Efficacy of automated insulin delivery in pregnant women with type 1 diabetes: a meta-analysis and trial sequential analysis of randomized controlled trials.

BACKGROUND: Automated insulin delivery (AID) devices have shown to be a promising treatment to improve glycemic control in patients with type 1 diabetes mellitus (T1DM). However, its efficacy in pregnant women with T1DM remains uncertain. METHODS: PubMed, Scopus, Cochrane Central and ClinicalTrials.gov were systematically searched for randomized controlled trials (RCTs) comparing AID to standard care (SC), defined as use of sensor-augmented pump and multiple daily insulin injections. Outcomes included time in range (TIR), nocturnal TIR, time in hypoglycemic and hyperglycemic ranges, among others. Sensitivity and trial sequential analyses (TSA) were performed. PROSPERO ID: CRD42023474398. RESULTS: We included five RCTs with a total of 236 pregnant women, of whom 117 (50.6%) received AID. There was a significant increase in nocturnal TIR (mean difference [MD] 12.69%; 95% CI 8.74-16.64; p < 0.01; I2 = 0%) and a decrease in glucose variability (standard deviation of glucose; MD -2.91; 95% CI -5.13 to -0.69; p = 0.01; I2 = 0%). No significant differences were observed for TIR, HBGI, LGBI, mean glucose and time spent in hyperglycemia and hypoglycemia. Regarding TSA, the statistical significance obtained in nocturnal TIR was conclusive and with minimal risk of a type I error. CONCLUSION: Our findings suggest that AID systems can significantly improve nocturnal glycemic control and potentially reduce glycemic variability in pregnant women with T1DM, with no effect in the risk of hypoglycemia and hyperglycemia compared with current insulin treatments.

Multiple basal infusion rates in open-loop insulin delivery systems: is there a metabolic benefit?

Objective: To evaluate glycemic control according to the number of daily basal rates (BRs) in type 1 diabetes patients using continuous subcutaneous insulin infusion (CSII). Subjects and methods: Cross-sectional study of patients treated with an open-loop CSII for at least 6 months and using a flash glucose monitoring system. Patients were divided into 2 groups: group 1 (G1) and group 2 (G2), with ≤4 and >4 BRs/24h, respectively. The groups were compared regarding HbA1c, time in range (TIR), time above range (TAR), time below range (TBR), glucose management indicator (GMI), glucose variability and data related to hypoglycemia. Regression models were performed. Results: The study included 99 patients (n = 55 in G1; n = 44 in G2). Median (Interquartile range) overall age was 30 (17) years, with 19.5 (48) and 51 (77) months of CSII use, respectively. The median number of different BRs was 3 (2) for G1 and 6 (2) for G2. There were no differences concerning age, sex, educational stage, weight, and insulin analog used. G2 had longer disease duration, longer CSII use, and higher total basal daily dose/kg. No significant differences regarding HbA1c, median glucose, GMI, TIR, TAR, and CV were found. G2 patients had more hypoglycemia, more asymptomatic hypoglycemia, and higher TBR. After adjusting for potential confounders, G1 maintained a lower risk of asymptomatic hypoglycemia. Conclusion: Programming open-loop CSII devices with more than 4 BRs does not improve metabolic control. Additionally, it seems to be a risk factor for hypoglycemia and was an independent predictor for asymptomatic hypoglycemia.

Maternal-fetal outcomes of pregnant women with type 1 diabetes treated with continuous subcutaneous insulin infusion or multiple daily injections during pregnancy - A Brazilian health care referral center cohort study.

Objective: Pregnant women with type 1 diabetes (T1D) have an increased risk of maternal-fetal complications. Regarding treatment, continuous subcutaneous insulin infusion (CSII) has advantages compared to multiple daily injections (MDI), but data about the best option during pregnancy are limited. This study's aim was to compare maternal-fetal outcomes among T1D patients treated with CSII or MDI during pregnancy. Subjects and methods: This study evaluated 174 pregnancies of T1D patients. Variables of interest were compared between the groups (CSII versus MDI), and logistic regression analysis was performed (p < 0.05). Results: Of the 174 included pregnancies, CSII was used in 21.3% (37) and MDI were used in 78.7% (137). HbA1c values improved throughout gestation in both groups, with no difference in the first and third trimesters. The frequency of cesarean section was significantly higher in the CSII group [94.1 vs. 75.4%, p = 0.017], but there was no significant difference in the frequency of other complications, such as miscarriage, premature delivery and preeclampsia. The mean birth weight and occurrence of neonatal complications were also similar, except for the proportion of congenital malformations, which was significantly lower in the CSII group [2.9 vs. 15.6%, p = 0.048]. In regression analysis, the association of CSII with cesarean section and malformations lost significance after adjusting for HbA1c and other covariates of interest. Conclusion: In this study, we observed a higher frequency of cesarean section and a lower occurrence of congenital malformations in the CSII group, but the adjusted results might indicate that these associations are influenced by glycemic control.

