bluuebunny/crossref_metadata_2025_split huggingface dataset:
1951-LB: Impact of Discontinuation of Automated Insulin Delivery Systems in the Emerging Adult with Type 1 Diabetes
Authors: WATERMAN LAUREN A. , COBRY ERIN C. , SAKAMOTO CASEY , PYLE LAURA , FORLENZA GREGORY P. , SHAH VIRAL N. , ALONSO GUY T. 
Published: June 2024

Introduction & Objectives: Automated insulin delivery (AID) systems can improve HbA1c in people with type 1 diabetes (T1D). Data are limited on rates and impact of discontinuation of newer AID in the emerging adult population.
Methods: Retrospective chart review was performed on 14-30 year olds with T1D of ≥ 1 year duration, started on an AID system (Medtronic 770G, Control-IQ, Omnipod 5) after 2018. HbA1c prior to and quarterly for 24 months after initiation were collected. Discontinuation of AID (≥ 1 visit without use) was noted. Mixed model was fit for HbA1c values and time, adjusting for age, sex, diabetes duration, race/ethnicity, and insurance. Contrasts generated to compare HbA1cs at each time point.
Results: In 613 emerging adults with T1D (mean age 21.1±4.2 years, diabetes duration 10.8±6.0 years, male 44.5%, non-Hispanic White 76.8%), 3109 HbA1c values were collected. Mean HbA1c decreased from 8.5% at baseline to 7.7% by 24 months (p&lt;0.001). Discontinuation was associated with higher HbA1c (p&lt;0.001). AID was discontinued at least temporarily by 15.3% of patients (N=94), with highest rates in 19-22 year olds (38 of 174, 21.8%). AID discontinuation reasons included supply (25.5%) or cost/insurance issues (15.3%).
Conclusion: Consistent AID usage in emerging adults is associated with sustained improvements in HbA1c levels. Further study on strategies to reduce discontinuation is required.

Disclosure
L.A. Waterman: None. E.C. Cobry: Advisory Panel; Dexcom, Inc. Other Relationship; Dexcom, Inc. C. Sakamoto: None. L. Pyle: None. G.P. Forlenza: Research Support; Abbott, Dexcom, Inc. Consultant; Dexcom, Inc. Research Support; Insulet Corporation. Consultant; Insulet Corporation. Research Support; Medtronic. Advisory Panel; Medtronic. Research Support; Tandem Diabetes Care, Inc. Consultant; Tandem Diabetes Care, Inc. V.N. Shah: Consultant; Dexcom, Inc., Insulet Corporation. Research Support; Insulet Corporation. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Sanofi, Medscape. Consultant; embecta, Tandem Diabetes Care, Inc. G.T. Alonso: Advisory Panel; MannKind Corporation.

Funding
National Institutes of Health (5T32DK063687)
1976-LB: Sleep Characteristics in Association with the Risk of Progression from Gestational Diabetes to Type 2 Diabetes—A Prospective Cohort Study
Authors: YIN XIN , BAO WEI , YANG JIAXI , YU GUOQI , LIU PEIPEI , ZHANG CUILIN 
Published: June 2024

Introduction & Objective: Sleep is a crucial lifestyle factor associated with cardiometabolic health, yet its role in the progression from gestational diabetes mellitus (GDM) to type 2 diabetes (T2D) is underexplored. Our study investigated the associations between sleep, T2D risk, and metabolic biomarkers in these high-risk women.
Methods: We followed 2,999 women with a history of GDM in the Nurses’ Health Study II for incident T2D between 2001 and 2019. Sleep characteristics, health-related and other lifestyle factors were ascertained in 2001 questionnaire. Glucose metabolic biomarkers were measured in a subset of participants with available fasting blood samples collected between 2012 and 2014 (n=536). Cox regression models were used to calculate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of T2D. Least-squares means (95% CIs) of metabolic biomarker levels were estimated according to sleep characteristics.
Results: During a mean of 14.8 years of follow-up, 520 women developed T2D. Compared to sleeping 7-8 hours per day, shorter sleep duration (≤6 hours/day) was significantly associated with a higher risk of T2D, with an adjusted HR of 1.28 (95% CI = 1.03-1.58). Compared with rarely snoring, occasional and regular snoring were significantly associated with a higher T2D risk, with adjusted HR of 1.44 (95% CI = 1.11-1.86) and 1.52 (95% CI = 1.16-2.00), respectively. The highest risk of T2D was observed in obese women who experienced shorter sleep duration (HR=6.99, 95% CI = 4.62 - 10.6), compared with non-obese women who sleep 7-8 hours per day. Furthermore, significant positive associations were observed between more frequent snoring and increased levels of HbA1c, C-peptide, and insulin (all P-values&lt;0.05).
Conclusion: Among women with a history of GDM, shorter sleep duration and more frequent snoring were significantly associated with increased risk of T2D and unfavorable cardiometabolic profile.

