Hybrid Closed-loop Systems Research Articles

Simplified meal announcement study (SMASH) using hybrid closed-loop insulin delivery in youth and young adults with type 1 diabetes: a randomised controlled two-centre crossover trial.

The majority of hybrid closed-loop systems still require carbohydrate counting (CC) but the evidence for its justification remains limited. Here, we evaluated glucose control with simplified meal announcement (SMA) vs CC in youth and young adults with type 1 diabetes using the mylife CamAPS FX system. We conducted a two-centre, randomised crossover, non-inferiority trial in two University Hospitals in Switzerland in46 participants (aged 12-20 years) with type 1 diabetes using multiple daily injections (n=35), sensor-augmented pump (n=4) or hybrid closed-loop (n=7) therapy before enrolment. Participants underwent two 3 month periods with the mylife CamAPS FX system (YpsoPump, Dexcom G6) to compare SMA (individualised carbohydrate meal sizes) with CC, in a randomly assigned order using computer-generated sequences. The primary endpoint was the proportion of time glucose was in target range (3.9-10.0 mmol/l) with a non-inferiority margin of 5 percentage points. Secondary endpoints were other sensor glucose and insulin metrics, usability and safety endpoints. Forty-three participants (18 women and girls) completed the trial. In the intention-to-treat analysis, time in range (mean±SD) was 69.9±12.4% with SMA and 70.7±13.0% with CC (estimated mean difference -0.6 percentage points [95% CI -2.4, 1.1], demonstrating non-inferiority). Time <3.9 mmol/l (median [IQR] 1.8 [1.2-2.2]% vs 1.9 [1.6-2.5]%) and >10.0 mmol/l (28.2±12.6% vs 27.2±13.4%) was similar between periods. Total daily insulin dose was higher with SMA (54.0±14.7U vs 51.7±12.1U, p=0.037). Three participants experienced serious adverse events, none of which were intervention-related. Glucose control using the CamAPS FX algorithm with SMA was non-inferior to its use with CC in youth and young adults with type 1 diabetes. ClinicalTrials.gov NCT05481034. The study was supported by the Swiss Diabetes Foundation and by a YTCR grant from the Bangerter-Rhyner Foundation and the Swiss Academy of Medical Sciences. Dexcom and Ypsomed provided product support.

Efficacy and Safety of Automated Insulin Delivery Systems in Patients with Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Automated insulin delivery (AID) systems studies are upsurging, half of which were published in the last 5 years. We aimed to evaluate the efficacy and safety of AID systems in patients with type 1 diabetes mellitus (T1DM). We searched PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov until August 31, 2023. Randomized clinical trials that compared AID systems with other insulin-based treatments in patients with T1DM were considered eligible. Studies characteristics and glycemic metrics was extracted by three researchers independently. Sixty-five trials (3,623 patients) were included. The percentage of time in range (TIR) was 11.74% (95% confidence interval [CI], 9.37 to 14.12; P<0.001) higher with AID systems compared with control treatments. Patients on AID systems had more pronounced improvement of time below range when diabetes duration was more than 20 years (??.80% vs. ??.86%, P=0.031) and baseline glycosylated hemoglobin lower than 7.5% (??.93% vs. ??.87%, P=0.033). Dual-hormone full closed-loop systems revealed a greater improvement in TIR compared with hybrid closed-loop systems (??9.64% vs. ??0.87%). Notably, glycemia risk index (GRI) (??.74; 95% CI, ??.34 to ??.14; P<0.01) was also improved with AID therapy. AID systems showed significant advantages compared to other insulin-based treatments in improving glucose control represented by TIR and GRI in patients with T1DM, with more favorable effect in euglycemia by dual-hormone full closedloop systems as well as less hypoglycemia for patients who are within target for glycemic control and have longer diabetes duration.