Early and sustained increase in time in range 1 year after initiation of hybrid close loop therapy via telemedicine in type 1 diabetes patients.

BACKGROUND AND AIMS: Evidence supports the efficacy and safety of the Hybrid Close loop (HCL) system in patients with type 1 diabetes (T1D). However, limited data are available on the long-term outcomes of patients on HCL with telemedicine follow-up. METHODS: A prospective observational cohort study including T1D patients, who were upgrading to HCL system. Virtual training and follow-up were done through telemedicine. CGM data were analyzed to compare the baseline time in range (TIR), time below range (TBR), glycemic variability and auto mode (AM), with measurements performed at 3, 6 and 12 months. RESULTS: 134 patients were included with baseline A1c 7.6% ± 1.1. 40.5% had a severe hypoglycemia event in the last year. Baseline TIR, measured two weeks after starting AM was 78.6 ± 9.94%. No changes were evident at three (Mean difference - 0.15;CI-2.47,2.17;p = 0.96), six (MD-1.09;CI-3.42,1.24;p = 0.12) and 12 months (MD-1.30;CI-3.64,1.04;p = 0.08). No significant changes were found in TBR or glycemic variability throughout the follow-up. Use of AM was 85.6 ± 17.5% and percentage of use of sensor was 88.75 ± 9.5% at 12 months. No severe hypoglycemic (SH) events were reported. CONCLUSIONS: HCL systems allow to improve TIR, TBR and glycemic variability safely, early and sustained up to 1 year of follow-up in patients with T1D and high risk of hypoglycemia followed through telemedicine.

Increased Technology Use Associated With Lower A1C in a Large Pediatric Clinical Population.

OBJECTIVE: While continuous glucose monitors (CGMs), insulin pumps, and hybrid closed-loop (HCL) systems each improve glycemic control in type 1 diabetes, it is unclear how the use of these technologies impacts real-world pediatric care. RESEARCH DESIGN AND METHODS: We found 1,455 patients aged <22 years, with type 1 diabetes duration >3 months, and who had data from a single center in between both 2016-2017 (n = 2,827) and 2020-2021 (n = 2,731). Patients were grouped by multiple daily injections or insulin pump, with or without an HCL system, and using a blood glucose monitor or CGM. Glycemic control was compared using linear mixed-effects models adjusting for age, diabetes duration, and race/ethnicity. RESULTS: CGM use increased from 32.9 to 75.3%, and HCL use increased from 0.3 to 27.9%. Overall A1C decreased from 8.9 to 8.6% (P < 0.0001). CONCLUSIONS: Adoption of CGM and HCL was associated with decreased A1C, suggesting promotion of these technologies may yield glycemic benefits.

Real-world performance of the MiniMed 780G advanced hybrid closed loop system in Latin America: Substantial improvement in glycaemic control with each technology iteration of the MiniMed automated insulin delivery system.

AIM: We studied real-world performance of MiniMed (MM) 780G system users from Argentina, Brazil, Colombia and Chile (geographical analysis), and the effect of each technology iteration of the MM system on glycaemic control (technology iteration analysis). MATERIALS AND METHODS: CareLink data from August 2020 to September 2022 were extracted. Endpoints included continuous glucose monitoring metrics. For the geographical analysis, aggregated endpoints for MM780G system users were calculated. For the technology iteration analysis, MM780G system user outcomes were compared with outcomes when the same individuals were still using the MM640G or MM670G system. RESULTS: On average, 1025 MM780G system users from the geographical analysis were followed for 136 (SD 135) days, spent 91.5 (14.3)% in advanced hybrid closed loop, showed a glucose management indicator (GMI) of 6.7 (0.3)%, a time in range between 70 and 180 mg/dl (TIR) of 76.5 (9.0)%, and a time below range 70 mg/dl (TBR) of 2.7 (2.1)%. The percentage of users reaching targets of GMI <7%, TIR >70% and TBR <4% was 80.8%, 78.1% and 80.1%, respectively. The technology iteration analysis on users transitioning from MM640G to MM780G system (N = 381) showed 0.4% decrease in GMI (7.1% to 6.7%, p < .0001), 10.7% increase in TIR (65.9% to 76.6%, p < .0001), while TBR remained. The percentage of insulin delivered automatically increased as well (47.5%-57.7%, p < .0001). Users transitioning from MM670G system (N = 78) showed a similar but less pronounced pattern. CONCLUSIONS: Real-world Latin American MM780G users on average showed good glucose control, achieving international targets. Glycaemic control increased with every technology iteration of the MM system, providing more automation each time.

First Outpatient Clinical Trial of a Full Closed-Loop Artificial Pancreas System in South America.

