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BACKGROUND: Whether improved glucose control with hybrid closed-loop therapy can preserve C-peptide secretion as compared with standard insulin therapy in persons with new-onset type 1 diabetes is unclear. METHODS: In a multicenter, open-label, parallel-group, randomized trial, we assigned youths 10.0 to 16.9 years of age within 21 days after a diagnosis of type 1 diabetes to receive hybrid closed-loop therapy or standard insulin therapy (control) for 24 months. The primary end point was the area under the curve (AUC) for the plasma C-peptide level (after a mixed-meal tolerance test) at 12 months after diagnosis. The analysis was performed on an intention-to-treat basis. RESULTS: A total of 97 participants (mean [±SD] age, 12±2 years) underwent randomization: 51 were assigned to receive closed-loop therapy and 46 to receive control therapy. The AUC for the C-peptide level at 12 months (primary end point) did not differ significantly between the two groups (geometric mean, 0.35 pmol per milliliter [interquartile range, 0.16 to 0.49] with closed-loop therapy and 0.46 pmol per milliliter [interquartile range, 0.22 to 0.69] with control therapy; mean adjusted difference, -0.06 pmol per milliliter [95% confidence interval {CI}, -0.14 to 0.03]). There was not a substantial between-group difference in the AUC for the C-peptide level at 24 months (geometric mean, 0.18 pmol per milliliter [interquartile range, 0.06 to 0.22] with closed-loop therapy and 0.24 pmol per milliliter [interquartile range, 0.05 to 0.30] with control therapy; mean adjusted difference, -0.04 pmol per milliliter [95% CI, -0.14 to 0.06]). The arithmetic mean glycated hemoglobin level was lower in the closed-loop group than in the control group by 4 mmol per mole (0.4 percentage points; 95% CI, 0 to 8 mmol per mole [0.0 to 0.7 percentage points]) at 12 months and by 11 mmol per mole (1.0 percentage points; 95% CI, 7 to 15 mmol per mole [0.5 to 1.5 percentage points]) at 24 months. Five cases of severe hypoglycemia occurred in the closed-loop group (in 3 participants), and one occurred in the control group; one case of diabetic ketoacidosis occurred in the closed-loop group. CONCLUSIONS: In youths with new-onset type 1 diabetes, intensive glucose control for 24 months did not appear to prevent the decline in residual C-peptide secretion. (Funded by the National Institute for Health and Care Research and others; CLOuD ClinicalTrials.gov number, NCT02871089.).
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Péptido C , Diabetes Mellitus Tipo 1 , Hipoglucemiantes , Insulina , Adolescente , Glucemia/análisis , Péptido C/metabolismo , Niño , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Sistemas de Infusión de InsulinaRESUMEN
BACKGROUND: The possible advantage of hybrid closed-loop therapy (i.e., artificial pancreas) over sensor-augmented pump therapy in very young children with type 1 diabetes is unclear. METHODS: In this multicenter, randomized, crossover trial, we recruited children 1 to 7 years of age with type 1 diabetes who were receiving insulin-pump therapy at seven centers across Austria, Germany, Luxembourg, and the United Kingdom. Participants received treatment in two 16-week periods, in random order, in which the closed-loop system was compared with sensor-augmented pump therapy (control). The primary end point was the between-treatment difference in the percentage of time that the sensor glucose measurement was in the target range (70 to 180 mg per deciliter) during each 16-week period. The analysis was conducted according to the intention-to-treat principle. Key secondary end points included the percentage of time spent in a hyperglycemic state (glucose level, >180 mg per deciliter), the glycated hemoglobin level, the mean sensor glucose level, and the percentage of time spent in a hypoglycemic state (glucose level, <70 mg per deciliter). Safety was assessed. RESULTS: A total of 74 participants underwent randomization. The mean (±SD) age of the participants was 5.6±1.6 years, and the baseline glycated hemoglobin level was 7.3±0.7%. The percentage of time with the glucose level in the target range was 8.7 percentage points (95% confidence interval [CI], 7.4 to 9.9) higher during the closed-loop period than during the control period (P<0.001). The mean adjusted difference (closed-loop minus control) in the percentage of time spent in a hyperglycemic state was -8.5 percentage points (95% CI, -9.9 to -7.1), the difference in the glycated hemoglobin level was -0.4 percentage points (95% CI, -0.5 to -0.3), and the difference in the mean sensor glucose level was -12.3 mg per deciliter (95% CI, -14.8 to -9.8) (P<0.001 for all comparisons). The time spent in a hypoglycemic state was similar with the two treatments (P = 0.74). The median time spent in the closed-loop mode was 95% (interquartile range, 92 to 97) over the 16-week closed-loop period. One serious adverse event of severe hypoglycemia occurred during the closed-loop period. One serious adverse event that was deemed to be unrelated to treatment occurred. CONCLUSIONS: A hybrid closed-loop system significantly improved glycemic control in very young children with type 1 diabetes, without increasing the time spent in hypoglycemia. (Funded by the European Commission and others; ClinicalTrials.gov number, NCT03784027.).
