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 dietary carbohydrate sources on plasma glucose, insulin and IGF-I levels in multiparous sows

Effects of different carbohydrate sources on plasma glucose, insulin and insulin-like growth factor-I (IGF-I) levels were compared to subsequently be able to study effects of insulin-stimulating diets on follicle development in sows. The following feed components were tested in 12 sows during six consecutive test periods of 9.5 days: dextrose (DEX), sucrose (SUC), lactose (LAC), dextrose plus lactose (DL), sucrose plus lactose (SL), dextrose plus sugarbeet pulp (DSBP) and control (CON). On day 2, 5 and 9 of each test period, plasma glucose (only at day 9), insulin and IGF-I profiles were determined. Despite similar glucose profiles for all diets, the postprandial insulin response was higher for DL and SL compared with CON and LAC; the other diets were intermediate. Plasma IGF-I levels were higher in CON, LAC and SL compared with DSBP, but differences were only marginal. It was concluded that dextrose and sucrose have the potential to stimulate fast and high insulin peaks, especially when combined with additional lactose. Despite the high dextrose in the DSBP diet, the insulin response was flattened, probably due to the viscosity of sugarbeet pulp. The results show that modulation of plasma insulin levels by dietary carbohydrates seems possible in anabolic sows, but IGF-I levels are less easily modified.     

Effects of diet and weight gain on circulating tumour necrosis factor‐α concentrations in Thoroughbred geldings

Low‐grade inflammation precedes the development of obesity‐related metabolic disorders in humans, but whether the same is true in the horse is not known. The objective of this study was to examine the effects of weight gain and diet on the inflammatory state of horses as determined by serum concentrations of tumour necrosis factor‐α (TNF), an inflammatory cytokine. Fifteen mature Thoroughbred geldings with an initial body weight (BW) of 519 ± 12 kg and body condition score (BCS) of 4.3 ± 0.1 were fed a diet of hay plus a concentrate that was either high in non‐structural carbohydrates (NSC) (i.e. starch and sugar), similar to those commercially available (CON) or one that had the energy source replaced with fat and fibre (FAT) for 32 weeks. Weight gain was achieved by feeding an additional 20 Mcal/day in excess of digestible energy maintenance requirements and resulted in a final BW of 608 ± 12 kg and BCS of 6.9 ± 0.1. Horses were exercised twice daily at a walk during the weight gain period. Horses were assessed bi‐weekly for BW and BCS. Serum TNF was analysed from blood samples collected at 4‐week intervals. Although treatment groups began the study with similar mean serum TNF concentrations, 12 weeks of FAT feeding promoted a decrease in circulating TNF that was maintained throughout the study with the exception of weeks 20 and 32. For either diet, there were no linear correlations between serum TNF concentration and BCS when horses increased in BCS from four to seven. The higher level of TNF observed in horses fed the CON diet indicates an increase in some level of systemic inflammation that was independent of their weight gain from a moderately thin to fleshy condition. The influence of diet on serum TNF concentrations should be investigated in horses fed to maintain body condition.     

Effect of dietary restriction on body condition,composition and welfare of overweight and obese pony mares

Reasons for performing study: Increased prevalence of obesity among UK horses and ponies demands evidence‐based advice to promote weight loss. Hypothesis: Restriction of dry matter intake (DMI) to 1% of body mass (BM, 6% of predicted maintenance digestible energy [DE] requirements) would promote weight loss without compromise to health. Methods: Five mature (mean ± s.e. 10 ± 2 years), overweight/obese pony mares (BM, 257 ± 20 kg: body condition score [BCS] 6.8/9 ± 0.5) were studied over 12 weeks. Animals were individually housed. Daily provision of a chaff‐based, complete diet (measured DE, 8.5 MJ/kg DM) was restricted to 1% of actual BM as DMI daily. BCS, girth measurements and ultrasound‐derived measures of subcutaneous fat depth overlying the gluteal region and 12th intercostal space (rib‐eye) were recorded weekly. Body fat content was estimated at the beginning and end of the study by deuterium oxide dilution methods. Clinical biochemistry was monitored weekly. Behaviour was observed (24 h, 3/5 ponies) on 3 occasions. Results: BM decreased by 4.3 ± 1.1% during the first week and thereafter by 0.7 ± 0.1% of BM at end of Week 1 each week. BCS remained constant. Heart and belly girths, rump width and subcutaneous fat depth at rib‐eye decreased significantly with time and BM. Fat comprised 45 ± 19% of BM loss. Fatter animals lost relatively more fat. With decreased feeding activity, time spent in ‘play’ and rest increased by 36 ± 11% and 438 ± 95%, respectively. Conclusions: This plane of nutrition resulted in an overall rate of weight loss of 1% of outset BM weekly. BCS was not a useful index of early weight loss but heart and belly girths and subcutaneous rib‐eye fat were identified as alternative markers. Potential relevance: This study provides an evidence‐base for the management of weight loss in obese animals, especially those for which exercise may be contra‐indicated.     

Measurement of C‐peptide concentrations and responses to somatostatin,glucose infusion,and insulin resistance in horses

Reasons for performing study: Hyperinsulinaemia is detected in horses with insulin resistance (IR) and has previously been attributed to increased pancreatic insulin secretion. Connecting peptide (C‐peptide) can be measured to assess pancreatic function because it is secreted in equimolar amounts with insulin and does not undergo hepatic clearance. Hypothesis: A human double antibody radioimmunoassay (RIA) detects C‐peptide in equine serum and concentrations would reflect responses to different stimuli and conditions. Methods: A validation procedure was performed to assess the RIA. Six mature mares were selected and somatostatin administered i.v. as a primed continuous rate infusion, followed by 50 nmol human C‐peptide i.v. Insulin and C‐peptide concentrations were measured in horses (n = 6) undergoing an insulin‐modified frequently sampled i.v. glucose tolerance test, and in horses with insulin resistance (n = 10) or normal insulin sensitivity (n = 20). Results: A human RIA was validated for use with equine sera. Endogenous C‐peptide secretion was suppressed by somatostatin and median (range) clearance rate was 0.83 (0.15–1.61) ml/min/kg bwt. Mean ± s.d. C‐peptide‐to‐insulin ratio significantly (P = 0.004) decreased during the glucose tolerance test from 3.60 ± 1.95 prior to infusion to 1.03 ± 0.18 during the first 20 min following dextrose administration. Median C‐peptide and insulin concentrations were 1.5‐ and 9.5‐fold higher, respectively in horses with IR, compared with healthy horses. Conclusions: Endogenous C‐peptide secretion decreases in response to somatostatin and increases after dextrose infusion. Results suggest that relative insulin clearance decreases as pancreatic secretion increases in response to dextrose infusion. Hyperinsulinaemia in insulin resistant horses may be associated with both increased insulin secretion and decreased insulin clearance. Potential relevance: Both C‐peptide and insulin concentrations should be measured to assess pancreatic secretion and insulin clearance in horses.     

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.     

A 90‐day adaptation to a high glycaemic diet alters postprandial lipid metabolism in non‐obese horses without affecting peripheral insulin sensitivity

High glycaemic feeds are associated with the development of insulin resistance in horses. However, studies that evaluated the effect of high glycaemic feeds used horses that either ranged in body condition from lean to obese or were fed to increase body condition over a period of months; thus, the ability of high glycaemic feeds to induce insulin resistance in lean horses has not been determined. This study evaluated the insulin sensitivity of 18 lean horses fed a 10% (LO; n = 6), 20% (MED; n = 6) or 60% (HI; n = 6) non‐structural carbohydrate complementary feed for 90 days. Although both the MED and HI diets increased insulinaemic responses to concentrate feeding in relation to the LO diet (p > 0.05), neither induced insulin resistance, as assessed by glucose tolerance test, following the 90‐day feeding trial. Interestingly, the post‐feeding suppression of plasma non‐esterified fatty acids was less pronounced in HI‐fed horses (p = 0.054) on days 30 and 90 of the study, potentially indicating that insulin‐induced suppression of adipose tissue lipolysis was reduced. As insulin‐resistant animals often have elevated plasma lipid concentrations, it is possible that altered lipid metabolism is an early event in the development of insulin resistance. The effects of high glycaemic feeds that are fed for a longer duration of time, on glucose and lipid metabolism, should be investigated further.     

Effects of intravenous ghrelin injection on plasma growth hormone,insulin and glucose concentrations in calves at weaning

Ghrelin action, which stimulates growth hormone (GH) secretion, may alter during the weaning period in calves. Our objective was to compare the effects of intravenous ghrelin injection on plasma GH, insulin and glucose concentrations in calves around the weaning period. Four Holstein bull calves were fed whole milk and allowed free access to solid feeds, and weaned at 7 weeks of age. Measurements were performed at weeks 1, 2, 4, 6, 7, 9, 11 and 13, when calves were intravenously injected with ghrelin (1.0 μg/kg body weight (BW)) through a catheter, and jugular blood samples were obtained temporally relative to the injection time. Estimated digestible energy intake per metabolic BW transiently decreased at week 7 because of low solid intake immediately after weaning, and thereafter gradually increased. Plasma insulin and glucose concentrations were not affected by ghrelin injection at all ages. In contrast, plasma GH concentrations increased with ghrelin injection at all ages. The incremental area of GH at week 7 was greatest and significantly higher compared with weeks 2, 4, 6 and 9. This result suggests that nutrient insufficiency immediately after weaning enhances GH responsiveness to ghrelin.     

