Insulin Resistance: What the Research Says

Evidence from 74 peer-reviewed studies

4 RCT

29 Cohort Study

12 Case Report

28 Expert Opinion

1 Thesis

What Professionals Should Know

•Obesity itself may not be the primary driver of insulin resistance in horses—other dietary or management factors warrant investigation before assuming overweight horses are inevitably insulin-dysregulated
•High-fat diets did not confer metabolic protection against obesity-related insulin changes, challenging assumptions that low-glycaemic feeding prevents insulin problems in obese individuals
•Once-daily glucose feeding unexpectedly improved insulin sensitivity markers; feeding patterns and meal frequency may be more important metabolic factors than previously recognized
•Metformin may be a useful therapeutic option for horses with insulin resistance by reducing post-meal blood glucose and insulin spikes, potentially reducing laminitis risk
•A single oral dose of metformin (30 mg/kg) administered 1 hour before feeding appears sufficient to dampen glycaemic responses in both healthy and insulin-resistant horses
•Further clinical trials in naturally occurring insulin-resistant horses are needed before making definitive feeding or treatment recommendations, but results are promising for metabolic disease management
•Chromium and magnesium supplements alone do not improve insulin sensitivity or aid weight loss in obese laminitic horses—alternative management strategies are needed
•Hyperinsulinaemia is highly prevalent in this population; clinicians should not rely on these supplements as a primary intervention for insulin resistance
•Further research is required to establish effective nutraceutical or pharmacological approaches for managing insulin resistance in horses
•Prompt identification and treatment of hyperinsulinaemia in horses with endocrinopathies is critical, as even 48 hours of elevated insulin levels can trigger laminitis
•Digital pulse assessment and hoof wall temperature monitoring may serve as early warning signs of insulin-related laminitis development in at-risk horses
•Insulin resistance management through diet, exercise, and medical intervention should be prioritized in horses with metabolic conditions to prevent laminitis
•Don't assume all overweight horses are metabolically abnormal—check insulin and glucose levels; obesity and hyperinsulinemia are independent risk factors requiring separate management strategies
•Hyperinsulinemia appears to be the primary driver of metabolic dysfunction rather than weight alone; focus diagnostic and management efforts on insulin status regardless of body condition
•Laminitis cases showed unexpected metabolic patterns (lower glucose, higher IGF-1); consider individual biochemical profiling rather than relying solely on body weight or condition scoring
•Arthrospira-based feed additive enriched with chromium, magnesium, and manganese may help manage insulin resistance and weight in metabolically affected horses as part of a comprehensive EMS management program
•This supplement shows promise for reducing inflammatory markers and improving body condition in horses with EMS, potentially reducing reliance on other management interventions
•Consider this as a complementary strategy alongside diet management and exercise for horses struggling with metabolic syndrome
•GLP-1 measurement should not be added to diagnostic protocols for identifying insulin dysregulation or resistance in ponies, as it does not differentiate affected from unaffected animals despite correlating with insulin levels
•High non-structural carbohydrate feeds (glucose tests and breakfast cereal) consistently trigger GLP-1 responses within 30 minutes; this may inform timing of metabolic testing protocols
•The strong GLP-1-insulin correlation confirms the incretin effect operates in ponies, but this relationship alone does not help identify dysregulation cases
•Measuring triglyceride and NEFA responses during oral glucose testing may help identify horses with tissue insulin resistance, potentially aiding in earlier detection of Equine Metabolic Syndrome
•Hyperinsulinemia alone without insulin resistance does not appear to alter lipid metabolism patterns during glucose challenge, suggesting different metabolic pathways may be involved
•Lipid markers during OGT could complement existing diagnostic protocols for metabolic screening in horses showing signs of metabolic syndrome
•Over 60% of Shetland and Welsh ponies in this Australian cohort had insulin dysregulation; cresty neck and high body condition score are practical visual indicators of metabolic risk in ponies
•Insulin dysregulation and insulin resistance are significant independent risk factors for laminitis in ponies—metabolic testing should inform preventive lameness management strategies
•Older ponies and those perceived by owners as overweight warrant metabolic screening; consider PPID testing as PPID status strongly associates with laminitis risk
•OGT and IV insulin response tests detect different aspects of insulin dysregulation; OGT identifies hyperinsulinemia while IV tests identify peripheral insulin resistance — use both or choose based on clinical suspicion to avoid missing cases
•A modified 2-step IRT with porcine zinc insulin may over-identify insulin resistance compared to oral testing; interpret results cautiously and consider combining tests for comprehensive metabolic assessment
•Not all hyperinsulinemic horses demonstrate proportional peripheral insulin resistance, so a normal IV glucose clearance does not rule out metabolic dysfunction or laminitis risk in susceptible breeds like Icelandic horses
•Sphingolipid profiling may help identify horses at risk for insulin dysregulation earlier than traditional glucose tolerance testing
•Understanding ceramide-insulin relationships could inform nutritional or management strategies to improve insulin sensitivity in susceptible horses
•This research supports monitoring metabolic markers beyond glucose alone when assessing insulin-related problems in equine practice
•Fasting insulin and proxy calculations (particularly RISQI and QUICKI) can be reliably used to screen for insulin resistance in clinical practice, avoiding the need for expensive and time-consuming clamp testing
•Use established cut-off values from this study when interpreting fasting insulin and proxy results to identify horses requiring dietary and management interventions for metabolic syndrome
