bluuebunny/crossref_metadata_2025_split huggingface dataset:
37-LB: Impacts and Influencing Factors of an Internet-Supported Diabetes Management Program in Beijing
Authors: WU YIMING 
Published: June 2023

Purpose: The aim of the study is to examine the impact of an Internet supported diabetes management program and to analyze the influencing factors of the improvement.
Methods: The Internet Diabetes Shared Care Program (IDSC) in Peking University Shougang Hospital was an application of DSMES (Diabetes Self-Management Education and Support) with Internet technologies. Interdisciplinary care team including diabetologist, nurses, dietitians and diabetes educators provide individualized consultation in hospital every 3 months, and continuous online lifestyle coaching via smartphone applications. Change of (HbA1c), BP, LDL-c, BMI at baseline and at last visit were compared. Multiple linear regression analysis were applied to analyze the data.
Results: Total of 349 patients (female 51%) were enrolled from 2018 to 2022 with average age 56.98±10.61 years, duration of DM 9.59±8.23 years. Patients were followed in the IDSC program for 1.78±0.90 years. At baseline, 41.8% used insulin. After the program. the HbA1c decreased 1.29±2.22%(8.41±2.23% vs 7.12±1.30%, t=10.32, P=0.000), BMI decreased 0.43±2.50 kg/m2(25.98±3.99kg/m2 vs 25.56±3.83 kg/m2, t=3.10, P=0.002). Multiple linear regression found and patient age (β=-0.036, P=0.001), followed duration (β=-0.349, P=0.004), baseline HbA1c achieved ≤7% (β=-2.477, P=0.000) and weekly communication with diabetes educators (β=0.828, P=0.013)were the impact factors for glycemic improvement.
Conclusion: The Internet supported diabetes management program significantly improved the glycemic control of DM patients, in which age, weekly communication and continuous care are essential factors for glycemic improvements.

Disclosure
Y. Wu: None.
372-OR: Long-Term Outcomes of Metabolic Surgery vs. Medical/Lifestyle Therapy on Nonalcoholic Fatty Liver Disease in Adults with Obesity and Type 2 Diabetes
Authors: LUNDHOLM MICHELLE D. , HU BO , KIRWAN JOHN P. , PATTI MARY-ELIZABETH , CUMMINGS DAVID E. , KASHYAP SANGEETA , CONSORTIUM ARMMS-T2D 
Published: June 2023

Introduction: Data are lacking on the long-term effects of metabolic surgery vs medical intervention on NAFLD in patients with obesity and T2D.
Methods: A multi-center, prospective, observational study was performed with adults enrolled in the Alliance of Randomized trials of Medicine vs Metabolic Surgery in Type 2 Diabetes (ARMMS-T2D) consortium. Patients with BMI 27-45 kg/m2 were randomized to medical therapy or surgery with gastric sleeve (GS), gastric band (GB), or Roux-en-Y gastric bypass (RYGB). The hepatic steatosis index (HSI), FIB-4 index, and AST-to-platelet ratio index (APRI) were calculated at baseline and follow-up at 6-15 years then compared by intention-to-treat analysis.
Results: We enrolled 262 patients, 49.9±8.3 yrs, 68.3% female, 67.2% white, HbA1c 8.5±1.5%, BMI 36.4±3.5 kg/m2. Liver steatosis was 100% positive by HSI. Fibrosis was rare by FIB-4 (&lt;1% advanced, 16.7% at-risk) and APRI (5.0% significant or severe). Steatosis and fibrosis rates did not differ between patients when randomized to medical (N=96) or surgical (N=166) therapies (GB N=36, GS N=41, RYGB N=89). At latest follow-up, the surgical group had greater decrease in weight (-20.1 vs -11.2 kg, p&lt;0.001), HbA1c (-1.10% vs -0.50%, p&lt;0.001), and greater diabetes remission (16.8% vs 2.2%, p&lt;0.001). Steatosis scores improved in both groups but to a greater extent after surgery (-8.5 vs -4.9, p&lt;0.001). Fibrosis scores were stable even though patients were 6-15 years older and values did not differ between surgical vs medical groups (FIB-4 -0.01 vs -0.02, p=0.77; APRI -0.04 vs -0.01, p=0.60).
Conclusion: Hepatic steatosis scores improved more in patients with T2D randomized to metabolic surgery vs medical management. Fibrosis scores did not worsen as would be expected with aging, suggesting a protective effect of both surgical and medical interventions. These results support a continued role for weight loss interventions to prevent and treat NAFLD.

