Hyperinsulinaemia: What the Research Says
Evidence from 36 peer-reviewed studies
What Professionals Should Know
- •Consider age (≥15 years), hypertrichosis, and delayed hair shedding as primary indicators for PPID testing; use TRH stimulation testing for improved diagnostic accuracy over basal ACTH alone, especially outside autumn months
- •Recognize that breed and seasonal factors substantially influence ACTH values—interpret results using equivocal ranges and pre-test probability rather than fixed cutoffs to avoid false positive diagnoses and unnecessary lifelong therapy
- •Start pergolide treatment based on clinical signs and diagnostic results; monitor clinical improvement rather than strictly chasing ACTH values, as hormone levels may normalize without full clinical resolution and compliance with treatment is often poor
- •Diagnosis of insulin dysregulation should investigate both tissue insulin resistance and enteroinsular axis function rather than relying on single tests
- •Account for breed, diet, fasting status, and seasonal variations when interpreting insulin dysregulation test results to avoid false negatives in at-risk horses
- •Focus on identifying horses with insulin dysregulation early to enable preventive laminitis management, as established laminitis remains difficult to treat effectively
- •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
- •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
- •GLP-2 does not worsen post-prandial glucose or insulin responses in healthy ponies, suggesting it may not directly drive hyperinsulinaemia development
- •Further research using alternative GLP-2 dosing strategies is needed before considering therapeutic applications in metabolically dysregulated horses
- •Understanding GLP-2's normal secretion patterns provides baseline data for investigating its role in equine metabolic disease
- •Connemara ponies show high prevalence of obesity and metabolic dysfunction; breed-specific screening and management protocols should be considered routine practice
- •Oral sugar testing detected hyperinsulinaemia more effectively than basal insulin measurement alone—clinicians should use both methods for comprehensive assessment in at-risk ponies
- •Nearly half of these ponies have laminitis history; aggressive weight management and metabolic monitoring are essential preventive strategies for this breed
- •Current evidence suggests therapies focused on improving lamellar blood perfusion may not be effective in preventing endocrinopathic laminitis development, as laminitis occurred without perfusion deficits
- •Hyperinsulinaemia appears to alter lamellar energy metabolism (increased lactate and pyruvate) in ways that do not follow typical hypoxic/ischaemic patterns, suggesting different pathogenic mechanisms than traditionally assumed
- •Management of laminitis risk in hyperinsulinaemic horses should focus on metabolic control rather than strategies aimed at enhancing tissue perfusion
- •Radiographically screen all PPID-diagnosed horses for laminitis regardless of owner-reported lameness history, as subclinical radiographic changes are present in 76% of cases
- •Insulin concentration severity correlates with laminitis severity; severely hyperinsulinaemic horses (>50 µU/ml) warrant more aggressive metabolic management and closer laminitis monitoring
- •Client education is critical—owners frequently miss chronic laminitis signs, so veterinarians should proactively discuss radiographic findings and explain the hyperinsulinaemia-laminitis link
- •Frog-supportive shoes show measurable biomechanical benefits within 72 hours, particularly for obese ponies that naturally load the toe area less during movement
- •These shoes may help normalize loading patterns between normal and obese animals, potentially reducing laminitis risk in high-risk populations
- •Consider frog-supportive shoes as part of management strategy for obese ponies, though welfare considerations limit evidence from acute laminitis cases
- •Monitor broodmare body condition throughout gestation as obesity correlates with increased foal birthweight, which may have implications for foal viability and dystocia risk
- •Leptin concentration in late gestation may serve as a predictive biomarker for foal birthweight, though further validation studies are needed before clinical application
- •Insulin resistance does not appear to be a significant factor in Thoroughbred mares affecting foal birthweight, contrary to some assumptions about obesity-related endocrine dysfunction
- •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
- •Dietary carbohydrate restriction reduces insulin receptor expression in digital laminae, providing mechanistic support for low-NSC feeding protocols in laminitis prevention and management
- •Laminar epithelial cells appear to respond to insulin primarily through IGF-1R rather than classical insulin receptors, suggesting therapeutic targeting of IGF-1R signaling pathways may benefit hyperinsulinaemic laminitis
