bluuebunny/crossref_metadata_2025_split huggingface dataset:
1025-P: Survey on Hypoglycemia in Patients on Insulin Driving More Than Three Times a Week Using Questionnaires and Continuous Glucose Monitoring
Authors: MAEDA RYUTARO , ONOUE TAKESHI , HANDA TOMOKO , KOBAYASHI TOMOKO , ARIMA HIROSHI 
Published: June 2024

Introduction & Objective: Antidiabetic agents increase the risk of traffic accidents due to hypoglycemia. The continuous glucose monitoring (CGM) system, which has recently seen widespread use, has facilitated the determination of hypoglycemia frequency, including asymptomatic hypoglycemia. However, limited research reports have been available on hypoglycemia while driving determined using CGM.
Methods: Questionnaire surveys and a 4-week blind CGM examination were conducted on patients using insulin who drove three or more times a week and visited the hospital regularly.
Results: Among the 29 participants who responded to the questionnaire, 22 (76%) had experienced hypoglycemia in the past, and 12 (41%) had experienced hypoglycemia while driving. CGM in 28 subjects analyzed indicated that all cases had low glucose levels (&lt;70 mg/dL), with 15 patients (54%) having levels &lt;54 mg/dL. The time below range (TBR) &lt;70 and &lt;54 mg/dL was 5.3% (standard deviation: 6.9%) and 0.8% (1.6%), respectively. Over 90% of those with low glucose levels had asymptomatic hypoglycemia. While driving, 15 (54%) and 1 (4%) patients had experienced glucose levels &lt;70 and &lt;54 mg/dL, respectively. While driving, the TBR &lt;70 and &lt; 54 mg/dL was 3.6% (7.1%) and 0.3% (1.6%), which tended to be lower than that during the whole period. Among the patients who had never reported hypoglycemia while driving in the questionnaire, 8 (53%) had low glucose levels while driving determined via CGM. For those who had and had not previously reported hypoglycemia while driving, the TBR &lt; 70 mg/dL was 5.6% (2.1%) and 2.2% (1.9%), respectively. Moreover, the TBR &lt; 70 mg/dL when awake and asleep was 4.3% (7.1%) and 8.1% (11.5%), respectively.
Conclusion: CGM of patients with diabetes using insulin who drive more than three times a week revealed that all cases had low glucose levels (&lt;70 mg/dL), with half experiencing this while driving.

Disclosure
R. Maeda: Research Support; Abbott. T. Onoue: None. T. Handa: None. T. Kobayashi: None. H. Arima: Research Support; Abbott.
1031-P: National Trend in Medical Expenditures in People with Diabetes in the U.S.—2000 to 2021
Authors: TANG SHICHAO , WANG YU , ZHOU XILIN , ZHANG PING 
Published: June 2024

Introduction & Objective: To examine the national trend in medical expenditures in people with diabetes from 2000 to 2021.
Methods: We used the 2000-2021 Medical Expenditure Panel Survey to estimate per person annual medical expenditures in adults &gt;=18 years old with self-reported diabetes. We estimated the medical expenditure (in 2021 US dollars) in total and by component including outpatient (OP), inpatient (IP), emergency room (ER), prescription drugs, and other medical services. We used join-point regression to identify trend changes.
Results: Estimated expenditure increased from $9,700 in 2000 to $16,203 (95% CI, $15,061-$17,344) in 2021 or by 67%. By component, spending on prescription drugs, OP, ER, and other medical services increased by 148%, 103%, 81%, and 89%, respectively, but spending on IP decreased by 17%. For total expenditure, the upward trend was significant from 2011 to 2018 and from 2000 to 2004. Trends in spending by component differed. Increases in prescription drug spending accelerated after 2013 and by 2021 prescription drugs accounted for the largest share of the total.
Conclusion: The overall economic burden of diabetes on the national health care system has been increasing. The composition of spending also changed. Preventing diabetes and its complications may help reduce this growing economic burden.

