Continuous intravenous infusion of glucose induces endogenous hyperinsulinaemia and lamellar histopathology in Standardbred horses.
Abstract: Endocrinopathic laminitis is frequently associated with hyperinsulinaemia but the role of glucose in the pathogenesis of the disease has not been fully investigated. This study aimed to determine the endogenous insulin response to a quantity of glucose equivalent to that administered during a laminitis-inducing, euglycaemic, hyperinsulinaemic clamp, over 48 h in insulin-sensitive Standardbred racehorses. In addition, the study investigated whether glucose infusion, in the absence of exogenous insulin administration, would result in the development of clinical and histopathological evidence of laminitis. Glucose (50% dextrose) was infused intravenously at a rate of 0.68 mL/kg/h for 48 h in treated horses (n=4) and control horses (n=3) received a balanced electrolyte solution (0.68 mL/kg/h). Lamellar histology was examined at the conclusion of the experiment. Horses in the treatment group were insulin sensitive (M value 0.039±0.0012 mmol/kg/min and M-to-I ratio (100×) 0.014±0.002) as determined by an approximated hyperglycaemic clamp. Treated horses developed glycosuria, hyperglycaemia (10.7±0.78 mmol/L) and hyperinsulinaemia (208±26.1 μIU/mL), whereas control horses did not. None of the horses became lame as a consequence of the experiment but all of the treated horses developed histopathological evidence of laminitis in at least one foot. Combined with earlier studies, the results showed that laminitis may be induced by either insulin alone or a combination of insulin and glucose, but that it is unlikely to be due to a glucose overload mechanism. Based on the histopathological data, the potential threshold for insulin toxicity (i.e., laminitis) in horses may be at or below a serum concentration of ∼200 μIU/mL.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication Date: 2011-08-27 PubMed ID: 21873088DOI: 10.1016/j.tvjl.2011.07.007Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study investigates the role of glucose in the development of endocrinopathic laminitis in horses. The researchers determined that a continuous intravenous infusion of glucose can cause an endogenous insulin response in the horse’s body and lead to clinical and histopathological symptoms of laminitis.
Study Objective and Methodology
- The aim of this study was to assess the body’s natural insulin response to an amount of glucose equivalent to that used in a euglycaemic, hyperinsulinaemic clamp procedure over a period of 48 hours in insulin-sensitive Standardbred racehorses.
- The study also explored whether the infusion of glucose without the addition of exogenous insulin would result in the development of laminitis – a condition that affects the horse’s lamellae, leading to severe pain and potential lameness.
- The researchers infused a 50% dextrose solution intravenously into the treated horses at a rate of 0.68 mL/kg/h for 48 hours. The control group of horses received a balanced electrolyte solution.
- At the end of the experiment, the researchers examined the lamellar histology of all horses involved in the study.
Results and Findings
- The treated horses displayed insulin sensitivity, developing hyperglycaemia (high blood sugar levels) and hyperinsulinaemia (an excessive amount of insulin).
- Unlike the control horses, those in the treatment group developed glycosuria – an excessive amount of glucose in the urine – indicating that their bodies were not processing the sugar appropriately.
- While none of the horses displayed overt signs of lameness following treatment, all treated horses showed signs of histopathological laminitis in one foot at least.
- On comparing with previous studies, the researchers inferred that laminitis could be caused by insulin alone or in combination with glucose, but it is unlikely to occur as a result of a glucose overload alone.
Conclusions and Implications
- The study concludes that the potential threshold for insulin toxicity that could lead to laminitis in horses may be at or below a serum concentration of around 200 μIU/mL.
- The findings suggest the need for further research to confirm the effects of glucose and insulin levels on the development of laminitis.
- The results have significant implications for the understanding of endocrinopathic laminitis and could help inform feeding and care practices for racehorses and other equines that may be at risk.
Cite This Article
APA
de Laat MA, Sillence MN, McGowan CM, Pollitt CC.
(2011).
Continuous intravenous infusion of glucose induces endogenous hyperinsulinaemia and lamellar histopathology in Standardbred horses.
Vet J, 191(3), 317-322.
https://doi.org/10.1016/j.tvjl.2011.07.007 Publication
Researcher Affiliations
- Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Gatton, Queensland 4343, Australia. m.delaat@uq.edu.au
MeSH Terms
- Animals
- Blood Glucose
- Drug Administration Schedule
- Foot Diseases / chemically induced
- Foot Diseases / pathology
- Foot Diseases / veterinary
- Glucose / administration & dosage
- Glucose / toxicity
- Hoof and Claw
- Horse Diseases / chemically induced
- Horses
- Hyperinsulinism / chemically induced
- Hyperinsulinism / complications
- Hyperinsulinism / veterinary
- Inflammation / chemically induced
- Inflammation / pathology
- Inflammation / veterinary
- Insulin Resistance
- Male
Citations
This article has been cited 18 times.- de Tonnerre DJ, Medina Torres CE, Stefanovski D, Robinson MA, Kemp KL, Bertin FR, van Eps AW. Effect of sirolimus on insulin dynamics in horses. J Vet Intern Med 2023 Mar;37(2):703-712.
