bluuebunny/crossref_metadata_2025 huggingface dataset:
1765-P: Inhibition of NLRP3 Inflammasome Activation and Reduction in T-Cell Migration Are Key Mechanisms by Which PAHSAs Protect against Type 1 Diabetes
Authors: SYED ISMAIL , MAGUPALLI VENKAT G. , ARYAL PRATIK , SANTORO ANNA , SIEGEL DIONICIO , KAHN BARBARA B.
Published: June 2024

Palmitic acid esters of hydroxy stearic acids (PAHSAs) are bioactive lipids with anti-inflammatory and anti-diabetic effects. PAHSAs markedly reduce the incidence and delay the onset of autoimmune T1D in NOD mice. PAHSAs attenuate autoimmune responses by lowering mature T helper cell activation and B cell number and increasing regulatory T cell activity in the islets of NOD mice. Toll-like receptors and NLRP3 (nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing protein 3) inflammasome pathways play an essential role in T1D pathogenesis. NLRP3 is critical for inducing expression of chemokines and their receptors which stimulate pathogenic T cell migration into islets. Here, we aimed to determine the mechanisms by which PAHSAs attenuate immune responses to prevent T1D.

Results: Adoptive transfer of splenocytes from PAHSA-treated NOD mice delays and attenuates T1D incidence in immunodeficient NOD.SCID mice. These effects are associated with decreased expression of NLRP3 inflammasome components by 25-55% and chemokines by 60-70% without altering chemokine receptor expression in immune cells isolated from PAHSA-treated NOD mouse islets. In human islets from normal and type 2 diabetic donors, clonal pancreatic β-cells (MIN6 cells) and bone marrow-derived macrophages, PAHSAs attenuate pro-inflammatory cytokine and chemokine gene expression and secretion in response to LPS or Nigericin (NLRP3 inflammasome activator). In co-culture studies of MIN6 cells and CD4+ T cells, PAHSAs attenuate LPS and Nigericin-induced CD4+ T cell migration by 65%. Conclusions: PAHSAs’ protective effects against T1D can be conferred by transfer of immune cells from PAHSA-treated mice. Inhibition of NLRP3 inflammasome activation and T cell migration into islets are key mechanisms by which PAHSAs protect islets from immune-mediated attack. Thus, PAHSAs may serve as therapeutic agents to prevent and/or treat T1D.

Disclosure

I. Syed: None. V.G. Magupalli: None. P. Aryal: Employee; Cellarity. A. Santoro: None. D. Siegel: None. B.B. Kahn: Advisory Panel; Janssen Pharmaceuticals, Inc. Consultant; Vida Ventures Advisors, Arrowhead Pharmaceuticals, Inc.

Funding

NIH K01 DK118041 (IS).Joslin Pilot & Feasibility Grant P30 DK046200 (IS).NIH R01 DK106210 (BBK).JPB Foundation (BBK).
178-OR: Assessing Hypoglycemia Awareness—Validating HypoA-Q within the T1D Exchange Registry
Authors: KUEI LIN YU , YE WEN , HEPWORTH EMILY , MATUS AUSTIN M. , FLATT ANNELIESE , DE ZOYSA NICOLE , SHAW JAMES A. , RICKELS MICHAEL R. , AMIEL STEPHANIE A. , SPEIGHT JANE
Published: June 2024

Introduction & Objective: Hypoglycemia awareness is commonly assessed using legacy patient-reported outcome measures (PROMs; e.g., Gold and Clarke). However, they may not meet current FDA PROM standards. The 5-item Impaired Awareness scale of the HypoA-Q short form (SF) was developed in accordance with FDA standards. Our aim was to validate it in a large cohort of US adults with type 1 diabetes.

Methods: We surveyed registrants of the national T1D Exchange registry, collecting demographics; 6-month severe hypoglycemia (SH) history; and responses to HypoA-Q SF, Gold and Clarke. The Clarke hypoglycemia awareness factor (“ClarkeHAF”) was calculated to exclude items about SH history. Analyses included Cronbach’s α (internal consistency reliability), Spearman correlations (convergent and divergent validity), multiple logistic regression analysis (predictive validity) and X2 test (SH odds with HypoA-Q SF score ≥12).