Effects of pre‐operative administration of medetomidine on plasma insulin and glucose concentrations in healthy dogs and dogs with insulinoma

ObjectiveTo investigate the effect of medetomidine on plasma glucose and insulin concentrations in dogs with insulinoma and in healthy dogs undergoing anesthesia and surgery.AnimalsTwenty–five dogs with insulinoma and 26 healthy dogs.MethodsIn dogs with insulinoma, medetomidine (5 μg kg^?1) was randomly included (n = 12) or omitted (n = 13) from the pre–anesthetic medication protocol, which typically contained an opioid and an anticholinergic. Healthy dogs received medetomidine (5 μg kg^?1; n = 13) or acepromazine (0.04 mg kg^?1; n = 13) plus an opioid (morphine 0.5 mg kg^?1) and an anticholinergic (atropine 0.04 mg kg^?1) as pre–anesthetic medications. Pre–anesthetic medications were given intramuscularly. Plasma glucose and insulin concentrations were measured before (sample 1) and 30 minutes after pre–anesthetic medication (sample 2), and at the end of surgery in dogs with insulinoma or at 2 hours of anesthesia in healthy dogs (sample 3). Glucose requirement to maintain intra–operative normoglycemia in dogs with insulinoma was quantified and compared. Data were analyzed with anova and Bonferroni post–test, t–tests or chi–square tests as appropriate with p < 0.05 considered significant. Data are shown as mean ± SD.ResultsMedetomidine significantly decreased plasma insulin concentrations and increased plasma glucose concentrations in healthy dogs and those with insulinoma. These variables did not change significantly in the dogs not receiving medetomidine. In the dogs with insulinoma, intra–operative glucose administration rate was significantly less in the animals that received medetomidine compared to those that did not.ConclusionsPre–anesthetic administration of medetomidine significantly suppressed insulin secretion and increased plasma glucose concentration in dogs with insulinoma and in healthy dogs undergoing anesthesia and surgery.Clinical relevanceThese findings support the judicious use of medetomidine at low doses as an adjunct to the anesthetic management of dogs with insulinoma.     

Age and body weight effects on glucose and insulin tolerance in colony cats maintained since weaning on high dietary carbohydrate

High dietary carbohydrate is suggested to promote development of diabetes mellitus in cats. Glucose tolerance, insulin sensitivity, and insulin secretion were assessed in young [0.8–2.3 (median = 1.1) years, n = 13] and mature [4.0–7.0 (median 5.8) years, n = 12] sexually intact females of a large (n ? 700) feline colony in which only dry‐type diets (35% metabolizable energy as carbohydrate) were fed from weaning. Insulin sensitivity was assessed from the ‘late‐phase’ (60–120 min) plasma insulin response of intravenous glucose tolerance tests (IVGTTs) and from fractional change in glycaemia from baseline 15 min after an insulin bolus (0.1 U/kg, i.v.). Insulin secretion was assessed from the ‘early‐phase’ (0–15 min) plasma insulin response of IVGTTs. Compared to the young cats, the mature cats had greater body weights [2.3–3.8 (median = 2.9) vs. 3.0–6.3 (median = 4.0) kg, p < 0.01], greater late‐phase insulin responses (p < 0.05), lower insulin‐induced glycaemic changes (p = 0.06), lower early‐phase insulin responses (p < 0.05), and non‐significantly different rates of glucose disposal. The late‐phase insulin response was correlated with body weight and age (p < 0.05). When group assignments were balanced for body weight, the age‐group differences and correlations became non‐significant. The findings indicate that body weight gain is more likely than dry‐type diets to induce the pre‐diabetic conditions of insulin resistance and secretion dysfunction.     

Effect of mixing dietary fibre (purified lignocellulose or purified pectin) and a corn meal on glucose and insulin responses in healthy horses

The aim of this study was to investigate the effect of the addition of a purified soluble (pectin) and insoluble (lignocellulose) fibre to a starchy meal on post‐prandial glucose and insulin responses in healthy horses. Four horses were fed in a randomized order three different diets: (i) cracked corn, (ii) cracked corn mixed with purified lignocellulose, and (iii) cracked corn mixed with purified pectin. Each diet was adjusted to a starch intake of 2 g/kg bodyweight (BW). Lignocellulose was aligned to an intake of 0.2 g/kg BW, and pectin was fed in a dosage of 0.1 g/kg BW. Each period consisted of a 10‐day acclimatization to the diet (fed once per day); during this time, the horses were fed 1.2 kg hay/100 kg BW/day. Blood was collected after each acclimatization period before and after the test meal was fed, without any hay. The increase in plasma glucose and insulin, peak values, and area under the curves were similar for all diets. The present findings suggest that adding purified soluble or insoluble fibre to a corn meal does not affect post‐prandial glucose and insulin responses in healthy horses. Feeding strategies for horses with a high energy requirement should include a starch reduction per meal, rather than the addition of purified fibre.     

