Insulin Therapy

Dr H B Chandalia*, Dr P S Lamba**
Insulin Therapy - Introduction
There is no really straightforward or simple formula that can be adopted to treat a child with diabetes mellitus (> 99 % of children with diabetes mellitus have type 1 diabetes). Definitely, a patient with type 1 diabetes mellitus who has overt hyperglycemia and glycosuria must be treated with insulin. Insulin acts directly to counteract the metabolic defects of Insulin deficiency. Additionally, there is now evidence that early, aggressive treatment with Insulin may have a beneficial effect on progression to total Insulin deficiency in type 1 diabetes by decreasing islet cell antigenicity and autoimmune destruction of b cells (1). For this reason, although temporary use of an oral hypoglycemic agent is possible in the early stages of type 1 diabetes, Insulin is preferred.

It is pertinent to mention that newly diagnosed type 1 diabetics who receive Insulin are at a greater risk of hypoglycemia and require small doses of Insulin because some recovery of residual Insulin secretion is possible. In the first few months of therapy, it is not unusual to see a decline, to very low levels, of the daily dose of Insulin necessary for glycemic control, and in many cases, use of Insulin could be stopped temporarily. This remission is often called "Honeymoon Phase" and may last for a few weeks to several months. During this period it is advisable to continue therapy with Insulin at a low dose rather than stop it entirely, because intermittent use of Insulin can increase it's antigenicity and as mentioned above, uninterrupted Insulin therapy may have a beneficial effect in preserving beta cell function.

Table 2: Intensive Insulin Therapy

- More rational control of blood Glucose with the ability to adjust Insulin doses to change in diet, activity and illness
- Delay in onset of and progression of: Retinopathy, Nephropathy (proteinuria and microalbuminuria), Neuropathy
- Reduced risk of hypercholesterolemia and hypertriglyceridemia
- Improved sense of well being
- Decreased fetal and maternal morbidity during pregnancy

- Increased episodes of severe hypoglycemia
- Hypoglycemia unawares
- Increased weight gain
- Transient exacerbation of pre-existing retinopathy (rare in children)
- Increased time, effort and cost
- In pump patients, increased ketoacidosis, and infection at infusion site
- Less suitable in young children (<7 years)

The major disadvantage of intensive Insulin therapy is that there is distinct increase in the incidence of clinically significant hypoglycemia. Furthermore, it may be associated with hypoglycemia unawareness. These effects may be attributable to increased threshold of secretory response of Adrenaline to hypoglycemia and enhanced suppression of neoglucogenesis in the liver by Insulin (5,6). Intensive Insulin regimes are associated with a significantly greater weight gain than standard therapy (7) and these children may be at a significant risk of developing obesity. Careful attention has thus to be given to diet and caloric restriction in these patients. Transient exacerbation of retinopathy has been reported with intensive Insulin therapy but this is rarely, if ever, encountered in the pediatric age group. Those small subset of patients who are on Insulin pump therapy(continuous subcutaneous Insulin infusion-CSII) may face the likelihood of increased risk of diabetic ketoacidosis due to pump failure and an increased incidence of infection at the pump infusion site (8). As great vigilance and frequent adjustment of doses is required for this type of regime, it is not generally recommended for very small children. Furthermore, intensive Insulin regimes require a great deal of time, motivation and effort on the part of the patient. They have additionally to be supported by a dedicated diabetes team especially to prevent frequent episodes of hypoglycemia. Notwithstanding the above, intensive Insulin regimes have come to stay and are perhaps the ideal mode of therapy for juvenile diabetics as they are the ones who will inevitably face both microvascular and macrovascular complications in their adult life.

If the child presents to the doctor with extreme hyperglycemia or diabetic ketoacidosis, the initial treatment is with human regular Insulin infused intravenously. Once the blood Glucose levels and electrolyte levels are stabilized and ketones are cleared from the circulation, they can be switched to a daily regime of subcutaneous Insulin injections. Patients, who present with lesser degree of hyperglycemia not associated with significant ketosis, can initially be treated with Insulin directly as out patients. Care must be taken at this time to ensure that patients receive a thorough education of how to use insulin, understand the rules for adjustment of Insulin doses, learn to recognize and treat hypoglycemia, understand the relation of Insulin to diet and exercise, are instructed on sick day guidelines and are familiarized with other aspects of diabetes such as foot care, dietary guidelines and hygiene (Table 3). Children, adolescents, those with acute illness or learning problems are better hospitalized initially. This can help in familiarizing the child and the parents with Insulin injection techniques and intensive education can be given over several days as well as Insulin dosage adjustments can be made under the supervision of a physician.

Table 3: Patient Education at First Visit/Initial Hospitalization
- Insulin injection technique and sites
- Insulin storage, instructions during travel and while at school
- Recognition and treatment of hypoglycemia
- Rules for adjusting Insulin dosages, especially in relation to exercise.
- Diet counseling. Importance of meal timings and snacks.
- Sick day guidelines
- Foot care and hygiene

With the advent of human insulins, bovine or porcine insulins have hardly any role to play in the management of type 1 diabetes in children. Avoiding use of bovine and porcine insulins can successfully obviate the attendant problems of Insulin resistance, Insulin antibodies, and lipoatrophy.

The introduction of rapid acting Insulin analogues, Lispro and Aspart Insulin has further facilitated intensive glycemic control by their use in the MDI regimes (16-18) (Fig 2). Further, substituting regular Insulin with these analogues can solve many a problem encountered in achieving adequate glycemic control. The foremost among these is a marked reduction in nocturnal hypoglycemic episodes. They also have a special role to play in cases of Somogyi phenomena, Dawn phenomena and brittle diabetes.

Ultralente Insulin (bovine) was the closest we had to good basal insulin. However, it was still woefully inadequate. The introduction of Glargine Insulin has shown great promise as it provides the near ideal, once a day, peakless, basal insulin.

Pulmonary aerosol (inhalant) Insulin is the next major blessing for young diabetics (19). With its introduction, giving a single bedtime dose of Glargine Insulin and metered doses of inhaled Insulin prior to each meal/snack may further facilitate intensive control. [Fig 2: Mean serum insulin concentration in non - diabetic subjects after subcutaneous injection (0.2 U/kg) of human insulin Aspart (*) and regular human insulin (o ) at various sites. A. Abdomen B. Deltoid C. Thigh. (20)
Insulin Therapy

Insulin Therapy Insulin Therapy 02/23/2001
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