Results: The survey was completed by 1,580 participants (52% women, median[IQR] age 43[33—58]y, diabetes duration 24[12—37]y, 87% non-Hispanic Caucasian, 94% using continuous glucose monitors). The HypoA-Q SF had satisfactory reliability (α=0.79). Convergent validity was supported by moderate-to-strong correlations with the single-item Gold (rs=.63), 8-item Clarke (rs=.79), and ClarkeHAF scores (rs=.82; P<.001 for all). Divergent validity was supported by weak correlation with diabetes duration (rs=.18, P<.001), and no correlation with HbA1c. After adjusting for age, sex and diabetes duration, higher HypoA-Q SF scores were associated with greater SH risk (95%CI: .59—.65, P<.001), performing comparably to Gold (.57—.63, P<.001) and ClarkeHAF (.59—.65, P<.001), while the 8-item Clarke score (retaining SH history items) performed better in predicting SH (.70—.75). HypoA-Q SF score ≥12 was associated with 5.2-fold higher odds of SH (P<.001).

Conclusion: These findings support future use of the HypoA-Q SF for assessing hypoglycemia awareness and risk for SH.

Disclosure

Y. Lin: None. W. Ye: None. E. Hepworth: None. A.M. Matus: None. A. Flatt: None. N. de Zoysa: None. J.A. Shaw: Advisory Panel; Mogrify. M.R. Rickels: Consultant; Vertex Pharmaceuticals Incorporated, Sernova, Corp. Research Support; Dompé. S.A. Amiel: Advisory Panel; Vertex Pharmaceuticals Incorporated. Other Relationship; Sanofi. J. Speight: None.

Funding

National Institutes of Health (U01DK135111, K23DK129724)
1790-LB: The Value of Duke Treadmill Score in Predicting Severity of Coronary Artery Disease In Diabetic Patients by SYNTAX Score
Authors: TAIMUR SYED D.M.
Published: June 2024

Aim & Object: One of the non invasive test is exercise tolerance test which carried out to identify prediction of severity of coronary artery disease and to assess the risk of major cardiac events. To establish prediction of coronary artery disease in patient having diabetic patient who performed exercise tolarence test by SYNTAX score.

Methodology: There were 520 patients included in this study, who were divided into groups based on their Duke tread mill scores. Diabetic patients with high Duke Treadmill score (DTS) (≤-11) were categorized in group I and diabetic patients with medium ( -10 to +4) and low Duke Treadmill score(≥+ 5) were included in group II.

Results: The mean age of the study population was 55.2 ± 9.0 years ranging from 18-75 years, According to the study, 52.58% of Group I patients were 51-65 years old, had more triple vessel disease, and had left main disease with or without other vessel involvement, which was significantly statistically significant (p=0.001).Patients with triple vessel disease had higher in SYNTAX score> 22 than SYNTAX score < 22 which was statistically significant (p=0.001). Diabetic patients with DTS < -11 (high-risk group) carry more than 8.1(95% CI = 5.91 - 14.04)-fold higher risk of having severe CAD (SYNTAX score > 22) than those with DTS ≥ -10 (low & medium risk) (p < 0.001). It is evident from DTS as well as SYNTAX score that they exhibit a significant negative correlation (r = - 0.541, p 0.0001).

Conclusion: By calculating SYNTAX scores, it was found that high DTS is positively correlated with severity of coronary artery disease. Cardiovascular disease is predicted in patients who score high on the Duke Treadmill.

Disclosure

S.D.M. Taimur: None.
1792-LB: Long-Term Impact of Glucose Status on Risk of Restenosis after Percutaneous Transluminal Coronary Angioplasty—A Six-Year Follow-up Study
Authors: GU YAN , ZHANG LEI , ZHANG QI , LIU ZHENYU , LIU YUQING , DONG YANHU
Published: June 2024

