Effects of endotoxaemia and carbohydrate overload on glucose and insulin dynamics and the development of laminitis in horses

Reasons for performing study: Insulin resistance (IR) is a risk factor for pasture‐associated laminitis in equids and alimentary carbohydrate overload may trigger laminitis. Whether glucose metabolism responses to carbohydrate overload are more pronounced in insulin‐resistant horses requires further study. Hypothesis: Horses pretreated with endotoxin to alter insulin sensitivity differ significantly in their glucose and insulin responses to carbohydrate overload. Methods: Horses (n = 24) were divided into 3 groups. A lipopolysaccharide (LPS; n = 8) group that received endotoxin as an 8 h 7.5 ng/kg bwt/h i.v. continuous rate infusion, an oligofructose (OF; n = 8) group that received an infusion of saline followed by 5 g/kg bwt OF via nasogastric intubation, and a LPS/OF (n = 8) group that received LPS followed 16 h later by OF. Glucose and insulin dynamics were evaluated at ‐24 h and 48 h using the frequently sampled i.v. glucose tolerance test and minimal model analysis. Physical examinations and haematology were performed and the severity of laminitis assessed. Results: Horses receiving LPS developed leucopenia and both LPS and OF induced clinical signs consistent with systemic inflammation. Insulin sensitivity significantly decreased (P<0.001) over time, but responses did not differ significantly among groups. Time (P<0.001) and treatment × time (P = 0.038) effects were detected for the acute insulin response to glucose, with mean values significantly increasing in LPS and LPS/OF groups, but not the OF group. Five horses in the LPS/OF group developed clinical laminitis compared with 0 and 2 horses in the LPS and OF groups, respectively. Conclusions: Endotoxaemia and carbohydrate overload reduce insulin sensitivity in horses. Endotoxin pretreatment does not affect the alterations in glucose metabolism induced by carbohydrate overload. Potential relevance: Insulin sensitivity decreases after carbohydrate overload in horses, which may be relevant to the development of pasture‐associated laminitis.     

Effects of a supplement containing chromium and magnesium on morphometric measurements, resting glucose, insulin concentrations and insulin sensitivity in laminitic obese horses

Reasons for performing study: Obesity and insulin resistance are risk factors for laminitis in equids and supplements containing chromium and magnesium might improve insulin sensitivity. Hypothesis: A supplement containing chromium, magnesium and other nutraceuticals would alter morphometric measurements, blood variables, and insulin sensitivity in laminitic obese horses. Methods: Twelve previously laminitic obese (body condition score ≥ 7/9) horses were randomly allocated to treatment (n = 6) and control (n = 6) groups and 2 obese horses with clinical laminitis were included in the treatment group. Treated animals received 56 g supplement with 0.25 kg oats once daily for 16 weeks. The supplement contained chromium (5 mg/day as yeast), magnesium (8.8 g/day as oxide/proteinate), and other nutraceuticals. Insulin‐modified frequently sampled i.v. glucose tolerance tests were performed with hay provided at 0, 8 and 16 weeks, and insulin sensitivity was estimated by minimal model analysis. Physical measurements were collected at the same points. Horses were not exercised. Results: Hyperinsulinaemia (>30 µu/ml) was detected in 12 of 14 horses prior to treatment. Glucose and insulin data from one mare with clinical laminitis were excluded because of persistent pain. Mean ± s.d. insulin sensitivity was 0.64 ± 0.62 × 10^?4 l/min/mu prior to treatment for the remaining 13 horses. Time and treatment × time effects were not significant for any of the variables examined, with the exception of resting insulin concentrations, which significantly increased over time (P = 0.018). Health status remained the same. Conclusions: The supplement containing chromium and magnesium evaluated in this study did not alter morphometric measurements, blood variables, resting insulin concentrations or insulin sensitivity in laminitic obese horses. Potential relevance: Additional research is required to determine the appropriate use of chromium and magnesium supplements in horses.     

Pain management for laminitis in the horse

The inability to control pain is the most common reason for cessation of treatment and euthanasia in cases of laminitis, yet pain also serves a unique protective function in these cases, particularly in the acute phase when lamellar integrity is weakened. Successful analgesia requires an understanding of the disease pathophysiology, the sources of pain in laminitis, methods of serial pain evaluation, and methods of analgesia including systemic and regional techniques. This review discusses the approach to analgesia including detail of traditional and novel analgesic medications and techniques with specific reference to the laminitis case.     

The effect of metformin on measurements of insulin sensitivity and beta cell response in 18 horses and ponies with insulin resistance

REASONS FOR PERFORMING STUDY: Laminitis in equids is a very common debilitating disease, and insulin resistance (IR) and hyperinsulinaemia are increasingly recognised as important predisposing factors. Pharmacological modification of IR and hyperinsulinaemia might reduce the risk of laminitis. HYPOTHESIS: Metformin, a drug commonly prescribed for treatment of human IR, may also decrease IR in equids. METHODS: Eighteen horses and ponies with IR and recurrent laminitis were treated with 15 mg/kg bwt metformin per os q. 12 h. Each animal served as its own control by comparing pre- and post treatment proxies for IR, insulin sensitivity (IS) and pancreatic beta cell function while controlling for possible dietary and managemental influences on IR. RESULTS: Evidence of significantly improved IS and decreased pancreatic beta cell secretion was found following metformin treatment. The magnitude of effect was greater at earlier resampling (6-14 days) than at later times (23-220 days). Apparent subjective clinical benefits were good but less favourable than effects on IR. CONCLUSIONS: Metformin is safe and appears to increase IS in equids. POTENTIAL RELEVANCE: Metformin may be indicated as a treatment for IR in equids. Further studies are required to define appropriate selection of subjects warranting therapy, dosing schedule and pharmacokinetics.     