- •Obese ponies on high-carbohydrate diets develop excessive laminar endothelial insulin receptor expression, supporting aggressive dietary management as a first-line laminitis prevention strategy in at-risk animals
- •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
- •Measure plasma insulin and leptin in at-risk ponies; values above the thresholds identify those needing strict pasture management to prevent laminitis
- •Assess cresty neck and body condition score regularly—a neck score ≥4 or BCS ≥7 signals substantially increased laminitis risk and warrants diet and grazing restriction
- •Focus management on reducing insulin and obesity rather than combining multiple tests; weight loss and pasture control are the practical interventions
- •This foundational work suggests dopamine may modulate insulin secretion in horses similarly to other species; future research may reveal dietary or management strategies to manipulate this pathway for laminitis prevention
- •The presence of dopamine in stomach contents implies the gastrointestinal tract is an active site of dopamine production—nutritional or probiotic interventions targeting this system warrant investigation
- •Current findings are descriptive only; do not change clinical practice until dynamic studies clarify dopamine's functional role in equine insulin regulation
- •Horses with PPID and clinical laminitis show consistent lamellar damage; screen fasting insulin in these cases as hyperinsulinaemia appears to be the driving factor for tissue pathology
- •Normal insulin levels in PPID horses without laminitis suggests good metabolic control; absence of lamellar lesions in these cases indicates laminitis risk may be preventable with insulin management
- •Variability in lamellar lesion severity independent of laminitis duration suggests acute exacerbations may occur; monitor insulin status closely rather than relying on historical disease timeline
- •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
- •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
- •Screen horses for signs of metabolic syndrome and obesity as part of routine preventive care, as early intervention can prevent severe laminitis
- •Understand the relationship between insulin dysregulation and laminitis risk to better counsel clients on management and dietary modifications
- •Familiarise yourself with current diagnostic tests and clinical recognition criteria for metabolic syndrome to enable prompt identification and treatment initiation
- •SGLT2i treatment shows promising results for managing hyperinsulinaemic horses with laminitis, with strong owner satisfaction and reported pain relief even in cases previously considered for euthanasia
- •Educate owners about common early adverse effects (especially polyuria and polydipsia) as these appear manageable and often temporary; 33% experience some initial side effects but these do not typically lead to treatment discontinuation
- •Current limitations include high medication cost, availability issues, and lack of long-term efficacy data—discuss realistic timelines and set management expectations around diet, exercise and monitoring alongside pharmacological intervention
- •Screen sedentary horses for insulin dysregulation using staged diagnostic approach (basal insulin/glucose followed by dynamic testing) to prevent laminitis development
- •Implement weight management as first-line treatment: restrict feed to ~1.25% body weight daily combined with individualized exercise programs tailored to horse's fitness level and breed
- •Consider pharmacological support (metformin, levothyroxine) for obese horses unable to exercise due to laminitis or those not responding adequately to diet and exercise alone
- •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.
- •Hyperinsulinaemia directly compromises lamellar strength in susceptible horses; aggressive metabolic management and insulin control are critical for laminitis prevention in endocrinopathic cases
- •Horses with underlying metabolic disorders require early identification and treatment to prevent irreversible lamellar damage, as insulin itself appears to be a causative factor rather than just a marker of disease
- •This research provides a foundation for testing therapeutic interventions targeting insulin signaling pathways as potential preventive strategies for endocrinopathic laminitis
- •Understanding tissue-specific insulin receptor expression patterns may help explain why some horses are more susceptible to hyperinsulinaemia-related laminitis
- •Dietary carbohydrate management and body condition assessment should consider individual variation in insulin receptor expression across tissues
- •Knowledge of receptor isoforms and hybrid receptors provides mechanistic basis for managing insulin-related laminitis prevention strategies
- •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
- •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
- •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.
