• 1

    Neel JV. Diabetes mellitus: a thrifty genotype rendered detrimental by progress. Am J Human Gen 1962;14:353362.

  • 2

    Brand-Miller JC, Colagirui S. Evolutionary aspects of diet and insulin resistance. World Rev Nutr Diet 1999;84:74105.

  • 3

    Treiber KH, Boston RC, Kronfeld DS, et al. Insulin resistance and compensation in Thoroughbred weanlings adapted to high-glycemic meals. J Anim Sci 2005;83:23572364.

    • Search Google Scholar
    • Export Citation
  • 4

    World Health Organization. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Geneva: World Health Organization, 1999.

    • Search Google Scholar
    • Export Citation
  • 5

    Adult Treatment Panel III. Third report of the expert panel on detection, evaluation, and treatment of high blood cholesterol in adults. NIH Pub. No. 02-5215. Bethesda, Md: National Institutes of Health, 2002;1284.

    • Search Google Scholar
    • Export Citation
  • 6

    Jeffcott LB, Field JR. Current concepts of hyperlipaemia in horses and ponies. Vet Rec 1985;116:461466.

  • 7

    Johnson PJ. The equine metabolic syndrome peripheral Cushing's syndrome. Vet Clin North Am Equine Pract 2002;18:271293.

  • 8

    USDA. Lameness and laminitis in U. S. horses. #N318.0400. Fort Collins, Colo: USDA, APHIS, VA, CEAH, National Animal Health Monitoring System, 2000.

    • Search Google Scholar
    • Export Citation
  • 9

    Bailey SR, Marr CM, Elliott J. Current research and theories on the pathogenesis of acute laminitis in the horse. Vet J 2004;167:129142.

    • Search Google Scholar
    • Export Citation
  • 10

    Moore RM. Laminitis: steps in an on-going battle. Grayson-Jockey Club Research Today 2005;22:34.

  • 11

    Hood DM. The mechanisms and consequences of structural failure of the foot. Vet Clin North Am Equine Pract 1999;15:437461.

  • 12

    Kahn R, Buse J, Ferrannini E, et al. The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2005;28:22892304.

    • Search Google Scholar
    • Export Citation
  • 13

    Kronfeld DS, Treiber KH, Geor RJ. Comparison of nonspecific indications and quantitative methods for the assessment of insulin resistance in horses and ponies. J Am Vet Med Assoc 2005;226:712719.

    • Search Google Scholar
    • Export Citation
  • 14

    Balkau B, Charles MA. Comment on the provisional report from the WHO consultation. European Group for the Study of Insulin Resistance (EGIR). Diabet Med 1999;16:442443.

    • Search Google Scholar
    • Export Citation
  • 15

    Ford ES, Giles WH. A comparison of the prevalence of the metabolic syndrome using two proposed definitions. Diabetes Care 2003;26:575581.

    • Search Google Scholar
    • Export Citation
  • 16

    Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988;37:15951607.

  • 17

    Kerem N, Guttmann H, Hochberg Z. The autosomal dominant trait of obesity, acanthosis nigricans, hypertension, ischemic heart disease and diabetes type 2. Horm Res 2001;55:298304.

    • Search Google Scholar
    • Export Citation
  • 18

    Henneke DR, Potter GD, Kreider JL, et al. Relationship between condition score, physical measurements and body fat percentage in mares. Equine Vet J 1983;15:371372.

    • Search Google Scholar
    • Export Citation
  • 19

    Reimers TJ, Cowan RG, McCann JP, et al. Validation of a rapid solid-phase radioimmunoassay for canine, bovine, and equine insulin. Am J Vet Res 1982;43:12741278.

    • Search Google Scholar
    • Export Citation
  • 20

    Alexander SL, Irvine CHG. The effect of social stress on adrenal axis activity in horses: the importance of monitoring corticosteroid-binding globulin capacity. J Endocrinol 1998;157:425432.

