bluuebunny/crossref_metadata_2025_split huggingface dataset:
335-OR: Participant Engagement and Weight Loss in the National Diabetes Prevention Program before and during COVID
Authors: SAN DIEGO EMILY , CHICHMARENKO MARIYA , SORIANO EMILY , SPIERLING BAGSIC SAMANTHA R. , ORENDAIN NATALIA , FORTMANN ADDIE L. , RUIZ MONICA , PHILIS-TSIMIKAS ATHENA 
Published: June 2023

The CDC’s National Diabetes Prevention Program (NDPP) aims to prevent or delay type 2 diabetes (T2D) through lifestyle change and weight loss. Due to challenges implementing in-person programs during the COVID-19 pandemic, many CDC-recognized organizations transitioned to offer the NDPP virtually. This analysis used NDPP data collected as part of routine care at Scripps Health, a large, non-profit health system in San Diego, CA. There were 273 individuals who participated in the NDPP before COVID (in-person sessions; October 2016 - January 2020) and 73 during COVID (virtual sessions; August 2020 - June 2021). Participants who attended virtually and in-person were, on average, 59.59±12.71 and 59.90±13.93 years old, and the majority were women (69% and 83%), White (65% and 45%), married (81% and 62%), and college graduates (66% and 44%), respectively. Chi-square, Fisher’s exact, and unpaired t-tests examined differences between the in-person vs. virtual cohorts. Compared to in-person, virtual participants consisted of significantly more men (31% vs. 17%, p= .01), but fewer Hispanics (14% vs. 43%, p&lt; .01), Spanish-speakers (1% vs. 17%, p &lt; .05), individuals with less than high school education (0% vs. 18%, p &lt; .05), and individuals with household income of less than $24,000 (1% vs. 17%, p &lt; .05). While the number of core sessions attended was not significantly different (M=20.19 vs. M=18.82; p&gt; .05), average percent weight loss was significantly lower for individuals in the virtual sessions than in the in-person sessions (M=3.35 vs. M=4.50; p= .05). Although the NDPP has continued to reach participants despite the pandemic’s challenges, participation by racial and ethnic minority and socioeconomically disadvantaged individuals declined when the program transitioned to virtual delivery. More research is needed to examine patient-centered approaches to improve outcomes and engage underserved communities that are disproportionately affected by prediabetes and T2D.

Disclosure
E.San diego: None. M.Chichmarenko: None. E.Soriano: None. S.R.Spierling bagsic: None. N.Orendain: None. A.L.Fortmann: Employee; Dexcom, Inc. M.Ruiz: None. A.Philis-tsimikas: Advisory Panel; Dexcom, Inc., Novo Nordisk A/S, Sanofi, Other Relationship; Medtronic, Research Support; Novo Nordisk A/S, Lilly, Viking Therapeutics, NIH - National Institutes of Health.

Funding
National Institutes of Health (UL1TR002550, KL2TR002552)
338-OR: Increased Glucose Time in Range following Active vs. Sedentary Days in Newly Diagnosed Youth with T1D—4T Exercise Results
Authors: ZAHARIEVA DESSI P. , RITTER VICTOR , RIDDELL MICHAEL , ADDALA ANANTA , BISHOP FRANZISKA K. , PRAHALAD PRIYA , DESAI MANISHA , HOOD KOREY K. , SCHEINKER DAVID , MAAHS DAVID M. 
Published: June 2023