- •PPID is a lifelong condition in older horses that cannot be cured but can be managed; excessive or abnormal hair coat shedding should prompt diagnostic testing in horses aged 15+ years
- •Test PPID-affected horses for insulin dysregulation as laminitis risk is directly associated with hyperinsulinaemia; dietary management specific to insulin sensitivity is essential alongside pergolide therapy
- •Combine pharmacological treatment (pergolide) with tailored nutrition and symptomatic management (e.g., clipping, unrestricted water access) for optimal clinical outcomes
- •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
- •Jejunal glucose absorption and GLP-2 secretion may contribute to post-prandial hyperinsulinaemia in horses with insulin dysregulation; dietary strategies targeting jejunal glucose handling warrant investigation
- •This foundational work on equine intestinal GLP-2 physiology opens potential therapeutic avenues for managing insulin dysregulation and laminitis prevention through intestinal hormone modulation
- •Further research may eventually enable targeted nutritional or pharmacological interventions at the jejunum to reduce hyperinsulinaemia risk in susceptible horses
Key Research Findings
PPID prevalence in horses aged ≥15 years is 21-27%; basal ACTH diagnostic accuracy ranges 88-92% in autumn and 70-86% in non-autumn depending on pre-test probability
TRH stimulation testing shows superior diagnostic accuracy (92-98% in autumn, 90-94% in non-autumn) compared to basal ACTH testing
Pergolide improves most clinical signs and lowers basal ACTH in majority of affected horses, but does not alter insulin dysregulation measures in most cases
Multiple factors including breed, latitude, diet, and coat colour significantly affect ACTH concentrations, requiring use of equivocal diagnostic ranges rather than fixed thresholds
Insulin dysregulation encompasses both tissue insulin resistance and dysfunction of the enteroinsular axis in horses
The equine enteroinsular axis plays a major role in insulin secretion and hyperinsulinaemia development
Multiple factors including breed, diet, fasting state, and season significantly influence diagnostic test results and must be considered during interpretation
Early detection of insulin dysregulation is critical for laminitis prophylaxis as treatment options for established laminitis remain inadequate
Metformin administration reduced peak glucose concentration in healthy horses (P = 0.002) and in dexamethasone-induced insulin-resistant horses (P < 0.001)
Metformin significantly reduced area under the glucose curve in both healthy horses (P < 0.001) and insulin-resistant horses (P < 0.001)
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)
Metformin showed efficacy in reducing glycaemic and insulinaemic responses at both baseline and in experimentally induced insulin resistance states
Chromium and magnesium supplementation did not significantly improve insulin sensitivity in laminitic obese horses over 16 weeks
Hyperinsulinaemia (>30 µu/ml) was present in 12 of 14 horses prior to treatment
Resting insulin concentrations significantly increased over time in both groups (P = 0.018), suggesting supplement inefficacy
Evidence Base
BEVA primary care clinical guidelines: Diagnosis and management of equine pituitary pars intermedia dysfunction.
Menzies-Gow Nicola J, Banse Heidi E, Duff Aimi et al. (2024) — Equine veterinary journal
The diagnosis of equine insulin dysregulation.
Bertin F R, de Laat M A (2017) — Equine veterinary journal
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
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
Equine laminitis: induced by 48 h hyperinsulinaemia in Standardbred horses.
de Laat, McGowan, Sillence et al. (2010) — Equine veterinary journal
Epidemiological investigation of insulin dysregulation in Shetland and Welsh ponies in Australia.
Clark Brianna L, Norton Elaine M, Bamford Nicholas J et al. (2024) — Equine veterinary journal
Associations between feeding and glucagon-like peptide-2 in healthy ponies.
Sibthorpe Poppy E M, Fitzgerald Danielle M, Sillence Martin N et al. (2024) — Equine veterinary journal
Obesity and obesity-associated metabolic disease conditions in Connemara ponies in Ireland.
Al-Ansari Ahmed Saleh, Golding Emma, Walshe Nicola et al. (2024) — Equine veterinary journal
Lamellar energy metabolism and perfusion in the euglycaemic hyperinsulinaemic clamp model of equine laminitis.
Stokes Simon M, Bertin Francois R, Stefanovski Darko et al. (2020) — Equine veterinary journal
Association between hyperinsulinaemia and laminitis severity at the time of pituitary pars intermedia dysfunction diagnosis.
Tadros E M, Fowlie J G, Refsal K R et al. (2019) — Equine veterinary journal
Mouldable, thermoplastic, glue-on frog-supportive shoes change hoof kinetics in normal and obese Shetland ponies.
Sleutjens J, Serra Bragança F M, van Empelen M W et al. (2018) — Equine veterinary journal
The effect of mare obesity and endocrine function on foal birthweight in Thoroughbreds.
Smith S, Marr C M, Dunnett C et al. (2017) — Equine veterinary journal
Diurnal rhythm and effects of feeding, exercise and recombinant equine growth hormone on serum insulin concentrations in the horse.
