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OBJECTIVE: To evaluate whether continuous glucose monitoring (CGM)-derived glycemic patterns observed throughout pregnancy were associated with adverse perinatal outcomes, specifically fetal growth disorders and hypertensive disorders of pregnancy (HDP). METHODS: We conducted a prospective observational study of individuals with viable singleton pregnancies and screening hemoglobin A1c levels less than 6.5%. Those with preexisting diabetes were excluded. Enrollment occurred at the earliest gestational age before 17 weeks. Participants wore blinded continuous glucose monitors consecutively as willing until delivery. Those with at least 14 days of CGM data were included in analysis. Rates of large-for-gestational-age (LGA) neonates, small-for-gestational age (SGA) neonates, and HDP were assessed. Continuous glucose monitoring-derived glycemic metrics were calculated, including mean glucose level and percent time above and below thresholds. Two-sample t tests were used to compare glycemic metrics between participants with and without adverse perinatal outcomes. RESULTS: Of 937 participants enrolled, 760 met inclusion criteria. Those delivering LGA neonates or who were diagnosed with HDP had higher mean glucose levels (102±9 vs 100±8, P=.01 and 103±8 vs 99±8, P<.001) and spent more time above 120 mg/dL (median 16% vs 12%, P=.006, and 16% vs 12%, P<.001, respectively) and above 140 mg/dL (median 3.9% vs 2.8%, P=.006, and 3.5% vs 2.8%, P<.001, respectively) throughout gestation than those without these outcomes. These findings were present regardless of gestational diabetes mellitus status. Participants with SGA neonates had lower mean glucose levels (97±7 vs 101±8, P=.01) and spent less time above 140 mg/dL (median 1.6% vs 2.3%, P=.01) and more time below 63 mg/dL (median 3.0% vs 2.3%, P=.02) than those without SGA neonates. CONCLUSION: Individuals with LGA neonates or HDP exhibit a slightly higher mean glucose levels and spend more time hyperglycemic in early pregnancy than those who do not experience these outcomes.
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Objective: To assess the performance of continuous glucose monitoring (CGM)-measured glycemic metrics in predicting development of gestational diabetes mellitus (GDM) and select perinatal complications. Research Methods: In a prospective observational study, CGM data were collected from 760 pregnant females throughout gestation after study enrollment. GDM was diagnosed using the oral glucose tolerance test (OGTT) at 24-34 weeks of gestation. Predictive models were built using logistic and elastic net regression. Predictive performance was assessed by the area under the receiver-operating characteristic (AUROC) curve. Results: The AUROCs of using second trimester percent time >140 mg/dL (TA140) and week 13-14 TA140 in predicting GDM were 0.81 and 0.74, respectively. The AUROCs for predicting large-for-gestational-age (LGA) births and hypertensive disorders of pregnancy (HDP) using second trimester TA140 were both 0.58. When matching the specificity of OGTT, a model using TA140 in weeks 13-14 achieved similar sensitivity to OGTT in predicting HDP (13% vs. 10%, respectively) and LGA (6% for both methods). Elastic net also demonstrated similar AUROC and diagnostic performance with no meaningful improvement by using multiple predictors. Conclusion: CGM-measured hyperglycemic metrics such as TA140 predicted GDM with high AUROCs as early as 13-14 weeks of gestation. These metrics were also similar statistically to the OGTT at 24-34 weeks in predicting perinatal complications, although sensitivity was low for both. CGM could potentially be used as an early screening tool for elevated hyperglycemia during gestation, which could be used in addition to or instead of the OGTT.
