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This information is provided by Provet for educational purposes only.

You should seek the advice of your veterinarian if your pet is ill as only he or she can correctly advise on the diagnosis and recommend the treatment that is most appropriate for your pet.

Stable glycaemic control is the main clinical aim in the management of patients with diabetes mellitus. However, from time to time the administration of insulin appears to be ineffective - why ?

Ineffectiveness of insulin should be considered when poor glycaemic control is present in patients that are given insulin at a dose rate of more than 1.5U/kg body weight twice daily and  : 

  • They are still showing the clinical signs typical of diabetes - weight loss, polydipsia, polyuria, polyphagia, lethargy, poor hair coat, neuropathy
  • Their blood glucose concentrations exceed 300mg/dl (16.8 mmol/l)
  • Their blood fructosamine concentrations exceed 500 mmol/l

Why does this occur? There are several reasons why the administration of insulin may not reduce blood glucose concentrations adequately :

  • Secondary insulin resistance - the most common cause of insulin ineffectiveness
    • Common causes in dogs include :
      • Chronic pancreatitis
      • Cushings syndrome (hyperadrenocorticism)
      • Dioestrus in bitches
      • Infections - oral and urinary tract
      • Hyperlipidaemia
      • Obesity
      • Renal insufficiency
    • Common causes in cats  include :
      • Acromegaly
      • Chronic pancreatitis
      • Cushings syndrome (hyperadrenocorticism)
      • Hyperthyroidism
      • Infections - oral
      • Obesity
      • Renal insufficiency
  • Insulin underdosage
    • The insulin has been inactivated 
      • out of date
      • exposed to high temperatures (inadequate refrigeration)
      • the solution has been shaken
    • Inaccurately measured out dose by the owner
    • Improperly administered by the owner
  • Somogyi effect. 
    • Caused by insulin overdose creating a physiological response to return blood glucose concentrations to normal once it falls to below 65mg/dl (3.64 mmol/l). The Somogyi effect also induces insulin resistance which complicates interpretation of poor glycaemic control. This is one of the most common reasons for insulin resistance and poor glycaemic control in cats.
  • Short duration of action
    • Most cats and dogs require two doses of insulin a day because the duration of action is 10-14 hours.
    • Insulin duration of effect is particularly short in cats which require ultralente or PZI forms of insulin 2 or even 3 times daily
  • Poor Insulin Absorption
    • In up to 20% of cats ultralente is absorbed poorly from a subcutaneous injection site
    • Thickening of the skin and subcutaneous tissues following repeat injections and  allergy may reduce absorption from the site
  • Insulin-binding antibodies
    • Up to 45% of dogs treated with beef/pork source insulin and 5% of dogs treated with human recombinant insulin develop antibodies to the insulin which results in insulin resistance and poor glycaemic control. 
    • This is less common in cats - affecting less than 5% of cats on human recombinant insulin.
  • Allergy to Insulin
    • Rare - causes a local tissue reaction at the injection site


Presentation given by Prof Richard Nelson DVM Diplomate ACVIM at the North American Veteriary Conference 2001.


Updated October 2013