Disclosure
X. Yin: None. W. Bao: None. J. Yang: None. G. Yu: None. P. Liu: None. C. Zhang: None.
1977-LB: Successful Occurrence of Two Separate Pregnancies in a Patient with Congenital Generalized Lipodystrophy Due to Homozygous AGPAT2 Mutations without Recombinant Leptin Therapy
Authors: SANTOMAURO JUNIOR AUGUSTO C. , FRANCO PEDRO C. , COSTA-RIQUETTO ALINE D. , JORGE ALEXANDER A. , TELES MILENA G. 
Published: June 2024

Introduction and Objective: Congenital generalized lipodystrophy (CGL) is a rare genetic disorder with a prevalence of approximately 1/2 million people, characterized by the absence of adipose tissue and associated with significant metabolic and hormonal complications that adversely affect fertility and pregnancy outcomes. We aim to report on two distinct successful pregnancies in a patient with CGL, attributed to homozygous mutations in the AGPAT2 gene, which were managed without the intervention of recombinant leptin.
Results: A 34-year-old woman diagnosed with CGL, bearing homozygous AGPAT2 mutations (c.299 G&gt;A and c.493 -1G&gt;C), displayed typical symptoms of the disorder, such as diabetes mellitus from the age of 15, pancreatitis secondary to hypertriglyceridemia at age 25, polycystic ovary syndrome, hepatic steatosis, and signs of muscular pseudohypertrophy, among others. After her diagnosis, she began a stringent low-carbohydrate diet. Her medication regime included solely metformin, 1500mg daily. The first pregnancy occurred naturally at 27y and was managed without complications with dietary measures alone and underwent a vaginal delivery of a 3500g baby. She is currently progressing well through her second pregnancy, expected in April 2024, with no complications thus far and only required insulin therapy in the third trimester to maintain optimal glycemic and lipid profiles.
Conclusions: Given the typically impaired fertility associated with CGL, the occurrence of pregnancies in this population is notably rare. The literature predominantly features cases that necessitate the use of recombinant leptin for metabolic management during pregnancy. However, this case study, suggests that despite the presence of homozygous mutations, CGL can manifest with less severe metabolic disruption, which may have implications for fertility and pregnancy prognosis in affected individuals.

Disclosure
M.G. Teles: None.
1979-LB: Factors Predicting Elevated LDL Cholesterol in a Type 1 Diabetes Cohort—A Cross-Sectional Study
Authors: LOVE KAITLIN , DART MARINA 
Published: June 2024

Introduction & Objective: Type 1 diabetes (T1D) confers substantial cardiovascular disease (CVD) risk. Major U.S. guidelines recommend statin use in all people with T1D ages 40-75, with target low density lipoprotein (LDL) cholesterol level &lt; 100 mg/dL. The objective of this study was to assess frequency of LDL above target and to examine demographic and socioeconomic characteristics associated with LDL above target in individuals with T1D.
Methods: We conducted a cross-sectional analysis of individuals with T1D ages 55-75 using Premier Healthcare Database (PHD) outpatient encounter data from January 2020 to December 2022. The outcome variable was LDL ≥ 100 mg/dL. Predictor variables included age, sex, race, ethnicity, CVD diagnosis, and insurance payor (Medicare/other government payor, Medicaid, Commercial, Managed Care, self-pay or other). Using SAS 9.4, a logistic regression model was used to determine covariates associated with LDL≥100 mg/dL after adjusting for other covariates.
Results: Of 5,344 individuals in the cohort (51.5% women, mean age 65.3 ± 5.9 years, and 6.3% with CVD diagnosis), 34.9% had LDL ≥100 mg/dL. Female sex (OR 1.59, 95% CI 1.42-1.77, p &lt; 0.0001) and insurance coverage by Medicaid (OR 1.74, 95% CI 1.94-2.53, p &lt; 0.01) were independently associated with increased odds of LDL above target. Older age (OR 0.98, 95% CI 0.97-0.99, p = 0.01) and CVD diagnosis (OR 0.60, 95% CI 0.46-0.77, p &lt; 0.0001) were independently associated with reduced odds of LDL above target. Race and ethnicity were not associated with LDL above target.
Conclusion: A large percentage of this cohort at high-risk for CVD had elevated LDL, and factors independently associated with elevated LDL levels were female sex, Medicaid insurance, younger age, and lack of CVD diagnosis. Female sex or Medicaid insurance increased odds of elevated LDL by 59% and 74% respectively adjusting for other covariates. Further study to understand cause of these disparities is needed.

