The Veterinary Journal 196 (2013) 139–140
Contents lists available at SciVerse ScienceDirect
The Veterinary Journal
journal homepage: www.elsevier.com/locate/tvjl
Guest Editorial
Equine laminitis: What is all the hype about hyperinsulinaemic laminitis?
Laminitis is a frustrating disease for horse-owners, veterinari-
ans and researchers alike. New research findings often disprove
older theories, and disparate results from both epidemiological
and pathophysiological investigations co-exist. When this is com-
pounded by the perpetuation of out-dated information and extrap-
olation of misleading data, the overall disease mosaic is further
complicated.
Recently, there has been a shift of research focus to the study of
endocrinopathic laminitis, defined as laminitis developing from
hormonal influences. Endocrinopathic laminitis constitutes two
categories of disease, namely, (1) those associated with glucocorti-
coids, including pituitary pars intermedia dysfunction (PPID) and
iatrogenic corticosteroids, and (2) those associated with insulin
resistance, namely equine metabolic syndrome (EMS) and
pasture-associated laminitis (now considered to reflect an abnor-
mal response to high carbohydrate content, rather than a true car-
bohydrate/fructan overload). Common to each of these conditions
is the dysregulation of glucose and insulin, potentiating insulin
resistance and the development of hyperinsulinaemia. Although
experimental and field studies have substantiated a link between
hyperinsulinaemia and endocrinopathic laminitis, what is the
strength of evidence to suggest that this is important?
The findings of three studies which canvassed opinion on the
speculated causes of laminitis in the general horse population are
frequently used to support the endocrinopathic laminitis research
focus. The first, a mailed survey of members of the British Equine
Veterinary Association and the Irish Draught Horse Society found
that most respondents considered ingestion of grass to be the main
trigger for laminitis, accounting for 70% and 38% of cases respec-
tively (Hinckley and Henderson, 1996). The National Animal
Health Monitoring System conducted interviews with owners of
operations in the USA with more than three horses (breeds that
stand over 14 hands1 when fully grown) and reported the most
common perceived cause of laminitis (45.6%) was grazing lush
pasture (Anon, 2000). The most recent survey, undertaken in Great
Britain, found that the most common (but speculated) causes of
laminitis in animals with a recently confirmed veterinary diagnosis
were grazing on lush pasture (29.8%), followed by PPID (21.3%),
obesity (12.8%) and EMS (8.5%) (Wylie et al., 2011b). While surveys
of speculated causes provide insight into current opinion, they are
not scientific data, are biased and they should not, therefore, be used
to infer the apparent frequency of causes or types of laminitis.
A systematic review of the frequency of equine laminitis estab-
lished a lack of high-quality evidence for the true disease
frequency and discussed the caveats concerning many of the
1
1 hand = 4 in. (or 10.16 cm).
1090-0233/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tvjl.2012.10.005
commonly cited estimates (Wylie et al., 2011a). The highest-
quality evidence came from a first opinion/referral study in the
USA (Dorn et al., 1975), presenting retrospective data from 1965
to 1971, although global estimates of the current incidence of lam-
initis in the general horse population remain to be established.
Only two studies have established the prevalence of underlying
endocrinopathic diseases in laminitic animals. A case-series from
an ambulatory clinic of a referral hospital in the USA suggested
that 70% of animals had PPID (Donaldson et al., 2004), while a
case-control study from a mixed first-opinion/referral setting in
Finland suggested that 89% of horses and ponies presented for lam-
initis had evidence of endocrinopathic disease – one-third sus-
pected PPID and two-thirds suspected EMS (Karikoski et al., 2011).
A recently completed epidemiological investigation of risk
factors for laminitis, conducted as a 2 year case-control study, sug-
gested that endocrinopathic laminitis may be responsible for the
majority of cases of clinically apparent equine laminitis attended
by veterinary practitioners in Great Britain (Wylie, 2012). If further
epidemiological research confirms these findings in other popula-
tions, research effort into endocrinopathic laminitis and the devel-
opment of hyperinsulinaemia may provide a key breakthrough
opportunity.
The true prevalence of hyperinsulinaemia in the general equine
population has yet to be accurately quantified, although estimates
suggest it may be between 10% and 22% in obese horses in the USA
(Geor et al., 2007; Muno, 2009), and approximately 28% in pony
herds in Australia (McGowan and McGowan, 2008). To date, the
proportion of hyperinsulinaemic animals which will progress to
develop laminitis remains unknown and the inability to diagnose
hyperinsulinaemic laminitis prior to the development of clinical
signs has hampered research progress. However, the study pub-
lished in the current edition of The Veterinary Journal by Dr. Melody
de Laat of the University of Queensland and her colleagues (de Laat
et al., 2013) provides novel information on lamellar pathology fol-
lowing induction of hyperinsulinaemia via a prolonged euglycae-
mic hyperinsulinaemic clamp technique. In this study, horses
were euthanased post-induction of hyperinsulinaemia and four
key areas of lamellar histology and morphometry were examined.