Disclosure
M.D.Lundholm: None. B.Hu: None. J.P.Kirwan: None. M.Patti: Consultant; MBX Biosciences, AstraZeneca, Hanmi Pharm. Co., Ltd., Other Relationship; Fractyl Health, Inc. D.E.Cummings: None. S.Kashyap: Consultant; GI Dynamics, Research Support; Fractyl Health, Inc., Stock/Shareholder; Gila therapuetics. Armms-t2d consortium: n/a.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (U01DK114156)
373-OR: Repetitive Transcranial Magnetic Stimulation—A Potential Antiobesity Approach for Long-Term Maintenance of Weight Loss
Authors: FERRULLI ANNA , MASSARINI STEFANO , MACRÌ CONCETTA , SENESI PAMELA , TERRUZZI ILEANA , CANNAVARO DANIELE , LUZI LIVIO 
Published: June 2023

Current anti-obesity interventions result in early rapid weight loss, but long-term maintenance of lost weight is much more challenging. Initial weight loss is typically followed by a weight plateau and progressive regain. We demonstrated the efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) in inducing long-term weight loss (up to 1 year) in individuals with obesity by modulating the brain dopaminergic system and the prefrontal cortex. In a post-hoc analysis, we re-evaluated body weight loss up to 3 years after, in 44 individuals treated with a 5-week high frequency rTMS or sham stimulation, for obesity. Out of 44 subjects, 30 individuals (21 F/9 M, BMI 35.3±2.8, age 49.9±9.3) did not undergo any further weight loss treatments (except diet), 9 subjects (5 F/4 M, BMI 40.4±4.7, age 44.7±.6.1) underwent bariatric surgery, and 5 patients were treated for persistent obesity with a GLP-1 receptor agonist (GLP1-RA) (5 F/0 M, BMI 36.8±6.5, age 53.2±13.9). Out of 30 subject who did not undergo any further weight loss intervention, the 16 patients who received real rTMS (10 F/6 M, BMI 34.6±3.2, age 49.2±7.5) reported a significant body weight loss compared to the Sham group (11 F/3M, BMI 36.1±2.0, age 50.7±2.0) at the end of the 5-week intervention (BMI:-4.5±1.7% vs -1.6±1.8%, p=0.0001). Crucially, they continued to lose body weight compared to the Sham even 3 years after the end of intervention (BMI: -9.5±7.6% vs -3.6±8.4%, p=0.056). As expected, during the 3-year follow-up, bariatric surgery was more effective in promoting weight loss compared to the rTMS and the GLP1-RA (p=0.0001), but rTMS has not been shown to be less effective than GLP1-RA in maintaining lost weight (p=0.621). This preliminary evidence of efficacy of rTMS in promoting long-term weight loss (over one year) may be explained via neuronal neuroplasticity. TMS alone or in combination with other anti-obesity approaches may open new ways to sustain the efficacy of weight control interventions.

Disclosure
A.Ferrulli: None. S.Massarini: None. C.Macrì: None. P.Senesi: None. I.Terruzzi: None. D.Cannavaro: None. L.Luzi: Advisory Panel; Eli Lilly and Company, Medtronic, Research Support; Gelesis, Speaker's Bureau; A. Menarini Diagnostics, Amgen Inc., Boehringer Ingelheim and Eli Lilly Alliance, Eli Lilly and Company, Novo Nordisk, Novartis.

