Equine Metabolic Syndrome

Equine metabolic syndrome (EMS) is important because of its association with laminitis. Obesity and insulin resistance are two important components of EMS, and the underlying cause of this syndrome is likely to be enhanced metabolic efficiency. Affected horses are often referred to as “easy keepers” because they require fewer calories to maintain body condition, and enhanced metabolic efficiency is an inherent risk factor for EMS that may be genetically determined. Pony breeds, Morgan horses, and Paso Finos are predisposed to EMS, but this problem can be prevented through effective management. Overfeeding, abundant pasture grass, and inadequate exercise are risk factors that relate to modern management practices. Obesity and adiposity induce insulin resistance, and recent research suggests that this is the determinant of laminitis susceptibility in ponies. Increased plasma insulin concentrations are detected in most affected horses and ponies, so this serves as a useful screening test for EMS. Physical characteristics also should be examined because horses with EMS exhibit regional adiposity in the form of a cresty neck or abnormal adipose tissue deposits close to the tailhead. All horses with enhanced metabolic efficiency, obesity, or regional adiposity should be screened for EMS. The combined intravenous glucose−insulin test can be performed to diagnose insulin resistance in mildly affected horses and quantify insulin sensitivity. Most horses with EMS can be effectively managed by reducing caloric intake, decreasing the starch and sugar content of the diet, increasing exercise, and limiting or eliminating access to pasture, but medical therapy is warranted in select cases.     

ECEIM consensus statement on equine metabolic syndrome

Equine metabolic syndrome (EMS) is a widely recognized collection of risk factors for endocrinopathic laminitis. The most important of these risk factors is insulin dysregulation (ID). Clinicians and horse owners must recognize the presence of these risk factors so that they can be targeted and controlled to reduce the risk of laminitis attacks. Diagnosis of EMS is based partly on the horse's history and clinical examination findings, and partly on laboratory testing. Several choices of test exist which examine different facets of ID and other related metabolic disturbances. EMS is controlled mainly by dietary strategies and exercise programs that aim to improve insulin regulation and decrease obesity where present. In some cases, pharmacologic aids might be useful. Management of an EMS case is a long‐term strategy requiring diligence and discipline by the horse's carer and support and guidance from their veterinarians.     

Neutrophil and cytokine dysregulation in hyperinsulinemic obese horses

Equine metabolic syndrome is characterized by obesity and regional adiposity coupled with evidence of recurrent laminitis. Although inflammation has been well characterized in several experimental models of acute laminitis, the inflammatory events associated with endocrinopathic laminitis are not well documented. The aim of this study was to characterize selected markers of inflammation in horses with clinical evidence of equine metabolic syndrome (EMS). Neutrophil phagocytosis and oxidative burst, as well as endogenous and stimulated cytokine expression were evaluated. A marked increase in neutrophil reactive oxygen species production upon phagocytosis was observed in horses with EMS that was strongly correlated to the blood insulin concentration. Increased oxidative burst activity of neutrophils in hyperinsulinemic horses may predispose horses with metabolic syndrome to laminitis. In contrast, peripheral blood cells of obese hyperinsulinemic horses showed decreased endogenous proinflammatory cytokine gene expression (IL-1 and IL-6) and similar cytokine response following immune stimulation compared to that of control horses. This may suggest that, unlike in people, cytokine-mediated inflammation does not increase in direct response to obesity or insulin resistance in horses. This species-specific disparity may explain the difference in clinical outcomes observed in obese horses compared to obese people.     

Current concepts of hyperlipaemia in horses and ponies

Hyperlipaemia is an important condition in ponies, not just because of the seriousness of the clinical signs and biochemical changes involved, but because of the distress it causes owners and breeders that have had animals suffer from it. Hyperlipaemia occurs most commonly in fat ponies in late pregnancy and is rarely seen in larger horses. The syndrome has similarities with conditions in other species but the definitive aetiologies are not yet known. The condition in ponies is undoubtedly related to stress. The biochemical mechanisms involved in equine hyperlipaemia are considered and an hypothesis of possible pathogenesis is put forward. This hypothesis is tested by presenting the results of a preliminary study to evaluate glucose and lipid metabolism in horses and ponies. It appears that the pony is markedly insensitive to insulin compared to larger horses which means that triglycerides are more readily mobilised and the animal is therefore susceptible to hyperlipaemia in a situation of negative energy balance. The effect of stress is to increase cortisol levels which only exacerbates the insulin insensitivity and so creates a vicious circle. The importance of an innate insulin insensitivity may also be important in the pathogenesis of such conditions as laminitis.     

