Diabetes technology & therapeutics最新文献

Introduction and Objective: Fasting presents unique metabolic challenges for individuals with T1D. The 25-h Yom Kippur complete fast provides an opportunity to evaluate whether automated insulin delivery (AID) systems can maintain metabolic stability, prevent hypoglycemia and ketosis, and determine basal insulin requirements during prolonged fasting. Methods: This real-world, noninterventional study included 54 adolescents and young adults with T1D (mean age 17.3 ± 3.3 years, HbA1c 6.8 ± 1.0%). Participants used MiniMed 780 G (n = 34), Control-IQ (n = 10), or open-source AID systems (n = 10). Common system-specific adjustments included setting a 150 mg/dL exercise target, activating sleep mode, and modifying basal or glucose targets, while 11 participants made no changes. Ketone levels were measured after the 25-h fast and a routine overnight fast. Analyses compared glucose and insulin across fasting periods and different 780 G settings and assessed predictors of hypoglycemia and ketone levels. Results: All participants successfully completed the fast. Mean TIR increased from 71.6 ± 13.9% during routine days to 82 ± 13.2% during fasting (P < 0.01), while time <70 mg/dL decreased from 2.6% to 2.2% (P = 0.017). Ten mild hypoglycemic events occurred after the pre-fast meal and one during fasting. A higher baseline percentage of time <70 mg/dL was the only predictor of hypoglycemia. No significant difference was found between 780 G users with exercise mode and those with no or minor changes. Participants received 43.4 ± 16.8% (range 9.3%-90%) of their usual insulin dose. Median (IQR) end-of-fast ketone levels were 0.4 (0.3, 0.7) mmol/L vs 0.1 (0, 0.1) mmol/L on a regular morning (n = 31); insulin doses <30% of usual dose were associated with higher ketone levels. No severe hypoglycemia or serious adverse events occurred. Conclusion: AID systems enable safe 25-h fasting by maintaining glucose control and reducing the risk of hypoglycemia and ketonuria. Fasting adjustments should be individualized and can often be minor.

Background: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) with or without glucose-dependent insulinotropic polypeptide (GIP) are Food and Drug Administration approved for patients with type 2 diabetes (T2D) and weight loss and are increasingly being used off-label in patients with type 1 diabetes (T1D). We evaluated all-cause mortality and health care resource utilization (HCRU) among patients with T1D receiving GLP-1 RA or GLP-1 RA/GIP dual agonist over a 2-year period. Methods: Using the TriNetX database, we identified patients with T1D using ICD-10 codes, excluding those with T2D or sodium-glucose cotransporter-2 inhibitor use. Patients with T1D were divided into two cohorts of 4212 patients each based on whether or not they received a GLP-1 single/dual receptor agonist (comparison cohort vs. control cohort). We performed 1:1 propensity matching for demographics (age, sex, race), body mass index, hemoglobin A1c, and several comorbidities. Primary outcomes included all-cause mortality, HCRU, endoscopic procedures, and use of gastrointestinal prescriptions. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for all outcomes except all-cause mortality, for which Cox regression analysis was performed to obtain the hazard ratio (HR) over 2 years. Results: The cohorts were predominantly white and female. Compared to the control cohort, patients taking GLP-1 single/dual receptor agonists had lower rates of all-cause mortality (HR = 0.18, 95% CI: 0.11-0.30, P < 0.0001), all-cause hospitalizations (OR = 0.30, 95% CI: 0.20-0.45, P < 0.0001), emergency department (ED) visits (OR = 0.56, 95% CI: 0.43-0.71, P < 0.0001), endoscopy use (OR = 0.52, 95% CI: 0.38-0.70, P < 0.0001), laxative prescription (OR = 0.52, 95% CI: 0.43-0.63, P < 0.0001), and prokinetic prescription (OR = 0.74, 95% CI: 0.57-0.96, P = 0.0238). No significant differences were observed for diabetic ketoacidosis (P = 0.1030), antiemetic prescription (P = 0.2950), and hypoglycemia (P = 0.7474). Discussion: These findings suggest that use of GLP-1 RA/GIP analogs in patients with T1D was associated with significantly lower HCRU, including hospitalizations and ED visits, and reduced all-cause mortality. Further studies are warranted to confirm these observational findings.

