Once-weekly insulin efsitora alfa versus once-daily insulin degludec in adults with type 1 diabetes (QWINT-5): a phase 3 randomised non-inferiority trial.

BACKGROUND: Insulin efsitora alfa (efsitora) is a once-weekly basal insulin. This phase 3 study aimed to assess the efficacy and safety of efsitora compared with insulin degludec (degludec) in adults with type 1 diabetes. METHODS: This randomised, 52-week, parallel-design, open-label, treat-to-target non-inferiority study conducted at 82 global health-care centres, randomly assigned (1:1) adults (ie, those aged ≥18 years) with type 1 diabetes glycated haemoglobin A1c (HbA1c) 7·0-10·0% (53·0-85·8 mmol/mol) to efsitora (n=343) or, degludec (n=349), both in combination with insulin lispro. The primary endpoint was the change in HbA1c from baseline to week-26 (non-inferiority margin=0·4%). The trial was registered at ClinicalTrials.gov (NCT05463744) and is completed. FINDINGS: Between Aug 12, 2022, and May 7, 2024, of 893 participants enrolled, 692 (77%) participants were randomly assigned to once-weekly efsitora or once-daily degludec, and 623 (90%) participants completed the study. Mean HbA1c decreased from 7·88% (62·66 mmol/mol) at baseline to 7·41% (57·5 mmol/mol) at week 26 with efsitora and from 7·94% (63·3 mmol/mol) at baseline to 7·36% (56·9 mmol/mol) at week 26 with degludec. Mean HbA1c change from baseline to week 26 was -0·51% with efsitora and -0·56% with degludec (estimated treatment difference 0·052%, 95% CI -0·077 to 0·181; p=0·43), confirming a non-inferiority margin of 0·4% for efsitora compared with degludec. Rates of combined level 2 (<54 mg/dL [3·0 mmol/L]) or level 3 severe hypoglycaemia were higher with efsitora compared with degludec (14·03 vs 11·59 events per patient year of exposure; estimated rate ratio 1·21, 95% CI 1·04 to 1·41; p=0·016) during weeks 0-52, with the highest rates during weeks 0-12. Severe hypoglycaemia incidence was higher with efsitora (35 [10%] of 343) versus degludec (11 [3%] of 349) during weeks 0-52. Overall incidence of treatment-emergent adverse events was similar across treatment groups. One death not related to the study treatment occurred in the degludec group. INTERPRETATION: In adults with type 1 diabetes, once-weekly efsitora showed non-inferior HbA1c reduction compared with daily insulin degludec. Higher rates of combined level 2 or level 3 hypoglycaemia and greater incidence of severe hypoglycaemia in participants treated with efsitora compared with participants treated with degludec might suggest the need for additional evaluation of efsitora dose initiation and optimisation in people with type 1 diabetes. FUNDING: Eli Lilly and Company.

Supporting the 'lived expertise' of older adults with type 1 diabetes: An applied focus group analysis to characterize barriers, facilitators, and strategies for self-management in a growing and understudied population.

INTRODUCTION: There is a growing number of older adults (≥65 years) who live with type 1 diabetes. We qualitatively explored experiences and perspectives regarding type 1 diabetes self-management and treatment decisions among older adults, focusing on adopting care advances such as continuous glucose monitoring (CGM). METHODS: Among a clinic-based sample of older adults ≥65 years with type 1 diabetes, we conducted a series of literature and expert informed focus groups with structured discussion activities. Groups were transcribed followed by inductive coding, theme identification, and inference verification. Medical records and surveys added clinical information. RESULTS: Twenty nine older adults (age 73.4 ± 4.5 years; 86% CGM users) and four caregivers (age 73.3 ± 2.9 years) participated. Participants were 58% female and 82% non-Hispanic White. Analysis revealed themes related to attitudes, behaviours, and experiences, as well as interpersonal and contextual factors that shape self-management and outcomes. These factors and their interactions drive variability in diabetes outcomes and optimal treatment strategies between individuals as well as within individuals over time (i.e. with ageing). Participants proposed strategies to address these factors: regular, holistic needs assessments to match people with effective self-care approaches and adapt them over the lifespan; longitudinal support (e.g., education, tactical help, sharing and validating experiences); tailored education and skills training; and leveraging of caregivers, family, and peers as resources. CONCLUSIONS: Our study of what influences self-management decisions and technology adoption among older adults with type 1 diabetes underscores the importance of ongoing assessments to address dynamic age-specific needs, as well as individualized multi-faceted support that integrates peers and caregivers.