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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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Glicemia , Peptídeo C , Diabetes Mellitus Tipo 1 , Sistemas de Infusão de Insulina , Insulina , Humanos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/metabolismo , Adolescente , Peptídeo C/sangue , Insulina/uso terapêutico , Insulina/administração & dosagem , Masculino , Criança , Feminino , Glicemia/metabolismo , Glicemia/efeitos dos fármacos , Controle Glicêmico/métodos , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/administração & dosagem , Hemoglobinas Glicadas/metabolismoRESUMO
OBJECTIVE: To determine whether continuous glucose monitoring (CGM)-derived glycemic patterns can characterize pregnancies with gestational diabetes mellitus (GDM) as diagnosed by standard oral glucose tolerance test at 24-28 weeks' gestation compared with those without GDM. RESEARCH DESIGN AND METHODS: The analysis includes 768 individuals enrolled from two sites prior to 17 weeks' gestation between June 2020 and December 2021 in a prospective observational study. Participants wore blinded Dexcom G6 CGMs throughout gestation. Main outcome of interest was a diagnosis of GDM by oral glucose tolerance test (OGTT). Glycemic levels in participants with GDM versus without GDM were characterized using CGM-measured glycemic metrics. RESULTS: Participants with GDM (n = 58 [8%]) had higher mean glucose (109 ± 13 vs. 100 ± 8 mg/dL [6.0 ± 0.7 vs. 5.6 ± 0.4 mmol/L], P < 0.001), greater glucose SD (23 ± 4 vs. 19 ± 3 mg/dL [1.3 ± 0.2 vs. 1.1 ± 0.2 mmol/L], P < 0.001), less time in range 63-120 mg/dL (3.5-6.7 mmol/L) (70% ± 17% vs. 84% ± 8%, P < 0.001), greater percent time >120 mg/dL (>6.7 mmol/L) (median 23% vs. 12%, P < 0.001), and greater percent time >140 mg/dL (>7.8 mmol/L) (median 7.4% vs. 2.7%, P < 0.001) than those without GDM throughout gestation prior to OGTT. Median percent time >120 mg/dL (>6.7 mmol/L) and time >140 mg/dL (>7.8 mmol/L) were higher as early as 13-14 weeks of gestation (32% vs. 14%, P < 0.001, and 5.2% vs. 2.0%, P < 0.001, respectively) and persisted during the entire study period prior to OGTT. CONCLUSIONS: Prior to OGTT at 24-34 weeks' gestation, pregnant individuals who develop GDM have higher CGM-measured glucose levels and more hyperglycemia compared with those who do not develop GDM.
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Automonitorização da Glicemia , Glicemia , Diabetes Gestacional , Teste de Tolerância a Glucose , Humanos , Diabetes Gestacional/sangue , Diabetes Gestacional/diagnóstico , Gravidez , Feminino , Glicemia/análise , Glicemia/metabolismo , Adulto , Estudos Prospectivos , Monitoramento Contínuo da GlicoseRESUMO
INTRODUCTION: To characterize glucose levels during uncomplicated pregnancies, defined as pregnancy with a hemoglobin A1c <5.7% (<39 mmol/mol) in early pregnancy, and without a large-for-gestational-age birth, hypertensive disorders of pregnancy, or gestational diabetes mellitus (ie, abnormal oral glucose tolerance test). RESEARCH DESIGN AND METHODS: Two sites enrolled 937 pregnant individuals aged 18 years and older prior to reaching 17 gestational weeks; 413 had an uncomplicated pregnancy (mean±SD body mass index (BMI) of 25.3±5.0 kg/m2) and wore Dexcom G6 continuous glucose monitoring (CGM) devices throughout the observed gestational period. Mealtimes were voluntarily recorded. Glycemic levels during gestation were characterized using CGM-measured glycemic metrics. RESULTS: Participants wore CGM for a median of 123 days each. Glucose levels were nearly stable throughout all three trimesters in uncomplicated pregnancies. Overall mean±SD glucose during gestation was 98±7 mg/dL (5.4±0.4 mmol/L), median per cent time 63-120 mg/dL (3.5-6.7 mmol/L) was 86% (IQR: 82-89%), median per cent time <63 mg/dL (3.5 mmol/L) was 1.8%, median per cent time >120 mg/dL (6.7 mmol/L) was 11%, and median per cent time >140 mg/dL (7.8 mmol/L) was 2.5%. Mean post-prandial peak glucose was 126±22 mg/dL (7.0±1.2 mmol/L), and mean post-prandial glycemic excursion was 36±22 mg/dL (2.0±1.2 mmol/L). Higher mean glucose levels were low to moderately associated with pregnant individuals with higher BMIs (103±6 mg/dL (5.7±0.3 mmol/L) for BMI ≥30.0 kg/m2 vs 96±7 mg/dL (5.3±0.4 mmol/L) for BMI 18.5-<25 kg/m2, r=0.35). CONCLUSIONS: Mean glucose levels and time 63-120 mg/dL (3.5-6.7 mmol/L) remained nearly stable throughout pregnancy and values above 140 mg/dL (7.8 mmol/L) were rare. Mean glucose levels in pregnancy trend higher as BMI increases into the overweight/obesity range. The glycemic metrics reported during uncomplicated pregnancies represent treatment targets for pregnant individuals.
