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1.
Reasons for performing study: Insulin resistance may be a risk factor for pasture‐associated laminitis. Diagnosis of insulin resistance could help identify individuals at increased risk of laminitis. Objective: To calculate proxy measurements of insulin sensitivity (reciprocal of the square root of insulin: RISQI and quantitative insulin sensitivity check index: QUICKI) and insulin secretory response (modified insulin‐to‐glucose ratio: MIRG) based on basal glucose and insulin concentrations in normal (NP) and previously laminitic (PLP) ponies. Methods: Proxies were calculated in 7 NP and 5 PLP from 20 separate measurements of insulin and glucose taken in spring, summer and winter when ponies were adapted to eating either pasture or hay. Proxies were RISQI: Insulin‐0.5, QUICKI: 1/(log[fasting Insulin]+ log[fasting Glucose]) and MIRG: (800?0.3×[Insulin‐50]2)/[Glucose‐30]. A modified insulin‐to‐glucose ratio for ponies (MIGRP) was investigated using: (3000?0.012 ×[Insulin‐500]2)/[Glucose‐30]. Statistical analysis used linear mixed models. Results: Diet did not significantly affect measurements, so values were pooled for further analysis. RISQI (mean ± s.d.) was lower in PLP (0.26 ± 0.15 [mu/l]‐0.5) than NP (0.29 ± 0.12 [mu/l]‐0.5; P = 0.05). QUICKI was lower in PLP (0.31 ± 0.05) than NP (0.33 ± 0.04; P = 0.047). There was no difference in MIRG between NP and PLP. MIGRP (median [interquartile range]) was greater in PLP (4.0 [7.9][muins]2/10·l·mggluc) than NP (2.6 [3.2][muins]2/10·l·mggluc; P = 0.022). In spring, NP had higher RISQI and QUICKI and lower MIGRP than PLP (P<0.001). In PLP, RISQI and QUICKI were higher in summer than spring (P<0.02) and MIGRP was lower in summer than other seasons (P<0.01). In NP, RISQI, QUICKI and MIGRP were each different between seasons (P<0.017). MIRG did not vary with season. Conclusions: RISQI, QUICKI and MIGRP, but not MIRG, differentiated between NP and PLP. None of the proxies accurately identified individual PLP. Seasonal changes in insulin sensitivity and insulin secretory response were apparent. Potential relevance: Current proxy measurements cannot determine an individual's laminitis susceptibility. MIGRP may be useful in hyperinsulinaemic animals.  相似文献   

2.
OBJECTIVE: To determine effects of dexamethasone on glucose dynamics and insulin sensitivity in healthy horses. ANIMALS: 6 adult Standardbreds. PROCEDURES: In a balanced crossover study, horses received dexamethasone (0.08 mg/ kg, IV, q 48 h) or an equivalent volume of saline (0.9% NaCl) solution (control treatment) during a 21-day period. Horses underwent a 3-hour frequently sampled IV glucose tolerance test (FSIGT) 2 days after treatment. Minimal model analysis of glucose and insulin data from FSIGTs were used to estimate insulin sensitivity (Si), glucose effectiveness (Sg), acute insulin response to glucose (AIRg), and disposition index. Proxies for Si (reciprocal of the inverse square of basal insulin concentration [RISQI]) and beta-cell responsiveness (modified insulin-to-glucose ratio [MIRG]) were calculated from basal plasma glucose and serum insulin concentrations. RESULTS: Mean serum insulin concentration was significantly higher in dexamethasone-treated horses than control horses on days 7, 14, and 21. Similarly, mean plasma glucose concentration was higher in dexamethasone-treated horses on days 7, 14, and 21; this value differed significantly on day 14 but not on days 7 or 21. Minimal model analysis of FSIGT data revealed a significant decrease in Si and a significant increase in AIRg after dexamethasone treatment, with no change in Sg or disposition index. Mean RISQI was significantly lower, whereas MIRG was higher, in dexamethasone-treated horses than control horses on days 7, 14, and 21. CONCLUSIONS AND CLINICAL RELEVANCE: The study revealed marked insulin resistance in healthy horses after 21 days of dexamethasone administration. Because insulin resistance has been associated with a predisposition to laminitis, a glucocorticoid-induced decrease in insulin sensitivity may increase risk for development of laminitis in some horses and ponies.  相似文献   

