bluuebunny/crossref_metadata_2025 huggingface dataset:
ON THE FOUNDATIONS OF METAPHYSICS
Authors: Solovyev N. A.
Published: June 2024

The article deals with the problem of establishing the main categories of metaphysics, which later unfold into the metaphysics of the Absolute, the Universe, and human. It is shown that the main categories of metaphysics are the categories of nous/Self, idea/form, substrate/pneuma. In this case, a person can be represented as an anthropic triad of Self-form-substrate, and the Absolute in the form of an absolute Trinity: absolute Self/absolute Form/absolute Substrate. At the same time, the anthropic triad can be considered as a “part” of the absolute Trinity. In the anthropic triad, the form-substrate dyad represents the physical body of a person, and the Self is an extraphysical governing authority. It is shown that the evil existing in the world is a payment for human freedom and the existence of human as a person. At the same time, human freedom is based on the possibility of choosing alternatives in the timeless world of potential possibilities of the Universe.
HISTORY OF CREATION AND METAPHYSICAL ASPECTS OF ELECTROWEAK THEORY: DEVELOPMENT AND MODIFICATIONS OF THE SYMMETRY PRINCIPLE
Authors: Vizgin Vl. P.
Published: June 2024

The history of the creation of a unified theory of electromagnetic and weak interactions (electroweak theory, also called the Weinberg-Salam theory), which is an essential part of the modern theory of elementary particles and fundamental interactions between them, called the standard model, is explored. The main turning points in this history are highlighted: the concept of non-Abelian gauge fields (Yang-Mills fields, 1954), the promotion of the idea of unifying electromagnetic and weak forces (1958-1959), the discovery of the global internal symmetry of electroweak interactions (1961, S. Glashow), the discovery of based on spontaneous symmetry breaking - the Higgs mechanism (1964), which made it possible to solve the problem of the mass of gauge particles (Weinberg-Salam theory, 1967). The metaphysical aspects of the theory and the process of its construction are considered, mainly related to the principle of symmetry and its various extensions and modifications.
Economic Development Theory of Ibnu Khaldun: Interrelation between Justice and Umran al-Alam
Authors: Mafrudlo Ahmad Mahfudzi , Mansur Zuhratul Aini , Mustofa Mustofa , Janwari Yadi
Published: June 2024

ABSTRACT – Leading Islamic thinker, Ibn Khaldun, proposed a nuanced theory of economic development that transcends mere material advancement. This theory integrates Islamic principles within a comprehensive framework. This study aims to delve deeper into Ibn Khaldun's economic development theory, focusing on its emphasis on the Islamic way of life and the concept of Umran al-Alam (prospering the earth). A descriptive analysis methodology was employed through a review of existing literature. Ibn Khaldun outlines eight key suggestions and various variables for achieving economic development. Significantly, he underscores the importance of Umran al-Alam, highlighting humanity's responsibility to cultivate the earth. From an Islamic perspective, economic development should prioritize socio-economic justice and maintain a balance between communal well-being and a healthy economy. This study contributes to a more profound understanding of Islamic economic thought and its potential connections to contemporary notions of sustainable development. Further research opportunities lie in exploring the practical applications of Ibn Khaldun's theories within Islamic economic models.==============================================================================================================ABSTRAK – Teori Pembangunan Ekonomi Perspektif Ibnu Khaldun: Interelasi Keadilan dan Umran al-Alam. Pemikir Islam terkemuka, Ibn Khaldun, menawarkan teori pembangunan ekonomi yang lebih bernuansa, tidak sekedar diukur dari sesuatu yang bersifat materi semata-mata. Teori ini mengintegrasikan prinsip-prinsip Islam ke dalam kerangka kerja yang komprehensif. Studi ini bertujuan untuk menggali secara dalam teori pembangunan ekonomi Ibn Khaldun, khususnya pada cara hidup Islami dan konsep "umran al-Alam" (pemakmuran bumi). Kajian ini menggunakan metodologi analisis deskriptif dengan data-data dari sejumlah literatur tersedia. Ibn Khaldun menguraikan delapan komponen inti dan sejumlah variabel untuk mencapai pembangunan ekonomi dimaksud. Ibnu Khaldun menggarisbawahi pentingnya umran al-Alam, yang menyoroti tanggung jawab manusia dalam memakmurkan bumi. Dari perspektif Islam, pembangunan ekonomi harus memprioritaskan keadilan sosial-ekonomi dan menjaga keseimbangan antara kesejahteraan bersama dan sistem ekonomi yang sehat. Studi ini berkontribusi pada pemahaman yang lebih mendalam tentang pemikiran ekonomi Islam dan potensi hubungannya dengan konsep pembangunan berkelanjutan kontemporer. Peluang penelitian lebih lanjut terletak pada eksplorasi aplikasi praktis teori-teori Ibn Khaldun dalam model ekonomi Islam.
Methodology for assessing the efficiency of horse breeding mechanization under conditions of extremely low temperatures
Authors:   North-Eastern Federal University named after M. K. Ammosov, Anisimov Evsey E. , Druzyanova Varvara P. ,   North-Eastern Federal University named after M. K. Ammosov, Kirillin Alexander A. ,   North-Eastern Federal University named after M. K. Ammosov
Published: June 2024

