How is the substitution of basal insulin secretion done

The substitution of basal insulin secretion is achieved by administering one or two insulin injections of intermediate or slow duration of action daily. More precisely:

• Isophane insulin (NPH). An injection before bedtime is first administered. The reason for this particular time lies in the avoidance of nighttime hypoglycaemia (if the injection is given earlier, the peak of action will coincide with the first morning hours of high insulin sensitivity, when the risk of hypoglycaemia is increased). The pre-bedtime injection aims at placing the peak of action near the waking time, when higher needs of insulin usually exist (a period of low insulin sensitivity because of counter-regulatory hormones secretion). If only one injection of isophane insulin is administered, there is often a lack of basal insulin after the noon of the following day (because of its relatively short duration of action, see Table 28.1). The problem can be managed

Breakfast Lunch Dinner

Lispro or Aspart

Lispro or Aspart

Insulin Nph Peak Diagram

Breakfast Lunch Dinner

Figure 28.2. Schematic representation: a) Therapeutic scheme with one injection of isophane insulin (NPH) before bedtime and regular insulin 30 minutes before each meal. Large part the lack of basal insulin for a interval of the day is covered by the relatively prolonged action of the repeatedly injected regular insulin. b) Therapeutic scheme with two injections of isophane insulin (before breakfast and at bedtime) and one injection of very rapid-acting insulin analogue before each meal. Notice the frequent overlaps among the insulins.

Breakfast Lunch Dinner

Figure 28.2. Schematic representation: a) Therapeutic scheme with one injection of isophane insulin (NPH) before bedtime and regular insulin 30 minutes before each meal. Large part the lack of basal insulin for a interval of the day is covered by the relatively prolonged action of the repeatedly injected regular insulin. b) Therapeutic scheme with two injections of isophane insulin (before breakfast and at bedtime) and one injection of very rapid-acting insulin analogue before each meal. Notice the frequent overlaps among the insulins.

either using only rapid-acting insulin as 'prandial' insulin (and not very rapid-acting analogues), whereby the relatively extended action of this kind of insulin is used to some degree as basal insulin, or by adding a second NPH injection (in smaller dose) in the morning (Figure 28.2). In this case it is preferable to use a very rapid-acting insulin analogue (Lispro or Aspart) as 'prandial' insulin, so that the overlap between the insulins is decreased. Moreover, the peak of the morning NPH dose should probably be taken into consideration and the dose of the noon 'prandial' insulin be decreased.

• Zinc insulin (Lente). Generally the same procedures mentioned above for isophane insulin are in effect. Zinc insulin has a slightly more extended action than isophane. These kinds of insulin are no longer used much in clinical practice.

• Zinc insulin of extended action (Ultralente). This insulin has a wide peak (12-16 hours after the injection) and increased variability (in the same patient as well as among different patients) in its action profile. Theoretically, it was constructed to cover the basal secretion administered once a day. However, the increased variability in its absorption often leads to unanticipated hyper- and hypoglycaemias.

• Insulin analogues. Glargine is the first insulin analogue of slow action to be used in clinical practice. It differs at the molecular level compared to human insulin both in chain A as well as in chain B (Table 28.2). Glargine is soluble in the slightly acidic environment of the solution in which it is supplied. After its injection in the subcutaneous tissue it is absorbed at a slow and constant rate. Its duration of action after subcutaneous injection is almost 24 hours (22 ± 4 hours) and, in contrast to the other slow-acting insulins, it does not have a peak. Moreover, it was found that its serum levels present smaller variability in the same and/or in different patients compared to isophane insulin. These characteristics allow the substitution of the basal secretion of insulin in the forms of basal-bolus treatment to be achieved. Thanks to its long action, the insulin Glargine can be administered only once a day, either after rising in the morning or before bedtime (Figure 28.3). Mixing with other insulins is not, for the time being at least, recommended.

Insulin Detemir is a slowly-acting analogue, the extended action of which is achieved mainly via connection of the molecule with plasma albumin. This analogue is derived after acylation of human insulin at position B29 (see Table 28.2). Detemir presents a slower onset and smaller peak of action compared to the isophane insulin. Its duration of action reaches up to 20 hours. This often renders essential its administration twice a day in intensified types of insulin therapy (morning and

Regular Insulin Peak And Duration

Figure 28.3. Schematic representation of a therapeutic scheme with administration of the insulin Glargine before bedtime and a) very rapid-acting-insulin analogue or b) regular insulin before each meal. Notice the flat action profile of Glargine and the absence of overlap among the insulins (particularly in scheme a) contrast to Figure 28.2.

Figure 28.3. Schematic representation of a therapeutic scheme with administration of the insulin Glargine before bedtime and a) very rapid-acting-insulin analogue or b) regular insulin before each meal. Notice the flat action profile of Glargine and the absence of overlap among the insulins (particularly in scheme a) contrast to Figure 28.2.

before bedtime). An advantage of Detemir is the considerably smaller variability and higher reproducibility of its plasma levels compared to other insulins, after subcutaneous injection, both in the same individual and among different patients.

Supplements For Diabetics

Supplements For Diabetics

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