Laminitis after 2000 years: Adding bricks to our wall of knowledge
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Guest Editorial Laminitis after 2000 years: Adding bricks to our wall of knowledge Laminitis is not a new condition, having been recognised for over 2000 years, with Aristotle referring to it around 350 BC as ‘barley disease’ for obvious reasons. The term ‘founder’ was in use by at least the end of the 16th century and apparently arose from the term morfounde used by mariners when referring to ves- sels that had been driven under the sea by a succession of waves (Wagner and Heymering, 1999). It was not until the 18th century that the term ‘laminitis’ was first employed and a distinction be- tween acute and chronic laminitis was made. The first full description or review was possibly commissioned by the Greek Emperor Constantine in the 4th century AD, although it was not apparently published until 900 AD. This noted (as we do today) that the condition, then referred to as ‘gout’ as well as ‘bar- ley disease’, could have multiple causes. Interestingly, considering today’s link between obesity and laminitis, this early work appar- ently recommended exercise and diet restriction as an important part of the treatment/management regimen! It is this question of multiple causes that makes many of us working in this area consider that laminitis is a syndrome rather than a single entity. Currently we have a number of core experi- mental models of laminitis, namely, (1) carbohydrate overload (high starch low fibre meal), (2) fructan overload, (3) black walnut extract administration, and (4) hyperinsulinaemia. This fourth model is discussed in more detail in the paper published in this is- sue of The Veterinary Journal by Melody de Laat of the University of Queensland and her colleagues (de Laat et al., 2012). The models support several interlinking theories on the patho- physiology of laminitis, including vascular, enzymatic, toxic, inflammatory and endocrinopathic (Harris and Geor, 2010). But I believe we still do not know how these experimental models (and theories on pathogenesis derived from these models) relate to the naturally occurring condition or syndrome. A link with insulin resistance was recognised in the early 1980s when Coffman and Colles (1983) suggested that laminitic ponies were significantly less sensitive to insulin than other equines. Insu- lin resistance was soon considered to be a possible contributing factor in the apparent association between obesity and laminitis (Jeffcott et al., 1986; Field and Jeffcott, 1989). This concept was fur- ther developed in the USA in the early 2000s, with the introduction of terms such as ‘pre-laminitic metabolic syndrome’ and ‘equine metabolic syndrome’ to describe horses and ponies with an appar- ent increased susceptibility to laminitis (Johnson, 2002; Hoffman et al., 2003; Treiber et al., 2006, 2007). More recently, workers in Australia have shown that laminitis can be induced in healthy po- nies and horses through maintaining a very high plasma insulin concentration with normal glucose (Asplin et al., 2007; de Laat et al., 2010). The latest work by de Laat et al. (2012) suggests that insulin at lower concentrations (but still relatively high glucose fluxes) over 48 h may result in changes within the laminae sugges- tive of laminitis. But this is the excitement/frustration of research – every brick of knowledge that we add just increases the number of bricks we need. The intriguing work reported by de Laat et al. (2012) leads to so many other important questions, not least does this have any relevance to laminitis seen by practitioners? If so, how high/ how long/how often does the hyperinsulinaemia have to occur for laminitis to be initiated in the field? Is it the hyperinsulinaemia or high glucose fluxes or both that are important? Does the sug- gested threshold of 200 lIU/mL hold true for all animals or is it lower in those with other predisposing factors or higher in those with protective factors? Thinking more broadly, what about the pregnant mare that naturally becomes insulin resistant and may respond to a feed with high plasma insulin concentrations? We have for example recently reported plasma insulin concentrations close to or greater than 200 lIU/mL for several hours following the feeding of high starch meals in such an animal but without appar- ent adverse effects (George et al., 2011). Are we missing subclinical episodes? Are such concentrations not sufficient to trigger damage if they only occur once or twice a day for a few hours? Or are there other mitigating factors? Interestingly in that study one animal with consistently high insulin concentrations, occasionally greater than 200 lIU/mL, did develop laminitis a few months later. Other obvious questions include: How does hyperinsulinaemia result in laminitis? And how many hyperinsulinaemic bouts in- crease the risk of laminitis? Certainly hyperinsulinaemia may cause vascular dysfunction, and recently it has been shown that IGF-1 receptors are present on lamellar epithelial cells and insulin may activate these receptors resulting in cellular proliferation (Bai- ley and Chockalingham, 2009). This could explain some of the his- tological changes observed in lamellar tissue from animals subjected to the insulin induced model (Nourian et al., 2009). The work by de Laat and colleagues (2012) does provide valu- able information but much more work is needed in this area. Very recently the American Association of Equine Practitioners (AAEP) conducted a survey of its members with respect to defining and prioritizing equine health research needs. Of the 10 most impor- tant diseases or disease categories that respondents felt required further research, laminitis had the highest return at 63%. Laminitis was also ranked the highest in the previous survey carried out in 2003 – highlighting the continued significance of this condition. However, despite the high demand for more knowledge and ad- vice, funding remains limited. It is therefore crucial that we build on the current momentum and continue to add bricks to our wall of knowledge about laminitis. We need to collaborate more, share 1090-0233/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.tvjl.2011.09.014 The Veterinary Journal 191 (2012) 273–274 Contents lists available at SciVerse ScienceDirect The Veterinary Journal journal homepage: www.elsevier.com/locate/tvjl
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Transcript of Laminitis after 2000 years: Adding bricks to our wall of knowledge
The Veterinary Journal 191 (2012) 273–274
Contents lists available at SciVerse ScienceDirect
The Veterinary Journal
journal homepage: www.elsevier .com/locate / tv j l
Guest Editorial
Laminitis after 2000 years: Adding bricks to our wall of knowledge
Laminitis is not a new condition, having been recognised forover 2000 years, with Aristotle referring to it around 350 BC as‘barley disease’ for obvious reasons. The term ‘founder’ was inuse by at least the end of the 16th century and apparently arosefrom the term morfounde used by mariners when referring to ves-sels that had been driven under the sea by a succession of waves(Wagner and Heymering, 1999). It was not until the 18th centurythat the term ‘laminitis’ was first employed and a distinction be-tween acute and chronic laminitis was made.