Funding
IRCCS MultiMedica (Ricerca Corrente)
374-OR: Exercise Training Decreases ß-Cell Senescence in Mice and Humans
Authors: CARAPETO PRISCILA , KAHNG JIHO , ALVES WAGNER ANA BARBARA T. , MIDDELBEEK ROELAND J.W. , HIRSHMAN MICHAEL F. , RUTTER GUY A. , GOODYEAR LAURIE , AGUAYO-MAZZUCATO CRISTINA 
Published: June 2023

Increased β-cell senescence contributes to the development of type 2 diabetes (T2D). Exercise is critical in the treatment of T2D and can attenuate aging-associated cellular changes, but exercise effects on β-cell senescence are unknown. We tested the effects of treadmill running (1h/day for 10 days) on two insulin resistance models: high-fat diet and insulin receptor antagonist (S961). Exercise improved glucose responsiveness and decreased senescence markers (SA-βGal activity, p21Cip1 and p16Ink4a mRNA and protein levels). RNAseq from pancreatic islets of exercised mice revealed decreased expression of senescence effector genes and senescence associated secretory phenotype factors. Exercise increased AMPK activity in islets as assessed by alpha catalytic subunit phosphorylation. Islets from sedentary mice cultured for 2 days with serum from exercised mice showed decreased senescence, suggesting a circulatory factor was responsible for these effects. Pathway analysis of RNASeq revealed that exercise upregulated glucagon type ligand receptors. Glucagon treatment of mouse and human islets activated AMPK and decreased senescence in β-cells, an affect attenuated by an AMPK inhibitor (compound C). Exercised mice treated with a glucagon antagonist (adomeglivant) blocked AMPK phosphorylation and increased p21Cip1 and p16Ink4. Exercise increased nuclear translocation of the AMPK substrate NRF2 in mouse islets while downregulation of Nrf2 with siRNA in MIN6 cells increased transcription of p16Ink4a, suggesting a potential mechanism linking exercise, AMPK activation and downregulation of β-cell senescence. Treatment of human donor islets with serum obtained pre- and post-exercise training for 10 weeks in people with T2D showed that training activated AMPK and decreased senescence markers. These findings demonstrate that exercise training decreases β-cell senescence and suggest that this important response to exercise occurs through circulating factors mediating an AMPK-dependent pathway.

Disclosure
P.Carapeto: None. J.Kahng: None. A.T.Alves wagner: None. R.J.W.Middelbeek: Research Support; Novo Nordisk. M.F.Hirshman: Stock/Shareholder; Abbott, AbbVie Inc., Amgen Inc., Colgate-Palmolive, Eli Lilly and Company, Medtronic. G.A.Rutter: Consultant; Sun Pharmaceutical Industries Ltd. L.Goodyear: None. C.Aguayo-mazzucato: None.

Funding
Joslin Diabetes Center (to C.A-M.); Richard and Susan Smith Family Foundation; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil (001)
375-OR: Epigenetic Control of Beta-Cell Stress Response and Senescence
Authors: VARGHESE SNEHA S. , PARVEEN NAZIA , WANG JEAN K. , HERNANDEZ-DE LA PENA ALESSANDRO G. , DHAWAN SANGEETA 
Published: June 2023

Both type 1 and type 2 diabetes (T1D and T2D) result from chronic insulin insufficiency due to progressive dysfunction and loss of beta cells, driven by cellular stress. Beta cell failure in both forms of diabetes involves defective stress-response and the onset of premature senescence, an irreversible form of cell-cycle arrest induced by chronic stress. However, the mechanisms by which cellular stress triggers beta cell senescence are not clear. We now show that CTCF, a stress-sensitive epigenetic regulator, controls the beta cell stress-response and senescence programs during beta cell maturation process along with the cohesin Smc3. Chromatin immunoprecipitation data suggest that CTCF and Smc3 differentially occupy genes associated with stress and DNA damage responses, functional maturation, and senescence in neonatal versus adult beta cells. Our data show that CTCF and cohesin Smc3 dependent control protects replicating beta cells from DNA damage, and is especially critical during the neonatal growth phase marked by high rates of replication. Beta cell specific loss of CTCF triggers a p53/p21 dependent senescence program, followed by beta cell dysfunction and eventual beta cell failure with advancing age. We further demonstrate that reduced CTCF levels in beta cells lead to adaptive failure in response to a high fat diet challenge, and recapitulate a neonatal beta cell like epigenetic landscape. Notably, CTCF levels are reduced in beta cells in T1D and T2D in mice and humans, and lead to reduced occupancy of CTCF and Smc3 at genes involved in senescence, DNA damage response, and beta cell function. Our data show that CTCF and cohesin collectively protect against senescence and govern beta cell function and fitness through a program established in the neonatal maturation phase.

