RESUMEN
AIM: Continuous intraperitoneal insulin infusion (CIPII) with the DiaPort system using regular insulin was compared to continuous subcutaneous insulin infusion (CSII) using insulin Lispro, to investigate the frequency of hypoglycemia, blood glucose control, quality of life, and safety. METHODS: In this open, randomized, controlled, cross-over, multinational, 12-month study, 60 type 1 diabetic patients with frequent hypoglycemia and/or HbA1c > 7.0% with CSII were randomized to CIPII or CSII. The aim was to obtain the best possible blood glucose while avoiding hypoglycemia. RESULTS: The frequency of any hypoglycemia was similar (CIPII 118.2 (SD 82.6) events / patient year, CSII 115.8 (SD 75.7) p = 0.910). The incidence of severe hypoglycemia with CSII was more than twice the one with CIPII (CIPII 34.8 events / 100 patient years, CSII 86.1, p = 0.013). HbA1c, mean blood glucose, and glucose fluctuations were not statistically different. Treatment-related severe complications occurred mainly during CIPII: port infections (0.47 events / patient year), abdominal pain (0.21 events / patient year), insulin underdelivery (0.14 events / patient year). Weight gain was greater with CSII (+ 1.5 kg vs. - 0.1 kg, p = 0.013), quality of life better with CIPII. CONCLUSIONS: In type 1 diabetes CIPII with DiaPort reduces the number of severe episodes of hypoglycemia and improves quality of life with no weight gain. Because of complications, indications for CIPII must be strictly controlled. CIPII with DiaPort is an alternative therapy when CSII is not fully successful and provides an easy method of intraperitoneal therapy.
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Glucemia/análisis , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemia/prevención & control , Hipoglucemiantes/administración & dosificación , Infusiones Parenterales/normas , Sistemas de Infusión de Insulina/normas , Insulina/administración & dosificación , Estudios Cruzados , Diabetes Mellitus Tipo 1/sangre , Europa (Continente) , Femenino , Humanos , Hipoglucemia/sangre , Hipoglucemia/epidemiología , Hipoglucemiantes/sangre , Insulina/análogos & derivados , Insulina/sangre , Insulina Lispro , Masculino , Persona de Mediana Edad , Calidad de Vida , Resultado del TratamientoRESUMEN
AIM: This randomised study was designed to investigate the impact of continuous glucose monitoring (CGM) for 48h on glycaemic control with a 3-month follow-up in patients with type 1 (T1D) or type 2 (T2D) diabetes. METHODS: A total of 48 patients with poor glycaemic control (HbA(1c): 8-10.5%) underwent CGM for 48h using the GlucoDay((R)) system (A. Menarini Diagnostics), after which they were randomly assigned to treatment adjustments based on either their CGM profile (CGM group) or their usual self-monitoring of blood glucose (SMBG group). HbA(1c) measurement and 48-h CGM were repeated 3 months later. RESULTS: Altogether, 34 patients with either T1D (n=9) or T2D (n=25) completed the study; seven patients chose to leave the study, and seven patients in the CGM group were excluded because their baseline CGM graphs were not interpretable. HbA(1c) levels decreased significantly in the CGM group (n=14, -0.63+/-0.27%; P=0.023), but not in the controls (n=20, -0.28+/-0.21%; P=0.30). In T2D patients, the improvement associated with CGM vs SMBG was due to HbA(1c) decreases (mean: -0.63+/-0.34%; P=0.05 vs -0.31+/-0.29%; P=0.18, respectively). However, HbA(1c) did not change significantly with CGM in T1D patients. Comparisons of CGM data at baseline and after 3 months showed no significant changes in glucose control, glucose variability or hypoglycaemia. No major adverse events related to the GlucoDay system were reported. CONCLUSION: This is the first randomised study showing that CGM improves glycaemic control in patients with T2D.