Use of proxy measurements of insulin sensitivity and insulin secretory response to distinguish between normal and previously laminitic ponies

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][mu_ins]²/10·l·mg_gluc) than NP (2.6 [3.2][mu_ins]²/10·l·mg_gluc; 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.     

Effects of fat supplementation on plasma glucose,insulin and fatty acid analysis in ponies maintained on a forage‐based diet

The objective of this study was to observe how fat incorporated into an equine forage‐based diet through supplementation altered levels of plasma glucose, insulin and fatty acids. Five Shetland/Hackney cross pony mares were fed alfalfa pellet diets top dressed with commercially available vegetable oil (blend of soya bean, canola and corn oils) at 0%, 5%, 10% or 15% of diet. Ponies were randomly assigned one of four diets to start, with a 14‐day adjustment period between transitioning to another one of the four diets. Ponies were gradually adapted to the new diet within the 14‐day period before a five‐day trial period. Each pony received all four diets by the end of the study. Each trial was a five‐day period with a three‐day sample collection. Blood samples for each collection week were taken 0, 30, 60, 90, 120, 150, 180, 210, 240 and 270 min and at 5, 6, 7, 8, 9 and 10 hr post‐feeding. Excess fat did not impact plasma glucose (p > .1), nor did it affect blood plasma insulin concentration. While there was no time alteration found for plasma fatty acid concentration (p > .1), C14:0 increased when ponies were fed 0% fat and C18:2 decreased when ponies were fed 0% fat. Plasma fatty acids (% of total FA) were higher in C18:0, C18:1, C18:2 and C20:1 in the added fat diets (p < .1). These findings suggest the amounts reported in this study of fat supplementation on a forage‐based diet did influence the fatty acid analysis within the pony, but did not negatively impact blood glucose and insulin concentrations.     

Pemphigus foliaceus in the horse: a retrospective study of 20 cases

Twenty horses with pemphigus foliaceus were seen over a period of 15 years in a veterinary medical teaching hospital. Breeds seen were seven quarterhorses, five thoroughbreds, three cross-bred horses, two Arabians and one of each of the following: standardbred, Tennessee walker and warmblood. There was no breed, age or sex predisposition. Nine were mares, ten were geldings and one was a stallion. Ages ranged from 2.5 months to 25 years, with a mean of 8.6 years. Sixteen (80%) of the pemphigus foliaceus horses first exhibited signs between September and February. There was a statistically significant more common occurrence of pemphigus foliaceus during those months. Signs in the four other horses were first noted in March, May or June. Three of those horses were < 13 months of age. Oedema (14/20) and crusts (13/20) were the most common lesions. Pain was present in 9/20 horses, pruritus in 7/20 and pyrexia in 7/20. Follow-up was available for 13 horses. Five of these horses were euthanased. In three horses the reason for euthanasia was laminitis secondary to treatment. Four horses remained lesion-free after medication was discontinued. Two horses required maintenance medication and are doing well at the time of writing.     

饲粮结构与非结构性碳水化合物比例对绵羊瘤胃代谢参数的影响

旨在探讨绵羊饲粮结构与非结构性碳水化合物比例(SC/NSC为1.57(Ⅰ)、1.95(Ⅱ)、2.29(Ⅲ))对瘤胃发酵参数(pH、VFA、总氮、NH3-N、尿素氮、蛋白氮)的影响。选用6只约1.5岁,体质量25~30 kg,装有瘤胃瘘管的甘肃高山细毛羊羯羊,按3×3重复拉丁方设计(预试期10 d,正试期9 d)。结果表明:采食饲粮Ⅰ的绵羊瘤胃液pH平均值显著低于采食饲粮Ⅱ(P<0.01)、Ⅲ(P<0.05)的绵羊;除处理Ⅰ采食后3 h的pH较低(5.86)外,所有pH测值均在6.2~7.0范围内。瘤胃液TVFA平均值(mmol.L-1)呈现Ⅰ、Ⅱ高于Ⅲ的趋势(P=0.09);处理间乙、丙及其他酸的摩尔比和乙酸/丙酸比均值无显著差异(P>0.05),Ⅰ的丁酸摩尔比均值显著高于Ⅲ(P<0.05)。瘤胃液总氮和蛋白氮均值随SC/NSC值增高而显著下降(P<0.01或P<0.05);氨氮与尿素氮均值在处理间无显著差异(P>0.05)。结果显示,饲粮粗料份额高于60%时,随SC/NSC值增高,绵羊瘤胃液pH上升,TVFA、总氮和蛋白氮平均浓度下降,对氨氮与尿素氮浓度则无显著影响。