bluuebunny/crossref_metadata_2025 huggingface dataset:
137-OR: Outcomes of Real-World Deployment of the Dulce Digital Texting Education Platform for Low-Income Diverse Populations with Diabetes
Authors: RUIZ MONICA , PHILIS-TSIMIKAS ATHENA , ORENDAIN NATALIA , TAVAKE-PASI OTOLOSE F. , STAVINOHA KERRY , ROMO NOEMI G. , EVANCHA NICOLE , LEVEN ERIC
Published: June 2024

Introduction: Minorities are disproportionally impacted by T2D and have higher disease morbidity; however, prognosis improves with good glucose control. Dulce Digital (DD), a simple low-cost text message program with educational, motivational and glucose reminder messages delivered 2-3 times/day over 6 months has lowered HbA1c in RCTs for diverse low SES populations.

Objective: Evaluate the reach and effectiveness of DD in real-world community settings.

Methods: DD was offered throughout Southwest US sites serving low income, mostly Hispanic and Pacific Islander communities with T2D. Tailored feedback was provided based on blood glucose (BG) responses. Responses to BG prompts were categorized as follows: below 70; 71-130; 131-180; 181-250; and over 250; and analyzed using chi-square.

Results: From Jan 2021 to Dec 2023, N=1724 participants were enrolled from 10 sites-Fig 1A. BG metrics demonstrate significant incremental improvements in time in target range (p < .00001)-Fig 1B. There was enthusiastic adoption of DD by community sites with simple enrollment processes and minimal staff effort for deployment.

Conclusion: DD texting program improved BG metrics, with greater time in range for low-income diverse communities. Outreach to enroll patients in community clinic settings and outreach events can be successful and serve as an enhanced approach to support DSME/S.

Disclosure

M. Ruiz: None. A. Philis-Tsimikas: Advisory Panel; Dexcom, Inc., Lilly Diabetes, Novo Nordisk, Sanofi, Medtronic, Bayer Inc. N. Orendain: None. O.F. Tavake-Pasi: None. K. Stavinoha: None. N.G. Romo: None. N. Evancha: None. E. Leven: None.

Funding

National Institutes of Health (1OT2 HL156812NCATS; UM1TR004407)
1383-P: In the 21st Century, African Immigrants to the United States Do Not Value Obesity—The Africans in America Study
Authors: HURSTON JAMAIICA , WORTHY CHARLITA , HUEFNER ELIZA A. , SAYED MARIAM , DUBOSE CHRISTOPHER , MABUNDO LILIAN , HORLYCK-ROMANOVSKY MARGRETHE F. , SUMNER ANNE E.
Published: June 2024

With acculturation superimposed on nutritional transitions, urbanization and globalization, 21st century attitudes of African immigrants towards optimal body size are unknown. To gain perspective on body image, we assessed in 412 Africans living in America: 1) ideal body size 2) body size dissatisfaction and 3) cardiometabolic health by body size category. Participants chose 2 silhouettes from the Stunkard Figure Rating Scale, one for their wish body size and one for their perceived body size. The scale has 9 silhouettes corresponding to body size categories: Underweight: 1-2; Normal-Weight: 3-4; Overweight: 5-7; Obesity: 8-9. Body size dissatisfaction was calculated as the difference between perceived and wish body size. Cardiometabolic health was determined by BP, glucose and lipids. Enrollees lived in the Washington, DC area (BMI 27.9±4.6 (mean±SD), range 19.5-47.3 kg/m2, female: 42% (174/412); age 39±11y, range 20-69y). As their wish body size, no one (0/412) chose silhouettes in the obese category. In fact, the body size silhouettes most preferred were in the normal-weight category. Dissatisfaction because perceived body size was too large occurred in 63% (260/412). Whereas dissatisfaction because body size was too small occurred in 12% (49/412). However, body size dissatisfaction was higher in women than men (84% (146/174) vs. 69% (164/238), P<0.001). BMI of women who thought they were too large was 30.3±4.6 kg/m2. Their wish body size silhouettes were: 1 to 6. BMI of women who thought they were too small was 23.4±3.3 kg/m2. Their wish body size silhouettes were: 3 to 6. BMI of men who thought they were too large was 29.2±3.9 kg/m2 and they chose for their wish body size: 1 to 5. BMI of men who thought they were too small was 23.0±2.7 kg/m2. Their wish silhouettes were: 4 to 6. Cardiometabolic health was most optimal for women and men with normal-weight BMI. Overall, Africans living in America did not value obesity and preferred a healthier normal-weight body size.

Disclosure

J. Hurston: None. C. Worthy: None. E.A. Huefner: None. M. Sayed: None. C. DuBose: None. L. Mabundo: None. M.F. Horlyck-Romanovsky: None. A.E. Sumner: None.
1386-P: Cause-Specific Mortality Is Diversifying in Those with Diabetes—A Multicountry Analysis
Authors: MAGLIANO DIANNA J. , MORTON JEDIDIAH I. , CHEN LEI , SACRE JULIAN W. , CARSTENSEN BENDIX , GREGG EDWARD W. , PAVKOV MEDA E. , ARFFMAN MARTTI , LUAN CHU MANH , EEG-OLOFSSON KATARINA , FLEETWOOD KELLY , FOSSE-EDORH SANDRINE , GUION MARIE , GUREVICIUS ROMUALDAS , HWA HA KYOUNG , KAUL PADMA , JUNG KIM DAE , LAURBERG TINNE , WILD SARAH , SHAW JONATHAN E.
Published: June 2024

Objective: This multi-country study explored trends in causes of death in people with diabetes.

Methods: We used cause-specific mortality data in people with diabetes from 9 high-income countries (2000-2020). Data were from registries, health insurance, or other administrative sources. Proportional contributions of causes of death to total deaths across 10 groups (cancer, cardiovascular [CVD], dementia, diabetes, influenza and pneumonia, infection, liver, renal, respiratory disease, and all others) were age-standardized and regressed against time.

Results: We included 1,624,100 deaths from 9 jurisdictions. In all jurisdictions, there was a shift in the most common causes of death away from CVD and diabetes. The decline in the proportion of deaths due to CVD ranged from 0.34% to 2.32% per year (all Ptrend < 0.001). Deaths due to diabetes declined in 8/9 jurisdictions with magnitudes from 0.09% to 0.87% per year but rose in Lithuania (0.64% per year). Dementia deaths rose in 8/9 jurisdictions (0.07% to 0.52% per year) as did the proportion of deaths due to ‘other’ causes. Cancer deaths rose in 5/9 jurisdictions. Trends in the remaining cause-of-death categories showed varied patterns.