Patients with diabetes (DM) are at high risk for restenosis after coronary stenting. Information relating the long-term outcome of percutaneous transluminal coronary angioplasty (PTCA) to prediabetes is, however, limited. We retrospectively analyzed data of 951 patients (mean age 59.5±4.2 yrs, 60.5% of men, mean history of coronary heart disease 9.1±1.1 yrs) who undertook PTCA at Emergency Department between Jan 2008 and Dec 2011. Baseline measures included blood pressure (BP), fasting plasma glucose, lipid profile, A1c, C-reactive protein (C-RP), and 2-hour capillary glucose. All patients had follow-up coronary CTA 6 year after PTCA. Restenosis was defined as ≧ 50% stenosis in stent or within 5 mm adjacent to stent. The rate of restenosis was compared among patients with normal glucose tolerance (NGT, n=407), impaired glucose regulation (IGR, n=263), and DM (n=281) according to their baseline glucose levels or prior history of DM. Patients with DM had highest levels of body mass index (BMI), BP, triglycerides (TG), and C-RP, followed by those with IGR and NGT (P<0.01).The number of lesion was 1.6, 1.8, and 2.6 in patients with NGT, IGR, and DM, respectively (p<0.05). At year 6, the rate of restenosis, evaluated by coronary CTA, were 4.8%, 6.5%, and 14.2% in patients with NGT, IGT, and DM, respectively (P<0.05). Among DM subgroup, compared with patients with A1c<8%, those with A1c>8% had increased rate of restenosis (15.8% vs. 12.4%, P<0.05). In the logistic regression model, the odd ratio (OR) of having restenosis was 1.52 (95%CI: 1.03-2.90) for DM and 1.11 (95% CI: 1.01-1.54) for IGR, after adjusting for age, history of CHD, BMI, BP, LDL-C, TG, A1c and C-RP. Restenosis is more frequent in patients with compared those without DM. Prediabetes is associated with increased risk of restenosis after PTCA during a long-term follow-up period. The data indicates that intervention of hyperglycemia should be addressed in CHD patients even in those with prediabetes.

Disclosure

Y. Gu: None. L. Zhang: None. Q. Zhang: None. Z. Liu: None. Y. Liu: None. Y. Dong: None.
1808-LB: NIK-Mediated Microglia Polarization Induces Endothelial Dysfunction in Diabetic Retinopathy
Authors: LI HONGXUE , KUANG HONGYU
Published: June 2024

Introduction & Objective: Chronic inflammation significantly contributes to endothelial dysfunction in diabetic retinopathy (DR). NIK, a central and specific signal component that regulates the activation of noncanonical NF-κB pathway, is overexpressed in inflammatory diseases, metabolic disorders, and cancer. Although some achievement have been made in the study of NIK, it is unknown whether NIK can participate in the progression of DR.

Methods: Mice fed a high-fat diet and injected with streptozotocin were induced to develop DR. At the same time, human microglial cells 3 (HMC3) and Human retina microvascular endothelial cells (hRMECs) were exposed to AGEs to mimic DR pathologies in vitro. B022 (a small-molecule inhibitor of NIK) was injected into DR mice and added into the cell culture medium to investigate the role of NIK in microglia polarization-induced endothelial dysfunction. To further explore the underlying mechanism, lentiviruses harboring a short hairpin RNA targeting NIK and an NIK overexpression were used to knock down and overexpress NIK, respectively.

Results: Compared with normal control, endothelial dysfunction, microglia M1/M2 polarization, and inflammatory factors they surged in both DR mice retinas and AGE-treated HMC3 cells or co-cultured model, according to HE staining, immunofluorescence, immunohistochemistry, TUNEL assay, vascular permeability assay, cell permeability assay, ELISA, RNA sequencing and western blotting. Moreover, NIK expression was higher in DR mice retinas and AGE-treated microglia. In the B022 treated mice or cells, endothelial dysfunction, M1/M2 polarization, and inflammatory microenvironment were improved. Manipulating NIK expression levels markedly regulated the non-classical NF-κB pathway and microglia polarization.

Conclusions: These results suggest that NIK maybe the potential target to treat diabetic retinopathy.

Disclosure

H. Li: None. H. Kuang: None.

Funding

National Natural Science Foundation of China (No. 82170832).
1816-LB: Examining the Human Diabetic Bone Marrow Niche
Authors: CIRKA HALEY , SAMANT AMRUTA , KOSTYRA DAVID M. , KHAIR LYNE , NGUYEN TAMMY T.
Published: June 2024

Introduction & Objective: Patients with diabetes mellitus (DM) have a 30-fold increased risk of developing diabetes foot ulcers (DFUs), with 43% requiring lower extremity amputations (LEAs). While the underlying cause of non-healing DFUs is not known, abnormalities in bone marrow (BM)-derived immune cell dysfunction may play a key role. To study the effect of DM on human BM-derived innate immunity, we developed a human BM organoid system to directly study the human DM immune system from patients with DFUs.