The article briefly characterizes the state of horse breeding in the Republic of Sakha (Yakutia). There are special features in breeding of the Yakutian horses. The Yakutian horses stay outdoors all year round and feed mainly on fodder. At present, villagers have started to maximize the number of horses due to the unpretentiousness of their feeding. However, another problem has arisen – due to the sharp increase in horse number there is not enough fodder. To solve this problem, it is proposed to organize mechanical distribution of additional feeding in the form of hay in decentralized areas. When calculating additional feeding norm, the following are taken into account: the required mass of hay, which is determined by the herd and the normative amount of hay per horse; the distance between hay distribution place and storage place, fuel consumption and pasture area. The aim of the study is to develop a methodology for forecasting the level of efficiency of herd horse breeding at the mechanized method of hay delivery and distribution by applying a mathematical dependence. It can help in choosing the location and distance for the organization of horse breeding bases in decentralized areas in the conditions of Yakutia. The calculations for preliminary assessment of proposed mathematical dependence efficiency were carried out. The initial data were taken for the existing horse breeding farm – LLC "Horse Farm Berte". The obtained results of forecast calculations have shown that the efficiency of production increases significantly, on average by 56.5% at mechanization of delivery and distribution of additional feeding in decentralized horse-breeding bases. At the farthest horse farm, located 60 km away from the central farmstead, it is possible to increase the number of animals from 145 to 227.
“Nomogram for predicting surgical modalities for initial treatment of CINIII after menopause”
Authors: Gao Xiao , Ma Ning-Ye , Jiao Yisheng
Published: June 2024

Objective:Currently, there is no established preoperative
evaluation standard for direct hysterectomy in CINIII patients who are
unable to undergo conectomy.We have developed a nomogram that can be
used to predict surgical modalities for initial treatment of CINIII
after menopause,and estimated the performance of the nomogram by
internal validations. Design：Case-control design within
retrospective study. Setting：Shengjing Hospital of China
Medical University. Population or Sample：A total of 454
postmenopausal participants diagnosed with CINIII. Methods:
Group A and group B were divided into two cohorts based on different
initial treatment modalities. Group A underwent direct hysterectomy (88
cases), while group B underwent conization followed by hysterectomy (366
cases). Based on the postoperative pathological findings, the patients
were categorized into the upgraded pathological grope (105 cases, with 8
in group A and 97 in group B) and the non-upgraded pathological grope
(349 cases, with 80 in group A and 269 in group B).Multiple logistic
regression analysis was used to identify predictors and establish
nomogram.The performance of the nomogram was evaluated by using the area
under the curve (AUC),calibration curve and the decision curve
analysis(DCA). Main Outcome Measures：Pathological upgrade.
Result:The independent risk factors identified in this study
include menopause years,post-coital bleeding, HPV16/18
infection,cervical lesion counts, SCCAg and TCT (P<0.05). The
six indicators were used to create a nomogram for predicting
pathological upgrade. The training set yielded an AUC of 0.959 (95%
confidence interval [CI], 0.936-0.982), while the validation set
showed an AUC of 0.850 (95% CI, 0.775-0.926).The nomogram was
well-calibrated.The DCA results demonstrate a higher net gain value.
Conclusion：The nomogram model predicts postoperative cervical
cancer risk in postmenopausal CINIII patients based on menopause years,
HPV16/18 positivity, TCT results, SCCAg levels, cervical lesion counts,
and post-coital bleeding. In cases of low risk, direct hysterectomy may
be considered as initial treatment. Our scoring system offers safer and
more efficient treatment options for patients.
Resolving the context-dependency of local heterogeneity - diversity relationships
Authors: Sola Jordi , Griffin John
Published: June 2024