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Automonitorización de la Glucosa Sanguínea/métodos , Glucemia/análisis , Diabetes Mellitus/sangre , Hemoglobina Glucada/análisis , Hiperglucemia/prevención & control , Hipoglucemia/prevención & control , Monitoreo Ambulatorio/instrumentación , Adulto , Automonitorización de la Glucosa Sanguínea/instrumentación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Cooperación del Paciente , Satisfacción del Paciente , Estadísticas no Paramétricas , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
AIM: To review clinical use of implantable insulin pumps and to suggest indications for this therapy. METHODS: The EVADIAC group performed a review of published reports on implantable insulin pumps for the last 15 years and analyzed its own centralized database. From this update, a position statement on indications of this therapy is drawn. RESULTS: Published papers mostly report safety and effectiveness data from observational cumulated experiences of 15-350 patient-years. While HbA(1c) reduction does not reach statistical significance in all reported studies, improvement of blood glucose stability and reduction of severe hypoglycaemia appear as constant characteristics of this therapy. When compared to subcutaneous insulin therapy in randomized controlled studies, implantable pumps allow significantly reduced blood glucose fluctuations and improved quality of life in both type 1 and type 2 diabetic patients, and a significant weight decrease in type 2 diabetic patients. While the EVADIAC registry shows the reduced occurrence of pump-pocket complications thanks to preventive measures and a lower incidence of catheter obstructions following improvements of catheter design, underdelivery due to insulin aggregation in pumps remains a recurrent although reversible issue. Determinants of increased anti-insulin antibody production in some patients remain elusive but impact on blood glucose control is limited in most cases. CONCLUSION: From analyzed data, the EVADIAC group states that implantable pumps can be safely indicated and provide metabolic improvements in type 1 diabetic patients who remain far from targeted HbA(1c) below 7% and/or experience large fluctuations of blood glucose including recurrent severe hypoglycaemia, in spite of intensive follow-up and education when treated by subcutaneous insulin.
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Sistemas de Infusión de Insulina/estadística & datos numéricos , Ensayos Clínicos como Asunto , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diseño de Equipo , Humanos , Estudios Multicéntricos como Asunto , SeguridadRESUMEN
The development of implanted insulin pump treatment has been particularly intense in France and French implanting centers joined to form an association called EVADIAC. The data collected by EVADIAC have clearly documented benefits as well possible problems with this treatment mode. In comparison with SC administration, intraperitoneal (IP) insulin infusion via an implanted pump achieves good metabolic control, improves long-term stability of diabetes and significantly reduces the risk of severe hypoglycemia. Problems can involve pump slowdown, catheter obstruction or local complication at the implantation site. With respect to the benefits, the rate of complications is highly acceptable. However, amongst the implanted diabetic patients, some elect to give up such a treatment mode. In a retrospective study we intended to examine their reasons for giving up this treatment. In our center, the patients who elected by themselves to give up the implanted pump account for 16% of all treated patients. This group of patients did not have, as compared to other implanted patients, less benefits nor more restrictions or incidents that could have impaired their well being. The reasons for giving up the implanted pump seem more often to be related to the refusal of a strict and institutional management linked to this treatment.
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Sistemas de Infusión de Insulina/psicología , Negativa del Paciente al Tratamiento , Glucemia/metabolismo , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/psicología , HumanosRESUMEN
OBJECTIVE: To study the reproducibility of plasma insulin kinetics during intraperitoneal (IP) insulin therapy using an implanted programmable pump in patients with type 1, insulin dependent, diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: In a group of ten type 1 IDDM patients beginning chronic IP insulin treatment with an implanted pump, plasma free insulin profiles were determined from 12: 00 am to 12: 30 pm on two separate test days, one month apart. Anti-insulin antibody (AIA) levels were measured on each test day. RESULTS: From test day 1 to test day 2, no difference was observed in morning fasting free insulin levels (m +/- SD): 9.7 +/- 5.4 mU/L versus 9.8 +/- 5.3 mU/L, insulin peak values: 19.1 +/- 17 mU/L versus 20.8 +/- 9.9 mU/L, time to peak: 40 +/- 15 versus 42.8 +/- 16 minutes or post-bolus area under the plasma free insulin curve (AUC): 40.7 +/- 29 mU/L.h versus 45.5 +/- 29 mU/L.h. The intrapatient coefficient of variation was 14.4 +/- 13% for insulin peaks and 16.9 +/- 9.2% for post-bolus AUC. A significant increase in AIA levels (m +/- SD) was observed from 16.5 +/- 18% on test day 1 to 28.1 +/- 28% on test day 2. CONCLUSIONS: The reproducibility of plasma free insulin profiles is highly satisfactory during insulin delivery by the IP route using an implanted device.