BACKGROUND: The first two studies of an artificial pancreas (AP) system carried out in Latin America took place in 2016 (phase 1) and 2017 (phase 2). They evaluated a hybrid algorithm from the University of Virginia (UVA) and the automatic regulation of glucose (ARG) algorithm in an inpatient setting using an AP platform developed by the UVA. The ARG algorithm does not require carbohydrate (CHO) counting and does not deliver meal priming insulin boluses. Here, the first outpatient trial of the ARG algorithm using an own AP platform and doubling the duration of previous phases is presented. METHOD: Phase 3 involved the evaluation of the ARG algorithm in five adult participants (n = 5) during 72 hours of closed-loop (CL) and 72 hours of open-loop (OL) control in an outpatient setting. This trial was performed with an own AP and remote monitoring platform developed from open-source resources, called InsuMate. The meals tested ranged its CHO content from 38 to 120 g and included challenging meals like pasta. Also, the participants performed mild exercise (3-5 km walks) daily. The clinical trial is registered in ClinicalTrials.gov with identifier: NCT04793165. RESULTS: The ARG algorithm showed an improvement in the time in hyperglycemia (52.2% [16.3%] OL vs 48.0% [15.4%] CL), time in range (46.9% [15.6%] OL vs 50.9% [14.4%] CL), and mean glucose (188.9 [25.5] mg/dl OL vs 186.2 [24.7] mg/dl CL) compared with the OL therapy. No severe hyperglycemia or hypoglycemia episodes occurred during the trial. The InsuMate platform achieved an average of more than 95% of the time in CL. CONCLUSION: The results obtained demonstrated the feasibility of outpatient full CL regulation of glucose levels involving the ARG algorithm and the InsuMate platform.

Bomba de insulina aumentada por sensor en pacientes con diabetes tipo 1 / Sensor-augmented insulin pump in patients with type 1 diabetes

