Problems with insulin therapy
Absorption is the crucial factor in determining insulin potency and duration of action, which together determine insulin effect.
Variability in absorption is an important cause of inconsistent response in humans and is due to injection technique, patient
characteristics and properties of the insulin. Under the most controlled experimental conditions, the intra-individual variability
in insulin pharmaco-kinetics in humans is 20 percent, and >50 percent in clinical conditions. The situation likely is similar
Potential handling errors include use of outdated insulin, inactivation by exposure to excessive heat or light, violent shaking
of the insulin bottle, insufficient mixing of the insulin preparation, drawing up an incorrect dose and dilution errors.
In humans, depth of injection, anatomic site and delay before needle withdrawal affect absorption, but temperature of the
insulin and speed of injection do not.
Injection factors in cats anecdotally associated with poor regulation include unsuccessful injection, rubbing the injection
site after injection, and interscapular vs. lateral thorax or flank injection. Variable injection technique is more likely
to result in inconsistent regulation than in persistent hyperglycemia. Owner technique should be reviewed and consistency
of injection emphasized.
If an insulin administration error is suspected, the cat may be hospitalized to ensure consistent injection and blood-glucose-lowering
effect.Injection problems may be solved in some cases by changing to injection pens or needle-free injection.
Transient insulin effect
The duration of insulin effect is not sufficiently long to achieve adequate BG control, which has been considered to be important
in cats. A transient effect may be due to rapid absorption and/or to a counter regulatory phenomenon. A transient effect can
be definitively diagnosed and distinguished from the Somogyi effect only by a blood-glucose curve.
The treatment is either to change to a longer-acting preparation or to give insulin twice a day. Increasing the dose will
increase the duration of insulin effect, but carries an unacceptable risk for hypoglycemia. When changing from a shorter to
longer-acting insulin preparation, the dose may be increased by 10 percent to 25percent to account for the reduced potency
of the longer-acting preparation, but this is difficult with the small doses used in cats.
When changing from once to twice daily insulin injections, the dose should be reduced by about 25 percent to account for potential
overlap in insulin effect. Cats are best regulated with twice-daily insulin, so this should be discussed with owners at the
onset of treatment.
Delayed insulin effect
Absorption of insulin is normally incomplete, and is more so in cats than in dogs or humans. Zinc and protamine-based, longer-acting
preparations are less completely absorbed than shorter-acting ones.
Absorption may be sufficiently incomplete that normoglycemia is not achieved with standard doses. This was primarily a problem
with ultralente. In other cases, absorption is delayed such that a good part of the day is required before glucose falls.
A blood-glucose curve demonstrates late-onset reduction in glucose or no effect.
The recommended treatment is to change insulin from PZI to NPH or pork lente, or, paradoxically, to glargine (different mechanism
of absorption). Increasing the dose is not recommended because this increases the risk of late-onset hypoglycemia.
Prolonged insulin effect
The insulin effect is sufficiently long so that an overlap occurs, resulting in a Somogyi effect. This is most likely to occur
with twice-daily injection of a long-acting preparation. Treatment options include changing to once-daily injection of the
existing preparation or to twice-daily injection of a shorter-acting preparation.
Too low a dose
The peak insulin effect does not result in an adequate blood-glucose nadir or sufficient reduction in glucose for the duration
of insulin action. Blood-glucose curve measurements every two hours usually are diagnostically adequate. The insulin dose
should be increased by 0.25 to 0.5 U, unless previous dose adjustments have demonstrated that larger increments are required.
Usually a minimum of seven days should be allowed for equilibration to the new dose before re-evaluation.