Journal of Veterinary Clinics (한국임상수의학회지)

The Korean Society of Veterinary Clinics (한국임상수의학회)
권호 표지

Decreased Insulin Secretion in Dogs with Chronic Mitral Valve Insufficiency

만성 이첨판 폐쇄부전증 개에서 인슐린 분비기능 감소

  • Accepted : 2014.04.10
  • Published : 2014.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Glucose metabolism abnormalities secondary to heart failure, including insulin resistance (IR) and impaired fasting glucose, have been gradually recognized as important prognostic factors in disease progression. However, to date, no study has investigated glucose abnormalities in dogs with chronic mitral valve insufficiency (CMVD). Thus, we hypothesized that glucose metabolism abnormalities due to heart failure may develop in dogs with CMVD. A prospective study was performed on 113 client-owned dogs with variable CMVD severities. Serum insulin, glucagon, fructosamine, and glucose concentrations were measured, and insulin resistance was determined using the homeostatic model assessment (HOMA) score. The serum insulin concentration had a significant inverse association with the heart failure severity. However, there was no significant association between the heart failure severity and fructosamine, HOMA score, and fasting blood glucose. Insulin, fructosamine, and HOMA had a significant positive association with body condition scores (BCS), whereas glucose had no association. This study found that insulin secretion in dogs with naturally occurring heart failure due to CMVD might be compromised as the disease worsens.

최근 사람연구에서는 심부전과 관련하여 발생하는 인슐린 저항성이나 공복혈당 이상과 같은 혈당 대사 이상 중요한 예후인자로 받아들여지고 있다. 그러나 심부전이 있는 개에서 이와 관련된 연구는 매우 드물다. 따라서 본 연구는 혈당대사이상이 이첨판 폐쇄 부전증이 있는 개에서도 나타날 것이라고 가정하였다. 총 113마리의 보호자가 있는 개를 대상으로 혈중 insulin, glucagon, fructosamine, glucose 를 측정하였으며, 인슐린 저항성은 homeostatic model assessment (HOMA) score를 이용하였다. 실험결과 혈중 인슐린 농도는 심장병이 심해짐에 따라서 유의성 있게 감소함을 확인하였다. 반면, fructosamine, HOMA score, and 공복 혈당은 심부전의 심각도와 어떠한 상관성도 보이지 않았다. 인슐린 농도, fructosamine, HOMA 의 경우 body condition scores (BCS)와 양의 유의적 상관관계를 보였으나, 혈당의 경우 그러지 않았다. 심부전과 BCS와의 음의 유의적 상관관계 또한 확인 되었다. 본 연구를 바탕으로 자연적으로 발생한 이첨판 폐쇄부전증에 따른 심부전 환자에서 심장 병이 심해짐에 따라서 인슐린 분비 기능이 감소함을 확인하였다.

Keywords

References

  1. Araujo JP, Lourenco P, Rocha-Goncalves F. Adiponectin is increased in cardiac cachexia irrespective of body mass index. Eur J Heart Fail 2009; 11: 567-572. https://doi.org/10.1093/eurjhf/hfp046
  2. Atkins C, Bonagura J, Ettinger S. Guidelines for the diagnosis and treatment of canine chronic valvular heart disease. J Vet Intern Med 2009; 23: 1142-1150. https://doi.org/10.1111/j.1939-1676.2009.0392.x
  3. Bailhache E, Nguyen P, Krempf M. Lipoproteins abnormalities in obese insulin-resistant dogs. Metabolism 2003; 52: 559-564. https://doi.org/10.1053/meta.2003.50110
  4. Barth RJ. Insulin resistance, obesity and the metabolic syndrome. S D Med 2011; Spec No: 22-27.
  5. Borgarelli M, Haggstrom J. Canine degenerative myxomatous mitral valve disease: natural history, clinical presentation and therapy. Vet Clin North Am Small Anim Pract 2010; 40: 651-663. https://doi.org/10.1016/j.cvsm.2010.03.008
  6. Bradley DC, Bergman RN. Hepatic glucagon sensitivity and fasting glucose concentration in normal dogs. Am J Physiol 1992; 262: E539-545.
  7. Braun TP, Marks DL. Pathophysiology and treatment of inflammatory anorexia in chronic disease. J Cachexia Sarcopenia Muscle 2010; 1: 135-145. https://doi.org/10.1007/s13539-010-0015-1
  8. Clodi M, Resl M, Stelzeneder D. Interactions of glucose metabolism and chronic heart failure. Exp Clin Endocrinol Diabetes 2009; 117: 99-106. https://doi.org/10.1055/s-2008-1081211
  9. Delpierre G, Collard F, Fortpied J. Fructosamine 3-kinase is involved in an intracellular deglycation pathway in human erythrocytes. Biochem J 2002; 365: 801-808. https://doi.org/10.1042/bj20020325
  10. Freeman LM, Rush JE. Nutrition and cardiomyopathy: lessons from spontaneous animal models. Curr Heart Fail Rep 2007; 4: 84-90. https://doi.org/10.1007/s11897-007-0005-6
  11. Freeman LM, Rush JE, Kehayias JJ. Nutritional alterations and the effect of fish oil supplementation in dogs with heart failure. J Vet Intern Med 1998; 12: 440-448. https://doi.org/10.1111/j.1939-1676.1998.tb02148.x
  12. Freeman LM. Interventional nutrition for cardiac disease. Clin Tech Small Anim Pract 1998; 13: 232-237. https://doi.org/10.1016/S1096-2867(98)80008-X
  13. Freeman LM. The pathophysiology of cardiac cachexia. Curr Opin Support Palliat Care 2009; 3: 276-281. https://doi.org/10.1097/SPC.0b013e32833237f1
  14. Freeman LM, Rush JE, Markwell PJ. Effects of dietary modification in dogs with early chronic valvular disease. J Vet Intern Med 2006; 20: 1116-1126. https://doi.org/10.1111/j.1939-1676.2006.tb00709.x
  15. Fisman EZ, Motro M, Tenenbaum A. Impaired fasting glucose concentrations in nondiabetic patients with ischemic heart disease: a marker for a worse prognosis. Am Heart J 2001; 141: 485-490. https://doi.org/10.1067/mhj.2001.113219
  16. Gayet C, Bailhache E, Dumon H. Insulin resistance and changes in plasma concentration of TNFalpha, IGF1, and NEFA in dogs during weight gain and obesity. J Anim Physiol Anim Nutr (Berl) 2004; 88: 157-165. https://doi.org/10.1111/j.1439-0396.2003.00473.x
  17. Held C, Gerstein HC, Yusuf S. Glucose levels predict hospitalization for congestive heart failure in patients at high cardiovascular risk. Circulation 2007; 115: 1371-1375. https://doi.org/10.1161/CIRCULATIONAHA.106.661405
  18. Hess RS, Kass PH, Van Winkle TJ. Association between diabetes mellitus, hypothyroidism or hyperadrenocorticism, and atherosclerosis in dogs. J Vet Intern Med 2003; 17: 489-494. https://doi.org/10.1111/j.1939-1676.2003.tb02469.x
  19. Hess RS. Insulin resistance in dogs. Vet Clin North Am Small Anim Pract 2010; 40: 309-316. https://doi.org/10.1016/j.cvsm.2009.12.001
  20. Innes KE, Vincent HK, Taylor AG. Chronic stress and insulin resistance-related indices of cardiovascular disease risk, part I: neurophysiological responses and pathological sequelae. Altern Ther Health Med 2007; 13: 46-52.
  21. Ionut V, Liu H, Mooradian V. Novel canine models of obese prediabetes and mild type 2 diabetes. Am J Physiol Endocrinol Metab 2010; 298: E38-48. https://doi.org/10.1152/ajpendo.00466.2009
  22. Kaaja RJ, Poyhonen-Alho MK. Insulin resistance and sympathetic overactivity in women. J Hypertens 2006; 24: 131-141. https://doi.org/10.1097/01.hjh.0000194121.19851.e5
