Summary of Research: Efficacy and Safety of the SGLT2 Inhibitor Empagliflozin Versus Placebo and the DPP-4 Inhibitor Linagliptin Versus Placebo in Young People with Type 2 Diabetes (DINAMO): A Multicentre, Randomised, Double-Blind, Parallel Group, Phase 3 Trial.

The increasing occurrence of childhood overweight and obesity has been followed by a substantial increase in youth-onset type 2 diabetes (T2D). Pharmacological treatment options for youth-onset T2D remain limited, with a clear unmet need for additional oral agents. This summary of research reports on the efficacy and safety of empagliflozin and linagliptin on glycaemic control in children and adolescents aged 10-17 years with T2D in the randomised, double-blind, parallel group, phase 3 DINAMO trial. Empagliflozin provided a clinically relevant, statistically significant, and durable improvement in glycaemic control; however, linagliptin did not. The safety profile of both empagliflozin and linagliptin was comparable to those observed in studies in adults. These results suggest that empagliflozin could be a new oral therapy option for youth-onset T2D.

Growth Hormone Mediators and Glycemic Control in Youths With Type 2 Diabetes: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Youth-onset type 2 diabetes (T2D) has a more aggressive phenotype than adult-onset T2D, including rapid loss of glycemic control and increased complication risk. Objective: To identify associations of growth hormone mediators with glycemic failure, beta cell function, and insulin sensitivity in youth-onset T2D. Design, Setting, and Participants: This post hoc secondary analysis of the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) randomized clinical trial, which enrolled participants from July 2004 to February 2009, included 398 participants from 15 university-affiliated medical centers with available plasma samples from baseline and 36 months. Participants were youths aged 10 to 17 years with a duration of T2D of less than 2 years who were randomized to metformin, metformin plus lifestyle intervention, or metformin plus rosiglitazone. Participants were followed up for a mean (SD) of 3.9 (1.5) years during the trial, ending in 2011. Statistical analysis was performed from August 2022 to November 2023. Exposure: Plasma insulin-like growth factor-1 (IGF-1), growth hormone receptor (GHR), and insulin-like growth factor binding protein 1 (IGFBP-1). Main Outcomes and Measures: Main outcomes were (1) loss of glycemic control during the TODAY study, defined as hemoglobin A1c (HbA1c) level of 8% or more for 6 months or inability to wean from insulin therapy, and (2) baseline and 36-month measures of glycemia (fasting glucose, HbA1c), insulin sensitivity (1/fasting C-peptide), high-molecular-weight adiponectin, and beta cell function (C-peptide index, C-peptide oral disposition index). Results: This analysis included 398 participants (mean [SD] age, 13.9 [2.0] years; 248 girls [62%]; 166 Hispanic participants [42%]; 134 non-Hispanic Black participants [34%], and 84 non-Hispanic White participants [21%]). A greater increase in IGF-1 level between baseline and 36 months was associated with lower odds of glycemic failure (odds ratio [OR], 0.995 [95% CI, 0.991-0.997]; P < .001) and higher C-peptide index per 100-ng/mL increase in IGF-1 (ß [SE], 0.015 [0.003]; P < .001). A greater increase in log2 GHR level between baseline and 36 months was associated with higher odds of glycemic failure (OR, 1.75 [95% CI, 1.05-2.99]; P = .04) and lower C-peptide index (ß [SE], -0.02 [0.006]; P < .001). A greater increase in log2 IGFBP-1 level between baseline and 36 months was associated with higher odds of glycemic failure (OR, 1.37 [95% CI, 1.09-1.74]; P = .007) and higher high-molecular-weight adiponectin (ß [SE], 431 [156]; P = .007). Conclusions and Relevance: This study suggests that changes in plasma growth hormone mediators are associated with loss of glycemic control in youth-onset T2D, with IGF-1 associated with lower risk and GHR and IGFBP-1 associated with increased risk. Trial Registration: ClinicalTrials.gov Identifier: NCT00081328.

