Analyze Diet
Journal of veterinary internal medicine2020; 34(2); 902-908; doi: 10.1111/jvim.15747

Blood glucose and insulin concentrations after alpha-2-agonists administration in horses with and without insulin dysregulation.

Abstract: In metabolically stable horses, alpha-2-agonists suppress insulin secretion with transient hyperglycemia and rebound hyperinsulinemia. In horses with insulin dysregulation (ID), the effect of alpha-2-agonists has not been investigated; however, both the alpha-2-agonist-induced suppression of insulin secretion and rebound hyperinsulinemia could have clinical relevance. Objective: In horses with ID, alpha-2-agonists will alter insulin and glucose dynamics. Methods: Seven horses with ID and 7 control horses. Methods: In this randomized crossover study, xylazine hydrochloride (1.1 mg/kg) or detomidine hydrochloride (30 μg/kg) were administered IV, and blood was collected for glucose and insulin concentrations at 0, 15, 30, 45, 60, 90, 120, 150, 180, and 300 minutes after administration. Horses received each drug in a random order with a 24-hour washout period between drugs. Percent change in glucose and insulin concentrations was compared between groups, drugs, and over time with P < .05 considered significant. Results: A significant time-dependent effect of both alpha-2-agonists on glucose and insulin concentrations in control and ID horses was identified (P = .01 for all comparisons). There was no significant effect of sedative selection and endocrine status on blood glucose concentration in either group; however, in ID horses, xylazine administration resulted in severe rebound hyperinsulinemia whereas detomidine administration did not (P = .02). Conclusions: Alpha-2-agonists have a significant effect on glucose and insulin concentrations in horses. In ID horses, detomidine could minimize hyperinsulinemia when compared to xylazine.
Publication Date: 2020-02-26 PubMed ID: 32100334PubMed Central: PMC7096659DOI: 10.1111/jvim.15747Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article
  • Randomized Controlled Trial
  • Veterinary

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research paper studies the effect of alpha-2-agonists on insulin and glucose levels in horses, especially those with insulin dysregulation. It concludes that while both alpha-2-agonists cause significant alterations in glucose and insulin concentrations, detomidine seems to cause less severe rebound hyperinsulinemia compared to xylazine in horses with insulin disorders.

Study Objective and Methods

  • The objective of the study was to determine the impact of alpha-2-agonists—chemicals that suppress insulin secretion—on blood insulin and glucose dynamics in horses with insulin dysregulation. Insulin dysregulation is when a horse’s body does not respond to insulin as it should, a condition which can lead to chronic endocrine disorders.
  • The research was a randomized crossover study, involving 14 horses—7 with insulin dysregulation and 7 without it. Two different drugs, xylazine hydrochloride and detomidine hydrochloride, both alpha-2 agonists, were administered to the horses.
  • After administering the drugs, blood samples were taken at various intervals, up to 300 minutes post administration. The insulin and glucose concentrations in each sample were measured.
  • The variations in insulin and glucose levels between the two groups of horses, and the two drugs, were compared. A statistical threshold (P) of less than .05 was used to identify significant changes. A lower P-value means the result has a higher chance of being statistically significant.

Study Results

  • The study found a significant time-dependent impact of both alpha-2-agonists on glucose and insulin concentrations, regardless of whether the horses had insulin dysregulation (P = .01 for all comparisons).
  • The type of sedative used and the endocrine status of the horses did not significantly impact the blood glucose concentrations in either group. However, a significant difference was observed in the effects of xylazine and detomidine on horses with insulin dysregulation.
  • In horses with insulin dysregulation, xylazine resulted in severe rebound hyperinsulinemia or a sharp spike in insulin following its initial suppression. In comparison, detomidine did not cause severe rebound hyperinsulinemia.

Conclusion

  • The study concluded that alpha-2-agonists significantly affect glucose and insulin concentrations in horses. In horses with insulin dysregulation, the use of detomidine can potentially reduce the risk of severe rebound hyperinsulinemia when compared to xylazine.
  • These findings could have clinical implications, particularly for the treatment and management of horses with insulin-related disorders. Appropriate use of alpha-2-agonists could help in controlling insulin spikes and maintaining healthy glucose levels in these animals.

Cite This Article

APA
Kritchevsky JE, Muir GS, Leschke DHZ, Hodgson JK, Hess EK, Bertin FR. (2020). Blood glucose and insulin concentrations after alpha-2-agonists administration in horses with and without insulin dysregulation. J Vet Intern Med, 34(2), 902-908. https://doi.org/10.1111/jvim.15747

Publication

ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 34
Issue: 2
Pages: 902-908

Researcher Affiliations

Kritchevsky, Janice E
  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana.
Muir, Genevieve S
  • School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia.
Leschke, Dakota H Z
  • School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia.
Hodgson, Jack K
  • School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia.
Hess, Emily K
  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana.
Bertin, Francois-Rene
  • School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia.