Sampled-data control of a class of stochastic feedforward nonlinear systems with large delays and sparse sampling

This paper investigates the problem of sampled-data control for a class of stochastic nonlinear systems with delays in the input and state. It is shown that under an upper-triangular linear growth condition, a linear memoryless sampled-data feedback controller is able to globally stabilise the stochastic nonlinear time-delay systems, no matter how large the time delay and sampling period are. The memoryless sampled-data feedback controller is designed by using the emulation method together with the feedback domination technique. With the aid of Lyapunov-Krasovskii functional method, the constructed memoryless sampled-data feedback controller achieves global exponential stability (GES) in mean square of the hybrid closed-loop systems. Application of the sampled-data control scheme is demonstrated through a practical example with simulation.

Do hybrid closed loop insulin pump systems improve glycemic control and reduce hospitalizations in poorly controlled type 1 diabetes?

Hybrid closed-loop (HCL) systems improve glycemic control in type 1 diabetes mellitus (T1D), but their effectiveness in young, poorly controlled populations is notestablished and requires study. A pre-post study was performed using electronic health records of patients 3-24 years with baseline HbA1c≥9 % prescribed HCL within the New York City Health+Hospitals System assessing HbA1c levels and hospitalizations before and after HCL initiation and factors associated with achieving HbA1c<9 % after HCLinitiation. Of 47 children and adolescents who met inclusion criteria, 4.68 % female, 95.72 % non-White, and 82.22 % covered by public insurance, with a baseline average HbA1c10.6 % (2.28 IQR). The most prevalent pump type wasOmnipod 5 (70.21 %). The HbA1c was significantly lowerinthe postperiod than baseline (HbA1c before=median 10.6 (IQR2.28), HbA1c after=median 9.33 (IQR 2.97), difference 1.00 (IQR 1.64), p<0.05) with a decrease in median diabetes-related hospitalizations (preperiod 1.00 (IQR 1.00), postperiod 0.00 (IQR 1.00), difference-1.00, IQR 2, p<0.05). Lower baseline HbA1c levels made reaching HbA1c<9 % more likely. Multivariable analysis showed thatthe odds of having HbA1c of <9 % was 2.1 times less likely for every one point increase in baseline HbA1c and 12.5 times less likely for those with a pump at (p<0.05). HCL therapy improved glycemic control and decreased diabetes-related hospitalizations in youth with poorly controlled T1DM. Higher baseline HbA1c levels predicted less success with HCL therapy so those who standto benefit most benefit least.

Automated insulin delivery systems in the treatment of diabetes: Benefits, challenges, and practical considerations in pediatric patients

At present, the majority of patients with type 1 diabetes mellitus do not achieve the recommended glycemic control goals to reduce the risk of acute and chronic complications. Hybrid closed-loop systems or automated insulin infusion systems emerged as an opportunity to improve metabolic control, quality of life and reduce the psychosocial impact of type 1 diabetes. This article analyzes the evidence regarding their effectiveness and safety, the challenges they pose and best practices to optimize results when implemented in clinical practice.

Characterising impaired awareness of hypoglycaemia and associated risks through HypoA-Q: findings from a T1D Exchange cohort.

