and initiates the translocation of Glut-4 to the cell membrane.  The insulin insensitivity may result in Glut 4 no longer moving to the cellular membrane, and the inability of glucose to enter into the lamellar tissue of the foot, thereby starving it of glucose.  A recent study looked at the presence of different glucose transporters  found in skeletal muscle, the coronary band and lamellar tissue.  Glut-4 is the insulin dependent transporter found primarily within muscle, while Glut 1 is found in other tissues which have non-insulin dependent uptake of glucose, such as the brain.  While Glut 4 was heavily expressed in skeletal muscle, only Glut 1 was found within hoof tissues of both normal and insulin resistant ponies.    Therefore, glucose uptake in the hoof is thought to be insulin independent  and glucose deprivation within the hoof is unlikely to be the cause behind laminitis.  However, in a subsequent study, laminitis was induced in normal healthy ponies using a hyperinsulinemia-euglycemia clamp technique.   In this model, insulin is infused into the ponies at a constant rate, while glucose is infused at a sufficient rate to maintain euglycemia, or normal blood glucose levels.   Therefore, it is not an absence of glucose which causes laminitis, but perhaps the sustained levels of insulin or other hormones which causes this disorder.  This would certainly support the observation of the increased laminitis risk to the insulin resistant horse which suffers from hyperinsulinemia.

If owners wish to try and avoid the development of insulin resistance, the diet the horse receives may be critical.  Diets which avoid high amounts of sugars and starches, and have a low glycemic response, result in less insulin release.  For horses which still need a significant amount of calories, diets which are fat and fiber based and properly formulated, rather than those which provide a higher glucose or insulinemic response, may prevent the development of insulin resistance.   Certainly just monitoring body condition in the horse may be the easiest way to avoid insulin resistance.  Although if you ask any horse owner if that is easy you may get a different response!  In addition, horses which receive regular exercise seem to be fairly protective against laminitis.  However, it is difficult to know whether the exercise regimen aids in increasing insulin sensitivity, or is simply protective against obesity.

Many horse owners wonder if there is a magic pill or supplement that they can provide their horse in order to prevent laminitis.   One approach is to reduce the gram positive, lactate producing bacteria which prefer to ferment sugars and fructans.  Antibiotics are commonly used in the livestock industry in order to promote growth by shifting the microbial population within the gut. Some antibiotics select against gram positive bacteria, thus have been studied in the horse as a way to prevent laminitis.  While this may work, the use of anti-biotics in livestock for growth promotion has been banned in the Europe Union over concerns of anti-biotic resistance.  Similarly many in the United States have followed suit, searching for other ways to influence growth and increase immune status.  The use of probiotics and prebiotics may influence the gut microflora in favor of less potentially problem causing bacteria.  Ironically enough, short chain fructo-oligosaccharides have been demonstrated to improve insulin sensitivity, if not glucose levels, in obese horses.   However, none of these methods have been proven to prevent laminitis.  I would caution individuals to monitor diet, grazing patterns, and body condition first, before relying on supplements to prevent laminitis.