bluuebunny/crossref_metadata_2025_split huggingface dataset:
208-LB: Plasma Lipidomics Reveals Sex-Specific Associations with? Brown Adipose Tissue in Asian Children
Authors: THWAY TINT MYA , CHEN LI , KOTHANDARAMAN NARASIMHAN , LEOW MELVIN K. , PRAKASH KN BHANU , YAP FABIAN , SENG LEE YUNG , THAM ELIZABETH H. , CHONG YAP-SENG , V FORTIER MARIELLE , GODFREY KEITH , WENK MARKUS , ERIKSSON JOHAN 
Published: June 2023

Brown adipose tissue (BAT) plays a crucial role in lipid metabolism. Activated BAT oxidizes fatty acids from triglycerides in lipid droplets during thermogenesis, increasing energy expenditure. The lipidomic profile of BAT has been primarily studied in animals but little in humans. We sought to identify the plasma lipidomic profile associated with BAT in a thermoneutral condition in 6-year-old children (n=134) in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. LC-MS/MS-based quantification of 480 lipids was performed on plasma samples; %BAT was quantified based on fat-signal-fractions of water-fat-MRI. Associations between plasma lipids and the child's %BAT were investigated using multivariate regression analysis adjusting for sex, ethnicity, and BMI. Sex stratification was applied to investigate the sex-specific lipid signatures of %BAT among the 68 boys and 66 girls. The inverse association between %BAT and BMI was stronger in boys (R2 =0.28) than in girls (R2 =0.07). More lipid signatures of %BAT were observed in boys compared to girls; of 63 unique lipid species significantly associated with %BAT, 12 were associated in both genders, 50 in boys and 11 in girls. In boys, lipid species representing triacylglycerol, cholesteryl ester, acylcarnitine, sphingomyelin, ceramide, hexosylceramides and lysophosphatidylcholine classes showed negative associations with %BAT, whereas several phosphatidylethanolamine lipids displayed positive association with %BAT. In girls, opposite trends in effect sizes (R=-0.44) were, however, observed; several lipids in acylcarnitine, diacylglycerol and sphingolipid classes presented positive association with %BAT, while phosphatidylethanolamine lipids showed negative associations with %BAT. These unique associations between plasma lipid species and BAT in a sex-specific manner provide insights into the different potential lipidomic pathways involved in BAT energy metabolism.

Disclosure
M. Tint: None. M. Fortier: None. K. Godfrey: Other Relationship; See box. M. Wenk: None. J. Eriksson: None. L. Chen: None. N. Kothandaraman: None. M. K. Leow: None. B. Kn: None. F. Yap: None. Y. Lee: None. E. H. Tham: None. Y. Chong: None.

Funding
Open Fund Large-Collaborative Grant (000504)
208-OR: Comparable Improvement in NAFLD, Weight Loss, and Lipid Metabolism in Rats Treated with Dual GLP-1–GIP Receptor Agonist (Tirzepatide) and Gastric Sleeve
Authors: ABUBAKER JEHAD , ALSABAH SALMAN , AL-KHAIRI IRINA , CHERIAN PREETHI T. , ABUKHALAF NERMEEN A. , AREFANIAN HOSSEIN , DSOUZA CAROL , AL-SABAH SULEIMAN , AL-MULLA FAHD , ABU-FARHA MOHAMED 
Published: June 2023

Background: Bariatric surgery is increasingly utilized as a weight management and metabolic control procedure, hence the name metabolic Surgery. Metabolic surgery is currently considered as an effective procedure for the treatment of diabetes providing a phenomenal hope for a long-lasting remission of diabetes. The use of combined GIPR and GLP-1R activation has recently emerged as a novel therapeutic tool in the treatment of T2D that produces profound weight loss, glycemic control, and lipid lowering. Tirzepatide (LY3298176) is a novel dual GIP and GLP-1 receptor agonist.
Objectives: The aim of this study is to evaluate the difference between GLP-1/GIP receptor agonist (Tirzepatide) treatment vs bariatric surgery on weight loss, NAFLD, insulin signaling and insulin resistance in SD rats.
Methods: Sprague-Dawley rats between the age of 4-6 weeks were either placed on regular rat chow diet (n=7) or cafeteria diet "high-fat/carbohydrate diet" ad libitum (n=42). After 21 weeks, rats on high fat diet were divided into either Obese control (n=6) gastric sleeve (n=6), Semaglutide 10nM/Kg (n=6), or various concentrations of Tirzepatide (10nM/Kg (n=6), 50nM/Kg (n=6) or 100nM/Kg (n=6). The treatments lasted for six weeks before animals were euthanized. Weight, OGTT, as well as liver biopsy analysis and gene expression analysis was performed.
Results: Gastric sleeve resulted in about 15.5 % weight loss compared to 10.7% in Semaglutide, and 5.0%, 14.9% and 17.7% in the 10, 50 and 100 nM/Kg Tirzepatide groups. Glucose tolerance was improved after all treatments. NAFLD was also improved in all treatment with surgery and 100 nM/Kg Tirzepatide showing highest improvement. Additionally, gene expression of lipid metabolism markers such as ANGPTL3 and 8 were markedly reduced in all treatments.
Conclusions: Tirzepatide is a novel dual GIP and GLP-1 receptor agonist that can lead to improved metabolic conditions similar to sleeve gastrectomy.