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Diabetes Mellitus Tipo 1/tratamiento farmacológico , Control Glucémico/instrumentación , Hipoglucemiantes/administración & dosificación , Sistemas de Infusión de Insulina , Insulina/administración & dosificación , Páncreas Artificial , Algoritmos , Glucemia/análisis , Niño , Preescolar , Estudios Cruzados , Diseño de Equipo , Femenino , Hemoglobina Glucada/análisis , Control Glucémico/métodos , Humanos , Hiperglucemia/diagnóstico , Lactante , MasculinoRESUMEN
AIMS: To explore parents' experiences of using remote monitoring technology when caring for a very young child with type 1 diabetes during a clinical trial. METHODS: Interviews were conducted with parents of 30 children (aged 1-7 years) participating in a trial (the KidsAP02 study) comparing hybrid closed-loop insulin delivery with sensor-augmented pump therapy. In both arms, parents had access to remote monitoring technology. Data analysis focused on identification of descriptive themes. RESULTS: Remote monitoring technology gave parents improved access to data which helped them pre-empt and manage glucose excursions. Parents observed how, when children were in their own care, they could be more absent while present, as their attention could shift to non-diabetes-related activities. Conversely, when children were others' care, remote monitoring enabled parents to be present while absent, by facilitating oversight and collaboration with caregivers. Parents described how remote monitoring made them feel more confident allowing others to care for their children. Parents' confidence increased when using a hybrid closed-loop system, as less work was required to keep glucose in range. Benefits to children were also highlighted, including being able to play and sleep uninterrupted and attend parties and sleepovers without their parents. While most parents welcomed the increased sense of control remote monitoring offered, some noted downsides, such as lack of respite from caregiving responsibilities. CONCLUSIONS: Remote monitoring can offer manifold benefits to both parents and very young children with type 1 diabetes. Some parents, however, may profit from opportunities to take 'time out'.
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Diabetes Mellitus Tipo 1 , Padres , Tecnología de Sensores Remotos , Glucemia , Automonitorización de la Glucosa Sanguínea , Niño , Preescolar , Ensayos Clínicos como Asunto , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Humanos , Lactante , Insulina/uso terapéutico , Sistemas de Infusión de Insulina , Padres/psicologíaRESUMEN
AIM: To examine changes in the lived experience of type 1 diabetes after use of hybrid closed loop (CL), including the CamAPS FX CL system. MATERIALS AND METHODS: The primary study was conducted as an open-label, single-period, randomized, parallel design contrasting CL versus insulin pump (with or without continuous glucose monitoring). Participants were asked to complete patient-reported outcomes before starting CL and 3 and 6 months later. Surveys assessed diabetes distress, hypoglycaemia concerns and quality of life. Qualitative focus group data were collected at the completion of the study. RESULTS: In this sample of 98 youth (age range 6-18, mean age 12.7 ± 2.8 years) and their parents, CL use was not associated with psychosocial benefits overall. However, the subgroup (n = 12) using the CamAPS FX system showed modest improvements in quality of life and parent distress, reinforced by both survey (p < .05) and focus group responses. There were no negative effects of CL use reported by study participants. CONCLUSIONS: Closed loop use via the CamAPS FX system was associated with modest improvements in aspects of the lived experience of managing type 1 diabetes in youth and their families. Further refinements of the system may optimize the user experience.
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Diabetes Mellitus Tipo 1 , Adolescente , Humanos , Niño , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Automonitorización de la Glucosa Sanguínea , Insulina/uso terapéutico , Calidad de Vida , Hipoglucemiantes/uso terapéutico , Glucemia , Resultado del Tratamiento , Sistemas de Infusión de Insulina , Padres/psicologíaRESUMEN
OBJECTIVES: We explored parents' views about healthcare professionals having remote access to their young child's insulin and glucose data during a clinical trial to inform use of data sharing in routine pediatric diabetes care. RESEARCH DESIGN AND METHODS: Interviews with 33 parents of 30 children (aged 1-7 years) with type 1 diabetes participating in a randomized trial (KidsAP02) comparing hybrid closed-loop system use with sensor-augmented pump therapy. Data were analyzed using a qualitative descriptive approach. RESULTS: Parents reported multiple benefits to healthcare professionals being able to remotely access their child's glucose and insulin data during the trial, despite some initial concerns regarding the insights offered into everyday family life. Key benefits included: less work uploading/sharing data; improved consultations; and, better clinical input and support from healthcare professionals between consultations. Parents noted how healthcare professionals' real-time data access facilitated remote delivery of consultations during the COVID-19 pandemic, and how these were more suitable for young children than face-to-face appointments. Parents endorsed use of real-time data sharing in routine clinical care, subject to caveats regarding data access, security, and privacy. They also proposed that, if data sharing were used, consultations for closed-loop system users in routine clinical care could be replaced with needs-driven, ad-hoc contact. CONCLUSIONS: Real-time data sharing can offer clinical, logistical, and quality-of-life benefits and enhance opportunities for remote consultations, which may be more appropriate for young children. Wider rollout would require consideration of ethical and cybersecurity issues and, given the heightened intrusion on families' privacy, a non-judgmental, collaborative approach by healthcare professionals.
