Insulin Therapy

There are essentially three types of insulin all of which currently require sub-cutaneous injection:

1. ultra-short acting (lispro = Humalog = H) which has onset at 10 minutes, peaks at 1-2 hours and is gone by 5 hours;
2. short acting insulin (regular = R = Toronto, also known as 'clear'), which has onset at 30-40 minutes, peaks at 2-4 hours and is gone by 8 hours, and
3. intermediate acting insulin (NPH = N, or Lente = L, Ultralente = U: also known as 'cloudy') which have an onset of action at 2 hours, peaks at 6-8 hours and is gone by 12-18 hours.

Premixed insulins have been more widely used in the past 5 years. These are named for their proportion of R to N insulin i.e. 30/70 has 30% R and 70% N. Their advantage is that mixing is not required; their disadvantage is lack of flexibility in relative proportions of R or N. Most insulin in current use is recombinant human insulin. The manufacture of Beef/pork insulins (Iletin) has been discontinued though some pharmacies still have stocks. Animal insulins are similar to human insulins but have slightly longer durations of action.

Insulin therapy should ideally be begun in a diabetes education centre. Once the technique has been mastered insulin adjustment can often be made by the patient in concert with the specialist or family doctor.

Insulin has traditionally been injected with a syringe system, though insulin "pens" have become more widely used. Their advantage is that insulin need not be drawn up manually. It is simply dialed up.

The principles of insulin therapy in Type 2 diabetes are somewhat different to those of Type 1 diabetes. In Type 1 diabetes, the patient makes no insulin whatsover, thus both short & long-acting insulins need be given. Because the majority of Type 2 diabetes patients, at least early in the course of their requiring insulin therapy, make some of their own insulin, it is often sufficient to give enough intermediate-acting insulin such that fasting and pre-meal glycemia is relatively normal. Thus twice daily intermediate-acting insulin, pre-mixed insulin such as 30/70 is often recommended for initial therapy. The starting dose is 0.15 units per kg 30 minutes before breakfast and dinner. The dose may be titrated up in increments of 2 units morning and/or evening until sugar falls under 8 mmol. At this stage finer adjustments may be made. Oral agents may be stopped "cold-turkey" when insulin therapy is begun. An alternate approach, particularly in the elderly, is to continue oral agents and to start with a single bedtime dose of intermediate-acting insulin at 0.15 U per kg.

Limitations of Current Therapies

Hypoglycemia is the main limiting factor of intensified and conventional insulin therapy. Hypoglycemia is much less of a problem in Type 2 than Type 1 diabetes because the former is associated, almost by definition, with insulin resistance. Patients who have unacceptable hypoglycemia despite good compliance with diet may be considered for ultra-short-acting insulin. Weight gain is another problem with insulin therapy. If dietary compliance is not problematic, consideration may also be given for ultra-short-acting insulin therapy, with cessation of regular snacks.

There continues to be 10-20 of patients who exhibit marked insulin resistance such that normalization of sugar by any dose of insulin and/or oral agents is not possible. The potential release of troglitazone may help reduce this number. Further developments in pharmacotherapy are awaited with great interest.

Dr. Tom Elliott is an active researcher and educator and the President of the BC Endocrine Research Foundation. He is also a busy physician treating individuals with endocrine disorders.

References

1. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33) The Lancet, 1998, Vol. 352; pg. 837-853.
2. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34) The Lancet, 1998, Vol. 352; pg. 853-865.