•Sampling on consecutive days shows good repeatability, so single-day fasting samples are adequate for clinical assessment; serial monitoring does not require multiple testing days
•Obese horses develop elevated blood pressure and cortisol levels that persist even after pasture access, suggesting these metabolic changes may require active management strategies beyond weight loss alone
•Pasture turnout improved insulin sensitivity in obese mares despite persistent hypertension and cortisol elevation, indicating multi-system benefits of exercise and grazing
•Monitor blood pressure and cortisol in obese horses as independent risk factors; improvements in one parameter do not guarantee normalization of others
•EMS horses have a cellular-level magnesium deficiency that correlates with their degree of insulin dysregulation; this may warrant investigation of magnesium status in EMS management protocols
•The relationship between intracellular magnesium and insulin suggests that improving insulin sensitivity through diet and exercise may help restore normal magnesium metabolism in affected horses
•Serum magnesium levels alone may not reflect intracellular status in EMS horses; practitioners should consider functional magnesium assessment in metabolic syndrome cases
•Monitor body condition score carefully in companion donkeys, as obesity significantly elevates basal insulin and may impair insulin sensitivity, increasing laminitis and metabolic disease risk
•Donkeys' naturally higher digestive efficiency and lower energy expenditure compared to horses makes them prone to rapid weight gain—adjust feeding and activity accordingly
•Elevated basal insulin in overweight donkeys is a measurable metabolic warning sign; consider glucose-insulin testing for donkeys with moderate to high BCS as part of preventive health screening
•Mare body condition at breeding significantly influences foal metabolic health and orthopaedic disease risk; maintain BCS ≤4 at insemination to reduce osteochondrosis risk in offspring
•Foals from obese mares warrant closer monitoring for metabolic and inflammatory markers during the first 6 months of life and orthopaedic examinations at 12 months
•Pre-conception mare nutrition and weight management programs may reduce developmental orthopaedic disease incidence in the resulting foal crop
•Obesity in horses is associated with altered gut bacterial communities; managing feed intake and energy density may help restore healthy microbiome balance and reduce metabolic dysfunction.
•Monitoring blood markers (leptin, glucose, triglycerides) alongside weight management can help identify metabolic changes linked to obesity and associated conditions like laminitis.
•Future therapies targeting specific bacterial populations may offer novel approaches to preventing obesity-related complications, though clinical applications require further development.
•OGT and OST cannot be used interchangeably for assessing insulin sensitivity in the field; choose one protocol and use it consistently for individual horse monitoring
•OST produces lower and faster insulin responses than OGT, so different reference thresholds for insulin dysregulation apply to each test
•When using either test, be aware that 15% of horses/ponies may be misclassified depending on which test is chosen; consider clinical context and repeat testing if borderline results
•Know which insulin assay your laboratory uses—results are not interchangeable between assays, and clinical reference ranges must match the specific assay method
•When diagnosing insulin resistance or dysregulation, ensure your diagnostic criteria (basal values, response to oral glucose tolerance test) align with the assay used by your lab
•Request species-specific assays when possible, as porcine-specific assays appear more reliable for equine samples than human-specific assays
•High-quality cultivated pastures increase body condition and insulin responses in grazing mares; monitor body condition and consider restricting grazing time or supplementing with lower-quality forage if laminitis risk is a concern.
•Gene expression changes during grazing season suggest adaptive metabolic responses; these protective mechanisms may break down under extreme obesity, so weight management remains critical for laminitis prevention.
•Semi-natural grassland grazing maintains lower body condition scores and more moderate metabolic responses compared to cultivated pasture, making it a potentially safer option for metabolically at-risk mares.
•Mares with equine metabolic syndrome have compromised fertility due to altered ovarian follicular environment; metabolic management should be a priority before breeding unsound mares
•The intrafollicular inflammatory state in metabolic syndrome may impair both oocyte maturation and subsequent offspring viability—addressing insulin resistance through diet and exercise is critical for reproductive soundness
•Consider screening breeding mares for insulin resistance using RISQI or MIRG proxies; metabolically compromised mares may benefit from pre-breeding metabolic stabilization protocols
•Do not rely solely on glucose curve results from a single CGIT to diagnose insulin resistance, as these results are unreliable and variable
•Insulin curve parameters are more trustworthy for repeated assessments and longitudinal monitoring of IR status
•Be aware that breed and recent stress (e.g., transport) can significantly influence glucose responses during testing, potentially leading to misinterpretation of results
•Do not use recombinant equine growth hormone to treat obesity in horses, particularly those with insulin resistance, as it consistently elevates insulin levels and worsens metabolic status
•Exercise alone does not reduce basal insulin concentrations, so weight management in insulin-resistant horses requires dietary intervention as a primary strategy
•Single pre-feeding morning blood samples provide reliable basal insulin measurements for monitoring metabolic status in individual horses
•Measuring peak insulin concentration 2 hours after a standard glucose challenge (1 g/kg) could help identify ponies at risk of laminitis before they show clinical signs—particularly valuable for spring/fall risk assessment
