Probably the most common complication associated with treatment of diabetes mellitus is persistence of clinical signs.
This is most commonly due to inadequate insulin effect.
The underdosage of insulin can be due to a number of factors and include absolute and relative underdosage.
Print off the owner factsheet on Diabetes mellitus and give to your client.
Absolute insulin underdose
Most cats can be stabilized on an insulin dose of <1.5 U/kg twice daily.
If the patient is receiving less than this and clinical signs persist then absolute under dosage of insulin is highly probable.
Increasing the dose of insulin in this situation may provide better control.
If the patient is receiving more than 1.5 U/kg twice daily first rule out poor owner technique as a cause of the inability to supply sufficient insulin.
Common reasons for delivering inadequate insulin are:
Out of date insulin.
Poorly handled insulin (shaken or heated).
Incorrect dilution.
Owner factors can be eliminated by having the insulin, from a new bottle, administered for a few days by a veterinary technician or veterinarian.
A full review of management such as diet, feeding schedules and exercise should be made at this time.
If the problem is still unresolved patients who are receiving once daily injections should have this dose divided and administered in two equal doses 12 hours apart.
It should be remembered that when dividing the dose animals may stabilize on less than half the once daily dose at each injection.
If patients are already receiving twice daily injections then a weekly increase in insulin dose of 1 U/injection should be instituted until the patient is receiving 1.5 U/kg twice daily.
At this point, if clinical signs are persisting, the patient and history should be thoroughly examined for potential causes of relative insulin underdosage and a blood glucose curve must be performed.
This should distinguish between Somogyi overswing, rapid insulin metabolism and insulin resistance.
Confirmation of insulin resistance requires further investigation to identify the source so that this can be managed.
The first stage in the investigation of any unstable diabetic cat should be directed at identification (or ruling out) of any factors contributing to insulin resistance.
Conditions such as hyperadrenocorticism or acromegaly may be present with no other typical signs.
Once identified, the cause of insulin resistance should be addressed if possible.
If it is not possible to treat the cause of insulin resistance then the dose of insulin should be increased as necessary to overcome the resistance.
If once daily injections are being given then switch to twice daily and use intermediate acting insulin, eg lente rather than long acting insulin.
Intermediate acting insulin has a more rapid absorption and is more efficient at lowering blood glucose.
In some cases mixing insulin, eg regular and lente may achieve better glycemic control.
Anti-insulin antibodies
The development of significant levels of anti-insulin antibodies is rare.
One study has shown that the levels of anti-insulin antibodies are similar in cats receiving beef and human insulin.
The presence of anti-insulin antibodies can cause insulin resistance with persistently high blood glucose concentrations or poor glycemic control with widely fluctuating glucose concentrations.
If antibodies are the cause, glycemic control should improve within 2 weeks of changing to a different source of insulin.
Poor absorption
Injection technique may play a part in determining the availability of injected insulin.
If insulin is inadvertently injected intradermally or intramuscularly its absorption will be very different from insulin given by the subcutaneous route.
Absorption may also 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 lente insulin is just absorbed too slowly from subcuticular sites to be effective and it may be necessary to switch to more rapidly acting formulation.
Inadequate duration of action
In some animals the duration of insulin may differ greatly from the norm.
It is important to perform a blood glucose curve in all patients around 10 days after starting insulin therapy and this will give an indication of the persistence of the insulin effect.
Duration of effect is largely determined by the rate of absorption and in most cats the effective duration of action of lente insulin is <12 hours.
This is the reason that twice daily injection is preferable to once daily insulin injection although some cats can be reasonably controlled on a single daily injection.
Insulin is occasionally metabolized very rapidly.
Shortened duration of action results in a considerable period of hyperglycemia with persistent morning glycosuria and sometimes evening polydipsia/polyuria.
This can be resolved by giving twice daily injections or switching to a longer acting insulin formulation.
This may cause clinical signs of nervousness, restlessness, disorientation, pupillary dilation, ataxia and coma which can be life threatening.
It is very important not to overdose diabetic cats as they frequently do not show hunger in response to hypoglycemia.