We aimed to: (1) externally validate the five-item Hypoglycaemia Awareness Questionnaire (HypoA-Q) impaired awareness subscale (HypoA-Q IA); (2) examine how impaired awareness of hypoglycaemia (IAH) relates to the risk of severe hypoglycaemia and level 2 hypoglycaemia; and (3) identify factors associated with IAH. Nationwide survey of T1D Exchange registrants was conducted to collect data on demographics, 6 month severe-hypoglycaemia history, hypoglycaemia awareness status (via HypoA-Q IA, the Gold instrument and the Clarke instrument) and continuous glucose monitor (CGM) measures. The Clarke hypoglycaemia awareness factor (Clarke-HAF) was calculated to exclude severe-hypoglycaemia history items. Analyses included Cronbach's α, Spearman correlations and logistic regression. Valid survey responses were collected from N=1580 adults with type 1 diabetes (median age, 44 years; 52% female participants; median HbA1c, 48 mmol/mol [6.5%]). Of these, 94% of participants were using CGMs and 69% were using hybrid closed-loop (HCL) systems; 30% had at least one severe-hypoglycaemia episode in the past 6 months. The HypoA-Q IA had satisfactory internal reliability (α=0.79) and construct validity. Higher HypoA-Q IA scores were independently associated with greater risk of severe hypoglycaemia (p<0.001), performing comparably to the Gold instrument and the Clarke-HAF instrument. HypoA-Q IA-determined IAH was independently associated with 88% higher odds of developing severe hypoglycaemia (p<0.001) and twofold higher odds for spending ≥1% of time in level 2 hypoglycaemia (p=0.011). Higher age and longer diabetes duration were associated with higher IAH risk (p<0.001). CGM and HCL use was associated with lower IAH risk (p<0.001). The HypoA-Q IA is a brief, valid and reliable tool for assessing IAH in today's technology-oriented era. IAH was independently associated with severe hypoglycaemia and level 2 hypoglycaemia in a cohort with high prevalence of advanced diabetes technology use and HbA1c within the recommended range. CGM and HCL use was related to lower IAH risk.

The Feasibility of an Experimental Hypobaric Simulation to Evaluate the Safety of Closed-Loop Insulin Delivery Systems in Flight-Related Atmospheric Pressure Changes.

Hybrid closed-loop (HCL) systems remain underexplored within aviation, and as atmospheric pressure changes can independently affect insulin pumps and continuous glucose monitoring readings, this preliminary study assessed the feasibility of HCL safety evaluation, in both fasting and post-prandial states, by using hypobaric chamber to simulate flights. Participants with type 1 diabetes and on HCL were studied: Medtronic Guardian 4-Medtronic 780G-SmartGuard (n = 4), Dexcom G6-Omnipod DASH-Android APS (n = 1), and Dexcom G6-Ypsomed Pump-CamAPS (n = 1). Flight cabin pressures of 550 mmHg and 750 mmHg were simulated in a hypobaric chamber. Seven-hundred-50 glucose measurements were taken, with glucose levels demonstrating a stable decline to 4 mmol/L during fasting. To maintain a tight fasting and post-prandial glucose range across the different pressure settings, the HCL administered insulin as expected. While not demonstrating any apparent issues, repeating flight simulation protocol with other systems, examining longer flights, and undertaking larger, powered randomised controlled trials can confirm their safety in aviation.

Time in range and mean glucose cut-off points for reduction of fetal outcomes in pregnant women with type 1 diabetes using automated insulin delivery systems

AimIn pregnant women with Type 1 Diabetes (T1D), achieving a lower recommended time in range (TIRp,63–140 mg/dl) could have an impact on fetal outcomes. To determine the TIRp and mean glucose cut-off point associated with better fetal outcomes in pregnant women using automated insulin delivery (AID) systems. MethodsA prospective cohort of pregnant women with T1D, using AID systems and followed-up in Latin America was analyzed. Optimal TIRp and mean glucose cut-off points for predicting large for gestational age (LGA) were determined using the Liu method. Fetal outcomes were evaluated for the identified cut-off point and the one recommended by guidelines (TIRp > 70 %). ResultsSixty-two patients were included (mean age 31.9 ± 5.9 years, HbA1c 7.57 %±1.29 %, TIRp 59.8 %±14.6 %). 27.5 % on advanced hybrid closed loop systems (AHCL). LGA (50 vs 17.9 %,p = 0.010) and hyperbilirubinemia (45 % vs 11.8 %,p = 0.016) were more common in patients with TIRp < 59.1 %. Optimal cut-off of TIRp in the second trimester for predicting LGA was < 59.1 % (sensitivity 75 %, specificity 61 %) with an AUC of 0.68(CI 0.48–0.88). Optimal cut-off for mean glucose was 133 mg/dL (sensitivity 69 %, specificity 70 %) with an AUC of 0.70(CI 0.51–0.88) in the same trimester. Better metabolic control during the third trimester was seen in the AHCL users compared to other devices. ConclusionsTIRp > 59.1 % and mean glucose < 133 mg/dl in the second trimester, is associated with lower fetal outcomes of large for gestational age. One of the strategies that would improve TIRp is the early use of AHCL systems. Further studies are needed before a strong recommendation can be made.

