Saturday, March 9, 2013

Insulin Resistance in Horses...from The Anvil Archives

Mr. Rob Edwards, Publisher Extraordinaire
IR Finally Gaining Traction In Horse Industry 


Matt & Susan Frederick
Dr. Ric Redden
[Note: The following editorial first appeared in Anvil Magazine, in January of 2002, following the presentation of a paper introduced by Matt and Susan Frederick at the previous year's  Laminitis Symposium, Galt House, Louisville, Kentucky.  And no, Matt and Susan offered no scientific or academic credentials to the attendees -- Matt, a Napa, California Farrier and his wife Susan, among other talents, an academic background in biochemistry.  How this meeting of minds occurred is the direct result of Dr. Ric Redden's firm belief that all folks, scientific AND lay...have something to bring to the table when combating a serious and devastating disease.  But we needed to first heal some real divisions that existed in the relationship between our own allied professions, before we had the slightest chance to unravel the many manifestations
of laminitis.  Ric and Nancy Redden opened that often pad-locked door.

Denise Dodero -- Think she just wanted my dog...
Enter Denise E. Dodero.  I spent a good portion of my life with this highly dedicated, somewhat rambunctious Italian woman.  Her background was academic medicine, while her personal history included Type I Diabetes (juvenile onset), the ravages of which ended her life at 50 years of age.  At the time of her death, she was a lobbyist in Washington DC, not only fighting for the future needs of Academic Medicine in this country, but as a spokesperson for the American Diabetes Association, of which she was both volunteer and an unpaid administrator for most of her adult life.  Quite sadly, her dream...the eradication of juvenile diabetes in her lifetime, has so far eluded science.  So next time you might feel tempted to condemn or compartmentalize all the lobbyists who skulk nefariously in the unseen corridors and back rooms of Congress, please remember people like Denise.  It is not always about money, some obscure cause or localized agenda.  Sometimes it is about the substance of life and death.
So why mention her?  An honest question here.  Well, when you live with a person, the disease travels with you.  And if you love that person, you fight the same fight.  And as one mobster noted, "You keep your friends close and your enemies closer."  I knew this damn disease personally.  When it showed up in the middle of the night, when she suddenly went blind in one eye.  So, sitting in that audience in Louisville, somewhat bored -- Matt and Susan's words lit a fire between my ears.  So I told Rob Edwards, publisher of Anvil Magazine, that we needed to bring these folks to Georgetown for a serious conversation, because they had just taken chronic laminitis and Cushing's Syndrome out of their tidy little box.  The rest as we say, is history.  Far too slow it seems, at least for me, but it represents the most substantial leap in thinking for decades.