3.
OBJECTIVE: To determine the metabolic phenotype of a group of laminitis-prone ponies when at pasture in summer, compared with when at pasture in winter. ANIMALS: 40 ponies of various breeds predisposed to recurrent pasture-associated laminitis and 40 unaffected control ponies. PROCEDURES: Body condition score and size of the crest of the neck were assessed, blood samples obtained, and blood pressure measured by use of an indirect oscillometric technique, while ponies were kept on winter pasture (last week of November or beginning of December) and again on summer pasture (June). Serum insulin concentration and plasma glucose, triglyceride, uric acid, and ACTH concentrations were measured. Insulin sensitivity was calculated with proxies derived from basal serum insulin and plasma glucose concentrations. RESULTS: No significant differences were apparent between ponies predisposed to laminitis and control ponies during winter. However, in June, laminitis-prone ponies had increased serum insulin concentration and plasma triglyceride and uric acid concentrations, compared with control ponies. Also, laminitis-prone ponies were relatively insulin resistant, compared with control ponies. Mean blood pressure was significantly higher during summer in laminitis-prone ponies (median [interquartile range], 89.6 mm Hg [78.3 to 96.9 mm Hg]), compared with control ponies (76.8 mm Hg [69.4 to 85.2 mm Hg]). CONCLUSIONS AND CLINICAL RELEVANCE: Summer pastures appear to induce metabolic responses in some ponies, leading to expression of the prelaminitic phenotype, which includes hypertension as well as insulin resistance. Signs of this metabolic syndrome may not be apparent in affected ponies during periods of grazing winter pasture. Understanding this syndrome may enable improved countermeasures to be devised to prevent laminitis.  相似文献   

4.
OBJECTIVE: To develop proxies calculated from basal plasma glucose and insulin concentrations that predict insulin sensitivity (SI; L.min(-1) x mU(-1)) and beta-cell responsiveness (ie, acute insulin response to glucose [AIRg]; mU/L x min(-1)) and to determine reference quintiles for these and minimal model variables. ANIMALS: 1 laminitic pony and 46 healthy horses. PROCEDURE: Basal plasma glucose (mg/dL) and insulin (mU/L) concentrations were determined from blood samples obtained between 8:00 AM and 9:00 AM. Minimal model results for 46 horses were compared by equivalence testing with proxies for screening SI and pancreatic beta-cell responsiveness in humans and with 2 new proxies for screening in horses (ie, reciprocal of the square root of insulin [RISQI] and modified insulin-to-glucose ratio [MIRG]). RESULTS: Best predictors of SI and AIRg were RISQI (r = 0.77) and MIRG (r = 0.75) as follows: SI = 7.93(RISQI) - 1.03 and AIRg = 70.1(MIRG) - 13.8, where RISQI equals plasma insulin concentration(-0.5) and MIRG equals [800 - 0.30(plasma insulin concentration 50)(2)]/(plasma glucose concentration - 30). Total predictive powers were 78% and 80% for RISQI and MIRG, respectively. Reference ranges and quintiles for a population of healthy horses were calculated nonparametrically. CONCLUSIONS AND CLINICAL RELEVANCE: Proxies for screening SI and pancreatic beta-cell responsiveness in horses from this study compared favorably with proxies used effectively for humans. Combined use of RISQI and MIRG will enable differentiation between compensated and uncompensated insulin resistance. The sample size of our study allowed for determination of sound reference range values and quintiles for healthy horses.  相似文献   

5.
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.  相似文献   

6.
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7.
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   