Noble G K, Sillence M N (2013) — Equine veterinary journal
Distribution of insulin receptor and insulin-like growth factor-1 receptor in the digital laminae of mixed-breed ponies: an immunohistochemical study.
Burns T A, Watts M R, Weber P S et al. (2013) — Equine veterinary journal
Increased plasma fructosamine concentrations in laminitic horses.
Knowles, Withers, Mair (2012) — Equine veterinary journal
Measurement of C-peptide concentrations and responses to somatostatin, glucose infusion, and insulin resistance in horses.
Tóth F, Frank N, Martin-Jiménez T et al. (2010) — Equine veterinary journal
Prediction of incipient pasture-associated laminitis from hyperinsulinaemia, hyperleptinaemia and generalised and localised obesity in a cohort of ponies.
Carter, Treiber, Geor et al. (2009) — Equine veterinary journal
Evidence for dopamine production and distribution of dopamine D2 receptors in the equine gastrointestinal mucosa and pancreas.
Galinelli Nicolas C, Bamford Nicholas J, de Laat Melody A et al. (2024) — PloS one
Lamellar pathology in horses with pituitary pars intermedia dysfunction.
Karikoski N P, Patterson-Kane J C, Singer E R et al. (2016) — Equine veterinary journal
Hyperinsulinaemia increases vascular resistance and endothelin-1 expression in the equine digit.
Gauff F, Patan-Zugaj B, Licka T F (2013) — Equine veterinary journal
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Histopathology of insulin-induced laminitis in ponies.
Asplin, Patterson-Kane, Sillence et al. (2010) — Equine veterinary journal
The effect of metformin on measurements of insulin sensitivity and beta cell response in 18 horses and ponies with insulin resistance.
Durham A E, Rendle D I, Newton J E (2008) — Equine veterinary journal
Insulin resistance versus dysregulation—a distinction without a difference
Kellon E. M. (2025) — Equine Veterinary Education
Equine metabolic syndrome: part 1
Philip J Johnson (2024) — UK-Vet Equine
Horse owner experiences and observations with the use of SGLT2i for the management of equine metabolic syndrome and hyperinsulinaemia‐associated laminitis
T. Sundra, E. Kelty, Gabriele Rossi et al. (2024) — Equine Veterinary Education
Focus on the epidemiology, pathophysiology, diagnosis, and management of insulin dysregulation in horses
Olumide Odunayo Akinniyi (2024) — Nutrition and Food Processing
Equine metabolic syndrome: Role of the enteroinsular axis in the insulin response to oral carbohydrate.
de Laat Melody A, Fitzgerald Danielle M (2023) — Veterinary journal (London, England : 1997)
Ex vivo effects of insulin on the structural integrity of equine digital lamellae.
Sandow C, Fugler L A, Leise B et al. (2019) — Equine veterinary journal
Equine insulin receptor and insulin-like growth factor-1 receptor expression in digital lamellar tissue and insulin target tissues.
Kullmann A, Weber P S, Bishop J B et al. (2016) — Equine veterinary journal
The impact of prolonged hyperinsulinaemia on glucose transport in equine skeletal muscle and digital lamellae.
de Laat M A, Clement C K, Sillence M N et al. (2015) — Equine veterinary journal
Glucose homeostasis and the enteroinsular axis in the horse: a possible role in equine metabolic syndrome.
de Graaf-Roelfsema Ellen (2014) — Veterinary journal (London, England : 1997)
Insulin dysregulation.
Frank N, Tadros E M (2014) — Equine veterinary journal
Insulin resistance in equine digital vessel rings: an in vitro model to study vascular dysfunction in equine laminitis.
Venugopal, Eades, Holmes et al. (2012) — Equine veterinary journal
Equine Pituitary Pars Intermedia Dysfunction
McFarlane Dianne (2011) — Veterinary Clinics of North America: Equine Practice
Induction of laminitis by prolonged hyperinsulinaemia in clinically normal ponies.
Asplin, Sillence, Pollitt et al. (2008) — Veterinary journal (London, England : 1997)
Studies in vitro of equine intestinal glucagon-like peptide-2 secretion.
Sibthorpe P E M, Fitzgerald D M, Sillence M N et al. (2024) — Journal of equine veterinary science