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1.
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.  相似文献   

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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.  相似文献   

5.
Equine insulin resistance is important because of its association with laminitis. The insulin-response test is described to diagnose insulin resistance in clinical settings. Practitioners may be reluctant to perform this test because of the time needed for the test and the fear of inducing hypoglycemia. The objective of the study was to compare a 2-step insulin-response test with a complete insulin-response test. A complete insulin-response test was performed on 6 insulin-resistant horses and 6 controls. A 2-step insulin-response test consisting of an intravenous injection of 0.1 IU/kg human insulin and blood glucose determination at 0 and 30 min after injection was performed on the same horses. Times to reach a 50% reduction of glucose baseline were compared between tests and horses. All the horses tolerated both tests well. No significant difference was observed between baseline glucose concentrations of insulin-resistant horses and controls (P = 0.09). Time to reach 50% reduction of glucose baseline for controls was not significantly different with the use of the complete insulin-response test or the 2-step test (P = 0.98). For insulin-resistant horses, the time to reach 50% reduction of glucose baseline with the use of the 2-step test was significantly longer than for controls (P = 0.004). With a cut-off time of 30 min, the 2-step test had the same characteristics as the complete test. The 2-step test provided a safe, rapid, and low-cost method to diagnose insulin resistance in horses in a clinical setting.  相似文献   

6.
A specific method of rehabilitation was used to manage obese horses with laminitis, and clinical outcome was evaluated after 5 to 20 months. Clinical data from 14 similar laminitis cases were statistically analyzed to evaluate response to rehabilitation. Data were analyzed using repeated measures or logistic regression methodologies. Each horse presented as obese and laminitic with no history of a systemic inflammatory disease. The rehabilitation method emphasized a mineral-balanced, low nonstructural carbohydrate diet; daily exercise; hoof trimming that minimized hoof wall loading; and sole protection in the form of rubber hoof boots and/or hoof casts. Distal phalanx alignment within the hoof capsule was significantly improved, and hoof wall thickness was significantly decreased (P < .0001) following treatment. Solar depth was significantly increased (P < .0015). Reduction of palmar angle measurements was detected in acutely and chronically affected horses. This treatment effect was statistically greater for horses with chronic laminitis than for horses with acute laminitis (P interaction < .0001). Horses were 5.5 times more likely to be sound post-treatment than before treatment. Daily exercise, dietary modification, and removal of ground reaction force from the hoof wall were foci of the rehabilitation program. Hoof care and husbandry as applied to these horses may be an effective method of rehabilitation of horses from obesity-associated laminitis.  相似文献   

7.
This study aimed to investigate endocrinologic test values and the response to treatment of two commonly encountered causes of endocrinopathic laminitis, equine Cushing's disease (ECD) and equine metabolic syndrome (EMS), in a veterinary practice setting. In particular, the study aimed to determine whether insulin concentration correlated to the severity of clinical laminitis in horses with EMS or ECD. Twenty-five horses were included in the study and assigned to one of three groups: ECD (n = 6), EMS (n = 10), and controls (n = 9). Blood samples were collected at an initial visit and then at regular intervals for the next 12 months. Plasma concentrations of adrenocorticotropin (ACTH), cortisol, and insulin and serum concentrations of glucose and total thyroxine (T4) were obtained. Horses with ECD had significantly higher plasma ACTH concentrations than EMS horses or controls. Horses with EMS and ECD both had significantly higher plasma insulin concentrations than control horses, which was correlated with the Obel grade of laminitis (r = 0.63). After treatment, there was a trend for a reduction in plasma ACTH concentration in horses with ECD. A program of diet and exercise for horses with EMS resulted in reductions in both plasma insulin concentrations and bodyweight, which was variable, depending on the individual. There was a significant correlation between the change in plasma insulin concentration and Obel grade of laminitis (r = 0.69). This study has highlighted the importance of baseline plasma insulin concentration as a potential indicator of the susceptibility of horses to laminitis and the response to a program of diet and exercise.  相似文献   