Genetic architecture and biology of youth-onset type 2 diabetes.

The prevalence of youth-onset type 2 diabetes (T2D) and childhood obesity has been rising steadily1, producing a growing public health concern1 that disproportionately affects minority groups2. The genetic basis of youth-onset T2D and its relationship to other forms of diabetes are unclear3. Here we report a detailed genetic characterization of youth-onset T2D by analysing exome sequences and common variant associations for 3,005 individuals with youth-onset T2D and 9,777 adult control participants matched for ancestry, including both males and females. We identify monogenic diabetes variants in 2.4% of individuals and three exome-wide significant (P < 2.6 × 10-6) gene-level associations (HNF1A, MC4R, ATXN2L). Furthermore, we report rare variant association enrichments within 25 gene sets related to obesity, monogenic diabetes and ß-cell function. Many youth-onset T2D associations are shared with adult-onset T2D, but genetic risk factors of all frequencies-and rare variants in particular-are enriched within youth-onset T2D cases (5.0-fold increase in the rare variant and 3.4-fold increase in common variant genetic liability relative to adult-onset cases). The clinical presentation of participants with youth-onset T2D is influenced in part by the frequency of genetic risk factors within each individual. These findings portray youth-onset T2D as a heterogeneous disease situated on a spectrum between monogenic diabetes and adult-onset T2D.

Glycemic Outcomes Persist for up to 2 Years in Very Young Children with the Omnipod® 5 Automated Insulin Delivery System.

Background: To evaluate the long-term safety and effectiveness of the Omnipod® 5 Automated Insulin Delivery (AID) System in very young children with type 1 diabetes with up to 2 years of use. Methods: Following a 13-week single-arm, multicenter, pivotal trial that took place after 14 days of standard therapy data collection, participating children (2-5.9 years of age at study enrollment) were provided the option to continue use of the AID system in an extension phase. HbA1c was measured every 3 months, up to 15 months of total use, and continuous glucose monitor metrics were collected through the completion of the extension study (for up to 2 years). Results: Participants (N = 80) completed 18.2 [17.4, 23.4] (median [interquartile range]) total months of AID, inclusive of the 3-month pivotal trial. During the pivotal trial, HbA1c decreased from 7.4% ± 1.0% (57 ± 10.9 mmol/mol) to 6.9% ± 0.7% (52 ± 7.7 mmol/mol, P < 0.0001) and was maintained at 7.0% ± 0.7% (53 ± 7.7 mmol/mol) after 15 months total use (P < 0.0001 from baseline). Time in target range (70-180 mg/dL) increased from 57.2% ± 15.3% during standard therapy to 68.1% ± 9.0% during the pivotal trial (P < 0.0001) and was maintained at 67.2% ± 9.3% during the extension phase (P < 0.0001 from standard therapy). Participants spent a median 97.1% of time in Automated Mode during the extension phase, with one episode of severe hypoglycemia and one episode of diabetic ketoacidosis. Conclusion: This evaluation of the Omnipod 5 AID System indicates that long-term use can safely maintain improvements in glycemic outcomes with up to 2 years of use in very young children with type 1 diabetes. Clinical Trials Registration Number: NCT04476472.

Effects of Macronutrient Intake and Number of Meals on Glycemic Outcomes Over 1 Year in Youth with Type 1 Diabetes.