MeSH Terms

  • Adrenergic alpha-2 Receptor Agonists / pharmacology
  • Animals
  • Blood Glucose / drug effects
  • Conscious Sedation / veterinary
  • Cross-Over Studies
  • Female
  • Horses / blood
  • Horses / physiology
  • Hypnotics and Sedatives / pharmacology
  • Imidazoles / pharmacology
  • Insulin / blood
  • Male
  • Xylazine / pharmacology

Grant Funding

  • John & Mary Kibble Trust

Conflict of Interest Statement

Authors declare no conflict of interest.

References

This article includes 24 references
  1. Rohrbach H, Korpivaara T, Schatzmann U, Spadavecchia C. Comparison of the effects of the alpha-2 agonists detomidine, romifidine and xylazine on nociceptive withdrawal reflex and temporal summation in horses.. Vet Anaesth Analg 2009 Jul;36(4):384-95.
  2. England GC, Clarke KW, Goossens L. A comparison of the sedative effects of three alpha 2-adrenoceptor agonists (romifidine, detomidine and xylazine) in the horse.. J Vet Pharmacol Ther 1992 Jun;15(2):194-201.
  3. Grimsrud KN, Ait-Oudhia S, Durbin-Johnson BP, Rocke DM, Mama KR, Rezende ML, Stanley SD, Jusko WJ. Pharmacokinetic and pharmacodynamic analysis comparing diverse effects of detomidine, medetomidine, and dexmedetomidine in the horse: a population analysis.. J Vet Pharmacol Ther 2015 Feb;38(1):24-34.
    pmc: PMC4286451pubmed: 25073816doi: 10.1111/jvp.12139google scholar: lookup
  4. Ringer SK, Schwarzwald CC, Portier K, Mauch J, Ritter A, Bettschart-Wolfensberger R. Blood glucose, acid-base and electrolyte changes during loading doses of alpha₂-adrenergic agonists followed by constant rate infusions in horses.. Vet J 2013 Dec;198(3):684-9.
    pubmed: 24215780doi: 10.1016/j.tvjl.2013.09.063google scholar: lookup
  5. Hirose H, Maruyama H, Ito K, Kido K, Koyama K, Saruta T. Effects of alpha 2- and beta-adrenergic agonism on glucagon secretion from perfused pancreata of normal and streptozocin-induced diabetic rats.. Metabolism 1993 Aug;42(8):1072-6.
    pubmed: 8102194doi: 10.1016/0026-0495(93)90025-jgoogle scholar: lookup
  6. de Laat MA, McGree JM, Sillence MN. Equine hyperinsulinemia: investigation of the enteroinsular axis during insulin dysregulation.. Am J Physiol Endocrinol Metab 2016 Jan 1;310(1):E61-72.
    pubmed: 26530154doi: 10.1152/ajpendo.00362.2015google scholar: lookup
  7. Bertin FR, Ruffin-Taylor D, Stewart AJ. Insulin dysregulation in horses with systemic inflammatory response syndrome.. J Vet Intern Med 2018 Jul;32(4):1420-1427.
    pmc: PMC6060318pubmed: 29749643doi: 10.1111/jvim.15138google scholar: lookup
  8. Frank N, Tadros EM. Insulin dysregulation.. Equine Vet J 2014 Jan;46(1):103-12.
    pubmed: 24033478doi: 10.1111/evj.12169google scholar: lookup
  9. Frank N, Geor RJ, Bailey SR, Durham AE, Johnson PJ. Equine metabolic syndrome.. J Vet Intern Med 2010 May-Jun;24(3):467-75.
  10. de Laat MA, McGowan CM, Sillence MN, Pollitt CC. Equine laminitis: induced by 48 h hyperinsulinaemia in Standardbred horses.. Equine Vet J 2010 Mar;42(2):129-35.
    pubmed: 20156248doi: 10.2746/042516409x475779google scholar: lookup
  11. de Laat MA, Sillence MN. The repeatability of an oral glucose test in ponies.. Equine Vet J 2017 Mar;49(2):238-243.
    pubmed: 27038020doi: 10.1111/evj.12579google scholar: lookup
  12. Schuver A, Frank N, Chameroy KA, Elliott SB. Assessment of insulin and glucose dynamics by using an oral sugar test in horses.. J Equine Vet 2014;34:465‐470.
  13. Bertin FR, Sojka-Kritchevsky JE. Comparison of a 2-step insulin-response test to conventional insulin-sensitivity testing in horses.. Domest Anim Endocrinol 2013 Jan;44(1):19-25.
  14. Bertin FR, Taylor SD, Bianco AW, Sojka-Kritchevsky JE. The Effect of Fasting Duration on Baseline Blood Glucose Concentration, Blood Insulin Concentration, Glucose/Insulin Ratio, Oral Sugar Test, and Insulin Response Test Results in Horses.. J Vet Intern Med 2016 Sep;30(5):1726-1731.
    pmc: PMC5032872pubmed: 27481572doi: 10.1111/jvim.14529google scholar: lookup
  15. Bertin FR, de Laat MA. The diagnosis of equine insulin dysregulation.. Equine Vet J 2017 Sep;49(5):570-576.
    pubmed: 28543410doi: 10.1111/evj.12703google scholar: lookup
  16. Bertin FR, Pader KS, Lescun TB, Sojka-Kritchevsky JE. Short-term effect of ovariectomy on measures of insulin sensitivity and response to dexamethasone administration in horses.. Am J Vet Res 2013 Dec;74(12):1506-13.
    pubmed: 24274888doi: 10.2460/ajvr.74.12.1506google scholar: lookup
  17. Warnken T, Huber K, Feige K. Comparison of three different methods for the quantification of equine insulin.. BMC Vet Res 2016 Sep 9;12(1):196.
    pmc: PMC5016943pubmed: 27613127doi: 10.1186/s12917-016-0828-zgoogle scholar: lookup
  18. Eiler H, Frank N, Andrews FM, Oliver JW, Fecteau KA. Physiologic assessment of blood glucose homeostasis via combined intravenous glucose and insulin testing in horses.. Am J Vet Res 2005 Sep;66(9):1598-604.
    pubmed: 16261835doi: 10.2460/ajvr.2005.66.1598google scholar: lookup
  19. Tóth F, Frank N, Elliott SB, Perdue K, Geor RJ, Boston RC. Optimisation of the frequently sampled intravenous glucose tolerance test to reduce urinary glucose spilling in horses.. Equine Vet J 2009 Dec;41(9):844-51.
    pubmed: 20383980doi: 10.2746/042516409x439661google scholar: lookup
  20. Pratt SE, Geor RJ, McCutcheon LJ. Repeatability of 2 methods for assessment of insulin sensitivity and glucose dynamics in horses.. J Vet Intern Med 2005 Nov-Dec;19(6):883-8.
  21. Schwartz DD, Clark TP. Affinity of detomidine, medetomidine and xylazine for alpha-2 adrenergic receptor subtypes.. J Vet Pharmacol Ther 1998 Apr;21(2):107-11.
  22. Fagerholm V, Haaparanta M, Scheinin M. α2-adrenoceptor regulation of blood glucose homeostasis.. Basic Clin Pharmacol Toxicol 2011 Jun;108(6):365-70.
  23. Ringer SK, Schwarzwald CC, Portier KG, Ritter A, Bettschart-Wolfensberger R. Effects on cardiopulmonary function and oxygen delivery of doses of romifidine and xylazine followed by constant rate infusions in standing horses.. Vet J 2013 Feb;195(2):228-34.
    pubmed: 22841452doi: 10.1016/j.tvjl.2012.06.036google scholar: lookup
  24. Carslake HB, Pinchbeck GL, McGowan CM. Evaluation of a Chemiluminescent Immunoassay for Measurement of Equine Insulin.. J Vet Intern Med 2017 Mar;31(2):568-574.
    pmc: PMC5354037pubmed: 28124389doi: 10.1111/jvim.14657google scholar: lookup