Use of continuous glucose monitoring and hybrid closed-loop therapy in pregnancy.

Continuous glucose monitoring (CGM) has led to a paradigm shift in the management of pregnant women with type 1 diabetes (T1D), with improved glycaemic control, less hypoglycaemia and fewer pregnancy complications. Data on CGM use in pregnant women with type 2 diabetes (T2D) are limited. A large randomized controlled trial (RCT) on CGM use in people with T2D in pregnancy is ongoing. Small studies on CGM use in women with gestational diabetes (GDM) have suggested improved glycaemic control and better qualification when insulin is needed. However, none of these studies was powered to evaluate pregnancy outcomes. Several large RCTs are ongoing in women with GDM. In addition to CGM, other technologies, such as advanced hybrid closed-loop (AHCL) systems have further improved glycaemic management in people with T1D. AHCL therapy adapts insulin delivery via a predictive algorithm integrated with CGM and an insulin pump. A large RCT with the AHCL CamAPS® FX demonstrated a 10% increase in time in range compared to standard insulin therapy in a pregnant population with T1D. Recently, an RCT of an AHCL system not approved for use in pregnancy (780G MiniMed) has also demonstrated additional benefits of AHCL therapy compared to standard insulin therapy, with improved time in range overnight, less hypoglycaemia and improved treatment satisfaction. More evidence is needed on the impact of AHCL therapy on maternal and neonatal outcomes and on which glycaemic targets with CGM should be used in pregnant women with T2D and GDM. We review the current evidence on the use of CGM and AHCL therapy in pregnancy.

Tecnología aplicada a la diabetes

Diabetes technology refers to devices and applications that people with diabetes use to help manage their disease. There are two main categories: blood glucose monitoring systems (including continuous glucose monitoring (CGM) systems) and insulin delivery devices (including insulin pumps and smart insulin pens). CGM devices measure interstitial blood glucose continuously or intermittently (flash measurements), showing alerts and trends that help predict glucose behavior. The data are represented by the ambulatory glucose profile, which provides measurements and a summary graph to aid in its interpretation. Insulin pumps or continuous subcutaneous insulin infusion systems are devices that infuse rapid-acting insulin continuously with the objective of maintaining glucose levels in range. Among these, hybrid closed loop systems are capable of adjusting insulin infusion according to CGM blood glucose figures. Smart insulin pens are linked to smartphone apps and have features that help patients manage their diabetes (dose reminder, bolus calculator, active insulin monitoring).

12-Month Time in Tight Range Improvement with Advanced Hybrid-Closed Loop System in Adults with Type1 Diabetes.

Time in tight range (TITR) is an emerging and valuable metric for assessing normoglycemia. The latest advancement in automated insulin delivery (AID) systems, the advanced hybrid closed-loop (AHCL) systems, are particularly noteworthy for managing type1 diabetes (T1D) and enhancing glycemic control. In a real-world clinical setting, we carried out a retrospective evaluation of TITR in 42 adult subjects with T1D using the AHCL Minimed™ 780G system over a 12-month period. Within just 14days of activating the automatic mode, the AHCL Minimed™ 780G system showed rapid improvement in TITR, and in the other continuous glucose monitoring (CGM) metrics. This improvement persisted over 12months, achieving the proposed 45-50% range for effective glycemic control. The AHCL Minimed™ 780G system significantly enhances TITR, demonstrating continuous improvement throughout a 12-month follow-up period.