•Ponies on fall pasture show more variable and elevated insulin responses; additional monitoring and dietary management during this season may be warranted for laminitis-prone individuals
•Fructose and inulin supplementation cause minimal glycemic and insulinemic responses compared to glucose, making them potentially safer carbohydrate choices for insulin-resistant ponies
•Feeding high glycaemic concentrates to lean horses for 90 days does not necessarily cause insulin resistance but does alter their metabolic response to feeding
•Changes in fat metabolism (NEFA suppression) may be an early warning sign of developing insulin resistance before traditional glucose tolerance tests become abnormal
•Long-term studies are needed to determine if continued high glycaemic feeding beyond 90 days eventually leads to insulin resistance in lean horses
•Plasma fructosamine may be a useful clinical marker to identify abnormal glucose homeostasis in laminitic horses, potentially helping identify insulin resistance as an underlying cause
•Measuring fructosamine alongside insulin and glucose could improve detection of metabolic dysfunction in laminitis cases and support targeted management strategies
•While fructosamine shows promise as a diagnostic marker, it did not predict outcome in this study, so clinical assessment must remain multifactorial
•C-peptide testing offers a more accurate assessment of pancreatic beta-cell function than insulin alone in horses suspected of insulin resistance, helping distinguish true hyperinsulinaemia from other metabolic issues
•This measurement tool can improve diagnostic accuracy for equine metabolic syndrome and insulin resistance, informing better management and treatment decisions
•Understanding C-peptide responses helps veterinarians evaluate horses with conditions associated with insulin resistance, such as laminitis and obesity
•Horses with concurrent endotoxaemia and carbohydrate overload face dramatically elevated laminitis risk (5/8 affected); monitor closely during illness if pasture access or grain availability is unrestricted.
•Insulin sensitivity decreases after carbohydrate overload regardless of endotoxin exposure, supporting strict carbohydrate restriction in laminitis-prone horses and during systemic illness.
•Systemic inflammation from either endotoxin or carbohydrate overload alone increases laminitis susceptibility; the combination is synergistic and particularly dangerous.
•Elevated TNF-alpha may be a useful biomarker to identify ponies at higher risk for recurrent laminitis, potentially supporting early intervention strategies
•The association between TNF-alpha and insulin resistance suggests metabolic management targeting inflammation could help prevent laminitis in susceptible ponies
•Standard inflammatory markers like fibrinogen may not adequately reflect laminitis risk; more specific cytokine testing may be warranted for at-risk populations
•Laminitis risk in susceptible ponies is seasonal and linked to summer pasture; metabolic screening during winter may not identify at-risk individuals
•Monitor blood pressure and insulin status during summer months in laminitis-prone ponies as markers of metabolic syndrome and laminitis risk
•Pasture management and dietary restriction during summer grazing periods may be critical preventive strategies for laminitis-prone ponies
•Laminitis-prone ponies should be managed on restricted hay diets rather than pasture; avoid dietary supplements containing inulin and other fructans that trigger marked insulin spikes
•High insulin response to stress (including medications like dexamethasone) in susceptible ponies warrants careful monitoring during illness or treatment protocols
•Identifying and managing insulin resistance through diet before clinical laminitis develops may be critical for prevention in predisposed animals
•Screen apparently healthy ponies with high body condition and family history for prelaminitic metabolic syndrome using blood markers (triglycerides, insulin, glucose) to identify at-risk individuals before clinical disease
•Restrict dietary starch in ponies identified with metabolic syndrome markers, as high pasture starch concentration significantly increases clinical laminitis risk
•Use basal blood insulin and glucose ratios (RISQI, MIRG) as practical preventive diagnostic tools to guide management decisions for individual ponies at risk of pasture laminitis
•Test at-risk ponies for plasma insulin, triglycerides, and glucose to identify those with metabolic predisposition to laminitis before clinical disease develops
•Ponies identified as PLMS-positive require stricter pasture management and controlled grazing, especially during high-starch growth periods, to prevent laminitis episodes
•Metabolic profiling enables targeted preventive interventions for predisposed individuals, reducing overall disease incidence and improving outcomes compared to blanket management approaches
•MSI-1436 shows promise as a novel therapeutic approach for managing equine metabolic syndrome by addressing multiple pathogenic mechanisms simultaneously
•Single-dose IV administration improved both metabolic markers and systemic inflammation in affected horses, suggesting potential clinical utility
•This research provides mechanistic rationale for targeting PTP1B inhibition in EMS management, though further clinical trials are needed before routine practice implementation
•PTP1B inhibition shows promise as a targeted approach to address the underlying metabolic dysfunction in EMS by simultaneously tackling inflammation, fibrosis, and glucose handling in the liver
•This research suggests that future therapeutic options for EMS may move beyond symptom management (diet, exercise) toward pharmacological restoration of hepatic metabolic capacity
•Results are currently limited to tissue culture studies; clinical efficacy and safety in live horses with EMS remain to be established in future trials
•Horses with poor insulin sensitivity may develop cardiac dysfunction affecting diastolic and systolic performance, warranting cardiac screening in metabolically compromised individuals
•Tissue Doppler imaging appears useful for detecting myocardial changes associated with insulin resistance, though further study is needed to establish clinical thresholds
•This pilot data suggests metabolic management to improve insulin sensitivity could have cardioprotective benefits, but larger studies are needed before changing clinical practice