Citations

This article has been cited 4 times.
  1. Timko KJ, Hostnik LD, Watts MR, Chen C, Bercz A, Toribio RE, Belknap JK, Burns TA. Diagnostic evaluation of insulin and glucose dynamics in light-breed horses receiving dexamethasone.. Can Vet J 2022 Jun;63(6):617-626.
    pubmed: 35656529
  2. Ryan A, Gurney M, Steinbacher R. Suspected vagal reflex and hyperkalaemia inducing asystole in an anaesthetised horse.. Equine Vet J 2022 Sep;54(5):927-933.
    doi: 10.1111/evj.13535pubmed: 34738246google scholar: lookup
  3. Hicks GR, Fraser NS, Bertin FR. Changes Associated with the Peri-Ovulatory Period, Age and Pregnancy in ACTH, Cortisol, Glucose and Insulin Concentrations in Mares.. Animals (Basel) 2021 Mar 20;11(3).
    doi: 10.3390/ani11030891pubmed: 33804751google scholar: lookup
  4. Kinsella HM, Hostnik LD, Rings LM, Swink JM, Burns TA, Toribio RE. Glucagon, insulin, adrenocorticotropic hormone, and cortisol in response to carbohydrates and fasting in healthy neonatal foals.. J Vet Intern Med 2021 Jan;35(1):550-559.
    doi: 10.1111/jvim.16024pubmed: 33415818google scholar: lookup