Understanding Providers' Readiness and Attitudes Toward Autoantibody Screening: A Mixed-Methods Study.

Screening for autoantibodies associated with type 1 diabetes can identify people most at risk for progressing to clinical type 1 diabetes and provide an opportunity for early intervention. Drawbacks and barriers to screening exist, and concerns arise, as methods for disease prevention are limited and no cure exists today. The availability of novel treatment options such as teplizumab to delay progression to clinical type 1 diabetes in high-risk individuals has led to the reassessment of screening programs. This study explored awareness, readiness, and attitudes of endocrinology providers toward type 1 diabetes autoantibody screening.

Patient-Reported Outcomes Improve with a Virtual Diabetes Care Model that Includes Continuous Glucose Monitoring.

Background: The objective was to examine patient-reported outcomes (PROs) associated with access to a virtual clinic model for diabetes care. Methods: Adults with diabetes (N = 234) received virtual care, including support for continuous glucose monitoring (CGM) over a 6-month study period. Care was led by a Certified Diabetes Care and Education Specialist and focused on optimizing self-management skills and response to glucose values observed on CGM. After 6 months of CGM use and access to diabetes education, participants could opt in to another 6 months of follow-up with access to the virtual care team. Participants completed PRO surveys and had health and glycemic measures collected at baseline, 3, 6, and 12 months. Results: Participants with type 1 diabetes (N = 160) were 44 ± 14 years and had mean baseline HbA1c of 61 mmol/mol (7.7%). Participants with type 2 diabetes (N = 74) were 52 ± 12 years and had mean baseline HbA1c of 66 mmol/mol (8.2%). Compared with baseline levels, at 6 months participants experienced less depression, diabetes distress, and hypoglycemic fears while also experiencing greater satisfaction with glucose monitoring, diabetes technology and specifically with CGM, and confidence for managing hypoglycemic (p < 0.05). For participants with type 1 diabetes, more time in the target range for glucose levels (70-180 mg/dL) was associated with less depression, diabetes distress, and hypoglycemic fears. Conclusions: PROs improved for adults with diabetes utilizing virtual diabetes care, including support for CGM use. Paired with the glycemic improvements observed in this virtual clinic study, there were robust benefits on the quality of life of adults with diabetes. ClinicalTrials.gov Identifier: NCT04765358.

Serum Urate Lowering with Allopurinol and Kidney Function in Type 1 Diabetes.

BACKGROUND: Higher serum urate levels are associated with an increased risk of diabetic kidney disease. Lowering of the serum urate level with allopurinol may slow the decrease in the glomerular filtration rate (GFR) in persons with type 1 diabetes and early-to-moderate diabetic kidney disease. METHODS: In a double-blind trial, we randomly assigned participants with type 1 diabetes, a serum urate level of at least 4.5 mg per deciliter, an estimated GFR of 40.0 to 99.9 ml per minute per 1.73 m2 of body-surface area, and evidence of diabetic kidney disease to receive allopurinol or placebo. The primary outcome was the baseline-adjusted GFR, as measured with iohexol, after 3 years plus a 2-month washout period. Secondary outcomes included the decrease in the iohexol-based GFR per year and the urinary albumin excretion rate after washout. Safety was also assessed. RESULTS: A total of 267 patients were assigned to receive allopurinol and 263 to receive placebo. The mean age was 51.1 years, the mean duration of diabetes 34.6 years, and the mean glycated hemoglobin level 8.2%. The mean baseline iohexol-based GFR was 68.7 ml per minute per 1.73 m2 in the allopurinol group and 67.3 ml per minute per 1.73 m2 in the placebo group. During the intervention period, the mean serum urate level decreased from 6.1 to 3.9 mg per deciliter with allopurinol and remained at 6.1 mg per deciliter with placebo. After washout, the between-group difference in the mean iohexol-based GFR was 0.001 ml per minute per 1.73 m2 (95% confidence interval [CI], -1.9 to 1.9; P = 0.99). The mean decrease in the iohexol-based GFR was -3.0 ml per minute per 1.73 m2 per year with allopurinol and -2.5 ml per minute per 1.73 m2 per year with placebo (between-group difference, -0.6 ml per minute per 1.73 m2 per year; 95% CI, -1.5 to 0.4). The mean urinary albumin excretion rate after washout was 40% (95% CI, 0 to 80) higher with allopurinol than with placebo. The frequency of serious adverse events was similar in the two groups. CONCLUSIONS: We found no evidence of clinically meaningful benefits of serum urate reduction with allopurinol on kidney outcomes among patients with type 1 diabetes and early-to-moderate diabetic kidney disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; PERL ClinicalTrials.gov number, NCT02017171.).