The 4T Exercise Study started newly diagnosed youth with T1D on CGM and physical activity (PA) trackers ~1-month post diagnosis. We examined real-world PA patterns and glycemia in youth with T1D during the first year post diagnosis. A physically active day was identified as ≥10 mins of continuous moderate-to-vigorous intensity PA, with moderate-intensity (MOD) defined as 3-6 metabolic equivalents (METS) and high-intensity (HIE) as &gt;6 METS. All other days were deemed as sedentary (SED) days. CGM data 24h after exercise were used to compute percent time below range (TBR; &lt;70 and TBR2; &lt;54 mg/dL), time in range (TIR; 70-180 mg/dL), and time above range (TAR; &gt;180 and TAR2; &gt;250 mg/dL). A total of 45 youth (age: 13 [IQR 12, 15] years, 38% female, 40% non-Hispanic White, 76% private insurance) wore activity trackers 13 [IQR: 8, 16] hours daily. Compared to SED days, higher intensity PA levels were associated with higher TIR (70% SED vs 72% with MOD, P=0.2; 76% with HIE, P=0.001) and lower TAR (28% SED vs 24% with MOD, P=0.08; 21% with HIE, P&lt;0.001), but no difference in TBR (2.8% SED vs 3.6% following MOD, P=0.2; 3.7% following HIE, P=0.14). Overall, higher levels of PA in youth with new onset T1D was associated with over an hour of increased TIR per day, without significant increases in TBR. Exercise education soon after diagnosis is an opportunity to improve care and establish safe and healthy PA habits.

Disclosure
D.P.Zaharieva: Advisory Panel; Dexcom, Inc., Research Support; Hemsley Charitable Trust, International Society for Pediatric and Adolescent Diabetes, Insulet Corporation, Speaker's Bureau; American Diabetes Association, Ascensia Diabetes Care, Medtronic. D.M.Maahs: Advisory Panel; Medtronic, LifeScan Diabetes Institute, MannKind Corporation, Consultant; Abbott, Research Support; Dexcom, Inc. V.Ritter: None. M.Riddell: Advisory Panel; Zealand Pharma A/S, Zucara Therapeutics, Indigo Diabetes, Consultant; Lilly Diabetes, Eli Lilly and Company, Jaeb Center for Health Research, Speaker's Bureau; Dexcom, Inc., Novo Nordisk, Sanofi, Stock/Shareholder; Supersapiens, Zucara Therapeutics. A.Addala: None. F.K.Bishop: None. P.Prahalad: None. M.Desai: None. K.K.Hood: Consultant; Cecelia Health. D.Scheinker: None.

Funding
National Institutes of Health (P30DK116074); Stanford Diabetes Research Center (R18DK122422 to D.M.M.); Dexcom, Inc.; Lucile Packard Children’s Hospital Auxiliaries Endowment; The Leona M. and Harry B. Helmsley Charitable Trust (G-2002-0425); Internationa
348-OR: Differentiation of Adult Islet Cell Precursors into ß- and α-like Cells for Islet Transplantation
Authors: DARDEN CARLY , KUNCHA JAYACHANDRA , MATTKE JORDAN D. , NAZIRUDDIN BASHOO , LAWRENCE MICHAEL C. 
Published: June 2023

Advances in protocols to convert human embryonic and inducible pluripotent stem cells (hESCs and iPSCs) into pancreatic β cells has allowed us to generate islet cell organoids in culture for potential use in islet cell transplantation. Here, we demonstrate that dedifferentiated β cells and/or NGN-/RGS16+ islet cell precursors (ICPs) can be harvested from adult pancreatic tissue and converted into β- and α-like cells. In this study, we used ICPs derived from COBE bag pancreatic tissue remnants from organ donors to produce islet cell organoids capable of releasing both insulin and glucagon in response to high (16.7 mM) and low (2.8 mM) glucose conditions, respectively. These organoids displayed zinc-containing granule staining by dithizone and exhibited GSIS with stimulation indices comparable to human islets. ICPs produced genetic profiles similar to hESC-derived endocrine progenitor cells at stages 5-7 (S5-7). Using small molecule ISX9 and GSK/DYRK inhibitors GNF and harmine to induce and activate calcineurin (CN)/NFAT signaling, we were able to expand and differentiate ICPs into β- and α-like cells. CN/NFAT upregulated genes that promote cell cycle and proliferation (S5) and islet cell differentiation genes (S5-7). Islet cell type fate and function could be modulated by hedgehog/GLI signaling. Whereas introduction of sonic hedgehog (Shh) inhibitor SANT-1 at S5 favored production of β-like cells, Shh signaling agonists promoted differentiation to α-like cells up to S7. Overall, these results indicate that adult ICPs can be harvested from donor tissue and expanded for differentiation into functional β- and α-like cells. The capability to expand and differentiate adult ICPs could potentially provide an unlimited supply of islet organoid tissue for islet cell transplantation.