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Automonitorização da Glicemia , Glicemia , Humanos , Feminino , Gravidez , Glicemia/análise , Adulto , Automonitorização da Glicemia/métodos , Hemoglobinas Glicadas/análise , Diabetes Gestacional/sangue , Diabetes Gestacional/diagnóstico , Teste de Tolerância a Glucose , Adulto Jovem , Seguimentos , Biomarcadores/sangue , Biomarcadores/análise , Monitoramento Contínuo da GlicoseRESUMO
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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BACKGROUND: Hybrid closed-loop insulin therapy has shown promise for management of type 1 diabetes during pregnancy; however, its efficacy is unclear. METHODS: In this multicenter, controlled trial, we randomly assigned pregnant women with type 1 diabetes and a glycated hemoglobin level of at least 6.5% at nine sites in the United Kingdom to receive standard insulin therapy or hybrid closed-loop therapy, with both groups using continuous glucose monitoring. The primary outcome was the percentage of time in the pregnancy-specific target glucose range (63 to 140 mg per deciliter [3.5 to 7.8 mmol per liter]) as measured by continuous glucose monitoring from 16 weeks' gestation until delivery. Analyses were performed according to the intention-to-treat principle. Key secondary outcomes were the percentage of time spent in a hyperglycemic state (glucose level >140 mg per deciliter), overnight time in the target range, the glycated hemoglobin level, and safety events. RESULTS: A total of 124 participants with a mean (±SD) age of 31.1±5.3 years and a mean baseline glycated hemoglobin level of 7.7±1.2% underwent randomization. The mean percentage of time that the maternal glucose level was in the target range was 68.2±10.5% in the closed-loop group and 55.6±12.5% in the standard-care group (mean adjusted difference, 10.5 percentage points; 95% confidence interval [CI], 7.0 to 14.0; P<0.001). Results for the secondary outcomes were consistent with those of the primary outcome; participants in the closed-loop group spent less time in a hyperglycemic state than those in the standard-care group (difference, -10.2 percentage points; 95% CI, -13.8 to -6.6); had more overnight time in the target range (difference, 12.3 percentage points; 95% CI, 8.3 to 16.2), and had lower glycated hemoglobin levels (difference, -0.31 percentage points; 95% CI, -0.50 to -0.12). Little time was spent in a hypoglycemic state. No unanticipated safety problems associated with the use of closed-loop therapy during pregnancy occurred (6 instances of severe hypoglycemia, vs. 5 in the standard-care group; 1 instance of diabetic ketoacidosis in each group; and 12 device-related adverse events in the closed-loop group, 7 related to closed-loop therapy). CONCLUSIONS: Hybrid closed-loop therapy significantly improved maternal glycemic control during pregnancy complicated by type 1 diabetes. (Funded by the Efficacy and Mechanism Evaluation Program; AiDAPT ISRCTN Registry number, ISRCTN56898625.).