Background: We have developed pancreatic beta-cell, antigen-specific, chimeric antigen receptor (CAR) T regulatory cells (Tregs) and explored their therapeutic potential for type 1 diabetes (T1D)/latent autoimmune diabetes of adults (LADA) in human pancreatic tissues ex vivo, and in a spontaneous humanized mouse model (T1D mice) in vivo. Results: Using live-cell imaging, we observed these glutamic acid decarboxylase, 65 kD isoform (GAD65)-CAR-Tregs home to human pancreatic islets exvivo and proliferate upon encountering the cognate GAD65 antigen in the islets. Furthermore, human pancreatic-islet activated GAD65-CAR-Tregs also suppressed human T1D cytotoxic T lymphocytes in co-cultures. We confirmed these findings in vivo, in a spontaneous humanized T1D mouse model (T1D mice) by showing that mouse GAD65-CAR-Tregs also suppressed diabetogenic T responsive (Tresp) cells and were superior to normal Tregs. We also show that mouse GAD65-CAR-Tregs homed to mouse pancreatic islets in vivo. Moreover, we conducted a 30-day preclinical trial in T1D mice, and observed normalization of fasting blood glucose, fasting insulin, and glucose tolerance tests in GAD65-CAR-Treg-treated T1D mice. We confirmed by histology, the advancement of Tregs, retreat of T effector cells in GAD65-CAR-Treg-treated mice, that led to the recovery/reconstitution of pancreatic islets. Discussion: Taken together, human GAD65-CAR-Tregs homed to human islets, suppressed diabetogenic T cells, and when used to treat T1D mice that mimic the human pathophysiology of T1D, GAD65-CAR-Tregs reversed T1D. Conceivably, the treatment of T1D with GAD65-CAR-Tregs will allow for recovery/reconstitution of beta cells in human patients as well.

Objective: This study evaluated the cost utility of the t:slim X2 insulin pump with Control-IQ technology (Control-IQ) relative to multiple daily injections (MDIs) and standard insulin pump therapy, both used in combination with continuous glucose monitoring (CGM), in adults with type 1 diabetes from a payer perspective in Belgium. Research Design and Methods: A lifetime cost-utility analysis was conducted using the IQVIA CORE Diabetes Model. Baseline characteristics and treatment effects were informed by the Belgian real-world, multicenter, prospective INRANGE study. Direct medical costs included treatment, complication management, and severe hypoglycemic events. Country-specific costs were based on RIZIV-INAMI data and other publicly available sources. Utility values were based on published literature and included the reduction in fear of hypoglycemia associated with Control-IQ as reported in the INRANGE study. Outcomes included quality-adjusted life years (QALYs) and incremental cost-utility ratios (ICURs). Scenario analyses explored variations in the comparator (MDI + CGM only), reduced HbA1c efficacy, and time horizon. Results: Control-IQ yielded 19.50 QALYs versus 17.92 for MDI and standard insulin pump therapy plus CGM, with total costs of €193,588 and €160,129, respectively, resulting in an ICUR of €21,111/QALY. Scenario analyses confirmed robustness: MDI + CGM as sole comparator (ICUR: €41,701/QALY), reduced HbA1c efficacy (ICUR: €25,967/QALY), and a 20-year time horizon (ICUR: €30,183/QALY). Conclusions: Control-IQ provides clinical benefits relative to MDI and standard insulin pump therapy plus CGM in adults with type 1 diabetes in Belgium and appears to be cost-effective in this setting, considering commonly used thresholds. These findings support the broader adoption of automated insulin delivery systems in diabetes management.

Introduction: Youth obesity is a strong risk factor for prediabetes (PD) and type 2 diabetes. Current criteria for the diagnosis of PD/diabetes, including fasting glucose, 2-h blood glucose after oral glucose tolerance test (OGTT), and HbA1c, have some acknowledged limitations in youth. Continuous glucose monitoring (CGM) offers the opportunity to record daily glucose profiles in a free-living conditions. This study aims to explore how the CGM metrics are related to PD in youths with obesity. Method: Youths with obesity (BMI-for-age > 2SD, age 10-18 years) wore a Freestyle Libre 2 CGM sensor for 2 weeks. Several CGM metrics were measured, including time in tight ranges (TITR) 70-140 and 70-120 mg/dL. All subjects underwent OGTT, and normal glucose tolerance (NGT) and prediabetes (PD) were defined by American Diabetes Association criteria. A nonparametric Wilcoxon rank-sum test was used to compare NGT and PD youths, and logistic regression analysis was performed to investigate the ability of CGM metrics to predict PD. Results: Overall, 84 youths (age 12.6 ± 1.9 years, 42.4% female, BMI 32.8 ± 6.6 kg/m², HbA1c5.4 ± 0.2%, CGM use >80%) were recruited. HbA1c, blood glucose measured at baseline, 30, 90, and 120 min, and the area under the curve of glucose after glucose load were significantly higher (P value <0.05) in PD than in NGT youths. TITR 70-140 mg/dL and TITR 70-120 mg/dL were significantly (P < 0.05) lower in PD than in NGT youths. No other CGM metrics differed between the two groups. Both TITR 70-140 and 70-120 mg/dL significantly predict PD (P = 0.02), independent of age and sex, though with modest discriminative ability. Conclusions: This exploratory study showed that TITR measured in free-living may aid the identification of PD in youths with obesity, although the discriminative ability of CGM metrics was limited. Future works will focus on the analysis of the concordance of plasma glucose and CGM during OGTT, as well as their predictive performance.