INTRODUCCIÓN: Este documento técnico se realiza a solicitud de la Dirección de Prevención y Control de Enfermedades No Transmisibles, Raras y Huérfanas del Ministerio de Salud; la cual motivó la realización de la pregunta PICO por parte de médicos y especialistas de la siguiente manera, P: pacientes con diabetes tipo 1; I: bomba de insulina aumentada por sensor; C: bomba de insulina convencional + monitoreo de glucosa no continuo; O: control glicémico, hiperglicemia, hipoglicemia, calidad de vida y eventos adversos. a. Cuadro clínico: La diabetes tipo 1 (DM1) es una enfermedad crónica que produce incremento de los niveles de glicemia debido a una deficiencia de insulina como consecuencia de la pérdida de células ß en el páncreas. En Perú, la incidencia estandarizada por edad es de 0.5 x 100 mil personas de 0-19 años. Las personas con DM1 tienen mayor riesgo de enfermedades cardiovasculares y complicaciones microvasculares como neuropatía, nefropatía y retinopatía. La terapia de reemplazo de insulina (usando bombas de insulina o múltiples inyecciones diarias) y el monitoreo de glucosa (mediante automonitoreo con glucómetro o dispositivos de monitoreo continuo) constituyen parte integral del manejo de la enfermedad. b. Tecnología sanitária: Las bombas de insulina aumentadas por sensor son dispositivos que administran insulina mediante infusión subcutánea de manera continua e incluyen un dispositivo integrado para el monitoreo continuo de glucosa. Cuentan con aprobación de FDA desde el 2006, mientras que en Perú no cuentan con ningún registro sanitario vigente. OBJETIVO: Describir la evidencia científica sobre la eficacia y seguridad de una bomba de insulina aumentada por sensor en pacientes con diabetes tipo 1. METODOLOGÍA: Se realizó una búsqueda sistemática en Medline (Ovid), The Cochrane Library y LILACS utilizando la estrategia de búsqueda descrita en el Anexo 01. Ésta se complementó con la búsqueda de evidencia en páginas institucionales de agencias gubernamentales y buscadores genéricos. Se priorizó la identificación y selección de ensayos clínicos aleatorizados controlados (ECA), revisiones sistemáticas (RS) de ECA, guías de práctica clínica (GPC), evaluaciones de tecnología sanitaria (ETS) y evaluaciones económicas (EE) de América Latina. La calidad de la evidencia se valoró usando: AMSTAR 2 para revisiones sistemáticas, la herramienta de la colaboración Cochrane para ensayos clínicos y AGREE II para valorar el rigor metodológico de las GPC. RESULTADOS Estudios en población general con DM1 (incluyendo niños, adolescentes y adultos): Tres estudios no observaron diferencias en la HbA1c entre los participantes asignados a una bomba de insulina aumentada por sensor y aquellos asignados a una bomba de insulina convencional, mientras en un estudio los niveles de HbA1c fueron menores en el grupo que usó una bomba de insulina aumentada por sensor. Cuando se limitó el análisis para incluir solo participantes con mayor uso del sensor de glucosa (>70% del tiempo), cuatro estudios fueron consistentes en mostrar mayor reducción de la HbA1c en los participantes que usaron una bomba de insulina aumentada por sensor. En dos estudios, los niveles de glicemia fueron significativamente más bajos en el grupo de bomba de insulina aumentada por sensor. Otros desenlaces como el tiempo en el rango, área bajo la curva y eventos de hipoglicemia e hiperglicemia fueron inconsistentes. Otros eventos adversos fueron similares entre los grupos. Estudios en población pediátrica con DM1 (incluyendo niños y adolescentes): Dos estudios no observaron diferencias en la HbA1c entre los grupos asignados a una bomba de insulina aumentada por sensor o una bomba de insulina convencional. Dos estudios, incluyendo participantes con uso del sensor de glucosa >70% del tiempo, mostraron mayor reducción de la HbA1c en el grupo tratado con bomba de insulina aumentada por sensor. No se observó diferencias en la glicemia, eventos de cetoacidosis diabética, ni en la calidad de vida. Los episodios de hipoglicemia severa fueron más altos en el grupo tratado con una bomba de insulina aumentada por sensor (0 vs. 4 episodios; p=0.046). Recomendaciones en GPC: Las GPC de la American Diabetes Association (ADA), National Institute for Health and Care Excellence (NICE) de Reino Unido, y del Ministerio de Salud de Colombia incluyen en sus recomendaciones el uso de una bomba de insulina aumentada por sensor en pacientes con DM1 que pueden usarlo en forma segura, con episodios de hipoglicemia incapacitante pese al manejo óptimo de una bomba de insulina convencional, o en quienes, pese al tratamiento con análogos de insulina, no hayan alcanzado un adecuado control metabólico, o presenten hipoglucemias severas o asintomáticas frecuentes. Evaluaciones de tecnología sanitária: Cuatro ETS desarrolladas por agencias estatales de Argentina, España, Perú y Canadá recomiendan no dar cobertura al uso de bombas de insulina aumentada por sensor en pacientes con DM1, principalmente por motivos de costo-efectividad desfavorable. La ETS de NICE recomienda la cobertura de una bomba de insulina aumentada por sensor en pacientes con DM1 y episodios de hipoglicemia incapacitante pese al manejo óptimo de una bomba de insulina convencional y solo si el paciente o cuidador se compromete a utilizar los sensores durante al menos el 70 % del tiempo. Evaluación de la calidad metodológica: La certeza de evidencia fue considerada baja para todos los desenlaces críticos en población general con DM1. En población pediátrica, el cambio en los niveles de HbA1c fue considerado como certeza de evidencia baja, mientras que el cambio en los niveles de glicemia y calidad de vida se consideró como certeza de evidencia moderada. La calidad metodológica de las GPC varió entre 67.1% y 81.6%. CONCLUSIONES: Se identificó seis ensayos clínicos, cinco evaluaciones de tecnología sanitaria y cuatro guías de práctica clínica. En niños y adultos con DM1, el control glicémico, evaluado según cambios en la hemoglobina glicosilada, solo mostró diferencias a favor del uso de bomba de insulina aumentada por sensor cuando se restringió el análisis a participantes con uso del sensor de glucosa mayor al 70%. En población general con DM1, los participantes con bomba de insulina aumentada por sensor redujeron los niveles de glicemia, comparado quienes usaron una bomba de insulina convencional. Los desenlaces relacionados con hipoglicemia e hiperglicemia fueron variables. Otros eventos adversos fueron similares entre ambos grupos. En población pediátrica mayor de 6 años, resultados de un único estudio no mostraron diferencias entre el uso de una bomba de insulina convencional o aumentada por sensor en la glicemia, eventos de cetoacidosis o calidad de vida. Los eventos de hipoglicemia severa fueron más frecuentes con el uso de una bomba de insulina aumentada por sensor. Las cuatro GPC incluidas consideran en sus recomendaciones el uso de una bomba de insulina aumentada por sensor en personas con DM1. Cuatro ETS de agencias estatales de Argentina, España, Perú y Canadá recomiendan no dar cobertura al uso de bombas de insulina aumentada por sensor. La ETS de NICE recomienda su uso como dispositivo de segunda línea y condicionada al uso del sensor >70% del tiempo. La certeza de evidencia fue baja para los desenlaces críticos en población general con DM1. En población pediátrica, la certeza de evidencia varió entre moderada y baja. La calidad metodológica de las GPC varió entre 67.1% y 81.6%.

Artificial pancreas systems: experiences from concept to commercialisation.

INTRODUCTION: Automated insulin delivery (AID) systems, known as artificial pancreas or closed-loop glucose control systems, have been developed to improve the glycemic outcomes of people with type 1 diabetes. These systems use a control algorithm that automatically modifies the amount of insulin infused into a patient based on real-time blood glucose measurements. This study presents a summary of key clinical and technical issues related to the development of the first commercial AID systems and their evolution into commercial biomedical devices. AREAS COVERED: Highlights of each AID system are summarized through timelines, ranging from the definition of the core strategy of the control algorithm to the practical application and subsequent commercial approval. Tabulated information regarding the conducted main clinical studies is also presented. EXPERT OPINION: Insulin therapy has evolved up to the current commercial AID systems available, which have provided patients access to a safer and more effective therapy owing to automatic adjustments to insulin. However, this technology is relatively new and can be significantly improved. Limitations include the resistance of healthcare providers, high costs, and the availability of this treatment. The future of this technology is directed toward obtaining fully automatic control systems.