Disclosure
K. Love: None. M. Dart: None.

Funding
National Institutes of Health (K23DK131327-01A1)
1985-LB: Assessing the Impact of Diabetes on Gastrointestinal Symptom Severity in Exocrine Pancreatic Insufficiency (EPI/PEI)—A Diabetes Subgroup Analysis of EPI/PEI-SS Scores
Authors: LEWIS DANA M. 
Published: June 2024

Introduction & Objective: Exocrine pancreatic insufficiency (known as EPI or PEI) has a high symptom burden and is present in as many as 3 of 10 PWD. A new symptom tool, the Exocrine Pancreatic Insufficiency Symptom Score (EPI/PEI-SS), has been evaluated in the general population to assess real-world symptom burden in individuals with (n=155) and without (n=169) EPI. A large cohort of PWD were analyzed to evaluate whether diabetes contributes to a difference in EPI/PEI-SS score.
Methods: EPI/PEI-SS scores were analyzed and compared between PWD (n=118), with EPI (T1D: n=14; T2D: n=20) or without EPI (T1D: n=78; T2D: n=6), and people without diabetes (n=206) with and without EPI.
Results: People with diabetes had statistically significant higher mean EPI/PEI-SS scores (102.62 out of 225, SD: 52.46) than did people with diabetes without EPI (33.64, SD: 30.38), irrespective of presence of other GI conditions (all group comparisons p&lt;0.001). T1D and T2D subgroups were similar.
Conclusion: EPI has a high symptom burden, irrespective of diabetes. High scores using the EPI/PEI-SS among people with diabetes can distinguish between EPI and other GI conditions. The EPI/PEI-SS should be further studied as a possible screening method for EPI and assessed as a tool to aid PWD in tracking changes to EPI symptoms over time based on PERT titration.

Disclosure
D.M. Lewis: None.
1989-LB: High Serum Ketone Emergencies and Diabetic Ketoacidosis (DKA) in People with Type 2 Diabetes, Prediabetes, and Obesity on Carbohydrate Restricted Nutrition Therapy (CRNT)
Authors: ROBERTS CAROLINE G.P. , ATHINARAYANAN SHAMINIE J. , RATNER ROBERT E. 
Published: June 2024

CRNT including nutritional ketosis is increasingly used by people with Type 2 diabetes (PWT2D), prediabetes (PWPreD), and obesity (PWO) for weight loss and glycemic control. The characteristics of high ketone emergencies in people on CRNT are not known. DKA is a known complication of diabetes; triggers include very low carbohydrate diet and SGLT2-inhibitors (SGLT2i). We reviewed all in-person medical assessments for high fingerstick beta hydroxybutyrate (BHB) readings self-reported by patients at a telemedicine clinic. From 2017 to 2023, 85 PWT2D (1.7/1k person-years) sought medical care for high BHB. Mean age was 55 years (SD 9), 35 (42%) were female, mean diabetes duration was 16 years (SD 9), 38 (45%) were on SGLT2i, and 32 (38%) were on insulin. The incidence of severe high ketone emergencies was extremely low (0.8/1k person-years). Home glucose and home BHB levels did not distinguish severe from mild conditions. Higher laboratory glucose (p&lt;0.001), lower pH and bicarbonate (p&lt;0.001), and greater anion gap (p&lt;0.001) were seen more often in more severe disease. Moderately abnormal values were common in both severe and moderate disease. These findings underscore CRNT’s potential as a remarkably safe and effective tool for metabolic disease management in the setting of remote biomarker monitoring.

Disclosure
C.G.P. Roberts: Other Relationship; Virta Health Corp. S.J. Athinarayanan: Employee; Virta Health Corp. R.E. Ratner: Stock/Shareholder; Abbott, AbbVie Inc. Other Relationship; American Diabetes Association, Juvenile Diabetes Research Foundation (JDRF). Advisory Panel; National Committee for Quality Assurance, National Institute of Diabetes and Digestive and Kidney Diseases, Virta Health Corp.
1992-LB: Area Deprivation Index of Participants in the Rare and Atypical Diabetes Network (RADIANT)
Authors: SON RACHEL G. , LETOURNEAU-FREIBERG LISA R. , POLLIN TONI I. , NAYLOR ROCHELLE N. , STUDY GROUP RADIANT 
Published: June 2024