Disclosure
S. Tang: None. Y. Wang: None. X. Zhou: None. P. Zhang: None.
1032-P: Behavioral Economics-Based Financial and Social Incentives for Glycemic Control in Newly Diagnosed Type 2 Diabetes—A Randomized Control Trial
Authors: YIN CHERYL LAI WAI , YE JIAXI , NG CARMEN S. , QUAN JIANCHAO 
Published: June 2024

Introduction & Objective: To assess the effectiveness of financial and social incentives using behavioral economics to improve glycemic control in patients with newly diagnosed type 2 diabetes.
Methods: We conducted a pragmatic randomized clinical trial with a 6-month intervention period from June 2021 to December 2023. Adults with newly diagnosed type 2 diabetes (glycated hemoglobin [HbA1c] 48-75 mmol/mol) were recruited at public primary care clinics. Participants were randomly assigned to three groups to incentivize physical activity: financial incentive, financial and social incentive, and control. Participants in the incentive groups received personalized weekly step targets along with loss-framed financial incentives starting at $128 USD. Participants lost $5 USD each week if their step target was not met. For the social incentive, participant weekly step performance was shared with their nominated supporters to provide peer encouragement. Intent-to-treat analysis using weighted generalized estimating equations (WGEE) was performed to assess changes in HbA1c. ClinicalTrials.gov identifier: NCT0491792.
Results: Among 104 adults newly diagnosed with type 2 diabetes, the mean age was 55.0 (53.9% female). Median baseline HbA1c for the financial incentive, financial and social incentive, and control group was 51.9, 53.0, and 50.8mmol/mol respectively. While step count increased, participants in the financial incentive group had a non-significant decrease in HbA1c (-0.8 mmol/mol) and no improvement in the financial and social incentive group compared to the control group.
Conclusion: The interventions using financial and social incentives had no significant impact on improving HbA1c in patients newly diagnosed with type 2 diabetes.

Disclosure
W. Lai: None. J. Ye: None. C.S. Ng: None. J. Quan: None.

Funding
Research Grants Council of the Hong Kong Special Administrative Region, China [17607619]
1047-P: Estimating QALY-Based Price Ranges for Diabetes Drugs under IRA Negotiation
Authors: LI PIAOPIAO , LEE JIEUN , HU XIN , VENKAT NARAYAN K M , UMPIERREZ GUILLERMO , SHI LIZHENG , FONSECA VIVIAN , ALI MOHAMMED K. , SHAO HUI 
Published: June 2024

Congress intends to exclude QALYs from the Inflation Reduction Act’s (IRA) Price Negotiation, yet these measures provide valuable pharmacoeconomic insights. Despite concerns of discrimination against the elderly and disabled, QALY could serve as an objective measure of cumulative health, and the discrimination can be addressed by choosing different willingness-to-pay (WTP) levels across subgroups. We used the BRAVO diabetes microsimulation model to project lifetime outcomes for four IRA-listed diabetes drugs (dapagliflozin, empagliflozin, sitagliptin, insulin aspart) for a weighted sample of 1.03 million Medicare beneficiaries with diabetes from the National Health and Nutrition Examination Survey. Drug and service costs were derived from 2018 Medicare claims and QALYs were calculated using Health Utilities Index equation, both adjusted at 3% discount rates. We calculated QALY-based price ranges for the four drugs under various WTP thresholds. Price ranges for diabetes drugs to be cost-effective at different WTP levels are much lower than current price references (Figure). Adjustment of prices for all four drugs may be necessary depending on the payers’ chosen WTP level. Our scale provides QALY-based price benchmarks for diabetes drug pricing to aid payers in negotiations. In September, upon the release of the IRA-determined price, we will evaluate its position on our price scale and assess the reflected WTP.