Psychosocial Factors Predicting Healthcare Usage in Young Adults with Youth-Onset Type 2 Diabetes: The TODAY2 iCount Observational Study.

BACKGROUND: Established diabetes care ("diabetes home") and regular healthcare visits are important to achieve optimal health. Nothing is known about psychosocial factors that predict healthcare usage (HCU) in young adults with youth-onset type 2 diabetes, at risk for early complications. OBJECTIVE: To identify psychosocial predictors of HCU in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY2) cohort. DESIGN: Longitudinal, measured at T1 (baseline) and T2 (1 year later). Logistic and linear regressions, adjusted for potential confounders, identified predictors of sub-optimal HCU (defined as no diabetes home, 0 visits for routine care, or ≥ 1 urgent care visit in prior 6 months). PARTICIPANTS: N = 366 TODAY2 participants with T1 and T2 data (381 consented). Mean age = 26.0 years, 67.8% female, 37.7% non-Hispanic Black, 35.8% Hispanic, 20.2% non-Hispanic white, 6.3% "other," mean HbA1c = 9.4%. MAIN MEASURES: HCU survey; reliable and valid measures of diabetes self-efficacy, depressive symptoms, anxiety symptoms, diabetes distress, beliefs about medicines, diabetes attitudes, material need insecurities, self-management support. KEY RESULTS: 25.4% had no diabetes home, 23.7% had 0 routine care visits, 46% had ≥ 1 urgent care visit (prior 6 months). Beliefs in the necessity of (adjusted odds ratio [OR] = 1.28; 95% confidence interval [CI] = 1.12, 1.46, p < 0.001), and concerns about (OR = 1.29;CI = 1.08,1.54, p = 0.004), diabetes medicines, and its negative psychosocial impacts (OR = 1.57;CI = 1.04, 2.38, p = 0.03), predicted higher odds of having a diabetes home at T2. Beliefs that medicines are harmful predicted lower odds of a diabetes home (OR = 0.56;CI = 0.37,0.85, p = 0.006). Necessity beliefs (OR = 1.2;CI = 1.06,1.36, p = 0.004), and self-management support (OR = 1.5;CI = 1.08,2.07, p = 0.01) predicted higher odds of having ≥ 1 diabetes care visit, harm beliefs predicted lower odds (OR = 0.6;CI = 0.41,0.88, p = 0.01). CONCLUSIONS: Sub-optimal healthcare usage, common in young adults with youth-onset type 2 diabetes, is predicted by beliefs about medicines, diabetes impact, and self-management support. We must address these factors to help this vulnerable group establish stable diabetes care.

Psychosocial factors predict medication adherence in young adults with youth-onset type 2 diabetes: Longitudinal results from the TODAY2 iCount study.

AIM: To identify psychosocial predictors of medication adherence in young adults with youth-onset type 2 diabetes in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY2) cohort. METHODS: Participants (mean age: 26 years) completed validated psychosocial measures. Unannounced telephone pill counts were completed at T1 (baseline) and T2 (follow-up, approximately 1 year later) to assess adherence to oral hypoglycaemia agents (OHAs). Adherence to insulin was assessed by self-report. Logistic and linear regressions identified factors that predicted 'low adherence' (<80% of pills/insulin) and per cent adherence, adjusted for potential confounders. RESULTS: Of 171 participants with OHA adherence scores at T1 and T2 (65% women, 43% Hispanic and 35% non-Hispanic Black), 65.4% were low adherent. After adjustment (including T1 adherence), concerns about diabetes medicines (adverse effects, dependence) at T1 predicted higher odds of being low adherent (categorical) at T2 (p = 0.019). Housing insecurity (p = 0.045) and reporting ≥2 need insecurities (p = 0.027) at T1 predicted lower per cent adherence (continuous) at T2. Of 157 participants with insulin adherence scores at T1 and T2 (69% women, 38% Hispanic and 38% non-Hispanic Black), 36.3% were low adherent. After adjustment (including T1 adherence), beliefs that medicines are overused predicted higher odds of insulin low adherence at T2 (p = 0.013), and beliefs that medicines are harmful (p = 0.004) and overused (p = 0.010) predicted lower per cent insulin adherence at T2. CONCLUSIONS: Suboptimal medication adherence, common in young adults with youth-onset type 2 diabetes, is predicted by interfering beliefs about medicines and social factors. We must address these beliefs and unmet needs to develop tailored interventions for this vulnerable group.