Comparison of glycaemic control across different ethnic and socioeconomic groups in a cohort of children using hybrid closed loop systems

Comparison of glycaemic control across different ethnic and socioeconomic groups in a cohort of children using hybrid closed loop systems

Age-related outcomes of hybrid closed-loop systems in children with type 1 diabetes

Age-related outcomes of hybrid closed-loop systems in children with type 1 diabetes

Temporary Target Versus Suspended Insulin Infusion in Patients with Type 1 Diabetes Using the MiniMed 780G Advanced Closed-Loop Hybrid System During Aerobic Exercise: A Randomized Crossover Clinical Trial.

Aim: To compare the safety in terms of hypoglycemic events and continuous glucose monitoring (CGM) metrics during aerobic exercise (AE) of using temporary target (TT) versus suspension of insulin infusion (SII) in adults with type 1 diabetes (T1D) using advanced hybrid closed-loop systems. Methods: This was a randomized crossover clinical trial. Two moderate-intensity AE sessions were performed, one with TT and one with SII. Hypoglycemic events and CGM metrics were analyzed during the immediate (baseline to 59 min), early (60 min to 6 h), and late (6 to 36 h) post-exercise phases. Results: In total, 33 patients were analyzed (44.6 ± 13.8 years), basal time in range (%TIR 70-180 mg/dL) was 79.4 ± 12%, and time below range (%TBR) <70 mg/dL was 1.8 ± 1.7% and %TBR <54 mg/dL was 0.5 ± 0.9%. No difference was found in the number of hypoglycemic events, %TBR <70 mg/dL and %TBR <54 mg/dL between TT and SII. Differences were found in the early phase, with better values when using TT for %TIR 70-180 mg/dL (83.0 vs. 65.3, P = 0.005), time in tight range (%TITR 70-140 mg/dL) (56.3 vs. 41.5, P = 0.04), and time above range (%TAR >180 mg/dL) (15.3 vs. 31.8, P = 0.01). In the diurnal period, again %TIR was better for TT use (82.1 vs. 73.1, P = 0.02) and %TAR (15.0 vs. 22.96, P = 0.04). No significant differences were found in the CGM metrics during the different phases of AE. Conclusion: Our data appear to show that the use of TT compared with SII is equally safe in all phases of AE. However, the use of TT allows for a better glycemic profile in the early phase of exercise.

Efficacy and Safety of Different Hybrid Closed Loop Systems for Automated Insulin Delivery in People With Type 1 Diabetes: A Systematic Review and Network Meta-Analysis.

To compare the efficacy and safety of different hybrid closed loop (HCL) systems in people with diabetes through a network meta-analysis. We searched MEDLINE, EMBASE, CENTRAL and PubMed for randomised clinical trials (RCTs) enrolling children, adolescents and/or adults with type 1 or type 2 diabetes, evaluating Minimed 670G, Minimed 780G, Control-IQ, CamAPS Fx, DBLG-1, DBLHU, and Omnipod 5 HCL systems against other types of insulin therapy, and reporting time in target range (TIR) as outcome. A total of 28 RCTs, all enrolling people with type 1 diabetes, were included. HCL systems significantly increased TIR compared with subcutaneous insulin therapy without continuous glucose monitoring (SIT). Minimed 780G achieved the highest TIR ahead of Control IQ (mean difference (MD) 5.1%, 95% confidence interval (95% CI) [0.68; 9.52], low certainty), Minimed 670G (MD 7.48%, 95% CI [4.27; 10.7], moderate certainty), CamAPS Fx (MD 8.94%, 95% CI [4.35; 13.54], low certainty), and DBLG1 (MD 10.69%, 95% CI [5.73; 15.65], low certainty). All HCL systems decreased time below target range, with DBLG1 (MD -3.69%, 95% CI [-5.2; -2.19], high certainty), Minimed 670G (MD -2.9%, 95% CI [-3.77; -2.04], moderate certainty) and Minimed 780G (MD -2.79%, 95% CI [-3.94; -1.64], high certainty) exhibiting the largest reductions compared to SIT. The risk of severe hypoglycaemia and diabetic ketoacidosis was similar to other types of insulin therapy. We show a hierarchy of efficacy among the different HCL systems in people with type 1 diabetes, thus providing support to clinical decision-making. PROSPERO CRD42023453717.