Disclosure
P. Li: None. J. Lee: None. X. Hu: Research Support; PhRMA Foundation. K. Narayan: None. G. Umpierrez: Research Support; Abbott, Bayer Inc., Dexcom, Inc., AstraZeneca. Advisory Panel; Dexcom, Inc. L. Shi: None. V. Fonseca: Consultant; Abbott, Bayer Inc. Stock/Shareholder; BRAVO4HEALTH, LLC. Consultant; Corcept Therapeutics. Speaker's Bureau; Eli Lilly and Company. Research Support; Fractyl Health, Inc. Consultant; Sun Pharmaceutical Industries Ltd. Stock/Shareholder; Amgen Inc. M.K. Ali: Advisory Panel; Eli Lilly and Company. H. Shao: Consultant; Eli Lilly and Company.
1054-P: Characterizing Clinical and Economic Outcomes among Patients with MASH and Type 2 Diabetes Mellitus Treated with Glucagon-Like Peptide 1 (GLP1)—A Cohort Study
Authors: KIM YESTLE , QIAN CHRISTINA , FISHMAN JESSE , SZABO SHELAGH M. , ROCHON HANNAH , SUN ROSIE , MEDICIS JOE , CHARLTON MICHAEL 
Published: June 2024

Introduction & Objective: Metabolic-dysfunction associated steatohepatitis (MASH; or NASH) affects 3-6% of adults in the US; many also receive GLP1 for type II diabetes mellitus (T2DM) and/or obesity. This study aimed to characterize clinical and economic outcomes among patients with MASH and T2DM with vs. without GLP1s; overall, and among patients with obesity and/or baseline cirrhosis.
Methods: Optum de-identified Clinformatics® Data Mart Database (2015-2022) was used to identify adults with NASH and T2DM. At baseline, patients with vs. without GLP1 use were matched 1:1 on age, sex, and diabetes complications severity index. Prevalence of a composite clinical outcome (mortality, liver transplant, +/- significant hepatic event) and mean total costs per patient per year (PPPY) were estimated and presented for patients overall, who were overweight/obese, and/or had baseline cirrhosis.
Results: NASH patients with T2DM on GLP1s (n=1,268) had a similar length of follow-up and prevalence of the composite outcome as patients without GLP1 (n=1,268; 30 vs. 33 months; 52% vs. 51%). Higher costs PPPY were observed among patients on GLP1s ($78k vs. $72k). This difference was driven by higher pharmacy costs ($11k) with lower medical costs ($5k) among GLP1 users. When restricted to patients overweight/obese, total PPPY costs and prevalence of composite outcome remained higher for GLP1 users; and the prevalence of composite outcome and total costs PPPY were consistently higher for patients with cirrhosis (87%-92%; mean $118k-$134k) vs without cirrhosis (19%-31%; $36k-$53k).
Conclusion: Irrespective of GLP1 treatment among MASH patients with T2DM, those with cirrhosis had worse clinical and economic outcomes. While this analysis did not restrict to indication for GLP1 use, end-stage liver disease events remain an unmet need for all MASH patients regardless of GLP1 use. Therapies that slow progression to cirrhosis are needed.

Disclosure
Y. Kim: Employee; Madrigal Pharmaceuticals, Inc. C. Qian: None. J. Fishman: Employee; Madrigal Pharmaceuticals, Inc. S.M. Szabo: None. H. Rochon: None. R. Sun: None. J. Medicis: Employee; Madrigal Pharmaceuticals, Inc. M. Charlton: Consultant; Madrigal Pharmaceuticals, Inc., 89bio, Inc., Novo Nordisk, Merck & Co., Inc., Sagimet Biosciences, Bristol-Myers Squibb Company, Novartis AG, Pfizer Inc., Terns Pharmaceuticals, Siemens Healthcare Diagnostics.
1065-P: Comparative Effectiveness of the Bivalent COVID-19 mRNA Vaccines mRNA1273-222 and BNT162b2 in Adults with Diabetes in the U.S.
Authors: KOPEL HAGIT , HUNG NGUYEN VAN , BOGDANOV ALINA , WINER ISABELLE , BOILEAU CATHERINE , DUCRUET THIERRY , ZENG NI , BAUSCH-JURKEN MARY , ESPOSITO DAINA B. , BECK EKKEHARD , BONAFEDE MAC , MANSI JAMES A. 
Published: June 2024