8.
Reasons for performing study: The use of plasma fructosamine concentration ([fructosamine]) as a marker of abnormal glucose homeostasis in laminitic horses has not been investigated. Hypothesis: Plasma fructosamine concentration may be higher amongst laminitic horses than normal horses; this might relate to underlying insulin resistance. Objectives: 1) To compare [fructosamine] between laminitic and normal horses. 2) To investigate associations between [fructosamine] at presentation in laminitic horses with a) single sample markers of insulin resistance and b) outcome. Methods: Plasma fructosamine concentration, fasting serum insulin concentration (insulin) and fasting plasma glucose concentration (glucose) were measured in 30 horses that presented with laminitis. Clinical details and follow‐up data were recorded. Plasma fructosamine concentration was also measured in 19 nonlaminitic control horses. Results: Laminitic horses had significantly higher mean [fructosamine] than normal horses (P<0.001). Thirteen of 30 laminitic horses had fasting hyperinsulinaemia, 2/30 had fasting hyperglycaemia. Statistically significant univariable correlations were identified between [fructosamine] and [glucose], [insulin] and the proxies RISQI and MIRG. Trends for association between [fructosamine] and negative outcome did not reach statistical significance. Conclusions and potential relevance: Increased mean [fructosamine] in laminitic horses may represent abnormal glycaemic control and [fructosamine] may become a clinically useful marker.  相似文献   

9.
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   

10.
Reasons for performing study: The ability to predict ponies at increased risk of laminitic episodes, when exposed to nutrient dense pasture, would facilitate management to avoid disease. Objectives: To identify variables and clinically useful cut‐off values with reproducible diagnostic accuracy for the prediction of ponies that subsequently developed laminitis when exposed to nutrient dense pasture. Methods: A cohort of predominantly Welsh and Dartmoor ponies from a closed herd was evaluated in March 2006 (n = 74) and March 2007 (n = 57). Ponies were categorised as never laminitic or previously laminitic according to reported laminitic history and as clinically laminitic (CL) if laminitis was observed within 3 months following evaluation. Body condition score (BCS), cresty neck score (CNS), girth and neck circumferences (NC), withers height, blood pressure and hoof surface temperature, and plasma insulin, glucose, triglyceride, leptin, cortisol, ACTH, uric acid and TNF‐α concentrations were measured. Analysis of sensitivity, specificity and receiver operating characteristic curves was used to evaluate the diagnostic accuracy for a variable to predict CL ponies. Results: Variables with diagnostic accuracy for the prediction of CL ponies included insulin, leptin, BCS, CNS, and NC:height ratio. Specific cut‐off values of insulin (>32 mu/l), leptin (>7.3 ng/ml), BCS (≥7), CNS (≥4) and NC:height ratio (>0.71) had reproducible diagnostic accuracy for the prediction of laminitis. Combining tests did not result in higher diagnostic accuracy than individual tests of insulin or leptin during either evaluation. Conclusions: Tests of insulin and leptin concentrations and measures of generalised (BCS) and localised (CNS or NC:height ratio) obesity were beneficial in the prediction of laminitic episodes. Potential relevance: These results highlight the importance of monitoring and reducing insulin concentration, and generalised and regional obesity in ponies to reduce risk of laminitis.  相似文献   

11.
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   

12.
Reasons for performing study: Ponies with laminitis associated with insulin resistance and hyperinsulinaemia lack systemic and/or intestinal inflammatory signs, suggesting a different pathogenesis potentially reflected in differing histopathology. Objectives: To describe the histological appearance and quantify morphological changes in primary and secondary epidermal lamellae (PEL and SEL) of laminitis lesions from ponies with insulin‐induced laminitis. Methods: Equine hoof lamellar tissue was obtained from 4 control ponies and 5 ponies with laminitis induced following infusion of insulin (1036 ± 55 µU/ml) while maintaining euglycaemia for 55.4 ± 5.5 h. Sections from all 4 hooves were stained and examined by a veterinary pathologist. Measurements of lamellar length (PEL and SEL) were made in mid‐dorsal sections of the right forefeet by 2 blinded observers. Immunolabelling for calprotectin was performed using a monoclonal antibody. Results: No lesions were detected in normal ponies. Lesions detected in ponies with laminitis were variable in severity between ponies. Within ponies, SEL lesions were more severe along the axial region of PEL. Lesions included swelling, disorganisation and abnormal keratinisation of epidermal cells, increased mitotic activity and apoptosis. Separation of basement membranes was minimal. Immunostaining revealed inflammatory cells within the lamellar dermis. SEL were significantly elongated in laminitic hooves relative to controls, with the greatest elongation in those attached to abaxial and middle regions of PEL. Conclusions: Laminitis induced by prolonged infusion of insulin lacked widespread basement membrane disintegration, and increases in epidermal cellular proliferation at axial aspects were marked for this acute stage of disease. Potential relevance: Defining equine laminitis entirely in terms of separation of the basement membrane may not be appropriate for laminitis associated with hyperinsulinaemia.  相似文献   