Ecological Momentary Assessment of Cognition in Clinical and Community Samples: Reliability and Validity Study.

BACKGROUND: The current methods of evaluating cognitive functioning typically rely on a single time point to assess and characterize an individual's performance. However, cognitive functioning fluctuates within individuals over time in relation to environmental, psychological, and physiological contexts. This limits the generalizability and diagnostic utility of single time point assessments, particularly among individuals who may exhibit large variations in cognition depending on physiological or psychological context (eg, those with type 1 diabetes [T1D], who may have fluctuating glucose concentrations throughout the day). OBJECTIVE: We aimed to report the reliability and validity of cognitive ecological momentary assessment (EMA) as a method for understanding between-person differences and capturing within-person variation in cognition over time in a community sample and sample of adults with T1D. METHODS: Cognitive performance was measured 3 times a day for 15 days in the sample of adults with T1D (n=198, recruited through endocrinology clinics) and for 10 days in the community sample (n=128, recruited from TestMyBrain, a web-based citizen science platform) using ultrabrief cognitive tests developed for cognitive EMA. Our cognitive EMA platform allowed for remote, automated assessment in participants' natural environments, enabling the measurement of within-person cognitive variation without the burden of repeated laboratory or clinic visits. This allowed us to evaluate reliability and validity in samples that differed in their expected degree of cognitive variability as well as the method of recruitment. RESULTS: The results demonstrate excellent between-person reliability (ranging from 0.95 to 0.99) and construct validity of cognitive EMA in both the sample of adults with T1D and community sample. Within-person reliability in both samples (ranging from 0.20 to 0.80) was comparable with that observed in previous studies in healthy older adults. As expected, the full-length baseline and EMA versions of TestMyBrain tests correlated highly with one another and loaded together on the expected cognitive domains when using exploratory factor analysis. Interruptions had higher negative impacts on accuracy-based outcomes (ß=-.34 to -.26; all P values <.001) than on reaction time-based outcomes (ß=-.07 to -.02; P<.001 to P=.40). CONCLUSIONS: We demonstrated that ultrabrief mobile assessments are both reliable and valid across 2 very different clinic versus community samples, despite the conditions in which cognitive EMAs are administered, which are often associated with more noise and variability. The psychometric characteristics described here should be leveraged appropriately depending on the goals of the cognitive assessment (eg, diagnostic vs everyday functioning) and the population being studied.

Reduced hypoglycaemia using liver-targeted insulin in individuals with type 1 diabetes.

AIM: To investigate whether an increased bolus: basal insulin ratio (BBR) with liver-targeted bolus insulin (BoI) would increase BoI use and decrease hypoglycaemic events (HEv). PATIENT POPULATION AND METHODS: We enrolled 52 persons (HbA1c 6.9% ± 0.12%, mean ± SEM) with type 1 diabetes using multiple daily injections. Hepatic-directed vesicle (HDV) was used to deliver 1% of peripheral injected BoI to the liver. A 90-day run-in period was used to introduce subjects to unblinded continuous glucose monitoring and optimize standard basal insulin (BaI) (degludec) and BoI (lispro) dosing. At 90 days, BoI was changed to HDV-insulin lispro and subjects were randomized to an immediate 10% or 40% decrease in BaI dose. RESULTS: At 90 days postrandomization, total insulin dosing was increased by ~7% in both cohorts. The -10% and -40% BaI cohorts were on 7.7% and 13% greater BoI with 6.9% and 30% (P = .02) increases in BBR, respectively. Compared with baseline at randomization, nocturnal level 2 HEv were reduced by 21% and 43%, with 54% and 59% reductions in patient-reported HEv in the -10% and -40% BaI cohorts, respectively. CONCLUSIONS: Our study shows that liver-targeted BoI safely decreases HEv and symptoms without compromising glucose control. We further show that with initiation of liver-targeted BoI, the BBR can be safely increased by significantly lowering BaI dosing, leading to greater BoI usage.

Association of psychosocial factors with medication adherence in emerging adults with youth-onset type 2 diabetes: The iCount study.