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Glicemia , Diabetes Mellitus Tipo 1 , Hipoglicemiantes , Sistemas de Infusão de Insulina , Insulina , Gravidez em Diabéticas , Adulto , Feminino , Humanos , Gravidez , Glicemia/análise , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hemoglobinas Glicadas/análise , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Insulina/administração & dosagem , Insulina/efeitos adversos , Insulina/uso terapêutico , Sistemas de Infusão de Insulina/efeitos adversos , Gravidez em Diabéticas/sangue , Gravidez em Diabéticas/tratamento farmacológico , Resultado do TratamentoRESUMO
Introduction: Multiple daily injection insulin therapy frequently fails to meet hospital glycemic goals and is prone to hypoglycemia. Automated insulin delivery (AID) with remote glucose monitoring offers a solution to these shortcomings. Research Design and Methods: In a single-arm multicenter pilot trial, we tested the feasibility, safety, and effectiveness of the Omnipod 5 AID System with real-time continuous glucose monitoring (CGM) for up to 10 days in hospitalized patients with insulin-requiring diabetes on nonintensive care unit medical-surgical units. Primary endpoints included the proportion of time in automated mode and percent time-in-range (TIR 70-180 mg/dL) among participants with >48 h of CGM data. Safety endpoints included incidence of severe hypoglycemia and diabetes-related ketoacidosis (DKA). Additional glycemic endpoints, CGM accuracy, and patient satisfaction were also explored. Results: Twenty-two participants were enrolled; 18 used the system for a total of 96 days (mean 5.3 ± 3.1 days per patient), and 16 had sufficient CGM data required for analysis. Median percent time in automated mode was 95% (interquartile range 92%-98%) for the 18 system users, and the 16 participants with >48 h of CGM data achieved an overall TIR of 68% ± 16%, with 0.17% ± 0.3% time <70 mg/dL and 0.06% ± 0.2% time <54 mg/dL. Sensor mean glucose was 167 ± 21 mg/dL. There were no DKA or severe hypoglycemic events. All participants reported satisfaction with the system at study end. Conclusions: The use of AID with a disposable tubeless patch-pump along with remote real-time CGM is feasible in the hospital setting. These results warrant further investigation in randomized trials.
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Diabetes Mellitus Tipo 1 , Cetoacidose Diabética , Hipoglicemia , Humanos , Glicemia , Automonitorização da Glicemia/métodos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Estudos de Viabilidade , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Sistemas de Infusão de Insulina , Insulina Regular Humana/uso terapêutico , Projetos PilotoRESUMO
OBJECTIVE: To evaluate the impact of CamAPS FX hybrid closed-loop (HCL) automated insulin delivery in very young children with type 1 diabetes (T1D) on caregivers' well-being, fear of hypoglycemia, and sleepiness. RESEARCH DESIGN AND METHODS: We conducted a multinational, open-label, randomized crossover study. Children (age 1-7 years) with T1D received treatment for two 4-month periods in random order, comparing HCL with sensor augmented pump (control). At baseline and after each treatment period, caregivers were invited to complete World Health Organization-Five Well-Being Index, Hypoglycemia Fear Survey, and Epworth Sleepiness Scale questionnaires. RESULTS: Caregivers of 74 children (mean ± SD age 5 ± 2 years and baseline HbA1c 7.3 ± 0.7%; 42% female) participated. Results revealed significantly lower scores for hypoglycemia fear (P < 0.001) and higher scores for well-being (P < 0.001) after HCL treatment. A trend toward a reduction in sleepiness score was observed (P = 0.09). CONCLUSIONS: Our results suggest better well-being and less hypoglycemia fear in caregivers of very young children with T1D on CamAPS FX HCL.
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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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Peptídeo C , Diabetes Mellitus Tipo 1 , Hipoglicemiantes , Insulina , Adolescente , Glicemia/análise , Peptídeo C/metabolismo , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Sistemas de Infusão de InsulinaRESUMO
The Medtronic advanced hybrid closed-loop (AHCL) and MiniMed™ 670G hybrid closed-loop (HCL) systems provide the option to temporarily increase the glucose target to 150 mg/dL (8.3 mmol/L). This analysis investigated the efficacy of the AHCL compared with that of the HCL after the use of this setting. Data from 60 participants in the Fuzzy Logic Automated Insulin Regulation (FLAIR) study were used to compare the AHCL and HCL systems after the use of the temporary target (TT), and during analogous periods where this setting was not used. Differences in time in range 70-180 mg/dL between the systems were similar after the use of the TT setting and during analogous non-TT periods (interaction P = 0.87). Similar trends were observed for mean glucose, percentage time >180 mg/dL, and percentage time >250 mg/dL. Differences between AHCL and HCL systems were similar after the use of the TT setting compared with those of non-TT periods. ClinicalTrials.gov NCT03040414.