Disclosure
S.S.Varghese: None. N.Parveen: None. J.K.Wang: Employee; Pfizer Inc., Johnson & Johnson. A.G.Hernandez-de la pena: None. S.Dhawan: None.

Funding
National Institutes of Health (R01DK120253)
377-OR: Stabilizing 14-3-3 and ChREBP Cytoplasmic Interaction to Rescue ß-Cells from Glucolipotoxicity
Authors: KATZ LIORA S. , TSE ISABELLE L. , VISSER EMIRA , BAUMEL-ALTERZON SHARON , KAISER MARKUS , BRUNSVELD LUC M. , PENNINGS MARLOES , OTTMANN CHRISTIAN , SCOTT DONALD 
Published: June 2023

Carbohydrate response element binding protein (ChREBP) is a glucose-responsive transcription factor with two splice isoforms (α and β). ChREBPα remains cytoplasmic by binding to 14-3-3. Increased glucose metabolism allows ChREBPα to enter the nucleus and induce ChREBPβ, a hyperactive isoform that is a key mediator of glucolipotoxicity. Using structure-guided stabilizer optimization, we have developed novel drugs that stabilize the protein-protein interaction between ChREBPα and 14-3-3, with a goal to prevent ChREBPα nuclear translocation, induction of ChREBPβ, and glucolipotoxicity. One hit compound, K391, has an EC50 of 0.3±0.1μM by fluorescent polarization assay and a Kd of 0.12μM by isotitration calorimetry. Using dual label analysis of the kinetics of cell growth and cell death, we found that K391 significantly reduced β-cell death by 31.8±3% and enabled proliferation in glucolipotoxic conditions in INS-1 cells (20mM glucose and 1mM palmitate). In response to glucose, 76.4±3.5 % of the cells stained for nuclear ChREBP. In the presence of K391, 39.75±5.3 % fewer cells displayed nuclear ChREBP in high glucose concentrations and 65.7±1.6% less in glucolipotoxic conditions, indicating that K391 retains ChREBPα in the cytoplasm and prevents transcription of ChREBPβ. Time course with an antibody against ChREBPα showed that ChREBPα transiently translocated to the nucleus at 30 min and then cleared out of the nucleus in high glucose, an effect blocked by K391 (N=3). In glucolipotoxic conditions, ChREBPα remained nuclear over time, an effect significantly attenuated by K391 (N=3). Txnip is an important mediator of glucose toxicity and a target gene of ChREBPβ. Importantly, K391 blocked the glucose response of the human Txnip promoter in a luciferase assay by 2±0.2 folds. We conclude that the K391 retains ChREBPα in the cytoplasm in high glucose and in glucolipotoxic conditions by stabilizing the ChREBPα and 14-3-3 interaction and thereby rescues β-cells from glucolipotoxicity.

Disclosure
L.S.Katz: None. I.L.Tse: None. E.Visser: None. S.Baumel-alterzon: None. M.Kaiser: None. L.M.Brunsveld: Consultant; Novartis, Ambagon Therapeutics, Research Support; Roche Diagnostics. M.Pennings: None. C.Ottmann: None. D.Scott: None.

Funding
National Institutes of Health (R01DK130300)
38-LB: Ex Vivo Immune Cell Function Analysis in Patients with CKD Undergoing Dialysis Treatment Monitors Exercise Treatment Effects on Immunosurveillance
Authors: HOFMANN SUSANNA M. , DINGES SOPHIA M. , WALTER MARC , VONKORN PIA , VONGERSDORFF GERO D. , ANDING-ROST KIRSTEN , HALLE MARTIN 
Published: June 2023

