Insulin kinetics in type I diabetic patients treated by continuous intraperitoneal insulin infusion: influence of anti-insulin antibodies.

Continuous intraperitoneal insulin infusion (CIPII) is a promising therapy of patients with Type 1 (insulin-dependent) diabetes mellitus (IDDM), since it improves metabolic control and decreases frequency of severe hypoglycaemia. This could be due to more appropriate insulin kinetics. Our aim, therefore, was to compare plasma free insulin levels achieved in patients with Type 1 diabetes chronically treated with CSII or CIPII. Furthermore, as anti-insulin antibodies increase with this treatment, we wanted to assess their influence upon insulin kinetics. Plasma free insulin profiles were obtained during the night and then after the bolus for breakfast and the bolus for lunch in 11 patients with Type 1 diabetes treated successively by CSII and CIPII. In another group of 16 patients with long-term Type 1 diabetes, treated by CIPII, we examined the influence of anti-insulin antibody level on insulin kinetics after a bolus. During the night, plasma free insulin levels were lower with CIPII than with CSII (12:00 am: 10.1 +/- 1.7 vs 18.5 +/- 2.6 mU l-1; 4:00 am: 9.1 +/- 2 vs 15 +/- 3 mU l-1), p < 0.01. After the bolus, CIPII lead to an earlier (1h vs 3h) and higher (25.8 +/- 3.3 vs 18 +/- 2.7, p < 0.05) plasma free insulin peak than CSII. With CIPII, the return to baseline level was observed within 3 h. Conversely, during CSII, insulin levels did not return to baseline until the next meal. After the bolus, high insulin-antibody levels were associated with a reduced maximal value of plasma free insulin peak. Taken together, these findings suggest that CIPII provides plasma free insulin profiles which are much closer to physiology than CSII. This could explain the lower rate of severe hypoglycaemia observed with this type of treatment. But in long-term CIPII treated patients with high anti-insulin antibody level, insulin profile could be moderately modified. This emphasizes the need for a less immunogenic insulin preparation.

[The implantable insulin pump in the treatment of diabetes. Hopes and reality?]. / La pompe à insuline implantable dans le traitement du diabète. Espoirs et réalité?

Advantages and drawbacks of the treatment of insulin-dependent diabetes by intra-peritoneal administration of insulin through an implanted infusion system are presented. This review is based upon our personal studies and the french experience centralized by the EVADIAC group. Between 1989 and 1994, 312 insulin-dependent patients were implanted in France. The mean followed up was 36 +/- 1 months, allowing an experience of 660 patients years. The main benefit is an important reduction in the incidence of severe hypoglycemia falling down from 15 per cent patient years before implantation to 2.5 per cent after. Although the patients were previously treated by intensive insulin treatment and well controlled, mean glycated hemoglobin was slightly improved and the glycemic stability increased as evidenced by the reduction of standard deviation of glycemia. Life duration of the implanted system averaged 38 months excepted for incidents requiring an explantation. Although the frequency of incidents was non negligible, they were acceptable. Vigilance, as performed by EVADIAC group is still necessary. This point can be illustrated by a technical problem which appeared recently and was due to a poor compatibility between a new preparation of insulin and the ejection chamber of the pump. Intraperitoneal administration of insulin allows to obtain plasma insulin concentration through the day closer to the physiology than that obtained with subcutaneous insulin infusion. Blood levels of some proteins, mainly SHBG and IGF1, return to normal values. However, this mode of administration is associated in some cases with an important increase of the insulin antibody levels, increase which does not seem to have a deleterious metabolic effect, but has to be carefully evaluated on the long term.