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Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Sistemas de Infusión de Insulina , Insulina/sangre , Insulina/uso terapéutico , Adulto , Edad de Inicio , Área Bajo la Curva , Índice de Masa Corporal , Diabetes Mellitus Tipo 1/inmunología , Humanos , Insulina/farmacocinética , Anticuerpos Insulínicos/sangre , Radioinmunoensayo , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: To report a long-term multicentre experience with implantable insulin pumps in type 1 diabetic patients, and to test safety and accuracy of the systems following improvements in infused insulin solutions and peritoneal catheter. RESEARCH DESIGN AND METHODS: Forty MiniMed Implantable Pumps model 2001 were consecutively implanted over a two-month period in type 1 diabetic volunteers. The systems were equipped by a new compliant sideport catheter and were refilled at 45-day intervals with HOE 21 PH ETP insulin batches showing enhanced physical stability in vitro. Safety was assessed from the incidence of acute adverse events and effectiveness from quarterly HbA(1c) assays. Accuracy of delivery was measured at each pump refill by comparing residual insulin in the pump reservoir with expected amount according to programmed infusion. The study lasted until pump battery depletion or premature pump explantation. RESULTS: Cumulated experience was 106 patient-years. Premature explantations occurred in 3 cases, due to one electronic pump failure and two "pump-pocket" infections. Near-normal insulin delivery was sustained until expected battery depletion in 13 cases. Forty underdelivery events occurred in 24 pumps, but 36 among them were related to pump slowdowns due to insulin aggregation in pumps that were promptly solved by an outpatient NaOH rinse procedure. Only 4 underdeliveries were caused by catheter obstructions that required laparoscopy to remove peritoneal tissue overgrowth around the catheter. Over pump lifetime, HbA(1c) was 7.2 +/- 0.2% in the 13 patients with no underdelivery and 7.7 +/- 0.5% in the other ones. Only one severe hypoglycemia and one ketoacidosis occurred during the whole study. CONCLUSION: Our current experience with improved implantable pumps and insulin solutions shows both long-term safety and effectiveness of this treatment in type 1 diabetic patients following improvement in infused insulin solutions and catheter. This therapy may be a good alternative for patients that experience frequent severe hypoglycemia with intensive subcutaneous insulin therapy.
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Diabetes Mellitus Tipo 1/tratamiento farmacológico , Sistemas de Infusión de Insulina , Adulto , Cateterismo/instrumentación , Diabetes Mellitus Tipo 1/sangre , Cetoacidosis Diabética/epidemiología , Falla de Equipo , Hemoglobina Glucada/análisis , Humanos , Hipoglucemia/epidemiología , Bombas de Infusión Implantables , Insulina/administración & dosificación , Sistemas de Infusión de Insulina/efectos adversos , Sistemas de Infusión de Insulina/normas , Persona de Mediana EdadRESUMEN
OBJECTIVE: To determine the utility of the continuous glucose monitoring system (CGMS) as an outpatient procedure to improve management of diabetes in adolescents. RESEARCH DESIGN AND METHODS: Twelve adolescents (mean age: 16.2 +/- 3 years) with poorly controlled type 1 diabetes (HbA(1c) > 8%) were included in this trial. Mean HbA(1c) during the previous year was 10.1 +/- 1.2%. Insulin treatment consisted of 2 or 3 daily injections in 10 cases and CSII in 2. At the beginning of the study, HbA(1c) was determined and low blood glucose index (LBGI) was calculated. Continuous glucose monitoring was performed for three days. After downloading and analyzing data, results were discussed with the patient and insulin treatment was adjusted. Two months later testing was repeated and all parameters were reassessed. RESULTS: Initial CGMS profiles demonstrated glycemic excursions unrecognized by capillary measurements in all twelve patients. Glycemia before and after meals varied from<60 mg/dL to > 200 mg/dL in 2 patients (2 episodes). Postprandial hyperglycemia exceeded 200 mg/dL in 10 patients (24 episodes). Prolonged overnight hyperglycemia was observed in 5 patients (7 episodes), dawn phenomenon in 4 patients (6 episodes) and nighttime hypoglycemia in 4 patients (4 episodes). A day-to-day reproducibility of glycemic profiles was observed in 8 patients. Then insulin treatment was adjusted according to CGMS data. Changes involved dose levels in 3 patients, insulin type in 7, number of injections, i.e. 3 instead of 2, in 5 or change from insulin injection to CSII in 1. Reassessment two months later demonstrated a significant reduction of glycemic excursions in 8 patients. HbA(1c) (m +/- SD) decreased from 10.3 +/- 2.1% to 8.75 +/- 1.06% (p<0.05). LBGI increased from 1.7 +/- 0.9 to 2.4 +/- 1.4 but the difference was not significant. CONCLUSIONS: Use of CGMS in diabetic adolescent outpatients achieved a significant improvement in metabolic control not only by providing accurate data for adjustment of insulin treatment but also by promoting patient communication and motivation.