Conclusion: There has been a shift in causes of death among those with diabetes away from CVD and diabetes. The increasing proportion of deaths due to dementia and cancer may require consideration when planning resource allocation.

Disclosure

D.J. Magliano: None. J.I. Morton: None. L. Chen: None. J.W. Sacre: None. B. Carstensen: Stock/Shareholder; Novo Nordisk. E.W. Gregg: None. M.E. Pavkov: None. M. Arffman: Research Support; Roche Pharmaceuticals. M. Chu: None. K. Eeg-Olofsson: Other Relationship; Abbott, Eli Lilly and Company, Novo Nordisk, Sanofi. K. Fleetwood: None. S. Fosse-Edorh: None. M. Guion: None. R. Gurevicius: None. K. Ha: None. P. Kaul: None. D. Kim: None. T. Laurberg: None. S. Wild: Other Relationship; Novo Nordisk, Novo Nordisk Foundation. J.E. Shaw: Advisory Panel; GlaxoSmithKline plc. Research Support; AstraZeneca. Advisory Panel; AstraZeneca. Speaker's Bureau; AstraZeneca, Roche Diabetes Care, Boehringer-Ingelheim, Zuellig Pharma Holdings Pte. Ltd. Advisory Panel; Novo Nordisk. Speaker's Bureau; Roche Diagnostics. Advisory Panel; Roche Diagnostics, Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Advisory Panel; Abbott, Mylan. Speaker's Bureau; Sanofi.

Funding

Centers for Disease Control and Prevention, United States
1397-P: Description of Prescribing Patterns of Antihyperglycemic Medications among Racially and Ethnically Diverse Populations in the All of Us Dataset
Authors: BRADY VERONICA J. , AKYIREM SAMUEL , PADHYE NIKHIL
Published: June 2024

Introduction & Objectives: Minorities living with diabetes are more likely to have poorer glycemic outcomes compared to their White counterparts. Equitable access to novel anti-hyperglycemic medications can help improve health outcomes. The purpose of this study is to determine racial and ethnic disparities in prescribing patterns of anti-diabetic medications among persons with type 2 diabetes (T2D).

Methods: Participants were drawn from the All of Us research (AoU) program. Cases of T2D were identified using pre-defined, validated phenotype algorithm. Additionally, we identified individuals with T2D who had ever had a prescription of metformin, sulfonylureas, insulin, GLP1-RA, and SGLT2i. Multivariable logistic regression was used to assess if prescription patterns differ by race and ethnicity while adjusting for sociodemographic and clinical variables.

Results: Our analytic sample included 10,016 persons with T2D. Most participants were women (56.6%), White (51.7%), and had average HbA1C of < 7% (57.2%). Blacks (aOR = 0.72, 95% CI: 0.66 - 0.79) and Hispanics (aOR = 0.81, 95% CI: 0.73 - 0.90) compared to White participants were less likely to receive GLP1-RA prescription. Additionally, Blacks were less likely to receive SGLT2i (aOR = 0.86, 95% CI: 0.78-0.96) but more likely to receive metformin (aOR = 1.33, 95% CI: 1.21-1.45). Blacks (aOR = 0.81, 95% CI: 0.74 - 0.88) and Hispanics (aOR = 0.75, 95% CI: 0.68 - 0.83) were less likely to receive insulin therapy.

Conclusions: Our findings, highlight racial and ethnic disparities in prescribing patterns. These findings provide evidence that these differences are independent of socioeconomic status and may be a factor in worse health outcomes experienced by racial minorities with T2D.

Disclosure

V.J. Brady: Board Member; Association of Diabetes Care & Education Specialists. Other Relationship; Diathrive. S. Akyirem: None. N. Padhye: None.

Funding

American Association of Colleges of Nursing (AACN)
1409-P: Changing Trends in Glucose-Lowering Drug Initiation for Type 2 Diabetes in the Era of Tirzepatide
Authors: PATORNO ELISABETTA , TESFAYE HELEN , ORTEGA-MONTIEL JANINNE , ALIX CAROLINE , DICESARE ELYSE C. , JANE CROMER SARA , WEXLER DEBORAH J. , PAIK JULIE M.
Published: June 2024

Introduction & Objective: Clinical trials in adults with type 2 diabetes (T2D) have shown remarkable reductions in A1c and body weight for tirzepatide, the first dual GIP/GLP-1 receptor agonist approved in the US for T2D. The utilization trends and uptake of tirzepatide in adults with T2D in the US remain unexplored.

Methods: Using a US commercial claims database, we identified adults ≥18 years with T2D who initiated glucose-lowering drugs between 1/2021 and 6/2023 and plotted monthly drug initiation trends before and after the approval of tirzepatide for T2D (5/2022). We also compared the uptake of tirzepatide to the historical uptake of other GLP-1 receptor agonists (GLP-1RA) during the first 13 months since their initial approval for T2D.

Results: Between 1/2021 and 6/2023, metformin use decreased (from 25.5% to 20.7% of all glucose-lowering drug initiators), whereas GLP-1RA and SGLT2i use increased (from 17.6% to 23.0% and from 15.6% to 20.0%) (Fig. Panel A). The use of tirzepatide increased steeply after 10/2022, reaching 11.5% in 6/2023. By 6/2023, GLP-1RA were the most frequently initiated glucose-lowering drugs. During the first 13 months after approval, tirzepatide uptake was much steeper than any other GLP-1RA (Fig. Panel B).

Conclusion: Tirzepatide and other GLP-1RA are now the most frequently initiated glucose-lowering drugs for T2D. The uptake of tirzepatide is unprecedented with respect to any other GLP-1RA.

Disclosure

E. Patorno: Research Support; Boehringer-Ingelheim, Food and Drug Administration (FDA), National Institutes of Health, Patient-Centered Outcomes Research Institute. H. Tesfaye: None. J. Ortega-Montiel: None. C. Alix: None. E.C. DiCesare: None. S. Cromer: Other Relationship; Johnson & Johnson Medical Devices Companies. Advisory Panel; Alexion Pharmaceuticals, Inc. Other Relationship; Wolters Kluwer Health. D.J. Wexler: Other Relationship; Novo Nordisk. J.M. Paik: None.

