Diabetes mellitus

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Mature cataracts in a dog with diabetes mellitus[2]

Diabetes mellitus (DM) is a relatively uncommon endocrine disease of dogs compared with type II diabetes mellitus in humans and cats.

Diabetes mellitus in other species is typically characterized by pancreatic islet cell destruction due to chronic pancreatitis or immune-mediated disease, leading to hyperglycemia and glycosuria[3]. In dogs, diabetes is usually observed in obese dogs where compensation for obesity-induced insulin resistance results in increased secretion of insulin[4], thus excluding them from the normal classification of diabetes mellitus. As well, natriuresis (urine sodium loss) and water loss-induced dehydration are not a feature of canine diabetes, which differs markedly from human and feline patients[5].

This disease should be distinguished from diabetes insipidus, a totally unrelated disorder characterized by vasopressin dysregulation due to central diabetes insipidus (hypothalamic-pituitary disorders) or nephrogenic diabetes insipidus (nephron impairment as a result of genetic or acquired disease).

Diabetes results in disorders in the metabolism of carbohydrates, lipids, and proteins[6], leading to multiple organ pathologies in numerous organs including the liver, kidney, pancreas, eyes and nervous system.

A number of forms of diabetes have been recognized in dogs:

  • Type I - juvenile (insulin-dependent) diabetes mellitus - common in dogs
  • Type II - adult-onset diabetes mellitus - rare in dogs compared with cats[7]
  • Type III - gestational diabetes mellitus in pregnant dogs - predisposition to diabetic ketoacidosis[8]

The underlying cause(s) of diabetes in dogs is poorly understood but includes:

Prevalence rates of diabetes in dogs varies from 10 - 20 dogs per 10,000, with rising rates probably related to increased obesity amongst this species. Females and neutered males appear to be over-represented. The peak age of occurrence is 7 - 11 years. It occurs rarely in dogs under 1 year of age[14].

Additional diseases associated with canine diabetes is increased predisposition to common infectious and inflammatory diseases such as cystitis, glomerulonephritis[15] and cataracts[16], due primarily to upregulation of proinflammatory cytokine production without a concurrent change in anti-inflammatory cytokine production.

Clinically affected dogs are middle-aged and commonly present with gradual weight loss, persistent hyperglycemia, hepatomegaly, polyuria secondary to osmotic diuresis (when blood glucose > 20 mmol/L), polydipsia and polyphagia and in protracted cases, ataxia due to diabetic polyneuropathy.

Urine testing usually reveals glucosuria and ketonuria is present in about 65% of dogs. Increased serum alkaline phosphatase, alanine amino transferase and hypertriglyceridaemia are common.

In most dogs, there is an associated elevation in blood glucagon and ketoacid production, due to mobilized fatty acids, resulting in diabetic ketoacidosis, characterized by hyperglycemia, metabolic acidosis (venous pH < 7.35)[17] and ketosis (BOHB concentration >2.0 mmol/L)[18]. Diabetic ketoacidosis is a serious consequence of diabetes, sometimes exacerbated by use of oral biguanide agents such as metformin.

Diagnosis is based on presenting clinical signs, blood test to confirm persistent hyperglycaemia and elevated fructosamine.

Additional testing may be performed including canine pancreatic lipase immunoreactivity (cPLI), urine culture, thoracic radiographs and abdominal ultrasonography.

A differential diagnosis would include diabetes insipidus, other causes of polyuria and Fanconi's syndrome.

Treatments include:

  • Weight loss in dogs with obesity - obese dogs have greater postprandial glucose, triglyceride, insulin concentrations[19] and insulin resistance[20]
  • Diet change - diabetic diet management- high in complex carbohydrates, low in simple sugars[21] and moderately restricted fats are recommended for the early cases of diabetes[22]
  • Oral diabetic agents
- Acarbose - modest improvement in glycemia control in dogs[23]
- Metformin - largely unreliable in dogs and not recommended[24]
- Glipizide - show variable efficacy at glucose control unless used in concert with insulin
- Glucagon-like peptide-1 receptor agonists - novel synthetic glucagon agonists which increase glucagon levels, resulting in reduce insulin secretion, reduced appetite and delayed gastric emptying[25]
- Lispro - short-duration effect, usually reserved for diabetic ketoacidosis
- Protamine zinc insulin - medium-duration effect, twice daily injections
- Caninsulin - intermediate effect, twice daily injections
- Glargine - long-duration insulin, once daily injections

Long-term glucose control can be monitored by serum fructosamine or glycosylated hemoglobin determinations[26].

Remission is a rare event that is possible after the resolution of insulin resistance conditions, especially those related to the estrus cycle[27] such as pregnancy, ovarian remnant syndrome and pyometra.

Long-term management of most canine diabetic patients must address quality of life issues such as long-term glucose testing (carpal pad prick testing[28]), long-term costs, time spent of monitoring glucose levels, concerns over leaving the dog for extended periods of time or in boarding care, and long-term secondary health issues[29].