The first full description or review was possibly commissionedby the Greek Emperor Constantine in the 4th century AD, althoughit was not apparently published until 900 AD. This noted (as we dotoday) that the condition, then referred to as ‘gout’ as well as ‘bar-ley disease’, could have multiple causes. Interestingly, consideringtoday’s link between obesity and laminitis, this early work appar-ently recommended exercise and diet restriction as an importantpart of the treatment/management regimen!
It is this question of multiple causes that makes many of usworking in this area consider that laminitis is a syndrome ratherthan a single entity. Currently we have a number of core experi-mental models of laminitis, namely, (1) carbohydrate overload(high starch low fibre meal), (2) fructan overload, (3) black walnutextract administration, and (4) hyperinsulinaemia. This fourthmodel is discussed in more detail in the paper published in this is-sue of The Veterinary Journal by Melody de Laat of the University ofQueensland and her colleagues (de Laat et al., 2012).
The models support several interlinking theories on the patho-physiology of laminitis, including vascular, enzymatic, toxic,inflammatory and endocrinopathic (Harris and Geor, 2010). But Ibelieve we still do not know how these experimental models(and theories on pathogenesis derived from these models) relateto the naturally occurring condition or syndrome.
A link with insulin resistance was recognised in the early 1980swhen Coffman and Colles (1983) suggested that laminitic ponieswere significantly less sensitive to insulin than other equines. Insu-lin resistance was soon considered to be a possible contributingfactor in the apparent association between obesity and laminitis(Jeffcott et al., 1986; Field and Jeffcott, 1989). This concept was fur-ther developed in the USA in the early 2000s, with the introductionof terms such as ‘pre-laminitic metabolic syndrome’ and ‘equinemetabolic syndrome’ to describe horses and ponies with an appar-ent increased susceptibility to laminitis (Johnson, 2002; Hoffmanet al., 2003; Treiber et al., 2006, 2007). More recently, workers inAustralia have shown that laminitis can be induced in healthy po-nies and horses through maintaining a very high plasma insulinconcentration with normal glucose (Asplin et al., 2007; de Laatet al., 2010). The latest work by de Laat et al. (2012) suggests that
1090-0233/$ - see front matter � 2011 Elsevier Ltd. All rights reserved.doi:10.1016/j.tvjl.2011.09.014
insulin at lower concentrations (but still relatively high glucosefluxes) over 48 h may result in changes within the laminae sugges-tive of laminitis.
But this is the excitement/frustration of research – every brickof knowledge that we add just increases the number of bricks weneed. The intriguing work reported by de Laat et al. (2012) leadsto so many other important questions, not least does this haveany relevance to laminitis seen by practitioners? If so, how high/how long/how often does the hyperinsulinaemia have to occurfor laminitis to be initiated in the field? Is it the hyperinsulinaemiaor high glucose fluxes or both that are important? Does the sug-gested threshold of �200 lIU/mL hold true for all animals or is itlower in those with other predisposing factors or higher in thosewith protective factors? Thinking more broadly, what about thepregnant mare that naturally becomes insulin resistant and mayrespond to a feed with high plasma insulin concentrations? Wehave for example recently reported plasma insulin concentrationsclose to or greater than 200 lIU/mL for several hours following thefeeding of high starch meals in such an animal but without appar-ent adverse effects (George et al., 2011). Are we missing subclinicalepisodes? Are such concentrations not sufficient to trigger damageif they only occur once or twice a day for a few hours? Or are thereother mitigating factors? Interestingly in that study one animalwith consistently high insulin concentrations, occasionally greaterthan 200 lIU/mL, did develop laminitis a few months later.