•Regenerative medicine using autologous stem cells may offer an adjunctive therapy option for EMS horses when combined with conventional management (caloric restriction and exercise)
•Pre-treatment of patient's own stem cells with specific compounds in the laboratory may enhance their therapeutic effectiveness before reintroduction
•Liver enzyme normalization following treatment suggests systemic metabolic improvement, though long-term clinical outcomes and feasibility in practice require further investigation
•Stem cell therapies derived from EMS horses may have reduced effectiveness due to cellular dysfunction; consider metabolic status when selecting donor horses for MSC isolation
•Oxidative stress and mitochondrial dysfunction in metabolically compromised horses could impact regenerative medicine outcomes; optimizing the metabolic health of donor animals may improve cell quality
•Understanding that diseased stem cells activate compensatory autophagy mechanisms could inform strategies to enhance cell therapy efficacy, such as pre-treatment protocols to reduce cellular stress before clinical use
•Spirulina platensis supplementation may offer a complementary dietary strategy to support management of EMS horses by improving insulin sensitivity and reducing systemic inflammation
•Weight loss coupled with improved insulin sensitivity suggests potential benefit as an adjunctive therapy alongside conventional EMS management (dietary restriction, exercise, medications)
•Results are preliminary in vivo findings; further controlled clinical trials with defined sample sizes and control groups are needed before recommending widespread use in practice
•Customized diet and exercise plans can effectively treat EMS in owner-managed settings without specialized facilities, though compliance requires careful owner guidance
•Weight loss alone correlates with measurable improvements in insulin sensitivity markers, making this a practical first-line intervention for laminitis prevention
•Regular monitoring of insulin dynamics through dynamic testing helps confirm treatment efficacy and may improve owner compliance by demonstrating objective improvement
•Investigate endocrine status (ACTH, dexamethasone suppression) in horses and ponies presenting with unexplained weight loss and marked hypertriglyceridaemia, as treatment of underlying pituitary or metabolic disease can resolve lipid abnormalities
•Monitor serum triglycerides and glucose in horses with pituitary pars intermedia dysfunction or insulin resistance, as severe hypertriglyceridaemia may develop silently without overt clinical signs despite hepatic lipidosis
•Expect variable treatment responses; biochemical abnormalities may persist long-term without apparent clinical deterioration, but early intervention with pergolide and insulin offers the best chance of normalising lipid profiles
•Hyperinsulinaemia may directly increase vascular resistance in the equine foot through ET-1 overexpression, providing a mechanistic link between insulin resistance and laminitis susceptibility
•Management of insulin-resistant horses should emphasize glycaemic control to prevent vascular changes in digital tissues that could precipitate or worsen laminitis
•Early detection and treatment of insulin resistance may help prevent the pathological vascular changes in the foot before clinical laminitis develops
•Insulin-associated laminitis may have a fundamentally different mechanism than other forms, potentially requiring different diagnostic and treatment approaches beyond standard basement membrane disruption focus
•Screening for hyperinsulinaemia in laminitis cases is clinically important, as these cases show distinct histological features and lack systemic inflammatory markers that typify other laminitis aetiologies
•The preservation of basement membrane integrity in insulin-induced laminitis suggests that farriery and therapeutic approaches targeting laminar separation may need modification for hyperinsulinaemic cases
•Metformin may reduce insulin resistance and associated laminitis risk in horses and ponies; consider as part of a multimodal management approach for IR cases
•Early response to metformin is greater (6-14 days) than longer-term response, so reassessment timing and treatment duration need careful planning
•While metformin improves metabolic markers, clinical lameness improvement may lag behind biochemical improvement—manage owner expectations accordingly
•Understanding Glut-4 distribution in equine tissues may help explain differences in how horses develop insulin resistance compared to humans, potentially informing nutritional and metabolic management strategies
•The elevated Glut-4 expression in adipose tissue compared to muscle in horses suggests unique metabolic characteristics in this species that warrant further investigation in insulin-resistant populations
•When discussing elevated insulin levels with colleagues, use 'insulin resistance' rather than 'insulin dysregulation'—the evidence supports this terminology and improves clinical communication
•Understand that hyperinsulinaemia in horses reflects failure of insulin-sensitive tissues to respond normally to insulin, not a separate metabolic condition
•Be aware that terminology matters in practice: using precise, evidence-based language helps standardise diagnosis and management of metabolic disease across the equine industry
•Educate owners that maintaining moderate body weight is critical prevention for laminitis and metabolic disease, even when horses are 'easy keepers'
•Monitor fasting insulin levels and body condition in middle-aged horses, as insulin resistance often precedes clinical laminitis
•Address overfeeding of concentrates and hay as the primary modifiable risk factor; feeding behavior change is essential for management
•Implement regular exercise conditioning programs as a primary intervention to improve insulin sensitivity and facilitate weight loss in obese horses at risk for metabolic disease and laminitis
•Even single exercise sessions provide metabolic benefits through improved glucose disposal, making consistent work schedules important for metabolic management
•Weight management through exercise is critical for laminitis prevention, particularly in horses with documented insulin resistance or obesity
•Insulin dysregulation appears to be a significant risk factor for hoof tissue degradation in cattle, independent of diet type or SARA status