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Diabetes Mellitus Tipo 1 , Sistemas de Infusão de Insulina , Humanos , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Glicemia , Insulina/uso terapêutico , GlucoseRESUMO
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 , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Automonitorização da Glicemia , Insulina/uso terapêutico , Qualidade de Vida , Hipoglicemiantes/uso terapêutico , Glicemia , Resultado do Tratamento , Sistemas de Infusão de Insulina , Pais/psicologiaRESUMO
Background: We recently reported that use of an "advanced" hybrid closed-loop system reduced hyperglycemia without increasing hypoglycemia compared to a first-generation system. The aim of this analysis was to evaluate whether this improved performance was specifically related to better mealtime glycemic control. Methods: We conducted a secondary analysis of postprandial glycemic control in an open-label, multinational, randomized crossover trial of 112 participants with type 1 diabetes, aged 14-29, of the Medtronic MiniMed™ 670G hybrid closed-loop system (670G) versus the Medtronic advanced hybrid closed-loop (AHCL) system, for 12 weeks each. We compared glycemic and insulin delivery metrics over a 3 h horizon across all meals to assess system performance and outcomes. Results: Overall meal size and premeal insulin on board were similar during run-in and between 670G and AHCL arms. Compared with 670G arm, premeal, peak, and mean glucose levels were numerically lower in the AHCL arm (167 ± 23, 231 ± 23, and 177 ± 20 mg/dL vs. 175 ± 23, 235 ± 23, and 180 ± 19 mg/dL, respectively), with a trend to lower hyperglycemia level 2 in AHCL arm. Adjusting for premeal glucose level, all postmeal outcomes between 670G and AHCL were statistically similar. Prandial insulin delivery also was similar in both treatment arms (21 ± 9 vs. 23 ± 10 U), with a shift in basal/bolus ratio from 28%/71% in 670G arm to 20%/80% in AHCL arm. Conclusions: Reduced hyperglycemia with AHCL compared to 670G was not related to early postprandial glycemic excursions after adjusting for premeal glucose level (<3 h after meal), but likely to later (>3 h) postprandial or overnight improvements. Further refinements to mealtime bolus algorithms and strategies may more optimally control prandial glycemic excursions.
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Diabetes Mellitus Tipo 1 , Hiperglicemia , Glicemia/análise , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Hiperglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Sistemas de Infusão de Insulina , Insulina Regular Humana/uso terapêuticoRESUMO
BACKGROUND: Pregnant women with type 1 diabetes strive for tight glucose targets (3.5-7.8 mmol/L) to minimise the risks of obstetric and neonatal complications. Despite using diabetes technologies including continuous glucose monitoring (CGM), insulin pumps and contemporary insulin analogues, most women struggle to achieve and maintain the recommended pregnancy glucose targets. This study aims to evaluate whether the use of automated closed-loop insulin delivery improves antenatal glucose levels in pregnant women with type 1 diabetes. METHODS/DESIGN: A multicentre, open label, randomized, controlled trial of pregnant women with type 1 diabetes and a HbA1c of ≥48 mmol/mol (6.5%) at pregnancy confirmation and ≤ 86 mmol/mol (10%) at randomization. Participants who provide written informed consent before 13 weeks 6 days gestation will be entered into a run-in phase to collect 96 h (24 h overnight) of CGM glucose values. Eligible participants will be randomized on a 1:1 basis to CGM (Dexcom G6) with usual insulin delivery (control) or closed-loop (intervention). The closed-loop system includes a model predictive control algorithm (CamAPS FX application), hosted on an android smartphone that communicates wirelessly with the insulin pump (Dana Diabecare RS) and CGM transmitter. Research visits and device training will be provided virtually or face-to-face in conjunction with 4-weekly antenatal clinic visits where possible. Randomization will stratify for clinic site. One hundred twenty-four participants will be recruited. This takes into account 10% attrition and 10% who experience miscarriage or pregnancy loss. Analyses will be performed according to intention to treat. The primary analysis will evaluate the change in the time spent in the target glucose range (3.5-7.8 mmol/l) between the intervention and control group from 16 weeks gestation until delivery. Secondary outcomes include overnight time in target, time above target (> 7.8 mmol/l), standard CGM metrics, HbA1c and psychosocial functioning and health economic measures. Safety outcomes include the number and severity of ketoacidosis, severe hypoglycaemia and adverse device events. DISCUSSION: This will be the largest randomized controlled trial to evaluate the impact of closed-loop insulin delivery during type 1 diabetes pregnancy. TRIAL REGISTRATION: ISRCTN 56898625 Registration Date: 10 April, 2018.