Funding

Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School
1446-P: Gender Inequalities in Cardiovascular Risk Factors in Primary Prevention Adults Living with Type 1 Diabetes in Germany and France—Findings from DPV and SFDT1
Authors: COSSON EMMANUEL , AUZANNEAU MARIE , AGUAYO GLORIA A. , KARGES WOLFGANG , RIVELINE JEAN-PIERRE , AUGSTEIN PETRA , SABLONE LAURA , JEHLE PETER M. , FAGHERAZZI GUY , HOLL REINHARD W. ,   STUDY GROUP SFDT1
Published: June 2024

Introduction & Objectives: To evaluate whether medical care for and level of cardiovascular risk factors differ in primary prevention between adult men and women with type 1 diabetes (T1D) in two European countries in 2020-2022.

Methods: We included 2657 participants from the DPV registry (Germany, mean age 40±15, diabetes duration 23±14 years; 50.9% men) and 1172 from the SFDT1 study (France, age 39±14, diabetes duration 22±13 years; 53.2% men).

Results: HbA1c levels and body mass indexes were similar in women and men with similar proportions of HbA1c<7% (DPV: 36.6 vs. 33.0%, respectively; SFDT1: 22.8 vs. 24.9%; both n.s.). Women had less overweight in DPV (55.4 vs. 61.0%, p<0.05) but not in SFDT1 (48.0 vs. 44.9%, n.s.) and were less prone to smoke (DPV: 19.7 vs. 25.8%, p<0.05; SFDT1: 21.0 vs. 26.0%, n.s.). Systolic blood pressure was lower in women than men (DPV: 124±15 vs. 129±15; SFDT1: 121±16 vs. 126±14mmHg, both p<0.05) with similar rates of antihypertensive therapy in case of systolic/diastolic blood pressure ≥140/90mmHg (DPV: 70.5 vs. 63.6%; SFDT1: 73.3 vs. 68.6%, both n.s.). In case of microalbuminuria, ACEi-ARB were less prescribed in women than men in DPV (21.4 vs 37.6%, p<0.05) but not SFDT1 (70.6 vs 62.0%, n.s.). In women compared to men, HDL-cholesterol levels were higher; triglycerides lower and LDL-cholesterol similar in DPV and SFDT1. In those with LDL-cholesterol >130 mg/dL (DPV: 19.9 vs. 23.9%; SFDT1 17.0 vs. 19.2%, both n.s.), statin therapy was less prescribed in women than men in DPV (7.9 vs. 17.0%, p<0.05), SFDT1 (18.2 vs. 21.0%, n.s.).

Conclusion: Women in primary prevention have a better cardiovascular risk profile than men in both studies. We observed a high rate of therapeutic inertia, which might be higher in women for statin and nephroprotection with ACEi-ARB especially in Germany.

Disclosure

E. Cosson: Advisory Panel; Abbott, AstraZeneca, Lilly Diabetes, Novo Nordisk, Sanofi, Roche Diagnostics, Novartis AG, Amgen Inc. M. Auzanneau: Other Relationship; Insulet Corporation. G.A. Aguayo: None. W. Karges: None. J. Riveline: Board Member; Abbott, Novo Nordisk A/S, Sanofi, Eli Lilly and Company, Medtronic, Dexcom, Inc., Insulet Corporation, Air Liquide, AstraZeneca. P. Augstein: None. L. Sablone: None. P.M. Jehle: None. G. Fagherazzi: Speaker's Bureau; Sanofi. Advisory Panel; Timkl, SAB Biotherapeutics, Inc., Vitalaire, Roche Diabetes Care. R.W. Holl: None.
1451-P: Burden of Type 1 Diabetes Mellitus (T1DM) and Its Trend in G20 Countries from 1990–2019—A Benchmarking Analysis
Authors: ISLAM HAMZA , POTLURI GEETHIKA , MARKANDU KEETHANSHAN , PARISAPOGU ANUSHA , TEJA CHINTHAPALLI MRUNAL , MADDINENI KAVYA , ISLAM RABIA , DEKHNE ANUSHKA , DINESHBHAI DESAI HARDIK
Published: June 2024

Introduction: Globally, Type 1 Diabetes (T1DM) has been increasing and affected 15.8 million people of all ages in G20 countries in 2019. This study aims to outline the T1DM burden in G20 countries, which hold substantial global population and economic influence.

Method: Using the Global Burden of Disease method, non-fatal health outcomes were estimated with DISMOD-MR 2.1, and fatal outcomes were evaluated using CODEm, stratified by age, gender, year, and location in G20 countries from 1990-2019.

Results: From 1990-2019, there was a substantial increase in T1DM prevalence, with a 99% rise in cases, a 31% increase in deaths, and a 40% increase in disability-adjusted life years (DALYs) within G20 countries. France and Saudi Arabia had the highest increases in age-standardized incidence rates (ASIR) at 138% and 112%, respectively. In terms of death rates, India had a 1% increase, while other countries showed decreases. Males had a higher burden than females, with higher incidence (27% vs. 22%), deaths (14% vs. -12%), and DALYs (17% vs. -0.03%) from 1990-2019. The highest incidence was among 5-9-year-olds, and the highest number of deaths occurred in those aged 95 and above in 2019.

Conclusion: T1DM contributed to 55.4% of all T1DM-related deaths worldwide within the G20 countries. Gender disparities are evident, with higher burdens observed in males, and age-specific care is crucial.

Disclosure

H. Islam: None. G. Potluri: None. K. Markandu: None. A. Parisapogu: None. M. Chinthapalli: None. K. Maddineni: None. R. Islam: None. A. Dekhne: None. H. Desai: None.
146-OR: Clustering Pediatric Type 2 Diabetes Patients Exposes Differential Responses to Therapeutic Interventions
Authors: KREIENKAMP RAYMOND J. , SMITH KIRK , WANGDEN THINLEY Y. , JENSEN ELIZABETH T. , SHAH AMY S. , PIHOKER CATHERINE , SZCZERBINSKI LUKASZ , FLOREZ JOSE C. , UDLER MIRIAM , SRINIVASAN SHYLAJA
Published: June 2024

Introduction & Objective: Diabetes is a heterogeneous disease, with patients displaying varying degrees of adiposity, beta-cell dysfunction, and insulin resistance. Ahlqvist et al. established five distinct sub-types of adult-onset diabetes, with differing disease progression and risk for complications, based on clustering of six clinical variables. These clusters were developed and validated in adult populations, but their reproducibility in pediatric diabetes remains unknown. We sought to determine if pediatric patients can be sub-classified into clusters based on the same variables, and if these clusters had differing responses to treatment.

