Journal of Equine Veterinary Science
Volume 28, Issue 12 , Pages 753-759 , December 2008

Metabolic Predispositions to Laminitis in Horses and Ponies: Obesity, Insulin Resistance and Metabolic Syndromes

  • Raymond J. Geor, BVSc, MVSc, PhD, Diplomate ACVIM

      Affiliations

    • Corresponding Author InformationReprint requests: Raymond J. Geor, Department of Large Animal Clinical Sciences, D202, Veterinary Medical Center, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824-1314.

References 

  1. Treiber KH, Kronfeld DS, Hess TM, Byrd BM, Staniar WB, Splan RK. Evaluation of genetic and metabolic predispositions and nutritional risk factors for pasture-associated laminitis in ponies. J Am Vet Med Assoc. 2006;228:1538–1545
  2. Treiber KH, Kronfeld DS, Geor RJ. Insulin resistance in equids: possible role in laminitis. J Nutr. 2006;136:2094S–2098S
  3. Frank N, Elliott SB, Brandt LE, Keisler DH. Physical characteristics, blood hormone concentrations, and plasma lipid concentrations in obese horses with insulin resistance. J Am Vet Med Assoc. 2006;228:1383–1390
  4. Bailey SR, Menzies-Gow NJ, Harris PA, Habsershon-Butcher JL, Crawford C, Berhane Y, et al. Effect of dietary fructans and dexamethasone administration on the insulin response of ponies predisposed to laminitis. J Am Vet Med Assoc. 2007;231:1365–1373
  5. Bailey SR, Habershon-Butcher JL, Ransom KJ, Elliott J, Menzies-Gow NJ. Hypertension and insulin resistance in a mixed-breed population of ponies predisposed to laminitis. Am J Vet Res. 2008;69:122–129
  6. Wild SH, Byrne CD. ABC of obesity: risk factors for diabetes and coronary heart disease. Br Med J. 2006;333:1009–1011
  7. De Lorenzo A, Del Gobbo V, Premrov MG, Bigioni M, Galvano F, Di Renzo L. Normal-weight obese syndrome: early inflammation. Am J Clin Nutr. 2007;85:40–45
  8. Henneke DR, Potter GD, Kreider JL, Yeates BF. Relationship between condition score, physical measurements and body fat percentage in mares. Equine Vet J. 1983;15:371–372
  9. Donaldson MT, Jorgensen AJ, Beech J. Evaluation of suspected pars pituitary intermedia dysfunction in horses with laminitis. J Am Vet Med Assoc. 2004;224:1123–1127
  10. Lee S, Bacha F, Gungor N, Arslanian SA. Waist circumference is an independent predictor of insulin resistance in black and white youths. J Pediatr. 2006;148:188–194
  11. Alberti KG, Zimmet P, Shaw J. Metabolic syndrome—a new world-wide definition. A consensus statement from the International Diabetes Federation. Diabet Med. 2006;23:469–480
  12. Carter RA, Treiber KH, Geor RJ, Douglas L, Harris PA. Prediction of incipient pasture-associated laminitis from hyperinsulinemia, hyperleptinemia, and generalized and localized obesity in a cohort of ponies. Equine Vet J 2008; epub ahead of print: September 22; doi:10.2746/042516408X342975.
  13. United States Department of Agriculture. NAHMS Equine ’98. Part III. Management and Health of Horses. Available at: www.aphis.usda.gov/vs/ceah/cahm. Accessed August 5, 2008.
  14. Saltiel AR, Kahn CR. Insulin signaling and the regulation of glucose and lipid metabolism. Nature. 2001;414:799–806
  15. Wilcox G. Insulin and insulin resistance. Clin Biochem Rev. 2005;26:19–39
  16. Hansen TK, Thiel S, Wouters PJ, Christiansen JS, Van Den Berghe G. Intensive insulin therapy exerts anti-inflammatory effects in critically ill patients and counteracts the adverse effects of low mannose-binding lectin levels. J Clin Endocrinol Metab. 2003;88:1082–1088
  17. Muniyappa R, Lee S, Chen H, Quon MJ. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations and appropriate usage. Am J Physiol Endocrinol Metab. 2008;294:E15–E26
  18. Kahn CR. Insulin resistance, insulin sensitivity, and insulin unresponsiveness: a necessary distinction. Metabolism. 1978;27:1893–1902
  19. Yudkin JS. Insulin resistance and the metabolic syndrome—or the pitfalls of epidemiology. Diabetologica. 2007;50:1576–1586
  20. Muoio DM, Newgard CB. Molecular and metabolic mechanisms of insulin resistance and β-cell failure in type 2 diabetes. Nature Reviews. 2008;9:193–205
  21. Carter RA, McCutcheon LJ, Burns TA, Belknap JK, Frank N, Geor RJ. Increased adiposity in horses is associated with decreased insulin sensitivity but unchanged inflammatory cytokine expression in subcutaneous adipose tissue. J Vet Intern Med. 2008;22:735;(abstr)
  22. Vick MM, Adams AA, Murphy BA, Sessions DR, Horohov DW, Cook RF, et al. Relationships among inflammatory cytokines, obesity, and insulin sensitivity in the horse. J Anim Sci. 2007;85:1144–1155
  23. Schott HC II. Pituitary pars intermedia dysfunction: challenges of diagnosis and treatment. Proc Am Assoc Equine Pract. 2006;52:60–73
  24. McGowan CM, Frost R, Pfeiffer DU. Serum insulin concentrations in horses with equine Cushing's syndrome: response to a cortisol inhibitor and prognostic value. Equine Vet J. 2004;36:295–298