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Diabetes Mellitus Tipo 1 , Glicemia/análise , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Recém-Nascido , Insulina/uso terapêutico , Sistemas de Infusão de Insulina , Estudos Multicêntricos como Assunto , Gravidez , Gestantes , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Closed-loop insulin delivery systems have the potential to address suboptimal glucose control in children and adolescents with type 1 diabetes. We compared safety and efficacy of the Cambridge hybrid closed-loop algorithm with usual care over 6 months in this population. METHODS: In a multicentre, multinational, parallel randomised controlled trial, participants aged 6-18 years using insulin pump therapy were recruited at seven UK and five US paediatric diabetes centres. Key inclusion criteria were diagnosis of type 1 diabetes for at least 12 months, insulin pump therapy for at least 3 months, and screening HbA1c levels between 53 and 86 mmol/mol (7·0-10·0%). Using block randomisation and central randomisation software, we randomly assigned participants to either closed-loop insulin delivery (closed-loop group) or to usual care with insulin pump therapy (control group) for 6 months. Randomisation was stratified at each centre by local baseline HbA1c. The Cambridge closed-loop algorithm running on a smartphone was used with either (1) a modified Medtronic 640G pump, Medtronic Guardian 3 sensor, and Medtronic prototype phone enclosure (FlorenceM configuration), or (2) a Sooil Dana RS pump and Dexcom G6 sensor (CamAPS FX configuration). The primary endpoint was change in HbA1c at 6 months combining data from both configurations. The primary analysis was done in all randomised patients (intention to treat). Trial registration ClinicalTrials.gov, NCT02925299. FINDINGS: Of 147 people initially screened, 133 participants (mean age 13·0 years [SD 2·8]; 57% female, 43% male) were randomly assigned to either the closed-loop group (n=65) or the control group (n=68). Mean baseline HbA1c was 8·2% (SD 0·7) in the closed-loop group and 8·3% (0·7) in the control group. At 6 months, HbA1c was lower in the closed-loop group than in the control group (between-group difference -3·5 mmol/mol (95% CI -6·5 to -0·5 [-0·32 percentage points, -0·59 to -0·04]; p=0·023). Closed-loop usage was low with FlorenceM due to failing phone enclosures (median 40% [IQR 26-53]), but consistently high with CamAPS FX (93% [88-96]), impacting efficacy. A total of 155 adverse events occurred after randomisation (67 in the closed-loop group, 88 in the control group), including seven severe hypoglycaemia events (four in the closed-loop group, three in the control group), two diabetic ketoacidosis events (both in the closed-loop group), and two non-treatment-related serious adverse events. There were 23 reportable hyperglycaemia events (11 in the closed-loop group, 12 in the control group), which did not meet criteria for diabetic ketoacidosis. INTERPRETATION: The Cambridge hybrid closed-loop algorithm had an acceptable safety profile, and improved glycaemic control in children and adolescents with type 1 diabetes. To ensure optimal efficacy of the closed-loop system, usage needs to be consistently high, as demonstrated with CamAPS FX. FUNDING: National Institute of Diabetes and Digestive and Kidney Diseases.
