Editorial Type:
Scientific Reports

Acid-base and hormonal abnormalities in dogs with naturally occurring diabetes mellitus

Lawren L. Durocher Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

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 DVM, MS, DACVIM
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Kenneth W. Hinchcliff Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

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 BVSc, PhD, DACVIM
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Stephen P. DiBartola Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

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Susan E. Johnson Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

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 DVM, MS, DACVIM
DOI:
https://doi.org/10.2460/javma.232.9.1310
Volume/Issue:
Volume 232: Issue 9
Online Publication Date:
01 May 2008
Restricted access
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Abstract

Objective—To examine acid-base and hormonal abnormalities in dogs with diabetes mellitus.

Design—Cross-sectional study.

Animals—48 dogs with diabetes mellitus and 17 healthy dogs.

Procedures—Blood was collected and serum ketone, glucose, lactate, electrolytes, insulin, glucagon, cortisol, epinephrine, norepinephrine, nonesterified fatty acid, and triglyceride concentrations were measured. Indicators of acid-base status were calculated and compared between groups.

Results—Serum ketone and glucose concentrations were significantly higher in diabetic than in healthy dogs, but there was no difference in venous blood pH or base excess between groups. Anion gap and strong ion difference were significantly higher and strong ion gap and serum bicarbonate concentration were significantly lower in the diabetic dogs. There were significant linear relationships between measures of acid-base status and serum ketone concentration, but not between measures of acid-base status and serum lactate concentration. Serum insulin concentration did not differ significantly between groups, but diabetic dogs had a wider range of values. All diabetic dogs with a serum ketone concentration > 1,000 μmol/L had a serum insulin concentration < 5 μU/mL. There were strong relationships between serum ketone concentration and serum glucagon-insulin ratio, serum cortisol concentration, and plasma norepinephrine concentration. Serum β-hydroxybutyrate concentration, expressed as a percentage of serum ketone concentration, decreased as serum ketone concentration increased.

Conclusions and Clinical Relevance—Results suggested that ketosis in diabetic dogs was related to the glucagon-insulin ratio with only low concentrations of insulin required to prevent ketosis. Acidosis in ketotic dogs was attributable largely to high serum ketone concentrations.

Abstract

Objective—To examine acid-base and hormonal abnormalities in dogs with diabetes mellitus.

Design—Cross-sectional study.

Animals—48 dogs with diabetes mellitus and 17 healthy dogs.

Procedures—Blood was collected and serum ketone, glucose, lactate, electrolytes, insulin, glucagon, cortisol, epinephrine, norepinephrine, nonesterified fatty acid, and triglyceride concentrations were measured. Indicators of acid-base status were calculated and compared between groups.

Results—Serum ketone and glucose concentrations were significantly higher in diabetic than in healthy dogs, but there was no difference in venous blood pH or base excess between groups. Anion gap and strong ion difference were significantly higher and strong ion gap and serum bicarbonate concentration were significantly lower in the diabetic dogs. There were significant linear relationships between measures of acid-base status and serum ketone concentration, but not between measures of acid-base status and serum lactate concentration. Serum insulin concentration did not differ significantly between groups, but diabetic dogs had a wider range of values. All diabetic dogs with a serum ketone concentration > 1,000 μmol/L had a serum insulin concentration < 5 μU/mL. There were strong relationships between serum ketone concentration and serum glucagon-insulin ratio, serum cortisol concentration, and plasma norepinephrine concentration. Serum β-hydroxybutyrate concentration, expressed as a percentage of serum ketone concentration, decreased as serum ketone concentration increased.

Conclusions and Clinical Relevance—Results suggested that ketosis in diabetic dogs was related to the glucagon-insulin ratio with only low concentrations of insulin required to prevent ketosis. Acidosis in ketotic dogs was attributable largely to high serum ketone concentrations.

Contributor Notes

Dr. Durocher's present address is Carolina Veterinary Specialists, 1600 Hanes Mall Blvd, Winston Salem, NC 27103.