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Diabetes Mellitus Tipo 1 , Padres , COVID-19 , Niño , Preescolar , Atención a la Salud , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Glucosa , Humanos , Lactante , Insulina/uso terapéutico , Pandemias , Padres/psicología , Investigación Cualitativa , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: The achievement of glycaemic control remains challenging for patients with type 1 diabetes. We assessed the effectiveness of day-and-night hybrid closed-loop insulin delivery compared with sensor-augmented pump therapy in people with suboptimally controlled type 1 diabetes aged 6 years and older. METHODS: In this open-label, multicentre, multinational, single-period, parallel randomised controlled trial, participants were recruited from diabetes outpatient clinics at four hospitals in the UK and two centres in the USA. We randomly assigned participants with type 1 diabetes aged 6 years and older treated with insulin pump and with suboptimal glycaemic control (glycated haemoglobin [HbA1c] 7·5-10·0%) to receive either hybrid closed-loop therapy or sensor-augmented pump therapy over 12 weeks of free living. Training on study insulin pump and continuous glucose monitoring took place over a 4-week run-in period. Eligible subjects were randomly assigned using central randomisation software. Allocation to the two study groups was unblinded, and randomisation was stratified within centre by low (<8·5%) or high (≥8·5%) HbA1c. The primary endpoint was the proportion of time that glucose concentration was within the target range of 3·9-10·0 mmol/L at 12 weeks post randomisation. Analyses of primary outcome and safety measures were done in all randomised patients. The trial is registered with ClinicalTrials.gov, number NCT02523131, and is closed to accrual. FINDINGS: From May 12, 2016, to Nov 17, 2017, 114 individuals were screened, and 86 eligible patients were randomly assigned to receive hybrid closed-loop therapy (n=46) or sensor-augmented pump therapy (n=40; control group). The proportion of time that glucose concentration was within the target range was significantly higher in the closed-loop group (65%, SD 8) compared with the control group (54%, SD 9; mean difference in change 10·8 percentage points, 95% CI 8·2 to 13·5; p<0·0001). In the closed-loop group, HbA1c was reduced from a screening value of 8·3% (SD 0·6) to 8·0% (SD 0·6) after the 4-week run-in, and to 7·4% (SD 0·6) after the 12-week intervention period. In the control group, the HbA1c values were 8·2% (SD 0·5) at screening, 7·8% (SD 0·6) after run-in, and 7·7% (SD 0·5) after intervention; reductions in HbA1c percentages were significantly greater in the closed-loop group compared with the control group (mean difference in change 0·36%, 95% CI 0·19 to 0·53; p<0·0001). The time spent with glucose concentrations below 3·9 mmol/L (mean difference in change -0·83 percentage points, -1·40 to -0·16; p=0·0013) and above 10·0 mmol/L (mean difference in change -10·3 percentage points, -13·2 to -7·5; p<0·0001) was shorter in the closed-loop group than the control group. The coefficient of variation of sensor-measured glucose was not different between interventions (mean difference in change -0·4%, 95% CI -1·4% to 0·7%; p=0·50). Similarly, total daily insulin dose was not different (mean difference in change 0·031 U/kg per day, 95% CI -0·005 to 0·067; p=0·09) and bodyweight did not differ (mean difference in change 0·68 kg, 95% CI -0·34 to 1·69; p=0·19). No severe hypoglycaemia occurred. One diabetic ketoacidosis occurred in the closed-loop group due to infusion set failure. Two participants in each study group had significant hyperglycaemia, and there were 13 other adverse events in the closed-loop group and three in the control group. INTERPRETATION: Hybrid closed-loop insulin delivery improves glucose control while reducing the risk of hypoglycaemia across a wide age range in patients with suboptimally controlled type 1 diabetes. FUNDING: JDRF, NIHR, and Wellcome Trust.
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Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hemoglobina Glucada/análisis , Hipoglucemiantes/administración & dosificación , Bombas de Infusión Implantables , Sistemas de Infusión de Insulina , Insulina/administración & dosificación , Adolescente , Adulto , Automonitorización de la Glucosa Sanguínea , Niño , Preescolar , Femenino , Humanos , Hipoglucemia/prevención & control , Masculino , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the experiences of families with very young children aged 1 to 7 years (inclusive) with type 1 diabetes using day-and-night hybrid closed-loop insulin delivery. METHODS: Parents/caregivers of 20 children aged 1 to 7 years with type 1 diabetes completed a closed-loop experience survey following two 3-week periods of unrestricted day-and-night hybrid closed-loop insulin therapy using Cambridge FlorenceM system at home. Benefits, limitations, and improvements of closed-loop technology were explored. RESULTS: Responders reported reduced burden of diabetes management, less time spent managing diabetes, and improved quality of sleep with closed-loop. Ninety percent of the responders felt less worried about their child's glucose control using closed-loop. Size of study devices, battery performance and connectivity issues were identified as areas for improvement. Parents/caregivers wished for more options to input information to the system such as temporary glucose targets. CONCLUSIONS: Parents/caregivers of very young children reported important quality of life benefits associated with using closed-loop, supporting adoption of this technology in this population.
