Furthermore, HbA1c was slightly, but significantly, lower with insulin aspart than with regular human insulin at 6 and 12 months. This improvement was not obtained at an increased risk of hypoglycaemia.

Comment
In recent years, analogues of human insulin have been designed in order to improve diabetes treatment. The introduction of these insulins represents a milestone in the therapy of diabetes.
Insulin aspart is a rapid-acting insulin analogue in which the proline at position B28 has been replaced by aspartic acid. This results in an earlier onset of action than is seen with regular human insulin [1, 2].
The present report is of a large, long, well-organized, randomized, open-label, parallel-group study conducted in 59 centres in the USA and Canada. It comprised 882 men and women, aged 18–75 years, who had had Type 1 diabetes for at least 18 months. The main findings clearly show that overall postprandial glycaemic control was better with insulin aspart than with regular human insulin, and, in addition HbA1c values were slightly, but significantly, lower with insulin aspart than with regular human insulin.
There is some evidence to indicate that increased postprandial glycaemia is independently associated with an increased risk of vascular disease [3]. This relation is most probably explained through the activation of protein kinase in the endothelial cells, which in turn stimulates the expression of adhesion molecules on these cells, facilitating the adhesion and uptake of leukocytes into the endothelium. Therefore, the findings of the present study indirectly suggest that the use of insulin aspart may, in the long term, result in a decrease in diabetic vascular disease.
Another interesting point that the authors make is that the observed overall metabolic improvement was not obtained at an increased risk of hypoglycaemia. Similar results have been obtained in a previous study [4]. Other authors have also shown that insulin aspart and soluble human insulin elicit the same counterregulatory responses to acute hypoglycaemia in patients with Type 1 diabetes [5].
The authors of the present article postulate that the lower HbA1c in patients using insulin aspart may be partly due to the slightly greater increase in basal NPH insulin used in this group. This is an interesting point from a practical point of view since it emphasizes the need to carefully optimize the dosage of basal NPH insulin especially when rapid-acting insulin analogues are used.
Other authors have evaluated prandial glycaemia in patients with Type 1 diabetes following the subcutaneous injection of regular human insulin and insulin aspart at different injection-meal intervals [6]. They have shown that insulin aspart is superior to regular human insulin even if the former is injected 15 min after a meal and the latter immediately before a meal. The more rapid onset of action of insulin aspart than of regular human insulin observed in adults was further confirmed in a paediatric population with Type 1 diabetes [7]. It has also been shown that the improved glucose control which was demonstrated with insulin aspart in Type 1 patients also applies to insulin-treated Type 2 diabetic subjects [8] and, in addition, that insulin aspart retains its pharmacodynamic properties in a premixed 30/70 formulation [9].
It is, however, worth noting that the overall intraindividual variability of the metabolic effect of insulin aspart as tested in healthy volunteers is comparable to that observed with soluble insulin [10].
As it concerns the mitogenic potency of insulin analogues, which is a matter of broader concern, it is noted that insulin aspart has been shown in this sense to resemble human insulin [11]. Therefore this insulin analogue (as well as insulin lispro) does not seem to possess an increased mitogenic potency.
In summary it seems that insulin aspart may represent a useful and promising new insulin preparation.

References
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 3. Haller H. Postprandial glucose and vascular disease. Diabetic Med 1997; 14: S50–6.
 4. Home PD, Lindholm A, Hylleberg B, Round P. Improved glycemic control with insulin aspart: a multicenter randomized double-blind crossover trial in type 1 diabetic patients. UK Insulin Aspart Study Group. Diabetes Care 1998; 21: 1904–9.
 5. Frier BM, Ewing FM, Lindholm A et al. Symptomatic and counterregulatory hormonal responses to acute hypoglycaemia induced by insulin aspart and soluble human insulin in type 1 diabetes. Diabetes Metab Res Rev 2000; 16: 262–8.
 6. Brunner GA, Hirschberger S, Sendlhofer G et al. Post-prandial administration of the insulin analogue insulin aspart in patients with Type 1 diabetes mellitus. Diabetic Med 2000; 17: 371–5.
 7. Mortensen HB, Lindholm A, Olsen BS, Hylleberg B. Rapid appearance and onset of action of insulin aspart in paediatric subjects with type 1 diabetes. Eur J Pediatr 2000; 159: 483–8.
 8. Rosenfalck AM, Thorsby P, Kjems L et al. Improved postprandial glycaemic control with insulin aspart in type 2 diabetic patients treated with insulin. Acta Diabetol 2000; 37: 41–6.
 9. Weyer C, Heise T, Heinemann L. Insulin aspart in a 30/70 premixed formulation. Pharmacodynamic properties of a rapid-acting insulin analog in stable mixture. Diabetes Care 1997; 20: 1612–4.
10. Heinemann L, Weyer C, Rauhaus M et al. Variability of the metabolic effect of soluble insulin and the rapid-acting insulin analog insulin aspart. Diabetes Care 1998; 21: 1910–4.
11. Kurtzhals P, Schaffer L, Sorensen A et al. Correlations of receptor binding and metabolic and mitogenic potencies of insulin analogs designed for clinical use. Diabetes 2000; 49: 999–1005.

Summary and Comment:
N. Katsilambros, Athens, Greece