A survey on the use of rugs in Australian horses

The practice of horse rugging has important implications for horse welfare and performance, but in Australia, rugging practices have not been properly documented. The objective of this study was to obtain an understanding of Australian horse rugging practices. An online survey reviewed the management of 2659 Australian horses over 12 months. Of the reported horses a total of 84.8% were rugged, although most owners (69.5%) indicated that they were unsure whether horses needed to be rugged at all. Rugging was felt by 59.8% of owners to be a requirement for horses in competition. Riding and competition were significantly associated with the use of rugs. Nearly all respondents (89.0%) felt that ‘over-rugging’ was a concern. However, 4.8% of owners would use up to 4 rugs at any one time on their horse and 21.4% of horses were still rugged in temperatures above 20°C in Australia. Many Australian horse owners (42.8%) also believe that horses feel cold if they are not rugged. Anthropomorphism when it comes to rugging horses cannot be justified as the horse has a much wider thermoneutral zone (TNZ) than humans. Australian climate, owner opinions, equestrian discipline and whether a horse is used for riding influence Australian horse rugging practices. However, current practices are based on limited available research and are not necessarily to the benefit of the horse. The major limitation was that the survey likely attracted respondents who are interested in the topic creating a self-selection bias.     

Relationships among inflammatory cytokines, obesity, and insulin sensitivity in the horse

Recent studies associate obesity and insulin resistance in horses with development of abnormal reproductive function and debilitating laminitis. The factors contributing to insulin resistance in obese horses are unknown. However, human studies provide evidence that elevated inflammatory cytokines such as tumor necrosis factor alpha (TNFalpha), IL1, and IL6 play direct roles in development of obesity-associated insulin resistance. Thus, inflammation may be a key link between obesity and insulin resistance in horses. The aim of the current investigation was to examine possible relationships between obesity, inflammatory cytokines, and insulin sensitivity (IS) in the horse. Age was recorded and BCS and percent body fat (% FAT) were determined as measures of obesity in 60 mares. In addition, blood mRNA expression of IL1, IL6, and TNFalpha and circulating concentrations of TNFalpha protein (TNFp) were determined in each mare. Finally, fasted concentrations of insulin were determined, and IS was determined using the hyperinsulinemic, euglycemic clamp. Significant correlations between several variables provided evidence for the design of 4 population regression models to estimate relationships between measures of obesity, inflammatory factors, and IS in the sample population. The results of these analyses revealed that IS decreased as BCS and % FAT increased (P < 0.001) in the sample population. Additionally, increased IL1 (P < 0.05) and TNFp (P < 0.01) were associated with decreased IS. However, increased TNFalpha (P < 0.001) was associated with decreased IS only in mares 20 yr of age and older. Increased BCS and % FAT were associated with increased expression of TNFalpha (P = 0.053) and IL1 (P < 0.05), and increased TNFp (P < 0.05). Surprisingly, increased BCS and % FAT were associated with decreased IL6 expression (P = 0.05) in mares <20 yr of age. Finally, evaluation of the influence of obesity and inflammatory cytokines on IS within the same model suggested that BCS and % FAT (P < 0.001) with TNFalpha [mRNA (P = 0.07) and protein (P < 0.05)] are inversely associated with IS independently of one another. Combined, these results provide the first evidence associating obesity with increased inflammatory factors in the horse. Furthermore, the results suggest that an interrelationship exists among obesity, inflammatory cytokines, and IS in the horse and emphasize the need for further studies to elucidate the nature of these relationships.     

Evaluation of systemic immunologic hyperreactivity after intradermal testing in horses with chronic laminitis

OBJECTIVE: To determine whether systemic immunologic hyperreactivity exists in horses with chronic laminitis, compared with responses for nonlaminitic horses. ANIMALS: 7 nonlaminitic horses and 7 CL horses. PROCEDURE: In experiment 1, intradermal testing (IDT) was performed on 7 nonlaminitic and 7 CL horses to evaluate the response to a combination of 70 allergens at 15 and 30 minutes and 4 and 24 hours after injection. Three nonlaminitic and 3 CL horses used in experiment 1 were used in experiment 2 to determine whether histologic differences existed between the 2 groups. The H&E-stained tissue sections were evaluated on the basis of 3 criteria. For all analyses, 2-sample t-tests were used to determine significant differences between the groups. RESULTS: In experiment 1, CL horses had significantly higher total responses to IDT than nonlaminitic horses at the first 3 time periods. Also, CL horses had significantly fewer total scores of 0 than nonlaminitic horses at all time periods, except at 24 hours. In experiment 2, we did not detect significant differences between groups for any criterion. CONCLUSIONS AND CLINICAL RELEVANCE: Results support the hypothesis that CL horses develop hyperreactivity to various antigenic stimuli, compared with responses for nonlaminitic horses. Therefore, the possibility that antigenic challenge may result in exacerbation of clinical signs of laminitis should be discussed with horse owners. Chronic laminitis should also be a consideration when a horse becomes lame following antigenic challenges.     