Introduction & Objective: RADIANT is a multicenter, US-based study of the causes of atypical diabetes and how it informs overall understanding of diabetes etiology and heterogeneity. A key goal is equitable inclusion so that knowledge gained will be broadly applicable. Populations at risk for underrepresentation in research include those with low socioeconomic status. We assessed area deprivation index (ADI), a census-based socioeconomic index, of RADIANT participants. We evaluated the relationship of ADI with participant characteristics.
Methods: Participants with valid U.S. addresses and available ADI ranking were included in the study. Participant characteristics were summarized; 2021 ADI values were constructed based on participant address. ADI values were compared to the expected value of 50th percentile via the Wilcoxon test and compared among groups via the Kruskal-Wallis test.
Results: There were 892 RADIANT participants included in the analysis. The median U.S. ADI of participants was 28, lower than the expected value of 50 (p&lt;0.001). Only 24.5% of participants had ADI &gt;50th percentile. Median ADI differed by race, but not ethnicity, with Asian participants having the lowest median ADI (13), compared to Blacks (29) and Whites (29) (p&lt;0.01). Median ADI did not differ by referral source (e.g., provider vs. self-referral). ADI compared across ~3 consecutive years was statistically different (Median ADI 24, 30, 29; p&lt;0.05), driven by an increase from year 1 to year 2.
Conclusion: This study found that a low number of RADIANT participants live in areas of high deprivation, suggesting ascertainment bias in enrollment and highlighting the need for continued development of recruitment practices that will engage individuals likely to face barriers to research participation and who simultaneously carry a higher disease burden from diabetes.

Disclosure
L.R. Letourneau-Freiberg: None. T.I. Pollin: None. R.N. Naylor: None.

Funding
National Institute of Health (DK118638); National Institute of Health (U54 DK118612)
20-OR: Digital Twin (DT) Technology in Type 2 Diabetes Remission and Glycemic Improvement—Eighteen Months Results from a Randomized Controlled Trial
Authors: SHAMANNA PARAMESH , DHARMALINGAM MALA , VADAVI ARUN , KESHAVAMURTHY ASHOK , BHONSLEY SUCHITRA , THAJUDEEN MOHAMED , SHA ASMIN , JOSHI SHASHANK R. 
Published: June 2024

This study assesses the impact of Digital Twin (DT) technology, utilizing AI for postprandial glucose prediction, on T2D remission. Of the 233 participants using DT, 18 months' results were available for 218, showing significant improvements. Key metrics included reductions in HbA1c levels, body weight, HOMA2-IR, and HOMA2B. The mean age and duration of diabetes were 44 years (±8.6) and 3.7 years (±2.7), respectively. Notable changes from baseline to eighteen months in these 218 participants included HbA1c (from 8.9 ± 1.9, 95% CI 8.7-9.2 to 6.4 ± 0.9, 95% CI 6.3-6.5), body weight (from 78.1 kg ± 14.3 to 72.8 kg ± 13.7), BMI (from 27.2 ± 4.3 to 25.2 ± 4.1), waist circumference (from 97.4 cm ± 11 to 88.1 cm ± 10.5), HOMA2-IR (from 1.9 ± 0.9 to 1.5 ± 0.8), and HOMA2B (from 51.9 ± 30.8 to 70.9 ± 32.9). Remission was defined as A1C levels less than 6.5% without medication for over 3 months. Out of the initial 233 DT participants, 207 completed a minimum of six months of the intervention, qualifying them for remission evaluation. Of these, 64.3% (133/207) achieved sustained remission at eighteen months. The standard care participants showed minimal HbA1c change (from 8.5 ± 1.8 to 8.3 ± 1.6). These findings underscore the potential of DT as a transformative tool in diabetes management, with significant correlations observed between reductions in A1c, body weight, and HOMA2B.

Disclosure
P. Shamanna: None. M. Dharmalingam: None. A. Vadavi: None. A. Keshavamurthy: None. S. Bhonsley: None. M. Thajudeen: None. A. Sha: None. S.R. Joshi: Consultant; Twin Health, Marico, Franco Indian, Zydus Cadila, Glenmark Pharmaceuticals. Other Relationship; Novo Nordisk, Sanofi, MSD, Abbott Nutrition, Abbott, Biocon, Alkem, USV Private Limited, Boehringer-Ingelheim.
200-OR: Postpartum Islet-Cell Function in Individuals With and Without Gestational Diabetes
Authors: EGAN AOIFE M. , CHRISTIE HANNAH E. , MOHAN SNEHA , VELLA ADRIAN 
Published: June 2024