8.
Equine pituitary pars intermedia dysfunction (PPID) is known to alter glucose/insulin metabolism. This study evaluated changes in parameters relating to glucose/insulin metabolism and determined whether there is a difference between pergolide-treated and untreated animals. We hypothesized that glucose/insulin dynamics in PPID horses receiving pergolide would be different than those in untreated horses. A total of 38 horses with diagnoses of PPID were included in the study (average age: 24 years). A total of 25 horses were untreated; 13 horses were treated with pergolide (>3 months). Parameters relating to glucose/insulin metabolism were determined in all horses, as follows: adrenocorticotropin-releasing hormone (ACTH), insulin, fructosamine, triglyceride, glucose, modified insulin-to-glucose ratio (MIRG), and reciprocal of the square root of insulin (RISQI). A combined glucose-insulin test (CGIT) was performed in 23 horses as not all owners agreed to the testing. Treated animals showed a tendency to have lower ACTH, but results were not significant. All animals had fructosamine levels exceeding reference values (mean value 314 ± 32 μmol/L; reference range: <280 μmol/L). There were no statistically significant differences between insulin, glucose, ACTH, triglycerides concentrations, RISQI/MIRG calculations, and CGIT results of pergolide-treated PPID and those of untreated horses. Five horses (13.2%) had combined hyperglycemia/hyperinsulinemia, whereas 7 horses (18.4%) displayed hyperglycemia, and 3 horses (7.9%) showed hyperinsulinemia alone. Forty percent of the horses with altered glucose/insulin metabolism were treated with pergolide. Based on RISQI and MIRG calculations, 19 animals displayed changes in glucose/insulin metabolism. Fourteen of twenty-three horses (61%) showed signs of insulin resistance in CGIT results. In conclusion, PPID horses frequently show alterations in glucose/insulin metabolism, but no significant differences were found between treated and untreated animals. Changes in insulin/glucose dynamics may not be a useful indicator of response to pergolide treatment.  相似文献   

9.
Straightforward testing procedures are needed to facilitate the diagnosis of insulin dysregulation in horses because hyperinsulinemia and insulin resistance are associated with laminitis. Results of an oral sugar test (OST) were compared with those of the intravenous glucose tolerance test (IVGTT). We hypothesized that OST and IVGTT area under the curve values for glucose (AUCg) and insulin (AUCi) would be closely correlated, as defined by a correlation coefficient value ≥0.90. Both tests were performed in 10 horses meeting the criteria for equine metabolic syndrome (EMS) and 8 Quarter horse crossbred mares from a university teaching herd (control group). The OST was also performed in 21 Quarter horse crossbred mares from the same herd, and test repeatability was evaluated in 8 of these horses. All testing was performed under fasting conditions. Median AUCg and AUCi values were 1.3- and 9.0-fold higher, respectively, for the IVGTT and 1.3- and 6.8-fold higher, respectively, for the OST in the EMS group than those in the control group. AUCg (Spearman correlation coefficient [rs] = 0.58; P = .012) and AUCi (rs = 0.90; P < .001) values for the two tests were positively correlated. Mean ± SD coefficients of variation for repeated tests in 8 mares were 6.4% ± 3.1% and 45.1% ± 36.2% for AUCg and AUCi, respectively. We conclude that OST and IVGTT insulin results are closely correlated, so the OST warrants further consideration as a field test for insulin dysregulation in horses.  相似文献   