13.
The purpose of this study was to determine the effects of prolonged administration of insulin, whilst maintaining normal glucose concentrations, on hoof lamellar integrity in vivo on healthy ponies with no known history of laminitis or insulin resistance. Nine clinically healthy, unrelated ponies were randomly allocated to either a treatment group (n =5; 5.9+/-1.7 years) or control group (n =4; 7.0+/-2.8 years). The treatment group received insulin via a euglycaemic hyperinsulinaemic clamp technique modified and prolonged for up to 72 h. Control ponies were infused with an equivalent volume of 0.9% saline. Ponies were euthanized at the Obel grade 2 stage of clinical laminitis and hoof lamellar tissues were harvested and examined for histopathological evidence of laminitis. Basal serum insulin and blood glucose concentrations were 15.7+/-1.8 microU/mL and 5.2+/-0.1 mmol/L, respectively (mean+/-SE) and were not significantly different between groups. Mean serum insulin concentration in treatment ponies was 1036+/-55 microU/mL vs. 14.6 microU/mL in controls. All ponies in the treatment group developed clinical and histological laminitis (Obel grade 2) in all four feet within 72 h (55.4+/-5.5h), whereas none of the control ponies developed laminitis. There was no clinical evidence of gastrointestinal involvement and the ponies showed no signs of systemic illness throughout the experiment. The data show that laminitis can be induced in healthy young ponies, with no prior history of laminitis, by maintaining prolonged hyperinsulinaemia with euglycaemia. This suggests a role for insulin in the pathogenesis of laminitis, independent of hyperglycaemia, or alterations in hind-gut fermentation. For the clinician, early detection and control of hyperinsulinaemia may facilitate management of endocrinopathic laminitis.  相似文献   

14.
Reasons for performing study: Several conditions associated with laminitis in horses are also associated with insulin resistance, which represents the failure of glucose uptake via the insulin‐responsive glucose transport proteins in certain tissues. Glucose starvation is a possible mechanism of laminitis, but glucose uptake mechanisms in the hoof are not well understood. Objectives: To determine whether glucose uptake in equine lamellae is dependent on insulin, to characterise the glucose transport mechanism in lamellae from healthy horses and ponies, and to compare this with ponies with laminitis. Methods: Study 1 investigated the effects of insulin (300 µU/ml; acute and 24 h) and various concentrations of glucose up to 24 mmol/l, on 2‐deoxy‐D‐[2,6‐3H]glucose uptake in hoof lamellar explants in vitro. Study 2 measured the mRNA expression of GLUT1 and GLUT4 transport proteins by PCR analysis in coronary band and lamellar tissue from healthy horses and ponies, ponies with insulin‐induced laminitis, and ponies suffering from chronic laminitis as a result of equine Cushing's syndrome. Results: Glucose uptake was not affected by insulin. Furthermore, the relationship between glucose concentration and glucose uptake was consistent with an insulin‐independent glucose transport system. GLUT1 mRNA expression was strong in brain, coronary band and lamellar tissue, but was weak in skeletal muscle. Expression of GLUT4 mRNA was strong in skeletal muscle, but was either absent or barely detectable in coronary band and lamellar tissue. Conclusions: The results do not support a glucose deprivation model for laminitis, in which glucose uptake in the hoof is impaired by reduced insulin sensitivity. Hoof lamellae rely on a GLUT1‐mediated glucose transport system, and it is unlikely that GLUT4 proteins play a substantial role in this tissue. Potential relevance: Laminitis associated with insulin resistance is unlikely to be due to impaired glucose uptake and subsequent glucose deprivation in lamellae.  相似文献   