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Costo de Enfermedad , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Sistemas de Infusión de Insulina , Insulina/administración & dosificación , Calidad de Vida , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Automonitorización de la Glucosa Sanguínea , Cuidadores/psicología , Cuidadores/estadística & datos numéricos , Niño , Preescolar , Ritmo Circadiano/fisiología , Estudios Cruzados , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/psicología , Familia/psicología , Femenino , Humanos , Lactante , Insulina/efectos adversos , Masculino , Padres/psicología , Encuestas y CuestionariosRESUMEN
AIMS/HYPOTHESIS: The aim of this study was to compare the pharmacokinetics of two different concentrations of insulin aspart (B28Asp human insulin) in children aged 3-6 years with type 1 diabetes. METHODS: Young children with type 1 diabetes underwent an open-label, randomised, two-period crossover study in a clinical research facility, 2-6 weeks apart. In random order, diluted (1:5 dilution with saline [154 mmol/l NaCl]; 20 U/ml) or standard strength (100 U/ml) insulin aspart was administered via an insulin pump as a meal bolus and then overnight by closed-loop insulin delivery as determined by a model predictive algorithm. Plasma insulin was measured every 30-60 min from 17:00 hours on day 1 to 8:00 hours on day 2. We measured the time-to-peak insulin concentration (tmax), insulin metabolic clearance rate (MCR(I)) and background insulin concentration (ins(c)) using compartmental modelling. RESULTS: Eleven children (six male; age range 3.75-6.96 years, HbA1c 7.6% ± 1.3% [60 ± 14 mmol/mol], BMI standard deviation score 1.0 ± 0.8, duration of diabetes 2.2 ± 1.0 years, total daily dose 12.9 [10.6-16.5] U, fasting C-peptide concentration 5 [5-17.1] pmol/l; mean ± SD or median [interquartile range]) participated in the study. No differences between standard and diluted insulin were observed in terms of t max (59.2 ± 14.4 vs 61.6 ± 8.7) min for standard vs diluted, p = 0.59; MCR I (1.98 × 10(-2) ± 0.99 × 10(-2) vs 1.89 × 10(-2) ± 0.82 × 10(-2) 1/kg/min, p = 0.47), and ins c (34 [1-72] vs 23 [3-65] pmol/l, p = 0.66). However, t max showed less intersubject variability following administration of diluted aspart (SD 14.4 vs 8.7 min, p = 0.047). CONCLUSIONS/INTERPRETATION: Diluting insulin aspart does not change its pharmacokinetics. However, it may result in less variable absorption and could be used in young children with type 1 diabetes undergoing closed-loop insulin delivery. TRIAL REGISTRATION: Clinicaltrials.gov NCT01557634. FUNDING: FUNDING was provided by the JDRF, 7th Framework Programme of the European Union, Wellcome Trust Strategic Award and the National Institute for Health Research Cambridge Biomedical Research Centre.
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Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemiantes/farmacocinética , Insulina Aspart/farmacocinética , Sistemas de Infusión de Insulina , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Niño , Preescolar , Estudios Cruzados , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/diagnóstico , Esquema de Medicación , Monitoreo de Drogas , Femenino , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/sangre , Insulina Aspart/administración & dosificación , Insulina Aspart/sangre , Masculino , Modelos Biológicos , Resultado del TratamientoRESUMEN
Introduction: The Closing the Loop in Adults With Type 1 Diabetes (CLEAR) randomized crossover study compared a novel fully closed-loop insulin delivery system with no carbohydrate entry or mealtime bolusing (CamAPS HX), with standard insulin pump therapy and glucose sensor in adults with type 1 diabetes and suboptimal glycemic outcomes. This qualitative substudy aimed to understand the psychosocial impact of using the fully automated system. Materials and Methods: Adults participating in the CLEAR study were invited to take part in a virtual semistructured interview after they had completed 8 weeks using the fully closed-loop system. Recruitment continued until there was adequate representation and data saturation occurred. Interviews were anonymized and transcribed for in-depth thematic analysis using an inductive-deductive approach. Study participants were also asked to complete questionnaires assessing diabetes distress, hypoglycemia confidence, and closed-loop treatment satisfaction. Results: Eleven participants (eight male and three female; age range 26-66 years) were interviewed. After an initial adjustment period, interviewees reported enjoying a reduction in diabetes burden, freed-up mental capacity, and improved mood. All were happy with overnight glycemic outcomes, with the majority reporting benefits on sleep. Although experiences of postprandial glucose outcomes varied, all found mealtimes easier and less stressful, particularly when eating out. Negatives raised by participants predominantly related to the insulin pump hardware, but some also reported increased snacking and challenges around resuming carbohydrate counting at trial closeout. Conclusions: In adults with type 1 diabetes, use of a fully closed-loop insulin delivery system had significant quality-of-life benefits and provided a welcome break from the day-to-day demands of living with diabetes. Clinical Trial Registration: NCT04977908.