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Automonitorización de la Glucosa Sanguínea/métodos , Diabetes Mellitus Tipo 1/terapia , Adolescente , Adulto , Glucemia/análisis , Automonitorización de la Glucosa Sanguínea/instrumentación , Diabetes Mellitus Tipo 1/sangre , Femenino , Alimentos , Hemoglobina Glucada/análisis , Humanos , Hiperglucemia/epidemiología , Hipoglucemia/epidemiología , Insulina/administración & dosificación , Masculino , Reproducibilidad de los Resultados , Factores de TiempoAsunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/fisiopatología , Bombas de Infusión Implantables , Sistemas de Infusión de Insulina , Embarazo en Diabéticas/tratamiento farmacológico , Adulto , Cesárea , Femenino , Hemoglobina Glucada/análisis , Humanos , Recién Nacido , Trabajo de Parto , Masculino , Embarazo , Resultado del EmbarazoAsunto(s)
Autoanticuerpos/análisis , Diabetes Mellitus Tipo 1/inmunología , Sistemas de Infusión de Insulina/efectos adversos , Insulina/inmunología , Adulto , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Femenino , Humanos , Bombas de Infusión Implantables , Insulina/administración & dosificación , Insulina/uso terapéutico , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To compare the efficacy of the short-acting insulin analog lispro (LP) with that of regular insulin in IDDM patients treated with an external pump. RESEARCH DESIGN AND METHODS: Thirty-nine IDDM patients (age, 39.4 +/- 1.5 years; sex ratio, 22M/17W; BMI, 24.4 +/- 0.4 kg/m2; diabetes duration, 22.5 +/- 1.6 years) who were treated by external pump for 5.1 +/- 0.5 years were involved in an open-label, randomized, crossover multicenter study comparing two periods of 3 months of continuous subcutaneous insulin infusion with LP or with Actrapid HM, U-100 (ACT). Boluses were given 0-5 min (LP) or 20-30 min (ACT) before meals. Blood glucose (BG) was monitored before and after the three meals every day. RESULTS: The decrease in HbA1c was more pronounced with LP than with ACT (-0.62 +/- 0.13 vs. -0.09 +/- 0.15%, P = 0.01). BG levels were lower with LP (7.93 +/- 0.15 vs. 8.61 +/- 0.18 mmol/l, P < 0.0001), particularly postprandial BG levels (8.26 +/- 0.19 vs. 9.90 +/- 0.20 mmol/l, P < 0.0001). Standard deviations of all the BG values (3.44 +/- 0.10 vs. 3.80 +/- 0.10 mmol/l, P = 0.0001) and of postprandial BG values (3.58 +/- 0.10 vs. 3.84 +/- 0.10 mmol/l. P < 0.02) were lower with LP. The rate of hypoglycemic events defined by BG < 3.0 mmol/l did not significantly differ between LP and ACT (7.03 +/- 0.94 vs. 7.94 +/- 0.88 per month, respectively), but the rate of occurrences of very low BG, defined as BG < 2.0 mmol/l, were significantly reduced with LP (0.05 +/- 0.05 vs. 0.47 +/- 0.19 per month, P < 0.05). At the end of the study, all but two (95%) of the patients chose LP for the extension phase. CONCLUSIONS: When used in external pumps, LP provides better glycemic control and stability than regular insulin and does not increase the frequency of hypoglycemic episodes.