Methods: BM was collected from a DM patient undergoing a LEA for treatment of a non-healing DFU. BM explants were cultured in a 3D protein matrix separately by two technicians. Resulting HSCs underwent in vitro differentiation into monocytes and macrophages. Human cord blood (HUCB)-derived HSCs cultured in a 3D protein matrix for expansion and characterized via FACS, a colony forming unit assay, and in vitro differentiation as a control.

Results: HUCB and BM derived HSCs were expanded in a 3D organoid culture. HSC pluripotency was tested by colony forming unit assay, FACS, and in vitro differentiation of HSCs to monocytes and macrophages. Monocytes and macrophages were produced in similar percentages and efficiencies before and after the 3D organoid culture. The in vitro differentiation of DM BM-derived HSCs yielded similar percentages of monocytes and macrophages and in similar efficiencies between technicians.

Conclusion: Our novel 3D organoid culture system successfully expands HSCs without altering HSC behavior. Expanded DM BM-derived HSCs are representative of inherent differences of the sample, as opposed to experimental handling. Therefore, this methodology can be used to directly understand the impact of DM on the human immune system and its role in DFUs.

Disclosure

H. Cirka: None. A. Samant: None. D.M. Kostyra: None. L. Khair: None.
1820-LB: Evaluating an HCP Diabetes Training Program in Kasese, Uganda
Authors: NARAYANAN SANDHYA , BASCH COREY , BAKER JASON ,   DIABETES CONSULTATION ASSOCIATION TEAM KASESE, UGANDA
Published: June 2024

Introduction & Objective: Health Care Provider (HCP) diabetes educational sessions are core to the mission of Diabetes Empowerment International (DEInt) in Kasese, Uganda. Understanding HCP profiles and their barriers to diabetes education access is essential to shape a successful training program. We evaluated the profile of the HCPs that are trained as well as the feedback received regarding how the training is implemented in patient care.

Methods: In person HCP diabetes seminars are held every 8 weeks DCA/DEINt Diabetes Education Center in Kasese, covering a curriculum of key topics related to care of diabetes. Each session hosts over 50 regional HCPs, and over 106 HCPs have attended 23 education seminars. Participant evaluations are performed for each seminar for impact on diabetes knowledge and patient care.

Results: The average distance traveled for the conferences was 29.4 km [range 0.5-63.2 km]. The majority of participants are enrolled nurses (n=51, 48.11 %), followed by assistant nursing officers (n=20, 18.87 %), and enrolled midwives (n=11, 10.38 %). The remainder of participants have varied healthcare provider titles. The majority of HCPs reported that there was a diabetes trained doctor in the facility where they worked (n=62, 58.49 %). The mean number of diabetes patients supported was 40 [range 0-418]. A total of 8,733 people with diabetes are being served by the HCPs with 289 type 1 diabetes patients and 770 type 2 diabetes patients. The topics that attendees expressed the most confidence in managing patients with diabetes was checking blood sugars and hypoglycemia. Topics that attendees indicated that they would change how they treat diabetes patients was insulin pumps (n=55, 62.5%) and carbohydrate counting (n=54, 61.36 %).

Conclusion: Our diabetes training programs supports a wide range of HCPs. HCP diabetes training can have a far-reaching impact on an underserved population of individuals with diabetes.

Disclosure

S. Narayanan: Employee; Dexcom, Inc. C. Basch: None. J. Baker: Speaker's Bureau; Insulet Corporation, Dexcom, Inc., Sanofi.
1831-LB: Digital Chronic Condition Management Personalized Newsletter Pilot Powered by Predictive Modeling Increased Coaching Utilization
Authors: KAPOOR KARAN , VISWANATH RAMASUBRAMANIAM AADITHYA , JIANG YUZE , BORASTON SARA , ROACH MERCEDES , EISELT ANNE-KATHRIN , LAWTON SHANNON , KOMPALA TEJASWI , YEDAPADI RAJARAM GOWTHAM
Published: June 2024

Introduction & Objective: Digital chronic condition programs (DCCP) offer education, coaching, and self-management tools to improve health behaviors. Engagement is key for behavior change and improved outcomes, and personalized recommendations have shown to increase engagement. This study examined 1:1 coaching utilization with certified diabetes care and education specialists (CDCES) between DCCP members who received a personalized ‘next best action’ e-newsletter powered by predictive modeling.