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Diabetes Mellitus Tipo 1 , Insulina , Adulto , Masculino , Humanos , Femenino , Persona de Mediana Edad , Anciano , Insulina/uso terapéutico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/psicología , Glucemia , Hipoglucemiantes/uso terapéutico , Estudios Cruzados , Resultado del Tratamiento , Sistemas de Infusión de Insulina , Insulina Regular Humana/uso terapéuticoRESUMEN
Objective: To evaluate postprandial glucose control when applying (1) faster-acting insulin aspart (Fiasp) compared to insulin aspart and (2) ultra-rapid insulin lispro (Lyumjev) compared to insulin lispro using the CamAPS FX hybrid closed-loop algorithm. Research Design and Methods: We undertook a secondary analysis of postprandial glucose excursions from two double-blind, randomized, crossover hybrid closed-loop studies contrasting Fiasp to standard insulin aspart, and Lyumjev to standard insulin lispro. Endpoints included incremental area under curve (iAUC)-2h, iAUC-4h, 4 h postprandial time in target range, time above range, and time below range. It was approved by independent research ethics committees. Results: Two trials with 8 weeks of data from 51 adults with type 1 diabetes were analyzed and 7137 eligible meals were included. During Lyumjev compared with insulin lispro, iAUC-2h and iAUC-4h were significantly decreased following breakfast (mean difference 92 mmol/L per 2 h (95% confidence interval [CI]: 56 to 127); P < 0.001 and 151 mmol/L per 4 h (95% CI: 74 to 229); P < 0.001, respectively) and the evening meal (P < 0.001 and P = 0.011, respectively). Mean time in target range (3.9-10.0 mmol/L) for 4 h postprandially significantly increased during Lyumjev with a mean difference of 6.7 percentage points (95% CI: 3.3 to 10) and 5.7 percentage points (95% CI: 1.4 to 9.9) for breakfast and evening meal, respectively. In contrast, there were no significant differences in iAUC-2h, iAUC-4h, and the other measures of postprandial glucose control between insulin aspart and Fiasp during breakfast, lunch, and evening meal (P > 0.05). Conclusion: The use of Lyumjev with CamAPS FX closed-loop system improved postprandial glucose excursions compared with insulin lispro, while the use of Fiasp did not provide any advantage compared with insulin aspart. Clinical Trial Registration numbers: NCT04055480, NCT05257460.
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Glucemia , Estudios Cruzados , Diabetes Mellitus Tipo 1 , Hipoglucemiantes , Insulina Aspart , Insulina Lispro , Periodo Posprandial , Humanos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/sangre , Adulto , Masculino , Femenino , Insulina Lispro/uso terapéutico , Insulina Lispro/administración & dosificación , Glucemia/análisis , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/administración & dosificación , Insulina Aspart/uso terapéutico , Insulina Aspart/administración & dosificación , Método Doble Ciego , Persona de Mediana Edad , Sistemas de Infusión de Insulina , AlgoritmosRESUMEN
The presence of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes (T1D) is associated with higher glycated hemoglobin levels over time. We evaluated whether hybrid-closed loop (HCL) therapy from onset of T1D could prevent the adverse impact of DKA at diagnosis on long-term glycemic outcomes. This was a posthoc analysis from 51 adolescents using HCL from diagnosis of T1D as part of the CLOuD trial (NCT02871089). We compared glycemic and insulin metrics between adolescents with (n = 17) and without (n = 34) DKA at diagnosis. Participants with and without DKA at diagnosis had similar time in target glucose range 3.9-10.0 mmol/L (70-180 mg/dL), time below range (<3.9 mmol/L, <70 mg/dL) and HbA1c at 6, 12, and 24 months. While insulin requirements at 6 months were higher in those with DKA at diagnosis, this was not statistically significant after adjusting for bodyweight. Residual C-peptide secretion was similar between groups. We conclude that HCL therapy may mitigate against the negative glycemic effects of DKA at T1D diagnosis.
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Diabetes Mellitus Tipo 1 , Cetoacidosis Diabética , Adolescente , Humanos , Insulina/uso terapéutico , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Cetoacidosis Diabética/etiología , Glucemia , Sistemas de Infusión de Insulina , Insulina Regular HumanaRESUMEN
BACKGROUND: CamAPS HX fully closed-loop (FCL) system, with no user input required at mealtimes, has been shown to be safe and effective in adults with type 1 and type 2 diabetes. We assessed whether time spent in hypoglycemia and hyperglycemia during FCL insulin delivery in adults varied by type of diabetes over the 24-hour period. METHODS: We retrospectively analyzed eight weeks of data from 52 participants (adults with type 1 diabetes and adults with insulin-treated type 2 diabetes) recruited to two single-center randomized controlled studies using FCL insulin delivery during unrestricted-living conditions. Key outcomes were time spent in hypoglycemia <70 mg/dL and marked hyperglycemia >300 mg/dL by type of diabetes. RESULTS: The median percentage of time spent in hypoglycemia <70 mg/dL over the 24-hour period was lower for those with type 2 diabetes than for those with type 1 diabetes (median [interquartile range (IQR)] 0.43% [0.20-0.77] vs 0.86%, [0.54-1.46]; mean difference 0.46 percentage points [95% CI 0.23-0.70]; P < .001). Median percentage time in marked hyperglycemia >300 mg/dL was lower for those with type 2 diabetes than for those with type 1 diabetes (median [IQR] 1.8% [0.6-3.5] vs 9.3% [6.9-11.8]; mean difference 7.8 percentage points [95% CI 5.5-10.0]; P < .001). CONCLUSIONS: Using the FCL system, hypoglycemia and marked hyperglycemia exposure were lower in type 2 diabetes than in type 1 diabetes.