Methods: We analyzed Progress in Diabetes Genetics in Youth (ProDiGY), a multi-ethnic resource that brings together youth with clinician-diagnosed type 2 diabetes (T2D) before age 20 years from SEARCH (n=428) and the Treatment Options for T2D in Adolescents and Youth (TODAY) study (n=455). In participants with negative autoantibodies, we used a k-means (k=3) clustering method, with variables BMI, HOMA2_B, HOMA2_IR, and HbA1c; we excluded age of diagnosis given its limited range in a pediatric population.

Results: We identified three distinct pediatric clusters in each cohort-sex group. Cluster 1 had high HbA1c and low HOMA2_B, denoting low beta-cell function. Cluster 2 had the highest BMI, HOMA2_IR, and HOMA2_B, denoting insulin resistance. Cluster 3 had intermediate levels of HOMA2_IR and HOMA2_B but the lowest HbA1c, denoting milder diabetes. In TODAY, participants in cluster 1 had the highest rates of treatment failure (76% versus 46% overall, p<0.0001). Metformin alone was most likely to be successful in cluster 3 (failure rate 19%) and had the highest rates of failure in cluster 1 (failure rate 86%, p<0.0001).

Conclusion: Clustering pediatric T2D by clinical measures reveals distinct sub-types with differing responses to treatment. Clustering might be used to inform treatment choices in pediatric T2D patients.

Disclosure

R.J. Kreienkamp: None. K. Smith: None. T.Y. Wangden: None. E.T. Jensen: Advisory Panel; TARGET PharmaSolutions, Inc. Research Support; TARGET PharmaSolutions, Inc. Consultant; Regeneron Pharmaceuticals Inc. A.S. Shah: None. C. Pihoker: None. L. Szczerbinski: None. J.C. Florez: Research Support; Novo Nordisk. Other Relationship; Novo Nordisk, AstraZeneca. M. Udler: Other Relationship; Up-To-Date. S. Srinivasan: None.

Funding

American Diabetes Association (11-22-PDFPM-03); RJK is supported by NIH (T32DK007699). JCF is supported by NIH/NHLBI (K24 HL157960). SS is supported by NIH (K23DK120932 and R03DK138213).
1499-P: Possible Association of GAD65 Antibody with Pancreatic Adenocarcinoma
Authors: VALLABH SEAN , PELTSVERGER MAYA Y. , YESAULAVA LIUDMILA
Published: June 2024

Objective: To demonstrate a role of serum anti-glutamic acid decarboxylase 65 antibodies titer (GAD65) as a possible paraneoplastic marker of pancreatic adenocarcinoma.

Case Presentation: A 29-year-old male with polysubstance abuse presented to the emergency room with polyuria, polydipsia, and polyphagia. Laboratory findings were consistent with DKA.

GAD65 antibody was elevated to over 25,000U/mL (0-5- U/mL) leading to a diagnosis of Type 1 Diabetes. The titer was confirmed on dilution and remained unchanged 3 months later Insulin regimen was initiated. Glycemic control was challenging.

Eight months later he presented with epigastric pain, dark urine, and jaundice. An endoscopic ultrasound demonstrated a 7 cm pancreatic head mass with venous abutment. Biopsy revealed a primary adenocarcinoma. Genomic microsatellite testing did not reveal actionable mutations.He underwent 7 cycles of neoadjuvant chemotherapy with Folfirnox; and second-line therapy with radiation and Gemcitabine, Abraxane. Upon completion of these therapies his GAD 65 antibody had decreased to 9,686.3U/mL(0-5 U/mL), his CA 19-9 tumor also decreased to 43.22 U/mL from 47.5 U/mL at diagnosis (0-35 U/mL); while his CEA increased to 4.09 ng/mL from 3.5 ng/mL at diagnosis (0-2.5 ng/mL). His disease is maintained with palliative Folfiri. Glycemic control remains suboptimal.

Conclusion: The degree of GAD65 antibody elevation via enzyme-linked immunosorbent assay could have a role in detecting pancreatic adenocarcinoma. There is no current literature placing the association between GAD65 and pancreatic adenocarcinoma, making this a novel case.

Disclosure

S. Vallabh: None. M.Y. Peltsverger: None. L. Yesaulava: None.
1503-P: Nano-thin Conformal Coating onto Human Islets to Preserve Cell Function and Induce Immunoprotection for Islet Transplantation
Authors: YITAYEW MICHAEL Y. , LI LING , TABRIZIAN MARYAM
Published: June 2024

Allogenic islet transplantation is a promising treatment option for patients with Type 1 Diabetes (T1D). Systemic immunosuppression is required to mitigate donor islet rejection, but this can present with adverse side-effects and reduce patient quality of life. To address this, it has been proposed that biocompatible materials can be used to form a protective capsule around islets and modulate islet-induced immune reactions while maintaining cellular and secretory functions. A key feature of such capsules is minimal implant volume to ensure cells have adequate diffusion across their membrane while allowing for islet infusion into the portal vein. Conformal coatings have been described in the literature to exhibit the desired characteristics of an ideal protective capsule mentioned above. Our work investigates a novel combination of non-immunogenic polyelectrolytes, namely tetrahydropyran triazole phenyl-alginate (TZ-AL) and quaternized phosphocholine-chitosan (PC-QCH), for a nano-thin film formation onto human islet surfaces. After thorough characterization of material properties, we demonstrated successful coating formation (540nm thickness), and biocompatibility using human-derived beta cell lines and donor human islets. Our results indicate that coated islets cultured upto 7 days in vitro preserved their cell viability, GSIS, and gene expression (INS, GLUT2, Glucagon, PDX1) compared to non-coated controls. In vitro immune assays revealed that our materials do not stimulate the innate immune system and reduce pro-inflammatory cytokine secretion. Furthermore, coated islets implanted into STZ-induced diabetic mice restored normoglycemia up to one month and islet morphology is maintained according to histology data. Additional studies to investigate the in vivo immunomodulatory properties of our coating are ongoing and ultimately, the findings from this study can help to further improve the outcomes of islet transplantation.

