bluuebunny/crossref_metadata_2025 huggingface dataset:
695-P: The Moderating Role of Worry on the Relationship between Diabetes Knowledge and Self-Management Activities
Authors: CLAYTON COLTER K. , LUFF BRENNA G. , POLK JAMES D. , LEE AARON A.
Published: June 2024

Introduction & Objective: Diabetes knowledge is a predictor of diabetes self-management and worry as a component of anxiety is underexplored. Our objective was to examine the moderating role of worry on the relationships of objective and perceived diabetes knowledge with diabetes self-management.

Methods: Adults with type 2 diabetes were recruited from a web-based panel. We cross-sectionally examined worry (Penn State Worry Questionnaire-3) as a moderator of the relationships of objective knowledge (Diabetes Knowledge Test-2) and perceived knowledge (Perceived Diabetes Knowledge Scale) with self-management activities (diet, exercise, glucose monitoring, foot care; Summary of Diabetes Self-Care Activities). Separate regression models examined the multiplicative interaction of worry with objective and perceived knowledge on self-management activities controlling for education, diabetes duration, and prior diabetes education.

Results: In our sample (N = 321; Mage = 64.4; 51.7% female; 85.7% White), worry moderated the association between perceived knowledge and diet (B = 0.07, 95% CI = .01, .13) such that greater perceived knowledge was more strongly associated with greater diet adherence among adults with high levels of worry. Worry moderated the association of objective knowledge and exercise (B = -0.04, 95% CI = -0.07, -0.01) such that greater objective knowledge was more strongly associated with lower exercise adherence at high levels of worry. Worry moderated the association of objective knowledge and foot care (B = -0.04, 95% CI = -0.06, -0.01) such that greater objective knowledge was more strongly associated with lower feet checking adherence at high levels of worry.

Conclusion: Results suggest that worry may play an important role in the relationship of diabetes knowledge to self-management activities. Findings may inform development and evaluation of interventions that promote diabetes knowledge and self-management by considering the role of worry.

Disclosure

C.K. Clayton: None. B.G. Luff: None. J.D. Polk: None. A.A. Lee: None.
7-OR: Causal Associations between Glyoxalase 1 Expression and Kidney Disease in Type 1 Diabetes
Authors: ADESHARA KRISHNA , DAHLSTROM EMMA H. , LEHTO MARKKU , GROOP PER-HENRIK , SANDHOLM NIINA , BEHALF OF THE FINN DIANE STUDY GROUP ON
Published: June 2024

Introduction & Objective: Glyoxalase 1 (GLO1) is a crucial enzyme detoxifying methylglyoxal, linked to diabetes and kidney disease. This study aims to unravel link between GLO1 expression and diabetic kidney disease (DKD) in type 1 diabetes using Mendelian randomization (MR).

Methods: The potential causality between GLO1 and DKD was analyzed by two-sample MR. As instrumental variables (IV) we selected cis-expression quantitative trait loci (eQTL) independently associated with GLO1 expression (r2<0.01) in blood, kidney, and other tissues from publicly available datasets (blood: eQTLGen, kidney tissue: Human Kidney eQTL atlas, other tissues: GTEx v8). Serum protein expression data were retrieved from genome-wide association study (GWAS) Catalogue (Study accession: GCST90090884). DKD outcome data were retrieved from JDRF-DNCRI GWAS on DKD, including 19406 individuals with type 1 diabetes, with spectrum of ten DKD definitions based on albuminuria and kidney function.

Results: MR suggested that higher GLO1 mRNA expression (eQTL threshold p<5.0x10-8) in skin (OR 0.86, [95%CI 0.77 - 0.97], p=0.01, three SNPs) and salivary gland (OR 0.83, [95%CI 0.72 - 0.97], p=0.02, one SNP) were associated with lower risk of chronic kidney disease (CKD). Interestingly, higher GLO1 protein expression (pQTL threshold p<0.05) in blood was associated with CKD (OR 1.43, [95%CI 1.11 - 1.84], p=0.005, 12 SNPs) and two other similar CKD/DKD definitions. No causal associations were observed in kidney-specific tissues or whole blood.

Conclusion: This study supports causality between GLO1 expression and DKD particularly in skin and salivary glands. On contrary, higher GLO1 protein expression was associated with CKD. These data suggest that altered GLO1 expression is involved in altered DKD susceptibility in type 1 diabetes.

Disclosure

K. Adeshara: None. E.H. Dahlstrom: None. M. Lehto: None. P. Groop: Advisory Panel; Bayer Inc. Speaker's Bureau; Bayer Inc. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Boehringer-Ingelheim. N. Sandholm: None.
70-PUB: Effect of H2O2-Induced Oxidative Stress on Volatile Organic Compounds in Differentiated 3T3-L1 Cells
Authors: OYERINDE ADEBOWALE S. , BOERSMA MELISSA D. , JEGANATHAN RAMESH B. , THANGIAH GEETHA
Published: June 2024

Introduction & Objective: In recent times, emerging diagnostic tools known as volatile organic compounds (VOCs) have shown promise as potential biomarkers for obesity and its related diseases. Accumulation of free radical damage over time can emerge as a significant contributor to various human diseases associated with oxidative stress. We hypothesize that in a pathological condition such as obesity, it has the potential to generate new VOCs or alter the ratio of normally produced VOCs due to an increase in oxidative stress (OS). This may provide valuable insights into the metabolic condition of an obese individual.

Methods: An oxidative stress induced obese model of differentiated 3T3-L1 cell lines was constructed using hydrogen peroxide treatment. The effect of OS on cell metabolism was in-depth studied by analyzing VOCs in the headspace of the cells using solid-phase microextraction (SPME) and analyzed by gas chromatography-mass spectrometry (GC-MS).

Results: Twenty VOCs were identified in samples used for this experiment. Eight VOCs showed an elevated trend, while four VOC peaks showed a significant increase (p < 0.05) with an increase in oxidative stress compared to the control adipocytes.

Conclusion: The VOC biomarkers identified predominantly included linear chain alkanes, branched-chain alkanes, straight chains, and aromatic alcohols, probably derived from lipid peroxidation and amino acid metabolism when OS is induced in differentiated adipocytes. This study revealed that VOCs are influenced by elevated OS in differentiated 3T3-L1 cells and offered insights into exploring the mechanism of exhaled biomarkers, thereby promoting the non-invasive prediction of obesity.

Disclosure

A.S. Oyerinde: None. M.D. Boersma: None. R.B. Jeganathan: None. G. Thangiah: None.

Funding

National Institutes of Health (R15HL168608)
700-P: Recent and Lifetime Experiences with Diabetes Distress in Adults with Type 1 Diabetes
Authors: CHAPMAN KATHERINE S.M. , CORNELIUS EMILEE M. , WOLF WENDY , PETER MEGAN , KELLY CAITLIN S.
Published: June 2024

Introduction & Objective: Measures of diabetes distress (DD) identify when individuals with T1D are struggling but are often limited to experiences within the past month. Lived experiences of DD may be more variable, as T1D is a lifetime illness. Thus, we examined qualitative experiences with recent versus lifetime DD, then compared two groups (with/without recent DD) on established measures of DD.

Methods: Adults from the T1D Exchange Registry (N = 272) completed an online survey and were asked (yes/no) if they had experienced recent DD (i.e., in the past 12 months). Then, participants described their DD experiences (‘yes’ = past 12 months experiences; ‘no’ = lifetime experiences). Thematic analysis was used to categorize responses. Participants also completed the DDS-2, and two T1DDS subscales: Powerlessness and Physician Distress. Welch's t-tests compared means between groups (DDyes vs. DDno).

Results: Most participants reported DD in the past 12 months (n DDyes = 241 vs. n DDno = 31). Both DDyes (32.0%) and DDno (34.4%) groups described DD around T1D management. The DDyes group described challenges in daily life with T1D (11.7%) and financial burden (11.3%). The DDno group described distress in adolescence (18.8%) and no experiences with DD (25.8%). Compared to the DDno group, the DDyes group was younger (t(37.7) = -2.9, p < 0.01), had T1D for fewer years (t(39.2)= -2.9, p < 0.01), and higher scores on all measures of DD: DDS-2 (t(58.3)= 10.1, p < 0.01), Powerlessness (t(52.2)= 9.3, p < 0.01), and Physician Distress (t(65.3)= 4.9, p<0.01). Yet, depending on measure, not all participants in the DDyes group met cutoff scores for ‘moderate-to-high’ DD: Physician Distress = 35.3%, DDS-2 = 49.8%, Powerlessness = 81.3%.

Conclusion: Most participants reported DD experiences within the past year. However, validated measures did not always classify those who reported recent experiences with higher DD. Thus, providers should consider using DD measures in conjunction with discussions of lived experiences in adults with T1D.

Disclosure

K.S.M. Chapman: None. E.M. Cornelius: None. W. Wolf: None. M. Peter: None. C.S. Kelly: None.

Funding

This research was supported in part by The Leona M. and Harry B. Helmsley Charitable Trust.
711-P: A Qualitative Exploration of Beliefs and Attitudes about Food Choices for Diabetes Self-Management among Adults with Type 1 Diabetes
Authors: LUCIEN JUNIAR , AGNI ANNIKA , AMJAD FOUZAAN A. , CHUISANO SAM , KUEI LIN YU , DEJONCKHEERE MELISSA
Published: June 2024

Introduction & Objective: More than 1.7 million adults in the U.S. live with type 1 diabetes (T1D), which requires daily management to maintain optimal glycemic levels and prevent serious complications. Daily self-management may lead to obsessionality over food choices and therefore affect self-management behaviors. For example, some adults with T1D may delay hypoglycemia treatment due to beliefs about fast-acting carbohydrates, while others may restrict particular foods or food groups to achieve glycemic control. This qualitative study explored the tension between food choices and beliefs about healthy living among adults with T1D.

Methods: As part of a larger study on experiences of hypoglycemia self-management, participants using continuous glucose monitors (CGMs) ≥70% of the time for more than six months were recruited from a Midwest academic medical center. Maximum variation sampling included adults with T1D across different percentages of time spent in level 2 hypoglycemia (glucose level <54 mg/dL). Diabetes history and sociodemographic data were collected. A semi-structured interview explored the thoughts and behaviors of participants using CGMs. Inductive thematic analysis was conducted focusing on relationships with food during self-management.

Results: Preliminary findings include the impact of food characterization (e.g., “healthy” or “unhealthy”) in hypoglycemia treatment, the influence of family/friends on treatment food choices, and ways adults with T1D reconcile their diabetes needs and personal lifestyle goals.

Conclusions: These findings will add to the few studies on the specific responses to dietary intake of adults with T1D, particularly related to self-management. The results suggest the need for more mixed-methods research to understand the role of food beliefs in daily and long-term T1D self-management to inform better diabetes education and interventions.

Disclosure

J. Lucien: None. A. Agni: None. F.A. Amjad: None. S. Chuisano: None. Y. Lin: None. M. DeJonckheere: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (K23DK129724); Michigan Diabetes Research Center Diabetes Interdisciplinary Study Program Award (P30DK020572)
713-P: Gestational Diabetes Mellitus Induces Neurodevelopmental Defects and Exacerbates ASD-Like Phenotype in Male Offspring by Downregulating Ahi1/B9D1/Shh Axis
Authors: XIAO XIAOQIU , QIN GUANGCHENG
Published: June 2024

Epidemiological data showed a positive correlation between GDM and the risk of autism spectrum disorder (ASD) in offspring, but specific mechanisms remain unclear. C57BL/6 female mice were fed with 60% HFD for 4 weeks, and then bred with healthy male mice. On gestational days 0.5 and 7.5, pregnant mice were injected with streptozocin (STZ, 110mg/kg, ip) to establish GDM model. Male offspring were selected for ASD related behavior at P42-P60. LC/MC was used to detect 5-hydroxytryptamine (5-HT) levels, while Western blot and immunofluorescence (IF) were used to detect functional indicators related to the dorsal raphe nucleus (DRN)5-HT system. Male GDM offspring showed impaired social function as evidenced by poor performance in three box test, and repetitive stereotypical behavior. LC/MS detection revealed a significant decrease in 5-HT levels in brain tissue and a significant increase in GDM offspring plasma. WB and IF showed that the abnormal differentiation of neural stem cells in DRN region in GDM offspring, with a significant decrease in the number of 5-HT positive neurons and 5-HT nerve fibers, and a significant downregulation of SYP and PSD95 protein levels. Ahi1, a highly susceptible gene to schizophrenia and ASD, as well as two key related proteins, B9D1 and Shh, were significantly downregulated. Treatment of meptazinol in GDM offspring increased Ahi1 mRNA and protein levels and effectively reversed the loss of 5-HT neurons in DRN and improved ASD-like behavioral signs. Notably, injection of AAV B9D1 shRNA into DRN, while decreasing B9D1 protein levels, attenuated the improvement of meptazinol on ASD-like behavioral changes in GDM offspring. Taken together, our studies suggested that GDM male offspring are susceptible to ASD, which may be related to the abnormal neural stem cells differentiation and maturation due to the impairment of Ahi1/ B9D1/Shh axis, resulting in the loss of 5-HT neurons in the DRN region.

Disclosure

X. Xiao: None. G. Qin: None.

Funding

The National Natural Science Foundation of China (82071734)
718-P: A High FODMAP Diet Reduces Glycemic Excursion without Increasing Gastrointestinal Symptoms in Individuals with Prediabetes Treated with Metformin—A Randomized Crossover Controlled-Feeding Trial
Authors: CHU NATURAL , POON EMILY W.M. , CHAN JULIANA C. , CHOW ELAINE
Published: June 2024

Introduction: Diet and gut microbiota interactions may influence efficacy and tolerability of metformin. Pre-treatment with a diet rich in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) may improve postprandial plasma glucose (PG) responses in individuals with prediabetes receiving metformin.

Methods: 26 individuals with impaired glucose tolerance (IGT) [age median(IQR) 58(48-60) years, 46% men, and 2-hour plasma glucose (2hPG) mean±SD 9.2±1.0 mmol/L] participated in a double-blinded, randomized, cross-over controlled-feeding trial. All participants received equicaloric, high or low FODMAP diets for 10 days in combination with 5 days of metformin XR 1000mg daily, separated by at least 2 weeks washout. Continuous glucose monitoring (CGM), oral glucose tolerance tests (OGTT) with insulin and glucagon-like peptide 1 (GLP-1), microbiota profiles and gastrointestinal symptoms were assessed at baseline and each study period.

Results: Both interventions with metformin reduced blood glucose and body weight compared with baseline. High FODMAPs, as compared with low FODMAPs with metformin, led to lower total postprandial CGM glucose incremental area-under-the-curve (ppiAUC0-3h) (891±269 vs 997±307 mmol/L.min-1, p=0.021) and 2h-PG (7.1±1.7 vs. 8.1±1.9 mmol/L, p=0.017). We observed higher 2-hour total GLP-1, lower high-sensitivity C-reactive protein and a higher relative abundance of Bifidobacterium longum after high-FODMAPs with metformin. There were no differences in gastrointestinal symptoms between interventions.

Conclusion: High FODMAPs with metformin improved postprandial PG without increasing gastrointestinal symptoms in people with IGT. Fermentable carbohydrates promote specific short-chain fatty acids-producing bacteria, which may improve glycemic regulation via gut hormones and anti-inflammation.

Disclosure

N. Chu: None. E.W.M. Poon: None. J.C. Chan: Research Support; AstraZeneca, Hua Medicine. Consultant; Sanofi. Research Support; Servier Laboratories. Consultant; Viatris Inc. Research Support; Merck & Co., Inc. Stock/Shareholder; GemVCare Ltd. Board Member; Asia Diabetes Foundation. Speaker's Bureau; Zuellig Pharma Holdings Pte. Ltd. Advisory Panel; Bayer Inc. Speaker's Bureau; Boehringer-Ingelheim. E. Chow: Research Support; Merck KGaA. Speaker's Bureau; AstraZeneca. Advisory Panel; Boehringer-Ingelheim. Research Support; Medtronic. Speaker's Bureau; Zuellig Pharma Holdings Pte. Ltd., Abbott.

Funding

Merck Investigator-sponsored study (MS200084_0060)
720-P: Cardiometabolic Markers Improve with Modest Weight Loss in Prediabetes Population after 12 Months in a Carbohydrate-Restricted Nutrition Therapy Program
Authors: ZOLLER ALISON R. , ADAMS REBECCA N. , ATHINARAYANAN SHAMINIE J. , ROBERTS CAROLINE G.P. , VOLK BRITTANIE M. , MCKENZIE AMY L.
Published: June 2024

Obesity increases the risk of metabolic conditions such as diabetes and heart disease. While losing weight improves metabolic health, the question remains if there is a minimum weight loss (WL) associated with clinically meaningful improvements in cardiometabolic health markers. Virta Health is a telemedicine clinic offering carbohydrate-restricted nutrition therapy (CRNT) via continuous remote care for patients including those with prediabetes (preD). This retrospective analysis examined the cardiometabolic outcomes of preD patients in five WL categories after 1 year on CRNT using eight linear mixed effect models. A random sample of 250 individuals was used to compare each WL cohort (<5%, 5-9%, 10-14%, 15-19%, ≥20%). Metabolic markers assessed were HbA1c, total cholesterol (TC), LDL-C, HDL-C, TG, ALT, AST, and ALP. Characteristics of WL cohorts combined were 51.7 ± 9.4 years, BMI 37 ± 7.4 kg/m2, 234.9 ± 54.7 lbs, HbA1c 5.8 ± 0.3%, and 65% female. Overall, all cardiometabolic markers improved over time. All markers except TC and LDL-C improved more with greater WL. LDL-C increased (but was still within normal range) with more WL and TC did not differ by WL group. Although greater WL was associated with greater improvements in metabolic health markers, 5% WL produced clinically meaningful improvements in TG and HDL-C in the preD population on CRNT.

Disclosure

A.R. Zoller: Employee; Virta Health Corp. Stock/Shareholder; Virta Health Corp. R.N. Adams: Employee; Virta Health Corp. Stock/Shareholder; Virta Health Corp. S.J. Athinarayanan: Employee; Virta Health Corp. C.G.P. Roberts: Other Relationship; Virta Health Corp. B.M. Volk: Employee; Virta Health Corp. Stock/Shareholder; Virta Health Corp. A.L. McKenzie: Employee; Virta Health Corp. Stock/Shareholder; Virta Health Corp. Employee; Abbott.
726-P: Preventing Glycolysis with the VACUETTE FC Mix Tube—An Accurate Diagnosis of Diabetes
Authors: GRIEBENOW SIRID , DE KOZLOWSKI SANDRA
Published: June 2024

Background: Diabetes continues to be one of the most prevalent diseases worldwide. According to the IDF (International Diabetes Federation), 537 million people were diagnosed with diabetes in 2021. This number is estimated to reach 643 million by 2030. Gestational Diabetes, which affects vulnerable populations, increased by 13% from 2019-20. Currently, the process for blood collection and analysis of glucose can require a transport time of up to 48 hours to the laboratory. The current practices used to stabilize glucose are to either place the sample in a centrifuge immediately or in an ice slurry and subsequently spin within 15-30 minutes. These practices are not consistently done across laboratories as it is not always practical. The impact of different storage conditions on glucose stability in the FC Mix tube was studied.

Method: The study took place at a laboratory in Austria. A European ethics committee approved the study. Apparently healthy subjects (n=20) were recruited and consented. Subjects were advised to fast prior to blood collection. Venous blood was drawn from each subject into four tubes. Tubes were inverted 10 times prior to centrifugation (1800 g for 10 minutes). Samples were spun and analyzed at different timepoints (0h, 7h, 24h, and 48h) to assess the stability of glucose. A portion of the samples remained in the original tube and a portion was aliquoted following spinning. The platform used was the Beckman Coulter AU680. Statistical evaluation was done using GLIMS.

Results: The evaluation of all results was based on a Total Change Limit of 3.55% for Glucose. Performance testing revealed no clinically significant differences between timepoints. Storage of whole blood specimens for 48h at RT led to a deviation of 3.34% and in a refrigerator for 48h led to a deviation of 2.36%. The measurement of plasma aliquots after 48h revealed a deviation of 1.45% compared to the plasma at 0h.

Conclusion: The FC Mix tube is suitable for stabilizing blood glucose under a variety of storage conditions up to 48h.

Disclosure

S. Griebenow: Other Relationship; Greiner Bio One GmbH. S. de Kozlowski: None.
728-P: Experience with Teplizumab in the PROTECT Type 1 Diabetes (T1D) Study during the COVID-19 Pandemic
Authors: GITELMAN STEPHEN E. , HEROLD KEVAN C. , SIMMONS KIMBER M. , SUMNIK ZDENEK , KNECHT LAURA , NIEMOELLER ELISABETH , TIAN WEI , COMER GAIL M. , MILLER DIANA E. , RAMOS ELEANOR L.
Published: June 2024

Background & aims: Teplizumab is a humanized anti-CD3 monoclonal antibody approved to delay Stage 3 T1D onset in individuals ≥8 years with Stage 2 T1D. The Phase 3 PROTECT study (NCT03875729) was conducted during the COVID-19 pandemic. COVID 19 incidence was similar between the teplizumab (22.6%) and placebo (PBO; 23.4%) groups. No participants with an AE of COVID-19 were hospitalized or received antiviral treatment. Here we report our experience of an immunomodulatory therapy during a pandemic.

Methods: Participants aged 8-17 years, diagnosed ≤6 weeks with Stage 3 T1D, were randomized 2:1 to two 12-day courses of teplizumab or PBO, administered 6 months apart. Due to the COVID-19 pandemic, modified dosing was permitted, allowing for the 2nd course to be given at 12 months, instead of 6 months. COVID-19 testing was required before each course.

Results: Rates of overall infections were similar (65.9% vs 63.1%) in the teplizumab and PBO groups, respectively. The rate of Grade ≥3 infections was similar between treatment groups; 1 (0.5%) participant had a Grade ≥3 infection in the teplizumab group (cellulitis), compared with 2 (1.8%) participants in the PBO group (cellulitis and gastroenteritis; n=1 each). No serious AEs of infection were reported for participants in the teplizumab group. Few participants experienced AEs of infection that led to study drug discontinuation: 1 (0.5%) participant in the teplizumab (COVID-19) and 2 (1.8%) participants experienced 3 AEs in the PBO group (COVID-19, cellulitis, and device-related bacteremia). COVID-19-related protocol deviations were comparable in both groups and were mainly related to study visit or laboratory testing.

Conclusions: Incidence of infections, and rates of study drug discontinuation related to AEs of infection, were similar for teplizumab and PBO. Notably, COVID-19-related AEs were not increased by teplizumab treatment, supporting the concept that teplizumab is immunomodulatory, rather than immunosuppressive, therapy.

Disclosure

S.E. Gitelman: Advisory Panel; Abata Therapeutics, Avotres Inc., Genentech, Inc., GentiBio, SAB Biotherapeutics, Inc., Sanofi. K.C. Herold: Consultant; Sanofi. K.M. Simmons: Advisory Panel; Provention Bio, Inc. Consultant; Provention Bio, Inc. Research Support; Provention Bio, Inc., Novartis AG. Consultant; Medtronic. Z. Sumnik: None. L. Knecht: Employee; Sanofi, Provention Bio, Inc. E. Niemoeller: Employee; Sanofi-Aventis Deutschland GmbH. Stock/Shareholder; Sanofi. W. Tian: Employee; Sanofi. G.M. Comer: Consultant; Provention Bio, Inc., Sanofi. D.E. Miller: Employee; Provention Bio, Inc., Sanofi. E.L. Ramos: None.

Funding

Provention Bio, a Sanofi company
731-P: Retrospective Observational Study on the Impact of Digital Therapy on Glycemic Control in Indian Type 2 Diabetes Patients
Authors: GUHA SHAIBAL , KUMAR SUBHASH , SINHA AJAY K. , SHANKAR ANAND , DAS AMIT K.
Published: June 2024

Introduction: Amidst increasing Type 2 Diabetes in India, novel diabetes management methods are essential. This study evaluates the real-world effects of a digital therapeutic on glycemic control in Indian T2DM patients, reflecting the potential of technology-based interventions.

Methods: A retrospective observational study involved 250 Indian T2DM patients using a digital therapeutic for at least six months. The platform provided personalized dietary, exercise guidance, medication reminders, and educational content. Primary outcomes measured were changes in Hemoglobin A1c (HbA1c) levels from baseline to six months. Secondary outcomes included fasting blood glucose changes and patient adherence. Data were analyzed using paired t-tests and regression models to adjust for confounders.

Results: After six months of using the digital therapeutic, patients showed a significant reduction in HbA1c levels (mean decrease of 0.9%, p<0.001). Fasting blood glucose also significantly decreased (average reduction of 20 mg/dL, p<0.01). High adherence to the application was associated with greater improvements in glycemic control. Subgroup analyses indicated more pronounced benefits in patients with higher baseline HbA1c levels.

Conclusion: The digital therapeutic significantly improved glycemic control in Indian T2DM patients, especially those with initially poor control. This indicates digital interventions as effective supplements to conventional diabetes management in India. More extensive, long-term studies are needed to validate these findings and explore lasting effects.

Disclosure

S. Guha: None. S. Kumar: None. A.K. Sinha: None. A. Shankar: None. A.K. Das: None.
738-P: Real-World Effectiveness among Patients with Type 2 Diabetes (T2D) Initiating Tirzepatide (TZP)
Authors: MODY REEMA , DESAI KARISHMA , TENG CHIA-CHEN , REZNOR GALLY , STOCKBOWER GRACE , GRABNER MICHAEL , BENNEYWORTH BRIAN D.
Published: June 2024

Introduction & Objective: TZP is a once weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist (RA) approved in the US for treatment of T2D and obesity. The goal of this single-cohort retrospective study was to assess effectiveness of TZP in patients (pts) with T2D in a US commercially insured population.

Methods: Adult pts diagnosed with T2D, initiating TZP between 5/2022 and 8/2023, with ≥1 A1C result around initiation and another 6 months post-initiation were identified from the Healthcare Integrated Research Database (HIRD®). Baseline demographics, A1C and weight outcomes at 6-month follow-up for overall cohort and stratified by prior GLP-1 RA use and baseline A1C (<7% vs ≥7%) were described.

Results: Among 2,247 identified pts: mean age 54 years, 58% female, 46% no prior GLP-1 RA use, 59% A1C ≥7%, 61% had overweight/obesity. At 6-month follow up, mean pre-post change in A1C was -1.0% in the overall cohort, -1.4% among pts with baseline A1C ≥7%, and -1.3% in those without prior GLP-1 RA use. Mean change in weight was -6.3 kgs for overall cohort, -5.8 kgs in pts with baseline A1C ≥7%, and -8.1 kgs in those without prior GLP-1 RA use. Further outcomes are summarized in Table 1.

Conclusion: At 6-month follow up, pts initiating TZP in the real world showed reductions in A1C and weight, with greater A1C decreases observed among pts with no prior GLP-1 RA use or with baseline A1C ≥7%.

Disclosure

R. Mody: Employee; Eli Lilly and Company. K. Desai: Employee; Carelon Research. Stock/Shareholder; Anthem, Inc. C. Teng: Employee; Carelon Research. G. Reznor: None. G. Stockbower: None. M. Grabner: Employee; Carelon Research. Stock/Shareholder; Anthem, Inc. B.D. Benneyworth: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company.
749-P: Tirzepatide as an Add-on for Participants with Inadequate Glycemic Control Using Basal Insulin—Pooled Subgroup Analysis of SURPASS-5 and -6
Authors: BAJAJ HARPREET S. , BILLINGS LIANA K. , LIU MINZHI , LEVINE JOSHUA A. , RODRÍGUEZ ÁNGEL , PATEL HIREN
Published: June 2024

Introduction & Objective: In SURPASS-5 and -6, tirzepatide (TZP) added to basal insulin significantly improved glycemic control vs. comparators in participants with type 2 diabetes (T2D) with inadequate glycemic control (HbA1c [%] 7.0-10.5 and 7.5-11.0, respectively). Analyses evaluated key clinical parameters at Week 40 within participant subgroups.

Methods: A post hoc analysis including TZP-treated participants using titrated insulin glargine (100 IU/mL) with or without metformin by subgroup: age (<65, ≥65 years), T2D duration (<10, ≥10 years), and baseline (BL) HbA1c (≤8.5%, >8.5%). Data were pooled for SURPASS-5 and -6 up to Week 40.

Results: Overall, 1072 participants were included. At BL, mean age was 59.3 years; 583 (54.4%) were female; mean T2D duration was 13.5 years; mean weight was 92.3 kg, mean HbA1c was 8.6%, and median insulin dose was 42 IU/day. For all subgroups, TZP treatment significantly reduced HbA1c and weight from BL to Week 40 without heterogeneity. Incidence of clinically significant hypoglycemia was numerically higher for participants in HbA1c >8.5% and T2D duration ≥10 years subgroups (Table).

Conclusion: In this post hoc analysis of people with T2D and inadequate glycemic control with basal insulin with or without metformin, participants treated with TZP experienced significantly improved HbA1c and weight across different subgroups.

Disclosure

H.S. Bajaj: Research Support; Abbott, Amgen Inc., Anji Pharmaceuticals, Boehringer-Ingelheim, Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc. L.K. Billings: Advisory Panel; Novo Nordisk, Pfizer Inc. M. Liu: Consultant; Eli Lilly and Company. J.A. Levine: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. Á. Rodríguez: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. H. Patel: None.
76-OR: Diabetes Technology and Waste—A Real-World Study in a Specialized Practice in Germany
Authors: PETRY SEBASTIAN F. , PETRY FRIEDRICH W. , PETRY JOHANNES K. , GAETH STEFAN , HEINEMANN LUTZ
Published: June 2024

Introduction & Objective: Diabetes technology is a pillar of modern diabetes therapy. No real-world data about the amount of waste generated was published before. The aim of our study was to quantify this “diabetes technology waste” in a real-world situation in a specialized diabetes practice in Germany. We also evaluated the awareness for this topic.

Methods: 68 patients with diabetes and insulin treatment were enrolled and completed the study. Patients were asked to collect all therapy-associated waste for three months. Their attitude towards sustainability of antidiabetic therapy, waste generation, and their own waste reduction/separation behavior was surveyed.

Results: In total, around 4,300 test strips, 500 glucose sensors, 12,600 lancets, 500 insulin cartridges, 550 pens and 1,000 pieces of aids for insulin pump therapy were collected. Extrapolating these data on the basis of people with intensified conventional insulin therapy, it can be estimated that at least 1.2 billion pieces of diabetes technology waste are generated in Germany per year. Type and quantity of waste clearly differed depending on diabetes type and type of antidiabetic therapy. Most patients (75%) were surprised by the amounts of waste which in turn led to an increased awareness towards the resource consumption of their therapy (69%), an enhanced interest in waste separation (83%) and a demand for the reduction and recycling of devices/aids (97%). Participants demand for disposal or recycling by the companies (76%), waste separation and collection points in medical practices, clinics, and pharmacies (86%), and more support for sustainability from the medical associations (97%).

Conclusion: This first real-world evaluation of the amounts of diabetes technology waste documents impressive data. Study participants complained about the limited number of recycling options. They expressed a demand for improved sustainability of medical products, especially after having collected the associated waste for three months.

Disclosure

S.F. Petry: None. F.W. Petry: None. J.K. Petry: None. S. Gaeth: None. L. Heinemann: Stock/Shareholder; Science Consulting in Diabetes GmbH, Profil Institut für Stoffwechselforschung GmbH. Advisory Panel; embecta. Board Member; Lifecare A/S. Stock/Shareholder; diateam GmbH.
762-P: Semaglutide Awareness among Clinical-Year Medical Students
Authors: NAHAR ALAM NAZMUN , IFFAT MEEM ANJUMAN , SHAMSHER SHIVALI , M NIAZUR RAHMAN S
Published: June 2024

Introduction & Objective: Semaglutide, a novel type 2 diabetes (T2D) medication, offers significant advantages over other antidiabetic drugs by facilitating weight reduction, preventing cardiovascular complications, and minimizing hypoglycemic risks. Prescriptions for Semaglutide, to treat obesity and T2D have surged by 150% in the past year, according to recent data. While medical students play a crucial role in the healthcare workforce, limited data exists regarding their knowledge on use of Semaglutide. Enhancing students' awareness and understanding of this drug is expected to improve the management of T2D. This study aims to evaluate the knowledge and academic practice of Semaglutide among clinical year medical students.

Methods: We conducted a cross-sectional survey among clinical year medical students (years 3 to 5). Data were collected by administering a questionnaire focused on Semaglutide awareness, including 14 knowledge-based and 8 academic practice-related questions.

Results: Among 243 respondents, the average student scored 57% on the knowledge questionnaire. Year 5 students exhibited higher knowledge scores (78%) compared to other years. The majority of participants reported minimal coverage of Semaglutide in classroom (72%), bedside (74%), and clinical clerkship (71%). Although 86% students agreed on the utility of learning newer drugs through PBL, lectures were chosen as the preferred method when selecting the single best (62%) choice. Participants from all academic years reported minimal observance of Semaglutide prescription during their clinical placements.

Conclusion: Our data highlights a knowledge gap among medical students regarding newer therapeutics for T2D. These results emphasize the importance of integrating educational content on emerging diabetes drugs into various teaching methods throughout the medical curriculum to enhance clinical care standards.

Disclosure

N. Alam: None. A. Meem: None. S. Shamsher: None. S. Rahman: None.
769-P: Efficacy and Safety of GLP1RAs in Liver-Transplanted People with Diabetes—Ad Interim Results of a 24-Month Trial
Authors: GRANCINI VALERIA , COGLIATI IRENE , GAGLIO ALESSIA , RESI VERONICA , ORSI EMANUELA
Published: June 2024

GLP1 RAs are first line drugs for DM2, due to their effects on glycemic control, cardiorenal protection and weight-loss action. However, consistent data about efficacy and safety in patients with liver transplant (LT) are lacking.

Aim: to assess the efficacy and safety of GLP1RAs in people with LT and diabetes in a period of 24 months.

Methods: 52 patients with DM and LT, were enrolled: follow up visits were planned 6-12-24 months after starting a GLP1RA-based therapy (dulaglutide or injectable semaglutide), as add on to metformin or insulin. We assessed glycemic control, body weight and composition (with bio-impedance analysis), liver fibrosis and steatosis (with transient elastography). Amylase, lipase levels and concomitant therapies were recorded at all visits. Patients had an e-mail contact to report any adverse events (AE). At the ad interim analysis, all patients enrolled underwent the first follow up visit, 29 patients completed the study.

Results: We observed a decrease in blood glucose (BG - 8.0±2.2 to 6.8±1.45 to 7.4±1.7mmol/L) and HbA1c (7.1±0.9 to 6.5±1.0 to 6.4±0.6%), p<0.01. BMI, fat mass e fat free mass showed a slight, non significative, improvement. We found no changes in data from elastography. 3 patients interrupted the treatment due to major AE (2 had pancreatitis 8 and 12 month from baseline, 1 had an increase of lipase > 3 times the normal values. Of them, all suffered from biliary strictures). At the short-term follow up, we already observed the improvement in BG and HbA1c (p<0.01), amylase and lipase didn’t increase significantly. 14 people (26.9%) reported mild nausea, but only 3 patients (5.8%) reduced the drug dose. Among 30 patients requiring insulin at enrollment, 15 (50%) and 5 (16.6%), respectively, reduced or suspended insulin therapy in the first 6 months.

Conclusions: GLP1RAs can be considered effective in patients with LT. Further studies are needed to assess if post-surgery biliary strictures could be a potential contraindication to their use.

Disclosure

V. Grancini: Speaker's Bureau; Vertex Pharmaceuticals Incorporated. I. Cogliati: None. A. Gaglio: Consultant; Boehringer-Ingelheim. V. Resi: None. E. Orsi: Speaker's Bureau; Sanofi, Lilly Diabetes, AstraZeneca.
771-P: Efficacy of CT-996, an Oral Small Molecule GLP-1 Receptor Agonist, in Human GLP-1 Receptor Knockin Mice and Obese Cynomolgus Monkeys
Authors: LUO JIAN , RODRIGUEZ RUBEN , HERGARDEN ANNE , TRACY TED , LAM DAVINA , GARAI SUMANTA , MARSHALL DAN , HANSEN STIG K. , CHAKRAVARTHY MANU
Published: June 2024

Since FDA approval of exenatide in 2005, injectable GLP-1 receptor agonists (RAs) have established their clinical utility in the management of type 2 diabetes and obesity. However, rising treatment utilization urgently necessitates cost-effective, simpler solutions. Here, we describe CT-996, a potent, oral small molecule GLP-1RA, and present preclinical efficacy studies to support its development for daily oral human use. In vitro, CT-996 was equally efficacious at stimulating cAMP accumulation in cells expressing human or cynomolgus monkey GLP-1R, and stimulated insulin secretion in a human β-cell line. In contrast to native GLP-1, CT-996 exhibited minimal β-arrestin recruitment and weaker GLP-1R internalization. In vivo, a single oral dose of CT-996 potently and effectively suppressed postprandial blood glucose following a mixed meal tolerance test (MMTT) in mice expressing the human GLP-1 receptor and, in obese monkeys, enhanced glucose stimulated insulin secretion (GSIS) during an intravenous glucose challenge. In a 4-week study in obese monkeys, daily CT-996 dosing markedly suppressed both plasma glucose and insulin excursion during MMTT. Compared to vehicle-treated animals, CT-996 significantly decreased food intake, body weight, and fat mass. All doses were well tolerated. In summary, CT-996 is a small molecule GLP-1RA that exhibits biased cAMP signaling and reduced receptor internalization. Oral dosing of CT-996 enhanced glucose homeostasis and reduced weight and fat mass after 4-week treatment in obese monkeys. These observations corroborate the continued development of CT-996 as a next-generation GLP-1RA. CT-996 is currently being evaluated in a Phase 1 clinical trial.

Disclosure

J. Luo: Employee; Carmot Therapeutics, Inc. R. Rodriguez: Employee; Carmot Therapeutics, Inc. A. Hergarden: Employee; Carmot Therapeutics, Inc. T. Tracy: Employee; Carmot Therapeutics, Inc. D. Lam: Employee; Carmot Therapeutics, Inc. S. Garai: None. D. Marshall: None. S.K. Hansen: Board Member; Carmot Therapeutics, Inc. M. Chakravarthy: Employee; Carmot Therapeutics, Inc.
787-P: Reducing Cardiometabolic Risk with Semaglutide in Type 1 Diabetes (RESET1)—A Double-Blinded Randomized Placebo-Controlled Trial (Study Protocol)
Authors: FRAMPTON RUTH , SNAITH JENNIFER R. , HOCKING SAMANTHA L. , GREENFIELD JERRY
Published: June 2024

Background: Therapies are needed to address excess cardiovascular risk in type 1 diabetes. Once-weekly semaglutide, a long-acting glucagon-like peptide-1 receptor agonist, has been shown to improve weight, glycemia and reduce cardiovascular events in type 2 diabetes and obesity. Semaglutide may offer cardiometabolic protective benefits in type 1 diabetes. The REducing cardiometabolic risk with SEmaglutide in Type 1 diabetes (RESET1) study is a double-blind randomized, placebo-controlled trial of semaglutide in T1D.

Methods: We will study 60 adults aged 25-70 years with type 1 diabetes (duration >2 years), body mass index ≥25 kg/m2, HbA1c ≥ 7% and at least 1 cardiovascular risk factor (microalbuminuria, hypertension or anti-hypertensive treatment, hyperlipidemia or lipid-lowering therapy, current smoking). Subjects will be randomized to semaglutide, titrated to 1.0mg weekly or volume-matched placebo for 26 weeks (supplied by Novo Nordisk A/S). The primary endpoint is carotid femoral pulse wave velocity, a measure of arterial stiffness and surrogate measure of cardiovascular risk. We will measure change in insulin sensitivity determined by hyperinsulinemic-euglycemic clamp; and incretin and pancreatic hormone action measured during mixed meal tolerance test to explore predictors and mechanisms for metabolic improvements. The trial is registered (Australian New Zealand Clinical Trial Registry, ACTRN12623001277639) and will be conducted in Sydney, Australia.

Conclusion: The RESET1 study will establish the effect of semaglutide on cardiometabolic health in adults with type 1 diabetes.

Disclosure

R. Frampton: None. J.R. Snaith: None. S.L. Hocking: Advisory Panel; Novo Nordisk. Other Relationship; Novo Nordisk. Advisory Panel; Eli Lilly and Company. Other Relationship; Eli Lilly and Company, iNova Pharmaceuticals Australia, Nestlé Health Science. Advisory Panel; Seqirus. Speaker's Bureau; AstraZeneca. Other Relationship; Amgen Inc., Sanofi. J. Greenfield: Other Relationship; Novo Nordisk.

Funding

Diabetes Australia Research Program (Charles Campbell Coghlan OAM Emerging Researcher Award), R.A.F. is supported by the University Postgraduate Award (University of New South Wales). J.R.S is supported by JDRF Australia (Grant# 3-SRA-2023-1296-M-N), the recipient of the Commonwealth of Australia grant for Accelerated Research under the Medical Research Future Fund
789-P: Discovery of a Novel, Long-Acting Amylin Receptor Agonist for Body Weight Control
Authors: LI YAN , ZOU HAIXIA , WU XINLE , ZHU RUI , WANG RUIPENG , HAO SUJUAN , LI ZHAOYING , WANG YAXU , DENG JIANHUI , WANG HONGYANG , PENG FEI , JONES CATHERINE L. , FENAUX MARTIJN
Published: June 2024

Introduction & Objective: Amylin, a hormone co-secreted with insulin from pancreatic beta-cells, reduces food intake and glucagon levels. Combination of GLP-1 and amylin analogs promotes weight loss and glucose control. However, treatment is complicated by the need to formulate the peptides in different buffers. The objective of this study was to discover a novel amylin analog that could be co-formulated with GLP-1 peptides at neutral pH.

Methods: Peptides were designed and assessed for thermal-stressed stability (pH 7.4 at 40 oC for 20 days), as well as tested in CHO-K1 CRE reporter cells overexpressing the amylin receptor complex (calcitonin receptor and Ramp3) (AMY3) or calcitonin receptor alone (CTR), and evaluated for body weight reduction by single subcutaneous injection in SD rats. Cmpd C was selected and further characterized by once daily injection for 10 days in diet-induced obese (DIO) rat and pharmacokinetic (PK) study in cynomolgus monkey. Cagrilintide (Novo Nordisk), an amylin analog in Phase 3 studies, was used as a comparator.

Results: Among the peptides tested, Cmpd C activated AMY3 and CTR with similar potencies to cagrilintide (EC50 for Cmpd C and cagrilintide, respectively, AMY3: 0.038 nM vs 0.045 nM; CTR: 0.41 nM vs 0.45 nM). In SD rats, Cmpd C decreased body weight by 7.36% compared to 6.28% for cagrilintide over 48 hours. In DIO rats, body weight loss after end of dosing (Day 11) was 8.19% for Cmpd C and 7.55% for cagrilintide. In cynomolgus monkeys, Cmpd C showed comparable PK to cagrilintide. Importantly, Cmpd C showed superior thermal stability to cagrilintide at pH 7.4. While 44.83% of cagrilintide was degraded after 10 days, Cmpd C was reduced by 4.26% after 20 day incubation.

Conclusion: Overall, Cmpd C demonstrated potency and PK comparable to cagrilintide. Moreover, Cmpd C exhibited greater stability at pH 7.4 than cagrilintide, providing the opportunity to co-formulate with GLP-1 analogs. Formulation of GLP-1 and amylin in a single vial will improve ease of use and reduce cost.

Disclosure

Y. Li: Employee; Sciwind Biosciences. H. Zou: Employee; Sciwind Biosciences. X. Wu: Employee; Sciwind Biosciences. R. Zhu: Employee; Sciwind Biosciences. R. Wang: Employee; Sciwind Biosciences. S. Hao: Employee; Sciwind Biosciences. Z. Li: Employee; Sciwind Biosciences. Y. Wang: Employee; Sciwind Biosciences. J. Deng: Employee; Sciwind Biosciences. H. Wang: Employee; Sciwind Biosciences. F. Peng: Employee; Sciwind Biosciences. C.L. Jones: Employee; Sciwind Biosciences. M. Fenaux: None.

Funding

Sciwind Biosciences
8-PUB: Peer Support Defined by Key Functions—Implementation, Predicting Outcomes, and Mediation of Intervention Effects in Peer Support for Diabetes Management in Shanghai, China
Authors: LIU YUEXING , CAI CHUN , WU XIAOYU , TANG PATRICK Y. , COUFAL MUCHIEH M. , SHEN LI , FISHER EDWIN B. , JIA WEIPING
Published: June 2024

What is peer support? Amidst great variation worldwide, Peers for Progress has promoted defining peer support (PS) by the “key functions” it provides. In a community PS program under the Shanghai Integration Model, key functions were measured by 15 items capturing participants’ reports of 1) Availability and Ongoing Support, 2) Assistance in Daily Management, 3) Social and Emotional Support, 4) Linkage to Clinical/Community Resources, 5) “Being There,” e.g., “people in the community diabetes program are there for you.”

The key functions documented implementation in 12 Intervention Communities (ICs) relative to 4 Comparison Communities (CCs) as well as relationships with outcomes and mediation of intervention effects.

At follow up, ICs scored higher than CCs on each of the 5 individual functions and their total, all, ps < 0.001. On 5-point scales, mean differences between ICs and CCs ranged from 0.74 to 0.81.

Individual functions and total scores across the key functions were correlated with improvements in HbA1c, all p-levels < 0.001. Similarly, each of the 5 and their total were also correlated with improvements in a 4-item measure of diabetes distress (ps ≤ 0.023) and the PHQ8 measure of depressed mood (ps < 0.001). These controlled for gender, age, duration, and education level, as well as corresponding baseline measures.

Regression analysis indicated the total score for the 5 key functions mediated the relationship between the intervention, IC vs CC, and improvements in HbA1c, diabetes distress, and PHQ8.

The key functions identify features of PS that are recognized by program participants and help define PS as they distinguish PS from control conditions. The key functions are correlated with program benefits, and the total of reported key functions mediates the relationship between intervention and clinical/quality-of-life benefits.

Disclosure

Y. Liu: None. C. Cai: None. X. Wu: None. P.Y. Tang: None. M.M. Coufal: None. L. Shen: None. E.B. Fisher: None. W. Jia: None.

Funding

Shanghai Key Discipline of Public Health Grants Award No. GWVI-11.1-20, and Shanghai Municipal Grants Award No. GWIV-3.1 to Professor Weiping Jia as principal investigator, Shanghai Municipal Health Commission ôHealth Promotion Talentö grant No.JKKPYC-2022-12 to Dr. Yuexing Liu as principal investigator, and by grants from The Merck Foundation and from Sanofi China, both to Professor Edwin Fisher as principal investigator, and by the UNC-Michigan Communnity, Family, and Peer Support Core of the Michigan Center for Diabetes Translational Research, P30 DK092926.