Introduction & Objective: Diabetes is associated with an increased risk for severe COVID-19. A subanalysis of a retrospective observational cohort study was conducted to evaluate the relative vaccine effectiveness (rVE) of 2 previously approved bivalent vaccines that target the ancestral SARS-CoV-2 and the omicron BA.4/BA.5 variant, mRNA-1273.222 (Moderna, Inc.) and BNT162b2 bivalent (Pfizer-BioNTech), in US adults with diabetes.
Methods: The study used a US electronic health record dataset (Veradigm) linked with medical claims data of adults aged ≥18 years with ≥1 underlying medical condition associated with increased risk of severe COVID-19 who received a dose of mRNA-1273.222 or BNT162b2 bivalent vaccines between August 31, 2022, and February 28, 2023. The current analysis included a subgroup of individuals with type 1 or type 2 diabetes identified in the dataset by ICD-10 diagnostic code. The rVE was measured against COVID-19-related hospitalizations and COVID-19-related outpatient visits. Follow-up started 7 days after vaccination until May 31, 2023. Propensity score weighting was used to adjust for baseline differences between groups.
Results: Of 639,868 individuals with diabetes included in the analysis, 252,635 received mRNA-1273.222, and 387,233 received BNT162b2 bivalent (post-weighting). After weighting, no variables had an SMD &gt;0.1 therefore no adjustments were made to rVE estimates. The adjusted rVEs of mRNA-1273.222 versus BNT162b2 bivalent vaccine against COVID-19-related hospitalizations and outpatient visits were 15.1% (95% CI, 8.7%-21.0%) and 3.7% (95% CI, 1.2%-6.2%), respectively.
Conclusion: We found greater effectiveness of mRNA-1273.222 compared with the BNT162b2 bivalent vaccine in preventing COVID-19—related hospitalizations in this cohort of individuals with diabetes. This study emphasizes the importance of assessing COVID-19 vaccine formulations in high-risk adults, including those with diabetes.

Disclosure
H. Kopel: Employee; Moderna, Inc. Stock/Shareholder; Moderna, Inc. V. Nguyen: Employee; VHN Consulting Inc. Other Relationship; Moderna, Inc. A. Bogdanov: Employee; Veradigm. Other Relationship; Moderna, Inc. I. Winer: Employee; Veradigm. Other Relationship; Moderna, Inc. C. Boileau: Employee; VHN Consulting Inc. Other Relationship; Moderna, Inc. T. Ducruet: Employee; VHN Consulting Inc. Other Relationship; Moderna, Inc. N. Zeng: Employee; Veradigm. Other Relationship; Moderna, Inc. M. Bausch-Jurken: Employee; Moderna, Inc. Stock/Shareholder; Moderna, Inc. D.B. Esposito: Employee; Moderna, Inc. Stock/Shareholder; Moderna, Inc. E. Beck: Employee; Moderna, Inc. Stock/Shareholder; Moderna, Inc. M. Bonafede: Employee; Veradigm. Other Relationship; Moderna, Inc. J.A. Mansi: Employee; Moderna, Inc. Stock/Shareholder; Moderna, Inc.
1145-P: Development of MLX-0871, a Potent, Isoform-Selective, Orally Available AMPK Activator, Displays Efficacy in Obese and Type 2 Diabetes Models
Authors: VANKAYALAPATI HARIPRASAD , LIN CHENYU , LI ZHAOLIANG , MEDLEY KYLE , BEARSS DAVID J. 
Published: June 2024

Introduction & Objective: AMPK is a αβγ heterotrimeric Ser/Thr kinase that acts as a cellular energy sensor and is activated by upstream enzymes when the cellular ratio of AMP to ATP is elevated due to nutrient deprivation. AMPK activity can be altered due to many physiological factors, such as hormones, cytokines, dietary nutrients, and pathological conditions, such as obesity, chronic inflammation, and type 2 diabetes. AMPK activation can lead to lower hepatic glucose and plasma glucose levels. Thus, AMPK is an attractive target for treating various metabolic diseases.
Methods: 12 isoforms of AMPK in activation mode using radiometric HotSpotTM assay. Glucose Uptake and Western Blot cell-based assays were conducted in human skeletal muscle, upper arm, white preadipocyte, abdomen, and hepatocyte cells. Male C57BL/6 DIO mice aged 20 weeks were fed with a high-fat diet (60 kcal%) for 14 weeks before initiating the experiment. A vehicle group was compared to two dose levels of 10 and 30 mg/kg, dosed orally for the 30-day treatment, with weight loss and serum glucose regulation measured at regular intervals.
Results: MLX-0871, MLX-0867, and analogs are orally available small molecule AMPK activators that have been shown to stimulate AMPK activity and enhance glucose uptake in human tissues dose-dependently. MLX-0871 and MLX-0867 do not cause any AMPK activation in healthy, obese, and diabetic patient cardiac muscle tissue samples and suggest selectivity to skeletal muscle. MLX compounds demonstrated safety and tissue specificity. Preclinical studies suggest that MLX-0871 may have therapeutic potential in the treatment of metabolic disorders such as obesity and type 2 diabetes.
Conclusion: These results suggest that AMPK activators induce insulin modulation and improve oxidative muscle function in obese and type 2 diabetes patient samples. In vitro data supporting studies will be presented, including DIO and db/db efficacy results.