Environmental heterogeneity has long been assumed to promote
biodiversity, but recent theory and evidence suggests substantial
variability in this relationship. Here, we resolve heterogeneity’s
influence on communities by considering its various facets and
contextual moderators, capitalising on >3000 effects
reported in 144 studies on rocky reefs worldwide. Our analyses reveal
generally positive saturating or weakly humped-shaped responses of
richness and abundance, with three-dimensional structure generating the
strongest effects of all facets. Small-bodied and swimming organisms
benefitted the most and larger-bodied benthic organisms the least, while
heterogeneity also mitigated grazing and enhanced recruitment. Community
responses strengthened on biogenic vs. abiotic substrates, and with
environmental stress, both towards the equator and on intertidal vs.
subtidal reefs. We propose that the key moderators unveiled here
(heterogeneity facet, benefactor traits, and environmental stress) will
more generally underpin context-dependent effects of heterogeneity on
biodiversity across organismal groups and ecosystems.
10-OR: Diffusion Tensor Imaging and T2 Mapping of the Tibial Nerve Can Detect Nerve Damage in Type 2 Diabetes
Authors: PARK HYEONG-KYU
Published: June 2024

Magnetic resonance imaging (MRI) has played little role for the study of peripheral nerve disease. However, recent technological advances in MRI have provided us more information about neural microstructure and higher resolution in peripheral nerves. The aim of this study is to evaluate whether diffusion tensor imaging (DTI) in MRI can detect peripheral nerve abnormalities in patients with type 2 diabetes (T2D).In this prospective, single-center study, 33 T2D patients (mean age, 60.5 ± 7.0 yr; 16 M/ 17F) and 12 healthy controls (61.8 ± 5.3 yr, 5M / 7 F) were included. All T2D patients underwent Michigan Neuropathy Screening Instrument questionnaire and quantitative sensory testing. MRI including DTI and axial T2-weight Dixon sequence was performed for each participant. DTI parameters of the tibial nerves such as fractional anisotropy (FA) and diffusivity (mean (MD), axial (AD), and radial (RD)) and T2 relaxation time were calculated. FA of the tibial nerves was significantly lower in T2D patients than healthy controls at both level 1 (0.42 ± 0.07 vs. 0.57 ± 0.09, P<0.001) and level 2 (0.44 ± 0.07 vs. 0.55 ± 0.08, P<0.001). AD was also significantly lower in T2D patients than controls at both level 1 (1.97 ± 0.43 vs. 2.40 ± 0.63, P<0.05) and level 2 (2.18 ± 0.37 vs. 2.59 ± 0.47, P<0.05). RD was significantly higher in T2D patients than controls at level 1 (0.97 ± 0.21 vs. 0.83 ± 0.13, P<0.05). However, there were no differences in DTI parameters between T2D patients with peripheral neuropathy (PN) and those without PN. T2D patients with and without PN had significantly longer T2 relaxation time for the tibial nerve compared to healthy controls. In summary, we demonstrated that DTI and T2 relaxation time can detect microstructural alterations of peripheral nerves in T2D patients with PN as well as those without PN, suggesting that the structural nerve damage can occur before the development of PN in T2D patients.

Disclosure

H. Park: None.
10-PUB: Single Nuclei RNA-seq to Map Adipose Cellular Populations and Senescent Cells in Response to a Lifestyle or Senolytic Intervention in Older Adults with Obesity—A Double-Blind, Placebo-Controlled, Randomized Trial
Authors: CONNOLLY GAVIN , ASLAMY ARIANNE , NIE JIA , KABIR MORVARID , SERRA MONICA C. , ESPINOZA SARA E. , MUSI NICOLAS
Published: June 2024

Introduction & Objective: Older adults with obesity are at an increased risk for metabolic diseases and diabetes. The underlying molecular mechanisms by which increased adiposity and aging predispose individuals to metabolic diseases are not well understood. Recent data suggests that variations in adipocyte cellular subpopulations influence whole-body metabolism, and an increased burden of adipocyte senescent cells has been implicated in metabolic diseases. The purpose of this study is to conduct a double-blinded, placebo-controlled, randomized trial investigating the relations between adipose molecular signatures and cellular senescence on metabolic outcomes.

Methods: Using single nuclei RNA sequencing (SnRNA-seq), we will develop a transcriptomic atlas of human adipose tissue and analyze molecular profiles pre- and post-intervention. We will recruit a cohort of older adults with obesity (≥65 years of age; BMI=30-39.9 kg/m2; n=72). We will obtain adipose biopsies to analyze cellular/molecular profiling via snRNA-seq as it relates to phenotypic measures of insulin sensitivity, glucose tolerance, beta cell function, and hepatic lipid content compared to cohorts of younger lean (18-30 years of age; BMI=18.5-24.9 kg/m2; n = 24) and older lean (≥65 years of age; BMI=18.5-24.9 kg/m2; n=24) participants. The cohort of older adults with obesity will be randomized to one of three groups for 10 weeks: lifestyle (diet- and exercise-induced weight loss of 8-10% of body mass), senolytic (dasatinib and quercetin), or placebo.