The Editorial:    
Napa, California, farrier Matt Frederick did not plan to "research laminitis."  As he stated in his opening remarks at the 2001 Laminitis Symposium in Louisville, Kentucky, in spite of proper shoeing, many horses would re-founder.  "Why did the acute episode last for only days is some horses and months in others?"
A meticulous note-taker, Matt began seeing connections in these so-called 'refractory' cases.  With the help of his wife Susan, whose background is in biochemistry, the pair created a field study involving 43 laminitic horses, of which 22 were declared refractory, or in effect, hopeless.  They were searching for connections or, in endocrinological terms, "the wiring diagram" that instigates the body to turn on itself with such devastating results.  Veterinarians and farriers are all too familiar with the tertiary aspects of this disease -- Styrofoam pads, pain-killers, anti-inflammatories, and ultimately that painful confrontation with the truth:  euthanasia.  The horse isn't terminal, but the situation is.  Their research produced definite connections -- some suspected, others rather startling, or largely ignored in the literature.  Vascular anomalies have always been a major culprit in laminitis, but as Matt asked, "Why?"
The key to the puzzle may lie in both genetics, the so-called "thrifty gene" inherent is specific breeds, and the insulin resistance, associated with Both Cushing's Syndrome and Diabetes Mellitus, Type II, or adult-onset Diabetes.  In simplest terms, insulin is a hormone that facillitates glucose transference to every cell in the body.  It's a bit like a car with a full tank of gas and a bad carburetor:  lots of fuel, but the engine is starving to death.  In the case of the laminae in the hoof, blood flow, as many authors have suggested, may not be nearly as critical as glucose absorption.  Flood the carburetor and these fragile tissues simply die because the endocrine system (the on-board computer), is receiving mixed messages.  Keep flooding it, and the case becomes refractory.
The genetic connection is the least complicated.  Frederick's study showed that a high percentage of cases were breed-specific, particularly ponies, Morgans, Arabs and gaited breeds, some sharing a common genetic pool, but most associated with that "thrifty gene" which allowed, over (evolutionary) history, for those animals to cope with a "feast or famine" environment.  Their endocrine system was highly adapted as a defense against starvation, and subsequently, the preservation of the species.  Two-hundred thousand years of evolution is not easily overturned by a few hundred years of rapid domestication and a new and rather refined diet.  The body is defending against the coming storm, but the lean times fail to materialize.  The "land of plenty" is little more than a fat farm with no hope of escape.
The American Diabetes Association recently released the results of a fifteen-year study focusing on the elevated incidence of Type II Diabetes among minority populations in the United States. [Author's note: it is now at epidemic proportions across the demographic/ethnic/racial spectrum.]  Highest on the list were African-Americans, Native Americans and Hispanics -- populations that fit, for the most part, a model that indicated an evolutionary tolerance to periods of famine.  These populations also had a predisposition to excess weight gain and a number of health problems associated with obesity, notably cardiac incidents.  The culprit:  High protein, high fat, and most importantly, high carbohydrates.
While it may seem impossible in this culture to overlook racial overtones, none exist.  European diets, as a rule, have a long history of plenty.  These populations have adjusted over the centuries to assimilating a high-carbohydrate diet -- carbohydrates being little more than simple or complex sugars.  A Shetland Pony scrounging out a living on a rock in the North Atlantic has never really had the chance to adjust to a free meal.  Fat storage and a reduced metabolic need guaranteed survival in a vicious environment.  An African in the Kalahari or a Hopi Indian in the desert Southwest faced the same of seasonal crisis.  Centuries of coping with marginal conditions made these populations highly versatile at assimilating anything or nothing.  Over time, three square meals virtually guaranteed a visit to the emergency room.
Why should horses be different?  Statistical information is sketchy at best, but a safe assumption is that North American feral horses, horses in the developing world -- i.e., Africa, Asia and South America -- even zebras, have an extremely low incidence of laminitis, other than captive or cultivated populations.  These equidae (as a rule), work hard, scrounge what they can directly from the environment and their metabolism works out the details.  The Serengeti is a great photo shoot in the African spring, but the dry season starves to death a fourth to a third of the grazing population.  As Frederick points, good intentions and aesthetic considerations are enough to "kill with kindness."  We tend to worship a thin, athletic human body, but when it comes to horses, counting a few ribs is grounds for calling out the Humane Society.  As almost all veterinarians know, and most farriers appreciate, the majority of 'companion animals' (dogs, cats, horse -- yes, even Bob the hamster) are chronically overfed, over-supplemented and overly protected.  Two much care can be as destructive as too little, particularly in a susceptible population.
Matt and Susan Frederick's search for the wiring diagram led them to both Cushing's Syndrome and Diabetes Mellitus, Type II, the former associated more commonly with canine populations;  the latter responsible for a sizable portion of human health care. (Recent studies suggest that one of every seven dollars spent on health care is spent on diabetic patients -- 1995 figures), as well as untold trips to the country's overburdened emergency rooms for potentially life-threatening complications, most notably vascular difficulties involving the eyes, kidneys, heart and not surprisingly, the lower extremities, particularly the digits.  A human can afford to lose a few toes, even a foot, as tragic as it is, but a horse is a digital animal, literally transporting itself on the equivalent of one rather complicated big toe.  The big question then is whether laminitis is really a circulatory response (either vasodilation or vasospasm, or constriction), or, as Frederick believes, insulin resistance, cutting off the laminae in certain susceptible populations from glucose absorption.  Add another element -- the body's response to shock, which normally sacrifices the extremities in order to save the major organs and the puzzle deepens.  We know that horses develop laminitis from a number of systemic insults -- everything from carbohydrate overload to endotoxicity, or basically an overwhelming systemic infection of some sort, to the use of artificial glucocorticords such as dexamethasone, betamethasone and trianmcinolone, the most common synthetic versions of cortisol used in the equine.  Cortisol, a regulatory secretion of the adrenal gland responsible for counter-regulating the body's inflammatory response (it is the body's 'natural' anti-inflammatory) and is also important in helping the body metabolize fats, proteins and MOST importantly, carbohydrates -- sugars.  It is so important in the regulation of sugar usage that it is classified as a GLUCOcorticoid.
Also of note, women experience "gestational" Type II Diabetes, possibly connected in some ways to the type of equine laminitis associated with a retained or tainted placenta -- so-called, foal founder.  In either case, pregnancy is both stressful to the endocrine system and in some case actually toxic to the host.  In Frederick's theory, foal founder and/or laminitis attributed to a retained placenta could also be explained by insulin resistance caused by increased hormone levels during pregnancy (e.g. growth hormone, cortisol, prolactin and other hormones), produced by the fetus and placenta.  In this hypothesis, laminitis would be comparable to the development of gestational Diabetes in humans.  This gestational Diabetes is usually manifested in the 3rd trimester.
As the Fredericks note in their research paper, studies suggest that in some mammals, the fetus produces a large spike of cortisol prior to parturition. [Roger Smith MD, Scientific American, March 1999] .  The Fredericks suspect that this additional "cortisol load" in a horse with a mild to severe unrecognized or undiagnosed Cushing's-like syndrome could worsen the inherent insulin resistance, leaving them at risk for the development of laminitis.
In humans, women who suffer from gestational Diabetes are suspected to be "pre-diabetics."  Although their Diabetes often resolves after birthing, many will progress to overt Diabetes Mellitus, Type II in the future.  In a like fashion, the Fredericks suspect that horses who suffer from laminitis during pregnancy are possibly "early or pre-Cushingoid" horses; being "pushed over the edge" due to the influence of high hormone levels which cause a certain degree of insulin resistance inherent in all pregnancies.
Please do note that this material was from studies/observations made in the mid to late 1990's and presented initially in 2001.  During the interview, a great deal of discussion also took place on the matters of USDA labeling practices (vis a vis -- carbohydrate values), protein sources, supplemental additives and especially the marketing of so-called Senior Feeds, which were often very high in carbohydrate levels.  Most of the above editorial was composed of both conversations with the Fredericks and my personal research.  The Fredericks probably never received the recognition, nor thanks they deserved for not only taking on such a tough topic, but presenting it to capacity crowd -- 2/3 of which were highly skeptical of the connection.  Well,  some 13 years later, nobody is dismissing the connection. 


  1. Thanks so much for posting this. I remember them so well, and their presentation at Louisville and other places. They were way ahead of their time in different ways. There are so many things in hoofcare and laminitis where, as research technology improves, things can be tested that couldn't be tested before and researchers are able to take credit for what others pioneered as theories but couldn't exactly prove. It's probably been generally true throughout history. Amazing thoughts they had, back in the day, and Ric Redden invited them to present. Thanks for reviving these memories. Thanks, Matt and Susan.

    1. Thanks for the nice words Fran. Tes, they questioned the status quo and more importantly, challenged it. Quite a revelation at the time.