10.
Equine laminitis, a disease of the lamellar structure of the horse's hoof, can be incited by numerous factors that include inflammatory and metabolic aetiologies. However, the role of inflammation in hyperinsulinaemic laminitis has not been adequately defined. Toll-like receptor (TLR) activation results in up-regulation of inflammatory pathways and the release of pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α), and may be a pathogenic factor in laminitis. The aim of this study was to determine whether TLR4 expression and subsequent pro-inflammatory cytokine production is increased in lamellae and skeletal muscle during equine hyperinsulinaemia. Standardbred horses were treated with either a prolonged, euglycaemic hyperinsulinaemic clamp (p-EHC) or a prolonged, glucose infusion (p-GI), which induced marked and moderate hyperinsulinaemia, respectively. Age-matched control horses were treated simultaneously with a balanced electrolyte solution. Treated horses developed clinical (p-EHC) or subclinical (p-GI) laminitis, whereas controls did not. Skeletal muscle and lamellar protein extracts were analysed by Western blotting for TLR4, IL-6, TNF-α and suppressor of cytokine signalling 3 (SOCS3) expression. Lamellar protein expression of TLR4 and TNF-α, but not IL-6, was increased by the p-EHC, compared to control horses. A significant positive correlation was found between lamellar TLR4 and SOCS3. Skeletal muscle protein expression of TLR4 signalling parameters did not differ between control and p-EHC-treated horses. Similarly, the p-GI did not result in up-regulation of lamellar protein expression of any parameter. The results suggest that insulin-sensitive tissues may not accurately reflect lamellar pathology during hyperinsulinaemia. While TLR4 is present in the lamellae, its activation appears unlikely to contribute significantly to the developmental pathogenesis of hyperinsulinaemic laminitis. However, inflammation may have a role to play in the later stages (e.g., repair or remodelling) of the disease.  相似文献   

11.
Insulin dysregulation is the hallmark of equine metabolic syndrome and has received attention because of its direct association with laminitis. In the absence of an adequate treatment for laminitis, a focus on prophylaxis is needed, making early detection of individuals at risk of developing laminitis one of the main challenges in equine endocrinology. Recent studies have shown that insulin dysregulation goes beyond tissue insulin resistance and it is now demonstrated that the equine enteroinsular axis plays a major role in insulin secretion and equine hyperinsulinaemia. In this review, we discuss the different tests currently available to diagnose insulin dysregulation in horses: the ones investigating tissue insulin resistance and those investigating the enteroinsular axis, detailing their goals, practicalities and limitations. This review supports the contention that the diagnosis of equine insulin dysregulation should now be based on the investigation of both tissue insulin resistance and the equine enteroinsular axis. Regardless of the tests used many factors of variation, such as breed, diet, fasting state or season, have been identified and could potentially confound the results of a specific test. Therefore, careful interpretation of the results of a given test in each individual situation is required to optimise the detection of horses at risk of laminitis.  相似文献   

12.
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.  相似文献   

13.
Administration of black walnut heartwood extract (BWHE) via nasogastric tube induces acute laminitis in horses. However, the processes responsible for the development of laminitis, including laminitis induced with BWHE, remain unclear. The results of recent studies indicate that administration of BWHE initiates an inflammatory response in the laminar tissues and that this response may be due to extravasation of activated leukocytes from the circulation. This study examines the effects of BWHE administration on the dynamics of circulating neutrophils and monocytes, and the capacity of blood leukocytes to produce radical oxygen species (ROS) over the time period from administration of BWHE to the development of lameness consistent with Obel grade I laminitis.

Individual horses, free of pre-existing musculoskeletal disease, were administered either 6 l of BWHE or an equal volume of water at time 0 (T = 0). Blood samples were collected prior to dosing and at 1, 2, 3, 4, 6, 8, 10 and 12 h after dosing, or until the onset of Obel grade I laminitis. For each sample, total leukocyte counts were determined followed by collection of buffy coats and removal of erythrocytes by hypotonic lysis. Leukocytes were either fixed for flow cytometric assessment of differential counts or maintained in culture to measure endogenous and phorbol ester-induced production of ROS. At each sample time, the number of cells recovered and the flow cytometric differential counts were compared with corresponding total leukocyte counts determined by the Clinical Pathology laboratory.

