OBJECTIVE: This study investigated the onset and the choice of treatment in children with very early onset of type 1 diabetes mellitus (T1D).
METHODS: The study included 5,763 patients from the German Diabetes Patient Follow-up registry with onset of T1D in the first 4 years of life from January 2010 - June 2022. The analysis included diabetes-specific parameters, anthropometric data, and mode of treatment at onset, within the first and second year of T1D. Three groups were compared according to age at onset (G1: 223 patients 6-<12 months, G2: 1519 patients 12-<24 months, G3: 4001 patients 24-48 months).
RESULTS: In 12.3% of all cases in childhood and adolescence, the incidence of diabetes in the first 4 years of life was rare. At the onset, clinical status was worse and diabetic ketoacidosis (DKA) rates were higher in G1 and G2 (52.3% and 46.5%, respectively) compared to G3 (27.3% (p<0.001)). G1 and G2 were significantly more likely to be treated with insulin pump therapy (CSII) 2 years after onset (98.1% and 94.1%, respectively)) compared to G3 (85.8%, p<0.001). Median HbA1c after 2 years did not differ between groups (G1: 7.27% (56.0 mmol/mol), G2: 7.34% (56.7 mmol/mol) and G3: 7.27% (56.0 mmol/mol)) or when comparing CSII vs MDI. The rate of severe hypoglycemia (SH) and DKA during the first 2 years of treatment did not differ among the three groups, ranging from 1.83-2.63/100 patient-years (PY) for DKA and 9.37-24.2/100 PY for SH. Children with T1D under 4 years of age are more likely to be diagnosed with celiac disease but less likely to have thyroiditis than older children with T1DM.
CONCLUSIONS: Young children with T1D had high rates of DKA at onset and were predominantly treated with insulin pump therapy during the first 2 years. The median HbA1c for all three groups was<7.5% (58 mmol/mol) without increased risk of SH or DKA. The use of continuous glucose monitoring (CGM) was not associated with lower HbA1c in children under 48 months.

BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
UNASSIGNED: CRD42022367493; https://www.crd.york.ac.uk/PROSPERO, Principal investigator: Zhen-feng Zhou, Date of registration: October 30, 2022.

OBJECTIVE: This study aimed to investigate the short-and long-term effect on diabetic retinopathy (DR) in individuals with type 1 diabetes treated with continuous subcutaneous insulin injections (CSII) compared to those using multiple daily injections (MDI).
METHODS: We conducted a register-based matched cohort study utilizing data from the Danish Registry of Diabetic Retinopathy as well as several other national Danish health registers. Our cohort consisted of all individuals with type 1 diabetes who attended the Danish screening program for DR from 2013 to 2022. We included individuals registered with CSII treatment, and compared them to individuals using MDI, matched by age, sex, and DR level. Cox regression analysis was performed to evaluate the outcomes.
RESULTS: The study included 674 individuals treated with CSII and 2006 matched MDI users. In our cohort 53.4 % were female and median age was 36 (IQR 27-47). Average follow-up risk-time was 4.8 years. There was no difference in the risk of DR worsening between the CSII group and MDI group (HR 1.05 [95%CI 0.91; 1.22], p = 0.49). However, an increased risk of focal photocoagulation was observed in the CSII group (HR 2.40 [95%CI 1.11; 5.19], p = 0.03).
CONCLUSIONS: Our findings indicate that CSII treatment does not confer a significant difference in the overall short- and long-term risk of DR worsening or ocular intervention compared to MDI treatment. These results provide insights into the DR outcomes of CSII treatment in individuals with type 1 diabetes.

The development of advanced diabetes technology has permitted persons with type 1 diabetes mellitus to improve metabolic control significantly, particularly with the development of advanced hybrid closed-loop systems which have improved the quality of life by reducing hypoglycemia, decreasing macroangiopathy and microangiopathy-related complications, ameliorating HbA1c and improving glycemic variability. Despite the progression made over the past few decades, there is still significant margin for improvement to be made in terms of attaining appropriate metabolic control. Various factors are responsible for poor glycemic control including inappropriate carbohydrate counting, repeated bouts of hypoglycemia, hypoglycemia unawareness, cutaneous manifestations due to localized insulin use and prolonged use of diabetes technology, psychosocial comorbidities such as eating disorders or \'diabulimia\', the coexistence of insulin resistance among people with type 1 diabetes and the inability to mirror physiological endogenous pancreatic insulin secretion appropriately. Hence, the aim of this review is to highlight and overcome the barriers in attaining appropriate metabolic control among people with type 1 diabetes by driving research into adjunctive treatment for coexistent insulin resistance and developing new advanced diabetic technologies to preserve β cell function and mirror as much as possible endogenous pancreatic functions.