Dr. Hinchcliff's present address is Veterinary Clinical Centre, Faculty of Veterinary Science, University of Melbourne, Princes Highway, Werribee, Victoria, Australia, 3030.

Supported by a grant from the Iams Company.

Presented in part at American College of Veterinary Internal Medicine Annual Forum, Seattle, June 2007.

Address correspondence to Dr. Hinchcliff.
Cover Journal of the American Veterinary Medical Association
Journal of the American Veterinary Medical Association
Publication Date:
01 May 2008
  • 1.

    Unger RH, Dobbs RE. Insulin, glucagon, and somatostatin secretion in the regulation of metabolism. Annu Rev Physiol 1978;40: 307–343.

  • 2.

    Kerl ME. Diabetic ketoacidosis: pathophysiology and clinical and laboratory presentation. Compend Contin Educ Pract Vet 2001; 23:220–229.

    • Search Google Scholar
    • Export Citation
  • 3.

    Jiang G, Zhang BB. Glucagon and regulation of glucose metabolism. Am J Physiol Endocrinol Metab 2003;284:E671–E678.

  • 4.

    Gustavson SM, Chu CA, Nishizawa M, et al. Glucagon's actions are modified by the combination of epinephrine and gluconeogenic precursor infusion. Am J Physiol Endocrinol Metab 2003;285:E534–E544.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Johnston DG, Pernet A, McCulloch A, et al. Some hormonal influences on glucose and ketone body metabolism in normal human subjects. In: Metabolic acidosis. London: Pitman Books Ltd (CIBA Foundation Symposium 87), 1982;168–191.

    • Search Google Scholar
    • Export Citation
  • 6.

    Shimazu T, Amakawa A. Regulation of glycogen metabolism in liver by the autonomic nervous system. 3. Differential effects of sympathetic-nerve stimulation and of catecholamines on liver phosphorylase. Biochim Biophys Acta 1968;165:349–356.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Chu CA, Sindelar DK, Neal DW. Comparison of the direct and indirect effects of epinephrine on hepatic glucose production. J Clin Invest 1997;99:1044–1056.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Connolly CC, Steiner KE, Stevenson RW, et al. Regulation of lipolysis and ketogenesis by norepinephrine in conscious dogs. Am J Physiol Endocrinol Metab 1991;261:E466–E472.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Basso LV, Havel RJ. Hepatic metabolism of free fatty acids in normal and diabetic dogs. J Clin Invest 1970;49:537–547.

  • 10.

    Christopher MJ, Rantzau C, McConell G, et al. Prevailing hyperglycemia is critical in the regulation of glucose metabolism during exercise in poorly controlled alloxan-diabetic dogs. J Appl Physiol 2005;98:930–939.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    Rozman J, Bunc M, Zorko B. Modulation of hormonal secretion by functional electrical stimulation of the intact and incompletely dysfunctional dog pancreas. Braz J Med Biol Res 2004;37:363–370.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Leyva-Ocariz H. Effect of hyperadrenocorticism and diabetes mellitus on serum progesterone concentrations during early metoestrus of pregnant and nonpregnant cycles induced by pregnant mare's serum gonadotropin in domestic dogs. J Reprod Fertil Suppl 1993;47:371–377.

    • Search Google Scholar
    • Export Citation
  • 13.

    Ford SL, Nelson RW, Feldman EC, et al. Insulin resistance in three dogs with hypothyroidism and diabetes mellitus. J Am Vet Med Assoc 1993;202:1478–1480.

    • Search Google Scholar
    • Export Citation
  • 14.

    Constable PD, Stampfli HR. Experimental determination of net protein charge and Atot and Ka of nonvolatile buffers in canine plasma. J Vet Intern Med 2005;19:507–514.

    • Search Google Scholar
    • Export Citation
  • 15.

