Insulin lispro therapy in pregnancies complicated by type 1 diabetes mellitus

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Abstract

Objective: To compare the efficacy and safety of preprandial administration of rapid-acting lispro analogue with regular short-acting insulin to pregnant women with type 1 diabetes. Study design: Open randomised multicentre study. Women were treated with multiple insulin injections aiming at normoglycaemia. Blood glucose was determined six times daily, HbA1c every 4 weeks. Diurnal profiles of blood glucose were analysed at gestational week 14 and during the study period at weeks 21, 28 and 34. Participants: 33 pregnant women with type 1 DM were randomised to treatment with lispro insulin (n=16) or regular insulin (n=17). Results: Blood glucose was significantly lower (P<0.01) after breakfast in the lispro group, while there were no significant group differences in glycemic control during the rest of the day. Severe hypoglycaemia occurred in two patients in the regular group but biochemical hypoglycaemia (blood glucose <3.0 mmol/l) was more frequent in the lispro than in the regular group (5.5 vs. 3.9%, respectively). HbA1c values at inclusion were 6.5 and 6.6% in the lispro and regular group respectively. HbA1c values declined during the study period and were similar in both groups. There was no perinatal mortality. Complications during pregnancy, route of delivery and foetal outcome did not differ between the groups. Retinopathy progressed in both groups, one patient in the regular group developed proliferative retinopathy. Conclusion: The results suggest that it is possible to achieve at least as adequate glycemic control with lispro as with regular insulin therapy in type 1 diabetic pregnancies.

Introduction

The importance of maintaining the blood glucose level close to or within the physiological range in pregnancies complicated by type 1 diabetes mellitus is well-recognised. The introduction of self-monitoring of blood glucose and multiple insulin injection regimens as well as continuous subcutaneous insulin infusion has further improved neonatal outcome. However, when attempts are made to achieve tight blood glucose control the risk of severe hypoglycaemia increases. In diabetic pregnancies several studies have reported a high incidence of severe hypoglycaemia (19–45%) defined as the need of assistance by another person to relieve the attack [1], [2], [3]. By individualising insulin therapy and allowing a higher glucose level in individual cases we recorded a lower incidence of severe hypoglycaemia (4.4%) without affecting pregnancy or neonatal outcome [4].

During normal pregnancy fasting blood glucose levels decrease whereas postprandial levels tend to increase. In non pregnant diabetic subjects the rapid-acting insulin analogue lispro improves postprandial blood glucose levels and reduces the incidence of hypoglycaemia, effects which have been ascribed to its pharmacokinetic and pharmacodynamic properties [5], [6]. So far there is little experience with lispro therapy during pregnancy. Concern has been expressed that lispro therapy in type 1 diabetic pregnancy might adversely influence foetal development or lead to progression of retinopathy [7], [8], [9], [10].

Lispro has been successfully used in women with gestational diabetes [11]. Glycemic control and levels of insulin antibodies in that study were similar to those observed in women randomised to receive regular human insulin. The group randomised to lispro therapy had however a lower incidence of hypoglycaemia.

The primary objectives of the present study were to compare the efficacy and safety of preprandial administration of rapid-acting lispro analogue with regular short-acting insulin to pregnant women with type 1 diabetes with respect to blood glucose control. The design of the study allowed evaluation of progression of retinopathy during the course of pregnancy.

Section snippets

Material and methods

Thirty-three women with type 1 diabetes participated in this open label randomised multicentre study. Type 1 diabetes was defined as diabetes with onset before age 35 and requiring insulin treatment within 1 year from diagnosis. Sixteen patients were randomised to lispro and 17 to regular insulin therapy. There were no significant differences between the two treatment groups with regard to baseline characteristics including age, duration of diabetes, presence of microangiopathy, BMI, initial HbA

HbA1c

The initial HbA1c values before randomisation were 6.5 (range 4.8–8.6) and 6.6 (4.5–8.6) in the lispro and regular groups, respectively (n.s.). A significant decrease in HbA1c was seen in both groups from initial value before randomisation until week 14 at randomisation, but thereafter neither the changes within the group nor the levels between groups were statistically significant (Table 2).

Blood glucose

There was no significant difference in a glycemic control (Table 3) in a 1-week diurnal profile before

Discussion

The present study clearly demonstrated that treatment of pregnant women with type 1 diabetes from gestational week 15 with the rapid acting insulin analogue lispro insulin resulted in significantly lower glycemic excursions after breakfast than in women treated with regular short acting insulin. This was in general agreement with several previous observations in non-pregnant type 1 diabetic patients [5], [13] and with the findings in gestational diabetic women of significantly lower area under

Acknowledgements

We gratefully acknowledge the help of Per Lennerhagen, MD, PhD, for recruiting patients at Södersjukhuset.

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