AIMS: To assess associations of psychosocial factors with medication adherence in young adults with youth-onset type 2 diabetes in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY2) cohort. METHODS: Participants (mean age 26 years) completed validated psychosocial measures. Adherence to oral hypoglycemia agents (OHAs) was assessed with 3-monthly unannounced phone pill counts; insulin adherence by self-report. Logistic and linear regressions identified factors associated with "low-adherence" (<80% of pills/insulin) controlling for confounders. RESULTS: Of 212 participants taking OHAs (67% female, 39% Hispanic, 36% non-Hispanic Black), 69.8% were low-adherent. After adjustment, beliefs that medicines are necessary was associated with lower odds of low-adherence (p = 0.040, dichotomous). Less self-management support (p = 0.008), no healthcare coverage (p = 0.001), ≥1 (p = 0.008)/≥2 (p = 0.045) need insecurities were associated with higher odds of low-adherence. Factors associated with lower % adherence (continuous) were beliefs that medicines are harmful (p < 0.001)/overused (p = 0.007)/less necessary (p = 0.022), low self-management support (p = 0.003), food insecurity (p = 0.036), no healthcare coverage (p < 0.001), ≥1 (p = 0.003)/≥2 (p = 0.018) need insecurities. Of 192 taking insulin (69% female, 36% Hispanic, 41% non-Hispanic Black, 16% non-Hispanic white), 37.0% were low-adherent. Beliefs that medicines are overused (p = 0.009), that diabetes is not serious (p = 0.010), low diabetes self-efficacy (p = 0.035), high distress (p = 0.027), low self-management support (p = 0.001), food insecurity (p = 0.020), ≥1 (p = 0.011)/≥2 (p = 0.015) insecurities increased odds of insulin low-adherence. CONCLUSIONS: Poor medication adherence, common in young adults with youth-onset type 2 diabetes, is associated with interfering beliefs, diabetes distress and social factors. We must address these factors to develop tailored interventions for this vulnerable group.

The association between depression symptom endorsement and glycemic outcomes in adolescents with type 1 diabetes.

OBJECTIVE: The prevalence of depression among adolescents with type 1 diabetes is estimated to be 2-3 times higher than in the general population. In adults with type 1 diabetes and depression, short-term outcomes are worse compared to individuals just diagnosed with type 1 diabetes. This study aims to determine if depressive symptom endorsement is associated with glycemic outcomes and short-term complications in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: Analysis was conducted using electronic medical records from the T1D Exchange Quality Improvement Collaborative. Adolescents with type 1 diabetes, aged 12-18, receiving treatment in a diabetes clinic who had been screened for depression with the PHQ-9 between 2016 and 2018 were eligible for inclusion. Individuals must have also had HbA1c data available from the day of depression screening and from 10 to 24 weeks after screening; the final sample size was 1714. RESULTS: Almost 30% of adolescents endorsed mild or greater (PHQ-9 ≥ 5) depressive symptoms. Endorsement of mild or greater depressive symptoms was associated with an 18% increased risk of an HbA1c ≥7.5% and a 42% increased risk of an HbA1c ≥9.0% on the day of screener administration. Depressive symptom endorsement was also associated with an 82% increased risk for DKA. CONCLUSIONS: This study suggests that depression symptoms are associated with an increased risk for elevated HbA1c and short-term complications. With the rising incidence of type 1 diabetes in youth, routine screening, and appropriate management of depression is needed.

Factors Associated With Improved A1C Among Adults With Type 1 Diabetes in the United States.

Many adults with diabetes do not reach optimal glycemic targets, and, despite advances in diabetes management, diabetes technology use remains significantly lower in racial/ethnic minority groups. This study aimed to identify factors associated with achieving the recommended A1C target of <7% using data on 12,035 adults with type 1 diabetes from 15 centers participating in the T1D Exchange Quality Improvement Collaborative. Individuals attaining the target A1C were more likely to be older, White, have private health insurance, and use diabetes technology and less likely to report depressive symptoms or episodes of severe hypoglycemia or diabetic ketoacidosis than those with higher A1C levels. These findings highlight the importance of overcoming inequities in diabetes care.

Making Diabetes Electronic Medical Record Data Actionable: Promoting Benchmarking and Population Health Improvement Using the T1D Exchange Quality Improvement Portal.

This article describes how the T1D Exchange Quality Improvement Collaborative leverages an innovative web platform, the QI Portal, to gather and store electronic medical record (EMR) data to promote benchmarking and population health improvement in a type 1 diabetes learning health system. The authors explain the value of the QI Portal, the process for mapping center-level data from EMRs using standardized data specifications, and the QI Portal's unique features for advancing population health.

The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).