•High-starch diets alone may not be the primary driver of claw horn lesions; metabolic factors like insulin resistance warrant closer investigation
•Further research is needed to clarify the role of insulin and IGF-1 imbalances in claw health before dietary management strategies can be refined
•PTP1B inhibitors like MSI-1436 show promise as a potential therapeutic avenue for managing equine metabolic syndrome at the molecular level, though clinical translation remains years away
•This research identifies mitochondrial dysfunction as a key mechanism in EMS-related insulin resistance, which may inform future nutritional and management strategies targeting metabolic health
•Current findings are limited to cell culture models; clinical efficacy and safety in live horses has not been established
•Oral carbohydrate testing that includes gastrointestinal assessment is important for diagnosing insulin dysregulation and identifying laminitis risk in horses, particularly measuring post-prandial insulin responses.
•Understanding how the gastrointestinal tract enhances insulin secretion through the enteroinsular axis can help inform dietary management strategies to reduce hyperinsulinaemia and laminitis risk.
•Current knowledge gaps remain regarding several gut peptides in horses; ongoing research into enteroinsular axis function may reveal new diagnostic or therapeutic targets for managing insulin dysregulation.
•SHBG may represent a novel therapeutic target for treating equine metabolic syndrome by improving cellular insulin sensitivity and reducing metabolic dysfunction at the molecular level
•This in vitro research provides foundational evidence for potential future clinical trials investigating SHBG as a treatment for EMS, but in vivo studies are needed before clinical application
•Understanding the mechanisms by which SHBG improves stem cell function in EMS could inform development of more targeted therapeutic protocols for insulin-resistant horses
•Iron supplementation in racehorses may not be necessary or beneficial given that typical diets already exceed recommended daily requirements by 9-10 fold
•Excess dietary iron should not be assumed to cause insulin resistance in horses based on current epidemiological evidence in Thoroughbred populations
•Review current iron supplementation protocols with clients, as unnecessary supplementation adds cost without apparent performance or health benefit
•This in vitro research suggests nortropane alkaloids may have therapeutic potential for horses with metabolic syndrome, though clinical application requires further development and testing in living animals
•The findings support exploring natural compounds with antioxidant and antidiabetic properties as adjunctive treatments for managing equine metabolic syndrome
•Results are preliminary laboratory work; translation to clinical practice for EMS management remains years away and requires in vivo validation
•Do not diagnose PPID based on elevated ACTH alone—always consider the horse's age, breed, season, body condition, and health status before starting lifelong medication
•Recognize that EMS diagnosis requires identifying which type of insulin dysregulation is present (resistance vs. postprandial excess) as this determines appropriate management strategy
•When interpreting endocrine test results, use clinical judgment and contextual horse factors rather than treating numbers in isolation to avoid unnecessary long-term drug therapy
•Identify high-risk horses (those showing signs of equine metabolic syndrome or insulin resistance) and prioritize metabolic management alongside pasture control as primary laminitis prevention strategies.
•Monitor and manage pasture nonstructural carbohydrate content—particularly simple sugars, starches, and fructans—through grazing management and forage testing to reduce laminitis risk in susceptible animals.
•Implement combined nutritional and management protocols addressing both the horse's metabolic status and environmental carbohydrate exposure rather than relying on single-factor interventions.
•AICAR shows promise as a potential pharmacological intervention for equine metabolic syndrome and insulin resistance, though further investigation is needed before clinical application
•The novel glucose transporter GLUT8 appears to be a key player in equine muscle glucose uptake and may be a target for managing metabolic disease in horses
•AMPK activation via AICAR enhances both muscle glucose uptake and pancreatic insulin secretion, suggesting multi-system metabolic benefits
•Recognition and management of insulin resistance is critical to prevent laminitis, as hyperinsulinaemia directly affects glucose transport in tissues vulnerable to laminitis
•Horses showing signs of metabolic disease require metabolic screening and dietary management to reduce circulating insulin levels and prevent digital lamellae dysfunction
•Understanding the molecular basis of laminitis development through glucose transporter dysfunction may guide future preventative and therapeutic strategies
•Horses with Cushing's disease or metabolic syndrome may have altered vascular reactivity in the laminae, increasing laminitis risk through cortisol-mediated changes in vein contraction
•Insulin resistance may compound laminitis risk by reducing the natural protective effects of insulin on laminar blood vessel contraction
•Management strategies targeting cortisol control and insulin sensitivity may help mitigate vascular mechanisms underlying laminitis in predisposed horses
•Managing EMS in horses requires attention to diet composition and meal structure to modulate postprandial insulin responses, not just caloric restriction
•Hyperinsulinaemia should be monitored and controlled as both a consequence and driver of metabolic dysfunction, as it perpetuates insulin resistance independent of initial causation
•Understanding how different tissues handle glucose helps explain why some horses remain insulin resistant despite weight loss, guiding more targeted nutritional and management strategies
•Screen horses at risk of laminitis for insulin dysregulation using oral sugar or glucose tolerance tests to enable early intervention
•Manage hyperinsulinaemia through dietary modification and weight control, as insulin dysregulation significantly increases laminitis risk