Disclosure
J.Abubaker: None. M.Abu-farha: None. S.Alsabah: None. I.Al-khairi: None. P.T.Cherian: None. N.A.Abukhalaf: None. H.Arefanian: None. C.Dsouza: None. S.Al-sabah: None. F.Al-mulla: None.
209-OR: DJB Surgery Improves Oxidative Stress and Alleviates Neuron Cell Injury of Hypothalamus in T2DM Rats by Nrf2/HO-1 Signal
Authors: WANG HUAIJIE , YAN QINGTAO , QU MEIHUA 
Published: June 2023

Metabolic surgery has become an effective treatment for type 2 diabetes mellitus (T2DM). T2DM is often accompanied with impaired glucose utilization and energy metabolism in the brain, leading to oxidative stress, neuron cells injury and inflammation. Previous studies showed that duodenal jejunal bypass (DJB) surgery significantly improves brain glucose metabolism in T2DM rats. This study investigated the protective effect and regulatory mechanism of DJB surgery on T2DM induced brain injury. In this study, differential expression of hypothalamic proteins and genes was analyzed by protein microarray, Flow cytometry, qRT-PCR, western blot and immunofluorescence. The protein microarray results showed that there were significant differences in the expression of hypothalamic hormone and redox regulation-related proteins between the T2DM-DJB rats and the T2DM-Sham rats. Western blot, qRT-PCR, and immunofluorescence results showed DJB surgery significantly down-regulated the expressions of GFAP, NF-κB, p-NF-κB, IL-1β and IL-6 in the hypothalamus of T2DM rats, and reduces hypothalamic inflammation and glial cell proliferation. DJB surgery up-regulated the expression of C-fos, Ki67, BCL-2 and BDNF, and down-regulated the expression of Caspase-3, Cleaved caspase-3 in the hypothalamus of T2DM rats, which played a neuroprotective role, and reduced the damage of hypothalamus cells. DJB surgery up-regulated the expression of Nrf2 and HO-1 in the hypothalamus of T2DM rats and reduces oxidative stress. Those results indicated that DJB surgery improves hypothalamic inflammation and alleviates neuron cells injury in T2DM rats by activating Nrf2/HO-1 mediated antioxidant signaling. Key words: DJB surgery; T2DM; Apoptosis; Inflammatory; Oxidative stress.

Disclosure
H.Wang: None. Q.Yan: None. M.Qu: None.

Funding
National Natural Science Foundation of China (82070856); Shandong Provincial Medicine and Health Commission (202102040075); Weifang Science and Technology Bureau (2021YX071)
210-LB: Impact of COVID-19 Pandemic on the Outcomes of Patients with Diabetes in Colombia
Authors: MORENO-MONTOYA JOSÉ , BALLESTEROS SILVIA , DE LA HOZ-VALLE JOSÉ 
Published: June 2023

Objective: Aside the direct health implications of COVID-19, pandemic has had multiple consequences, especially in chronic patients. This paper aimed to evaluate the impact of the COVID-19 pandemic on mortality and the search for health care of patients with diabetes in Colombia.
Methods: Nationwide ecological panel study of secondary data from the Colombian official records of mortality and medical attentions due to diabetes between 2015 and 2021. Hospitalizations, ambulatory and emergency care visits, as well as death rates were assessed once adjusted by the availability of specialized health institutions and rurality.
Results: During the COVID-19 pandemic, the mortality rate from diabetes increased by 30.4% (pre-pandemic average by semester: 7.73 deaths per 100,000 inhabitants; pandemic average: 10.08 deaths per 100,000 inhabitants), the average rate of medical attention increased by 67.2% (pre-pandemic: 3163 per 100.000; pandemic: 5290 per 100.000), in which, ambulatory care arose by 44.6% and hospitalizations by 42.3%. Rurality was inversely associated with health visits, and the availability of tertiary care institutions was associated with both diabetes mortality and medical consultations.
Conclusions: Beyond the direct effect of the COVID-19 virus on patients with diabetes, their overall health outcomes worsened during pandemic. Availability of high specialized health facilities is related to the number of medical consultations, which suggests that people who did not have access to specialized health services were neglected. Actual and total impact of COVID-19 pandemic in patients with diabetes remains unclear.