Chronic kidney disease (CKD) is marked by a pre-aging and dysfunctional immune system and chronic inflammation. Recent research indicates that chronic physical exercise training (ET) increases regulatory monocytes and T-cells thus modulating the inflammatory status associated with cardio-metabolic diseases. In particular, ET primes monocytes and T-cells towards a less inflammatory phenotype. We hypothesized that intradialytic ET is beneficial to patients with CKD by improving certain immune cell features and decreasing systemic inflammation. We isolated PBMCs from a subset of 18 patients with CKD (58-90 years, 38 % females) enrolled in the prospective intervention trial DiaTT (Dialysis Training Therapy; ClinicalTrials.gov: NCT03885102) at the beginning and after a 12-months intradialytic ET intervention (aerobic endurance + resistance training). Circulating immune cell populations were characterized by FACS. Ex-vivo basal and PMA-induced T-cell activation was determined by cell surface expression analysis of CD69. We found that ET reversed the shift towards intermediate monocytes, a known marker for CKD morbidity and mortality, and nonclassical monocytes in patients with CKD undergoing dialysis treatment. We observed an increase in naïve T-cells and Recent Thymic Emigrants (RTE) indicating an improvement of T-cell function. On T-cells, basal CD69 expression was significantly enhanced and PMA-induced CD69 expression was severely impaired in patients with CKD compared to healthy control subjects (n= 7). When patients with CKD underwent ET this specific T-cell function was restored to normal levels. Here, we show that even in these severely sick patients certain circulating immune cell functions can be regained potentially leading to an enhanced immunosurveillance. Our ex-vivo immune cell characterization and function analysis can be used to monitor exercise treatment effects on systemic inflammation.

Disclosure
S. M. Hofmann: None. S. M. Dinges: None. M. Walter: None. P. Vonkorn: None. G. D. Vongersdorff: None. K. Anding-rost: None. M. Halle: Advisory Panel; Abbott, Speaker's Bureau; Boehringer Ingelheim (Canada) Ltd., Daiichi Sankyo, Amgen Inc., BMS.
383-P: Intranasal (IN) Naloxone as a Novel Therapy to Preserve Hypoglycemia Counterregulatory (CR) Response after Exercise in Type 1 Diabetes (T1D)
Authors: MOHEET AMIR , EBERLY LYNN E. , INKOLLU SINDHURA , KUMAR ANJALI , ALVEAR ALISON C. , ZHANG YUAN , COLES LISA , EVANOFF NICHOLAS , DENGEL DONALD R. , SEAQUIST ELIZABETH R. 
Published: June 2023

Hypoglycemia (HG) is common after exercise in people with T1D. Antecedent exercise leads to attenuation of CR response during subsequent HG. In healthy humans, IV administration of naloxone during exercise preserved CR response to HG the following day. We tested the hypothesis that IN administration of naloxone during exercise will preserve CR response to HG in people with T1D with intact awareness of HG. We performed a single-blind randomized cross over trial to compare the impact of IN naloxone vs. IN saline administered during exercise on day 1 (D1) on the symptoms and epinephrine (Epi) response to HG on day 2 (D2). On D1, participants underwent two 90-min hyperinsulinemic-euglycemic clamps during exercise at 60% VO2max with IN naloxone (4 mg at start and +45 min each exercise period) or IN saline exposure; on D2 a HG clamp (target 50 mg/dl) was performed. 27 subjects (10F, age 29 ± 8 yrs) participated in the protocol. Outcomes included D2 average symptom scores (SS) and peak Epi level over HG clamp’s last 30 min. A general linear mixed model for each of SS and Epi with effects for naloxone vs. saline, treatment order (naloxone 1st vs. 2nd), and time (Part 1 vs. Part 2) was performed. SS and Epi response on D2 were not different following IN naloxone compared to placebo. In people with T1D, administration of IN naloxone during exercise did not alter symptom or EPI response to subsequent HG.

Disclosure
A.Moheet: None. E.R.Seaquist: Consultant; Zucara Therapeutics. L.E.Eberly: None. S.Inkollu: None. A.Kumar: None. A.C.Alvear: None. Y.Zhang: None. L.Coles: None. N.Evanoff: None. D.R.Dengel: None.

