Insulin treatment

Unstable diabetes mellitus

• Most diabetic dogs can be stabilized and managed without difficulty:
  • Stable diabetic dogs:
    • Exhibit adequate resolution of clinical signs such as polyuria/polydipsia.
    • Maintain a good appetite and optimal body condition.
    • Have a resonable quality of life as judged by their owners.
    • Show minimal complications such as ketosis Diabetic ketoacidosis , infections and other diabetic complications.
    • Have reasonable fructosamine Blood biochemistry: fructosamine concentrations.
    • Receive conventional insulin doses between 1 and 1.5 IU/kg /injection.
    • Have acceptable blood glucose concentrations Blood biochemistry: glucose although not necessarily euglycemia during inter-injection intervals.
• Some diabetic dogs require investigation because of persistence or recurrence of diabetes mellitus despite what is considered adequate treatment:
  • Unstable diabetic dogs:
    • Exhibit poor control of clinical signs.
    • Are at high risk of diabetic complications such as ketoacidosis.
    • Have inappropriately high blood glucose concentrations during the inter-injection interval but not always at the nadir point.
    • Have high or rising fructosamine concentrations.
    • Usually receive increasing doses of insulin to control clinical signs, often >/= 2 IU/kg/injection with associated risks of developing hypoglycemia Hypoglycemia.
• The potential causes of diabetic instability can be broadly divided into 3 categories.
• Management issues:
  • Problems with insulin administration:
    • Incorrect preparation of dose.
    • Inappropriate syringe type for insulin strength.
    • Injection into hair.
    • Injection into fat.
    • Injection into single fibrosed site.
  • Timing of insulin injections:
    • Variable timing.
    • Frequently missed injections.
  • Feeding:
    • Variable diet.
    • Inappropriate timing.
    • Snack feeding.
  • Exercise:
    • Variable exercise regimen.
    • Intense exercise protocol.
  • Handling of insulin:
    • Dilution.
    • Improper storage.
    • Inactivation due to vigorous shaking.
    • Use of out-of-date insulin.
• Insulin problems:
  • Inadequate dose.
  • Short duration of activity.
  • Prolonged duration of activity.
  • Excessive dose resulting in Somogyi overswing.
• Insulin resistance:
  • Obesity/poor body condition.
  • Infections/inflammation:
    • Urinary tract infection Cystitis.
    • Pancreatitis Pancreatitis: acute.
    • Pyometra Pyometra.
    • Pyelonephritis Kidney: pyelonephritis.
  • Organ failure:
    • Renal.
    • Hepatic.
    • Exocrine pancreatic insufficiency Exocrine pancreatic insufficiency.
  • Drug induced:
    • Glucocorticoids.
    • Progestagens.
  • Hormonal antagonism:
    • Diestrus.
    • Pregnancy.
    • Hyperadrencorticism Hyperadrenocorticism.
    • Hypothyroidism Hypothyroidism.
    • Acromegaly Acromegaly.
    • Glucagonoma.
    • Phaechromocytoma Pheochromocytoma.
  • Problems with insulin antibodies.
  • Poor absorption.

Investigation of unstable diabetes mellitus

• Full review of management issues such as diet, feeding schedules, exercise and handling and administration of insulin:
  • If the dog is receiving significantly <1.5 IU/kg/injection then absolute under dosage of insulin is possible:
    • Increasing the dose of insulin in this situation may provide better control.
  • If the dog is receiving intermediate acting insulin once daily, then short duration of activity is likely:
    • Dividing the dose and administering in two equal doses 12 hours apart may provide better control.
  • Problems with owner administration can be eliminated by reviewing owner technique.
  • Problems with insulin may be investigated by injection with a new bottle of insulin.
• Detailed clinical examination:
  • This should aim to confirm those signs caused by diabetes mellitus and identifying features indicative of a concurrent disease process.
  • In many cases the cause of the problem is diagnosed at this stage.
• Serial blood glucose curve Serial blood glucose :
  • If a diagnosis has not been reached, a blood glucose curve is indicated.
  • This provides information on:
    • Somogyi overswing:
      • Decrease dose and re-evaluate.
    • Duration of insulin activity:
      • Increase/decrease frequency of injection depending on results.
    • Insulin resistance:
      • Investigate for underlying disorder.
      • Consider insulin antibodies.
      • Consider poor absorption.

Somogyi overswing

• When blood glucose concentrations decrease to approximately 3.5 mmol/L or below, the hypoglycemia induces release of diabetogenic hormones, in particular epinephrine and glucagon.
• These hormones act to increase blood glucose concentrations and the result is a hyperglycemia that develops rapidly after the glucose nadir.
• Diagnosis requires the demonstration of hypoglycemia followed by a severe and precipitous hyperglycemia within a 24 h period. The insulin dose should susequently be reduced by at least 25% and the animal re-evaluated.
• The Somogyi overswing can result in significant hyperglycemia for several days.

Inadequate duration of action

• In some animals the duration of insulin action may differ from that predicted.
• Short duration of action is almost predictable in animals administered once daily intermediate-acting insulin such as lente preparations.
• This can be resolved by giving twice daily injections or switching to a longer acting insulin formulation.
• Occasionally there may be a duration of effect slightly longer than the inter-injection interval resulting in an overlapping effect.

Insulin antibodies

• The development of significant insulin antibodies is rare.
• Many dogs are treated with porcine insulin Insulin: pharmacology and formulations that has an identical structure to canine insulin and so antibody development is unlikely.
• Human and bovine origin insulin is also available and when used antibodies may be produced.
• The presence of anti-insulin antibodies has been asociated with insulin resistance in some dogs.
• Changing the source of insulin from one species to another may overcome this problem.
  If antibodies are the cause, glycemic control should improve within 2 weeks of changing to a different source of insulin.

Poor absorption

• Absorption may vary according to the site of a subcutaneous injection, ie absorption from the scruff may be different from that on the flank.
• The development of tissue reaction at the site of frequent injection may reduce absorption.
• In some animals insulin preparations particularly long-acting ones are so slowly absorbed as to be ineffective in achieving good glycemic control.
  Follow the diagnostic tree for Persistent Hyperglycemia in Diabetic Dogs and Cats Persistent Hyperglycemia in Diabetic Dogs and Cats.

Other complications

Further Reading

Publications

Refereed papers

• Recent references from PubMed and VetMedResource.
• Hess R S (2010) Insulin resistance in dogs. Vet Clin North Am Small Anim Pract 40 (2), 309-316 PubMed.
• Davison L J, Walding B, Herrtage M E et al (2008) Anti-insulin antibodies in diabetic dogs before and after treatment with different insulin preparations. JVIM 22 (6), 1317-1325 PubMed.
• Fall T, Johansson Kreuger S, Juberget A et al (2008) Gestational diabetes mellitus in 13 dogs. JVIM 22 (6), 1296-1300 PubMed.
• Hess R S, Saunders H M, van Winkle T J et al (2000) Concurrent disorders in dogs with diabetes mellitus: 221 cases (1993-1998). JAVMA 217 (8), 1166-1173 PubMed.
• Whitley N T, Drobatz K J & Panciera D L (1997) Insulin overdose in dogs and cats - 28 cases (1986-1993). JAVMA 211 (3), 326-330 PubMed.
• Feldman E C & Nelson R W (1982) Insulin-induced hyperglycaemia in diabetic dogs. JAVMA 180 (12), 1432-1437 PubMed.