In some animals there may be no signs associated with hypoglycemia and occasionally hypoglycemia is detected in clinically normal diabetic patients during routine follow-up.
Some cats can be classified as 'brittle diabetics' meaning that they are very sensitive to the effects of exogenous insulin and are particularly sensitive to the effects of an overdose.
However, many animals are able to produce a compensatory response to this hypoglycemia with the release of hormones antagonistic to insulin.
This response averts the immediate crisis but a rebound effect occurs as the effects of the injected insulin wane with blood glucose levels rising outside the normal range.
This is the so called Somogyi overswing.
Somogyi overswing
When blood glucose concentrations drop below 3.6 mmol/l hypoglycemia induces release of diabetogenic hormones, in particular adrenaline and glucagon.
These hormones act to increase blood glucose concentrations and the result is a hyperglycemia around 12 hours after the blood glucose nadir.
Diagnosis requires the demonstration of a hypoglycemia and hyperglycemia within a 24 hour period.
In order to counteract this phenomenon the insulin dose must be decreased.
In animals receiving <1.5 U/kg per injection the dose should be reduced by 25%.
In animals receiving a higher insulin dose the dose can be halved or reduced to the equivalent of 0.5 U/kg per injection.
It may be necessary to further adjust the dose of insulin up or down based on blood glucose curves and urine testing for a few weeks after this correction.
The problem is easily identified from a serial blood glucose curve and can be corrected by reducing the insulin dose.
Insulin overdose may occur years after the start of treatment and can be due to:
Altered insulin dose:
Incorrect dilution.
Change in syringe resulting in owner error.
Change in preparation having different pharmacological properties.
Overlapping insulin effect on twice daily dosing.
Altered insulin requirement:
Appetite change.
Transient diabetes mellitus.
Vomiting.
Maldigestion.
Insulin dose should be reduced if hypoglycemia is present as long term complications can develop.
Following acute overdosage prompt therapy is important.
Although insulin may induce a hypoglycemia that lasts for several days the first 24 hours of hypoglycemia are a critical time for treatment.
Glucose solution should be administered (orally 1 g glucose/kg if patient is conscious or intravenously if unconscious).
Animals showing hypoglycemia should be hospitalized until stabilized again - the administration of a bolus of glucose may bring about normoglycemia quickly but residual effects of the insulin may cause a further hypoglycemic episode later.
Insulin requirements may decrease with time so continue treatment for 2-4 weeks after any alteration in regime before making further changes.
Thoresen S I, Bjerkas E, Aleksandersen M & Peiffer R L (2002) Diabetes mellitus and bilateral cataracts in a kitten. J Feline Med Surg.4 (2), 115-122.
Elliott D A, Feldman E D, Koblin P P et al (2000) Prevalence of pituitary tumours amongst diabetic cats with insulin resistance.JAVMA216, 1765-1768.
Goossens M M C, Nelson R W, Feldman E C & Griffey S M (1998) Response to insulin treatment and survival in 104 cats with diabetes mellitus (1985-1995).JVIM12, 1-6.
Kraus M S, Calvert C A, Jacobs G J & Brown J (1997) Feline diabetes mellitus - a retrospective mortality study of 55 cats (1982-1994).JAAHA33, 107-111.
Whitley N T, Drobatz K J & Panciera D L (1997) Insulin overdose in dogs and cats - 28 cases. (1986-1993).JAVMA211, 326-330.
Hatchell D L, Toth C A, Barden C A & Saloupis P (1995) Diabetic retinopathy in a cat.Exp Eye Res 60, 591-593.
Macintire D K (1995) Emergency therapy of diabetic crises - insulin overdose diabetic acidosis and hyperosmolar coma.Vet Clin NA5, 639-650.
McMillan F D & Feldman E C (1986) Rebound hypoglycaemia following overdosage of insulin in cats with diabetes mellitus.JAVMA188, 1426-1431.
Print off the owner factsheet on Diabetes mellitus 
It should be remembered that when dividing the dose animals may stabilize on less than half the once daily dose at each injection. 