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OBJECTIVE: We evaluated the effect of long-term intensive metabolic control with hybrid closed-loop (CL) on residual C-peptide secretion and glucose control compared with standard insulin therapy in youth with type 1 diabetes over 48 months. RESEARCH DESIGN AND METHODS: Following the 24-month primary phase of a multicenter, randomized, parallel trial of 96 newly diagnosed youth aged 10 to 16.9 years, participants were invited to an extension phase using treatment allocated at randomization. They continued with hybrid CL using the Cambridge algorithm or standard insulin therapy (control) until 48 months after diagnosis. Analysis was by intention-to-treat. RESULTS: At 24 months after diagnosis, 81 participants (mean ± SD age 14 ± 2 years) continued in the extension phase (47 CL, 34 control). There was no difference in fasting C-peptide corrected for fasting glucose at 48 months between groups (CL: 5 ± 9 vs. control: 6 ± 14 pmol/L per mmol/L; mean adjusted difference -2 [95% CI -7, 4; P = 0.54]). Central laboratory HbA1c remained lower in the CL group by 0.9% (10 mmol/mol [95% CI 0.2, 1.5; 3, 17 mmol/mol); P = 0.009). Time in target range of 3.9 to 10.0 mmol/L was 12 percentage points (95% CI 3, 20; P = 0.008) higher in the CL group compared with control. There were 11 severe hypoglycemic events (6 CL, 5 control) and 7 diabetic ketoacidosis events (3 CL, 4 control) during the extension phase. CONCLUSIONS: Improved glycemic control was sustained over 48 months after diagnosis with CL insulin delivery compared with standard therapy in youth with type 1 diabetes. This did not appear to confer a protective effect on residual C-peptide secretion.
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Glucemia , Péptido C , Diabetes Mellitus Tipo 1 , Sistemas de Infusión de Insulina , Insulina , Humanos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/metabolismo , Adolescente , Péptido C/sangre , Insulina/uso terapéutico , Insulina/administración & dosificación , Masculino , Niño , Femenino , Glucemia/metabolismo , Glucemia/efectos de los fármacos , Control Glucémico/métodos , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/administración & dosificación , Hemoglobina Glucada/metabolismoRESUMEN
BACKGROUND/OBJECTIVE: The main objective of this study is to evaluate the incremental cost-effectiveness (ICER) of the Cambridge hybrid closed-loop automated insulin delivery (AID) algorithm versus usual care for children and adolescents with type 1 diabetes (T1D). METHODS: This multicenter, binational, parallel-controlled trial randomized 133 insulin pump using participants aged 6 to 18 years to either AID (n = 65) or usual care (n = 68) for 6 months. Both within-trial and lifetime cost-effectiveness were analyzed. Analysis focused on the treatment subgroup (n = 21) who received the much more reliable CamAPS FX hardware iteration and their contemporaneous control group (n = 24). Lifetime complications and costs were simulated via an updated Sheffield T1D policy model. RESULTS: Within-trial, both groups had indistinguishable and statistically unchanged health-related quality of life, and statistically similar hypoglycemia, severe hypoglycemia, and diabetic ketoacidosis (DKA) event rates. Total health care utilization was higher in the treatment group. Both the overall treatment group and CamAPS FX subgroup exhibited improved HbA1C (-0.32%, 95% CI: -0.59 to -0.04; P = .02, and -1.05%, 95% CI: -1.43 to -0.67; P < .001, respectively). Modeling projected increased expected lifespan of 5.36 years and discounted quality-adjusted life years (QALYs) of 1.16 (U.K. tariffs) and 1.52 (U.S. tariffs) in the CamAPS FX subgroup. Estimated ICERs for the subgroup were £19 324/QALY (United Kingdom) and -$3917/QALY (United States). For subgroup patients already using continuous glucose monitors (CGM), ICERs were £10 096/QALY (United Kingdom) and -$33 616/QALY (United States). Probabilistic sensitivity analysis generated mean ICERs of £19 342/QALY (95% CI: £15 903/QALY to £22 929/QALY) (United Kingdom) and -$28 283/QALY (95% CI: -$59 607/QALY to $1858/QALY) (United States). CONCLUSIONS: For children and adolescents with T1D on insulin pump therapy, AID using the Cambridge algorithm appears cost-effective below a £20 000/QALY threshold (United Kingdom) and cost saving (United States).
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INTRODUCTION: Closed-loop (CL) systems modulate insulin delivery according to glucose levels without nurse input. In a prospective randomized controlled trial, we evaluated the feasibility of an automated closed-loop approach based on subcutaneous glucose measurements in comparison with a local sliding-scale insulin-therapy protocol. METHODS: Twenty-four critically ill adults (predominantly trauma and neuroscience patients) with hyperglycemia (glucose, ≥10 mM) or already receiving insulin therapy, were randomized to receive either fully automated closed-loop therapy (model predictive control algorithm directing insulin and 20% dextrose infusion based on FreeStyle Navigator continuous subcutaneous glucose values, n = 12) or a local protocol (n = 12) with intravenous sliding-scale insulin, over a 48-hour period. The primary end point was percentage of time when arterial blood glucose was between 6.0 and 8.0 mM. RESULTS: The time when glucose was in the target range was significantly increased during closed-loop therapy (54.3% (44.1 to 72.8) versus 18.5% (0.1 to 39.9), P = 0.001; median (interquartile range)), and so was time in wider targets, 5.6 to 10.0 mM and 4.0 to 10.0 mM (P ≤ 0.002), reflecting a reduced glucose exposure >8 and >10 mM (P ≤ 0.002). Mean glucose was significantly lower during CL (7.8 (7.4 to 8.2) versus 9.1 (8.3 to 13.0] mM; P = 0.001) without hypoglycemia (<4 mM) during either therapy. CONCLUSIONS: Fully automated closed-loop control based on subcutaneous glucose measurements is feasible and may provide efficacious and hypoglycemia-free glucose control in critically ill adults. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT01440842.