Methods: Members with type 2 diabetes and no reported insulin use were included in a weekly e-newsletter pilot from 11/20/2023 - 1/29/2024 to evaluate predictive models that recommend next best action from member’s past engagement. Control and treatment groups were block randomized by age, gender, time in program, A1c, and historical email engagement rates. Control 1 (C1) received original design and content. C2 received new design and original content. Treatment 1 (T1) received new design and personalized activity graphic. T2 received new design and next best action. T3 received new design, activity graphic, and next best action. First time utilization of coaching compared between groups was measured by any coaching completed after first newsletter open date. Standard two sample independent proportions test was used to measure utilization differences. Results: Average age was 55.6 years old (SD 10.6) with each group 50% female. All treatment groups with next best action had increased utilization of coaching in members with no coaching engagement prior to pilot (N = 137,283) (C1 0.14%, C2 0.12%, T1 0.14%, T2 0.17%, T3 0.21%). Statistically significant increases were shown for T3 compared to both C1 (p=0.02) and C2 (p=0.007).

Conclusion: Use of predictive modeling to recommend next best action from past engagement in a DCCP was shown to be effective in increasing short-term coaching engagement that has been associated with improved glycemic control.

Disclosure

K. Kapoor: Employee; Teladoc Health. A. Ramasubramaniam: Employee; Teladoc Health. Y. Jiang: Employee; Teladoc Health. S. Boraston: Employee; Teladoc Health. M. Roach: Employee; Teladoc Health. A. Eiselt: Employee; Teladoc Health. Stock/Shareholder; Teladoc Health. Research Support; Teladoc Health. S. Lawton: None. T. Kompala: None. G. Yedapadi Rajaram: Employee; Teladoc Health.
1832-LB: Exercise Training and Cold Exposure Trigger Distinct Molecular Adaptations to Inguinal White Adipose Tissue
Authors: VAMVINI MARIA , NIGRO PASQUALE , STANFORD KRISTIN I. , HIRSHMAN MICHAEL F. , MIDDELBEEK ROELAND J. , GOODYEAR LAURIE
Published: June 2024

Exercise training and cold exposure are physiological stimuli that both improve systemic glucose metabolism, but the mechanisms are not well understood. Here, we tested the hypothesis that adaptations to inguinal white adipose tissue (iWAT) are critical for the beneficial effects of exercise-trained and cold-exposed iWAT on metabolism. First, we utilized an iWAT transplantation model. Male donor mice were sedentary, exercise trained by voluntary wheel running, or cold exposed (5°C) for 11 days (n=5/group). Transplanting iWAT from exercised into sedentary mice enhanced glucose tolerance, yet cold-exposed iWAT had no effect, suggesting unique adaptations to trained iWAT that confer beneficial effects on glucose homeostasis. To determine exercise-specific effects on iWAT, quantitative proteomic profiling (QPP) of iWAT was done from sedentary, trained, and cold-exposed mice. Cold down-regulated >2,000 proteins in iWAT, but also resulted in a protein signature of enhanced mitochondrial biogenesis, energy production, and fatty acid metabolism. Training also regulated protein expression, but interestingly only training-specific proteins (>50 proteins), and not cold proteins, were inversely correlated with fasting glucose. This suggests that training results in fundamental changes in iWAT that mediate systemic glucose homeostasis, consistent with the transplantation glucose tolerance data. Training also upregulated iWAT extracellular space and vesicle transport proteins. Consistent with this finding, isolation of adipocyte-derived EVs from sedentary and trained mice revealed a significant increase in EV release from trained adipocytes. In sum, exercise training facilitates the release of iWAT-derived molecules, fostering inter-tissue communication. We define the unique exercise training- and cold exposure-induced iWAT proteomes, revealing distinct mechanisms for the beneficial effects of these interventions on metabolic health.

Disclosure

M. Vamvini: None. P. Nigro: None. K.I. Stanford: None. M.F. Hirshman: None. R.J. Middelbeek: Research Support; Novo Nordisk. L. Goodyear: None.