The impact of hybrid closed loop systems on glycemic control in elderly patients with type 1 Diabetes Mellitus: a review

Diabetes mellitus is a condition that has become increasingly common in people aged 65 and over (2). It is well known that elderly people with diabetes face significant challenges in therapeutic management, such as cognitive impairment and polypharmacy, and disease management is made more complex in these patients by the variability of the conditions and comorbidities presented (5). In this context, this review aims to assess how the development of the hybrid closed-loop system can contribute to optimizing the treatment of the elderly with type 1 Diabetes Mellitus (DM1). To this end, this narrative review was carried out using studies in the Pubmed database and considering the latest recommendations published in Diabetes Care. Thus, a reduction in the frequency of hypoglycemia and better glycemic stability were observed with these new insulin infusion systems (7) (19), which allows us to conclude that the growing prevalence of DM1 among the elderly requires an adapted approach and the use of advanced technologies to ensure effective glycemic control and a better quality of life.

Excellence in the management of Advanced Hybrid Closed-Loop Systems: Lessons from the Polish cohort

BackgroundThe aim of the study was to analyze the real-world performance of MiniMed 780G (MM780G) Advanced Hybrid Closed Loop (AHCL) system users from Poland (PL) and compare it to the European region excluding Poland (EU-PL) in order to identify factors contributing to potential differences. The former achieved some of the best Time in Range (TIR) results globally using this technology. MethodsCareLink Personal data uploaded by MM780G system users from August 2020 to December 2022 were analyzed. ResultsThe Polish users (N=1304) on average reached to TIR of 79.1 ± 8.7 % (vs 73.0 ± 10.0 % for EU-PL, N=55659), a TBR<54 mg/dL of 0.6 ± 0.7 % (vs 0.4 ± 0.6 %) and a TBR<70 mg/dL of 2.9 ± 2.1 % (vs 2.1 ± 1.8 %). The adoption rate of optimal settings (i.e, GT=100 mg/dL, AIT=2hr) in PL was high (19.7 % vs 6.3 %), and filtering on optimal setting users led to less pronounced differences in glycemic control between PL and EU-PL. A univariable analysis with post-AHCL TIR showed that geography itself (PL vs EU-PL) is not a significant contributor to a high post-AHCL TIR (p = 0.15), and that much of the Polish post-AHCL TIR can be explained by the high pre-AHCL TIR. ConclusionThe Polish MM780G users achieved better glycemic control than the general European population (excluding Poland). This is largely attributable to the adoption of optimal settings in Poland and the already high glycemic outcomes at system start. As these characteristics can be implemented elsewhere, we believe this outstanding result can be obtained in other countries as well.

Applying technologies to simplify strategies for exercise in type 1 diabetes.

Challenges and fears related to managing glucose levels around planned and spontaneous exercise affect outcomes and quality of life in people living with type 1 diabetes. Advances in technology, including continuous glucose monitoring, open-loop insulin pump therapy and hybrid closed-loop (HCL) systems for exercise management in type 1 diabetes, address some of these challenges. In this review, three research or clinical experts, each living with type 1 diabetes, leverage published literature and clinical and personal experiences to translate research findings into simplified, patient-centred strategies. With an understanding of limitations in insulin pharmacokinetics, variable intra-individual responses to aerobic and anaerobic exercise, and the features of the technologies, six steps are proposed to guide clinicians in efficiently communicating simplified actions more effectively to individuals with type 1 diabetes. Fundamentally, the six steps centre on two aspects. First, regardless of insulin therapy type, and especially needed for spontaneous exercise, we provide an estimate of glucose disposal into active muscle meant to be consumed as extra carbohydrates for exercise ('ExCarbs'; a common example is 0.5 g/kg body mass per hour for adults and 1.0 g/kg body mass per hour for youth). Second, for planned exercise using open-loop pump therapy or HCL systems, we additionally recommend pre-emptive basal insulin reduction or using HCL exercise modes initiated 90 min (1-2 h) before the start of exercise until the end of exercise. Modifications for aerobic- and anaerobic-type exercise are discussed. The burden of pre-emptive basal insulin reductions and consumption of ExCarbs are the limitations of HCL systems, which may be overcome by future innovations but are unquestionably required for currently available systems.

