The diagnosis of equine insulin dysregulation

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.     

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.     

Endocrine disorders and laminitis

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

Insulin resistance in equine digital vessel rings: an in vitro model to study vascular dysfunction in equine laminitis

Reasons for performing study: One of the causes of equine laminitis is hyperinsulinaemia, which may be associated with endothelial dysfunction and insulin resistance of vessels. Hypothesis and objectives: Insulin resistance can be induced in palmar digital vessels by continued exposure to insulin in vitro. The objective was to evaluate this in vitro model for future studies. Methods: Palmar digital vessel segments were collected immediately after euthanasia from horses with normal insulin/glucose blood values. Four arterial and 4 venous rings (3 mm wide) were prepared and each ring mounted in a tissue bath, containing Tyrode's solution at 37°C, 2 g tension was applied and the rings allowed to equilibrate for 45 min. Of the 4 rings of each vessel type, one was used as a control. One each of the remaining 3 rings was used for incubation with insulin (to induce resistance), wortmannin (to block PI3‐kinase) and PD‐098059 (to block MAP‐kinase), respectively, for 30 min. After the incubation period, the rings were contracted with phenylephrine. When the response reached a plateau, a single dose of insulin was added to the baths and the response of each ring monitored for 30 min. Results: Insulin relaxed the control rings and those treated with PD 098059 but contracted those pretreated with insulin and wortmannin. Normal relaxation responses of the rings were converted to contractions by insulin resistance. Insulin resistance was confirmed by the qualitative response of insulin‐incubated and wortmannin‐incubated rings. Conclusions: This study demonstrated successful induction of insulin resistance in both arterial and venous rings. It also suggested that the MAP‐kinase pathway plays a minor role in controlling vasomotor tone under normal physiological conditions. Potential relevance: The study suggests that the induction of insulin resistance in equine palmar digital vessel rings is reliable and provides a good in vitro model for studying the vascular insulin resistance which may occur in equine laminitis.     

Glucose transport in the equine hoof

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.     

Equine laminitis: Induced by 48 h hyperinsulinaemia in Standardbred horses

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

Factors affecting clinical assessment of insulin sensitivity in horses

Insulin resistance is thought to be involved in the pathogenesis of many equine conditions such as pars intermedia dysfunction, equine metabolic syndrome, diabetes mellitus, hyperlipaemia, laminitis, endotoxaemia and osteochondrosis dissecans (OCD); whereas polysaccharide storage myopathy in Quarter Horses and equine motor neuron disease (EMD) have been associated with increased insulin sensitivity. However, it is clear that there is not one ideal test, in terms of both practicality and accuracy, for evaluating insulin sensitivity in horses and improved diagnostic techniques are required. This review sets out the background to the subject and identifies current knowledge regarding the measurement of insulin sensitivity by tolerance testing and clamping techniques. Factors affecting insulin sensitivity, such as breed, pregnancy, lactation, obesity and nutritional factors are discussed. In addition, the relationship with training, nutritional supplementation and drug administration are considered.     

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

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

Short‐term incubation of equine laminar veins with cortisol and insulin alters contractility in vitro: possible implications for the pathogenesis of equine laminitis

This study investigated the effects of cortisol and insulin, hormones that affect both glycaemic status and vascular function, on the in vitro contractility of isolated healthy equine small laminar veins. Small veins (150–500 μm) draining the digital laminae from healthy horses or ponies were investigated by wire myography. Concentration response curves were constructed for noradrenaline (NA), phenylephrine (PE), endothelin‐1 (ET‐1) and 5‐hydroxytryptamine (5‐HT) in the presence of either cortisol (10^?6 m ) or insulin (1000 μIU/mL). Cortisol significantly increased the maximum contractility of laminar veins to the vasoconstrictors NA and 5‐HT but decreased the maximal contraction to ET‐1. Insulin decreased the contractility of vessels to PE and ET‐1. It is possible that short‐term cortisol excess could enhance venoconstrictor responses to 5‐HT and NA in laminar veins in vivo, thereby predisposing to laminitis. Additionally, a reduction in the ability of insulin to counteract alpha‐adrenoreceptor and ET‐1‐mediated contraction, likely to occur in subjects with insulin resistance, may further exacerbate venoconstriction in animals prone to laminitis. These mechanisms may also predispose horses with disorders such as equine Cushing's disease and equine metabolic syndrome to laminitis.     