Results & Conclusion: The findings from this study will help elucidate whether changes in global adipose molecular signatures and cellular senescence are mechanisms by which lifestyle or senolytic therapy intervention improves metabolic parameters. This information may help identify molecular targets for treating metabolic diseases.

Disclosure

G. Connolly: None. A. Aslamy: None. J. Nie: None. M. Kabir: None. M.C. Serra: None. S.E. Espinoza: None. N. Musi: None.

Funding

National Institutes of Health/National Institute on Aging (R01AG075684)
1001-P: Improvements in Data Availability with the G7 CGM System
Authors: JEPSON LAUREN H. , ANDRADE SARAH B. , WELSH JOHN
Published: June 2024

Introduction & Objective: The G6 CGM system offers a 2-hour warmup and a 10-day lifespan; the G7 system (both from Dexcom) offers a 30-minute warmup and a 12-hour grace period of functionality after 10 days. We examined data gaps and alert availability with the two systems.

Methods: Real-world data were analyzed from 59,285 users in the US and Europe who uploaded ≥60 days of data from G6, transitioned to G7, and then uploaded ≥60 days of data from G7. Comparisons between the last 60 days of G6 use and the first 60 days of G7 use were analyzed.

Results: After switching to G7, the median between-session data gap duration decreased by 1.8 hours, and the proportion of gaps lasting ≥1 hour increased from 0.1% to 54.3% (Table). Most G7 sessions exceeded the 10-day lifespan and extended into the 12-hour grace period. Median time between sensor replacements was 14 minutes shorter with G7 than with G6.

Conclusion: The simpler sensor insertion and shorter warm-up time for G7 provide users with access to the CGM data sooner for more timely diabetes management decisions and the 12-hour grace period provides users flexibility in their schedules with continued access to CGM data.

Disclosure

L.H. Jepson: Employee; Dexcom, Inc. Stock/Shareholder; Dexcom, Inc. S.B. Andrade: Employee; Dexcom, Inc. J. Welsh: Employee; Dexcom, Inc.
1016-P: Development of Highly Accurate Measurement Method of Salivary Glycated Albumin by HPLC
Authors: AIHARA MASAKAZU , KUBOTA NAOTO , YAMAUCHI TOSHIMASA
Published: June 2024

Objective: Measurements diabetes-related biomarkers are necessary to determine glycemic management, however commonly used home finger-prick blood glucose test and HbA1c measurements at hospital are invasive. Blood glycated albumin (GA) is also commonly measured in an invasive manner. This study aimed to develop a non-invasive method for evaluating glycemic control: measurement of salivary GA using high-performance liquid chromatography (HPLC) method with high accuracy.

Research Design & Methods: Participants with diabetes mellitus, who admitted to The University of Tokyo Hospital for glycemic management, were recruited for this study. Blood and saliva samples were collected three times (fasting and 2-hour postprandial on admission and fasting on discharge). Blood and saliva samples after the partial purification using antibody-based column were measured for GA levels using HPLC method.

Results: We enrolled 56 participants with diabetes mellitus in the study. There was a correlation between GA levels in blood and saliva collected fasting and 2-hour postprandial on admission and fasting on discharge. Multiple regression analysis revealed the associations were maintained even after adjustments for age, BMI, and nephropathy stage.

Conclusions: In this study, preprocessed saliva samples were measured for GA levels using HPLC method. Salivary GA levels measured by this method were so accurate to replace blood GA measurement. In the future, we would like to develop post-in or home salivary GA measurement method so that people with diabetes can easily and non-invasively monitor and improve their own glycemic management status.