Objective: Insulin bolus doses derive from glucose levels and planned carbohydrate intake, although fat and protein impact glycemic excursions. We examined the impact of macronutrients and number of daily meals/snacks on glycemic outcomes in youth with type 1 diabetes. Methods: Youth (N = 136, ages 8-17) with type 1 diabetes completed 3-day food records, wore 3-day masked continuous glucose monitoring, and had A1c measurements every 3 months for 1 year. Diet data were analyzed using Nutrition Data System for Research. Longitudinal mixed models assessed effects of macronutrient intake and number of meals/snacks on glycemic outcomes. Results: At baseline, youth (48% male) had mean age of 12.8 ± 2.5 years and diabetes duration of 5.9 ± 3.1 years; 73% used insulin pumps. Baseline A1c was 8.1% ± 1.0%, percent time in range 70-180 mg/dL (%TIR) was 49% ± 17%, % time below range <70 mg/dL (%TBR) was 6% ± 8%, % time above range >180 mg/dL (%TAR) was 44% ± 20%, and glycemic variability as coefficient of variation (CV) was 41% ± 8%; macronutrient intake included 48% ± 5% carbohydrate, 36% ± 5% fat, and 16% ± 2% protein. Most youth (56%) reported 3-4 meals/snacks daily (range 1-9). Over 1 year, greater carbohydrate intake was associated with lower A1c (P = 0.0003), more %TBR (P = 0.0006), less %TAR (P = 0.002), and higher CV (P = 0.03). Greater fat intake was associated with higher A1c (P = 0.006), less %TBR (P = 0.002), and more %TAR (P = 0.005). Greater protein intake was associated with higher A1c (P = 0.01). More daily meals/snacks were associated with lower A1c (P = 0.001), higher %TIR (P = 0.0006), and less %TAR (P = 0.0001). Conclusions: Both fat and protein impact glycemic outcomes. Future automated insulin delivery systems should consider all macronutrients for timely insulin provision. The present research study derived from secondary analysis of the study registered under NCT00999375.

Severe Hypoglycemia and Impaired Awareness of Hypoglycemia Persist in People With Type 1 Diabetes Despite Use of Diabetes Technology: Results From a Cross-Sectional Survey.

OBJECTIVE: To determine how diabetes technologies, including continuous glucose monitoring (CGM) and automated insulin delivery (AID) systems, impact glycemic metrics, prevalence of severe hypoglycemic events (SHEs), and impaired awareness of hypoglycemia (IAH) in people with type 1 diabetes in a real-world setting within the U.S. RESEARCH DESIGN AND METHODS: In this retrospective, observational study with cross-sectional elements, participants aged ≥18 years were enrolled from the T1D Exchange Registry/online community. Participants completed a one-time online survey describing glycemic metrics, SHEs, and IAH. The primary objective was to determine the proportions of participants who reported achieving glycemic targets (assessed according to self-reported hemoglobin A1c) and had SHEs and/or IAH. We performed additional subgroup analyses focusing on the impact of CGM and insulin delivery modality. RESULTS: A total of 2,074 individuals with type 1 diabetes were enrolled (mean ± SD age 43.0 ± 15.6 years and duration of type 1 diabetes 26.3 ± 15.3 years). The majority of participants (91.7%) were using CGM, with one-half (50.8%) incorporating AID. Despite high use of diabetes technologies, only 57.7% reported achieving glycemic targets (hemoglobin A1c <7%). SHEs and IAH still occurred, with ∼20% of respondents experiencing at least one SHE within the prior 12 months and 30.7% (95% CI 28.7, 32.7) reporting IAH, regardless of CGM or AID use. CONCLUSIONS: Despite use of advanced diabetes technologies, a high proportion of people with type 1 diabetes do not achieve glycemic targets and continue to experience SHEs and IAH, suggesting an ongoing need for improved treatment strategies.

Two Years with a Tubeless Automated Insulin Delivery System: A Single-Arm Multicenter Trial in Children, Adolescents, and Adults with Type 1 Diabetes.