15.
Glucose tolerance and insulin sensitivity in ponies and Standardbred horses   总被引：3，自引：0，他引：3  
The existence of an innate insulin insensitivity in ponies was investigated and compared with the situation in larger breeds of horse. Ponies that were fat or had previously suffered laminitis were found to be far more intolerant to oral glucose loading (1 g/kg bodyweight [bwt]) than normal ponies or Standardbreds. These ponies also exhibited a far greater response in plasma insulin levels after glucose loading. Insulin response tests (0.4 iu/kg bwt insulin intravenously) showed only a minimal and very protracted response in both the fat and laminitic groups. The relevance of these findings in regulation of carbohydrate and lipid metabolism, and their role in the pathogenesis of hyperlipaemia, are discussed.  相似文献   

16.
In the horse, resting insulin concentration (INS), the glucose-to-insulin ratio (G:I), and the reciprocal of the square root of insulin (RISQI = 1/√INS) are commonly used to estimate insulin sensitivity, whereas the modified insulin-to-glucose ratio (MIRG = [800 – 0.30 × (INS -50)2]/(GLU – 30) is used to estimate pancreatic beta-cell responsiveness. Because no estimates of their within-horse variability and repeatability have been reported, the objective of this study was to evaluate the within-horse variation of these estimates. Resting blood samples were obtained from six healthy equids (three geldings, two mares; mean ± SD body weight, 525.0 ± 43.36 kg; mean age, 9.8 ± 8.2 years; and one pony gelding: 293 kg; 12 years) on three consecutive days in week 1 and again in week 2. Samples were collected at 12:00 noon, approximately 6 hours postprandially. Serum insulin and plasma glucose (GLU) concentrations were analyzed and used to calculate G:I, RISQI, and MIRG, as well as the insulin to glucose ratio (I:G). The coefficient of variation was used to determine within-horse variation, and repeatability was determined using the repeatability coefficient (RC; measurements from a single horse should differ less than the RC for 95% of the pairs). The mean coefficients of variation (CVs) for resting GLU, INS, G:I, I:G, MIRG, and RISQI were 5.5%, 33.7%, 36.0%, 31.6%, 22.3%, and 18.6%, respectively. All variables had values that differed more than the RC in at least one horse. These data suggest that care should be taken when interpreting insulin sensitivity estimates from a single blood sample.  相似文献   

17.
Reasons for performing study: Anatomical changes in the hoof lamellar tissue induced by prolonged hyperinsulinaemia have not been described previously. Analysis of the induced lesions may promote understanding of hyperinsulinaemic laminitis pathogenesis and produce clinical benefit. Objectives: To use light and transmission electron microscopy (TEM) to document hoof lamellar lesions in ponies clinically lame after prolonged hyperinsulinaemia. Methods: Nine clinically normal, mature ponies were allocated randomly to either a treatment group (n = 5) or control group (n = 4). The treatment group received insulin via a modified, prolonged euglycaemic hyperinsulinaemic clamp technique (EHCT) and were subjected to euthanasia when clinical signs of Obel grade II laminitis occurred. The control group was sham treated with an equivalent volume of 0.9% saline and killed at 72 h. Lamellar tissues of the right front feet were harvested and processed for TEM. Results: Lamellae from insulin treated ponies were attenuated and elongated with many epidermal basal cells (EBC) in mitosis. Unlike carbohydrate induced laminitis in horses there was no global separation at the lamellar dermal/epidermal interface among ponies. Sporadic EBC basement membrane (BM) separation was associated with the proximity of infiltrating leucocytes. In 2 ponies, the lamellar BM was thickened. The number of hemidesmosomes/μm of BM was decreased in all insulin treated ponies. Conclusions: Prolonged hyperinsulinaemia causes unique lamellar lesions normally characteristic of acute and chronic laminitis. Lamellar proliferation may be an insulin effect through its mitogenic pathway. Aberrant lamellar mitosis may lengthen and weaken the lamellar, distal phalanx attachment apparatus and contribute to the clinical signs that developed. Potential relevance: The study shows that insulin alone, in higher than normal circulating concentrations, induces profound, changes in lamellar anatomy. Medical control of insulin resistance and hyperinsulinaemia may ameliorate lesions and produce clinical benefit.  相似文献   

