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[IP] Assessment of In Vivo Stability of a New Insulin...implantable...







Assessment of In Vivo Stability of a New Insulin Preparation for 
Implantable Insulin Pumps 


A randomized multicenter prospective trial 


Programmable implantable insulin pumps have proven to be safe and 
effective devices for achieving good metabolic control (1) and 
decreasing the risk of severe hypoglycemia (2). In 1993, changes in the 
insulin production process resulted in increased insulin precipitation 
in the pumps, worsening the clinical performances of the devices. 
Evaluation Dans le Diabète du Traitement par Implants Actifs (EVADIAC) 
proposed improved pump rinse procedures and a shortening of the interval 
between refills (3), and the MiniMed catheter was improved. Hoechst 
Marion Roussel (Frankfurt, Germany) produced a new insulin variant (21 
PH ETP). EVADIAC designed a protocol study to examine the in vivo 
stability of 21 PH ETP using a multicentric, prospective randomized 
study with intervals of 3 months as compared with 45 days between 

A total of 176 patients were randomized into two groups, G45 (45 days) 
and G90 (90 days), between refills. The study criteria was the accuracy 
of insulin infusion with 21 PH ETP (human semisynthetic insulin, Genapol 
stabilized, 400U/ml; Hoechst). 

A total of 196 MiniMed MIP 2001 (MiniMed Technologies, Sylmar, CA) pumps 
were studied: 122 (pumps A) without polyethylene-polypropylene glycol 
coating, previously used with other batches of insulin and washed with 
an alkaline procedure before the study, and 74 new pumps (pumps B) with 
polyethylene-polypropylene glycol coating on the inside. 

The infusion accuracy (% error) was calculated as the ratio between 
theoretical and real volume infused difference over the theoretical 
volume infused. 

The evolution of percent error, i.e.,the delta of % (%) error at 6, 9, 
and 12 months vs. 3 months, was compared between G45 and G90 and between 
pumps A and B, using nonpaired t tests. An analysis of variance was used 
to determine whether G45, G90, pumps A or B, and high percent error were 

A total of 88 pumps were randomized into G45 and 108 pumps into G90. 
There was no difference between G45 and G90 in terms of % error at 6, 9, 
and 12 months as compared with 3 months. 

However, pumps B showed a greater % error at 6 months (P = 0.006 for G45
 and 0.024 for G90). This higher increase in the percent error tended to 
attenuate during the following months. The analysis of variance showed 
that independently from groups G45 and G90, pumps B presented a higher 
percent error than pumps A (P = 0.0003). 

On the basis of the results of this study we may conclude that the 
stability of 21 PH ETP was comparable at 90 days to that at 45 days in 
implantable pumps in vivo. As this study was not designed to compare the 
two groups of pumps together, the difference observed between pumps A 
and pumps B must be interpreted with caution. This problem is currently 
under investigation. 

We conclude that using 21 PH ETP, the clinical performances of 
implantable pumps are comparable in intervals of 45 and 90 days between 
refills and that an acceptable 3-month interval between refills may be 

Sophie Boivin, MD 
Pauline Belicar, MD 
Vincent Melki, MD 


Acknowledgments— We are grateful to Sylvie Boullu-Sanchis, MD, for her 
support in statistical analysis. 


1. Pinget M, Jeandidier N: Long-term safety and efficacy of 
intraperitoneal insulin infusion by means of implantable pumps. Horm Met 
Res 30:475–486, 1998 

2. Jeandidier N, Selam JL, Renard E, Guerci B, Lassmann-Vague V, Rocher 
L, Hanaire-Broutin H, EVADIAC Study Group: Decreased severe hypoglycemia 
frequency during intraperitoneal insulin infusion using programmable 
implantable pumps (Letter). Diabetes Care 19:780, 1996 

3. Boivin S, Jeandidier N, Boullu S, Pinget M: Impact of recent changes 
in the management of implantable pumps: reduction of pump/catheter 
dysfunctioning (Abstract). Horm Metab Res 29:A2, 1997 


>From the Service d'Endocrinologie et Maladies Métaboliques (S.B.), 
Hôpitaux Universitaires de Strasbourg, Strasbourg; Service 
d'Endocrinologie Maladies Métaboliques et Nutrition (P.B.), CHRU de 
Marseille, Hôpital La Timone, Marseille; Service 
d'Endocrinologie-Diabétologie (V.M.), CHU Rangueil, Toulouse, France. 

Address correspondence to Sophie Boivin, MD, Service d'Endocrinologie et 
Maladies Métaboliques, Hôpitaux Universitaires de Strasbourg, 1 Place de 
l'Hôpital, 67091 Strasbourg cedex, France.  <A 
>Assessment of In Vivo Stability of a New Insu...</A> 
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