Disclosure

M. Aihara: None. N. Kubota: None. T. Yamauchi: Research Support; Mitsubishi Tanabe Pharma Corporation. Other Relationship; Covidien Japan Inc. (Medtronic Japan Co., Ltd.). Research Support; Novo Nordisk. Other Relationship; Astellas Pharma Inc., AstraZeneca K.K. Research Support; Ono Pharmaceutical Co., Ltd. Other Relationship; Novartis International AG. Research Support; Boehringer Ingelheim GmbH Japan. Other Relationship; Kyowa Kirin Co., Ltd. Research Support; Kowa Company, Ltd. Other Relationship; Merck Sharp & Dohme Corp., Sanofi, SANWA KAGAKU KENKYUSHO CO., LTD., Daiichi Sankyo, Taisho Pharmaceutical Holdings Co., Ltd. Research Support; Eli Lilly and Company, Sumitomo Pharma Co., Ltd., Asahi Mutual Life Insurance Company, Nipro Corporation, Otsuka Pharmaceutical Co., Ltd., Teijin Pharma Limited, Shionogi & Co., Ltd. Other Relationship; Abbott Japan Co., Ltd. Research Support; Boehringer Ingelheim GmbH. Other Relationship; Terumo Corporation, Viatris Inc., LifeScan Japan Co., Ltd., Roche DC Japan Co., Ltd., Cosmic Corporation Co., Ltd., ARKRAY Marketing Co., Ltd.
102-OR: A Novel Strategy for Detecting In Vivo Functional ß-Cells Using Positron Emission Tomography (PET) Imaging
Authors: LI JUNFENG , YIN RUNKAI , RAWSON JEFFREY , KANDEEL FOUAD R.
Published: June 2024

Introduction & Objective: Autopsy studies in individuals with T1D demonstrated residual β cells. There are significant challenges in accurately evaluating in vivo insulin secretion from functional β-cells, hampering therapeutic translations of β-cell regeneration to human. Zn2+ is an excellent biomarker of β-cell insulin release. Tracking pancreatic free Zn2+ could provide a window to detect β-cell function. We aimed to investigate if a chelating-zinc PET probe could detect Zn2+ released from β-cells to evaluate their insulin secretion.

Methods: 18F-labeled Tripicolylamine (TPA) demonstrated high specific affinity to Zn2+. We evaluated 18F-TPA PET imaging in two mice models with/without glucose stimulation: in vivo healthy NODscid mice and ex vivo STZ-induced diabetic mice. Following PET imaging, biodistribution and immunostaining were conducted and analyzed.

Results: 18F-TPA PET imaging could efficiently detect change in healthy mice without/with glucose stimulation (Figure). There was low imaging interference from organs adjacent to pancreas. 18F-TPA could detect the functional residue β-cells in diabetic mice. Biodistribution and immunostaining validated PET imaging results.

Conclusion: 18F-TPA PET imaging detected Zn2+ released from β-cells, reflecting insulin secretion capacity. It can be valuable for tracking in vivo β-cell function in future T1D treatment strategies.

Disclosure

J. Li: None. R. Yin: None. J. Rawson: None. F.R. Kandeel: Advisory Panel; Vertex Pharmaceuticals Incorporated.

Funding

the Oxnard Foundation (50214-2012049); WFP Mid-Term Innovative Award (10014-2011440)
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 (<70 mg/dL), with 15 patients (54%) having levels <54 mg/dL. The time below range (TBR) <70 and <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 <70 and <54 mg/dL, respectively. While driving, the TBR <70 and < 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 < 70 mg/dL was 5.6% (2.1%) and 2.2% (1.9%), respectively. Moreover, the TBR < 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 (<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 >=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 >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<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<.001). A greater proportion of Latinx youth had elevated depression (25% v. 16%) and disordered eating (30% v. 15%) than NHW youth (ps<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<.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)
1179-P: Deletion of IER3IP1 in ß-Cells Causes Glucose Intolerance via Disruption of IRE1α-XBP1 Signaling
Authors: MEN LILI , QIAO LU , DU JIANLING , REN DECHENG
Published: June 2024

Background: Mutations in the gene for immediate early response 3 interacting protein 1 (IER3IP1) caused permanent neonatal diabetes in human. In previous report, we showed IER3IP1 KD induced cell death and decreased proliferation in MIN6 cells. In this study, we define the role of IER3IP1 in β-cells in vivo, and identify the mechanism of diabetes induced by IER3IP1 deficiency in mice.

Methods: In order to determine the role of IER3IP1 in β-cells and molecular mechanism by which IER3IP1 deficiency cause diabetes, IER3IP1 specific β-cell knockout mice lines were generated using RIP-Cre transgenic mice (βKO).

Results: There was no significant difference in the body weight between Βko mice and WT (IER3IP1+/+Cre+) mice. βKO mice develop glucose intolerance and decreased insulin secretion response to glucose in vivo as well as in isolated islets compared to WT mice. Moreover, βKO mice showed a decrease in β-cell mass due to the increase in β-cell death. Furthermore, deletion of IER3IP1 in β-cells causes ER stress. Both mRNA and protein levels of IRE1α were increased while spliced XBP1 (sXBP1), a downstream target of IRE1α, was decreased in the two animal models.

Conclusion: IER3IP1 deficiency in β-cells induces diabetes via disruption IRE1α-XBP1 signaling pathway.

Disclosure

L. Men: None. L. Qiao: None. J. Du: None. D. Ren: None.