Horses administered BWHE had a significant reduction in circulating leukocytes at 3–4 h relative to values for horses administered the same volume of water. Horses that developed Obel grade I laminitis had a significant reduction in circulating leukocytes when compared to values for horses administered BWHE that did not become lame. Flow cytometric analysis revealed a consistent decrease in the total number of monocytes obtained from horses that developed laminitis. In these same horses, the endogenous level of ROS production was significantly higher at T = 0 than for horses that did not become lame. Furthermore, production of ROS by leukocytes from horses that developed laminitis increased significantly and coincided with the decrease in circulating leukocytes.

Collectively, these findings support a role for systemic activation of leukocytes and induction of inflammation by BWHE as a factor in the early pathogenesis of acute laminitis. Because laminitis often develops as a sequel to diseases characterized by systemic inflammatory events, activation and emigration of neutrophils and monocytes may be important factors in the early pathogenesis of laminitis in clinical cases.  相似文献   


14.
The pathophysiology of pituitary pars intermedia dysfunction (PPID) and its connection to laminitis have been the focus of much recent research. This article reviews the pathophysiology, diagnostics, and treatments of PPID, as well as the proposed pathogenesis of laminitis in these horses. An increased understanding of the disease process, along with appropriate diagnosis and treatment, can often minimize the devastating laminitis often associated with PPID.  相似文献   

15.
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.  相似文献   

16.

Background

Increased blood insulin levels are associated with an increased risk of pasture‐associated laminitis in equids.

Objective

To determine the relationship between plasma insulin, leptin, and lipid levels, and measures of oxidative stress with adiposity in mature light breed horses.

Animals

300 randomly selected light breed horses, aged 4–20 years.

Methods

A random sample of horses (140 mares, 151 geldings, and 9 stallions) was drawn from the VMRCVM Equine Field Service practice client list. Evaluations occurred June 15 – August 15, 2006, with all sampling performed between 0600 and 1200 hours. Concentrate feed was withheld for at least 10 hours before sampling. Plasma was analyzed for insulin, glucose, leptin, triglycerides, nonesterified fatty acids, and measures of oxidative stress. Body condition score was determined as the average of 2 independent investigators.

Results

Overconditioned and obese horses had higher plasma insulin (< .001) and leptin (< .01) levels than optimally conditioned horses. Obese horses had higher triglyceride levels (= .006) and lower red blood cell gluthathione peroxidase activities (= .001) than optimally conditioned horses.

Conclusions and Clinical Importance

Maintaining horses at a BCS <7 might be important for decreasing the risk of pasture‐associated laminitis.  相似文献   

17.
Background: Pentoxifylline (PTX) possesses a number of vasomotor, immunomodulatory, and hemorheologic properties. Based upon the hypothesis that equine laminitis and navicular disease result from microthrombosis, the inhibitory effects of PTX on inflammatory cytokines, and its inhibitory effects on human platelet aggregation, PTX has been widely used to treat equine endotoxemia, navicular disease, and laminitis. Despite this, the effects of PTX on equine platelet aggregation have not been investigated previously. Hypothesis: PTX decreases platelet aggregation in equine whole blood at concentrations approximating those achieved in horses given clinically relevant doses of PTX. Animals: Seven healthy adult horses from a research herd. Methods: Whole blood impedance aggregometry using whole equine blood incubated with varying concentrations of PTX. Adenosine diphosphate (ADP) and collagen were used to initiate aggregation. Results: The onset time of collagen‐induced equine platelet aggregation was significantly shortened by PTX. The maximum slope of resistance change (dR/dt) and total resistance change of collagen‐induced platelet aggregation were unaffected by PTX. No effects of PTX on ADP‐induced onset time of aggregation, dR/dt, or total resistance change were observed. Conclusions and Clinical Importance: Our hypothesis is not supported by the results. PTX hastens the onset of collagen‐induced platelet aggregation in equine whole blood, but has no effect on the rate of collagen‐induced aggregation. PTX does not affect ADP‐dependent equine platelet aggregation. Given these findings, PTX may not be a reasonable therapeutic option to decrease platelet aggregation in horses.  相似文献   

18.
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.  相似文献   

19.
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.  相似文献   

20.
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.  相似文献   

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