干奶期不同能量摄入对围产期乳牛血液葡萄糖胰高血糖素和胰岛素浓度的影响

将围产期健康乳牛30头随机分为3组，分别于产前第28d开始饲喂标准日粮（能量摄入i00％组）、标准日粮增加20％的日粮（能量摄入120％组）和标准日粮减少20％的日粮（能量摄入80％组），产后备组乳牛均饲喂标准泌乳日粮，至产后第56d结束，观察干奶期不同能量摄入水平对围产期健康乳牛血液葡萄糖、胰高血糖素和胰岛素浓度的影响。结果表明，产前低能饲喂可以增加围产期乳牛血浆葡萄糖浓度，干奶期不同能量摄入水平对围产期健康乳牛血液葡萄糖、胰高血糖素和胰岛素浓度起重要调节作用。     

Post‐glucose load changes of plasma key metabolite and insulin concentrations during pregnancy and lactation in ewes with different susceptibility to pregnancy toxaemia

Insulin resistance during late gestation may act as a predisposing factor of ovine pregnancy toxaemia (OPT). To evaluate the insulin action on energy metabolism in ewes with different susceptibilities to OPT, intravenous glucose tolerance tests (1 mmol glucose/kg body weight) were performed in 5.6 ± 0.7 year old, slightly underfed German Blackheaded Mutton ewes [high‐risk (HR) ewes] and 2.5 year old, overnourished Finnish Landrace ewes [low‐risk (LR) ewes] during mid and late pregnancy, during early lactation and during the dry period. Plasma samples were analysed for glucose, insulin, non‐esterified fatty acids (NEFA) and β‐hydroxybutyrate (β‐HB). The glucose elimination rate and the glucose‐stimulated first‐phase insulin secretion were significantly (p < 0.05) lower in the HR, in relation to the LR group combining the data of all gestational stages. The basal rate of lipolysis was significantly increased in the HR ewes during late pregnancy, but the NEFA clearance after the glucose load was similar in both groups during all reproductive stages. Plasma β‐HB concentrations decreased only in the LR ewes after the glucose load during late pregnancy. Results indicate an insulin resistance in the HR ewes regarding the glucose utilization and the ketone body formation during late pregnancy. The insulin resistance in the HR ewes may represent one predisposing factor responsible for the susceptibility to OPT. Further scientific work is necessary to elucidate whether this insulin resistance was due to breed, age or nutritional state.     

The effects of maternal health and body condition on the endocrine responses of neonatal foals

Reasons for performing the study: Chronic and acute alterations in maternal nutrient intake during pregnancy alter pancreatic and hypothalamo‐pituitary‐adrenal (HPA) axis function in the offspring, before and after birth. Little is known about these effects. Objective: To determine whether maternal nutrient restriction caused by natural infection with Streptococcus equi altered endocrine function in neonatal foals born from mares fed a maintenance or high plane of nutrition throughout pregnancy. Methods: Ten primiparous mares received either a diet to maintain moderate body condition score (Moderate, n = 5) or a near ad libitum feeding regime to maintain a high body condition score (High, n = 5) throughout pregnancy. All mares inadvertently became infected with Streptococcus equi in mid gestation and lost approximately 10% body mass. Results: Maternal insulin and glucose concentrations decreased (P<0.05) during, and one month following, the weight loss period. High mares weighed more (P<0.05) at parturition than Moderate mares; all foals were healthy. Gestational age, foal bodyweights, placental and clinical parameters after birth were no different between the 2 groups. Foal plasma cortisol and glucose responses to exogenous adrenocorticotrophic hormone and insulin, respectively, were similar for both groups. Insulin concentrations during glucose tolerance test were significantly higher (P<0.05) in foals from Moderate than High mares and compared with foals studied previously from healthy, well‐fed mares, suggesting that the β cell sensitivity to glucose was enhanced in Moderate. Conclusion: Acute nutrient restriction in mid gestation caused by maternal illness and inappetence, superimposed on a maintenance feed intake throughout pregnancy, enhanced insulin secretion to glucose in foals. Nutritional programming of pancreatic β cells, but not the HPA axis, appeared to depend on the level of nutrition before and after the weight loss period. Potential relevance: Disturbances in neonatal pancreatic β cell function programmed during pregnancy may predispose foals to metabolic problems in later life.