This model has reliably induced both clinical and histological signs
of laminitis in four Standardbred horses previously (de Laat et al.,
2010), with the development of early clinical signs of laminitis
(digital pulses, restlessness and episodic shifting of the feet) not
occurring until approximately 30 h post-induction. Therefore, in
their latest study, evaluation at 6, 12 and 24 h was taken to reflect
the pre-clinical or developmental phase, of hyperinsulinaemic lam-
initis (de Laat et al., 2013).
The developmental stage of laminitis has previously been de-
fined as the period between initiation of mechanisms that result
140 Guest Editorial / The Veterinary Journal 196 (2013) 139–140
in the disease and the appearance of acute lameness, and is consid-
ered to reflect the greatest potential to influence outcome. The
encouraging research findings by de Laat et al. (2013) suggest that
lamellar cell proliferation and differentiation are occurring as early
primary events in hyperinsulinaemic laminitis. This has an impor-
tant bearing on future work as it provides further evidence to sup-
port a unique pathophysiology for hyperinsulinaemic laminitis,
and suggests there may be opportunity to intervene to prevent
the onset of inflammation and progression to the often devastating
effects of basement membrane pathology. The latter presents an
attractive therapeutic prospect.
However, whilst induced models of disease provide potential
insights into the pathogenetic mechanisms, the research focus
must now concentrate on establishing whether the experimental
model of hyperinsulinaemic laminitis induces the same pathology
as the naturally-occurring endocrinopathic disease and so confirm
the findings of de Laat et al. (2013). The next logical step in evalu-
ating the temporal sequence of endocrinopathic laminitis would be
the development of a cohort study to gather time-varying informa-
tion on animals in the general population yet to develop laminitis.
Although these large-scale investigations are expensive and time-
consuming to conduct, they would provide the gold-standard epi-
demiological evidence for laminitis identified to be so sorely lack-
ing (Wylie et al., 2011a,2012).
For a disease where prevention is undoubtedly better than cure,
perhaps the cumulative efforts of pathophysiologists and epidem-
iologists to make practical application of experimental findings to
epidemiological investigations can make greatest advances in con-
quering equine laminitis.
Claire E. Wylie
Universitat Autònoma Barcelona,
Departamento de Medicina y Cirugía Animal,
Campus Bellaterra, Edificio V, Cerdanyola del Vallès,
Barcelona 08290, Spain
E-mail address: claire.wylie@uab.cat
References
Anon, 2000. Lameness & laminitis in U.S. horses. In: USDA, APHIS, CEAH, National
Animal Health Monitoring System (Eds.), Fort Collins, Co.
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 Veterinary
Journal 42, 129–135.
de Laat, M.A., Patterson-Kane, J.C., Pollitt, C.C., Sillence, M.N., McGowan, C.M., 2013.
Histological and morphometric lesions in the pre-clinical, developmental phase
of insulin-induced laminitis in Standardbred horses. The Veterinary Journal 195,
305–312.
Donaldson, M.T., Jorgensen, A.J., Beech, J., 2004. Evaluation of suspected pituitary
pars intermedia dysfunction in horses with laminitis. Journal of the American
Veterinary Medical Association 224, 1123–1127.
Dorn, C.R., Garner, H.E., Coffman, J.R., Hahn, A.W., Tritschler, L.G., 1975. Castration
and other factors affecting the risk of equine laminitis. Cornell Veterinarian 65,
57–64.
Geor, R.J., Thatcher, C.D., Pleasant, R.S., Elvinger, F., Gay, L., Werre, S.R., 2007.
Prevalence of hyperinsulinemia in mature horses: Relationship to adiposity.
Journal of Veterinary Internal Medicine 21, 601.
Hinckley, K.A., Henderson, I.W., 1996. The epidemiology of equine laminitis in the
UK. In: British Equine Veterinary Congress. Warwick, United Kingdom, pp. 62–
63.
Karikoski, N.P., Horn, I., McGowan, T.W., McGowan, C.M., 2011. The prevalence of
endocrinopathic laminitis among horses presented for laminitis at a first-
opinion/referral equine hospital. Domestic Animal Endocrinology 41, 111–117.
McGowan, C.M., McGowan, T.W., 2008. Prevalence and risk factors for
hyperinsulinemia in ponies. Journal of Veterinary Internal Medicine 22, 734.
Muno, J.D., 2009. Prevalence, Risk Factors and Seasonality of Plasma Insulin
Concentrations in Normal Horses in Central Ohio. MSc Thesis, The Ohio State
University.
Wylie, C.E., 2012. Epidemiological investigations of equine laminitis in Great Britain
2009–2011. PhD Thesis, University of London.
Wylie, C.E., Collins, S.N., Verheyen, K.L., Richard Newton, J., 2011a. Frequency of
equine laminitis: A systematic review with quality appraisal of published
evidence. The Veterinary Journal 189, 248–256.
Wylie, C.E., Collins, S.N., Verheyen, K.L.P., Newton, J.R., 2011b. Frequency and
speculated causes of equine laminitis in Great Britain. In: Proceedings of the
50th British Equine Veterinary Association Congress 2011. Liverpool, United
Kingdom, p. 87.
Wylie, C.E., Collins, S.N., Verheyen, K.L.P., Newton, J.R., 2012. Risk factors for equine
laminitis: a systematic review with quality appraisal of published evidence. The
Veterinary Journal 193, 58–66.