Rhett Marshall BVSc MACVSc
The Cat Clinic
189 Creek Road,
Mt Gravatt, 4122
- Glargine must not be diluted or mixed with anything because the prolonged action is dependent on its pH
- Glargine has a shelf-life of 4 weeks after opening and kept at room temperature. Refrigeration prolongs its shelf-life and allows opened vials to be used for up to 6 months. The manufacturer however recommends discarding opened vials after 4 weeks
- When performing a blood glucose curve, samples probably only need to be taken every 4hrs over 12 hr in many cats (ie. 0h [before morning insulin], 4h, 8h and 12h after morning insulin)
- Dose changes should be made based on pre-insulin glucose concentration, nadir (lowest) glucose concentration, daily water drunk, and urine glucose concentration.
- Better glycaemic control is achieved with twice daily dosing rather than once daily
- More accurate dosing may be achieved using 0.3ml U-100 insulin syringes
Indications for starting glargine
- All newly diagnosed diabetic cats (to increase chance of remission)
- Poorly controlled or unstable diabetic cats (glargine’s long duration of action is likely to benefit these cats)
- When SID dosing is desired or demanded (glycaemic control and remission rates are higher if glargine is dosed BID)
- Ketoacidosis – replaces regular insulin and can be used IM or IV
- When corticosteroid administration is required in cats at high risk of developing clinical signs of diabetes or cats in remission.
For initial insulin dose,
- BG > 20mmol/L à start with 0.5U/kg ideal body weight twice daily (BID)
- BG < 20mmol/L à start with 0.25U/kg ideal body weight BID
Blood glucose should be sampled every 3-4hrs for several days, either at home or in hospital. Dose reductions can be made (based on the blood glucose parameters in Table 1) but it is suggested that you do not increase the dose until about 7 days of therapy as many cats have negligible glucose lowering effect in the first few days despite being on an adequate dose of insulin.
After this, cats should have their blood glucose sampled weekly (or more frequently) as outpatients and insulin dose adjusted according to Table 1. If biochemical hypoglycaemia develops and is not severe, it can usually be managed by feeding the cat a higher carbohydrate containing meal. Renal diets and many supermarket lines of dry food are high in carbohydrates. Clinical hypoglycaemia requires immediate IV glucose therapy.
Table 1. Blood glucose parameters used for adjusting insulin dose
|Blood Glucose Parameter||Insulin Dose|
|Pre-insulin >20mmol/L||increase 0.5U|
and/or nadir 7-9mmol/L
|Pre-insulin 12-14mmol/L||reduce by 0.5U|
|Pre-insulin <12mmol/L||withhold and check for remission|
|nadir 5-7mmol/L||reduce by 0.5U|
|Nadir <5mmol/L||reduce by 1U|
|Clinical hypoglycemia||reduce by 50%|
Urine glucose measurements
With the long duration of action of glargine, there should be minimal periods when blood glucose is >14mmol/L (240mg/dL) for cats treated for more than 2 to 3 weeks, and hence well controlled cats should almost always be 0 or 1+ for urine glucose. A value 2+ or greater likely indicates that an increase in dose is required.
Serial blood glucose curves or single blood glucose sampling?
The aim of dosing, when using shorter-acting insulins, is to select the maximum dose that can be safely given without causing hypoglycaemia. To determine this, we use nadir glucose (lowest) and aim for 7-10mmol/L. A serial blood glucose curve is required to determine the nadir hence single outpatient blood glucose samples have traditionally been considered meaningless.
After several days of glargine therapy, the long duration of action and carry-over effects (Marshall et al, 2008) usually results in a flatter blood glucose curve and a much smaller difference between pre-insulin levels and the nadir. For this reason, most cats can be monitored as outpatients with single blood glucose sampling. In most cats, glargine exerts its peak effect approximately 14hrs after injection (Marshall et al, 2008), so sampling blood glucose just prior to injection is recommended. This also allows insulin dose to be changed immediately (if required) rather than waiting until the next injection. Single glucose sampling provides less information than a serial curve but has the added benefit of reduced stress for the cat and costs for the owner as no hospitalisation is required. Confusing or unexpected single glucose samples should be investigated with a serial blood glucose curve.