Background: The Omnipod® 5 Automated Insulin Delivery (AID) System was shown to be safe and effective following 3 months of use in people with type 1 diabetes (T1D); however, data on the durability of these results are limited. This study evaluated the long-term safety and effectiveness of Omnipod 5 use in people with T1D during up to 2 years of use. Materials and Methods: After a 3-month single-arm, multicenter, pivotal trial in children (6-13.9 years) and adolescents/adults (14-70 years), participants could continue system use in an extension phase. HbA1c was measured every 3 months for up to 15 months; continuous glucose monitor metrics were collected for up to 2 years. Results: Participants (N = 224) completed median (interquartile range) 22.3 (21.7, 22.7) months of AID. HbA1c was reduced in the pivotal trial from 7.7% ± 0.9% in children and 7.2% ± 0.9% in adolescents/adults to 7.0% ± 0.6% and 6.8% ± 0.7%, respectively, (P < 0.0001), and was maintained at 7.2% ± 0.7% and 6.9% ± 0.6% after 15 months (P < 0.0001 from baseline). Time in target range (70-180 mg/dL) increased from 52.4% ± 15.6% in children and 63.6% ± 16.5% in adolescents/adults at baseline to 67.9% ± 8.0% and 73.8% ± 10.8%, respectively, during the pivotal trial (P < 0.0001) and was maintained at 65.9% ± 8.9% and 72.9% ± 11.3% during the extension (P < 0.0001 from baseline). One episode of diabetic ketoacidosis and seven episodes of severe hypoglycemia occurred during the extension. Children and adolescents/adults spent median 96.1% and 96.3% of time in Automated Mode, respectively. Conclusion: Our study supports that long-term use of the Omnipod 5 AID System can safely maintain improvements in glycemic outcomes for up to 2 years of use in people with T1D. Clinical Trials Registration Number: NCT04196140.

Ketone-Based Alert System for Insulin Pump Failures.

BACKGROUND: An increasing number of individuals with type 1 diabetes (T1D) manage glycemia with insulin pumps containing short-acting insulin. If insulin delivery is interrupted for even a few hours due to pump or infusion site malfunction, the resulting insulin deficiency can rapidly initiate ketogenesis and diabetic ketoacidosis (DKA). METHODS: To detect an event of accidental cessation of insulin delivery, we propose the design of ketone-based alert system (K-AS). This system relies on an extended Kalman filter based on plasma 3-beta-hydroxybutyrate (BOHB) measurements to estimate the disturbance acting on the insulin infusion/injection input. The alert system is based on a novel physiological model capable of simulating the ketone body turnover in response to a change in plasma insulin levels. Simulated plasma BOHB levels were compared with plasma BOHB levels available in the literature. We evaluated the performance of the K-AS on 10 in silico subjects using the S2014 UVA/Padova simulator for two different scenarios. RESULTS: The K-AS achieves an average detection time of 84 and 55.5 minutes in fasting and postprandial conditions, respectively, which compares favorably and improves against a detection time of 193 and 120 minutes, respectively, based on the current guidelines. CONCLUSIONS: The K-AS leverages the rapid rate of increase of plasma BOHB to achieve short detection time in order to prevent BOHB levels from rising to dangerous levels, without any false-positive alarms. Moreover, the proposed novel insulin-BOHB model will allow us to understand the efficacy of treatment without compromising patient safety.

Utility and precision evidence of technology in the treatment of type 1 diabetes: a systematic review.

BACKGROUND: The greatest change in the treatment of people living with type 1 diabetes in the last decade has been the explosion of technology assisting in all aspects of diabetes therapy, from glucose monitoring to insulin delivery and decision making. As such, the aim of our systematic review was to assess the utility of these technologies as well as identify any precision medicine-directed findings to personalize care. METHODS: Screening of 835 peer-reviewed articles was followed by systematic review of 70 of them (focusing on randomized trials and extension studies with ≥50 participants from the past 10 years). RESULTS: We find that novel technologies, ranging from continuous glucose monitoring systems, insulin pumps and decision support tools to the most advanced hybrid closed loop systems, improve important measures like HbA1c, time in range, and glycemic variability, while reducing hypoglycemia risk. Several studies included person-reported outcomes, allowing assessment of the burden or benefit of the technology in the lives of those with type 1 diabetes, demonstrating positive results or, at a minimum, no increase in self-care burden compared with standard care. Important limitations of the trials to date are their small size, the scarcity of pre-planned or powered analyses in sub-populations such as children, racial/ethnic minorities, people with advanced complications, and variations in baseline glycemic levels. In addition, confounders including education with device initiation, concomitant behavioral modifications, and frequent contact with the healthcare team are rarely described in enough detail to assess their impact. CONCLUSIONS: Our review highlights the potential of technology in the treatment of people living with type 1 diabetes and provides suggestions for optimization of outcomes and areas of further study for precision medicine-directed technology use in type 1 diabetes.