18.
Abnormalities of insulin metabolism include hyperinsulinaemia and insulin resistance, and these problems are collectively referred to as insulin dysregulation in this review. Insulin dysregulation is a key component of equine metabolic syndrome: a collection of endocrine and metabolic abnormalities associated with the development of laminitis in horses, ponies and donkeys. Insulin dysregulation can also accompany prematurity and systemic illness in foals. Causes of insulin resistance are discussed, including pathological conditions of obesity, systemic inflammation and pituitary pars intermedia dysfunction, as well as the physiological responses to stress and pregnancy. Most of the discussion of insulin dysregulation to date has focused on insulin resistance, but there is increasing interest in hyperinsulinaemia itself and insulin responses to feeding. An oral sugar test or in‐feed oral glucose tolerance test can be performed to assess insulin responses to dietary carbohydrates, and these tests are now recommended for use in clinical practice. Incretin hormones are likely to play an important role in postprandial hyperinsulinaemia and are the subject of current research. Insulin resistance exacerbates hyperinsulinaemia, and insulin sensitivity can be measured by performing a combined glucose‐insulin test or i.v. insulin tolerance test. In both of these tests, exogenous insulin is administered and the rate of glucose uptake into tissues measured. Diagnosis and management of hyperinsulinaemia is recommended to reduce the risk of laminitis. The term insulin dysregulation is introduced here to refer collectively to excessive insulin responses to sugars, fasting hyperinsulinaemia and insulin resistance, which are all components of equine metabolic syndrome.  相似文献   

19.
OBJECTIVE: To determine whether pasture, and specifically the addition of fructan carbohydrate to the diet, induces exaggerated changes in serum insulin concentration in laminitispredisposed (LP) ponies, compared with ponies with no history of the condition, and also to determine insulin responses to the dexamethasone suppression test. DESIGN: Prospective study. ANIMALS: 10 LP and 11 control adult nonobese mixed-breed ponies. PROCEDURES: Insulin-modified IV glucose tolerance tests were performed (5 ponies/group). In diet studies, ponies were kept on pasture and then changed to a hay diet (10 ponies/group). Second, ponies were maintained on a basal hay diet (4 weeks) before being fed a hay diet supplemented with inulin (3 g/kg/d [1.4 g/lb/d]). Serum insulin and plasma glucose concentrations were analyzed before and after dietary changes. Serum cortisol and insulin concentrations were also measured in a standard dexamethasone suppression test. RESULTS: The LP ponies were insulin resistant (median insulin sensitivity of 0.27 x 10(4) L min(-1) mU(-1) in LP ponies, compared with 0.64 x 10(4) L min(-1) mU(-1) in control ponies). Median insulin concentration in LP ponies was significantly greater than that in control ponies at pasture, decreased in response to feeding hay, and was markedly increased (5.5-fold) following the feeding of inulin with hay. The LP ponies had a greater increase in serum insulin concentration at 19 hours after dexamethasone administration (median, 222.9 mU/L), compared with control ponies (45.6 mU/L). CONCLUSIONS AND CLINICAL RELEVANCE: Nonobese ponies predisposed to develop laminitis had compensated insulin resistance, and this phenotype was revealed by feeding plant fructan carbohydrate or by dexamethasone administration.  相似文献   

20.
Ponies were evaluated for their response to feed withholding and exogenous administration of corticosteroids (dexamethasone 0.04 mg/kg intramuscular [IM]) in an attempt to reproduce the hyperlipemia syndrome. Because insulin resistance has been associated with hyperlipemia, all ponies were initially evaluated for insulin response to an oral glucose load and normal dexamethasone suppression of serum cortisol. Four ponies were identified as hyperinsulinemic reflecting insulin resistance. All ponies had suppressed cortisol concentrations following dexamethasone administration. Feed withdrawal resulted in hypertriglyceridemia by 48 hours in all ponies. Very low density lipoprotein-triglyceride (VLDL) fraction was primarily elevated. The administration of dexamethasone failed to increase the degree of triglyceridemia. Although insulin resistance has been proposed as the likely cause of the hypertriglyceridemia in ponies, in this study four of eight ponies were considered to have normal insulin responses and yet still developed hypertriglyceridemia.  相似文献   

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