BACKGROUND: The purpose of this systematic review and meta-analysis was to synthesize the current literature to determine the safety and efficacy of using subcutaneous insulin compared to an intravenous (IV) insulin infusion in managing diabetic ketoacidosis (DKA).
METHODS: We searched Ovid-Medline, EMBASE, SCOPUS, BIOSIS and CENTRAL from inception to April 26, 2024. Randomized controlled trials (RCTs) and observational studies that assessed the use of subcutaneous compared to intravenous insulin for the treatment of mild to moderate DKA were included. Data extraction and quality assessment were performed by two independent reviewers and disagreements were resolved through further discussion or by a third reviewer. The Cochrane Risk of Bias tool version 2.0 was used to evaluate the RCTs and the Risk of Bias in Non-randomized Studies of Interventions (ROBINS)-I tool was used to evaluate the observational studies. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Meta-analyses were conducted using random-effects models. We followed the PRISMA guidelines for reporting our findings.
RESULTS: Six RCTs (245 participants) and four observational studies (8444 patients) met our inclusion criteria. Some studies showed a decreased length of stay (Mean Difference [MD] in days: -0.39; 95% CI: -2.83 to 2.08; I2: 0%) among individuals treated with subcutaneous insulin compared to intravenous insulin. There was no difference in the risk of all-cause mortality, time to resolution of DKA (MD in hours: 0.17; 95% confidence interval [CI]: -3.45 to 3.79; I2: 0%) and hypoglycemia (Risk Ratio [RR]: 1.02; 95% CI: 0.88 to 1.19; I2: 0%) between the two groups.
CONCLUSIONS: Treatment of DKA with subcutaneous insulin may be a safe and effective alternative to IV insulin in selected patients. The limited available evidence underscores the need for further studies to explore optimal dosing, patient selection criteria and long-term outcomes.

BACKGROUND: Use of Continuous Subcutaneous Insulin Infusion (CSII) has been shown to improve glycemic outcomes in Type 1 Diabetes (T1D), but high costs limit accessibility. To address this issue, an inter-operable, open-source Ultra-Low-Cost Insulin Pump (ULCIP) was developed and previously shown to demonstrate comparable delivery accuracy to commercial models in standardised laboratory tests. This study aims to evaluate the updated ULCIP in-vivo, assessing its viability as an affordable alternative for those who cannot afford commercially available devices.
METHODS: This first-in-human feasibility study recruited six participants with T1D. During a nine-hour inpatient stay, participants used the ULCIP under clinical supervision. Venous glucose, insulin, and β-Hydroxybutyrate were monitored to assess device performance.
RESULTS: Participants displayed expected blood glucose and blood insulin levels in response to programmed basal and bolus insulin dosing. One participant developed mild ketosis, which was treated and did not recur when a new pump reservoir was placed. All other participants maintained β-Hydroxybutyrate < 0.6 mmol/L throughout.
CONCLUSIONS: The ULCIP safely delivered insulin therapy to users in a supervised inpatient environment. Future work should focus on correcting a pump hardware issue identified in this trial and extending device capabilities for use in closed loop control. Longer-term outpatient studies are warranted.
BACKGROUND: The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12623001288617) on the 11 December 2023.

New diabetes drugs such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and glucose-dependent insulinotropic peptide/GLP-1 RAs have emerged to show hemoglobin A1c (HbA1c) reduction, weight loss, and cardiovascular benefits. Similarly, sodium-glucose cotransporter 2 inhibitors\' benefits span from HbA1c decrease to cardiovascular and renoprotective effects. Diabetes technology has expanded to include type 2 diabetes mellitus, with literature supporting its use in T2DM on any insulin regimen. Connected insulin pens and insulin delivery devices have opened new solutions to insulin users and automated insulin delivery systems have become the standard of care therapy for type 1 diabetes mellitus.

The care of pregnant individuals with type 1 diabetes mellitus has experienced significant advancements in recent years. Preconception counseling has re-emerged as a core dimension of management. Continuous glucose monitoring plays an increasingly useful and beneficial role in gestational glycemic monitoring, a practice informed by improved maternofetal outcomes. While studies have not shown that continuous subcutaneous insulin infusion is superior to multiple daily injections of insulin for glycemic control, recent work has signaled that hybrid closed-loop systems with pregnancy-specific targets could meaningfully improve glycemic control and potentially ameliorate maternofetal outcomes while reducing self-care burden.

The introduction of closed-loop systems in the pediatric population has been a revolution in the management and evolution of diabetes. However, there are not many published studies in situations in which the feeding, schedules, and activities of the children deviate from the routine for which the systems were programmed, as in the case of a summer camp for children and adolescents with diabetes, where the specific programming of this device is not well known. It was a single-center prospective preliminary study. A total of twenty-seven patients (mean age 11.9 ± 1.9 years, 40% male, duration of diabetes 6.44 ± 2.83 years) were included (twenty with Medtronic MiniMed 780G system and seven with Tandem Control-IQ). Glucometric variables and pump functionality were monitored during the 7-day camp and in the following 3 weeks. There was no decrease from the objective TIR 70% at any moment. The worst results in Time Below Range were at 72 h from starting the camp, and the worst results in Time Above Range were in the first 24 h, with a progressive improvement after that. No episodes of level 3 hypoglycemia or ketoacidosis occurred. The use of specific programming in two integrated systems, with complex blood glucose regulation algorithms and not-prepared-for situations with increased levels of physical activity or abrupt changes in feeding routines, did not result in an increased risk of level 3 hypoglycemia and ketoacidosis for our pediatric type 1 diabetes (T1D) patients, regardless of the closed-loop device.

The achievement of glycemic management is challenging in patients with diabetes on enteral nutrition, limited literature exists on hybrid closed-loop systems\' efficacy in such a situation. We described the case of a patient with type 1 diabetes treated by advanced hybrid closed loop on enteral nutrition with satisfactory glycemic management.