Serial album on Continuous Insulin Infusion System as an innovative educational technology in diabetes.

OBJECTIVE: to build and validate a serial album content and appearance on insulin therapy using a Continuous Infusion System. METHOD: a methodological study, carried out in three stages in Fortaleza, Ceará, Brazil, from August to November 2018. The serial album construction and content and appearance validity were carried out by experts, and assessment, by the target audience. Content Validity Index and Concordance Index were calculated. RESULTS: the judges considered the serial album content and appearance to be valid, which means that the material is suitable as an educational technology. Experts suggested adjustments, incorporated into the material for print production of the final version. The target audience also assessed the serial album positively. CONCLUSION: we realized that the serial album was considered an innovative educational technology in diabetes, valuable for promoting knowledge about Continuous Insulin Infusion System, with rich, updated content, combined with clarity, suitable format and explanatory illustrations.

The Relationship Between Different Bench Test Methodologies and Accuracy of Insulin Infusion Pumps: A Systematic Literature Review.

Diabetes technology has rapidly evolved, and insulin infusion pumps (IIPs) have gained worldwide acceptance in diabetes care. The safety of medical equipment is highly discussed, imposing complex challenges in its use. The accuracy of IIPs can be determined through laboratory tests, generally following the IEC 60601-2-24 protocol. Studies have evaluated the accuracy and precision of IIPs, and there are discrepant results. So, we conducted a Systematic Literature Review to assess the methodologies used to evaluate the accuracy of IIPs, organizing the findings in a compiled perspective. The methodology was based on Kitchenham and Biolchini guidelines, and when possible it was carried out the Bayesian meta-analyses to compare the accuracy of IIPs. Most studies used the microgravimetric technique to evaluate the device accuracy, and some proposed adaptations for the standard protocol. The variation of results was recurrent, and the establishment of a protocol, especially to evaluate patch pumps, is necessary. The present study gives enough data to understand the scenario of the IIPs evaluation, as well as the different protocols that can be explored for its evaluation. This highlights the need for a reliable, practical, and low-cost methodology to assist the evaluation of IIPs.

Bolus versus continuous insulin infusion in immediate postoperative blood glucose control in liver transplantation: pragmatic clinical trial.

OBJECTIVE: To analyze the effectiveness and safety of two insulin therapy techniques (continuous and intermittent infusion) in the blood glucose control of people who have undergone liver transplantation, in the immediate postoperative period. METHODS: The study was a prospective, open, pragmatic clinical trial with 42 participants, divided into two groups of 21 patients each, in the immediate postoperative period following liver transplantation. Participants in the Experimental Group and Control Group received continuous infusion and bolus insulin, respectively, starting at capillary blood glucose ≥150mg/dL. RESULTS: There were no statistically significant differences in the blood glucose reduction time to reach the target range between the Experimental Group and Control Group in the transplanted patients (p=0.919). No statistically significant differences regarding the presence of low blood glucose (p=0.500) and in the initial blood glucose value (p=0.345) were found. The study identified the final blood glucose value in postoperative intensive care unit lower and statistically significant in the continuous infusion pump group in relation to the Bolus Group (p<0.001). Additionally, the variation of blood glucose reduction was higher and statistically significant in the continuous method group (p<0.05). CONCLUSION: The continuous infusion method was more effective in the blood glucose control of patients in the postoperative period following liver transplantation. BRAZILIAN REGISTRY OF CLINICAL TRIALS: RBR-9Y5tbp.

Practical constraint definition in safety schemes for artificial pancreas systems.

INTRODUCTION: Artificial pancreas systems usually define an insulin-on-board constraint (IOB¯) for safety schemes to limit the insulin infusion and avoid hypoglycemia during the closed-loop performance. Several methods have been proposed with impractical considerations requiring information from the prandial events or complex procedures for ambulatory use. METHODS: This paper presents a simple method that consists of two novel rules that allow finding an IOB¯ based only on common clinical parameters that do not require patient intervention. The method robustness was evaluated using a control system coupled to a safety layer under demanding scenarios implemented on the FDA-approved simulator for preclinical studies. RESULTS: The method maintains a safe performance, even in the face of interpatient variability, hybrid and fully automatic implementations of an artificial pancreas system, and uncertain settings. Both proposed rules work as effectively or even better and without the patient intervention than other methods that have already been clinically validated. CONCLUSION: This method can be used to define a constant IOB¯ that ensures performance and safety of the control system, even under scenarios with incorrect clinical data. Unlike other methods, this method only requires reliable information that is easily obtained from the patient, such as their total daily dose of insulin or body mass.