How to recognise and approach remission
Good glycemic control soon after diagnosis reverses glucose toxicity and many newly-diagnosed diabetic cats can have their insulin dose gradually reduced and many can have their insulin completely withdrawn. It is suggested that insulin not be withdrawn completely for at least two weeks after starting insulin therapy to ensure adequate time for beta cells to recover from glucose toxicity.
Insulin dose can be reduced when indicated by low blood glucose parameters listed above. If pre-insulin glucose is below 10mmol/L and insulin dose has been reduced to 1U, insulin should be withheld and blood glucose measured for 12hrs (if the pre-insulin glucose is below 10mmol/L and insulin dose greater than 1U, insulin dose should be reduced to 1U rather than withheld and pre-insulin glucose measured again in 3-7 days). In most cases, if when insulin is withheld the blood glucose concentration
- rises rapidly or significantly over 10mmol/L cats should be discharged on 1U twice daily
- rises slowly towards or just above 10mmol/L, then cats should be discharged on 1U once daily
- remains below 10mmol/L for 12hrs with no insulin, they can be assumed to be non-insulin dependant and cats should be discharged without insulin with their blood glucose monitored every 2-3 days for several weeks. Confirmed non-insulin dependant diabetic cats should have their blood glucose checked weekly for 3 months and then monthly forever.
Some cats may have a pre-insulin glucose concentration below 10mmol/L within 2 weeks, but insulin therapy should be maintained for at least 2 weeks to give beta cells adequate time to recover from glucose toxicity. Use 1U BID or SID until insulin is withdrawn.
What to do with the diabetic cat in remission
Once remission has occurred, it is vital that blood glucose concentration be measured regularly (initially weekly then monthly) to quickly diagnose a relapse. To facilitate the cat remaining in diabetic remission, it is recommended that a low carbohydrate diet is fed, physical activity is increased, calories are restricted to avoid obesity, and that diabetogenic drugs are contraindicated unless a life threatening situation arises.
How to increase the chance of remission
Our study in diabetic cats (Marshall et al, awaiting publication) found better glycaemic control and higher remission rates when newly diagnosed diabetic cats were treated with glargine compared to lente or PZI insulins. This study also showed that, regardless of insulin type, good glycaemic control soon after diagnosis (within 3 weeks) increases the chance of achieving remission.
For reasons that are presently unknown, glargine treated cats appear to tolerate slight overdosing with insulin very well. For this reason, it is suggested that for the first 4-6 weeks of therapy, insulin be slightly overdosed and cats monitored carefully. Slightly overdosing with glargine increases the risk of hypoglycemia but usually results in achieving early good glycemic control which reverses glucose toxicity and results in a non-insulin dependant state. The benefits of remission far outweighs the risks of hypoglycaemia.
To maximise glycaemic control and hence the chance of remission
- select glargine as initial insulin
- administer glargine TWICE daily rather than once daily
- slightly overdose with insulin for the first 4-6 weeks
- use a low carbohydrate diet
- restrict calories if overweight and encourage physical activity
Concurrent corticosteroid administration
Corticosteroid administration causes insulin resistance and should be avoided in diabetic cats. When required, local or topically acting preparations should be used to reduce systemic levels. Budesonide (1mg/cat sid or bid) is useful for treating inflammatory bowel disease. Asthmatic cats should be treated with inhaled steroids such as Flixotide (Fluticasone proprionate) which maximises the concentration of steroid delivered to the respiratory mucosa without significant systemic release.
Glargine is very useful to use in cats requiring intermittent or chronic corticosteroid administration that are either in remission or at risk of developing diabetes. Most cats can be safely be placed on 1U SID or BID with very little monitoring.