  23. Kil DY, Swanson KS. Endocrinology of obesity. Vet Clin North Am Small Anim Pract 2010; 40: 205-219. https://doi.org/10.1016/j.cvsm.2009.10.004
  24. Mack R, Skurnick B, Sterling-Jean Y. Fasting insulin levels as a measure of insulin resistance in American blacks. J Med 2003; 34: 31-38.
  25. Martin LJ, Siliart B, Dumon HJ. Hormonal disturbances associated with obesity in dogs. J Anim Physiol Anim Nutr (Berl) 2006; 90: 355-360. https://doi.org/10.1111/j.1439-0396.2005.00589.x
  26. Mawby DI, Bartges JW, d'Avignon A. Comparison of various methods for estimating body fat in dogs. J Am Anim Hosp Assoc 2004; 40: 109-114. https://doi.org/10.5326/0400109
  27. McAuley KA, Williams SM, Mann JI. Diagnosing insulin resistance in the general population. Diabetes Care 2001; 24: 460-464. https://doi.org/10.2337/diacare.24.3.460
  28. Mourouzis I, Forini F, Pantos C. Thyroid hormone and cardiac disease: from basic concepts to clinical application. J Thyroid Res 2011; 2011: 958626.
  29. Nikolaidis LA, Sturzu A, Stolarski C. The development of myocardial insulin resistance in conscious dogs with advanced dilated cardiomyopathy. Cardiovasc Res 2004; 61: 297-306. https://doi.org/10.1016/j.cardiores.2003.11.027
  30. Paolisso G, De Riu S, Marrazzo G. Insulin resistance and hyperinsulinemia in patients with chronic congestive heart failure. Metabolism 1991; 40: 972-977. https://doi.org/10.1016/0026-0495(91)90075-8
  31. Porte D, Jr., Graber AL, Kuzuya T. The effect of epinephrine on immunoreactive insulin levels in man. J Clin Invest 1966; 45: 228-236. https://doi.org/10.1172/JCI105335
  32. Rizza RA, Cryer PE, Haymond MW. Adrenergic mechanisms for the effects of epinephrine on glucose production and clearance in man. J Clin Invest 1980; 65: 682-689. https://doi.org/10.1172/JCI109714
  33. Robins SJ, Lyass A, Zachariah JP. Insulin resistance and the relationship of a dyslipidemia to coronary heart disease: the Framingham Heart Study. Arterioscler Thromb Vasc Biol 2011; 31: 1208-1214. https://doi.org/10.1161/ATVBAHA.110.219055
  34. Rowe JW, Young JB, Minaker KL. Effect of insulin and glucose infusions on sympathetic nervous system activity in normal man. Diabetes 1981; 30: 219-225. https://doi.org/10.2337/diab.30.3.219
  35. Scott-Moncrieff JC. Insulin resistance in cats. Vet Clin North Am Small Anim Pract 2010; 40: 241-257. https://doi.org/10.1016/j.cvsm.2009.10.007
  36. Scott-Moncrieff JC. Clinical signs and concurrent diseases of hypothyroidism in dogs and cats. Vet Clin North Am Small Anim Pract 2007; 37: 709-722. https://doi.org/10.1016/j.cvsm.2007.03.003
  37. Serisier S, Gayet C, Leray V. Hypertriglyceridaemic insulin-resistant obese dog model: effects of high-fat diet depending on age. J Anim Physiol Anim Nutr (Berl) 2008; 92: 419-425. https://doi.org/10.1111/j.1439-0396.2007.00785.x
  38. Silverberg AB, Shah SD, Haymond MW. Norepinephrine: hormone and neurotransmitter in man. Am J Physiol 1978; 234: E252-256.
  39. Son HR, d'Avignon DA, Laflamme DP. Comparison of dual-energy x-ray absorptiometry and measurement of total body water content by deuterium oxide dilution for estimating body composition in dogs. Am J Vet Res 1998; 59: 529-532.
  40. Swan JW, Walton C, Godsland IF. Insulin resistance in chronic heart failure. Eur Heart J 1994; 15: 1528-1532. https://doi.org/10.1093/oxfordjournals.eurheartj.a060425
  41. Swan JW, Anker SD, Walton C. Insulin resistance in chronic heart failure: relation to severity and etiology of heart failure. J Am Coll Cardiol 1997; 30: 527-532. https://doi.org/10.1016/S0735-1097(97)00185-X
  42. Tenenbaum A, Fisman EZ. Impaired glucose metabolism in patients with heart failure: pathophysiology and possible treatment strategies. Am J Cardiovasc Drugs 2004; 4: 269-280. https://doi.org/10.2165/00129784-200404050-00001
  43. von Haehling S, Anker SD. Cachexia as a major underestimated and unmet medical need: facts and numbers. J Cachexia Sarcopenia Muscle 2010; 1: 1-5. https://doi.org/10.1007/s13539-010-0002-6
  44. Xenoulis PG, Levinski MD, Suchodolski JS. Association of hypertriglyceridemia with insulin resistance in healthy Miniature Schnauzers. J Am Vet Med Assoc 2011; 238: 1011-1016. https://doi.org/10.2460/javma.238.8.1011
  45. Zoran DL. Obesity in dogs and cats: a metabolic and endocrine disorder. Vet Clin North Am Small Anim Pract 2010; 40: 221-239. https://doi.org/10.1016/j.cvsm.2009.10.009