  25. Hoffman RM, Boston RC, Stefanovski D, Kronfeld DS, Harris PA. Obesity and diet affect glucose dynamics and insulin sensitivity in Thoroughbred geldings. J Anim Sci. 2003;81:2333–2342
  26. Grundy SM. Does a diagnosis of metabolic syndrome have value in clinical practice?. Am J Clin Nutr. 2006;83:1248–1251
  27. Kahn R, Buse J, Ferrannini E, Stern M. American Diabetes Association, European Association for the Study of Diabetes. The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and European Association for the Study of Diabetes. Diabetes Care. 2005;28:2289–2304
  28. Reaven GM. The insulin resistance syndrome: definition and dietary approaches to treatment. Ann Rev Nutr. 2005;25:391–406
  29. Johnson PJ. The equine metabolic syndrome: peripheral Cushing's syndrome. Vet Clin North Am: Equine Pract. 2002;18:271–293
  30. Coffman JR, Colles CM. Insulin tolerance in laminitic ponies. Can J Comp Med. 1983;47:347–351
  31. Field JR, Jeffcott LB. Equine laminitis: another hypothesis for pathogenesis. Med Hypoth. 1989;30:203–210
  32. Treiber KH, Hess TM, Kronfeld DS, Geor RJ, Boston RC, Harris PA. Insulin resistance and compensation in laminitis-predisposed ponies characterized by the minimal model. Pferdeheilkunde. 2007;21:91–92
  33. Asplin KE, Sillence MN, Pollitt CC, McGowan CM. Induction of laminitis by prolonged hyperinsulinaemia in clinically normal ponies. Vet J. 2007;174:530–535
  34. Frank N. Insulin resistance in horses. Proc Am Assoc Equine Pract. 2006;52:51–54
  35. Alford P, Geller S, Richardson B, Slater M, Honnas C, Foreman J, et al. A multicenter, matched case-control study of risk factors for equine laminitis. Prev Vet Med. 2001;49:209–222
  36. Pass MA, Pollitt S, Pollitt CC. Decreased glucose metabolism causes separation of hoof lamellae in vitro: a trigger for laminitis?. Equine Vet J. 1998;(Suppl 26):133–138
  37. French KR, Pollitt CC. Equine laminitis: glucose deprivation and MMP activation induce dermo-epidermal separation in vitro. Equine Vet J. 2004;36:261–266
  38. Mobasheri A, Critchlow K, Clegg PD, Carter SD, Canessa CM. Chronic equine laminitis is characterised by loss of GLUT1, GLUT4 and ENaC positive laminar keratinocytes. Equine Vet J. 2004;36:248–254
  39. Asplin KE, McGowan CM, Pollitt CC, Sillence MN. Role of insulin in glucose uptake in the equine hoof. J Vet Int Med. 2007;21:668;(abstr)
  40. Kim JK, Montagnani M, Koh KK, Quon MJ. Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms. Circulation. 2006;113:1888–1904
  41. Shoelson SE, Herrero L, Naaz A. Obesity, inflammation and insulin resistance. Gastroenterology. 2007;132:2169–2180
  42. Dandona P, Aljada A, Bandyopadhyay A. Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol. 2004;25:4–7
  43. Hutley L, Prins JB. Fat as an endocrine organ: relationship to the metabolic syndrome. Am J Med Sci. 2005;330:280–289
  44. Treiber K, Carter R, Gay L, Williams C, Geor R. Inflammatory and redox status of ponies with a history of pasture-associated laminitis. Vet Immunol Immunopathol 2008; In press.
  45. Tiley HA, Geor RJ, McCutcheon LJ. Effects of dexamethasone on glucose dynamics and insulin sensitivity in healthy horses. Am J Vet Res. 2007;68:753–759
  46. Tóth F, Frank N, Elliott SB, Geor RJ, Boston RC. Effects of intravenous endotoxin on glucose and insulin dynamics in horses. Am J Vet Res. 2008;69:82–88
  47. Treiber KH, Carter RA, Harris PA, Geor RJ. Seasonal changes in energy metabolism of ponies coincides with changes in pasture carbohydrates: implications for laminitis. J Vet Intern Med. 2008;22:735–736(abstr)
  48. van Eps AW, Pollitt CC. Equine laminitis induced with oligofructose. Equine Vet J. 2006;38:203–208
  49. Milinovich GJ, Burrell PC, Pollitt CC, Klieve AV, Blackall LL, Ouwerkerk D, et al. Microbial ecology of the equine hindgut during oligofructose-induced laminitis. ISME J 2008; epub ahead of print: June 26; doi:10:1038/ismej.2008.67.
  50. Bailey SR, Marr CM, Elliott J. Current research and theories on the pathogenesis of acute laminitis in the horse. Vet J. 2004;167:129–142
  51. Belknap JK, Giguere S, Pettigrew A, Cochran AM, Van Eps AW, Pollitt CC. Lamellar pro-inflammatory cytokine expression patterns in laminitis at the developmental stage and at the onset of lameness: innate vs. adaptive immune response. Equine Vet J. 2007;39:42–47
  52. Harris PA, Bailey SR, Elliott J, Longland A. Countermeasures to pasture-associated laminitis in horses. J Nutr. 2006;136:2114S–2121S
  53. Durham AE, Rendle DI, Newton JE. The effect of metformin on measurements of insulin sensitivity and beta cell response in 18 horses and ponies with insulin resistance. Equine Vet J. 2008;40:493–500

 Presented at the 4th International Equine Conference on Laminitis and Diseases of the Foot, November 1–4, 2007, West Palm Beach, Florida.

 Refereed

PII: S0737-0806(08)00346-8

doi: 10.1016/j.jevs.2008.10.016

Journal of Equine Veterinary Science
Volume 28, Issue 12 , Pages 753-759 , December 2008