Disclosure

M.Y. Yitayew: None. L. Li: None. M. Tabrizian: None.

Funding

Canadian Institutes of Health Research (91435)
1519-P: Endothelial Injury Predicts Carbohydrate Metabolism Trajectories after COVID-19
Authors: REUSCH JANE E.B. , ALBERS DAVID , WANG YANRAN , BRIGGS JENNIFER , MAICKI RICHARD , STROH J.N. , GUPTA AANCHAL , GARCIA ANN , SINGH VATSALA , HILLER TERRA D. , SHERMAN ARTHUR , RASOULI NEDA , DOUGLAS IVOR S.
Published: June 2024

Introduction & Objective: Diabetes and SARS-CoV-2 infection target the endothelium causing perfusion abnormalities. We hypothesized that COVID-19 impairs insulin action and/or insulin secretion, and that systemic endothelial injury (EI) slows post-hospitalization recovery of these parameters.

Methods: 20 hospitalized adults with COVID-19 and acute hypoxemia (8 with DM) were tested for markers of endothelial function (hospital discharge, 1, 3 months) and oral glucose tolerance tests (OGTT) (1 and 3 months). Insulin sensitivity and insulin & C-peptide secretion metrics were assessed with empirical models (HOMA β, HOMA-IR) and mathematical ordinary differential equation (ODE) based models [(ISS (Sigma, SI), CSR (CSR0 (fasting), CSR-km (non-fasting)), ISR (ISR-km (non-fasting)), and ultradian ULS (a1, Rg)].

Results: Table 1 indicates significant correlations between patient-specific changes normalized over time (slopes) in EI and endocrine metrics. Uncertainty was estimated with linear mixed models adjusted for diabetes status and sex, respectively for each metric. Individually paired marker and metric slopes characterizing changes in participant physiological states were associated using linear regression models. Significance of predictive impact was interpreted from associated p-values of each slope pairing.

Conclusion: Changes in EI predict post-hospital recovery of carbohydrate metabolism.

Disclosure

J.E.B. Reusch: Advisory Panel; Medtronic. D. Albers: None. Y. Wang: None. J. Briggs: None. R. Maicki: None. J. Stroh: None. A. Gupta: None. A. Garcia: None. V. Singh: None. T.D. Hiller: None. A. Sherman: None. N. Rasouli: Advisory Panel; Eli Lilly and Company, Novo Nordisk. Research Support; Novo Nordisk. I.S. Douglas: None.

Funding

R01 DK130351
1520-P: Pyridylnidulin, a Semisynthesized Fungal Metabolite, Exerts the Insulin-Mimicking Effect and Improves Glucose Homeostasis in Mice
Authors: TEPAAMORNDECH SURAPUN , ISAKA MASAHIKO , CHANTARASAKHA KANITTHA , LIKITNUKUL SUTHARINEE
Published: June 2024

Fungal metabolites have contributed significantly to medication development. However, there are few reports of the fungal metabolites beneficial for type 2 diabetes (T2D) treatment. This study performed a semi-synthesis converting nornidulin, a secondary metabolite of Aspergillus unguis ATCC10032, to pyridylnidulin. We aimed to investigate the stimulatory effect of pyridylnidulin on glucose uptake and the mechanism of action, and determine an improvement in glucose homeostasis in mice fed high-fat diet. Our results showed that pyridylnidulin stimulated 2-[3H]-deoxy-glucose greater than nornidulin in 3T3-L1 adipocytes and L6 myotubes. Pyridylnidulin-stimulated glucose uptake was found in a dose- and time-dependent manner. Our study also provided evidence that pyridylnidulin enhanced upregulation of GLUT4, and phosphorylation of IRS1, AKT, and AMPK. Importantly, the levels of GLUT4 in the plasma membrane were increased in response to nidulin treatment. The presence of the PI3K/AKT inhibitor, wortmannin, but not AMPK inhibitor, compound C, largely lowered pyridylnidulin-stimulated glucose uptake. In addition, pyridylnidulin triggered p42/p44 MAPK phosphorylation of which inhibition by PD98059 limited pyridylnidulin-stimulated glucose uptake. In palmitic acid-induced insulin resistance in myotubes, pyridylnidulin-stimulated glucose uptake remained significant. In C57BL/6 mice fed high-fat diet for 10 weeks, oral administration of 120 mg/kg pyridylnidulin for 4 weeks not only improved glucose homeostasis in IPGTT, but also ameliorated hepatic steatosis. Taken together, pyridylnidulin exerts the insulin-mimicking effect stimulating glucose uptake mainly through PI3K/AKT-dependent GLUT4 translocation, and improved T2D pathogenesis in a mouse model.

Disclosure

S. Tepaamorndech: None. M. Isaka: None. K. Chantarasakha: None. S. Likitnukul: None.

Funding

Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn University (RA67/015); Development of new faculty staff, Ratchadaphiseksomphot Fund, Chulalongkorn University (DNS_66_089_3000_011); Thailand Research Fund (DBG6280008)
1527-P: G Protein Gsα Is Required for Normal Glucose Sensing in POMC Neurons
Authors: LAYTON DANIEL , SUN HUI , GUPTA MEENAKSHI , CUI ZHENZHONG , CHEN MIN , GAVRILOVA OKSANA , COLLINS MICHAEL T. , WEINSTEIN LEE
Published: June 2024

Proopiomelanocortin (POMC) neurons are glucose-sensing neurons in which increased ambient glucose concentrations lead to neuronal activation by a mechanism involving KATP channels. Since glucose sensing in pancreatic β-cells occurs by a similar mechanism and requires G protein Gsα/cAMP signaling, we hypothesized that Gsα may also be involved in glucose sensing in POMC neurons. To test this hypothesis, we generated mouse models with POMC neuron-specific Gsα deficiency (POMCGsKO) or expression of a constitutively activated Gsα (POMCGsR201C). Despite having normal body weight and composition, POMCGsKO mice were hyperglycemic, hypoinsulinemic, glucose intolerant, and had impaired insulin response to glucose loading in vivo. In contrast, POMCGsR201C mice showed increased fat mass but improved glucose tolerance and enhanced insulin response to i.p. glucose administration. This altered glucose homeostasis by Gsα deficiency or activation in POMC neurons was not due to an autonomous pancreatic β-cell defect as both POMCGsKO and POMCGsR201C mice displayed normal pancreatic islet size and number, unchanged β-cell mass and intact glucose-stimulated insulin secretion from isolated islets ex vivo compared to controls. Instead, POMCGsKO mice lacked glucose-stimulated POMC neuron activation as determined by induction of c-fos expression, while POMCGsR201C mice exhibited higher basal c-fos activity in POMC neurons. These results indicate that Gsα is required for normal glucose sensing in POMC neurons which provide feedback to pancreatic islets to maintain glucose homeostasis.

