Kudva, Yogish C.

Introduction: The objective of the study was to evaluate the prevalence of cardiovascular, renal, and hepatic biomarkers that fall outside guideline-based thresholds in adults with type 1 diabetes (T1D), and to identify demographic and clinical factors associated with these biomarkers. Methods: This observational study linked data on 2,923 adults with T1D from the T1D Exchange Registry and NorstellaLinQ’s laboratory data (2022–2023). Prevalence of biomarkers outside guideline-recommended thresholds was calculated. Generalized estimating equations (GEE) were used to model associations with age, sex, race/ethnicity, insurance, T1D duration, body mass index (BMI), and hemoglobin A1c (HbA1c), while accounting for within-subject correlation due to repeated measures. Results: Elevated low-density lipoprotein (LDL) cholesterol (≥70 mg/dL, above the recommended goal for individuals with diabetes at high risk for atherosclerotic cardiovascular disease) was common (80.2%), as were overweight (33.8%) and obesity (30.3%). Additional findings included high total cholesterol (≥200 mg/dL, 22.6%), low high-density lipoprotein (HDL) cholesterol (<40 mg/dL males, <50 mg/dL females, 13.4%), elevated urinary albumin-to-creatinine ratio (≥30 mg/g, 13.0%), reduced estimated glomerular filtration rate (<60 mL/min/1.73 m 2 , 6.2%), and elevated fibrosis-4 index (FIB-4) (≥1.3, 14.4%). In adjusted GEE models, higher HbA1c was significantly associated with increased odds of abnormal cardiovascular and renal biomarkers across most measures. Male sex and BMI were linked to lower HDL cholesterol, while older age was strongly associated with elevated FIB-4. Conclusion: Obesity and elevated LDL cholesterol are highly prevalent in adults with T1D, indicating substantial cardiometabolic risk. The lack of outcome trials in this population underscores the need for studies to evaluate strategies to improve weight and lipid management and thereby reduce cardiovascular and renal risk in adults with T1D.

ABSTRACT Objective Automated insulin delivery (AID) has been established as an effective therapy for individuals with type 1 diabetes. This analysis evaluates the clinical and economic outcomes of AID compared with multiple daily injections plus continuous glucose monitoring (MDI/CGM) in adults with type 2 diabetes. Materials and Methods The IQVIA CORE Diabetes Model v10.0 was employed to simulate the impact of using the t:slim X2 insulin pump with Control‐IQ+ technology (Control‐IQ+) versus MDI/CGM over a 50‐year period using data from the 2IQP randomized controlled trial (NCT05785832). Trial data informed cohort demographics, intervention effects and resource utilization while literature sources provided health state utilities and costs. Scenario analyses examined the effect of Control‐IQ+ on reducing HbA1c based on alternative HbA1c progression estimates from the Swedish National Diabetes Registry and alternative resource use and treatment effects from real‐world evidence. Results The base case analysis indicated that direct medical costs per individual for type 2 diabetes management with Control‐IQ+ were $239 935 compared to $209 792 with MDI/CGM use. Control‐IQ+ resulted in 0.51 additional quality‐adjusted life years (QALYs: 10.36 vs. 9.85 for MDI/CGM), yielding an incremental cost‐effectiveness ratio (ICER) of $59 417 per QALY, 95% CI: ($55 836, $62 998). In probabilistic sensitivity analyses, 89% of simulations produced ICERs below $100 000/QALY. ICERs across all scenarios remained below $100 000 per QALY. Conclusions Control‐IQ+ is associated with increased life expectancy, higher QALYs and reduced complication rates. These findings suggest that Control‐IQ+ is cost‐effective relative to MDI/CGM for managing patients with type 2 diabetes in the United States.