    • Search Google Scholar
    • Export Citation
  • 21

    Treiber KH, Kronfeld DS, Hess TM, et al. Use of proxies and reference quintiles obtained from minimal model analysis for determination of insulin sensitivity and pancreatic beta-cell responsiveness in horses. Am J Vet Res 2005;66:21142121.

    • Search Google Scholar
    • Export Citation
  • 22

    Gibson RS. Principles of nutritional assessment. New York: Oxford University Press, 1990.

  • 23

    McLaughlin T, Abbasi F, Cheal K, et al. Use of metabolic markers to identify overweight individuals who are insulin resistant. Ann Intern Med 2003;139:802809.

    • Search Google Scholar
    • Export Citation
  • 24

    LaCasha PA, Brady HA, Allen VG, et al. Voluntary intake, digestibility, and subsequent selection of Matua bromegrass, coastal bermudagrass, and alfalfa hays by yearling horses. J Anim Sci 1999;77:27662773.

    • Search Google Scholar
    • Export Citation
  • 25

    Pearson RA, Archibald RF, Muirhead RH. The effect of forage quality and level of feeding on digestibility and gastrointestinal transit time of oat straw and alfalfa given to ponies and donkeys. Br J Nutr 2001;85:599606.

    • Search Google Scholar
    • Export Citation
  • 26

    Hales CN, Barker DJP. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia 1992;35:595601.

    • Search Google Scholar
    • Export Citation
  • 27

    Lindsay RS, Prochazka M, Baier LJ, et al. Currently identified genes affecting insulin resistance are not associated with birth weight in the Pima population. Diabetic Med 2002;19:881886.

    • Search Google Scholar
    • Export Citation
  • 28

    Alford P, Gellar S, Richardson B, et al. A multicenter, matched case-control study of risk factors for equine laminitis. Prev Vet Med 2001;49:209222.

    • Search Google Scholar
    • Export Citation
  • 29

    Dorn RC, Garner HE, Coffman JR, et al. Castration and other risk factors for equine laminitis. Prev Vet Med 1975;49:209222.

  • 30

    Polzer J, Slater MR. Age, breed, sex and seasonality as risk factors for equine laminitis. Prev Vet Med 1996;29:179184.

  • 31

    Junien C, Gallou-Kabani C, Vige A, et al. Nutritional epigenomics of metabolic syndrome. Med Sci 2005;21:396404.

  • 32

    Hoffman RM, Boston RC, Stefanovski D, et al. Obesity and diet affect glucose dynamics and insulin sensitivity in Thoroughbred gelding. J Anim Sci 2003;81:23332342.

    • Search Google Scholar
    • Export Citation
  • 33

    Lyon CJ, Law RE, Hsueh WA. Minireview: adiposity, inflammation, and atherogenesis. Endocrinology 2003;144:21952200.

  • 34

    Lewis GF, Carpentier A, Adeli K, et al. Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. Endocr Rev 2002;23:201229.

    • Search Google Scholar
    • Export Citation
  • 35

    Yu C, Chen Y, Cline GW, et al. Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle. J Biol Chem 2002;277:5023050236.

    • Search Google Scholar
    • Export Citation
  • 36

    Montague CT, O'Rahilly S. The perils of portliness: causes and consequences of visceral adiposity. Diabetes 2000;49:883888.

  • 37

    Abate N, Garg A, Reshock RM, et al. Relationship of generalized and regional adiposity to insulin sensitivity in men with NIDDM. Diabetes 1996;45:16841694.

    • Search Google Scholar
    • Export Citation
  • 38

    Johnson PJ, Messer NT, Ganjam VK. Cushing's syndromes, insulin resistance and endocrinopathic laminitis. Equine Vet J 2004;36:194198.

  • 39

    Watson T. Equine hyperlipaemia. In: Watson T, ed. Metabolic and endocrine problems of the horse. London: WB Saunders Co, 1998;2340.

  • 40

    Bell AW, Bauman DE. Adaptations of glucose metabolism during pregnancy and lactation. J Mammary Gland Biol Neoplasia 1997;2:265278.

  • 41

    Hoffman RM, Kronfeld DS, Cooper WL, et al. Glucose clearance in grazing mares is affected by diet, pregnancy, and lactation. J Anim Sci 2003;81:17641771.