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Glucemia/metabolismo , Enfermedad Crítica , Monitoreo Fisiológico/métodos , Tejido Subcutáneo/irrigación sanguínea , Tejido Subcutáneo/metabolismo , Glucemia/efectos de los fármacos , Enfermedad Crítica/terapia , Estudios Cruzados , Estudios de Factibilidad , Femenino , Humanos , Infusiones Intravenosas , Insulina/administración & dosificación , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/instrumentación , Estudios Prospectivos , Tejido Subcutáneo/efectos de los fármacosRESUMEN
Introduction: To evaluate hybrid closed-loop with ultra-rapid insulin lispro (Lyumjev) compared with hybrid closed-loop with standard insulin lispro in adults with type 1 diabetes. Materials and Methods: In a single-center, double-blind, randomized, crossover study, 28 adults with type 1 diabetes (mean ± standard deviation [SD]: age 44.5 ± 10.7 years, glycated hemoglobin (HbA1c) 7.1 ± 0.9% [54 ± 10 mmol/mol]) underwent two 8-week periods comparing hybrid closed-loop with ultra-rapid insulin lispro and hybrid closed-loop with standard insulin lispro in random order. The same CamAPS FX closed-loop algorithm was used in both periods. Results: In an intention-to-treat analysis, the proportion of time sensor glucose was in target range (3.9-10 mmol/L [70-180 mg/dL]; primary endpoint) was greater with ultra-rapid lispro compared with standard insulin lispro (mean ± SD: 78.7 ± 9.8% vs. 76.2 ± 9.6%; mean difference 2.5 percentage points [95% confidence interval 0.8 to 4.2]; P = 0.005). Mean sensor glucose was lower with ultra-rapid lispro compared with standard insulin lispro (7.9 ± 0.8 mmol/L [142 ± 14 mg/dL] vs. 8.1 ± 0.9 mmol/L [146 ± 16 mg/dL]; P = 0.048). The proportion of time with sensor glucose <3.9 mmol/L [70 mg/dL] was similar between interventions (median [interquartile range] ultra-rapid lispro 2.3% [1.3%-2.7%] vs. standard insulin lispro 2.1% [1.4%-3.3%]; P = 0.33). No severe hypoglycemia or ketoacidosis occurred. Conclusions: The use of ultra-rapid lispro with CamAPS FX hybrid closed-loop increases time in range and reduces mean glucose with no difference in hypoglycemia compared with standard insulin lispro in adults with type 1 diabetes. ClinicalTrials.gov: Trial registration number NCT05257460.
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Diabetes Mellitus Tipo 1 , Hipoglucemia , Humanos , Adulto , Persona de Mediana Edad , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Insulina Lispro/uso terapéutico , Hipoglucemiantes/uso terapéutico , Estudios Cruzados , Insulina/uso terapéutico , Glucemia , Sistemas de Infusión de Insulina , Hipoglucemia/tratamiento farmacológico , GlucosaRESUMEN
OBJECTIVE: We evaluated the safety and efficacy of fully closed-loop with ultrarapid insulin lispro in adults with type 1 diabetes and suboptimal glycemic control compared with insulin pump therapy with continuous glucose monitoring (CGM). RESEARCH DESIGN AND METHODS: This single-center, randomized, crossover study enrolled 26 adults with type 1 diabetes using insulin pump therapy with suboptimal glycemic control (mean ± SD, age 41 ± 12 years, HbA1c 9.2 ± 1.1% [77 ± 12 mmol/mol]). Participants underwent two 8-week periods of unrestricted living to compare fully closed-loop with ultrarapid insulin lispro (CamAPS HX system) with insulin pump therapy with CGM in random order. RESULTS: In an intention-to-treat analysis, the proportion of time glucose was in range (primary end point 3.9-10.0 mmol/L) was higher during closed-loop than during pump with CGM (mean ± SD 50.0 ± 9.6% vs. 36.2 ± 12.2%, mean difference 13.2 percentage points [95% CI 9.5, 16.9], P < 0.001). Time with glucose >10.0 mmol/L and mean glucose were lower during closed-loop than during pump with CGM (mean ± SD time >10.0 mmol/L: 49.0 ± 9.9 vs. 62.9 ± 12.6%, mean difference -13.3 percentage points [95% CI -17.2, -9.5], P < 0.001; mean ± SD glucose 10.7 ± 1.1 vs. 12.0 ± 1.6 mmol/L, mean difference -1.2 mmol/L [95% CI -1.8, -0.7], P < 0.001). The proportion of time with glucose <3.9 mmol/L was similar between periods (median [interquartile range (IQR)] closed-loop 0.88% [0.51-1.55] vs. pump with CGM 0.64% [0.28-1.10], P = 0.102). Total daily insulin requirements did not differ (median [IQR] closed-loop 51.9 units/day [35.7-91.2] vs. pump with CGM 50.7 units/day [34.0-70.0], P = 0.704). No severe hypoglycemia or ketoacidosis occurred. CONCLUSIONS: Fully closed-loop insulin delivery with CamAPS HX improved glucose control compared with insulin pump therapy with CGM in adults with type 1 diabetes and suboptimal glycemic control.
