MULTIPLE DAILY INJECTIONS :-

For a tighter control of blood glucose, usually a minimum of three daily injections is required (Fig 1C). Intensive therapy implies that not only are the symptoms of diabetes alleviated, but also the average blood glucose values are maintained in a range as close as possible to the normal non-diabetic individual. For this to be achieved insulin must be given in a manner that duplicates the diurnal patterns of insulin secretion from the islets in the basal and postprandial states (Fig 1D). To achieve this the basal insulin levels have to be, maintained throughout the 24 hours by use of intermediate or long acting insulin and postprandial peaks have to be provided by boluses of regular insulin or fast acting insulin analogues. This can be achieved in a number of ways as follows.  

The most commonly used regime is the mixture of intermediate acting (NPH or lente) with regular insulin before breakfast, regular insulin at lunch, and similar mixture as used at breakfast before dinner. This is easily evolved from the split mix regime and is especially useful for patients having night hypoglycemia. Modifications involve the use of Lyspro or Aspart insulin analogues instead of regular insulin for a relatively better and fast postprandial control (12).

The second regime, where regular or fast acting insulin analogues are used prior to each meal and an intermediate acting insulin is given at bedtime enables the patient to vary their meal times and offers much more flexibility. The patients can also vary their doses to cover individual variations in carbohydrate content of their meals and exercise schedules.

Algorithms have been designed to determine the dose of regular insulin to be administered prior to the meal, depending on the premeal blood glucose value (Table 4). These are guidelines mainly for initiating the therapy. Sooner or later patients and their physicians learn to adapt to the individual needs and the final dosing may be well different from that shown in the algorithm. The availability of pen type insulin injections has greatly facilitated the adoption of this regime.

Good glycemic control can also be achieved by using ultralente and now Glargine insulin (Lantus) instead of an intermediate acting insulin to cover the basal needs, with regular insulin or fast acting insulin analogues given before each meal. The ultralente insulin may be given in a single dose, but is more effective if divided into two injections before breakfast and dinner. Insulin Glargine can be given as a single dose at bedtime as it has a flat curve and is effective over 24hrs (13, 14). Approximately half the total dose of insulin is given in the long acting form, but the proportion will vary from patient to patient.

Table: 4: Intensive Insulin Therapy Algorithm. Example of Four Injections a Day Regime

	Regular Insulin Pre-meal Dose
Blood glucose (mg/dl)	Breakfast units	Lunch units	Dinner units	Bedtime units
0-50	4	3	3	-
51-100	6	5	5	-
101-150	7	6	6	-
151-200	8	7	7	2
201-250	9	8	8	2
301-350	11	10	10	4
351-400	12	11	11	5
>400	13	12	12	6

*These values are representative of what a patient with type 1 diabetes, weighing 50kgs, may require. The actual insulin requirement, as well as gradation in the algorithm, will vary widely as per age, weight of the child and from patient to patient.

Goals of Intensive Therapy :-

In all the regimes mentioned above, fasting or premeal blood glucose levels are used as a guide for adjustment of the dose of whatever the type of insulin is used. Fasting blood glucose levels should ideally be kept between 70-120 mg/dl for optimal control. In younger children such rigid control may be associated with unacceptable episodic hypoglycemia and more liberal values between 80-140 mg/dl are acceptable. To avoid nocturnal hypoglycemia, patients should check the blood glucose levels at 3 am once a week or so and ensure that it is above 70mg/dl. Patients should be willing to check their blood glucose levels four times a day, before each meal and at bedtime. Glucose levels before each meal should be generally within the same range as the fasting blood glucose levels. In addition, 2hr postprandial blood glucose level should be monitored with a goal of maintaining it between 80-150mg/dl. Careful adherence to the monitoring schedule with frequent communication with the physician and diabetic nurse are essential for the success of intensive insulin regimes.