The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) convened a writing group to develop a consensus statement on the management of type 1 diabetes in adults. The writing group has considered the rapid development of new treatments and technologies and addressed the following topics: diagnosis, aims of management, schedule of care, diabetes self-management education and support, glucose monitoring, insulin therapy, hypoglycaemia, behavioural considerations, psychosocial care, diabetic ketoacidosis, pancreas and islet transplantation, adjunctive therapies, special populations, inpatient management and future perspectives. Although we discuss the schedule for follow-up examinations and testing, we have not included the evaluation and treatment of the chronic microvascular and macrovascular complications of diabetes as these are well-reviewed and discussed elsewhere. The writing group was aware of both national and international guidance on type 1 diabetes and did not seek to replicate this but rather aimed to highlight the major areas that healthcare professionals should consider when managing adults with type 1 diabetes. Though evidence-based where possible, the recommendations in the report represent the consensus opinion of the authors. Graphical abstract.

Exenatide extended release in patients with type 1 diabetes with and without residual insulin production.

AIMS: To test whether a long-acting GLP-1 receptor agonist would improve glucose control in patients with type 1 diabetes (T1D) and to determine whether the presence of residual beta cell function would affect the response. In addition, we sought to determine whether the drug would affect beta cell function. METHODS: We performed a randomized placebo-controlled trial of exenatide extended release (ER) in participants with T1D with and without detectable levels of C-peptide. Seventy-nine participants were randomized to exenatide ER 2 mcg weekly, or placebo, stratified by the presence or absence of detectable C-peptide levels. The primary outcome was the difference in glycated haemoglobin (HbA1c) levels at 24 weeks. Participants were followed for another 6 months off study drug. RESULTS: At week 24, the time of the primary outcome, the least squares (LS) mean HbA1c level was 7.76% (95% confidence interval [CI] 7.42, 8.10) in the exenatide ER group versus 8.0% (95% CI 7.64, 8.35) in the placebo group (P = 0.08). At week 12 the LS mean HbA1c levels were 7.71% (95% CI 7.37, 8.05) in the exenatide ER group versus 8.05% (95% CI 7.7, 8.4) in the placebo group (P = 0.01). The improvement at week 12 was driven mainly by those with detectable levels of C-peptide. Those treated with exenatide ER lost weight at 12 and 24 weeks compared to those treated with placebo (P <0.001 and P = 0.007). The total insulin dose was lower, but not when corrected for body weight, and was not affected by residual insulin production. Adverse events were more frequent with exenatide ER, but hypoglycaemia was not increased. CONCLUSION: Treatment with exenatide ER may have short-term benefits in some individuals with T1D who are overweight or who have detectable levels of C-peptide, but short-term improvements were not sustained.

Undertreatment of cardiovascular risk factors in the type 1 diabetes exchange clinic network (United States) and the prospective diabetes follow-up (Germany/Austria) registries.

AIM: To examine the control of cardiovascular risk factors in type 1 diabetes (T1D) registries from the United States and Germany/Austria. MATERIALS AND METHODS: Data on individuals aged ≥12 years with T1D for ≥1 year, from the T1D Exchange Clinic Network (T1DX, United States) and the Prospective Diabetes Follow-up Registry (DPV, Germany/Austria) from 1 January 2016 to 31 March 2018 were analysed. Linear and logistic regression models adjusted for age groups, sex, duration of diabetes and minority status were used to compare clinical characteristics and achievement of diabetes management targets between registries. RESULTS: The cohort consisted of 47 936 patients (T1DX, n = 19 442; DPV, n = 28 494). Achievement of HbA1c goals (<7.0%, ages 18-65 years; all others, <7.5%) was better in the DPV for those aged <65 years (all P < .001). However, more older adults (aged ≥65 years) in the T1DX achieved an HbA1c goal of <7.5% compared with DPV (70% vs. 50%, P < .001). The frequency of patients with overweight (53% vs. 51%, P < .001) and obesity (19% vs. 9%, P < .001) was higher in T1DX. The frequency of meeting blood pressure goals (84% vs. 66%, P < .001) and lipid goals (73% vs. 62%, P < .001) was higher in T1DX; this was observed across all age groups (all P < .001). Few young adults aged <26 years received antihypertensive and lipid-lowering medications, respectively, despite indications in both registries (T1DX: 5% and 3%, DPV: 3% and 1%). CONCLUSION: A minority of patients with T1D achieve glycaemic targets and the majority are inadequately treated for hypertension and dyslipidaemia. This highlights the need for improved diabetes and cardiovascular risk management strategies in T1D.