Disclosure
H. Vankayalapati: Board Member; Biolexis Therapeutics, Inc. Stock/Shareholder; Arrien Pharmaceuticals. Board Member; Oncolexis Therapeutics, Inc. C. Lin: None. Z. Li: None. K. Medley: None. D.J. Bearss: Employee; BioLexis Therapeutics, Halia Therapeutics.

Funding
Biolexis Therapeutics, Inc.
1146-P: Familial Associations of the Metabolic Syndrome and Its Interrelated Traits
Authors: RAMIREZ-LUZURIAGA MARIA J. , VAZQUEZ ARREOLA ELSA , HANSON ROBERT L. , KNOWLER WILLIAM C. , SINHA MADHUMITA 
Published: June 2024

Introduction: Metabolic syndrome (MetS) risk factors emerge in childhood. The precursors may include familial association through genetic inheritance or cohabitation.
Objective: Examine familial associations of MetS components between spouses and between parents and their 5-19-year-old offspring.
Methods: Data were obtained from 1,255 mother-father-offspring triads enrolled in a longitudinal study in Arizona (1965-2007). Parent-offspring measures of waist circumference, triglycerides, high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), diastolic blood pressure (DBP), and fasting glucose were used for MetS diagnosis. Parental MetS and its components were defined according to the modified criteria of Adult Treatment Panel III. Additional offspring measures included HbA1c, fasting insulin, HOMA-IR, and type 2 diabetes (T2D).
Results: Parental MetS components associated significantly with higher odds of diabetes and with higher central adiposity, triglycerides, SBP, fasting glucose and insulin, HOMA-IR, and with lower HDL-C in the offspring. These associations were stronger during adolescence and more pronounced between maternal-offspring dyads. For instance, offspring of mothers with hyperglycemia had 10.3 mg/dL higher fasting glucose at ages 12-19 years (vs 2.61 mg/dL higher fasting glucose at ages 05-11 years) than offspring of mothers with normal glucose levels. Parental diabetes partially explained some of these associations. We also found significant spousal concordance in metabolic risk attributes.
Conclusions: Parental MetS characteristics were significantly associated with T2D and cardiometabolic risk factors in offspring. Associations were stronger during adolescence and between maternal-offspring pairs. These findings strongly support the need for family-based interventions directed at modifying health behaviors in high-risk population groups.

Disclosure
M.J. Ramirez-Luzuriaga: None. E. Vazquez Arreola: None. R.L. Hanson: None. W.C. Knowler: None. M. Sinha: None.
1174-P: Circulating MicroRNA in Youth with Type 1 Diabetes in Response to a Meal Challenge
Authors: HAN LEE WAI , NELSON BENJAMIN , TEAGUE APRIL M. , SHORT KEVIN R. , TRYGGESTAD JEANIE B. 
Published: June 2024