Assuntos
Diabetes Mellitus Tipo 1 , Cetoacidose Diabética , Adolescente , Algoritmos , Glicemia/análise , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Cetoacidose Diabética/induzido quimicamente , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Sistemas de Infusão de Insulina , MasculinoRESUMO
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.).
Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Controle Glicêmico/instrumentação , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Pâncreas Artificial , Algoritmos , Glicemia/análise , Criança , Pré-Escolar , Estudos Cross-Over , Desenho de Equipamento , Feminino , Hemoglobinas Glicadas/análise , Controle Glicêmico/métodos , Humanos , Hiperglicemia/diagnóstico , Lactente , MasculinoRESUMO
Background: Type 1 diabetes in young children is a heavy parental burden. As part of pilot phase of the KIDSAP01 study, we conducted a baseline assessment in parents to study the association between hypoglycemia fear, parental well-being and child behavior. Methods: All parents were invited to fill in baseline questionnaires: hypoglycemia fear survey (HFS), WHO-5, Epworth Sleepiness Scale and Strength and Difficulties Questionnaire (SDQ). Results: 24 children (median age: 5-year, range 1-7 years, 63% male, mean diabetes duration: 3 ± 1.7 years) participated. 23/24 parents filled out the questionnaires. We found a higher score for the hypoglycemia fear behavior 33.9 ± 5.6 compared to hypoglycemia worry 34.6 ± 12.2. Median WHO-5 score was 16 (8 - 22) with poor well-being in two parents. Median daytime sleepiness score was high in five parents (>10). For six children a high total behavioral difficulty score (>16) was reported. Pro social behavior score was lower than normal in six children (<6). Parental well-being was negatively associated with HFS total (r = - 0.50, p <.05) and subscale scores (r = - 0.44, p <.05 for HFS-Worry and HFS-Behavior), child behavior (r = - 0.45, p = .05) and positively with child age and diabetes duration (r = 0.58, p <.01, r = 0.6, p <.01). HFS, parental well-being nor daytime sleepiness are associated with the HbA1c. Conclusion: Regular screening of parental well-being, hypoglycemia fear and child behavior should be part of routine care to target early intervention.
Assuntos
Diabetes Mellitus Tipo 1/psicologia , Pais/psicologia , Adulto , Idade de Início , Ansiedade/epidemiologia , Ansiedade/psicologia , Criança , Comportamento Infantil/psicologia , Pré-Escolar , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/epidemiologia , Europa (Continente)/epidemiologia , Medo/psicologia , Feminino , Humanos , Hipoglicemia/prevenção & controle , Hipoglicemia/psicologia , Lactente , Insulina/administração & dosagem , Insulina/efeitos adversos , Sistemas de Infusão de Insulina , Masculino , Inquéritos e QuestionáriosRESUMO
This article reports on the lived experience of Medtronic advanced hybrid closed-loop (AHCL) in comparison to first generation hybrid closed-loop (HCL) in a randomized, open-label, two-period crossover trial. Patient-reported outcome (PROs) measures were administered before randomization and at the end of each study period in 113 adolescents and young adults with type 1 diabetes. Glucose monitoring satisfaction subscales for emotional burden and behavioral burden improved significantly (P < 0.01) over time with use of AHCL versus HCL and co-occurred with glycemic improvements (reduced percent time above 180 mg/dL during the day and no change in % time less than 54 mg/dL across 24 h) and greater time in Auto Mode. PROs, including distress, technology attitudes, and hypoglycemia confidence, were not different. AHCL use was associated with improved glucose monitoring satisfaction. Satisfaction was greater in those participants who had more appreciable glycemic benefit and stayed in Auto Mode more often. Clinical Trial Registration number: NCT03040414.