Disclosure
C.Darden: None. J.Kuncha: None. J.D.Mattke: None. B.Naziruddin: None. M.C.Lawrence: None.

Funding
Baylor Scott & White Health
35-LB: The Impact of the COVID-19 Pandemic on A1C Reductions in Patients with Diabetes Mellitus Who Attended an ADA-Recognized DSMES Program
Authors: STONEKING KENT B. , LATIF KASHIF , MOORE MARIAN , WHITE HANNAH 
Published: June 2023

AM Diabetes Centers of America, an independent endocrinology practice in Bartlett, Tennessee, offers a diabetes self-management, education, and support (DSMES) program that has been recognized by the American Diabetes Association (ADA) since 2010. The program typically serves 450-500 participants per year, all from the Memphis/Mid-South area. Per ADA requirements, participants’ pre- and post-program attendance glycated hemoglobin (A1C), weight, blood pressure, and lipids, are reported annually. Of these, A1C was observed as a key metric indicating blood glucose control. Data sets from ADA Chronicle Diabetes were analyzed quantitatively to compare program attendance and A1C reductions between 2013-2019 and the pandemic peak in 2020-2021. From 2013-2018, program attendance grew at an average rate of 26% per year. Attendance dropped by 30% in 2019, but average A1C reduction among participants in 2019 was 0.8%, and average A1C reduction for all participants in 2013-2019 was 0.64% (SD=0.346; p=0.003). In 2020-2021, attendance dropped by an average of 30% per year, and average A1C reduction was only 0.45% (SD=0.05; p=0.035). In the first post-pandemic year, program attendance rebounded by 18% and average A1C reduction was 1.1%. Because a direct correlation exists between waning program attendance and reduced impact upon participants’ A1C levels during COVID-19, and because these trends reversed as soon as pandemic restrictions were lifted, it may be reasonably ascertained that the mandated restrictions on in-person meetings and outside activities were key factors in producing these results.

Disclosure
K. B. Stoneking: None. K. Latif: None. M. Moore: None. H. White: None.
351-OR: Two Different Ways to Replace Beta-Cell Mass after Partial Pancreatectomy
Authors: JOON KIM BYUNG , PARK HEEKYOUNG , SHIN JUN-SEOP , KIM KWANG-WON 
Published: June 2023

Treatment of diabetes in which beta cell mass is reduced is islet transplantation (IT), which replaces beta cells, and insulin therapy, which rests beta cells. Although both methods show significant results in preventing the progression of diabetes, it is controversial whether the two treatments work through the same mechanism. To evaluate this hypothesis, insulin injection or IT was performed on mice that had undergone 50% partial pancreatectomy, and the IPGTT and histological changes of the remnant pancreas were examined. In the IPGTT conducted after IT or insulin treatment after pancreatectomy for 7 days, the blood glucose profile of the IT mice was similar to that of normal, but the insulin-treated mice showed a significantly higher blood glucose level than normal. In histology of the remnant pancreas in the insulin-treated group, alpha cells increases, and the alpha/beta ratio was significantly higher than in the normal or IT group. There was no difference in islet proliferation or apoptosis in the insulin-treated group, but PDX-1 expression was significantly higher in alpha cells of the insulin-treated group. In conclusion, insulin or IT as a treatment method to replace beta cells is known in a similar way. But, IT is a more physiological method than insulin treatment, and it needs to be worked more detail whether notable increases of alpha cell mass in the remnant pancreas due to insulin treatment is a short-term or a continuous change.