Gestational diabetes mellitus (GDM) affects approximately 10% of pregnancies. Although &gt;60% individuals with GDM develop a disorder of glucose metabolism by 10 years postpartum, preventive care is lacking as the mechanisms leading to overt diabetes following pregnancy remain elusive. As part of a series of studies to understand the pathogenesis of GDM, we examined islet function at 3, 6 and 12 months postpartum. We included women with (n=10), and without (n=10) GDM in the preceding pregnancy. There were no differences in age, body mass index, or lean body mass between groups. At each study visit, subjects presented following an overnight fast and ingested a 75g oral glucose solution at time 0. Venous blood was drawn fasting and at frequent intervals over 180 minutes for measurement of glucose and hormone concentrations. At 3 months postpartum, those with GDM had higher fasting glucose (4.9 ± 0.1 v 4.5 ± 0.1 mmol/L, GDM vs normal respectively, p=0.04) but no differences in peak / integrated glucose compared to those without. Fasting insulin (31 ± 6 vs 14 ± 1 pmol/L, p=0.01) and C-peptide (0.64 ± 0.09 vs 0.44 ± 0.02 mmol/L, p=0.04) were higher in those with GDM with no differences in peak / integrated concentrations. Fasting (4.9 ± 0.4 vs 3.4 ± 0.3 pmol/L, p=0.01) and area under the curve (398 ± 21 v 340 ± 11pmol / 180 min, p=0.03) glucagon were higher in those with GDM. At 6 and 12 months postpartum, these differences were no longer evident with similar glucose and hormone concentrations between groups. These data suggest that both α- and β-cell dysfunction likely contribute to GDM with residual dysfunction present at 3 months postpartum. This is no longer evident by 6 months postpartum. Further longitudinal work is needed to determine progression of fasting and post-challenge islet cell function throughout pregnancy and postpartum to understand how those with GDM are primed for early onset type 2 diabetes.

Disclosure
A.M. Egan: None. H.E. Christie: None. S. Mohan: None. A. Vella: Research Support; Novo Nordisk. Consultant; Hanmi Pharm. Co., Ltd., Crinetics Pharmaceuticals, Inc. Advisory Panel; Rezolute, Inc.

Funding
National Institutes of Health (K23DK134767)
2001-LB: Small RNA-seq Identifies Distinct miRNAs Involved in Familial and Sporadic Type 1 Diabetes Cases from Kuwait
Authors: NIZAM RASHEEBA , ZUBBAIR MALIK MD. , JACOB SINDHU , KOISTINEN HEIKKI A. , TUOMILEHTO JAAKKO , ALKANDARI HESSA , ALMULLA FAHD , THANGAVEL ALPHONSE T. 
Published: June 2024

Clinical diagnosis of Type 1 Diabetes (T1D) has been hallmarked by the presence of serum biomarkers such as circulating autoantibodies and c-peptide; however, identification of additional biomarkers associated with T1D is crucial for better diagnosis of the disease and for developing effective therapeutic strategies. Epigenetic modifications, such as dysregulated expression of miRNAs, have also been shown to have a major impact on diabetes and related metabolic complications. In the present study, we aimed to identify the key miRNAs involved in T1D by screening familial and sporadic cases using Next-generation sequencing (NGS) methodology, followed by quantitative real time PCR. The major questions addressed in this study include, what are the key microRNAs, their target genes and molecular pathways involved in T1D. Blood samples were collected from a total of eight families consisting of 18 people with T1D and 18 unaffected first-degree relatives and tested by NGS, followed by validation of key markers in a cohort of 110 sporadic T1D cases and 15 controls without T1D. Our study highlights 23 miRNAs that are differentially expressed in individuals with T1D compared to controls. Functional enrichment analysis of differentially expressed miRNAs highlighted PI3K-AKT as one of the key pathways involved in T1D. We validated the highest order network motif comprising miRNA, key transcription factors and the key miRNA target genes using quantitative real time PCR. Our study portrays hsa-miR-320a, CAV1, GSK3B and MYC as novel transcriptional biomarkers with diagnostic potential for T1D and may lay the foundation for further in-depth research catering better outcome and treatment of T1D.

Disclosure
R. Nizam: None. M. Malik: None. S. Jacob: None. H.A. Koistinen: Other Relationship; AstraZeneca, Novo Nordisk. J. Tuomilehto: Stock/Shareholder; Orion Pharma, Aktivolabs, Digostics. F. Almulla: None.

Funding
This study was supported by institutional funding from the Kuwait Foundation for the Advancement of Sciences to Dasman Diabetes Institute.