•Consider insulin dysregulation in foals presenting with prematurity or systemic illness, as it can accompany these conditions
•High fructan pastures (especially in spring and fall) may increase laminitis risk in susceptible horses through mechanisms involving intestinal bacteria-mediated fructose generation and hepatic metabolism
•Managing fructan intake through grazing time restrictions, hay feeding, or pasture selection could be a preventive strategy for metabolic syndrome and laminitis-prone horses
•Further research is needed to confirm these mechanisms before making definitive dietary recommendations, but reducing fructan exposure in horses with insulin resistance or laminitis history warrants consideration
•Review feeding practices and exercise regimens for overweight horses, particularly those showing signs of insulin resistance, as these are modifiable risk factors for laminitis
•Screen obese or insulin-resistant horses for EMS and monitor closely for laminitis development, which may require euthanasia in severe cases
•Focus management on reducing sugar and starch intake while increasing physical activity to mitigate metabolic syndrome risk
•This in vitro model provides a reliable laboratory tool for investigating vascular dysfunction mechanisms in hyperinsulinaemic laminitis, potentially leading to better therapeutic targets.
•Understanding that insulin resistance causes abnormal vascular contraction rather than relaxation may explain reduced blood flow to laminae in insulin-associated laminitis cases.
•The PI3-kinase pathway's central role suggests potential future therapeutic interventions could target this pathway to restore normal vascular insulin sensitivity in laminitis-prone horses.
•Monitor body condition in horses as obesity-related inflammation may be a key driver of insulin resistance development and associated metabolic disease
•Consider that inflammatory mechanisms similar to those in obese humans may underlie equine insulin resistance, informing both prevention and management strategies
•Weight management and obesity prevention should be prioritized as potential interventions to reduce inflammatory cytokine production and improve insulin sensitivity
•Understanding glucose transport in the hoof may provide new insights into laminitis prevention and treatment strategies
•Horses with insulin resistance should be monitored closely as they may have compromised glucose delivery to hoof tissues
•Further research is needed to clarify glucose uptake mechanisms before clinical recommendations can be made
•Implement regular exercise programs for laminitis-prone horses as it directly reduces insulin resistance and inflammatory markers
•Modify diet to improve insulin sensitivity—this is a primary prevention strategy for horses with endocrinopathic predisposition
•Combine both exercise and dietary interventions for maximum effect in managing recurrent laminitis cases
•Identify and manage hyperinsulinemia in at-risk horses as a direct laminitis prevention strategy, not just as a marker of insulin resistance
•Focus on dietary and metabolic management to reduce circulating insulin levels in horses with laminitis risk factors
•Recognize that insulin-associated laminitis is increasingly common in modern equine populations and requires targeted metabolic intervention
•Assess pasture forage quality and carbohydrate content in horses with metabolic risk factors; consider strip grazing, hay nets, or dry lot management during high fructan periods (spring, autumn)
•Screen at-risk horses (overweight, insulin-resistant, or with abnormal insulin dynamics) before turnout to identify those requiring modified grazing management to prevent laminitis
•Understanding the inflammatory cascade from carbohydrate overload helps frame prevention and early intervention strategies focused on limiting fermentable carbohydrate intake rather than treating advanced lamellar damage
•Screen horses for metabolic syndrome components (obesity, elevated insulin, triglycerides) as these increase laminitis risk—early identification enables preventive management
•Weight management and insulin resistance control may reduce laminitis predisposition in affected horses, though specific mechanisms require further research
•Consider inflammatory and vascular dysfunction pathways when managing laminitis in metabolically compromised horses, not just mechanical load factors
•Hyperinsulinaemia alone can induce laminitis through a distinct pathological mechanism; medical management of insulin resistance should be a priority in at-risk ponies and horses before clinical lameness develops
•The lesions produced by hyperinsulinaemia differ significantly from carbohydrate-induced laminitis, suggesting different treatment and prevention strategies may be required
•Early intervention targeting insulin control may prevent or ameliorate the lamellar changes before they progress to clinical grades of laminitis
•Early detection and aggressive management of hyperinsulinaemia should be a priority in endocrinopathic laminitis cases, as insulin itself appears causative independent of blood glucose levels
•Insulin resistance and resulting hyperinsulinaemia may be a critical risk factor even in apparently healthy ponies, warranting baseline insulin screening for at-risk populations
•This research strengthens the case for insulin-lowering strategies (diet management, exercise, medications) as primary prevention and treatment protocols for insulin-related laminitis
•Consider discontinuing phenylbutazone in Cushing's cases with refractory laminitis due to its adverse effects on intestinal barrier function
•Implement nutritional and intestinal wall healing protocols alongside conventional therapies to improve laminitis management outcomes
•Use multimodal treatment combining good farriery, nutrition, and complementary therapies rather than relying solely on NSAIDs
•Improved understanding of equine adipocyte function provides a research foundation for developing better management and treatment strategies for obesity and EMS in horses
•This in vitro model may facilitate testing of dietary supplements, pharmaceutical interventions, and management approaches targeting adipose tissue dysfunction in metabolically compromised horses
•Research on equine adipocyte insulin sensitivity and lipid metabolism can inform nutritional recommendations and metabolic monitoring protocols for at-risk horses