Évaluation des systèmes de pompes à insuline chez les patients atteints du diabète de type 1 / Assessment of insulin pump systems for type 1 diabetes patients

MANDAT: L'Institut national d'excellence en santé et en services sociaux (INESSS) a reçu le mandat du ministère de la Santé et des Services sociaux (MSSS) de produire un avis sur la valeur des systèmes de pompes à insuline au sein de la couverture du régime public pour les patients adultes atteints de diabète de type 1 (DT1). Dans le but d'éclairer la prise de décision, l'INESSS a également procédé à l'évaluation clinique et économique des pompes disponibles pour la population pédiatrique. DÉMARCHE DE L'ÉVALUATION: L'évaluation a été réalisée selon une approche basée sur l'appréciation globale de la valeur préconisée par l'Institut. Une revue rapide de la littérature a été réalisée pour repérer les données probantes et compléter l'information transmise par les fabricants. Les savoirs contextuels et expérientiels ont été recueillis par l'intermédiaire de consultations d'experts, de patients et proches aidants, utilisateurs et non-utilisateurs de la technologie à l'étude. L'ensemble des savoirs mobilisés et intégrés a été présenté au Comité scientifique de l'évaluation des médicaments aux fins d'inscription (CSEMI) en vue de l'élaboration des recommandations. BESOINS DE SANTÉ: Le DT1 est une maladie chronique qui nécessite une insulinothérapie intensive et une gestion constante des taux de glucose. Ce trai

MANDATE: The Institut national d'excellence en santé et en services sociaux (INESSS) was mandated by the Ministère de la Santé et des Services sociaux (MSSS) to evaluate insulin pumps and their public coverage for adult patients with type 1 diabetes (T1D). With a view to promoting an informed decision-making process, the INESSS also conducted a clinical and economic assessment of the insulin pumps available to the pediatric population. ASSESSMENT PROCESS: The evaluation was performed by adopting an approach based on the overall assessment of value favoured by the INESSS. A quick review of the literature was done, to obtain evidence-based data and supplement the information provided by manufacturers. Background and experience-based knowledge were gathered by reaching out to experts, patients and caregivers, as well as users and non-users of the technology in question. All of the information obtained, once integrated, was submitted to the Comité scientifique de l'évaluation des médicaments aux fins d'inscription (CSEMI) so that recommendations could be developed. HEALTH NEEDS: Type 1 diabetes is a chronic disease that requires intensive insulin therapy and ongoing man

Interval Safety Layer Coupled With an Impulsive MPC for Artificial Pancreas to Handle Intrapatient Variability.

The aim of control strategies for artificial pancreas systems is to calculate the insulin doses required by a subject with type 1 diabetes to regulate blood glucose levels by reducing hyperglycemia and avoiding the induction of hypoglycemia. Several control formulations developed for this end involve a safety constraint given by the insulin on board (IOB) estimation. This constraint has the purpose of reducing hypoglycemic episodes caused by insulin stacking. However, intrapatient variability constantly changes the patient's response to insulin, and thus, an adaptive method is required to restrict the control action according to the current situation of the subject. In this work, the control action computed by an impulsive model predictive controller is modulated with a safety layer to satisfy an adaptive IOB constraint. This constraint is established with two main steps. First, upper and lower IOB bounds are generated with an interval model that accounts for parameter uncertainty, and thus, define the possible system responses. Second, the constraint is selected according to the current value of glycemia, an estimation of the plant-model mismatch, and their corresponding first and second time derivatives to anticipate the changes of both glucose levels and physiological variations. With this strategy satisfactory results were obtained in an adult cohort where random circadian variability and sensor noise were considered. A 92% time in normoglycemia was obtained, representing an increase of time in range compared to previous MPC strategies, and a reduction of time in hypoglycemia to 0% was achieved without dangerously increasing the time in hyperglycemia.

Use of continuous subcutaneous insulin infusion in children and adolescents with type 1 diabetes mellitus: a systematic mapping review.

BACKGROUND: Among the treatments for type 1 diabetes mellitus (T1DM), Continuous Subcutaneous Insulin Infusion (CSII) is a device that infuses insulin through the subcutaneous tissue in an uninterrupted manner and that comes closest to the physiological secretion of insulin. The use of CSII can provide the family with greater security and children and adolescents have more autonomy in relation to the treatment of T1DM. There is a lack of reviews that systematically gather the mounting evidence about the use of CSII in children and adolescents with T1DM. Therefore, the aim of this review was to group and describe primary and secondary studies on the use of CSII in children and adolescents with T1DM. METHODS: A systematic mapping review was performed based on searches in the following databases: PubMed, Embase, CINAHL, Lilacs and PsycINFO, using a combination of descriptors and keywords. The screening of the studies was carried out with the aid of the Rayyan software and reading in full was conducted independently by two reviewers. The data extraction of the studies was performed using an extraction tool adapted and validated by researchers specialized in diabetes. The data were analyzed according to the content analysis technique. The map from geocoding of the studies was produced using the ArcGis 10.5 software. RESULTS: A total of 113 studies were included in the review, including primary studies, literature reviews and gray literature publications. The content analysis of the results of the studies allowed for the identification of four categories: 1) metabolic control; 2) support networks; 3) benefits of using CSII; and 4) challenges of using CSII, each category having its respective subcategories. The review also made it possible to conduct a rigorous mapping of the literature on the use of CSII considering the location of development and the design of the studies. CONCLUSIONS: The use of CSII should be indicated by health professionals able to prepare children, adolescents, and their families for the treatment of T1DM, and, despite being a technological device, it may not be suitable for the entire pediatric population.