    • Search Google Scholar
    • Export Citation
  • 42

    Forhead AJ, Dobson H. Plasma glucose and cortisol responses to exogenous insulin in fasted donkeys. Vet Sci 1997;62:265269.

  • 43

    Reeves HJ, Lees R, McGowan CM. Measurement of basal serum insulin concentrations in the diagnosis of Cushing's disease in ponies. Vet Rec 2001;149:449452.

    • Search Google Scholar
    • Export Citation
  • 44

    Beech J, Garcia M. Hormonal response to thyrotropin-releasing hormone in healthy horses and in horses with pituitary adenoma. Am J Vet Res 1985;46:19411943.

    • Search Google Scholar
    • Export Citation
  • 45

    Donaldson MT, Jorgensen AJ, Beech J. Evaluation of suspected pituitary pars intermedia dysfunction in horses with laminitis. J Am Vet Med Assoc 2004;224:11231127.

    • Search Google Scholar
    • Export Citation
  • 46

    Treiber KH, Hess TM, Kronfeld DS, et al. Insulin resistance and compensation in laminitis-predisposed ponies characterized by the minimal model. Pferdeheilkunde 2005;21:9192.

    • Search Google Scholar
    • Export Citation
  • 47

    Kyaw-Tanner M, Pollitt CC. Equine laminitis: increased transcription of matrix-metalloproteinase-2 (MMP-2) occurs during the development phase. Equine Vet J 2004;36:221225.

    • Search Google Scholar
    • Export Citation
  • 48

    Hinckley KA, Fearn S, Howard BR, et al. Nitric oxide donors as treatment for grass induced acute laminitis in ponies. Equine Vet J 1996;28:1728.

    • Search Google Scholar
    • Export Citation
  • 49

    Hood DM, Amoss MS, Hightower D, et al. Equine laminitis I: radioisotopic analysis of the foot during the acute disease. Equine Laminitis 1978;2:439444.

    • Search Google Scholar
    • Export Citation
  • 50

    Zeng G, Quon MJ. Insulin-stimulated production of nitric oxide is inhibited by wortmannin. J Clin Invest 1996;98:894898.

  • 51

    DeFronzo RA, Ferrannini E. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 1991;14:173194.

    • Search Google Scholar
    • Export Citation
  • 52

    Fonseca V, DeSouza C, Asnani S. Nontraditional risk factors for cardiovascular disease in diabetes. Endocr Rev 2004;25:153175.

  • 53

    Juan C, Shen Y, Chien Y, et al. Insulin infusion induces endothelin-1-dependent hypertension in rats. Am J Physiol 2004;287:E948E954.

  • 54

    Pass MA, Pollitt S, Pollitt CC. Decreased glucose metabolism causes separation of hoof lamellae in vitro: a trigger for laminitis?. Equine Vet J Suppl 1999;26:133138.

    • Search Google Scholar
    • Export Citation
  • 55

    Mobasheri A, Critchlow K, Clegg PD, et al. Chronic equine laminitis is characterised by loss of GLUT1, GLUT4 and ENaC positive laminar keratinocytes. Equine Vet J 2004;36:248254.

    • Search Google Scholar
    • Export Citation

Advertisement

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

Kibby H. TreiberDepartment of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0306

Search for other papers by Kibby H. Treiber in
Current site
Google Scholar
PubMed
Close
 MS
,
David S. KronfeldDepartment of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0306

Search for other papers by David S. Kronfeld in
Current site
Google Scholar
PubMed
Close
 PhD, DSc, MVSc
,
Tanja M. HessDepartment of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0306

Search for other papers by Tanja M. Hess in
Current site
Google Scholar
PubMed
Close
 DVM, PhD
,
Bridgett M. ByrdDepartment of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0306

Search for other papers by Bridgett M. Byrd in
Current site
Google Scholar
PubMed
Close
 MS
,
Rebecca K. SplanDepartment of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0306

Search for other papers by Rebecca K. Splan in
Current site
Google Scholar
PubMed
Close
 PhD
, and
W. Burton StaniarDepartment of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0306

Search for other papers by W. Burton Staniar in
Current site
Google Scholar
PubMed
Close
 PhD
View More View Less

Abstract

Objective—To evaluate genetic and metabolic predis-positions and nutritional risk factors for development of pasture-associated laminitis in ponies.