Key Research Findings

Increased adiposity alone did not reduce insulin sensitivity in horses and ponies fed either high-fat or control diets over 20 weeks

Bamford N J, 2016

Once-daily high glycaemic glucose meal unexpectedly increased insulin-dependent (SI) and insulin-independent (Sg) glucose disposal compared to high-fat and control groups (P=0.006 and P=0.03 respectively)

Bamford N J, 2016

Leptin concentrations were elevated in obese groups (FAT and GLU) compared to controls (P=0.003), but adiponectin, TNF-α and SAA showed no significant differences between groups

Bamford N J, 2016

Body condition score and total body fat mass increased similarly in both FAT and GLU groups, suggesting dietary macronutrient composition rather than caloric load drives metabolic differences

Bamford N J, 2016

Metformin administration reduced peak glucose concentration in healthy horses (P = 0.002) and in dexamethasone-induced insulin-resistant horses (P < 0.001)

Rendle D I, 2013

Metformin significantly reduced area under the glucose curve in both healthy horses (P < 0.001) and insulin-resistant horses (P < 0.001)

Rendle D I, 2013

Insulin concentration at 120 minutes post-dextrose was significantly lower with metformin in healthy horses (P = 0.011) and at 120 and 150 minutes in insulin-resistant horses (P = 0.034 and P = 0.014 respectively)

Rendle D I, 2013

Metformin showed efficacy in reducing glycaemic and insulinaemic responses at both baseline and in experimentally induced insulin resistance states

Rendle D I, 2013

Chromium and magnesium supplementation did not significantly improve insulin sensitivity in laminitic obese horses over 16 weeks

Chameroy K A, 2011

Hyperinsulinaemia (>30 µu/ml) was present in 12 of 14 horses prior to treatment

Chameroy K A, 2011

Resting insulin concentrations significantly increased over time in both groups (P = 0.018), suggesting supplement inefficacy

Chameroy K A, 2011

No changes in morphometric measurements or blood variables were observed with supplementation

Chameroy K A, 2011

All 4 treated horses developed clinical laminitis within 48 hours of prolonged euglycaemic hyperinsulinaemic clamp infusion, compared to 0/4 control horses (P = 0.01)

de Laat, 2010

Pronounced digital pulses were present in all treated horses but absent in controls, indicating increased vascular activity associated with laminitis development

de Laat, 2010

Hoof wall surface temperature was significantly higher and less variable in treated horses once hyperinsulinaemia was established

de Laat, 2010

Evidence Base

Effect of increased adiposity on insulin sensitivity and adipokine concentrations in horses and ponies fed a high fat diet, with or without a once daily high glycaemic meal.

Bamford N J, Potter S J, Harris P A et al. (2016) — Equine veterinary journal

RCT

Effects of metformin hydrochloride on blood glucose and insulin responses to oral dextrose in horses.

Rendle D I, Rutledge F, Hughes K J et al. (2013) — Equine veterinary journal

RCT

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

Chameroy K A, Frank N, Elliott S B et al. (2011) — Equine veterinary journal

RCT

Equine laminitis: induced by 48 h hyperinsulinaemia in Standardbred horses.

de Laat, McGowan, Sillence et al. (2010) — Equine veterinary journal

RCT

Investigations on metabolic diseases of horses in Egypt.

Aboelmaaty Amal M, Ahdy Ahmed M, El-Khodery Sabry et al. (2025) — Frontiers in veterinary science

Insulin Resistance: What the Research Says

What Professionals Should Know

Key Research Findings

Evidence Base

Effect of increased adiposity on insulin sensitivity and adipokine concentrations in horses and ponies fed a high fat diet, with or without a once daily high glycaemic meal.

Effects of metformin hydrochloride on blood glucose and insulin responses to oral dextrose in horses.

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

Equine laminitis: induced by 48 h hyperinsulinaemia in Standardbred horses.

Investigations on metabolic diseases of horses in Egypt.

Arthrospira platensis enriched with Cr(III), Mg(II), and Mn(II) ions improves insulin sensitivity and reduces systemic inflammation in equine metabolic affected horses.

Investigation of glucagon-like peptide-1 response to six oral carbohydrates in ponies.

Value of measuring markers of lipid metabolism in horses during an oral glucose test.

Epidemiological investigation of insulin dysregulation in Shetland and Welsh ponies in Australia.

Comparison of a modified 2-step insulin response test performed with porcine zinc insulin and an oral glucose test to detect hyperinsulinemic Icelandic horses.

Associations of plasma sphingolipid profiles with insulin response during oral glucose testing in Icelandic horses.

Evaluation of fasting plasma insulin and proxy measurements to assess insulin sensitivity in horses.

The effect of diet-induced obesity and pasture on blood pressure and serum cortisol in Standardbred mares.

Relationship between intracellular free magnesium concentration and the degree of insulin resistance in horses with equine metabolic syndrome

Insulin Resistance as a Result of Body Condition Categorized as Thin, Moderate, and Obese in Domesticated U.S. Donkeys (Equus asinus).

Maternal obesity increases insulin resistance, low-grade inflammation and osteochondrosis lesions in foals and yearlings until 18 months of age.

Microbiome and Blood Analyte Differences Point to Community and Metabolic Signatures in Lean and Obese Horses.

Comparison of the in-feed glucose test and the oral sugar test.