Circulating abundance of microRNAs (miRNA) are altered in youth with type 1 diabetes (T1D) and in response to a high fat meal, but whether T1D modifies the miRNA response to a meal is unknown. We identified miRNAs altered in youth with T1D compared to youth without T1D (control) after a high fat meal challenge, a novel approach to understanding how metabolic stress responses may be altered by T1D. Each group had 6 girls and 6 boys, similar in age (17.9±1.5 y), with normal BMI (65±22 and 43±15 percentile, respectively). Serum samples were collected at baseline and 150 min after meal consumption. The meal composition was 75 g carbohydrate, 50 g fat (31 g saturated fat), and 20 g protein. Participants with T1D administered insulin before the meal. Total RNA was extracted using the Qiagen miRNeasy Serum/Plasma Advanced Kit. The Nanostring nCounter Human v3 miRNA Panel was used for miRNA profiling. Abundance values were normalized for the number of reads across all samples. The data were fit to a linear model, and an empirical Baysean test was used to determine differences in circulating miRNAs between groups at baseline and after meal consumption. Significance was set as fold change greater than 0.5 with p&lt;0.05. At baseline 17 miRNA species were lower in abundance in the youth with T1D while 16 were higher. In response to the meal, 3 miRNAs declined, and 4 miRNAs increased in the control group while 4 miRNAs declined, and 2 miRNAs increased in the T1D group. Compared to the control group, the T1D group had 19 miRNAs with smaller post-meal changes and 10 with larger changes. The changes in miR-573, miR-655-3p, and miR-769-5p were negatively correlated with glucose AUC and HbA1c, while the change in miR-3192-5p was positively correlated with glucose AUC and HbA1c. These finding show that T1D modifies responses in serum miRNA abundance following a high fat meal, and some of those differences are associated with glycemia. We postulate that the changes in miRNAs are mediated by glycemia, and future investigations will explore this mechanism.

Disclosure
W. Lee: None. B. Nelson: None. A.M. Teague: None. K.R. Short: None. J.B. Tryggestad: Other Relationship; Ascendis Pharma A/S.

Funding
Tracktenburg Endowment
1175-P: Mental Health and Glycemic Control Disparities among Latinx Adolescents with Type 1 Diabetes
Authors: VARGAS ELIZABETH , TANNER BAILEY , SHOMAKER LAUREN B. , O'DONNELL HOLLY K. 
Published: June 2024

Introduction & Objectives: Latinx youth with type 1 diabetes (T1D) experience disparities and worse health outcomes compared to their Non-Hispanic White (NHW) peers, yet very little is known about mental health in Latinx youth with T1D. This study aimed to describe mental health, glycemic control, and connections between these factors among Latinx and NHW youth with T1D.
Methods: Youth 10-17y (M±SDage=14.3±1.7y) with T1D participating in an observational study completed validated questionnaires within six months of their last HbA1c to assess domains recommended by ADA clinical guidelines: depression, anxiety, fear of hypoglycemia, fear of hyperglycemia, disordered eating, diabetes distress, quality of life, family conflict, and self-reported barriers to adherence. Independent t-tests and chi-square tests compared Latinx v. NHW youth on mental/behavioral health (MBH) indices and glycemic control; associations of MBH with glycemic control, and moderation by race, were tested with regressions.
Results: Latinx youth (n=84) with T1D had worse HbA1c (8.5±0.2% v. 7.9±0.1%) and greater depression, disordered eating, diabetes distress, quality of life, and self-reported barriers to diabetes adherence, compared to NHW youth (n=359; ps&lt;.001). A greater proportion of Latinx youth had elevated depression (25% v. 16%) and disordered eating (30% v. 15%) than NHW youth (ps&lt;0.01). In Latinx youth only, anxiety related to worse HbA1c (p=.04). In all youth, most psychological measures were associated with worse HbA1c, except for anxiety and the cognitive subscales related to fear of hypoglycemia (ps&lt;.05).
Conclusion: In addition to poorer glycemic control, Latinx youth with T1D have worse MBH than NHW youth on most psychological constructs ADA recommends assessing. Given the associations between mental health and HbA1c, addressing mental health in Latinx adolescents with T1D may play a critical role in achieving glycemic control targets in this historically vulnerable population.

Disclosure
E. Vargas: None. B. Tanner: None. L.B. Shomaker: None. H.K. O'Donnell: None.

Funding
National Institute of Health and National Institute of Diabetes and Digestive and Kidney Diseases (T32 5T32DK063687-20)