The prevalence of endocrinopathic laminitis among horses presented for laminitis at a first-opinion/referral equine hospital

Endocrinopathic causes of laminitis may be a common underlying causative pathogenesis in first-opinion or field cases presenting with laminitis, as opposed to laminitis produced in inflammatory research models. This study aimed to determine whether evidence of an underlying endocrinopathy was present in horses presented for laminitis to a first-opinion/referral veterinary teaching hospital. A second aim was to compare the signalment of horses and ponies with laminitis with the equine hospital population during the same period. All horses presenting for laminitis at Helsinki University Equine Teaching Hospital, Finland, over a 16-month period were examined for an underlying endocrinopathy. Horses presenting for laminitis were compared with the hospitalized population over the same period. There were 36 horses presented for laminitis, and evidence of endocrinopathy was present in 89%. Of the horses showing an underlying endocrinopathy, one-third had a diagnosis of pituitary pars intermedia dysfunction, and two-thirds showed basal hyperinsulinemia indicative of insulin resistance, without evidence of hirsutism. Phenotypic indicators of obesity were present in 95% of horses with basal hyperinsulinemia without hirsutism. Compared with the hospital population during the same period, horses with laminitis associated with an underlying endocrinopathy were significantly older and more likely to be pony breeds. Our data support that endocrine testing should be performed on all cases of laminitis that do not have a clear inflammatory or gastrointestinal origin.     

Assessment of Resting Insulin and Leptin Concentrations and Their Association With Managerial and Innate Factors in Horses

The purpose of this study was to determine how insulin and leptin concentrations varied in a large population of privately owned horses. Further, the study was designed to examine the relationships between insulin and leptin with innate (sex, age, breed) and managerial (diet, exercise) factors in these horses. Resting blood samples (for determination of glucose, insulin, and leptin concentrations), body condition scores, feed information, and health history were collected from 366 privately owned horses. In this group of horses, 48% were considered overweight (Body Condition Score ≥6) and 8% were considered hyperinsulinemic (insulin concentrations >30 μU/mL). Confirming the findings of studies within research herds, both insulin and leptin concentrations were found to be correlated with body condition score (P < .001). It was also found that geldings had higher insulin concentrations than mares (P < .05). Ponies were found to have higher insulin and leptin concentrations as well as higher body condition scores, than several other breeds examined. While not a specific measure of insulin sensitivity, resting insulin concentrations have been associated with quantitative measurements of insulin sensitivity and may be useful in large-scale studies for estimating insulin and glucose dynamics. Because of the association between insulin resistance and obesity with diseases such as laminitis, the findings of the present study may help owners identify horses that may be at risk for the development of such conditions.     

A Survey of Horse Owner's Compliance with the Finnish Vaccination Program

Finnish Trotting and Breeding Association's electronic database (IT register) in Finland does not include vaccination entries of all horses. Especially, vaccination status of horses outside sport arenas is unclear. Objectives were to investigate vaccination practices of horse owners in Finland, to look for reasons associated with nonvaccination, and to evaluate the accuracy of the other statistics in Finland. The questionnaire study was executed. Horse owners (n = 1,198) told their vaccination practices, vaccinations used, and reasons for nonvaccination. Horses were mainly (85%–95%) vaccinated depending on the number of horses per horse owner. Equine influenza vaccine was mainly favored (94%). One reason for nonvaccination is that the horse is inactive in equine sport arenas (43%). Other reasons (53%) were age, horse does not take part in competitions but stay at home, and the owner decides that the horse does not need vaccination. Differences between age groups (young and old), competition types, and regions were not found by one-variable analysis, but vaccination status of horses outside equine sport arenas differed from horses active in competitions. By logistic regression analysis, it was indicated that purpose of use had influence on vaccination status. Reasons for nonvaccination surveyed in UK were confirmed. The control of the competition rules and possible sanctions exercised in competition venue are better explanatory factors than age, type of competition, and geographic home area. However, the risk to meet a nonvaccinated horse increases when going to the northern part of Finland.     