Effect of Continuous Glucose Monitoring on Glycemic Control in Adolescents and Young Adults With Type 1 Diabetes: A Randomized Clinical Trial.

Importance: Adolescents and young adults with type 1 diabetes exhibit the worst glycemic control among individuals with type 1 diabetes across the lifespan. Although continuous glucose monitoring (CGM) has been shown to improve glycemic control in adults, its benefit in adolescents and young adults has not been demonstrated. Objective: To determine the effect of CGM on glycemic control in adolescents and young adults with type 1 diabetes. Design, Setting, and Participants: Randomized clinical trial conducted between January 2018 and May 2019 at 14 endocrinology practices in the US including 153 individuals aged 14 to 24 years with type 1 diabetes and screening hemoglobin A1c (HbA1c) of 7.5% to 10.9%. Interventions: Participants were randomized 1:1 to undergo CGM (CGM group; n = 74) or usual care using a blood glucose meter for glucose monitoring (blood glucose monitoring [BGM] group; n = 79). Main Outcomes and Measures: The primary outcome was change in HbA1c from baseline to 26 weeks. There were 20 secondary outcomes, including additional HbA1c outcomes, CGM glucose metrics, and patient-reported outcomes with adjustment for multiple comparisons to control for the false discovery rate. Results: Among the 153 participants (mean [SD] age, 17 [3] years; 76 [50%] were female; mean [SD] diabetes duration, 9 [5] years), 142 (93%) completed the study. In the CGM group, 68% of participants used CGM at least 5 days per week in month 6. Mean HbA1c was 8.9% at baseline and 8.5% at 26 weeks in the CGM group and 8.9% at both baseline and 26 weeks in the BGM group (adjusted between-group difference, -0.37% [95% CI, -0.66% to -0.08%]; P = .01). Of 20 prespecified secondary outcomes, there were statistically significant differences in 3 of 7 binary HbA1c outcomes, 8 of 9 CGM metrics, and 1 of 4 patient-reported outcomes. The most commonly reported adverse events in the CGM and BGM groups were severe hypoglycemia (3 participants with an event in the CGM group and 2 in the BGM group), hyperglycemia/ketosis (1 participant with an event in CGM group and 4 in the BGM group), and diabetic ketoacidosis (3 participants with an event in the CGM group and 1 in the BGM group). Conclusions and Relevance: Among adolescents and young adults with type 1 diabetes, continuous glucose monitoring compared with standard blood glucose monitoring resulted in a small but statistically significant improvement in glycemic control over 26 weeks. Further research is needed to understand the clinical importance of the findings. Trial Registration: ClinicalTrials.gov Identifier: NCT03263494.

Effect of Continuous Glucose Monitoring on Hypoglycemia in Older Adults With Type 1 Diabetes: A Randomized Clinical Trial.

Importance: Continuous glucose monitoring (CGM) provides real-time assessment of glucose levels and may be beneficial in reducing hypoglycemia in older adults with type 1 diabetes. Objective: To determine whether CGM is effective in reducing hypoglycemia compared with standard blood glucose monitoring (BGM) in older adults with type 1 diabetes. Design, Setting, and Participants: Randomized clinical trial conducted at 22 endocrinology practices in the United States among 203 adults at least 60 years of age with type 1 diabetes. Interventions: Participants were randomly assigned in a 1:1 ratio to use CGM (n = 103) or standard BGM (n = 100). Main Outcomes and Measures: The primary outcome was CGM-measured percentage of time that sensor glucose values were less than 70 mg/dL during 6 months of follow-up. There were 31 prespecified secondary outcomes, including additional CGM metrics for hypoglycemia, hyperglycemia, and glucose control; hemoglobin A1c (HbA1c); and cognition and patient-reported outcomes, with adjustment for multiple comparisons to control for false-discovery rate. Results: Of the 203 participants (median age, 68 [interquartile range {IQR}, 65-71] years; median type 1 diabetes duration, 36 [IQR, 25-48] years; 52% female; 53% insulin pump use; mean HbA1c, 7.5% [SD, 0.9%]), 83% used CGM at least 6 days per week during month 6. Median time with glucose levels less than 70 mg/dL was 5.1% (73 minutes per day) at baseline and 2.7% (39 minutes per day) during follow-up in the CGM group vs 4.7% (68 minutes per day) and 4.9% (70 minutes per day), respectively, in the standard BGM group (adjusted treatment difference, -1.9% (-27 minutes per day); 95% CI, -2.8% to -1.1% [-40 to -16 minutes per day]; P <.001). Of the 31 prespecified secondary end points, there were statistically significant differences for all 9 CGM metrics, 6 of 7 HbA1c outcomes, and none of the 15 cognitive and patient-reported outcomes. Mean HbA1c decreased in the CGM group compared with the standard BGM group (adjusted group difference, -0.3%; 95% CI, -0.4% to -0.1%; P <.001). The most commonly reported adverse events using CGM and standard BGM, respectively, were severe hypoglycemia (1 and 10), fractures (5 and 1), falls (4 and 3), and emergency department visits (6 and 8). Conclusions and Relevance: Among adults aged 60 years or older with type 1 diabetes, continuous glucose monitoring compared with standard blood glucose monitoring resulted in a small but statistically significant improvement in hypoglycemia over 6 months. Further research is needed to understand the long-term clinical benefit. Trial Registration: ClinicalTrials.gov Identifier: NCT03240432.