Disclosure

D. Layton: None. H. Sun: None. M. Gupta: None. Z. Cui: None. M. Chen: None. O. Gavrilova: None. M.T. Collins: None. L. Weinstein: None.

Funding

NIDDK Intramural Research Program
1545-P: Differences in Brain Anatomy between Diabetes Endotypes—Results from the UK-Biobank
Authors: CERRAI CERONI MARIACLAUDIA , HUMMEL JULIA , PRYSTUPA KATSIARYNA , MÜLLER HANS-PETER , YAMAZAKI HAJIME , KASSUBEK JAN , WAGNER ROBERT , HENI MARTIN
Published: June 2024

Introduction & Objectives: Research suggests that reduced regional brain volumes in specific areas are important for cognitive functions in persons with type 2 diabetes. How this relates to novel diabetes endotypes is unknown.

Methods: We therefore investigated MRI-derived brain volumes from 464 participants of the UK-Biobank, who had up to 5 years of type 2 diabetes duration and available clinical data. We estimated group membership to the diabetes clusters introduced by Ahlqvist et al. using the approach proposed by Antonio-Villa et al. that relies on BMI, HDL, triglycerides, waist, height, age at fMRI and age at diagnosis, sex, glucose, and HbA1c. Differences in brain volumetry between endotypes were tested by ANCOVA adjusting for age with Bonferroni correction for multiple comparisons and post-hoc Tukey tests.

Results: Grey matter volume (p < 0.0001) as well as bilateral volumes of hippocampus (p < 0.01), and ventral striatum (p < 0.0001) showed differences between endotypes. This remained significant even after adjustment for age and correction for multiple testing. Lowest volumes in these brain areas were present in patients of the insulin deficient SIID cluster, who also had significantly lower volumes than healthy controls. Volumes of white matter, thalamus, caudate, putamen, pallidum, and amygdala did not show significant differences between groups.

Conclusion: There are differences in global and subcortical brain volumes between diabetes endotypes even after a short diabetes duration. Most affected areas are important for cognitive functions, suggesting higher risks for cognitive decline especially in the insulin-deficient SIID endotype.

Disclosure

M. Cerrai Ceroni: None. J. Hummel: None. K. Prystupa: None. H. Müller: None. H. Yamazaki: Other Relationship; AstraZeneca, Janssen Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma Corporation, Kowa Company, Ltd., Kyorin Pharmaceutical Co. Ltd, Takeda Pharmaceutical Company Limited, Takeda Pharmaceutical Company Limited, Magmitt Pharmaceutical Co. J. Kassubek: None. R. Wagner: Speaker's Bureau; Sanofi. Advisory Panel; Lilly Diabetes. Speaker's Bureau; Boehringer-Ingelheim, Novo Nordisk. M. Heni: Research Support; Boehringer-Ingelheim. Advisory Panel; Amryt Pharma Plc. Speaker's Bureau; Amryt Pharma Plc. Advisory Panel; Boehringer-Ingelheim, Boehringer-Ingelheim. Speaker's Bureau; Lilly Diabetes, Novartis AG, Novo Nordisk, Sanofi.
1548-P: Functional and Behavioral Dynamics of GLP-1 Receptors in the Central Amygdala
Authors: DURAN MIGUEL , VIRKUS SONJA , HARDAWAY JAMES A.
Published: June 2024

Introduction: Glucagon-like peptide-1 receptor (GLP-1R) activation reduces food intake via multiple brain sites, i.e., hypothalamus, hindbrain, and limbic systems. Peripheral and central administration of GLP-1R agonists activate the central nucleus of the amygdala (CeA), yet the mechanisms mediating this action are understudied. In the present study, in vivo fiber photometry and calcium indicator, GCaMP, in the CeA in freely behaving mice was used to determine the role of GLP-1Rs in modulating neural activity in response to peripheral administration of a GLP-1R agonist.

Methods: Fiber photometry

Results: Freely behaving mice with fiber optic cannulas implanted in CeA were attached to a fiber photometry system and neural activity recorded in response to intraperitoneal administration of saline, Exendin-4 (5 µg/kg, Ex4, agonist), or Exendin-9 (50 µg/kg, Ex9, antagonist). We found that Ex4 activates CeA neurons, and this effect is blocked by prior administration of Ex9.

Conclusion: These measurements from freely behaving mice suggest that CeA GLP-1Rs are potentially mediating changes in neuronal activity when activated by a GLP-1R agonist. Currently, we are assessing the behavioral consequences of inhibiting the neuronal signaling of the CeA and its GLP-1R on feeding behavior.

Disclosure

M. Duran: None. S. Virkus: None. J.A. Hardaway: None.

Funding

National Institutes of Diabetes and Digestion and Kidney Disease (K01DK115902, R03DK129561); Dr. Tim Gavey (P30DK079626); Dr. James Hill (P30DK056336)
1565-P: Morning Hyperglucagonemia Disrupts the Priming Action of AM Insulin
Authors: WATERMAN HANNAH L. , MOORE MARY C. , SMITH MARTA S. , FARMER BEN , YANKEY KALISHA , EDGERTON DALE S. , CHERRINGTON ALAN D.
Published: June 2024