Radiographic and radiological assessment of laminitis

Radiographic studies are an essential component in evaluation of horses with laminitis. The standard radiographs that should be obtained to aid assessment of horses with laminitis are the lateromedial, horizontal dorsopalmar and dorsal 45° proximal palmarodistal oblique views. This article will summarise the assessment of these 3 projections in the laminitic horse as well as discuss the prognostic significance of common radiological abnormalities in horses with laminitis.     

Modulation of leptin, insulin, and growth hormone in obese pony mares under chronic nutritional restriction and supplementation with ractopamine hydrochloride

Horses fed beyond their nutritional requirement and that are physically inactive will develop obesity, which is often accompanied by insulin resistance and heightened risk of laminitis. The use of pharmacologic agents in combination with nutritional restriction may promote weight loss in obese horses unable to exercise because of laminitic pain. This study shows that reducing feed intake of brome grass hay to 75% of ad libitum intake in obese pony mares reduces body weight without induced exercise. Additional supplementation of ractopamine hydrochloride for 6 weeks resulted in a tendency for increased weight loss. Subsequent modulation of obesity-associated hormones, leptin and insulin, as a result of caloric restriction was observed.     

Glucocorticoid therapy and the risk of equine laminitis

Although glucocorticoids have been used successfully for the treatment of noninfectious inflammatory diseases of horses for more than 35 years, their use has been attended by a fear of the induction of laminitis. This paper reviews the evidence for this fear and the possible mechanisms whereby glucocorticoids could participate in laminitis induction. Although the association of laminitis with elevated serum cortisol in pituitary pars intermedia dysfunction suggests that chronic exposure to glucocorticoids may be part of laminitis pathogenesis, review of published reports and databases suggests that glucocorticoid‐induced laminitis is a relatively rare occurrence. However, several of the actions of glucocorticoids are similar to those known to be involved in laminitis pathogenesis. Glucocorticoid administration can induce insulin resistance, lead to vascular dysfunction that potentiates vasoconstriction, and interfere with keratinocyte proliferation and differentiation as well as matrix integrity, all mechanisms that could possibly induce laminitis. Drug formulation, dose and route of administration, and the systemic and hoof disease history of the horse must all be considered when assessing laminitis risk during glucocorticoid treatment. Generally, local glucocorticoid administration presents little risk as does systemic treatment of recurrent airway obstruction without concurrent disease. Caution should be used however in horses that are overweight and/or insulin resistant, or have had a recent bout of acute laminitis of alimentary or endotoxic origin. Overall, however, the risk of laminitis after glucocorticoid treatment, especially local use, is acceptable compared to the many benefits of these drugs.     

Equine laminitis: Induced by 48 h hyperinsulinaemia in Standardbred horses

Reasons for performing study: Hyperinsulinaemia is known to induce laminitis experimentally in healthy ponies with no history of the condition. Horses are more insulin sensitive than ponies and whether prolonged hyperinsulinaemia and euglycaemia would have a similar laminitogenic effect requires study. Objectives: To determine if laminitis results when the prolonged euglycaemic hyperinsulinaemic clamp technique (p‐EHC) is applied to clinically normal Standardbred horses, and to monitor hoof wall temperature seeking an association between vascular activity and laminitis development. Methods: Eight young, clinically normal Standardbred horses were assigned into 4 pairs and within each pair, one was assigned randomly to either treatment (n = 4) or control (n = 4) groups. Treated horses received continuous infusions of insulin and glucose until clinical signs of laminitis developed, at which point the horses were subjected to euthanasia. Control horses received an equivalent volume of a balanced electrolyte infusion for the same period. Hoof wall surface temperature (HWST) was monitored continuously throughout the experimental period. Results: All horses in the treatment group were calculated to have normal insulin sensitivity. All treated horses, and none in the control group, developed laminitis (P = 0.01). Pronounced digital pulses were a feature of the treatment group, while insignificant digital pulses occurred in control horses. HWST was higher and less variable in treated horses once hyperinsulinaemia was established. Conclusions: Healthy Standardbred horses subjected to prolonged hyperinsulinaemia develop laminitis within 48 h, demonstrating that laminitis in horses can be triggered by insulin. Potential relevance: Insulin resistance and the associated hyperinsulinaemia place horses and ponies at risk of developing laminitis. This study demonstrates a need for prompt management of the persistent hyperinsulinaemia seen in some endocrinopathies.     