Disclosure
J. Moreno-montoya: None. S. Ballesteros: None. J. De la hoz-valle: None.
210-OR: Long-Acting GIPR Agonism Enhances Body Weight Regulation of Multiple Weight-Reducing Agents in Diet-Induced Obese Mice
Authors: ROELL WILLIAM , O'FARRELL LIBBEY , REGMI AJIT , COSKUN TAMER 
Published: June 2023

The development of multi-agonists targeting the glucose-dependent insulinotropic polypeptide receptor (GIPR) has resulted in significant clinical improvements in body weight management, however the contribution of GIPR agonism to this effect is incompletely understood. Using a diet induced obese (DIO) mouse model, GIPR agonism (LAGIPRA) alone has demonstrated little to no efficacy in weight management, whereas the addition of LAGIPRA to long acting GLP-1R agonism decreased food intake and increased energy expenditure resulting in greater weight loss compared with GLP-1R agonism alone suggesting a synergistic benefit. To determine whether GIPR agonism would provide similar synergistic improvements in energy metabolism with additional pharmacologic drivers of weight loss, we treated DIO mice with various weight reducing agents plus and minus LAGIPRA in metabolic chambers. Interestingly, addition of LAGIPRA enhanced weight loss, fat mass reduction, energy expenditure, and lipid oxidation whether combined with T3, FGF21, or long-acting glucagon (IUB288); consistent with earlier experiments, it had little effect on its own. Assessment of adipose tissue engagement in these and subsequent studies suggest GIPR agonism in this tissue may enhance lipolysis, potentially enabling greater energy expenditure via release of stored lipids. These findings suggest a unique role for GIPR agonism to regulate energy expenditure when combined with molecules that reduce body weight generating a greater negative caloric balance and enhancing body weight reduction.

Disclosure
W.Roell: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. L.O'farrell: None. A.Regmi: Employee; Eli Lilly and Company. T.Coskun: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company.
212-LB: Implementation of the Avantect Pancreatic Cancer Test in Newly Diagnosed Type 2 Diabetes Patients in a Clinical Setting
Authors: CHOWDHURY SHIMUL , VILALTA ADRIAN , COLLINS MICAH , RIVIERE MICHAEL , LOPEZ VANESSA , LEIGHTON ANNA , ANTONY MARTY , NILSON ERIC , BERGAMASCHI ANNA , HAAN DAVID , VOLKMUTH WAYNE , LEVY SAMUEL 
Published: June 2023

Pancreatic Cancer (PaC) is the 3rd leading cause of cancer mortality and is predicted to be the 2nd-leading cause by 2030. PaC and lacks effective early detection tools. Studies have identified patients with new-onset type II diabetes (diagnosis made ≤36 months; NOD) as a high-risk patient population that could benefit from early detection of PaC. ClearNote Health has validated a non-invasive, blood-based, epigenomic early-detection pancreatic test called Avantect. The test has been validated in a large case-control study, including patients with NOD. A pilot program to deploy the test in a clinical setting of NOD was conducted to assess the feasibility and integration of the test into a clinical workflow. Fifty patients received the Avantect test from ClearNote Health. Test results were delivered to the clinical site for post-test follow-up. Feedback on the clinical impact of the testing and logistics were reviewed at the conclusion of testing. The cohort consisted of 30 males (60%) and 20 females (40%). The average patient age was 68 years (range 38-87), and patients had an average time from diabetes diagnosis to testing of 22.9 months (range 1-36). A family history of PaC was observed in 29/50 patients (58%). Of the 50 total test orders, the required test blood volume of 10 mL was obtained in 45 patients (90%). These results included 43 patients with no abnormal signal detected (95.6%), and two patients with an abnormal signal detected (4.4%). The two abnormal signal-detected results are awaiting further clinical evaluation. These results demonstrate early success in the delivery of the Avantect test to the clinical practice of diabetic patients. The test is tailored to facilitate clinical implementation because of its non-invasive nature and its high-performance characteristics (sensitivity - 66.7%; sensitivity- 96.9%).