Disclosure
B.Kim: None. H.Park: None. J.Shin: None. K.Kim: None.
363-OR: Brown Adipose Tissue m6A mRNA Methylation Regulates Systemic Insulin Sensitivity via a Prostaglandin Interorgan Axis
Authors: XIAO LING , DE JESUS DARIO F. , JU CHENG-WEI , WEI JIANGBO , HU JIANG , TSUJI TADATAKA , CERO CHERYL , KAMINSKA DOROTA , CYPESS AARON M. , PIHLAJAMAKI JUSSI , TSENG YU-HUA , KULKARNI ROHIT 
Published: June 2023

Brown adipose tissue (BAT) has the capacity to regulate peripheral insulin sensitivity via the secretion of signaling lipids. N6-methyladenosine (m6A) is among the most prevalent and abundant post-transcriptional RNA modifications in eukaryotes. Recently, m6A has been shown to regulate islet and hepatic metabolism as well as BAT adipogenesis and energy expenditure. Here, we demonstrate that deficiency of m6A methyltransferase-like 14 (M14) in BAT positively regulates BAT-secretory function to improve systemic insulin sensitivity through inter-organ communication. Using lipidomic approaches, we identified prostaglandin E2 (PGE2) and prostaglandin F2a (PGF2a) as M14KOBAT-secreted insulin sensitizers. Notably, circulatory PGE2 and PGF2a showed significant inverse correlation with HOMA-IR in humans. Furthermore, in vivo administration of PGE2 and PGF2a in HFD-induced insulin resistant obese mice recapitulated the phenotypes of M14KO mice. Exogenous PGE2 or PGF2a significantly improved insulin stimulated-pAKT by suppressing expression of specific phosphatases in human hepatocyte cell line. Mechanistically, M14-mediated m6A installation destabilizes transcripts encoding PGE2 and PGF2a synthases in brown adipocytes in an YTHDF2/3-dependent manner. Collectively, these results unveil a new mechanism by which m6A-facilitated BAT-secretory function enables the regulation of whole body insulin sensitivity.

Disclosure
L.Xiao: None. J.Pihlajamaki: None. Y.Tseng: Consultant; Cellarity, LyGenesis. R.Kulkarni: Advisory Panel; Novo Nordisk, Inversago, Biomea Fusion, Inc., REDD Pharma, Research Support; Inversago. D.F.De jesus: None. C.Ju: None. J.Wei: None. J.Hu: None. T.Tsuji: None. C.Cero: None. D.Kaminska: None. A.M.Cypess: None.
365-OR: A Machine-Learning Approach to Estimate Insulin Resistance from Untargeted Metabolomics Data
Authors: ALLRED NICHOLETTE , HSU FANG-CHI , CHEN SHYH-HUEI , NG MAGGIE , GOODARZI MARK O. , ROTTER JEROME I. , WAGENKNECHT LYNNE E. , BANCKS MICHAEL , BERGMAN RICHARD N. , BOWDEN DONALD W. 
Published: June 2023

Insulin resistance (IR) is constantly invoked as a contributor to numerous common diseases, e.g. diabetes, cardiovascular disease and Alzheimer’s disease; however, with the exception of a narrow segment of diabetes-related studies, IR is infrequently measured and rarely measured well. Our goal was to develop IR estimation models for the dynamic measure of insulin sensitivity (SI) and the basal measure of homeostatic model assessment of IR (HOMAIR) from metabolomics data combined with minimal clinical data, e.g. age, sex, BMI. Least Absolute Shrinkage and Selection Operator (LASSO) and Elastic Net regression were used to build estimation models using 1274 metabolites, prioritized by trait associations and collected in the Insulin Resistance Atherosclerosis Family Study (IRASFS). Three metabolite transformations were implemented (inverse normal transformation, standardization, and Box Cox transformation) to account for distributional differences and tested to optimize estimation. The analysis was performed in one Mexican American (MA) recruitment site (San Luis Valley, CO (SLV), N=450) and tested in another MA recruitment site (San Antonio, TX (SA), N=473). In addition, the two MA recruitment sites were combined and estimation models tested in the African American recruitment site (AA; Los Angeles, California, N=495) to assess generalizability. Estimated SI was correlated with empiric SI in the SA (r2=0.77) and AA (r2=0.74) testing datasets. Further, we tested estimated SI for association with BMI, low-density lipoprotein cholesterol and triglycerides with results consistent with those observed for empiric SI. The same framework was used to estimate HOMAIR, and yielded similar results. In summary, we have developed methods for estimating multiple measures of IR from a single blood sample. This approach will greatly expand our ability to provide meaningful insight into the role of IR in disease, supporting the potential for application to a wide-range of biomedical studies.