Endocrine disorders and laminitis

Two common endocrine disorders, pituitary pars intermedia dysfunction and equine metabolic syndrome, predispose horses and ponies to laminitis and may even induce the condition. The exact mechanisms involved in endocrinopathic laminitis have not been elucidated but hyperinsulinaemia and insulin resistance are currently being investigated. Obesity and regional adiposity may also contribute to laminitis susceptibility through the release of inflammatory cytokines and adipokines. In the case of pituitary pars intermedia dysfunction, glucocorticoid excess is likely to weaken hoof structures, alter vascular dynamics within the foot and induce or exacerbate insulin resistance. This review will summarise current theories regarding the pathophysiology of endocrinopathic laminitis and provide recommendations for the diagnosis and management of these common equine endocrine disorders.     

Resistance to benzimidazole anthelmintics in small strongyles (Cyathostominae) of horses in Denmark.

This study was undertaken to establish whether anthelmintic resistance was present in nematode parasites of horses in Denmark. Sixteen horse farms were selected for faecal egg count reduction (FECR) tests to measure the efficacy of the anthelmintic used. Resistance to benzimidazole anthelmintics was found on 13 of the 16 farms, with FECR values ranging from 80.0% to -101.3%. On the remaining 3 farms FECR was 100.0%, 99.3% and 97.2%. Results of a questionnaire study on anthelmintic usage, parasite control measures and management practices showed that horses in this study were treated on average 7.1 times/year. Horse owners changed between preparations of drugs but almost only within the same class of anthelmintics. Nine owners gave an anthelmintic treatment to purchased horses before they were introduced on the farm. On 14 farms, the same paddock was grazed every year and the average stocking rate was estimated to be 2.4 horses/ha. Strategies to avoid development of anthelmintic resistance are discussed and recommendations of parasite control on horse farms are presented.     

Glucose homeostasis and the enteroinsular axis in the horse: A possible role in equine metabolic syndrome

One of the principal components of equine metabolic syndrome (EMS) is hyperinsulinaemia combined with insulin resistance. It has long been known that hyperinsulinaemia occurs after the development of insulin resistance. But it is also known that hyperinsulinaemia itself can induce insulin resistance and obesity and might play a key role in the development of metabolic syndrome. This review focuses on the physiology of glucose and insulin metabolism and the pathophysiological mechanisms in glucose homeostasis in the horse (compared with what is already known in humans) in order to gain insight into the pathophysiological principles underlying EMS. The review summarizes new insights on the oral uptake of glucose by the gut and the enteroinsular axis, the role of diet in incretin hormone and postprandial insulin responses, the handling of glucose by the liver, muscle and fat tissue, and the production and secretion of insulin by the pancreas under healthy and disrupted glucose homeostatic conditions in horses.     

Continuous intravenous infusion of glucose induces endogenous hyperinsulinaemia and lamellar histopathology in Standardbred horses

Endocrinopathic laminitis is frequently associated with hyperinsulinaemia but the role of glucose in the pathogenesis of the disease has not been fully investigated. This study aimed to determine the endogenous insulin response to a quantity of glucose equivalent to that administered during a laminitis-inducing, euglycaemic, hyperinsulinaemic clamp, over 48 h in insulin-sensitive Standardbred racehorses. In addition, the study investigated whether glucose infusion, in the absence of exogenous insulin administration, would result in the development of clinical and histopathological evidence of laminitis. Glucose (50% dextrose) was infused intravenously at a rate of 0.68 mL/kg/h for 48 h in treated horses (n=4) and control horses (n=3) received a balanced electrolyte solution (0.68 mL/kg/h). Lamellar histology was examined at the conclusion of the experiment. Horses in the treatment group were insulin sensitive (M value 0.039±0.0012 mmol/kg/min and M-to-I ratio (100×) 0.014±0.002) as determined by an approximated hyperglycaemic clamp. Treated horses developed glycosuria, hyperglycaemia (10.7±0.78 mmol/L) and hyperinsulinaemia (208±26.1 μIU/mL), whereas control horses did not. None of the horses became lame as a consequence of the experiment but all of the treated horses developed histopathological evidence of laminitis in at least one foot. Combined with earlier studies, the results showed that laminitis may be induced by either insulin alone or a combination of insulin and glucose, but that it is unlikely to be due to a glucose overload mechanism. Based on the histopathological data, the potential threshold for insulin toxicity (i.e., laminitis) in horses may be at or below a serum concentration of ～200 μIU/mL.