Funding

This work was supported by NIH grant (R01DK099511, R01DK101043 (to L.J.G.)), (T32DK00726042, F32DK12643201) and Joslin DRC (P30 DK36836) Pilot and Feasibility Program award (to M.V.), K23DK114550 (to R.J.W.M), and the Joslin Diabetes Center DRC (P30 DK36836).
1838-LB: Effects of VLCDs on Weight Loss and Glycemic Control among Kuwaiti Adults with Type 2 Diabetes
Authors: ALSUMAITI DURRA , ALLAHOU BADREYA , ALMATROOK REEM
Published: June 2024

Introduction: Kuwait faces significant health challenges with high rates of obesity and T2D. Although very low-calorie diet plans (VLCDs) have proven effective for weight loss and glycemic control, their impact has not yet been assessed among Kuwaiti adults. This study aimed to evaluate the effectiveness of two VLCDs on weight loss and glycemic control in Kuwaiti adults with T2D.

Methods: We analyzed data from 32 adults with T2D who were not on weight loss medications at the Dasman Diabetes Institute between 2021 and 2023. Adults chose between two diet plans: TDR providing 800 kcal/day liquid formula, or a VLCD providing 900 kcal/day food-based regimen. Weight and HbA1c were measured at baseline and 3-month. Within-group changes were analyzed using paired t-tests and Wilcoxon ranked tests.

Results: Groups were comparable at baseline, with no significant differences in age or sex distribution (TDR: 52.4 ± 10.7 years and 88.9% male; VLCD: 57.6 ± 10.7 years and 78.3% male; P >0.05). The TDR group achieved a mean weight loss of 10.0 ± 3.5 kg (10.2% of initial weight) and a median HbA1c reduction of 1.0 (IQR= 0.80), whereas the VLCD group achieved a mean weight loss of 7.2 ± 3.9 kg (7.7% of initial weight) and a median HbA1c reduction of 0.9 (IQR= 0.60). Adherence differed significantly, with one-third completing the TDR (n= 9 out of 26) compared to two-thirds in the VLCD group (n= 23 out of 33, P= 0.03).

Conclusion: VLCDs demonstrated potential in reducing weight and HbA1c in Kuwaiti adults with T2D over three months. However, adherence to the TDR proved more challenging. Further research with larger samples and longer duration is warranted.

Disclosure

D. Alsumaiti: None. B. Allahou: None. R. Almatrook: None.
184-OR: Association between Composite Dietary Antioxidant Index and Stroke among U.S. Adults with Diabetes—Insights from NHANES
Authors: ZHANG HONGQIANG , SHI JIE , YUE TONG , WENG JIAHAO , WANG XULIN , ZHENG XUEYING , LUO SIHUI , DING YU , WANG CHAOFAN
Published: June 2024

Introduction & Objective: While previous research suggests a negative correlation between the Composite Dietary Antioxidant Index (CDAI) and stroke prevalence, particularly in pre-diabetes, data on this relationship in diabetic individuals remain limited. This study aims to assess the association between CDAI and stroke risk in individuals with diabetes.

Methods: This cross-sectional study analyzed data from the NHANES from 2003 to 2018, including 6735 participants aged ≥20 with diabetes. Stroke status was determined based on self-report. The CDAI was calculated using dietary intake data of six antioxidants (vitamins A, C, E, carotenoids, selenium, zinc) obtained from 24-hour dietary recall interviews. The association between CDAI and stroke risk was assessed using multivariate logistic regression and restricted cubic spline analysis.

Results: The mean age of participants was 59.6 ± 13.6 years, 51.5% were male, with 611 (9.1%) reporting a stroke. Higher CDAI levels were associated with a lower risk of stroke after adjusting confounding factors (OR = 0.96; 95% CI 0.92-0.99, P<0.001). Specifically, participants in the highest CDAI quintile had a 43% lower stroke prevalence compared to those in the lowest quintile (OR = 0.57, 95%CI 0.40-0.83, P = 0.003). Restricted cubic spline showed that there was a negative linear association between CDAI and stroke.

Conclusion: This study found a negative relationship between CDAI and stroke risk in US diabetic adults, highlighting the potential role of antioxidant-rich diets in stroke prevention.

Disclosure

H. Zhang: None. J. Shi: None. T. Yue: None. J. Weng: None. X. Wang: None. X. Zheng: None. S. Luo: None. Y. Ding: None. C. Wang: None.