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Diabetes Mellitus Tipo 1 , Humanos , Adulto , Persona de Mediana Edad , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Glucemia , Estudios Cruzados , Automonitorización de la Glucosa Sanguínea , Insulina Lispro/uso terapéutico , Resultado del Tratamiento , Sistemas de Infusión de Insulina , Insulina Regular Humana/uso terapéuticoRESUMEN
We evaluated the use of hybrid closed-loop (HCL) insulin delivery with faster insulin aspart (Fiasp) in very young children with type 1 diabetes (T1D). In a double-blind, multicenter, randomized, crossover study, children aged 2-6 years with T1D underwent two 8-week periods of HCL using CamAPS FX with Fiasp and standard insulin aspart (IAsp), in random order. Primary endpoint was between-treatment difference in time in target range 3.9-10.0 mmol/L. We randomized 25 participants: mean (±standard deviation) age 5.1 ± 1.3 years, baseline HbA1c 55 ± 9 mmol/mol. Time in range was not significantly different between interventions (64% ± 9% vs. 65% ± 9% for HCL with Fiasp vs. IAsp; mean difference -0.33% [95% confidence interval: -2.13 to 1.47; P = 0.71]). There was no significant difference in time with glucose <3.9 mmol/L. No post-randomization severe hypoglycemia or diabetic ketoacidosis events occurred. Use of Fiasp with CamAPS FX HCL demonstrated no significant difference in glycemic outcomes compared with IAsp in very young children with T1D. Clinical trials registration: NCT04759144.
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Diabetes Mellitus Tipo 1 , Humanos , Niño , Preescolar , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Insulina Aspart/uso terapéutico , Hipoglucemiantes/uso terapéutico , Estudios Cruzados , Glucemia , Insulina/uso terapéutico , Método Doble CiegoRESUMEN
Objective: We aimed to assess whether percentage of time spent in hypoglycemia during closed-loop insulin delivery differs by age group and time of day. Methods: We retrospectively analyzed data from hybrid closed-loop studies involving young children (2-7 years), children and adolescents (8-18 years), adults (19-59 years), and older adults (≥60 years) with type 1 diabetes. Main outcome was time spent in hypoglycemia <3.9 mmol/L (<70 mg/dL). Eight weeks of data for 88 participants were analyzed. Results: Median time spent in hypoglycemia over the 24-h period was highest in children and adolescents (4.4% [interquartile range 2.4-5.0]) and very young children (4.0% [3.4-5.2]), followed by adults (2.7% [1.7-4.0]), and older adults (1.8% [1.2-2.2]); P < 0.001 for difference between age groups. Time spent in hypoglycemia during nighttime (midnight-05:59) was lower than during daytime (06:00-23:59) across all age groups. Conclusion: Time in hypoglycemia was highest in the pediatric age group during closed-loop insulin delivery. Hypoglycemia burden was lowest overnight across all age groups.
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Diabetes Mellitus Tipo 1 , Hipoglucemia , Adolescente , Anciano , Niño , Preescolar , Humanos , Glucemia , Estudios Cruzados , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemia/inducido químicamente , Hipoglucemia/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina/efectos adversos , Sistemas de Infusión de Insulina , Insulina Regular Humana/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven , Adulto , Persona de Mediana EdadRESUMEN
OBJECTIVE: To evaluate an ambulatory, portable prototype, overnight automated closed-loop (CL) system and to explore optimal time of CL initiation. METHODS: We performed a randomized crossover study and compared automated overnight glucose control started at the time of an evening-meal or at bedtime. Eight young people with type 1 diabetes (T1D) on insulin pump therapy [M = 4; age = 14.3 (1.7) yr; HbA1c = 8.2 (1.3)%; mean (SD)] were studied on two occasions at clinical research facility. A standardized self-selected evening meal [70 (11)g CHO] and snack [22 (4)g CHO] accompanied by prandial insulin boluses were given at 18:00 and 21:00 hours, respectively. In random order, automated CL was started at 18:00 or 21:00 hours and ran until 8:00 hours the next day. Basal insulin delivery was automatically adjusted by a model predictive control algorithm based on real-time continuous glucose monitor readings. RESULTS: Overnight plasma glucose levels (between 21:00 and 08:00 hours) were within the target range (71-145 mg/dL) for 82 (59, 98)% of time when CL started at 18:00 hours and 64 (48, 70)% when CL started at 21:00 hours [median (IQR), p = 0.036]. Time spent above 180 mg/dL [8 (0, 17) vs. 13 (3, 26)%, p = 0.310] or below 70 mg/dL [0 (0,7) vs. 0 (0, 8)%, p = 1.000] did not differ between the two occasions. Mean overnight glucose [121 (14) vs. 137 (13) mg/dL, p = 0.731) was also similar. Overnight insulin infusion rates were comparable [0.8 (0.5, 1.3) vs. 0.8 (0.6, 1.4) U/h, p = 0.263]. No interruptions to CL delivery were observed. CONCLUSION: Automated CL delivery can be applied reliably and safely to control glucose levels overnight in young people with T1D. Tighter glucose levels may be achieved with an earlier time of CL initiation.