The second meal effect describes an improvement in the glycemic response seen following the consumption of a 2nd identical meal. We previously showed that morning (AM) exposure of the liver to hyperinsulinemia can prime the liver so that there is increased hepatic glucose uptake and glycogen storage later in the day, with no effect on non-hepatic glucose uptake (non-HGU). Considering that most individuals consume meals that prompt both insulin and glucagon secretion, we sought to determine if AM hyperglucagonemia can alter the priming effect of AM hyperinsulinemia on PM hepatic glucose metabolism. To explore this aim, canines were exposed to 4h of hyperinsulinemia in the AM in a delivery pattern that mimicked the insulin secretory profile previously observed during a 4h AM duodenal glucose infusion. This 4h period of hyperinsulinemia was accompanied by either basal (INS, n=6) or elevated (I + G, n=8) glucagon. After a 1.5h non-clamp period, the dogs were challenged using a 2.5h afternoon (PM) hyperinsulinemic-hyperglycemic (HIHG) clamp during which the glucose load, insulin and glucagon levels, and the artery to portal vein glucose gradient were identical between the two groups. During the PM clamp, the mean NHGB in I+G was only 54% of that in INS (mean NHGB of -3.3±0.5 vs. -6.2±0.5 mg/kg/min; net AUC of 415±70 vs. 785±73 mg/kg/2.5h, P<0.003), respectively. Additionally, glycogen synthesized during the PM clamp was twice as high in INS vs. I+G (mean PM glycogen storage of 23.6±1.3 vs. 12.0±1.9 mg/g liver, P<0.001), respectively. There was no significant difference in mean PM non-HGU between the two groups. The mean PM NHGB for a group that received basal insulin and basal glucagon in the AM (No Prime) was -2.7±0.5 mg/kg/min, which is not statistically different from PM NHGB for I+G.

In conclusion, exposing the liver to hyperglucagonemia in the morning has the potential to block the priming action of meal-induced AM hyperinsulinemia, preventing enhanced glucose uptake and glycogen storage by the liver later in the day.

Disclosure

H.L. Waterman: None. M.C. Moore: None. M.S. Smith: None. B. Farmer: None. K. Yankey: None. D.S. Edgerton: None. A.D. Cherrington: Consultant; Abvance Therapeutics. Research Support; Abvance Therapeutics. Advisory Panel; AdipoPharma. Research Support; Cellular Longevity, Inc. dba Loyal. Advisory Panel; Fractyl Health, Inc. Consultant; Fractyl Health, Inc. Research Support; Fractyl Health, Inc. Consultant; Novo Nordisk. Research Support; Novo Nordisk. Consultant; Paratus, Portal Insulin. Advisory Panel; Sekkei Bio, Sensulin Labs, LLC. Consultant; Thetis Pharmaceuticals, LLC.

Funding

National Institutes of Health (5R01DK131082); National Institutes of Health (5T32DK007563)
1566-P: Growth Hormone Replacement Treatment Improves Nonalcoholic Fatty Liver Disease in Patients with Pituitary Stalk Interruption Syndrome—A Randomized, Single-Blind, Placebo-Controlled Prospective Cohort Study
Authors: ZHANG JUNYI , WU XUEYAN
Published: June 2024

Background: Non-alcoholic fatty liver disease (NAFLD) commonly coexists as a comorbidity among patients with pituitary stalk interruption syndrome (PSIS) with growth hormone deficiency (GHD). This study aimed to investigate the impact of GH replacement therapy on liver fat content and metabolic parameters in PSIS patients with GHD and NAFLD.

Methods: In this randomized, single-blind, placebo-controlled prospective trial, 14 adults with PSIS, who have GHD and LFC ≥ 6%, aged 20 to 50 years without diabetes, were randomized to weekly subcutaneous GH (n=8) or placebo (n=6), targeting insulin-like growth factor 1 to normal quartile. The primary endpoint was LFC assessed before and after 32-week treatment using magnetic resonance imaging-derived proton density fat fraction.

Results: The GH group had significantly greater reduction in LFC compared to placebo group (mean ± SD: -11.48±9.26 % vs -3.12±4.12, P=0.046). Additionally, GH group showed a more substantial median decrease in gamma-glutamyl transferase levels than placebo group [-5.50, interquartile range(IQR) -42.75 to -2.25 vs 5.00, IQR -14.75 to 25.00 U/L, P 0.029]. No significant differences were observed in the changes of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). In GH group, both AST and ALT levels after 32-week treatment were significantly lower than baseline values [21.50 (18.50, 30.50) vs 28.00 (21.75, 64.50) IU/L, P = 0.012; 24.00(19.75, 36.00) vs 31.50(23.50, 90.50) IU/L, P = 0.012; respectively), while no such changes could be obtained in placebo group.

Conclusion: GH replacement therapy can reduce LFC in patients with GHD and NAFLD, which may emphasize the need for prompt GH treatment in such specific patient population.

Disclosure

J. Zhang: None. X. Wu: None.

Funding

Project of National Natural Science Foundation of China (81771576); and the Beijing Municipal Natural Science Foundation (7202151)
1569-P: Quantification of Postprandial Hepatic Glucose Disposal in Roux-en-Y Gastric Bypass and Non-operated Controls Using Stable Isotope Labelling and Liver Metabolic Imaging
Authors: BRUNASSO ALESSANDRO , DALLA MAN CHIARA , POLI SIMONE , HERZIG DAVID , KREIS ROLAND , BALLY LIA , SCHIAVON MICHELE
Published: June 2024

Roux-en-Y gastric bypass surgery (RYGB) alters postprandial glucose metabolism due to changes in gastrointestinal tract anatomy and large weight loss. Here, we propose a model quantifying postprandial hepatic and peripheral glucose fluxes in post-RYGB patients at steady weight loss and healthy controls (HC). Ten RYGB (2M, age=39.2±3.1 y, BMI=28±1 kg/m2 - mean±SE) and 10 HC (5M, age=36.4±3.2 y, BMI=26±1 kg/m2) underwent Deuterium Metabolic Imaging (DMI) at a 7 Tesla MR scanner before and after ingesting 60g of [6,6-2H2]-glucose (D-Glc). Venous blood was sampled to measure plasma insulin (I) and D-Glc (GP). Hepatic DMI was used to track liver D-Glc levels (GL) over 150min. Data was used to develop a model describing postprandial hepatic and peripheral glucose appearance (RaL and RaP) and disposal (RdL and RdP) as well as first-pass hepatic glucose extraction (ISE). Incremental Area Under the Curve (iAUC) of GL was greater in RYGB compared to HC (iAUC(GL)0-150min = 620±39 vs 467±41 mM·min, p=0.010), as was iAUC(I)0-150min (49.8±4.9 vs 29.2±3.4 nM·min, p=0.003), while iAUC(GP)0-150min was not significantly different (628±69 vs 520±26 mM·min). iAUCs of RaL and RaP normalized to 60g were higher in the first 60min in RYGB vs HC (63.0±3.0 vs 27.8±2.7 %; 60.5±3.1 vs 26.0±2.6 %, p<0.001), as were iAUCs of RdL and RdP after 150 min (24.6±1.1 vs 18.0±1.7 %, p=0.005; 53.6±2.9 vs 32.1±4.1 %, p<0.001). Conversely, model-derived ISE was similar (8.6±0.3 vs 8.8±0.7 %) in the two groups. A model using stable isotope and liver DMI data was developed to quantify peripheral and organ-level glucose turnover without portal vein catheterization. Results showed that the difference in glucose time course in RYGB vs HC is explained by the faster rate of appearance in RYGB, while disposal, at both liver and periphery, appears to be intact. The model also suggests that no saturation arises in the first-pass extraction, despite the high glucose levels.