In the last decade, there have been significant advances in how technology is used in the treatment of people living with type 1 diabetes. These technologies primarily aim to help manage blood sugar levels. Here, we reviewed research published over the last decade to evaluate the impact of such technologies on type 1 diabetes treatment. We find that various types of novel technologies, such as devices to monitor blood sugar levels continuously or deliver insulin, improve important diabetes-related measures and can reduce the risk of having low blood sugar levels. Importantly, several studies showed a positive impact of technologies on quality of life in people living with diabetes. Our findings highlight the benefits of novel technologies in the treatment of type 1 diabetes and identify areas for further research to optimize and personalize diabetes care.

School Nurses' Comfort With Diabetes Management and Technology From 2012 to 2019.

Objective: School nurses are integral to optimizing diabetes management for students with type 1 diabetes. The aim of this study was to describe the use of diabetes technology in schools over time and assess school nurses' comfort level performing diabetes management tasks. Study design: From 2012 to 2019, school nurses who attended a diabetes education program completed a survey about their experience and comfort level with diabetes management. Results: A total of 1,796 school nurses completed the survey; 56% had at least 5 years of school nursing experience. Most (86%) had at least one student with type 1 diabetes. Among school nurses with at least one student with type 1 diabetes, 73% had at least one student using insulin pump therapy, and 48% had at least one student using continuous glucose monitoring (CGM). There was no change in pump use over time, but the percentage of nurses who had a student using CGM increased significantly from 24% in 2012 to 86% in 2019 (P <0.001). School nurses' comfort level using pumps remained stable over time. Overall, 47% reported being mostly/very comfortable giving boluses using a pump, and 17% reported being mostly/very comfortable troubleshooting problems with a pump. However, there was a significant increase in school nurses reporting feeling mostly/very comfortable working with CGM devices, increasing from 9% in 2012 to 44% in 2019 (P <0.001). Conclusion: School nurses are an important part of diabetes management for school-aged youth with type 1 diabetes. There is a need for additional diabetes education and support to build their confidence with diabetes management and technology, especially with further technological advancements in management.

New-Onset Type 1 Diabetes in a Child With Diabetic Ketoacidosis and Severe Hypertriglyceridemia Without Pancreatitis.

Hypertriglyceridemia is a complication of diabetic ketoacidosis (DKA) secondary to insulin deficiency inhibiting lipoprotein lipase and increasing lipolysis, but it is rare in children. A 7-year-old boy with history of autism spectrum disorder (ASD) presented with abdominal pain, vomiting, and "heavy breathing." Initial laboratory tests revealed pH 6.87 and glucose 385 mg/dL (21.4 mmol/L), consistent with new-onset diabetes and DKA. His blood appeared lipemic; triglycerides were 17 675 mg/dL (199.6 mmol/L) with normal lipase (10 units/L). He received intravenous insulin and DKA resolved within 24 hours. Insulin infusion continued through day 6 for management of hypertriglyceridemia; triglycerides decreased to 1290 mg/dL (14.6 mmol/L) during this period. He never developed pancreatitis (lipase peaked at 68 units/L) or required plasmapheresis. With his ASD history, he had a restrictive diet high in saturated fat, which included up to 30 breakfast sausages daily. His triglycerides normalized after discharge. Severe hypertriglyceridemia can complicate DKA in newly diagnosed type 1 diabetes (T1D). Hypertriglyceridemia can be safely managed with insulin infusion in the absence of end-organ dysfunction. This complication should be considered in patients with DKA at diagnosis of T1D.

Twelve-month psychosocial outcomes of continuous glucose monitoring with behavioural support in parents of young children with type 1 diabetes.

