The DCCT ( Diabetes Control and Complications Trial) has changed the question from whether to how by definitively proving that improved control reduces the occurance of long term complications. The trial also highlighted major adverse side effects of current approaches to severe hypoglycemia.

In the DCCT 1422 patients were followed for a mean of 6.5 years. The results showed that intensive therapy reduced the risk of complications by the following: Retinopathy 76% Neuropathy 60% Nephropathy 35-56% Cardiac and macrovascular events 44%

Hypoglycemia worsened by increasing threefold.

Intensive therapy for IDDM patients is a total behavioural and education package, one element of which is the insulin, its administration and regimen. Follow ups and education demonstrated in the DCCT, with weekly telephone calls and monthly visits, is probably impracticable in a clinical setting and too expensive to implement in the UK. The DCCT cost $168 million (£100+ million) which would result in an annual cost per patient of $18,000 (£10,000).

The DCCT recommends that the UK needs bigger diabetes care teams and more contact time for patient education. It is important that treatment plans be fitted into the patient's life and not vice versa.

New developments include external insulin pumps which are available. On the horizon are implanted pumps, nasal insulin and inhaled insulin. Still others for the future include hybrid artificial pancreases and closed loop implanted pumps. In the USA pancreas transplants are done primarily in patients in need of coexisting kidney transplantation. (14)

Biosynthetic Human Insulin

The daily treatment of more than 2 million patients worldwide with one brand of rDNA human insulin demonstrates the value of rDNA technology in providing an important medical product and an assurance that diabetic patients will have a guaranteed supply of this vital hormone. The classical structural work performed by Watson and Crick in the 1950's and on insulin by Sanger led to the introduction of the first human healthcare product to be derived from rDNA technology being introduced in 1982. The first rDNA human insulin was in fact administered to a normal volunteer at Guy's Hospital, London, in July 1980. Approvals to market human insulin were given in August 1982 in the UK; and in October 1982 in Germany and the USA. By 1992 registration had been achieved in 65 countries worldwide.

In the UK in 1985 5% of the insulin market was human insulin however by 1989 the share had risen to over 80% mainly as a result of campaigning by insulin manufacturers. (15

Insulin Therapy in Pediatrics

The introduction of human insulin and daily self monitoring of blood glucose instead of urine monitoring for those diabetics not affected by blood phobia has changed the therapy for the treatment of IDDM. With the introduction of more purified insulins in the late 1970's localised skin reactions and allergic reactions decreased.

During the first few weeks after diagnosis insulin requirements often decrease in children as endogenous insulin secretory capacity is restored during the honeymoon phase of IDDM. During puberty it is not uncommon to have to increase insulin doses by 20-30%. The relative insulin resistance which accompanies puberty is closely correlated with increased concentrations of sex hormones and growth factors. These changes occur about two years earlier in girls than in boys.

Dramatic decreases in insulin intake are often required in periods of marked physical activity, and for example during summer camps doses often have to be reduced by 25-50% despite a marked increase in food uptake. These reductions are attributable to increased levels in physical activity and at such times close glucose monitoring is usually required.

Generally human insulins are absorbed more rapidly than animal insulins and have a slightly shorter duration of action. Common scenarios are an increase in prelunch hypoglycemia due to rapid absorption of human insulin injected before breakfast and is often noted if no mid-morning snack is taken.

Symptoms of hypoglycemia frequently change with time, sometimes in subtle ways. Hypoglycemia unawareness and severe hypoglycemia in Europe in the 1980's may have resulted from over zealous treatment by well meaning physicians. Increasing the dose of pre-supper insulin can increase the risk of pre-dawn hypoglycemia and dawn hyperglycemia, sometimes resulting in noctural seizures.

Pen injectors are widely used in Europe however in the USA they have not become popular. This may be because currently available pen injectors do not readily allow dose-to-dose modification of rapidly and long acting insulins.

Insulins can go bad prior to expiry date especially in the summer months. This is possibly due to the reduced zinc content of many formulations leading to instability at higher temperatures.

The main reason for bedtime and 01.00-03.00 glucose monitoring is safety to prevent severe hypoglycemia.

In the event of irrational behaviour treatment with glucose should be implemented immediately and blood glucose tests can be performed immediately afterwards when the situation has settled. Hypoglycemia unawareness is common with younger children and in children with a longer duration of diabetes. It is important that family, teachers, friends are aware what to do in the event of hypoglycemia as recurrent hypoglycemia may be associated with defects in neurobehavioural function in later life.

Treatment for IDDM children has improved over the last decade however hypoglycemia and inconvenience remain major problems and it appears that no real cure is just around the corner. (16)