Objective: Continuous glucose monitoring (CGM) and hemoglobin A1c (HbA1c) provide estimates of mean glycemia that may differ, in part, due to the effects of variation in red blood cell (RBC) age and turnover on HbA1c. Measurements derived from the complete blood count (CBC) may vary with RBC age and might be used to reduce the difference between glycemia estimates derived from CGM and HbA1c. Methods: We analyzed CBC measurements from 1,325 individuals with type 2 diabetes who participated in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) CGM substudy. Mean glycemia was estimated from HbA1c (eAG_A1c) using the A1c-Derived Average Glucose (ADAG) formula and from CGM by averaging 10 days of measurements (eAG_CGM). We evaluated the association between CBC-derived data and the difference (eAG_A1c - eAG_CGM) using linear models, both unadjusted and adjusted for age and self-identified sex. Results: In adjusted analyses, several CBC-derived measurements were significantly associated with the difference between eAG_A1c and eAG_CGM. Platelet count and RBC distribution width (RDW) were positively associated, while hemoglobin concentration (HGB), reticulocyte fraction, mean corpuscular volume (MCV), mean corpuscular hemoglobin content (MCH), mean corpuscular hemoglobin concentration (MCHC), and reticulocyte MCHC were negatively associated. A linear model from HbA1c to eAG_CGM adjusted with all significantly associated CBC measurements (CBC_all-AG_A1c) provided modestly improved estimates of eAG_CGM compared with ADAG, with R² (SD) for ADAG of 0.68 (0.07) and for CBC_all-AG_A1c 0.72 (0.06). Conclusions: CBC measurements are associated with differences between estimates of glycemia derived from HbA1c and CGM. Further studies with longer periods of CGM are needed to determine whether CBCs can complement HbA1c and CGM and can help reconcile differences in estimates of mean glycemia provided by HbA1c and CGM.

Background: Time in tight range (TITR, 70-140 mg/dL) has emerged as a glycemic metric offering stricter assessment than conventional time in range (TIR, 70-180 mg/dL). Whether TITR provides additional prognostic value for diabetic retinopathy (DR) in adults with type 1 diabetes (T1D) remains unclear. Methods: We conducted a retrospective cohort study of 309 adults with T1D on multiple daily insulin injections using intermittently scanned continuous glucose monitoring (CGM) system. Ophthalmological assessments were performed at baseline and after 12 months (May 2024-May 2025). DR incidence (in those free of DR at baseline) and progression (in those with established DR) were defined according to Early Treatment Diabetic Retinopathy Study criteria. Longitudinal TITR and TIR were extracted every 14-28 days. Multivariable logistic regression adjusted for age, sex, diabetes duration, HbA1c, hypertension, Low-density lipoprotein (LDL) cholesterol, body mass index, and smoking was applied. Results: At baseline, 198 participants (64.1%) had no DR, 71 (23.0%) nonproliferative, and 40 (12.9%) proliferative DR. During follow-up, 10/198 (5.1%) developed DR and 26/111 (23.4%) with baseline DR progressed. Higher TITR was independently associated with lower risk of incident DR (adjusted OR per % increase: 0.965; 95% CI: 0.950-0.980), whereas TIR was not. Receiver operating characteristic analysis confirmed superior discrimination for TITR versus TIR (area under the curve 0.580 vs. 0.430; P < 0.001). In stratified analyses, TITR predicted incident DR only among participants with HbA1c below the cohort median (7.1%). Both TITR and TIR were associated with lower risk of DR progression in models including HbA1c, with similar discriminative performance. Diabetes duration, HbA1c, hypertension, and smoking were independently associated with DR outcomes alongside CGM metrics. Conclusions: TITR provides modestly superior predictive value over TIR for incident DR, particularly in individuals with near-target HbA1c, but both metrics perform similarly for predicting progression. CGM-derived metrics should be interpreted in the context of overall glycemic control and clinical risk factors.