Background: Given the faster onset and shorter duration of action of ultra-rapid insulin lispro-aabc (URLi, Lyumjev™ insulin), compared with insulin lispro (a rapid-acting insulin [RAI]), the present study investigated the safety and glycemic outcomes of MiniMed™ 780G advanced hybrid closed-loop (AHCL) use with URLi in youths and adults with T1D. Methods: This 19-site, single-arm, clinical trial enrolled children and adolescents (aged 7–17 years) and adults (aged 18–80 years) with T1D who underwent a run-in period (∼2 weeks) using open loop or automated basal only with an RAI (aspart or lispro), followed by a 3-month study period using URLi with AHCL (AHCL + URLi). End-of-study glycemic metrics and A1c were compared to predefined thresholds and to data from baseline/run-in. Use of recommended optimal settings (ROS, 100 mg/dL glucose target with an active insulin time [AIT] of 2 h) was also assessed. Results: In an intention-to-treat population ( N = 101 pediatric and N = 110 adult participants), percentage of time in range (%TIR) during the last ∼6 weeks of the study period was significantly greater than the predefined thresholds for both the pediatric and adult participants. A1c was unchanged in the pediatric cohort but significantly reduced in the adult cohort (from 7.4 ± 0.9% to 6.9 ± 0.6% [ P < 0.001]). Compared with run-in, study period %TIR and percentage of time in tight target range (%TITR) were significantly increased (pediatric mean %TIRΔ [17.4%] and %TITRΔ [16.0%], respectively, and adult mean %TIRΔ [10.6%] and %TITRΔ [11.6%], respectively; P < 0.001 for all). Additionally, % time above range for both groups was significantly reduced. Use of ROS allowed more participants to achieve recommended glycemic targets. There were no severe hypoglycemia or diabetic ketoacidosis events. Most caregivers agreed that mealtime versus premeal URLi delivery simplified pediatric meal management. Conclusions: Similar to previous studies investigating automated URLi delivery, URLi use in the MiniMed™ 780G system was safe, and glycemic outcomes were favorable for pediatric and adult participants.

Abstract Disclosure: L.J. Plaza Enriquez: None. R. ibrahim: None. L. Ayari: None. R. Gavrilova: None. Y. Kudva: None. Introduction: Mitochondrial diabetes(mtDB) is a rare disease; hence its prevalence and associated comorbidities are not well defined. The aim of this study is to describe prevalence, glycemic control, treatment used for diabetes and comorbidities associated with this condition using a Mayo Clinic cohort of patients with mitochondrial mutations. Methods: We identified 23 patients with diabetes from an institutional cohort of patients with, mitochondrial mutations. Genetic mutations included the classic MTTL1 m.3243A&gt;G in 22 of the patients and MTND5m.13513G&gt;A in one patient. Statistical analysis was performed using BlueSky Statistics version 10.3.4 software. Categorical variables were compared using Fisher’s exact test and continuous variables were compared using ANOVA. Kaplan Meier survival curves were created. Unless otherwise stated, value of p of &lt;0.05 was considered significant. Results: The cohort consisted of predominantly females (14 vs 9). The mean age at initial diabetes diagnosis was 39.5 years (CI: 30.6–48.4) for females and 32.0 years (CI: 20.9–43.1) for males (p = 0.253). Over 75% of patients were initially diagnosed with type 2 diabetes (T2D). The mean age at mtDB diagnosis was 51.7 years (SD 11.9) for females and 46.0 years (SD 8.5) for males, reflecting a &gt;15-year gap between T2D and mtDB diagnosis. The mean BMI at initial diagnosis was similar between males and females (26.0 (CI: -8.4, 60.4)), though it was higher than the average reported in the literature. Most patients had multiple comorbidities associated with mtDB, including retinopathy, macular defects, cerebrovascular disease, CVD, arrhythmias, nephropathy, and gastrointestinal conditions. Retinopathy and macular defects typically developed within 5-10 years of diabetes diagnosis, while cerebrovascular disease and CVD had a later onset, at a mean of 8.25 years (SD = 6.76) and 5.0 years (SD = 5.75), respectively. However, the difference in onset times between these comorbidities was not statistically significant (p = 0.3228).Regarding glycemic control, there was no significant difference in HbA1c levels at diagnosis or later (HbA1c &lt; 8% in &gt;90% of the cohort). Various treatment modalities (13 on insulin therapy vs 10 on non-insulin treatments) did not show significant differences in glycemic control (p = 0.463), with mean HbA1c of 6.59 (SD 1.36). Mortality rates increased 10-15 years after initial diagnosis of mtDB, with 3 patients dying from complications related to the mitochondrial disorder. Conclusion: mtDB is associated with significant comorbidities/complications that developed earlier compared to T2D or even T1D from the literature. Initial misdiagnosis of this condition as T2D remains high. Different treatment modalities (insulin vs non-insulin) did not differ in glycemic control hence consideration as first options of treatment should be given to oral hypoglycemics. Presentation: Saturday, July 12, 2025