Assuntos
Automonitorização da Glicemia , Diabetes Mellitus Tipo 1 , Adolescente , Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Sistemas de Infusão de Insulina , Medidas de Resultados Relatados pelo Paciente , Adulto JovemRESUMO
INTRODUCTION: Diabetes management in very young children remains challenging. Glycaemic targets are achieved at the expense of high parental diabetes management burden and frequent hypoglycaemia, impacting quality of life for the whole family. Our objective is to assess whether automated insulin delivery can improve glycaemic control and alleviate the burden of diabetes management in this particular age group. METHODS AND ANALYSIS: The study adopts an open-label, multinational, multicentre, randomised, crossover design and aims to randomise 72 children aged 1-7 years with type 1 diabetes on insulin pump therapy. Following screening, participants will receive training on study insulin pump and study continuous glucose monitoring devices. Participants will be randomised to 16-week use of the hybrid closed-loop system (intervention period) or to 16-week use of sensor-augmented pump therapy (control period) with 1-4 weeks washout period before crossing over to the other arm. The order of the two study periods will be random. The primary endpoint is the between-group difference in time spent in the target glucose range from 3.9 to 10.0 mmol/L based on sensor glucose readings during the 16-week study periods. Analyses will be conducted on an intention-to-treat basis. Key secondary endpoints are between group differences in time spent above and below target glucose range, glycated haemoglobin and average sensor glucose. Participants' and caregivers' experiences will be evaluated using questionnaires and qualitative interviews, and sleep quality will be assessed. A health economic analysis will be performed. ETHICS AND DISSEMINATION: Ethics approval has been obtained from Cambridge East Research Ethics Committee (UK), Ethics Committees of the University of Innsbruck, the University of Vienna and the University of Graz (Austria), Ethics Committee of the Medical Faculty of the University of Leipzig (Germany) and Comité National d'Ethique de Recherche (Luxembourg). The results will be disseminated by peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03784027.
Assuntos
Glicemia , Diabetes Mellitus Tipo 1 , Áustria , Automonitorização da Glicemia , Criança , Pré-Escolar , Estudos Cross-Over , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Hipoglicemiantes/uso terapêutico , Lactente , Insulina/uso terapêutico , Sistemas de Infusão de Insulina , Luxemburgo , Estudos Multicêntricos como Assunto , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
AIM: To evaluate the use of hybrid closed-loop glucose control with faster-acting insulin aspart (Fiasp) in adults with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: In a double-blind, multinational, randomized, crossover study, 25 adults with T1D using insulin pump therapy (mean ± SD, age 38 ± 9 years, HbA1c 7.4% ± 0.8% [57 ± 8 mmol/mol]) underwent two 8-week periods of unrestricted living comparing hybrid closed-loop with Fiasp and hybrid closed-loop with standard insulin aspart in random order. During both interventions the CamAPS FX closed-loop system incorporating the Cambridge model predictive control algorithm was used. RESULTS: In an intention-to-treat analysis, the proportion of time sensor glucose was in the target range (3.9-10.0 mmol/L; primary endpoint) was not different between interventions (75% ± 8% vs. 75% ± 8% for hybrid closed-loop with Fiasp vs. hybrid closed-loop with standard insulin aspart; mean-adjusted difference -0.6% [95% CI -1.8% to 0.7%]; p < .001 for non-inferiority [non-inferiority margin 5%]). The proportion of time with sensor glucose less than 3.9 mmol/L (median [IQR] 2.4% [1.2%-3.2%] vs. 2.9% [1.7%-4.0%]; p = .01) and less than 3.0 mmol/L (median [IQR] 0.4% [0.2%-0.7%] vs. 0.7% [0.2%-0.9%]; p = .03) was reduced with Fiasp versus standard insulin aspart. There was no difference in mean glucose (8.1 ± 0.8 vs. 8.0 ± 0.8 mmol/L; p = .13) or glucose variability (SD of sensor glucose 2.9 ± 0.5 vs. 2.9 ± 0.5 mmol/L; p = .90). Total daily insulin requirements did not differ (49 ± 15 vs. 49 ± 15 units/day; p = .45). No severe hypoglycaemia or ketoacidosis occurred. CONCLUSIONS: The use of Fiasp in the CamAPS FX closed-loop system may reduce hypoglycaemia without compromising glucose control compared with standard insulin aspart in adults with T1D.