Background: CGM is associated with improved diabetes management. Prior studies have evaluated its effects on health care utilization and costs among individuals using insulin, particularly those prescribed rapid- and short-acting regimens. The present study compared clinical and economic outcomes between CGM users and nonusers in a large, diverse, real-world population of rapid- and short-acting insulin users. Methods: Using the Mariner Commercial Claims Database, adults with diabetes and at least one claim for rapid- or short-acting insulin between January 1, 2010, and October 31, 2022, were identified. Two cohorts were defined based on receipt of CGM: those with CGM (wCGM) and those without CGM (xCGM). Direct matching was applied to ensure comparability between groups. Outcomes included total medical costs, emergency room (ER) days, inpatient (IP) days, ER and IP days associated with hypoglycemia, diabetic ketoacidosis (DKA), or mixed events, and the likelihood of achieving glycated hemoglobin (HbA1c) <9%. The National Committee for Quality Assurance considers HbA1c >9% as "poor control". Results: After applying exclusion criteria, 3,139,979 individuals met inclusion criteria. Of these, 536,512 received a CGM and 2,603,467 did not, meaning approximately 83% of eligible individuals had no evidence of CGM use. Total health care costs were significantly lower in the wCGM cohort ($6,245) compared with the xCGM cohort ($7,786; t(698,086) = -71.41, P < 0.001). The wCGM group also had significantly fewer ER days and IP days at 3, 6, 9, and 12 months. CGM users had 19% higher odds of achieving HbA1c <9% compared with nonusers (odds ratio [OR] = 1.19). A significantly smaller proportion of individuals in the wCGM cohort had ER/IP days associated with hypoglycemia, DKA, or both. Conclusions: These findings reinforce the clinical and economic value of CGM and support recent policy updates expanding access for insulin-treated populations.

Background: Physical activity (PA) poses significant challenges in glucose management for individuals with type 1 diabetes (T1D). Real-world PA is more frequent than structured PA, but remains underexplored. We analyzed 8171 real-world PA sessions comprising 45 activity types from the Type 1 Diabetes Exercise Initiative, examining hypoglycemia risk correlations with PA-level and population-level factors. Methods: Hypoglycemia risk was measured by change in continuous glucose monitoring (ΔCGM) from PA onset to end, low blood glucose index (LBGI), and hypoglycemia event occurrence. Primary analyses used analysis of variance and Tukey's range test to measure correlations. Secondary analyses compared risk across activity types and categories (aerobic, mixed, and anaerobic). Results: Higher hypoglycemia risk was associated with longer PA duration (median [Interquartile Range (IQR)] ΔCGM -24 [-60, 11] mg/dL for 60-120 min vs. -12 [-31, 5] mg/dL for 15-30 min), lower starting glucose (90% of sessions starting <50 mg/dL had hypoglycemia), and declining glucose rates before PA (all P < 0.05). Carbohydrate (CHO) intake 2-4 h before and during PA was associated with higher hypoglycemia risk (ΔCGM -37 [-67, -14] mg/dL with rescue CHO vs. -15 [-42, 8] mg/dL without, P < 0.05), but this paradoxical effect was explained by higher insulin on board (IoB) and lower starting glucose. Males had larger glucose drops (ΔCGM -20 [-46, 4] mg/dL vs. -16 [-44, 7] mg/dL in females, P < 0.05). Closed-loop users exhibited lower LBGI compared with open-loop users (P < 0.05). Secondary analyses showed significant glycemic variability across activity types (P < 0.05). Aerobic activities caused the greatest glucose drop, followed by mixed and anaerobic (P < 0.05), whereas LBGI differences were nonsignificant (P = 0.32). Conclusions: Real-world PA has a highly variable glycemic impact, with longer duration, lower starting glucose, and higher IoB increasing hypoglycemia risk. Glycemic responses differed significantly by activity type, with aerobic activities resulting in the greatest decline. These findings highlight the need for tailored strategies to mitigate PA-related hypoglycemia in T1D.