Disclosure
S. Chowdhury: Employee; ClearNote Health. D. Haan: Employee; ClearNote Health. W. Volkmuth: Employee; ClearNote Health. S. Levy: Employee; ClearNote Health. A. Vilalta: Consultant; ClearNote Health. M. Collins: Employee; ClearNote Health. M. Riviere: Employee; ClearNote Health. V. Lopez: Employee; ClearNote Health. A. Leighton: Employee; ClearNote Health. M. Antony: Employee; ClearNote Health. E. Nilson: Employee; ClearNote Health. A. Bergamaschi: Employee; ClearNote Health.
212-OR: Leptin Reduction as a Required Component for Weight Loss
Authors: ZHAO SHANGANG , SCHERER PHILIPP E. 
Published: June 2023

A significant reduction in circulating leptin levels is well corelated with substantial weight loss. However, it is still not clear whether the observed leptin reduction is a cause or consequence of weight reduction. Here, we showed that FGF21 and liraglutide could rapidly induce leptin reduction, and this reduction contributes to the beneficial effects of FGF21 and liraglutide, as blocking the leptin reduction by a transgenic approach curtails the beneficial effects. Moreover, a higher degree of leptin reduction, induced by combination of leptin neutralizing antibody with either FGF21 or liraglutide, synergistically induced greater weight loss and better glucose tolerance in diet-induced obese mice. Furthermore, after removing liraglutide and FGF21, a significant weight gain is associated with rapid increase in circulating leptin levels and prevention of leptin surge by leptin neutralizing antibody slows down weight gain and preserves a better glucose tolerance. Mechanically, a significant reduction in leptin reduction induces a higher degree of leptin sensitivity in neurons, located in hypothalamic region, other than AP. In conclusion, this study supports a model that leptin reduction is required for substantial weight loss and partial leptin reduction may be a novel strategy to treat obesity and its associated metabolic syndromes.

Disclosure
S.Zhao: None. P.E.Scherer: None.
215-LB: Comparison of Clinical and Serological Features among Type III APS, Isolated T1DM, and LADY/LADA
Authors: QIU YAWEI , GUO JING , WEI PENGFEI , HE HUAQIU , JIN MINGYUE , ZHAO HUIJUAN , LI HUAIZHI , LI QIANG 
Published: June 2023

Type III autoimmune polyendocrine syndromes (APS) is characterized by the coexistence of autoimmune thyroid disease (AITD) and T1DM. There is a rare series of studies on APS in Chinese population. This paper retrospectively analyzed the clinical and serological features of Chinese patients with type III APS who admitted to our center from Sept 2018 to Oct 2022, and compared the similarities and differences with isolated T1DM, LADY/LADA patients at the same time. The study included 69 patients, 18 patients with type III APS, 20 patients with T1DM, and 31 patients with LADY/LADA. Type III APS was predominantly female, while T1DM and LADY/LADA groups were the opposite (72.22% vs 35.00% vs 38.71%, P = 0.037). The median age of onset of diabetes in the three groups was 30.50, 23.00 and 41.00 years, respectively (P &lt; 0.001). Hashimoto's thyroiditis (HT) (n=13, 72.22%) was the main AITD in type III APS group, followed by Graves’ disease (Table 1). The median of GADAb in the three groups were 1501.43, 115.01 and 301.02 U/mL, respectively (P = 0.022). And the levels of TPOAb and TGAb in type III APS group were significantly higher than those in the other two groups (P &lt;0.05). Type III APS is more common in women with diabetes onset later than those with isolated T1DM and earlier than those with LADY/LADA. HT is the main AITD in type III APS patients, and the levels of GADAb and thyroid autoantibodies in patients with type III APS are often higher.

Disclosure
Y. Qiu: None. J. Guo: None. P. Wei: None. H. He: None. M. Jin: None. H. Zhao: None. H. Li: None. Q. Li: None.
215-OR: Barriers and Facilitators of Implementing a Pediatric Type 1 Diabetes Psychosocial Intervention—Provider and Leader Perspectives
Authors: PRICE JULIA , THOMAS COURTNEY , DEATRICK JANET A. , OKONAK KATHERINE , KAZAK ANNE 
Published: June 2023