Cardiac Biomarkers in Youth with Type 2 Diabetes Mellitus: Results from the TODAY Study.

OBJECTIVES: To examine cardiac biomarkers over time in youth-onset type 2 diabetes, and relate serum concentrations to cardiovascular disease risk factors, and left ventricular structure and function. STUDY DESIGN: TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) was a multicenter randomized trial of 3 treatments including 521 participants with type 2 diabetes, aged 10-17 years, and with 2-6 years of follow-up. Participants were 36% male, obese, and ethnically diverse. Annual serum concentrations of brain natriuretic peptide, troponin, tumor necrosis factor (TNF)-α, receptors 1 and 2 were related to blood pressure, body mass index, hemoglobin A1c, and left ventricular ejection fraction, diastolic function, relative wall thickness, and mass. RESULTS: Elevated concentrations of brain natriuretic peptide (≥100 pg/mL), TNF-α (≥5.6 pg/mL) and troponin (≥0.01 ng/mL), were present in 17.8%, 18.3%, and 34.2% of the cohort, respectively, at baseline, and in 15.4%, 17.1%, and 31.1% at the end of the study, with wide variability over time, without persistence in individuals or clear relationship to glycemia or cardiovascular structure/function. TNF receptors concentrations were increased at baseline and not significantly different from end-of-study concentrations. Adverse echocardiographic measures were more likely in the highest TNF receptor tertile (all P < .05): higher left ventricular mass (39.3 ± 9.0 g/m2.7), left atrial internal dimension (3.7 ± 0.4 cm) and E/Em ratio, a measure of diastolic dysfunction (6.2 ± 1.9). After adjustment for body mass index, these relationships were no longer significant. CONCLUSIONS: Elevated serum concentrations of cardiac biomarkers were common in youth with type 2 diabetes, but their clinical significance is unclear and will require further long-term study. TRIAL REGISTRATION: ClinicalTrials.govNCT00081328.

Lipid Profiles, Inflammatory Markers, and Insulin Therapy in Youth with Type 2 Diabetes.

OBJECTIVES: Data regarding atherogenic dyslipidemia and the inflammation profile in youth with type 2 diabetes is limited and the effect of insulin therapy on these variables has not previously been studied in youth. We determined the impact of insulin therapy on lipid and inflammatory markers in youth with poorly controlled type 2 diabetes. STUDY DESIGN: In the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) multicenter trial, 285 participants failed to sustain glycemic control on randomized treatment (primary outcome, glycated hemoglobin A1c [HbA1c] at ≥8% for 6 months); 363 maintained glycemic control (never reached primary outcome). Statins were used for a low-density lipoprotein cholesterol of ≥130 mg/dL. Upon reaching the primary outcome, insulin was started. Changes in lipids and inflammatory markers (slopes over time) were examined. RESULTS: Progression of dyslipidemia was related to glycemic control. In those with the primary outcome, insulin therapy impacted HbA1c modestly, and dampened the increase in total cholesterol, low-density lipoprotein cholesterol, and total apolipoprotein B, although statin use increased from 8.6% to 22% year after the primary outcome. The increase in triglycerides and plasma nonesterified fatty acids stabilized after insulin was started, independent of HbA1c. There was an increase in high-sensitivity C-reactive protein that continued after insulin initiation, related to HbA1c and percent overweight. CONCLUSIONS: Worsening dyslipidemia and inflammation over time raise concern regarding premature development of atherosclerosis in youth with type 2 diabetes. Insulin therapy has a limited benefit in the absence of glycemic control. Strategies to achieve better glycemic control are needed. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00081328.