Too high a dose (Somogyi effect)
Too high a dose of insulin results in hypoglycemia, followed by rebound hyperglycemia due to counter regulatory hormone secretion.
In one series, hypoglycemia developed within four to eight hours of insulin injection and rebound hyperglycemia (>17 mmol/L
[300 mg/dl]) within three to six hours of the hypoglycemic nadir.
Signs of hypoglycemia may be seen — most likely lethargy, weakness and glazed expression. Somogyi effects may result in either
persistent hyperglycemia or inconsistent regulation. The latter occurs because the counter regulatory hormones have a hyperglycemic
effect for one to three days after the over-swing. During this period the excessive insulin dose results in good glycemic
control. When the counter regulatory effect is over, the insulin dose causes hypoglycemia. A Somogyi effect recurs, and the
cycle begins again.
Diagnosis requires a blood-glucose curve. Hourly measurements are recommended during the period of the anticipated blood-glucose
nadir. It may be necessary to obtain consecutive BG curves in order to catch the day in which the over-swing occurs. Because
this is labor-intensive and expensive, another approach is to reduce the dose of insulin and observe response.
Inconsistent insulin absorption
Insulin absorption is normally inconsistent to a certain extent. If this variation is excessive it will result in inconsistent
regulation. This is most likely to occur with a long-acting preparation. Daily blood-glucose curves will confirm inconsistent
regulation, but it is difficult to prove that inconsistent absorption is the cause because insulin sensitivity may also vary
daily. The most practical approach is to change insulin preparation and observe response.
The term "insulin resistance (IR)" is used in different ways. It refers to peripheral IR, which is reduced sensitivity of
fat and muscle to insulin due to receptor and post-receptor defects. This is often a pathophysiologic event in Type 2 diabetes
and is present in most diabetic cats.
Or, IR refers to therapeutic IR, where high doses of insulin are needed to regulate a diabetic patient. Therapeutic IR may
be suspected when a dose >1.5 units/kg per injection is having a minimum effect on hyperglycemia, or when a cat is well-regulated
but requires >2 units/kg per injection. This definition is imprecise and does not take into account potency of the insulin
Some cats with no apparent concurrent disease require higher doses of insulin to be well-regulated, presumably due to incomplete
absorption. One approach in this case is to continue therapy unchanged and not perform a potentially fruitless diagnostic
search. Disadvantage of this approach is the opportunity may be missed to reverse diabetes if it is secondary. If there are
increasing insulin requirements, a concurrent/underlying disorder should definitely be pursued.
Anti-insulin antibodies formed in humans treated with animal-source insulin, especially with the less pure older preparations.
Antibodies may bind insulin in the subcutaneous depot or in circulation, and, depending upon affinity, may have no effect,
may result in inconsistent response, or may cause insulin resistance.
Antibody formation in cats is probably of minimal significance. Nonetheless, if a cat is poorly regulated and it appears to
be an insulin-related problem, then a change in insulin is required, which could be a change in insulin species of origin.
Concurrent diseases cause IR by variably causing receptor defects, post-receptor defects and secretion of counter-pregulatory
hormones. This may result in either persistent or fluctuating IR and cause-and-effect with the diabetes may not be clear.
If a concurrent disease is identified, it should be noted that it may not be the (sole) cause of difficult regulation; curative
treatment may not be possible or well-defined; or successful treatment may not resolve receptor or post-receptor defects.
Diabetes increases the risk for bacterial or fungal infection, which in turn causes IR.
A common site of infection is the urinary tract. Urinalysis may not be diagnostic, so urine culture should be performed early
in the investigation. Many diabetic cats will have concurrent periodontal disease. Dentistry should be considered and the
effect on regulation noted.
If a cause of IR has not been identified during work-up, a therapeutic trial with antibiotics may be considered to treat sub-clinical
Diabetic cats may have chronic pancreatitis or exocrine pancreatic neoplasia. Pancreatic lipase immunoreactivity and ultrasound
examination are currently the best non-invasive tests for pancreatitis.
Unfortunately, treatment of chronic pancreatitis is not well-defined, but prednisolone has been recommended. It is not known
if excision of pancreatic tumors will improve regulation — in one study concurrent pancreatic neoplasia had no effect on survival.
Diabetic cats may also have hepatic lipidosis and cholangiohepatitis. Ultrasound study may identify hepatic abnormalities;
definitive diagnosis is by liver biopsy. Concurrent liver diseases should be treated using standard recommendations. Nutritional
support is important to facilitate insulin therapy by minimizing the risk for hypoglycemia. Pancreatitis, hepatic lipidosis
and cholangiohepatitis may be risk factors for ketoacidosis.
Inflammatory and infectious disorders unrelated to diabetes may occur. The former include asthma and inflammatory bowel disease,
which should be confirmed by standard work-up. Poorly regulated cats at risk should be tested for feline leukemia virus and
feline immunodeficiency virus.
Sub-clinical cardiomyopathy is an uncommon cause of poor regulation. Echocardiography may be considered if other causes of
poor regulation have been ruled-out and/or there are signs of heart disease.
Diabetes may result in hypertension, which is a cause of cardiac hypertrophy. However, hypertension is usually mild, and if
heart disease is diagnosed it is probably primary.
Other concurrent diseases are those common to mature and geriatric cats. Hyperthyroidism and chronic renal disease are most
common; neoplasia may also occur.
Hyperthyroidism causes insulin resistance, but secondary diabetes is rare and the need for very high doses of insulin is uncommon.
Treatment of hyperthyroidism does, however, reduce insulin doses and improves consistency of regulation. Fructosamine levels
are lowered in hyperthyroid cats and this should be taken into account when using this value to assess regulation.
Dr. Hoskins is owner of Docu-Tech Services. He is a diplomate of the American College of Veterinary Internal Medicine with
specialities in small animal pediatrics. He can be reached at (225) 955-3252, fax: (214) 242-2200 or e-mail: