bluuebunny/crossref_metadata_2025_split huggingface dataset:
645-P: Experiences of Managing Comorbid Obstructive Sleep Apnea and Type 2 Diabetes among Veterans
Authors: SONG YEONSU , CHOI SARAH E. , PAPAZYAN ANNA , MACEY PAUL M. , ALESSI CATHY , FUNG CONSTANCE H. , MARTIN JENNIFER 
Published: June 2023

Obstructive sleep apnea (OSA) is highly prevalent in patients with type 2 diabetes (T2DM), more so in veterans compared to non-veterans. Positive airway pressure (PAP) is the recommended first-line treatment for OSA. However, adherence to both PAP and to diabetes management regimens can be challenging to older adults. This study describes older veterans’ experiences managing comorbid OSA and T2DM, and the types of support they receive from family and friends.
Methods: We conducted a postal survey of 900 randomly selected veterans (aged ≥50 years with medical diagnoses of OSA and T2DM) from one VA healthcare system. Questions included the Diabetes Patient Behavior Checklist and perceived benefits of and assistance with PAP use. Results: Of the 145 respondents (97% men, 51% White, 21% Black, mean age 72 years), 43% received help for diabetes from family or a friend, including preparing healthy food (91%), providing encouragement for diabetes self-care (89%), and eating at the same time (89%). Almost two thirds of the respondents were current PAP users. Among the respondents, 27% received help using PAP from a household member, including putting on the mask (68%), filling the water reservoir (59%), and cleaning the device (59%). Current PAP users had significantly lower levels of hemoglobin A1c than nonusers (6.7 ± 1.1 vs. 7.3± 1.6 %, respectively, p=0.008). Current PAP users also reported significantly higher perceived benefits of PAP use on improving sleep quality, sleep apnea, diabetes, and general health than nonusers. Married or non-White respondents thought it would be more helpful for a family member or friend to receive education on treatment of both OSA and T2DM.
Conclusion: Future studies should investigate feasible strategies for addressing adherence to PAP use as part of diabetes self-management to improve glycemic control and overall health outcomes among patients with T2DM and comorbid OSA. Family support and social/demographic factors should be considered.

Disclosure
Y.Song: None. S.E.Choi: None. A.Papazyan: None. P.M.Macey: None. C.Alessi: None. C.H.Fung: None. J.Martin: None.

Funding
National Institutes of Health (K23AG055668); University of California, Los Angeles Clinical and Translational Science Institute School of Nursing
687-P: Risk Patterns for Suicide Attempts among People with Diabetes Using Association Rules Mining
Authors: NARINDRARANGKURA PLOYPUN , ALAFAIREET PATRICIA , KHAN UZMA Z. , KIM MIN 
Published: June 2023

Prevalence of suicide attempts among people with diabetes was approximately 10%, higher than the general population (&lt;5%). This is the first study using association rules mining to discover the risk patterns for suicide attempts in people with diabetes using large multi-centered EHR data. We retrieved data on 3,265,041 diabetes patients from 2010-2020, and 0.2% had a record of suicide attempts. Figure 1 shows the visualization of the top ten association rules. The first rule, {benzodiazepines, no. antidepressants ≥2} ≤ {suicide=Yes}, Support=0.19, Confidence=0.87, means “19% of patients had a record of benzodiazepines, the number of antidepressants ≥2 and suicide attempts together.” In addition, “87% of patients with benzodiazepines and the number of antidepressants ≥2 also had a record of suicide attempts.” We found new findings related to suicide attempts in people with diabetes, including the use of benzodiazepines, atypical antipsychotic agents, two and more antidepressants, none or one diabetes medication, and white in the race. Further studies are needed to validate the results and investigate the causality of suicide attempts and diabetes. Our results can be explainable and practically used by providers during outpatient clinic visits.

Figure 1. Visualization of the top ten association rules represented by circles. Darker color denotes higher confidence, and a larger circle means greater support.

Disclosure
P.Narindrarangkura: None. P.Alafaireet: None. U.Z.Khan: None. M.Kim: None.
694-P: Differences in Diabetes-Related Stigma by Demographic Group and Intensity of Diabetes Management
Authors: ZENG ALISON , LIN EMILY , COX EVELYN , XU EMILY , BELL TREVOR , BRISTOW TRACY L. 
Published: June 2023

The social stigma surrounding diabetes refers to the negative attitudes, discrimination, or prejudice someone may face due to their diabetes. For many people with diabetes (PWD), stigma is a major challenge and often results in significant negative consequences, such as poor psychological well-being and worse clinical outcomes. This study aimed to identify groups who may be at greater risk of experiencing stigma. From October-December 2022, 10,338 adults living with diabetes in the United States, Canada, France, Germany, Italy, Netherlands, Sweden, and United Kingdom took an online survey assessing stigma associated with diabetes. Stigma was measured using four items about concealing or difficulty disclosing one's diabetes as well as diabetes-related embarrassment and isolation. These four items were averaged to create a composite variable on degree of stigma experienced (α = 0.87, M = 1.82, SD = 0.89). Subsequent responses were analyzed by various demographic factors and diabetes management strategies using SPSS. Stigma levels differ by intensity of diabetes management; respondents with more demanding diabetes management regimens experience greater levels of stigma. CGM users (p&lt;0.001) and insulin users (p&lt;0.001) experience more stigma than non-users, and PWD taking multiple daily injections experience more stigma than pump users (p=0.027). Stigma also varies across several demographic factors. French respondents report the highest stigma score, while German respondents report the lowest. Further, people with T1D experience more stigma than those with T2D (p&lt;0.001). This research reveals differences in diabetes-related stigma by country and diabetes type and suggests that stigma becomes more prevalent with more intensive diabetes management. Additional research is needed to further explore experiences of stigma and identify methods of support, especially for at-risk groups.

Disclosure
A.Zeng: Employee; dQ&A. E.Lin: Employee; dQ&A. E.Cox: Employee; dQ&A. E.Xu: Employee; dQ&A. T.Bell: Employee; dQ&A. T.L.Bristow: Employee; dQ&A.
72-LB: DD01, a Novel Once-Weekly Dual GLP-1/Glucagon Receptor Agonist, Improves Metabolic Health and Achieves Rapid, Clinically Significant Reductions in Hepatic Steatosis following Only Four Weeks of Treatment and without the Need for Significant Weight Loss in Overweight/Diabetic Subjects with NAFLD
Authors: TO DENNIS , SHIN JAEHEE , KARANTH SUBBU , LIN YEN-HUEI , SOSNOVTSEVA SVETLANA , BELL ADAM C. 
Published: June 2023

DD01 is a dual GLP-1/glucagon receptor agonist acting through two independent pathways to provide rapid resolution of hepatic steatosis, improve glucose control, an reduce body weight in subjects with type 2 diabetes who are obese/overweight and have NAFLD. In a recently completed Phase 1 single and repeat dose safety and pharmacology study, DD01 was well tolerated and improved fasting and fed glucose while providing significant reductions in liver fat as measured by MRI-PDFF. Following only 4 weeks of once-weekly treatment, up to 100% of patients achieved ≥30% reduction in MRI-PDFF. In the high dose group, all subjects achieved at least a 40% reduction in liver fat with a mean reduction of 52% whereas the change from baseline liver fat in the placebo group was only 2.8%. Meaningful and rapid improvements in steatosis were observed at well-tolerated doses that did not cause significant weight loss, thus uncoupling the need for weight loss to precede or coincide with significant improvements in liver health.

Disclosure
D. To: Employee; Neuraly Inc. J. Shin: Employee; D&D Pharmatech. S. Karanth: None. Y. Lin: None. S. Sosnovtseva: None. A. C. Bell: None.
75-LB: CT-388, a Novel Once-Weekly Dual GLP-1 and GIP Receptor Modulator, Is Safe, Well-Tolerated, and Produces More than 8% Weight Loss in Four Weeks in Overweight and Obese Adults
Authors: CHAKRAVARTHY MANU , ARGÜELLES-TELLO FEDERICO A. , SUN ANA LIZA A. , ELLIOTT MICHAEL , ACOSTA LUIS , RANKIN JONATHON E. , HANSEN STIG K. 
Published: June 2023

GLP-1 and GIP can deliver complementary pharmacology when combined. CT-388 is a biased dual GLP-1 and GIP receptor modulator that exhibits no to minimal β-arrestin coupling at either receptor, designed for once-weekly subcutaneous dosing. A Phase 1, randomized, placebo-controlled, double-blind study was conducted where single ascending doses (0.5-7.5 mg) and multiple ascending doses (MAD; doses 5-12 mg via titration in 3 cohorts) for 4 weeks were administered to overweight/obese adults. Primary objective was to investigate safety and tolerability of CT-388. Total of 64 participants (men/women: 28/36; median age/BMI: 34 years/33 kg/m2) received at least 1 dose of CT-388 or placebo. PK profile was investigated over a wide dose range (0.5-12 mg) and supports once-weekly administration. Percent change in body weight from baseline at Day 29 was dose responsive and significantly greater in CT-388 treated participants versus placebo (p &lt;0.0001) across the 3 MAD cohorts with Least Square Mean difference [95% CI] of -4.8% [-6.3, -3.3], -6.4% [-7.8, -5.0], and -8.5% [-10.4, -6.7]. Mean percent decrease from baseline at Day 23 in fasting glucose (↓8-10%), insulin (↓20-26%), HOMA-IR (↓26-33%), AUC0-120min glucose (↓26-28%) and AUC0-120min insulin (↓33-58%) during oGTT were seen in cohorts dosed up to 12 mg CT-388, suggestive of improved insulin sensitivity. Over the 4-week treatment period, CT-388 was generally well tolerated with no treatment-related discontinuations. The most frequent side effects reported were gastrointestinal (decreased appetite, nausea, vomiting, diarrhea), which were mostly mild in severity.
In summary, CT-388 delivers clinically meaningful weight loss and metabolic control with a favorable tolerability profile. These data warrant further clinical evaluation of CT-388, possibly with minimal to no titration, for the treatment of obesity, T2DM, and other weight-related comorbidities.

Disclosure
M. Chakravarthy: Employee; Carmot Therapeutics, Inc. F. A. Argüelles-Tello: Research Support; Carmot Therapeutics, Inc. A. A. Sun: None. M. Elliott: Employee; Carmot Therapeutics, Inc. L. Acosta: None. J. E. Rankin: None. S. K. Hansen: Board Member; Carmot Therapeutics, Inc.
753-P: Tirzepatide Improves HRQoL Compared with Insulin Lispro in Poorly Controlled Basal Insulin–Treated Adults with Long-Standing T2D (SURPASS-6)
Authors: BOYE KRISTINA , SAPIN HELENE , LING POON JIAT , FERNANDEZ LANDO LAURA , HUH RUTH , WANG MIANBO , PATEL HIREN 
Published: June 2023

Tirzepatide, a first-in-class GIP/GLP-1 receptor agonist, resulted in significant improvements in HbA1c and body weight compared to insulin lispro (iLispro) at 52 weeks in the SURPASS-6 study. We compared the HRQoL of participants with T2D treated with tirzepatide (all doses pooled) versus iLispro, both added to basal insulin, in SURPASS-6.
Adults with T2D and inadequate glycemic control were randomized (1:1:1:3) to tirzepatide 5, 10, or 15 mg QW, or iLispro TID, as add-on to optimized insulin glargine, with or without metformin, for 52 weeks in this open-label, multicenter, Phase 3b study. HRQoL was measured at baseline and endpoint (Week 52) using the SF-36v2 acute form comprised of 8 domains and 2 component summary scores.
Overall, 1428 participants with mean baseline age 59 y, T2D duration 14 y, HbA1c 8.8% and BMI 33.1 kg/m2 were randomized. At endpoint, tirzepatide-treated participants had statistically significantly improved scores across all SF-36v2 domains and component summaries compared to iLispro-treated participants, with the largest differences observed in the General health (LS mean [SE] change 3.0 [0.31] vs. -0.1 [0.32]) and Vitality (1.5 [0.31] vs. -1.1 [0.32]) domains (Table).
Tirzepatide treatment resulted in greater improvements across multiple domains of HRQoL than iLispro in adults with long standing T2D already treated with basal insulin.

Disclosure
K.Boye: Employee; Eli Lilly and Company. H.Sapin: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. J.Poon: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. L.Fernandez lando: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. R.Huh: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. M.Wang: None. H.Patel: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company.

Funding
Eli Lilly and Company
754-P: A First-in-Human Single Ascending Dose Study of GSBR-1290, a Novel Small Molecule GLP-1 Receptor Agonist, in Healthy Volunteers
Authors: COLL BLAI , ZHANG JINQIANG J. , JACOBER SCOTT J. , ARGENT CHRISTOPHER , IBARRA LANI , SNYDER MARGO , BACH MARK A. 
Published: June 2023

Introduction: Type 2 Diabetes Mellitus (T2DM) and obesity incidences are rising globally. The risk:benefit ratio of peptide GLP-1 receptor agonists (RAs) has been established; however, new therapeutic options are still needed. We report the results of a single ascending dose (SAD) study with GSBR-1290, a highly potent, orally bioavailable, fully biased small molecule GLP-1 RA.
Methods: The study enrolled 48 healthy volunteers in 6 Cohorts, randomized 3:1 to receive GSBR-1290 (1, 10, 15, 30, 60, and 90 mg) or placebo, under fasting conditions. The safety, tolerability, and pharmacokinetics (PK) of a single dose of GSBR-1290 were investigated. The food effect on PK was also assessed in the 15 mg cohort.
Results: Participants were well-balanced across the treatment groups: female (60%), white (66%), mean age (SD) 30 (8) years, and BMI (SD) 24.5 (3.0). All randomized subjects completed the study and there were no deaths or serious adverse events. Treatment-emergent adverse events (TEAEs) were reported for 32/36 participants (89%) following fasted administration of GSBR-1290 and for 7/12 participants (58%) following administration of placebo. The majority (94%) were mild or moderate in severity. As expected, the most common TEAEs were gastrointestinal-related and included nausea, vomiting, decreased appetite and diarrhea, consistent with other drugs in this class. No clinically significant changes in laboratory safety parameters were reported. PK (Cmax and AUC) of GSBR-1290 increased with dose, and a high fat meal was associated with a 20% decrease in the geometric mean AUC and a 36% decrease in Cmax.
Conclusion: GSBR-1290 is a promising orally available GLP-1 RA and was well-tolerated in this SAD study in healthy volunteers. These data support further clinical development in a multiple ascending dose study in individuals with T2DM and obesity.

Disclosure
B.Coll: Employee; Amgen Inc., ShouTi Pharma Inc. J.J.Zhang: Employee; Structure Therapeutics Inc. S.J.Jacober: Consultant; Structure Therapeutics, Inc., Adocia, Employee; Sanofi-Aventis U.S., Applied Therapeutics Inc., Other Relationship; Eli Lilly and Company. C.Argent: None. L.Ibarra: Employee; Structure Therapeutics. M.Snyder: None. M.A.Bach: Employee; Structure Therapeutics, Stock/Shareholder; Johnson & Johnson.

Funding
Structure Therapeutics Inc.
77-OR: Targeting JunB Induces a Shift from Low- to High-Thermogenic Adipocytes and Ameliorates Diet-Induced Insulin Resistance
Authors: ZHANG XING , WANG CHUNQING , LIU MEILIAN 
Published: June 2023

The coexistence of brown adipocytes with low and high thermogenic activity is a fundamental feature of brown adipose tissue (BAT) heterogeneity and plasticity. However, the mechanisms that govern thermogenic adipocyte heterogeneity and its significance in obesity and metabolic disease remain poorly understood. In the current study, we identified a population of JunB-enriched adipocytes (JunB+ adipocytes) within the brown fat depot that exhibits lower thermogenic capacity and fewer and smaller lipid droplets compared to high-thermogenic adipocytes. This population of JunB+ adipocytes exhibited marked expansion during obesity, in part through induction of pro-inflammatory cytokines TNFα and IL-6. Depletion of JunB in adipocytes or UCP1+ adipocytes increased the fraction of adipocytes exhibiting high mitochondrial content and thermogenic capacity, leading to enhanced basal and cold-induced energy expenditure and protection against diet-induced obesity and insulin resistance. Mechanistically, JunB directly binds to the promoter of estrogen-related receptor α (Errα), a downstream effector of PGC1α, and suppresses its transcriptional function. JunB antagonizes the stimulatory effects of PGC1α-ERRα on mitochondrial biogenesis and high-thermogenic adipocyte development. Taken together, our studies uncover a novel mechanism involving JunB that shapes thermogenic adipocyte heterogeneity and serves a critical role in maintaining systemic metabolic health.

Disclosure
X.Zhang: None. C.Wang: None. M.Liu: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (DK110439); American Heart Association (20POST35120020)
777-P: Early Weight Loss and Late Metabolic Outcomes in Tirzepatide-Treated Participants with Type 2 Diabetes
Authors: LINGVAY ILDIKO , GIORGINO FRANCESCO , VAN GAAL LUC , LIU MINZHI , RODRÍGUEZ ÁNGEL , TORCELLO-GOMEZ AMELIA , KILJANSKI JACEK I. 
Published: June 2023

Tirzepatide (TZP), a novel, once-weekly GIP/GLP-1 receptor agonist, significantly improved glycemic control with robust weight loss vs comparators in the SURPASS 1-5 trials. The aim of this analysis was to assess whether the magnitude of early weight loss with TZP (&lt;5% or ≥5% at Week 8) would be associated with different clinical response in terms of HbA1c and weight at Week 40/42 across the SURPASS 1-5 trials.
These phase 3 trials included participants with type 2 diabetes receiving TZP as monotherapy or add-on to background antihyperglycemic medications. This post-hoc analysis used pooled data from all TZP arms (5, 10, and 15 mg) across trials.
Participants achieving ≥5% early weight loss at Week 8 had lower HbA1c and weight at baseline, and experienced greater reductions in HbA1c and weight at Week 40/42 vs those achieving &lt;5% early weight loss (Table). Among participants achieving ≥5% early weight loss, greater proportions met HbA1c &lt;7% and ≤6.5%, ≥10% weight loss, and the composite endpoint of HbA1c &lt;7% and ≥10% weight loss.
Early weight loss with TZP predicts greater reductions of HbA1c and weight at Week 40/42. However, even the one third of participants achieving &lt;5% weight loss early in the course of therapy are likely to meet the ADA/EASD dual treatment goals of HbA1c &lt;7% and ≥10% weight loss.

Disclosure
I.Lingvay: Advisory Panel; Novo Nordisk A/S, Lilly Diabetes, Boehringer-Ingelheim, Sanofi, Consultant; Carmot Therapeutics, Inc., Merck Sharp & Dohme Corp., Janssen Scientific Affairs, LLC, Pfizer Inc., Intercept, Intarcia, Valeritas, TargetRWE, Shionogi, Zealand Pharma, Structure, Bayer, Research Support; Novo Nordisk A/S, Boehringer-Ingelheim. F.Giorgino: Advisory Panel; Boehringer-Ingelheim, Amarin Corporation, Medtronic, Roche Diabetes Care, Sanofi, Bayer Inc., Novo Nordisk, Consultant; Novo Nordisk, Lilly, Research Support; Lilly, Roche Diabetes Care, AlfaSigma, Speaker's Bureau; Abbott, Boehringer-Ingelheim, Lilly, Sanofi, Medscape. L.Van gaal: Advisory Panel; Merck Sharp & Dohme Corp., Speaker's Bureau; Boehringer Ingelheim Pharma GmbH&Co.KG, Eli Lilly and Company, Novo Nordisk. M.Liu: Consultant; Eli Lilly and Company. Á.Rodríguez: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. A.Torcello-gomez: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. J.I.Kiljanski: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company.

Funding
Eli Lilly and Company
810-P: Do People Living with T1D Use the Dosing Flexibility of Degludec and Does This Depend on Patient Characteristics?
Authors: WINHOFER YVONNE , KAAS ANNE , KNUDSEN NIKOLINE N. , MARTINY JOHANNES H.J. , MATHIEU CHANTAL 
Published: June 2023

Flexibility in insulin degludec injection timing of 8-40 hrs between doses allows people with diabetes to adapt their treatment around daily life. This real-world multinational study explored flexible dosing (≥6hr difference in time of day [clock-time] between consecutive doses) in terms of prevalence and associated characteristics in 1136 people with T1D (mean [SD] age 31.3 [17.7] years, 54% male, median observation period 124 days [IQR 41, 234]) who were administering insulin degludec with smart pens. Of these participants, 14.4% regularly flexed dosing time (≥1 time every month). The probability of having ≥1 flexible dose in a given 2-week period was shown by a generalized linear mixed model (log link) with participant ID as a random effect and individual characteristics as fixed effects. Estimated LS-mean probability of ≥1 flexible dose in a given 2-week period was 25.0% (95% CI: 21.5%, 28.9%), with higher probability for young adults (aged 18-25), those who usually inject 9am-6pm, and those with a higher (&gt;30 U/day) basal dose (all p&lt;0.01). Probability decreased with time from smart pen initiation (p&lt;0.01). In the subgroup of 455 adults with CGM data, flexibility in dosing time did not affect glycemic control. Overall, a group of people with T1D used the degludec dosing flexibility; these were most often young adults aged 18-25, those injecting 9am-6pm, and those requiring higher degludec doses.

Disclosure
Y.Winhofer: Speaker's Bureau; Abbott Diabetes, Amgen Inc., Boehringer-Ingelheim, Eli Lilly and Company, Novartis, Novo Nordisk, Medtronic, Sanofi-Aventis Deutschland GmbH, Daiichi Sankyo. A.Kaas: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. N.N.Knudsen: Employee; Novo Nordisk. J.H.J.Martiny: Employee; Novo Nordisk. C.Mathieu: Advisory Panel; Novo Nordisk A/S, Boehringer Ingelheim Inc., Eli Lilly and Company, Medtronic, Vertex Pharmaceuticals Incorporated, Roche Diabetes Care, Imcyse, Speaker's Bureau; Novo Nordisk A/S, AstraZeneca, Boehringer Ingelheim Inc., Eli Lilly and Company, Medtronic, Vertex Pharmaceuticals Incorporated.

Funding
Novo Nordisk A/S