[Sensor-Augmented Pump Therapy: description of pediatric patients with Type 1 Diabetes Mellitus (T1D) and initial metabolic outcomes]. / Uso de microinfusor de insulina con sistema integrado en pacientes pediátricos con diabetes tipo 1: resultados metabólicos iniciales.

The insulin microinfuser with integrated system (SAPT) for patients with type 1 Diabetes Mellitus (T1D) is included in the national financial protection system for high-cost treatments. OBJECTIVE: To describe the initial and first-year metabolic outcomes and epidemiological and nutritional characteristics of T1D pediatric patients treated with SAPT. PATIENTS AND METHOD: Retrospective, descriptive and analytical study of clinical records from 2017 to 2019, of 12 patients with T1D users of SAPT, attended in a referral hospital. VARIABLES: age at program entry, time of evolution of the disease, type of insulin treatment and type of glucose monitoring (capillary: sample or Continuous Glucose Monitoring [CGM]) at program entry, cause of application to the program, nutritional status, rural or urban origin, educational level of the main guardian, HbA1c at application and in the last month of each quarter after SAPT installation, over a 12-month period. HbA1c analysis was venous sample by High-Performance Liquid Chromatography and follow-up was capillary sample by Latex Particle Agglutination Inhibition. RESULTS: The median variables at 12 months of treatment were Total Daily Dose (TDD) 0.74, %Basal (%B) 49%, Time In Range (TIR) 39%, Time Below Range (TBR) 1%, and HbA1c 7.7%. The sensor usage time was met in all cases and only half of them achieved a correct execution of hyperglycemia and hypoglycemia treatment. Inadvertent severe hypoglycemia was the main cause of application to the program. CONCLUSION: TDD and %B increased, approaching physiological requirement, although without statistical significance, which could be attributed to the administra tion of adequate insulin with lower risk of hypoglycemia due to predictive suspension and CGM. TIR presented a favorable increase, although not significant, nor reaching the target range, attributable to the short observation time, difficulties in understanding and execution of our patients, and the learning process of the treating clinical team. SAPT was effective in hypoglycemia management and effective in improving HbA1c.

Six-Month Glycemic Control with a Hybrid Closed-Loop System in Type 1 Diabetes Patients in a Latin American Country.

The goal of this study was to assess the 6-month effectiveness of hybrid closed loop on glycemic control in type 1 diabetes (T1D) patients in Latin America. An exploratory analysis of data prospectively collected from non-selected consecutive patients with T1D who initiated treatment with the MiniMed™ 670G system in Argentina was conducted. Baseline and follow-up visits at days 7, 28, 90, and 180 were carried out and data were downloaded at each visit. A total of 30 patients (age range 9-57 years, female 63.3%), 73.3% (n = 22) of whom previously used sensor augmented pump-predictive low glucose management (SAP-PLGM), with baseline glycated hemoglobin 7.4% ± 1% were included. Time in range between 70 and 180 mg/dL significantly increased from 65.1% at baseline to 77.3%, 76.2%, 75.7%, and 75.2% at days 7, 28, 90 and 180, respectively. Time above range (>180 mg/dL) significantly decreased from 33% to 22.5% (P < 0.001), while time below range (<70 mg/dL) did not change. Mean glucose levels were reduced from 163.5 mg/dL at baseline to 150.9 mg/dL (P = 0.001) at last visit. The Auto Mode feature was used > 90% of the time. Virtual training was successfully completed with a Net Promoter Score® (NPS®) of 87%. This analysis confirms that MiniMed 670G system use allowed successful achievement of glycemic control within recommended targets in a non-selected Latin American patient population who underwent virtual system training.

Páncreas artificial con liberación dual de insulina y pramlintida para tratamiento de diabetes mellitus tipo I / Artificial pancreas with dual release of insulin and pramlintide for treatment of type 1 diabetes mellitus

Este documento es una ficha de Evaluación de Tecnologías Nuevas y Emergentes. Su objetivo es proporcionar la información disponible, críticamente valorada, que permita que la evaluación pueda llevarse a cabo en una fase temprana de la aparición de una técnica, tecnología o procedimiento que se prevé va a tener impacto en la calidad de vida de las personas y en el sistema sanitario. Se contribuye así a facilitar la toma de decisiones sobre la incorporación de las tecnologías nuevas y emergentes en el sistema sanitario, cuando corresponda llevarla a cabo. • La diabetes mellitus tipo 1 (DM1) es una enfermedad que requiere un control continuo de los niveles de glucosa para la correcta administración de insulina, y así evitar episodios de hiper- e hipoglucemia que deriven en complicaciones a corto y largo plazo. Esta enfermedad tiende a desarrollarse en niños y adolescentes entre quienes es una de las enfermedades crónicas más frecuentes en el mundo. • El páncreas artificial (PA) es un dispositivo que combina la monitorización continua de glucosa y la administración automática de insulina, tratando de imitar el funcionamiento del páncreas biológico. Estudios recientes muestran que el PA ayuda a reducir los eventos de hiper e hipoglucemia. Sin embargo, los resultados muestran aún largos periodos de hiperglucemia (5-8 h / día por encima de 180 mg/gL), particularmente después de la comida, por lo que los pacientes siguen necesitando hacer ajustes manuales en la infusión de insulina para evitar la hiperglucemia postprandial. El uso de un PA con infusión dual de insulina y pramlintida (PR) podría ayudar a controlar los niveles glucémicos postprandiales y avanzar en el logro de un sistema totalmente cerrado, que no necesite de ajustes manuales del usuario. • Se han identificado 4 estudios, publicados en 3 artículos por el mismo grupo de investigación, con muestras pequeñas e intervenciones limitadas a un día, en 3 de ellos (en régimen interno); y 12 días en régimen externo, en otro. En un estudio donde se aplicaba conteo preciso de carbohidratos para las comidas, el PA con insulina rápida y PR se mostró superior al PA con insulina rápida sola: durante el periodo diurno, en el tiempo en rango objetivo de glucosa, así como en sus niveles promedio y variabilidad. En otro estudio, un sistema dual (con insulina ultra rápida) totalmente cerrado (sin ajustes manuales en las comidas) mostró peores resultados de tiempo en rango objetivo e hiperglucemia que el PA solo con insulina ultra rápida. • En cuanto a la seguridad, en todos los casos se observaron más efectos gastrointestinales en la fase de PA dual, aunque no hubo efectos adversos graves de ningún tipo. Se necesitan estudios con tamaños muestrales apropiados y seguimiento en la vida real. • Para el uso adecuado de esta tecnología es preciso disponer de profesionales sanitarios con formación adecuada, que garantice su uso apropiado. Es necesario además la formación de los pacientes en el uso de estos dispositivos, de manera que sepan responder a la información proporcionada por los sistemas y a la posible aparición de fallos técnicos.

This document is a New and Emerging Technologies Assessment sheet. Its objective is to provide the information available, critically valued, that allows the evaluation to be carried out at an early stage of the appearance of a technique, technology or procedure that is expected to have an impact on the quality of life of people and in the healthcare system. In this way, it contributes to facilitating decision-making on the incorporation of new and emerging technologies in the health system, when it corresponds to carry it out. • Type 1 diabetes (DM1) is a disease that requires continuous control of glucose levels for the correct administration of insulin, thus avoiding episodes of hyper- and hypoglycemia that lead to short- and long-term complications. This disease tends to develop in children and adolescents, among whom it is one of the most frequent chronic diseases in the world. • The artificial pancreas (AP) is a device that combines continuous glucose monitoring and automatic insulin administration, trying to mimic the functioning of the biological pancreas. Recent studies show that PA helps reduce hyper and hypoglycemic events. However, the results still show long periods of hyperglycemia (5- 8 h / day above 180 mg / gL), particularly after meals, so patients continue to need to make manual adjustments in insulin infusion to avoid postprandial hyperglycemia. The use of a PA with dual infusion of insulin and pramlintide could help control postprandial glycemic levels and advance the achievement of a totally closed system, which does not require manual user adjustments. • 4 studies have been identified, published in 3 articles by the same research group, with small samples and interventions limited to one day, in 3 of them (internal); and 12 days in external regime, in another. In a study where precise carbohydrate counting was applied for meals, the BP with rapid insulin and pramlintide was superior to the BP with rapid insulin alone: during the daytime period, in time in the target glucose range, as well as in glucose levels. average and variability. In another study, a fully enclosed dual system (with ultra-rapid insulin) (without manual adjustments to meals) showed worse results for time in target range and hyperglycemia than BP alone with ultra-rapid insulin. • Regarding safety, in all cases more gastrointestinal effects were observed in the dual AP phase, although there were no serious adverse effects of any kind. Studies with appropriate sample sizes and real-life follow-up are needed. • For the proper use of this technology, it is necessary to have health professionals with adequate training, to guarantee its appropriate use. It is also necessary to train patients in the use of these devices, so that they know how to respond to the information provided by the systems and to the possible appearance of technical failures.