Three months use of Hybrid Closed Loop Systems improves glycated hemoglobin levels in adolescents and children with type 1 diabetes: A meta-analysis.

Longer outpatient studies have demonstrated that hybrid closed loop (HCL) use has led to a concomitant reduction in glycated hemoglobin(HbA1c) by 0.3%-0.7%. However, reports have also indicated that HbA1c levels are not declined in the long-term use of HCL. Therefore, we wonder that 3 months use of HCL could improve glycated hemoglobin levels in adolescents and children with T1D. Relevant studies were searched electronically in the Cochrane Library, PubMed, and Embase utilizing the key words "Pediatrics or Child or Adolescent", "Insulin Infusion Systems" and "Diabetes Mellitus" from inception to 17th March 2024 to evaluate the performance of HCL on HbA1c in adolescents, and children with T1D. Nine studies involving 927 patients were identified. Three months use of HCL show a beneficial effect on HbA1c management (p <0.001) as compared to standard of care in adolescents and children with T1D, without evidence of heterogeneity between articles (I2 = 40%, p = 0.10). HCL did significantly increase the overall average percentage of hypoglycemic time between 70 and 180 mg/dL (TIR) (p <0.001; I2 = 51%). HCL did not show a beneficial effect on hypoglycemic time <70 mg/dL and <54 mg/dL (p >0.05). The overall percentage of hyperglycemic time was significantly decreased in HCL group compared to the control group when it was defined as >180 mg/dL (p <0.001; I2 = 83%), >250 mg/dL (p = 0.007, I2 = 86%) and >300 mg/dL (p = 0.005; I2 = 76%). The mean glucose level was significantly decreased by HCL (p <0.001; I2 = 58%), however, no significant difference was found in coefficient of variation of sensor glucose (p = 0.82; I2 = 71%) and daily insulin dose (p = 0.94; I2 <0.001) between the HCL group and the control group. HCL had a beneficial effect on HbA1c management and TIR without increased hypoglycemic time as compared to standard of care in adolescents and children with T1D when therapy duration of HCL was not less than three months. CRD42022367493; https://www.crd.york.ac.uk/PROSPERO, Principal investigator: Zhen-feng Zhou, Date of registration: October 30, 2022.

Advances in Type 1 Diabetes Mellitus Management in Children.

Recent advancements in the management of type 1 diabetes mellitus (T1DM) have significantly improved outcomes and quality of life for patients, particularly children. Technological innovations, such as continuous glucose monitoring (CGM) systems and insulin pump therapy, including hybrid closed-loop systems, have enhanced glycemic control by providing real-time data and automated insulin delivery. Ultrarapid-acting insulins and adjunctive pharmacotherapies, like sodium-glucose transport protein 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists, offer improved postprandial glucose management and reduced insulin requirements. Immunotherapy and beta-cell replacement therapies, including stem cell research and encapsulation devices, aim to preserve or restore endogenous insulin production. Digital health platforms and telemedicine have expanded access to education and support, fostering better self-management. Future directions in precision medicine, artificial intelligence, and microbiome research hold promise for personalized and potentially curative treatments. Collectively, these advances are transforming T1DM management, reducing disease burden, and enhancing the prospects for children with T1DM.