Disclosure

A. Brunasso: None. C. Dalla Man: None. S. Poli: None. D. Herzig: Speaker's Bureau; Ypsomed AG. R. Kreis: None. L. Bally: None. M. Schiavon: None.

Funding

PNRR Next Generation EU (ex DM 118/23)-Swiss National Science Foundation (PCEGP3_186978)
1574-P: Catecholamine-Induced Adipose Lipolysis Drives Hepatic Steatosis in Pnpla3I148M Knockin Mice
Authors: PRAKASH GOLLA JAYA , SUH REBECCA , PAOLELLA LAUREN M. , STROBER JORDAN W. , ZHANG FENGRUI , PHILBRICK WILLIAM M. , VATNER DANIEL F.
Published: June 2024

PNPLA3 (Patatin like phospholipid domain containing protein 3) I148M is the most common human genetic mutation associated with hepatic steatosis. Alterations in white adipose tissue (WAT) function are often linked to hepatic lipid accumulation, but current understanding of the effect of PNPLA3I148M on WAT function is limited to the finding that this mutation does not appear to impact WAT insulin responsiveness. We evaluated WAT catecholamine responsiveness using the β3-adrenergic agonist CL 316243 (CL) in Pnpla3I148M mice. In vivo, the plasma NEFA response to CL was increased in mutant mice (Basal NEFA: WT 0.65 ± 0.07 mM, MUT 0.66 ± 0.07 mM, P = 0.5; CL stimulated NEFA: WT 1.3 ± 0.1 mM, MUT 1.6 ± 0.1 mM, P = 0.03). Ex vivo, CL-induced fatty acid release from gonadal WAT was increased in mutant mice (1.22-fold increased NEFA release, P = 0.03). High sucrose diet fed Pnpla3I148M mice are a known model of increased hepatic steatosis; beta adrenergic blockade with propranolol did not alter hepatic triglyceride content in WT mice as compared with vehicle, but markedly decreased hepatic triglyceride in Pnpla3I148M mice (WT: VEH 37 ± 5 mg/g; PRO 36 ± 6 mg/g. MUT: VEH 55 ± 6 mg/g; PRO 19 ± 4mg/g, P = 0.0002). Acipimox, an inhibitor of WAT lipolysis, similarly had no effect on WT hepatic steatosis and markedly decreased hepatic triglyceride in Pnpla3I148M mice (WT: VEH 46 ± 5 mg/g; ACI 49 ± 10 mg/g. MUT: VEH 78 ± 11 mg/g; ACI 40 ± 5mg/g, P = 0.006).

Conclusions: WAT catecholamine responsiveness is increased in Pnpla3I148M mice contributing to hepatic steatosis in these mice. As human hepatic triglyceride biosynthesis is strongly weighted towards esterification of preformed fatty acids from extrahepatic sources, this biology may contribute to the increased susceptibility to fatty liver seen in patients with the PNPLA3I148M mutation.

Disclosure

J. Golla: None. R. Suh: None. L.M. Paolella: None. J.W. Strober: None. F. Zhang: None. W.M. Philbrick: None. D.F. Vatner: None.

Funding

National Institutes of Health (RO1DK124272;T32DK007058; P30DK045735)
1575-P: Differential Effects of Rising Glucagon Concentrations on Hepatic Amino Acid Extraction
Authors: CHRISTIE HANNAH E. , MOHAN SNEHA , EGAN AOIFE M. , VELLA ADRIAN
Published: June 2024

To understand the actions of glucagon on hepatic amino acid (AA) metabolism, we studied nondiabetic individuals on one occasion after an overnight fast. On the morning of the study, femoral artery (FA), femoral vein (FV) and hepatic vein (HV) catheters were placed under fluoroscopic guidance in the interventional radiology suite. Infusion of indocyanine green (0.25mg/min), allowed measurement of splanchnic blood flow (SBF) throughout the experiment. At the start of the experiment (0 min), somatostatin was infused (60 ng/kg/min) to block endogenous hormone secretion. Insulin was infused at 0.8 mU/Kg/min together with glucagon at 1.5 ng/kg/min. To mimic ingestion of a protein load, Clinisol (15%, 0.003ml/kg/min; 51% essential AA, 18% branched-chain AA, 9% aromatic AA; Baxter, Healthcare, Deerfield, IL) was infused. Glucose was infused to maintain peripheral arterial concentrations at 160mg/dL. At 120 min glucagon infusion was increased to 3 ng/kg/min. AAs and their metabolites were measured using derivatized standards. Samples were analyzed on a triple quadrupole mass spectrometer coupled with an Ultra Pressure Liquid Chromatography system. Distinct patterns of % hepatic AA extraction (calculated using HV-FA difference as a function of SBF) were noted. The majority of AAs’ extraction increased in response to AA and glucagon infusion (e.g. Leucine [8 ± 5 vs. 14 ± 6 %], Serine, Glycine, Tyrosine and Methionine [27 ± 5 vs. 39 ± 5 %]). Notable exceptions included α-aminoadipic acid which is released by the liver in the fasting state (-9.0 ± 12%) and in response to AA and glucagon infusion (-13 ± 7%). Aspartate changed from net release (-40 ± 34%) to uptake (29 ± 14%) in response to glucagon. In other cases, hepatic extraction was unchanged (e.g. Threonine, Alanine [56 ± 10 vs. 55 ± 6%], Valine, Lysine and Cysteine). It remains to be ascertained if such patterns of hepatic extraction of AAs in response to glucagon differ in metabolic disease states thereby identifying novel therapeutic targets.

Disclosure

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

Funding

DK116723