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Glucemia/metabolismo , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hemoglobina Glucada/análisis , Hipoglucemiantes/uso terapéutico , Sistemas de Infusión de Insulina , Insulina/análogos & derivados , Insulina/uso terapéutico , Adulto , Estudios Cruzados , Femenino , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/epidemiología , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Insulina Lispro , Insulina Regular Porcina , Masculino , Satisfacción del Paciente , Encuestas y CuestionariosAsunto(s)
Bombas de Infusión Implantables/efectos adversos , Insulina/uso terapéutico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/epidemiología , Estudios de Seguimiento , Francia/epidemiología , Humanos , Insulina/administración & dosificación , Estudios Retrospectivos , Factores de TiempoRESUMEN
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.
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Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/inmunología , Anticuerpos Insulínicos/sangre , Insulina/farmacocinética , Adulto , Análisis de Varianza , Glucemia/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Femenino , Humanos , Infusiones Parenterales , Insulina/administración & dosificación , Insulina/sangre , Sistemas de Infusión de Insulina , Cinética , Masculino , Cavidad PeritonealRESUMEN
The pituitary-specific transcription factor Pit-1/GHF1 regulates the expression of PRL, GH, and TSH beta genes through binding to specific regions of the promoters of these genes. Mutations of the Pit-1 gene have been shown to be responsible for a syndrome of combined pituitary hormone deficiency (CPHD), including complete GH and PRL deficiencies and central hypothyroidism. We studied four siblings presenting with CPHD born to healthy consanguinous parents. All four affected children had complete GH deficiency diagnosed in early childhood. They later developed hypothyroidism and were found to have undetectable PRL levels. The pituitary gland was hypoplastic at magnetic resonance examination in one of the patients. Amplification of genomic DNA and subsequent sequencing of the six exons of the Pit-1 gene allowed identification in the four patients with CPHD of an as yet undescribed mutation in exon 3. A substitution of T go G induced a change from a Phe to a Cys residue at position 135 within the hydrophobic core of the POU-specific DNA-binding domain of the Pit-1 protein. All affected children were homozygous for the mutation, whereas the mother was heterozygous, suggesting a recessive mode of inheritance. Molecular studies in other affected families will allow instructive genotype-phenotype correlations concerning the Pit-1 gene.
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Proteínas de Unión al ADN/genética , Genes , Mutación , Hormonas Hipofisarias/deficiencia , Factores de Transcripción/genética , Adolescente , Adulto , Secuencia de Bases , Niño , ADN/genética , Femenino , Genoma , Hormonas/sangre , Humanos , Imagen por Resonancia Magnética , Masculino , Sondas Moleculares/genética , Datos de Secuencia Molecular , Linaje , Hipófisis/patología , Factor de Transcripción Pit-1RESUMEN
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.
Asunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Bombas de Infusión Implantables , Sistemas de Infusión de Insulina , Adulto , Diabetes Mellitus Tipo 1/sangre , Humanos , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
OBJECTIVE: To assess immunogenicity of intraperitoneal insulin infusion via implanted pumps by two methods and to evaluate the possible influence of an increased antibody level on metabolic and clinical parameters. RESEARCH DESIGN AND METHODS: We studied insulin antibody levels in 17 type I diabetic patients before and until 24 months after implantation of a programmable pump delivering insulin intraperitoneally. Antibody levels were determined by radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA). They were correlated with HbA1c, insulin requirements, free insulin, and the incidence of hypoglycemia. RESULTS: Insulin antibodies increased as soon as the 3rd month after implantation. This increase was sustained throughout the study period (month 0, 25.4 +/- 16.2%; month 3, 41.2 +/- 23.5%; month 12, 45.9 +/- 26%; month 24, 48.7 +/- 25%). The data was correlated with the two assay methods (RIA and ELISA). Postimplantation level was correlated with preimplantation level, which could indicate a predictive value of the latter . No correlation was observed with any metabolic parameters, particularly the number of hypoglycemic episodes. CONCLUSIONS: Our results indicate that intraperitoneal insulin administration by implantable programmable pumps leads to an increase of insulin antibodies, which are probably high-affinity antibodies (recognized by both RIA and ELISA). This increase in insulin immunogenicity did not induce significant metabolic consequences, which is reassuring for the future of programmable insulin pumps.