Recombinant human insulin analogues: recommendations for optimal use.
The recent introduction of recombinant DNA technology has made possible the manufacture of insulin analogues with altered pharmacokinetic properties. Such analogues include insulins with single or multiple amino acid substitution(s) in the A or B chains of human insulin. The modification of the amino acid sequence results in a lower tendency towards aggregation of the insulin analogues when compared with human insulin. In particular, the subcutaneous injection of rapid-acting insulin analogues generates a peak that is superimposable on the peripheral plasma insulin profile of healthy individuals after a meal, without the need for a time interval between the injection and the meal. However, long term multicentre trials with rapid-acting insulin analogues have not shown an improvement in glycated haemoglobin (HbA(1c)) values despite an improvement in post-meal (2 hour) glycaemic control. This result is probably due to the shorter action of insulin analogues compared with human regular insulin, causing higher glycaemic values at 4 hours after insulin administration despite lower values at 2 hours. Thus, the simple substitution of rapid-acting analogues for regular insulin can lead to a potential deterioration of metabolic control, causing hyperketonaemia in patients without residual C-peptide secretion. Such patients should receive supplemental intermediate insulin at bedtime and also, at low dosages and on the basis of glucose values, at any time the interval between meals is longer than 4 hours.
Torlone
E
E
Dipartimento di Medicina Interna, Scienze Endocrine e Metaboliche, Università di Perugia, Perugia, Italy. torlone@dimisem.med.unipg.it