Disclosure
N.Allred: None. D.W.Bowden: None. F.Hsu: None. S.Chen: None. M.Ng: None. M.O.Goodarzi: Advisory Panel; Nestlé Health Science, Other Relationship; Nestlé Health Science. J.I.Rotter: None. L.E.Wagenknecht: None. M.Bancks: None. R.N.Bergman: Consultant; Lilly, ReCor Medical, Inc., Research Support; AstraZeneca.

Funding
National Institutes of Health (DK118062)
366-OR: Regulation of Metabolite Pools Influences Adipocyte Differentiation and Antioxidant Capacity
Authors: FELIX JESSICA B. , SAHA PRADIP , COX AARON , SHARP ROBERT A. , MASSCHELIN PETER M. , HARTIG SEAN M. 
Published: June 2023

Obesity and related metabolic disorders, such as insulin resistance and type 2 diabetes (T2D), affect over 40% of U.S. adults and increase the risk of death from cardiovascular disease. Understanding the mechanisms connecting obesity, T2D, and defective adipocyte function bring us closer to developing therapeutic strategies. We discovered expression of the enzyme aspartoacylase (ASPA) in white adipose tissue (WAT) correlates with adipocyte function and insulin sensitivity in mice and people. In the brain, ASPA contributes to the acetate pool necessary for lipid synthesis, and ASPA deficiency causes progressive myelin degeneration and death at a young age. We also observed abundant ASPA expression in WAT at significantly higher levels than whole brain. Aspa is induced during adipocyte differentiation in vitro along with known adipogenic markers. These observations led us to hypothesize that ASPA and its metabolite byproducts regulate adipocyte differentiation and systemic energy balance. When assessing the in vivo effects of Aspa deficiency, Aspa-/- mice accumulated less body mass than Aspa+/+ when fed normal chow diet for 12 weeks. Morphometric tissue analyses indicated Aspa-/- mice maintain smaller adipocytes, corresponding with lower WAT mass at necropsy. Glucose tracing experiments suggested Aspa knockout cells exhibit greater pyruvate carboxylase (PC) anaplerosis that feeds amino acid pools for glutathione synthesis. Mass spectrometry data also indicated higher PC anaplerosis in the adipose tissues of Aspa knockout mice. Persistent and prolonged oxidative stress hinders adipocyte function and insulin sensitivity, while PC activity supports antioxidant capacity. In line with this, Aspa knockout cells showed increased expression of proteins that sustain antioxidant activities. In summary, our studies establish a new role for ASPA outside the brain that contributes to redox activities in adipocytes.

Disclosure
J.B.Felix: None. P.Saha: None. A.Cox: None. R.A.Sharp: None. P.M.Masschelin: None. S.M.Hartig: None.