- Daradics Z, Crecan CM, Rus MA, Morar IA, Mircean MV, Cătoi AF, Cecan AD, Cătoi C. Obesity-Related Metabolic Dysfunction in Dairy Cows and Horses: Comparison to Human Metabolic Syndrome. Life (Basel) 2021 Dec 16;11(12).
- Stokes SM, Stefanovski D, Bertin FR, Medina-Torres CE, Belknap JK, van Eps AW. Plasma amino acid concentrations during experimental hyperinsulinemia in 2 laminitis models. J Vet Intern Med 2021 May;35(3):1589-1596.
- Gehlen H, Schwarz B, Bartmann C, Gernhardt J, Stöckle SD. Pituitary Pars Intermedia Dysfunction and Metabolic Syndrome in Donkeys. Animals (Basel) 2020 Dec 8;10(12).
- Taylor S. A review of equine sepsis. Equine Vet Educ 2015 Feb;27(2):99-109.
- Fitzgerald DM, Pollitt CC, Walsh DM, Sillence MN, de Laat MA. The effect of different grazing conditions on the insulin and incretin response to the oral glucose test in ponies. BMC Vet Res 2019 Oct 16;15(1):345.
- Durham AE, Frank N, McGowan CM, Menzies-Gow NJ, Roelfsema E, Vervuert I, Feige K, Fey K. ECEIM consensus statement on equine metabolic syndrome. J Vet Intern Med 2019 Mar;33(2):335-349.
- Fitzgerald DM, Walsh DM, Sillence MN, Pollitt CC, de Laat MA. Insulin and incretin responses to grazing in insulin-dysregulated and healthy ponies. J Vet Intern Med 2019 Jan;33(1):225-232.
- Jacob SI, Murray KJ, Rendahl AK, Geor RJ, Schultz NE, McCue ME. Metabolic perturbations in Welsh Ponies with insulin dysregulation, obesity, and laminitis. J Vet Intern Med 2018 May;32(3):1215-1233.
- Morgan R, Keen J, McGowan C. Equine metabolic syndrome. Vet Rec 2015 Aug 15;177(7):173-9.
- Ertelt A, Barton AK, Schmitz RR, Gehlen H. Metabolic syndrome: is equine disease comparable to what we know in humans?. Endocr Connect 2014 Sep;3(3):R81-93.
- Gauff FC, Patan-Zugaj B, Licka TF. Effect of short-term hyperinsulinemia on the localization and expression of endothelin receptors A and B in lamellar tissue of the forelimbs of horses. Am J Vet Res 2014 Apr;75(4):367-74.
- Gauff F, Patan-Zugaj B, Licka TF. Hyperinsulinaemia increases vascular resistance and endothelin-1 expression in the equine digit. Equine Vet J 2013 Sep;45(5):613-8.
- Palmer AT, Watts MR, Timko KJ, Pinnell EF, Keefer KA, Gorman O, Hostnik LD, Burns TA. Corticosteroid Administration Enhances the Glycemic, Insulinemic, and Incretin Responses to a High-Protein Mixed Meal in Adult Horses. J Vet Intern Med 2025 Mar-Apr;39(2):e17305.
- Nolen-Walston RD, Kulp JC, Stefanovski D, van Eps AW. Evaluation of an Automated Fluorescence Enzyme Immunoassay for Quantification of Equine Insulin and Comparison to Five Other Immunoassays. J Vet Intern Med 2025 Mar-Apr;39(2):e70038.
- Galinelli NC, Bamford NJ, Erdody ML, Mackenzie SA, Warnken T, Harris PA, Sillence MN, Bailey SR. Effect of pergolide treatment on insulin dysregulation in horses and ponies with pituitary pars intermedia dysfunction. Equine Vet J 2025 Nov;57(6):1612-1622.
- Hallowell KL, Dembek K, Horne CR, Knych HK, Messenger KM, Schnabel LV. Systemic absorption of triamcinolone acetonide is increased from intrasynovial versus extrasynovial sites and induces hyperglycemia, hyperinsulinemia, and suppression of the hypothalamic-pituitary-adrenal axis. Front Vet Sci 2024;11:1388470.
- de Laat MA, Fitzgerald DM, Harris PA, Bailey SR. A glucagon-like peptide-1 receptor antagonist reduces the insulin response to a glycemic meal in ponies. J Anim Sci 2023 Jan 3;101.
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