Introduction: Behavioral Family Systems Therapy for Diabetes (BFST-D) is an efficacious, family-based pediatric psychosocial type 1 diabetes (T1D) intervention that improves family conflict and glycemic levels. A briefer group-based version (bBFST-D) has some evidence of effectiveness. However, few families receive this care. Using the Consolidated Framework for Implementation Research, this national qualitative study examined T1D provider and hospital leader perspectives on barriers and facilitators of implementing bBFST-D.
Methods: Psychosocial (n = 10) and medical T1D providers (n = 10), clinical leaders (n = 11), and billing/practice managers (n = 9) were recruited from 5 children's hospitals across the US. Across these 4 stakeholder groups, participants (M age = 42.22 - 55.10 yrs, SD Age = 9.15 - 12.98 yrs) largely identified as female (55-100%), White (67-100%), and non-LatinX (90-100%). A minority were African American (0-22%) or Asian (0-11%). Each participant completed a qualitative phone interview, which was recorded, transcribed, and analyzed using a rapid analysis approach.
Results: Stakeholder groups identified multi-level factors that influence implementation of bBFST-D, such as those specific to the intervention (delivery format, required evidence of effectiveness), the providers (knowledge, beliefs about bBFST-D), the hospital setting (leadership engagement, available resources), and factors outside of the hospital (family needs, billing, national performance guidelines). The most important factors among leaders were evidence bBFST-D improves health outcomes and among providers were buy-in from hospital leadership and hospital resources (staffing, space, scheduling).
Conclusions: Study findings offer foundational knowledge on factors that influence implementation of evidence-based pediatric psychosocial T1D care, which can be used to develop and then test strategies to increase delivery of this care.

Disclosure
J.Price: None. C.Thomas: None. J.A.Deatrick: None. K.Okonak: None. A.Kazak: None.

Funding
National Institutes of Health (1K23DK125666)
218-LB: Younger Veterans with Adult-Onset Diabetes Who Have High Type 1 Diabetes (T1D) Genetic Risk Are Disproportionately of Minority Ancestry and Have Features Typical of T1D but Are Often Unrecognized—A Health Disparity
Authors: YANG PETER K. , SUN YAN , RAGHAVAN SRIDHARAN , LITKOWSKI ELIZABETH M. , LEGVOLD BRIAN T. , RHEE MARY K. , VUJKOVIC MARIJANA , REAVEN PETER , LEONG AARON , PHILLIPS LAWRENCE S. 
Published: June 2023

Diabetes in Veterans is usually presumed to be T2D because T1D precludes enlistment, but T1D may present in adults; how T1D genetic risk impacts different racial/ethnic groups is unknown. To assess the contributions of T1D genetic risk, we examined 109,954 Veterans in the VA's Million Veteran Program (MVP), using a 30 SNP T1D genetic risk score (GRS) for those with European, Hispanic, and Asian ancestry, and a separate 7-SNP GRS for those of African ancestry. High T1D genetic risk (GRS ≥90th percentile) was characterized according to age at diabetes onset (20-39, 40-59, and 60+ years). High T1D genetic risk was more common with the earliest onset group (13.2%, 10.0% and 9.0%, respectively), and that group had the highest proportion of minority ancestry (47%, 37%, and 25%), all p&lt;0.001. The three high T1D risk groups had similar follow-up (13, 12, and 11 years), GAD antibodies if tested (39%, 41%, and 40%), and low C-peptide levels if measured (36%, 23%, and 33%). However, typical T1D features were more common with earlier onset: use of insulin (80%, 63%, and 43%), time to insulin (0.2, 2.4, and 1.4 yr), diabetic ketoacidosis (11%, 3%, and 0.8%), and severe hypoglycemia prompting an ED visit (10%, 5%, and 3%), all p&lt;0.001. While earlier age of onset groups had more use of T1D ICD codes (50%, 25% and 13%), testing for GAD antibodies (18%, 4%, and 2%), and testing for C-peptide (24%, 9%, and 3%), respectively, all p&lt;0.001, less than half of any group had diagnostic testing for T1D. Conclusions: Increased T1D genetic risk is associated with earlier age of diabetes onset in adults and increased prevalence of typical T1D characteristics, but similar GAD antibodies and C-peptide levels. Since individuals with high T1D risk and early diabetes onset are disproportionately of minority ancestry, health policies aimed to improve T1D recognition and management are needed to remedy this health disparity.

Disclosure
P. K. Yang: None. L. S. Phillips: Other Relationship; Diasyst Inc., Research Support; Abbott Diabetes, Janssen Pharmaceuticals, Inc., Pfizer Inc., Kowa Pharmaceuticals America, Inc., GlaxoSmithKline plc. Y. Sun: None. S. Raghavan: None. E. M. Litkowski: None. B. T. Legvold: None. M. K. Rhee: Research Support; Kowa Research Institute, Inc. M. Vujkovic: None. P. Reaven: Research Support; Dexcom, Inc. A. Leong: Other Relationship; Merck & Co., Inc.

Funding
National Institutes of Health (U01DK098245, P30DK111024, AI156161, DK127083); U.S. Department of Veterans Affairs (I01-CX001025, I01-BX005831, I01-BX003340, CX001899, I01CX001737)