    Kogika MM, Lustoza MD, Notomi MK, et al. Serum ionized calcium in dogs with chronic renal failure and metabolic acidosis. Vet Clin Pathol 2006;35:441–445.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Umpierrez GE, DiGirolamo M, Tuvlin JA, et al. Differences in metabolic and hormonal milieu in diabetic- and alcohol-induced ketoacidosis. J Crit Care 2000;15:52–59.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    Alberti KG. Role of glucagon and other hormones in development of diabetic ketoacidosis. Lancet 1975;1:1307–1311.

  • 18.

    Sakurai H, Dobbs RE, Unger RH. The role of glucagon in the pathogenesis of the endogenous hyperglycemia of diabetes mellitus. Metabolism 1975;24:1287–1297.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Dobbs R, Sakurai J, Sasaki H, et al. Glucagon: role in the hyperglycemia of diabetes mellitus. Science 1975;187:544–547.

  • 20.

    Hume DZ, Drobatz KJ, Hess RS. Outcome of dogs with diabetic ketoacidosis: 127 dogs (1993–2003). J Vet Intern Med 2006;20:547–555.

  • 21.

    Laffel L. Ketone bodies: a review of physiology, pathophysiology and application to monitoring to diabetes. Diabetes Metab Res Rev 1999;15:412–426.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22.

    Luzi L, Barrett EJ, Groop LC, et al. Metabolic effects of low-dose insulin therapy on glucose metabolism in diabetic ketoacidosis. Diabetes 1988;37:1470–1477.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23.

    Steiner KE, Fuchs H, Williams PE, et al. Regulation of ketogenesis by epinephrine and norepinephrine in the overnight-fasted, conscious dog. Diabetes 1985;34:425–432.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24.

    Johnston DG, Alberti KG, Nattrass M, et al. Hormonal and metabolic rhythms in Cushing's syndrome. Metabolism 1980;29:1046–1052.

  • 25.

    McGarry JD, Woeltje KF, Kuwajima M, et al. Regulation of ketogenesis and the renaissance of carnitine palmitoyltransferase. Diabetes Metab Rev 1989;5:271–284.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26.

    Rogers WA, Donovan EF, Kociba GJ. Lipids and lipoproteins in normal dogs and in dogs with secondary hyperlipoproteinemia. J Am Vet Med Assoc 1975;166:1092–1100.

    • Search Google Scholar
    • Export Citation
  • 27.

    Hess RS, Saunders HM, Van Winkle TJ, et al. Concurrent disorders in dogs with diabetes mellitus: 221 cases (1993–1998). J Am Vet Med Assoc 2000;217:1166–1173.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28.

    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.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29.

    van Keulen LJ, Wesdorp JL, Kooistra HS. Diabetes mellitus in a dog with a growth hormone-producing acidophilic adenoma of the adenohypophysis. Vet Pathol 1996;33:451–453.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30.

    Mattheeuws D, Rottiers R, Kaneko JJ, et al. Diabetes mellitus in dogs: relationship of obesity to glucose tolerance and insulin response. Am J Vet Res 1984;45:98–103.

    • Search Google Scholar
    • Export Citation
  • 31.

    Kandel G, Aberman A. Selected developments in the understanding of diabetic ketoacidosis. Can Med Assoc J 1983;128:392–397.

  • 32.

    Catchpole B, Ristic JM, Fleeman LM, et al. Canine diabetes mellitus: can old dogs teach us new tricks? Diabetologia 2005;48:1948–1956.

  • 33.

    Goldstein DE. Tests of glycemia in diabetes. Diabetes Care 1995;18:896–909.

  • 34.

    Li PK, Lee JT, Macgillivray MH, et al. Direct, fixed-time kinetic assays for β-hydroxybutyrate and acetoacetetate with a centrifugal analyzer or a computer-baked spectrophotometer. Clin Chem 1980;26:1713–1717.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35.

    Duarte R, Simoes DMN, Franchini ML, et al. Accuracy of serum β-hydroxybutyrate measurements for the diagnosis of diabetic ketoacidosis in 116 dogs. J Vet Intern Med 2002;16: 411–417.

    • Search Google Scholar
    • Export Citation

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