Equine laminitis: Ultrastructural lesions detected in ponies following hyperinsulinaemia

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.     

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.     

Assessment of Insulin and Glucose Dynamics by Using an Oral Sugar Test in Horses

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 [r_s] = 0.58; P = .012) and AUCi (r_s = 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.     

Induction of laminitis by prolonged hyperinsulinaemia in clinically normal ponies

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.     

Histopathology of insulin-induced laminitis in ponies

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.     

Investigation of the Effects of a Dietary Supplement on Insulin and Adipokine Concentrations in Equine Metabolic Syndrome/Insulin Dysregulation

High insulin concentrations are a common clinical feature of equine metabolic syndrome (EMS) and insulin dysregulation. Hyperinsulinemia can induce laminitis, so reduction of insulin concentrations in response to an oral challenge should decrease risk. In human studies, diets containing a polyphenol (resveratrol) led to improvements in insulin sensitivity. In rodents, the addition of leucine to a resveratrol supplement caused a decrease in the amount of resveratrol needed to achieve a clinical effect. We hypothesize a supplementation with a low dose of a synergistic polyphenol and amino acid blend including leucine (SPB+L) would improve metabolic health in EMS/insulin dysregulated horses. Fifteen EMS/ID horses received a high or low dose of SPB+ L daily for 6 weeks. Insulin during an oral sugar test (OST), body condition score, weight, baseline high-molecular-weight (HMW) adiponectin, triglycerides, nonesterified fatty acids, and tumor necrosis factor alpha were assessed before supplementation (PRE) and after supplementation (POST) via paired Student’s t-tests and a repeated-measures mixed-model analysis of variance (significant at P < .05). There were no differences between doses. Horses in the POST group weighed significantly less, had significantly higher baseline HMW adiponectin concentrations, and had significantly lower insulin concentrations at 60- and 75-minute time points (P < .05). Insulin concentrations of the horsesin the POST group, but not in the PRE group, were lower and similar to results from the study conducted three years before the present study (PRIOR) for 0- and 60-minute time points (P < .002). An increased HMW adiponectin level supports increasing insulin sensitivity after supplementation. These results suggest that SPB + L supplementation at either dose leads to improvements in the clinical manifestations of EMS/insulin dysregulation, potentially reducing laminitis risk.     

The equine metabolic syndrome peripheral Cushing's syndrome.

Certain management practices tend to promote the development of obesity (metabolic syndrome) in mature horses as they enter their teenage years. These management practices include the provision of starch-rich (high glycemic index) and fat-supplemented rations to healthy horses that are relatively inactive. Some horse breeds and ponies appear to be genetically predisposed to metabolic syndrome. The accretion of intra-abdominal adiposity by equids is associated with the development of insulin insensitivity (hyperinsulinemia), glucose intolerance, dyslipidemia, hypertension, and insidious-onset laminitis. Omental adipocytes are metabolically active, secreting free fatty acids and hormonally active mediators including cortisol, leptin, and resistin that might contribute to persistence and worsening of insulin refractoriness and the obese phenotype. We have hypothesized that obesity-associated laminitis arises as a consequence of vascular changes and a hypercoagulable state, similar to the development of atherosclerosis in human type 2 diabetes. Several molecular mechanisms that might serve to explain the development of insulin insensitivity as a result of excessive adiposity have been incriminated. Little investigation into the relationship between obesity, insulin insensitivity, and laminitis in horses has been reported to date. Insulin sensitivity and glucose tolerance can be improved by dietary restriction and exercise aimed at reversing omental obesity. Management practices that promote the development of obesity are likely initiated during the first 10 years of the horse's life. Veterinarians and horse owners must recognize that mature-onset obesity in adult horses is associated with a risk for development of laminitis. Obesity and insulin insensitivity might be prevented if horse owners can be educated to feed rations with a relatively lower glycemic index to inactive horses. Investigative research pertaining to the development of antiobesity drugs for human patients is continuing. Greater than 30 new pharmaceuticals are in various stages of research. However, it will likely take many years before any of these drugs are shown to be useful and safe in horses. Lifestyle changes in the form of diet and exercise patterns are still the crux of therapy for both human and equine patients.     

ECEIM consensus statement on equine metabolic syndrome

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

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.     

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.     

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.