Other obvious questions include: How does hyperinsulinaemiaresult in laminitis? And how many hyperinsulinaemic bouts in-crease the risk of laminitis? Certainly hyperinsulinaemia maycause vascular dysfunction, and recently it has been shown thatIGF-1 receptors are present on lamellar epithelial cells and insulinmay activate these receptors resulting in cellular proliferation (Bai-ley and Chockalingham, 2009). This could explain some of the his-tological changes observed in lamellar tissue from animalssubjected to the insulin induced model (Nourian et al., 2009).
The work by de Laat and colleagues (2012) does provide valu-able information but much more work is needed in this area. Veryrecently the American Association of Equine Practitioners (AAEP)conducted a survey of its members with respect to defining andprioritizing equine health research needs. Of the 10 most impor-tant diseases or disease categories that respondents felt requiredfurther research, laminitis had the highest return at 63%. Laminitiswas also ranked the highest in the previous survey carried out in2003 – highlighting the continued significance of this condition.
However, despite the high demand for more knowledge and ad-vice, funding remains limited. It is therefore crucial that we buildon the current momentum and continue to add bricks to our wallof knowledge about laminitis. We need to collaborate more, share
274 Guest Editorial / The Veterinary Journal 191 (2012) 273–274
knowledge and samples, and encourage the funding bodies to sup-port further research into this important condition. The horses andponies in our care must not have to wait another 2000 years to se-cure relief from this devastating condition.
Patricia HarrisEquine Studies Group,
WALTHAM Centre for Pet Nutrition,Freeby Lane, Waltham-On-The-Wolds,
Leicestershire LE14 4RT, UKE-mail address: [email protected]
References
Asplin, K.E., Sillence, M.N., Pollitt, C.C., McGowan, C.M., 2007. Induction of laminitisby prolonged hyperinsulinaemia in clinically normal ponies. The VeterinaryJournal 174, 530–535.
Bailey, S.R., Chockalingham, S., 2009. Proliferative effects of insulin on equinelamellar epithelial cells mediated by the IGF-1 receptor. In: Proceedings of 2ndAAEP Foundation Equine Laminitis Research Workshop, West Palm Beach,Florida, p. 26.
Coffman, J.R., Colles, C.M., 1983. Insulin tolerance in laminitic ponies. CanadianJournal of Comparative Medicine 47, 347–351.
de Laat, M.A., McGowan, C.M., Sillence, M.N., Pollitt, C.C., 2010. Equine laminitis:Induced by 48 h hyperinsulinaemia in Standardbred horses. Equine VeterinaryJournal 42, 129–135.
de Laat, M.A., Sillence, M.N., McGowan, C.M., Pollitt, C.C., 2012. Continuousintravenous infusion of glucose induces endogenous hyperinsulinaemia andlamellar histopathology in Standardbred horses. The Veterinary Journal 191,317–322.
Field, J.R., Jeffcott, L.B., 1989. Equine laminitis – Another hypothesis forpathogenesis. Medical Hypotheses 30, 203–210.
George, L.A., Staniar, W.B., Treiber, K.H., Harris, P.A., Geor, R., 2011. Evaluation of theeffects of pregnancy on insulin sensitivity, insulin secretion, and glucosedynamics in thoroughbred mares. American Journal of Veterinary Research 72,666–674.
Harris, P.A., Geor, R., 2010. Recent advances in the understanding of laminitis andobesity. In: Ellis, A.D., Longland, A.C., Coenen, M., Miraglia, N. (Eds.), The Impactof Nutrition on the Health and Welfare of Horses. Wageningen AcademicPublishers, pp. 215–233 (EAAP Publication 128).
Hoffman, R.M., Boston, R.C., Stefanovski, D., Kronfeld, D.S., Harris, P.A., 2003. Obesityand diet affect glucose dynamics and insulin sensitivity in Thoroughbredgeldings. Journal of Animal Science 81, 2333–2342.
Jeffcott, L.B., Field, J.R., McLean, J.G., Odea, K., 1986. Glucose tolerance and insulinsensitivity in ponies and Standardbred horses. Equine Veterinary Journal 18,97–101.
Johnson, P.J., 2002. Equine metabolic syndrome (peripheral Cushing’s syndrome).Veterinary Clinics of North America: Equine Practice 18, 271–293.
Nourian, A.R., Asplin, K.E., McGowan, C.M., Sillence, M.N., Pollitt, C.C., 2009. Equinelaminitis: ultrastructural lesions detected in ponies followinghyperinsulinaemia. Equine Veterinary Journal 41, 671–677.
Treiber, K.H., Kronfeld, D.S., Hess, T.M., Byrd, B.M., Splan, R.K., 2006. Evaluation ofgenetic and metabolic predispositions and nutritional risk factors for pasture-associated laminitis in ponies. Journal of the American Veterinary MedicalAssociation 228, 1538–1545.
Treiber, K.H., Hess, T.M., Kronfeld, D.S., Boston, R.C., Geor, R.J., Harris, P.A., 2007.Insulin resistance and compensation in laminitis-predisposed poniescharacterised by the minimal model. Pferdeheilkunde 23, 237–240.
Wagner, I.P., Heymering, H., 1999. Historical perspectives on laminitis VeterinaryClinics of North America. Equine Practice 15, 295–309.