Objective: To evaluate the function and safety of the SteadiSet™ infusion set over a continuous 7-day wear period in adults with type 1 diabetes. Research Design and Methods: Participants used a SteadiSet infusion set with a t:slim X2™ insulin pump with Control-IQ™ technology, and either insulin aspart or insulin lispro, for a target of 7 days for 12 consecutive wear periods. Each set removed before 7 days was adjudicated by an independent committee to assess the cause of early removal and to determine whether criteria for primary or key secondary endpoints were met. Results: There were 260 participants who inserted 3028 infusion sets. For the primary endpoint, the Kaplan–Meier 7-day survival estimate was 95% (95% CI 94% to 96%). For the key secondary endpoint, which expanded the reasons for a failed infusion set, the Kaplan–Meier 7-day survival estimate was 84% (95% CI 82% to 86%). For both endpoints, the P value was <0.001 compared with a prespecified survival rate of 75%. Time-in-range 70–180 mg/dL (TIR) increased through day 3 of set wear and then decreased through day 7, with the average TIR being 70.6% over the entire wear period across all infusion sets, including those that failed. An increase in total daily insulin was observed from day 4 through day 7. Conclusions: The 7-day survival of the SteadiSet infusion set was very high for the primary endpoint and at an acceptable level with respect to early removal for any reason related to the device.

OBJECTIVE The Centers for Medicare & Medicaid Services (CMS) requires a low C-peptide level for insulin pump coverage unless the individual is β-cell autoantibody positive, which precludes coverage of automated insulin delivery (AID) systems for many people with type 2 diabetes. RESEARCH DESIGN AND METHODS In the Randomized Trial Evaluating the Efficacy and Safety of Control-IQ+ Technology in Adults With Type 2 Diabetes Using Basal-Bolus Insulin Therapy study evaluating the t:slim X2 insulin pump with Control-IQ+ technology, adults with insulin-treated type 2 diabetes were categorized into high C-peptide (n = 195) and low C-peptide (n = 59) groups based on CMS criteria. RESULTS In the AID group, mean HbA1c decreased from baseline by 0.8%, which was significantly greater than in the control group with both high (P &lt; 0.001) and low (P = 0.02) C-peptide levels. Results were similar in participants ≥65 years old. CONCLUSIONS The benefit of AID is present with high and low C-peptide levels. Thus, requiring a low C-peptide level as a prerequisite for AID therapy is not warranted.

Pancreatogenic or type 3c diabetes, which occurs as a consequence of pancreatitis, may have several mechanisms. Mechanisms overlapping with those of type 2 diabetes have been explored, including insulin resistance and insulin deficiency. However, autoimmune mechanisms in response to unmasking β-cell antigens, similar to those of type 1 diabetes (T1D), have not been thoroughly examined. We performed cross-sectional T1D autoantibody profiling in a large prospective cohort (N = 927) of adults with acute, recurrent acute, or chronic pancreatitis. We examined correlations of prevalence of autoantibodies against GAD (GAD antibody), IA-2 (IA-2 antibody), zinc transporter 8 (ZnT8; ZnT8 antibody), and insulin (insulin autoantibody [IAA]) with clinical and demographic features, including presence of diabetes, diabetes treatment, and family history of diabetes. Diabetes was present in 11 (12%) of 94 participants with acute pancreatitis, 69 (27%) of 273 with recurrent acute pancreatitis, and 235 (43%) of 560 with chronic pancreatitis. Among these groups, islet autoantibodies were respectively found in five (5.3%) of 94, 48 (17.6%) of 273, and 127 (22.6%) of 560. The proportions of individuals with diabetes who were autoantibody positive were 45%, 70%, and 54%, respectively (most commonly IAA, which may reflect exogenous insulin use). However, across the entire cohort, 27 participants (2.9%) had two, two (0.2%) had three, and one (0.1%) had four T1D-associated autoantibodies, respectively, suggesting a potential pathogenic link that should be further explored. ARTICLE HIGHLIGHTS Type 1 diabetes–associated autoimmune mechanisms have not been thoroughly examined in pancreatitis-associated diabetes. We assessed the prevalence of four islet autoantibodies in serum from a large prospective cohort of patients with acute, recurrent acute, or chronic pancreatitis. Diabetes was present in 11 (12%) of 94 participants with acute pancreatitis, 69 (27%) of 273 with recurrent acute pancreatitis, and 235 (43%) of 560 with chronic pancreatitis. Excluding those with only insulin autoantibody positivity, which is confounded by insulin treatment, islet autoantibodies were identified in 51 (5.5%) of 927 participants, and 30 (3.2%) of 297 were positive for two or more autoantibodies. Our findings suggest pancreatitis may elicit islet autoimmunity in a subset of patients, necessitating prospective longitudinal follow-up.

The development of automated insulin delivery systems has seen tremendous improvements from individual components to interoperable system combinations of devices and new drugs besides insulin. The components have become progressively smaller, more accurate, and more user friendly. This article summarizes the history of the artificial pancreas from the earliest concepts to fully functional systems to research into further improvements in the future. The authors include many of the developers of this technology who received research support from the National Institute of Diabetes and Digestive and Kidney Diseases at various stages to develop these systems.