Comparison of three different methods for the quantification of equine insulin.

Relationships among Body Condition, Insulin Resistance and Subcutaneous Adipose Tissue Gene Expression during the Grazing Season in Mares.

The effect of equine metabolic syndrome on the ovarian follicular environment.

Repeatability of the combined glucose-insulin tolerance test and the effect of a stressor before testing in horses of 2 breeds.

Diurnal rhythm and effects of feeding, exercise and recombinant equine growth hormone on serum insulin concentrations in the horse.

Effect of feeding glucose, fructose, and inulin on blood glucose and insulin concentrations in normal ponies and those predisposed to laminitis.

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

Increased plasma fructosamine concentrations in laminitic horses.

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

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

Inflammatory and redox status of ponies with a history of pasture-associated laminitis.

Hypertension and insulin resistance in a mixed-breed population of ponies predisposed to laminitis.

Effect of dietary fructans and dexamethasone administration on the insulin response of ponies predisposed to laminitis.

Evaluation of genetic and metabolic predispositions and nutritional risk factors for pasture-associated laminitis in ponies.

10.1093/jn/136.7.2090S.

The PTP1B inhibitor MSI-1436 ameliorates liver insulin sensitivity by modulating autophagy, ER stress and systemic inflammation in Equine metabolic syndrome affected horses

The PTP1B Inhibitor Trodusquemine (MSI-1436) Improves Glucose Uptake in Equine Metabolic Syndrome Affected Liver through Anti-Inflammatory and Antifibrotic Activity

Investigating the Relationship Between Cardiac Function and Insulin Sensitivity in Horses: A Pilot Study.

Systemic Administration of Rejuvenated Adipose-Derived Mesenchymal Stem Cells Improves Liver Metabolism in Equine Metabolic Syndrome (EMS)- New Approach in Veterinary Regenerative Medicine

Evaluation of Oxidative Stress and Mitophagy during Adipogenic Differentiation of Adipose-Derived Stem Cells Isolated from Equine Metabolic Syndrome (EMS) Horses

Spirulina platensis Improves Mitochondrial Function Impaired by Elevated Oxidative Stress in Adipose-Derived Mesenchymal Stromal Cells (ASCs) and Intestinal Epithelial Cells (IECs), and Enhances Insulin Sensitivity in Equine Metabolic Syndrome (EMS) Horses

Treatment of equine metabolic syndrome: A clinical case series.

Severe hypertriglyceridaemia in horses and ponies with endocrine disorders.

Hyperinsulinaemia increases vascular resistance and endothelin-1 expression in the equine digit.

Histopathology of insulin-induced laminitis in ponies.

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

Novel findings regarding Glut-4 expression in adipose tissue and muscle in horses--a preliminary report.

Insulin resistance versus dysregulation—a distinction without a difference

Equine metabolic syndrome

Effect of Exercise Conditioning on Countering the Effects of Obesity and Insulin Resistance in Horses-A Review.

Exploring the impact of high-energy diets on cattle: Insights into subacute rumen acidosis, insulin resistance, and hoof health.

Trodusquemine (MSI-1436) Restores Metabolic Flexibility and Mitochondrial Dynamics in Insulin-Resistant Equine Hepatic Progenitor Cells (HPCs)

Equine metabolic syndrome: Role of the enteroinsular axis in the insulin response to oral carbohydrate.

Sex hormone-binding globulin (SHBG) mitigates ER stress and improves viability and insulin sensitivity in adipose-derived mesenchymal stem cells (ASC) of equine metabolic syndrome (EMS)-affected horses

Dietary Iron Unlikely to Cause Insulin Resistance in Horses.

Nortropane alkaloids as pharmacological chaperones in the rescue of equine adipose-derived mesenchymal stromal stem cells affected by metabolic syndrome through mitochondrial potentiation, endoplasmic reticulum stress mitigation and insulin resistance alleviation

Diagnostic Testing for Equine Endocrine Diseases: Confirmation Versus Confusion.

Nutritional Management for Avoidance of Pasture‐Associated Laminitis

AICAR administration affects glucose metabolism by upregulating the novel glucose transporter, GLUT8, in equine skeletal muscle.

The impact of prolonged hyperinsulinaemia on glucose transport in equine skeletal muscle and digital lamellae.

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

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

Insulin dysregulation.

Fructokinase, Fructans, Intestinal Permeability, and Metabolic Syndrome: An Equine Connection?

Diabetes, Insulin Resistance, and Metabolic Syndrome in Horses

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

A Potential Role for Pro-Inflammatory Cytokines in the Development of Insulin Resistance in Horses.

Glucose transport in the equine hoof.

Endocrinopathic Laminitis: Reducing the Risk Through Diet and Exercise

Hyperinsulinemic laminitis.

Current concepts on the pathophysiology of pasture-associated laminitis.

Metabolic syndrome-From human organ disease to laminar failure in equids.

Equine laminitis: ultrastructural lesions detected in ponies following hyperinsulinaemia.

Induction of laminitis by prolonged hyperinsulinaemia in clinically normal ponies.

The role of nutritional therapy in the treatment of equine Cushing's syndrome and laminitis.

Isolation method and characterization of adipocytes as a tool for equine obesity research - In vitro study.