AIM: Managing type 1 diabetes in young children can cause significant stress for parents. Continuous glucose monitoring (CGM) may reduce parental burden. The Strategies to Enhance CGM Use in Early Childhood (SENCE) trial randomized parents of children (ages 2 to <8 years) with type 1 diabetes to CGM with family behavioural intervention (CGM + FBI), CGM alone (Standard-CGM) or blood glucose monitoring for 26 weeks before receiving CGM + FBI (BGM-Crossover). This report assesses changes in psychosocial outcomes for all groups over 52 weeks. METHODS: CGM + FBI (n = 45), Standard-CGM (n = 42) and BGM-Crossover (n = 44) participants completed psychosocial assessments at baseline, 26 weeks and 52 weeks. Repeated measures linear regression models evaluated change within and between treatment groups. RESULTS: The BGM-Crossover group reported improved diabetes burden (Δ -6.9, 95% CI [-11.3, -2.6], p = 0.003), fear of hypoglycaemia (Δ -6.4, CI [-10.1, -2.6], p = 0.002) and technology satisfaction (Δ 7.3, CI [2.4, 12.2], p = 0.005) from 26 to 52 weeks, similar to published findings in the CGM + FBI group over the first 26 weeks. The Standard-CGM group reported increased technology satisfaction (Δ 7.3, CI [0.6, 14.0], p = 0.027) from baseline to 52 weeks. The CGM + FBI group reported less diabetes burden and fear of hypoglycaemia from baseline to 52 weeks, but changes were not statistically significant. Scores from 26 to 52 weeks did not deteriorate. CONCLUSIONS: Parents demonstrated psychosocial benefits following FBI that appeared to maintain without additional intervention. CGM-focused education with behavioural support likely helps parents of young children with type 1 diabetes reduce burden and worry in the short- and long-term.

Updated Psychosocial Surveys With Continuous Glucose Monitoring Items for Youth With Type 1 Diabetes and Their Caregivers.

AIM: We added items relevant to continuous glucose monitoring (CGM) to the Diabetes Family Conflict Scale (DFC), Diabetes Family Responsibility Questionnaire (DFR), and Blood Glucose Monitoring Communication Questionnaire (GMC) and evaluated the psychometric properties of the updated surveys. RESEARCH DESIGN AND METHODS: Youth with type 1 diabetes who recently started CGM and their parents completed the updated surveys and additional psychosocial surveys. Medical data were collected from self-reports and review of the medical record. RESULTS: Youth (N = 114, 49% adolescent girls) were aged 13.3 ± 2.7 years and had mean glycated hemoglobin (HbA1c) 7.9 ± 0.9%; 87% of them used pump therapy. The updated surveys demonstrated high internal consistency (DFC youth: α = .91, parent: α = .81; DFR youth: α = .88, parent: α = .93; and GMC youth: α = .88, parent: α = .86). Higher youth and parent DFC scores (more diabetes-specific family conflict) and GMC scores (more negative affect related to glucose monitoring) were associated with more youth and parent depressive symptoms (r = 0.28-0.60, P ≤ .003), more diabetes burden (r = 0.31-0.71, P ≤ .0009), more state anxiety (r = 0.24 to r = 0.46, P ≤ .01), and lower youth quality of life (r = -0.29 to -0.50, P ≤ .002). Higher youth and parent DFR scores (more parent involvement in diabetes management) were associated with younger youth age (youth: r = -0.76, P < .0001; parent: r = -0.81, P < .0001) and more frequent blood glucose monitoring (youth: r = 0.27, P = .003; parent: r = 0.35, P = .0002). CONCLUSIONS: The updated DFC, DFR, and GMC surveys maintain good psychometric properties. The addition of CGM items expands the relevance of these surveys for youth with type 1 diabetes who are using CGM and other diabetes technologies.

Efficacy and safety of the SGLT2 inhibitor empagliflozin versus placebo and the DPP-4 inhibitor linagliptin versus placebo in young people with type 2 diabetes (DINAMO): a multicentre, randomised, double-blind, parallel group, phase 3 trial.