Funding
American Diabetes Association (1-18-IBS-105 to S.M.H.); National Institutes of Health (F31DK130596, R01DK114356)
369-OR: Continued Weight Loss with Semaglutide Once-Weekly in Patients without Type 2 Diabetes and Postbariatric Treatment Failure
Authors: LAUTENBACH ANNE , WAGNER JONAS , STOLL FABIAN D. , ABERLE JENS 
Published: June 2023

Purpose: Recently, we published promising retrospective 6-months follow-up data on the effectiveness of semaglutide 0.5mg once-weekly in patients with weight regain (WR) or insufficient weight loss (IWL) following bariatric metabolic surgery (BS). Therefore, we aimed to investigate whether weight loss was sustained over a 12-months period with semaglutide in patients without type 2 diabetes (T2D) with WR or IWL.
Materials and Methods: Postbariatric patients without T2D with WR or IWL (n=29) were included in the analysis. The primary endpoint was weight loss 12 months after initiation of adjunct treatment. Secondary endpoints included change in BMI, HbA1c, lipid profile, hs-CRP and liver enzymes.
Results: Total weight loss during semaglutide treatment added up to 14.7±8.9% (mean±SD, p&lt;0.001) after 12 months. Categorical weight loss was &gt;5% in 89.7% of patients, &gt;10% in 62.1% of patients, &gt;15% in 34.5% of patients, &gt;20% in 24.1% of patients and &gt;25% in 17.2% of patients. Among patients with prediabetes at baseline (n=6), 12-months treatment led to normoglycemia in all patients (p&lt;0.05).
Conclusion: Treatment options to manage postbariatric treatment failure are scarce, weight loss medications are not approved for use in the postbariatric patient population. Our results imply a clear benefit of adjunct treatment with semaglutide in postbariatric patients.

Disclosure
A.Lautenbach: Other Relationship; Novo Nordisk, Lilly. J.Wagner: None. F.D.Stoll: None. J.Aberle: Advisory Panel; Novo Nordisk, Speaker's Bureau; Novo Nordisk.
371-OR: Mortality in the Swedish Obese Subjects Study over up to 30 Years in Relation to Two-Year Diabetes Remission after Bariatric Surgery or Usual Care
Authors: SJÖHOLM KAJSA , ANDERSSON ASSARSSON JOHANNA C. , TAUBE MAGDALENA , CARLSSON EKANDER LENA 
Published: June 2023

Introduction: Patients with obesity and concomitant type 2 diabetes (T2D) have reduced life expectancy, which may to some extent be explained by an increased risk of developing vascular diseases and cancer. Remission of T2D is known to reduce the risk of diabetes-related diseases. Here, we examined whether 2-year diabetes remission after bariatric surgery or usual care is associated with long-term mortality in patients from the Swedish Obese Subjects (SOS) study.
Methods: This report includes 586 patients with obesity and baseline T2D; 338 underwent bariatric surgery and 248 obtained usual obesity care, median follow up was 26 years. The Swedish Cause of Death Register, case sheets and autopsy reports were assessed to determine the direct cause of death. Analyses were adjusted for preselected risk factors (age, sex, BMI and smoking at baseline, and year of inclusion in the study).
Results: Overall, 284 patients were in remission at the 2-year examination whereas 302 were not. During follow-up, mortality rates were 16.6 deaths per 1000 person-years (95% CI:13.7-20.1) in the remission subgroup and 26.0 deaths per 1000 person-years (95% CI:22.2-30.4) in the non-remission subgroup (adjusted hazard ratio (AdjHR) 0.59, 95% CI:0.46-0.77, p&lt;0.001). Specifically, cardiovascular mortality was decreased in the remission subgroup (Adj sub-HR 0.53, 95% CI:0.35-0.81, p=0.003). Moreover, 2-year remission was associated with reduced mortality after both surgery and usual care (AdjHR 0.57 (95% CI:0.39-0.83), p=0.003 and AdjHR 0.53 (95% CI:0.32-0.90), p=0.018, respectively).
Conclusions: Remission of T2D after bariatric surgery or usual obesity care is associated with reduced long-term mortality, mainly due to decreased cardiovascular death.

Disclosure
K.Sjöholm: None. J.C.Andersson assarsson: None. M.Taube: None. L.Carlsson ekander: None.

Funding
Swedish Research Council; Swedish State; Swedish Heart and Lung Foundation; Swedish Diabetes Foundation; Adlerbert Research Foundation