Design—Observational cohort study.

Animals—160 ponies.

Procedures—A previous diagnosis of laminitis was used to differentiate 54 ponies (PL group) from 106 nonlaminitic ponies (NL group). Pedigree analysis was used to determine a mode of inheritance for ponies with a previous diagnosis of laminitis. In early March, ponies were weighed and scored for body condition and basal venous blood samples were obtained. Plasma was analyzed for glucose, insulin, triglycerides, nonesterified fatty acids, and cortisol concentrations. Basal proxies for insulin sensitivity (reciprocal of the square root of insulin [RISQI]) and insulin secretory response (modified insulin-to-glucose ratio [MIRG]) were calculated. Observations were repeated in May, when some ponies had signs of clinical laminitis.

Results—A previous diagnosis of laminitis was consistent with the expected inheritance of a dominant major gene or genes with reduced penetrance. A prelaminitic metabolic profile was defined on the basis of body condition, plasma triglyceride concentration, RISQI, and MIRG. Meeting ≥ 3 of these criteria differentiated PL-from NL-group ponies with a total predictive power of 78%. Determination of prelaminitic metabolic syndrome in March predicted 11 of 13 cases of clinical laminitis observed in May when pasture starch concentration was high.

Conclusions and Clinical Relevance—Prelaminitic metabolic syndrome in apparently healthy ponies is comparable to metabolic syndromes in humans and is the first such set of risk factors to be supported by data in equids. Prelaminitic metabolic syndrome identifies ponies requiring special management, such as avoiding high starch intake that exacerbates insulin resistance.

Abstract

Objective—To evaluate genetic and metabolic predis-positions and nutritional risk factors for development of pasture-associated laminitis in ponies.

Design—Observational cohort study.

Animals—160 ponies.

Procedures—A previous diagnosis of laminitis was used to differentiate 54 ponies (PL group) from 106 nonlaminitic ponies (NL group). Pedigree analysis was used to determine a mode of inheritance for ponies with a previous diagnosis of laminitis. In early March, ponies were weighed and scored for body condition and basal venous blood samples were obtained. Plasma was analyzed for glucose, insulin, triglycerides, nonesterified fatty acids, and cortisol concentrations. Basal proxies for insulin sensitivity (reciprocal of the square root of insulin [RISQI]) and insulin secretory response (modified insulin-to-glucose ratio [MIRG]) were calculated. Observations were repeated in May, when some ponies had signs of clinical laminitis.

Results—A previous diagnosis of laminitis was consistent with the expected inheritance of a dominant major gene or genes with reduced penetrance. A prelaminitic metabolic profile was defined on the basis of body condition, plasma triglyceride concentration, RISQI, and MIRG. Meeting ≥ 3 of these criteria differentiated PL-from NL-group ponies with a total predictive power of 78%. Determination of prelaminitic metabolic syndrome in March predicted 11 of 13 cases of clinical laminitis observed in May when pasture starch concentration was high.

Conclusions and Clinical Relevance—Prelaminitic metabolic syndrome in apparently healthy ponies is comparable to metabolic syndromes in humans and is the first such set of risk factors to be supported by data in equids. Prelaminitic metabolic syndrome identifies ponies requiring special management, such as avoiding high starch intake that exacerbates insulin resistance.

Contributor Notes

Supported in part by the late Paul Mellon, John Lee Pratt Graduate Fellowship Program in Animal Nutrition, Bernice Barbour Foundation, and Virginia Horse Industry Board.

Presented in part as abstracts at the American Academy of Veterinary, Nutrition Symposium, Baltimore, June 2005 and the Annual Meeting of the Equine Science Society, Tucson, June 2005.

Address correspondence to Ms. Treiber