BACKGROUND: The incidence of type 2 diabetes in young people is increasing, but treatments remain limited. We aimed to assess the efficacy and safety of an empagliflozin dosing regimen versus placebo and linagliptin versus placebo on glycaemic control in young people with type 2 diabetes. METHODS: In this double-blind, placebo-controlled trial done in 108 centres in 15 countries, participants with type 2 diabetes (aged 10-17 years; HbA1c 6·5-10·5% [48-91 mmol/mol]) who had been previously treated with metformin or insulin were randomly assigned (1:1:1) to oral empagliflozin 10 mg, oral linagliptin 5 mg, or placebo. Participants in the empagliflozin group who did not have HbA1c below 7·0% (<53 mmol/mol) by week 12 underwent a second double-blinded randomisation (1:1) at week 14, either remaining on 10 mg or increasing to 25 mg. Participants in the placebo group were randomly reassigned (1:1:1) in a double-blinded manner at week 26 to linagliptin 5 mg or one of the empagliflozin doses (10 mg or 25 mg). Investigators were masked throughout the trial and received assignments of blinded medication kits through interactive response technology for all participants at the initial randomisation and for the re-randomisations at weeks 14 and 26. The primary outcome was change from baseline in HbA1c at 26 weeks. For empagliflozin, results were based on a pooled analysis for all participants on empagliflozin. Safety was assessed until week 52. This trial is registered with ClinicalTrials.gov, NCT03429543. FINDINGS: Between April 26, 2018, and May 26, 2022, of 262 screened participants, 158 (60%) were randomly assigned to treatment (53 [34%] to placebo, 52 [33%] to empagliflozin 10 mg, and 53 [34%] to linagliptin). For the primary outcome, the adjusted mean HbA1c change from baseline at week 26 was -0·84% [-9·2 mmol/mol] in the empagliflozin pooled group versus placebo (95% CI -1·50 to -0·19 [-16·4 to -2·1]; p=0·012); the corresponding change from baseline for linagliptin versus placebo was -0·34% [-3·8 mmol/mol; 95% CI -0·99 to 0·30 [-10·8 to 3·3]; p=0·29). Adverse events occurred in 34 (64%) participants in the placebo group, 40 (77%) in the empagliflozin pooled group, and 37 (71%) in the linagliptin group, up to week 26. Of these, severe adverse events were reported in two (4%) participants in the placebo group, one (2%) in the empagliflozin pooled group, and one (2%) in the linagliptin group. Hypoglycaemia was the most frequently reported adverse event with higher rates for those on active drug treatment compared with placebo. No severe hypoglycaemia cases were reported. INTERPRETATION: Empagliflozin provided clinically relevant placebo-corrected reductions in HbA1c, whereas linagliptin did not, and might offer a new treatment option for young people with type 2 diabetes. FUNDING: The Boehringer Ingelheim and Eli Lilly and Company Alliance.

Associations of Executive Function With Diabetes Management and Glycemic Control in Adolescents With Type 1 Diabetes.

Aims: The aims of this study were to assess domains of executive function in relation to diabetes management and glycemic control in adolescents with type 1 diabetes and to compare adolescent self-report and parent proxy-report of adolescent executive function. Methods: Adolescents with type 1 diabetes (N = 169, 46% female, age 15.9 ± 1.3 years) and their parents completed self-report and parent proxy-report versions of the Behavior Rating Inventory of Executive Function (BRIEF). Results: Self-report and parent proxy-report BRIEF T scores were moderately to strongly correlated; parent proxy scores were significantly higher than self-report scores. Executive function problems (Global Executive Composite T score ≥60) occurred in 9% of adolescents by self-report and 26% by parent proxy-report. For almost all Metacognition Index scales, elevated (T score ≥60) parent proxy scores were associated with lower adherence, lower adolescent diabetes self-efficacy, and more parent involvement in diabetes management. Elevated scores on several Metacognition Index scales were associated with less pump use (Plan/Organize by self-report, Initiate by parent proxy-report, and Monitor by parent proxy-report) and higher A1C (Plan/Organize by self-report and parent proxy-report and Organization of Materials by parent proxy-report). The only significant associations for the Behavioral Regulation Index scales occurred for adherence (by parent proxy-report) and diabetes self-efficacy (by self-report and parent-report). Conclusion: Adolescents with type 1 diabetes who have problems with metacognition may need additional support for diabetes self-management.