References

  1. Pet Medicine Supply
  2. Veterinary Ophthalmology Services
  3. Monroe, WE (2009) Canine diabetes mellitus. In Bonagura, JD & Twedt, DC (Eds) Kirk's current veterinary therapy XIV. Saunders Elsevier, St Louis. pp:196
  4. Verkest KR et al (2011) Evaluation of beta-cell sensitivity to glucose and first-phase insulin secretion in obese dogs. Am J Vet Res 72(3):357-366
  5. Manhiani MM et al (2011) Chronic sodium-retaining action of insulin in diabetic dogs. Am J Physiol Renal Physiol 300(4):F957-F965
  6. Okumuş Z (1999) Diabetes mellitus in dogs and cats Part 1: Etyology, pathogenesis and treatment. Kafkas Univ Vet Fak Derg 5:223–231
  7. Rand JS et al (2004) Canine and feline diabetes mellitus: nature or nurture? J Nutr 134(8):2072S–2080S
  8. Armenise A et al (2011) Gestational diabetes mellitus with diabetic ketoacidosis in a Yorkshire terrier bitch. J Am Anim Hosp Assoc 47(4):285-289
  9. Hofer-Inteeworn N et al (2012) Effect of hypothyroidism on insulin sensitivity and glucose tolerance in dogs. Am J Vet Res 73(4):529-538
  10. Catchpole B et al (2013) Genetics of canine diabetes mellitus: Are the diabetes susceptibility genes identified in humans involved in breed susceptibility to diabetes mellitus in dogs? Vet J 195(2):139-147
  11. Elie M & Hoenig M (1995) Canine immune-mediated diabetes mellitus: a case report. J Am Anim Hosp Assoc. 1995 Jul-Aug;31(4):295-9
  12. Briggs, C et al (2000) Reliability of history and physical examination findings for assessing control of glycaemia in dogs with diabetes mellitus: 53 cases (1995-1998). J Am Vet Med Assoc 217:48
  13. Watson P (2012) Chronic pancreatitis in dogs. Top Companion Anim Med 27(3):133-139
  14. Guptill, L, Glickman, L & Glickman, N (2003) Time trends and risk factors for diabetes mellitus in dogs: analysis of veterinary medical data base records (1970-1999). Vet J 165:240
  15. DeClue AE et al (2012) Upregulation of proinflammatory cytokine production in response to bacterial pathogen-associated molecular patterns in dogs with diabetes mellitus undergoing insulin therapy. J Diabetes Sci Technol 6(3):496-502
  16. Kador PF et al (2010) Topical KINOSTAT™ ameliorates the clinical development and progression of cataracts in dogs with diabetes mellitus. Vet Ophthalmol 13(6):363-368
  17. O'Neill S et al (2012) Evaluation of cytokines and hormones in dogs before and after treatment of diabetic ketoacidosis and in uncomplicated diabetes mellitus. Vet Immunol Immunopathol 148(3-4):276-283
  18. Sears KW et al (2012) Use of lispro insulin for treatment of diabetic ketoacidosis in dogs. J Vet Emerg Crit Care (San Antonio) 22(2):211-218
  19. Verkest KR et al (2012) Spontaneously obese dogs exhibit greater postprandial glucose, triglyceride, and insulin concentrations than lean dogs. Domest Anim Endocrinol 42(2):103-112
  20. Wakshlag JJ et al (2011) The effects of weight loss on adipokines and markers of inflammation in dogs. Br J Nutr 106(1):S11-S14
  21. Elliott KF et al (2012) A diet lower in digestible carbohydrate results in lower postprandial glucose concentrations compared with a traditional canine diabetes diet and an adult maintenance diet in healthy dogs. Res Vet Sci 93(1):288-295
  22. Fleeman, LM & Rand, JS (2003) Evaluation of day-to-day variability of serial blood glucose concentration curves in diabetic dogs. J Am Vet Med Assoc 222:317
  23. Nelson RW (2000) Oral medications for treating diabetes mellitus in dogs and cats. J Small Anim Pract 41(11):486-490
  24. Nelson RW (2000) Oral medications for treating diabetes mellitus in dogs and cats. J Small Anim Pract 41(11):486-490
  25. Vilsbøll T et al (2009) The spectrum of antidiabetic actions of GLP-1 in patients with diabetes. Best Pract Res Clin Endocrinol Metab 23(4):453–462
  26. Miller E (1995) Long-term monitoring of the diabetic dog and cat. Clinical signs, serial blood glucose determinations, urine glucose, and glycated blood proteins. Vet Clin North Am Small Anim Pract 25(3):571-584
  27. Pöppl AG et al (2012) Diabetes mellitus remission after resolution of inflammatory and progesterone-related conditions in bitches. Res Vet Sci Nov 16
  28. Borin-Crivellenti S et al (2012) The carpal pad as an alternative sampling site for blood glucose testing in dogs. J Small Anim Pract 53(12):684-686
  29. Niessen SJ et al (2012) Evaluation of a quality-of-life tool for dogs with diabetes mellitus. J Vet Intern Med 26(4):953-961