Funding
JDRF
384-P: Inadequate Follow-up and Intervention after Severe Hypoglycemia Treated by Emergency Medical Services (EMS)
Authors: RODE MATTHEW , BOGGUST BRETT , MANGGAARD JENNIFER M. , SWANSON KRISTI , MCCOY ROZALINA G. 
Published: June 2023

Severe hypoglycemia incurs substantial morbidity and distress in patients with diabetes. Prior studies found that clinicians fail to screen for hypoglycemia and deintensify therapy after detected events. Whether patients treated by EMS for hypoglycemia receive follow-up or treatment modification to prevent hypoglycemia recurrence is unknown. We analyzed all 911 calls for hypoglycemia made by adults with diabetes to Mayo Clinic Ambulance Service (serving a large geographic area across Minnesota and Wisconsin) between 1/1/2013-12/31/2019, manually linked to Mayo Clinic electronic health records. Encounters within 7 days of the hypoglycemic event were analyzed for type of encounter, provider, discussion of hypoglycemia, prescription of glucagon, change of diabetes medications, and referral to a diabetes provider. Hypoglycemia was addressed more often with escalating levels of care (Figure). In-patient endocrinologists addressed hypoglycemia most often (96% discussion, 83% med changes), followed by hospitalists (87% discussion, 50% med changes). Primary care providers (74% discussion, 25% med changes) and emergency medicine providers (88% discussion, 14% med changes) addressed hypoglycemia less often. Results did not change when patients had experienced previous ED visits/hospitalization for hypoglycemia. Such therapeutic inertia hinders hypoglycemia prevention.

Disclosure
M.Rode: None. B.Boggust: None. J.M.Manggaard: None. K.Swanson: None. R.G.Mccoy: Consultant; Emmi.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (K23DK114497)
387-P: High Incidences of Level 3 Severe Hypoglycemia Reported by T2DM Secretagogue-Users (iNPHORM, USA)
Authors: RATZKI-LEEWING ALEXANDRIA , BLACK JASON E. , ZOU GUANGYONG , RYAN BRIDGET L. , HARRIS STEWART B. 
Published: June 2023

In the US, &gt;90% of people with T2DM on oral antihyperglycemics use secretagogues. The present analysis is the first to quantify the real-world, US frequency of Level 3 severe hypoglycaemia (SH) in this population. Longitudinal, prospective data were leveraged from the iNPHORM study. Adults (≥18 years old) with secretagogue-treated T2DM (not on insulin) were recruited from a US-wide, probability-based internet panel. Data on participant characteristics and Level 3 SH occurrence were captured across a screener, baseline and 12 monthly follow-ups. Multivariable negative binomial regression with cluster bootstrapping for repeated measures modelled the annualized rate of SH for individuals completing ≥1 follow-up(s). A repeated lasso regression ‘voting’ procedure selected all risk factors. Multiple imputation addressed missingness. Of the 353 respondents (male: 51.1%; age: 54.6 [SD: 13.2] years; diabetes duration: 10 [IQR: 12] years; retention rate: 84.4%), the incidence proportion of SH over follow-up was 21.8 (95% CI: 17.8-26.3)%, and the rate was 3.8 (95% CI: 2.5-5.7) events per person-year. Our final model included age, continuous/flash glucose monitoring use, corticosteroid use, number of healthcare visits, fear of hypoglycemia, number of past-year SH requiring hospital care, retinopathy, and other diabetes complications. The rate of annualized Level 3 SH statistically increased with younger age, more frequent healthcare visits, greater fear of hypoglycemia, higher number of past-year healthcare-related SH, and presence of retinopathy. Our results indicate disturbingly high incidences of Level 3 SH among secretagogue users. Whenever logical and feasible, clinicians should prioritize one of the many other available antihyperglycemics that confer little to no hypoglycemia risk. Else, other hypoglycemia prevention strategies—risk-tailored to this ubiquitous T2DM population—are urgently warranted.

Disclosure
A.Ratzki-leewing: Consultant; Novo Nordisk, Eli Lilly and Company, Research Support; Sanofi. J.E.Black: None. G.Zou: None. B.L.Ryan: None. S.B.Harris: Advisory Panel; Bayer Inc., AstraZeneca, Eli Lilly and Company, Dexcom, Inc., Novo Nordisk A/S, Novo Nordisk Canada Inc., Sanofi, Consultant; Abbott Diabetes, Janssen Pharmaceuticals, Inc., Other Relationship; American Diabetes Association, Research Support; Abvance Therapeutics, Canadian Institutes of Health Research.

Funding
Sanofi Global