Observed Characteristics Associated with Diabetes Device Use Among Teens with Type 1 Diabetes.

BACKGROUND: Despite advancements in diabetes technologies, disparities remain with respect to diabetes device use in youth with type 1 diabetes (T1D). We compared sociodemographic, diabetes, and psychosocial characteristics associated with device (pump and continuous glucose monitor [CGM]) use in 13- to 17-year-old teens with T1D. MATERIALS/METHODS: Data were derived from a multicenter clinical trial to optimize self-care and glycemic control in teens with T1D. We categorized teens as pump users versus non-users and CGM users versus non-users based on their diabetes device usage. Chi-square and t-tests compared characteristics according to device use. RESULTS: The sample comprised 301 teens (50% female) with baseline mean ± SD age 15.0 ± 1.3 years, T1D duration 6.5 ± 3.7 years, and HbA1c 8.5 ± 1.1% (69 ± 12 mmol/mol). Two-thirds (65%) were pump users, and 27% were CGM users. Pump users and CGM users (vs. non-users) were more likely to have a family annual household income ≥$150,000, private health insurance, and a parent with a college education (all P < .001). Pump users and CGM users (vs. non-users) also performed more frequent daily blood glucose (BG) checks (both P < .001) and reported more diabetes self-care behaviors (both P < .05). Pump users were less likely to have baseline HbA1c ≥9% (75 mmol/mol) (P = .005) and to report fewer depressive symptoms (P = .02) than pump non-users. Parents of both CGM and pump users reported a higher quality of life in their youth (P < .05). CONCLUSION: There were many sociodemographic, diabetes-specific, and psychosocial factors associated with device use. Modifiable factors can serve as the target for clinical interventions; youth with non-modifiable factors can receive extra support to overcome potential barriers to device use.

Accuracy of a Seventh-Generation Continuous Glucose Monitoring System in Children and Adolescents With Type 1 Diabetes.

BACKGROUND: Accuracy of a seventh-generation "G7" continuous glucose monitoring (CGM) system was evaluated in children and adolescents with type 1 diabetes (T1D). METHODS: Sensors were worn on the upper arm and abdomen. The CGM data were available from 127 of 132 participants, ages 7 to 17 years, across 10.5 days of use, various glucose concentration ranges, and various rates of glucose change for comparisons with temporally matched venous blood glucose measurements (YSI). Data were also available from 28 of 32 participants, ages 2 to 6 years, for whom capillary (fingerstick) blood provided comparator glucose values. Accuracy metrics included the mean absolute relative difference (MARD) between CGM and comparator glucose pairs, the proportion of CGM values within 15 mg/dL or 15% of comparator values <100 or ≥100 mg/dL, respectively, and the analogous %20/20 and %30/30 agreement rates. RESULTS: For participants aged 7 to 17, a total of 15 437 matched pairs were obtained from 122 arm-placed and 118 abdomen-placed sensors. For arm-placed sensors, the overall MARD was 8.1% and overall %15/15, %20/20, and %30/30 agreement rates were 88.8%, 95.3%, and 98.7%, respectively. For abdomen-placed sensors, the overall MARD was 9.0% and overall %15/15, %20/20, and %30/30 agreement rates were 86.0%, 92.9%, and 97.7%, respectively. Good accuracy was maintained across wear days, glucose ranges, and rates of glucose change. Among those aged 2 to 6, a total of 343 matched pairs provided an overall MARD of 9.3% and an overall %20/20 agreement rate of 91.5%. CONCLUSIONS: The G7 CGM placed on the arm or abdomen was accurate in children and adolescents with T1D. NCT#: NCT04794478.