Funding

Clinical Medical Research Transformation Project of Anhui Province (Grant No. 202204295107020026)
1846-LB: Developing Best Practices for Preventing "Diabulimia"—Focusing on Health Care Professionals' Knowledge of Insulin Omission/Restriction
Authors: BORDNER CANDACE , STUCKEY-PEYROT HEATHER L. , LAFFEL LORI M. , PROKOP AMIE , TOSCHI ELENA , GOEBEL-FABBRI ANN E.
Published: June 2024

Introduction: Disordered eating behaviors (DEB) are common in type 1 diabetes (T1D), occurring in ~25% of young adults. DEBs are often characterized by insulin restriction and chronic hyperglycemia, increasing risk for future microvascular complications. This study focused on identification, prevention, and treatment of this high-risk condition by investigating healthcare professional (HCP) perceptions of the problem.

Methods: A semi-structured interview guide was developed to address topics such as: general eating disorder knowledge, knowledge of “diabulimia”, and resources needed to identify, prevent, and treat “diabulimia.” T1D HCPs identified by study team members underwent screening for eligibility based upon experience caring for patients with T1D prior to interviewing. Codes were developed inductively, with coding performed by two researchers attaining a kappa >0.70 (MAXQDA).

Results: Individual interviews (n=11) were conducted with T1D HCPs (2 MD/DO; 1 BSN/CDCES; 4 RD/CDCES; 3 NP/MSN; 1 NP/CDCES). Themes included a lack of: (a) information on DEBs, especially “diabulimia”, as these are not addressed in formal medical education; (b) knowledge about how best to initiate conversations and communicate with patients about DEBs; and (c) lack of diabetes mental health professionals available for referral. Suggested educational interventions included quick reference guides on communication techniques to use in the clinic; live training sessions to practice with standardized patients; and available referral networks for mental health professionals through the ADA and APA.

Conclusions: T1D HCPs identified need for more resources and education to help identify, discuss, and manage DEBs in people with T1D. Notably, a lack of mental health professionals remains a major hindrance. Future interviews with people with T1D in recovery from DEB can help guide HCPs in best practices to help manage DEBs.

Disclosure

C. Bordner: None. H.L. Stuckey-Peyrot: None. L.M. Laffel: Consultant; Dexcom, Inc. Advisory Panel; Medscape, Medtronic, Vertex Pharmaceuticals Incorporated. Consultant; Novo Nordisk. Advisory Panel; Lilly Diabetes, Provention Bio, Inc., Sanofi-Aventis U.S., Janssen Pharmaceuticals, Inc., MannKind Corporation. A. Prokop: None. E. Toschi: Consultant; Vertex Pharmaceuticals Incorporated, Sanofi. A.E. Goebel-Fabbri: None.

Funding

Juvenile Diabetes Research Foundation International (3-SRA-2024-1457-M-B)
1850-LB: Role of Cardiovascular Risk Communication in Motivating Self-Management of Young-Onset Type 2 Diabetes (YOD)—A Mixed-Methods Study
Authors: ABRAHA MOSANA , SENGA JOYEUSE , YU CATHERINE H. , SHAH BAIJU R. , KE CALVIN
Published: June 2024

Introduction & Objective: Optimal self-management may help mitigate the high cardiovascular risk of YOD (defined as age at type 2 diabetes diagnosis <40 years). However, perceptions of cardiovascular risk communication have never been studied in YOD. We determined the accessibility, emotional impact, and perceived role of various formats of cardiovascular risk communication in influencing YOD self-management behaviors.

Methods: We depicted cardiovascular risk predictions using 6 different visual formats for this mixed-methods study. Participants rated each format using validated scales (accessibility, emotional responses). Semi-structured interviews were conducted and thematically analyzed to understand perceptions using the Behavior Change Wheel framework.

Results: We recruited 18 participants (52.6% women, mean age 41.0 years, 7 ethnic groups). Accessibility and emotional response ratings varied (Table). Lifetime risk formats were perceived as the most clear, accessible, urgent, and motivating to change self-management behavior, while 5-year risk predictions were perceived as reassuringly low and unmotivating. Cardiovascular age was perceived as confusing and unclear.

Conclusion: Cardiovascular risk communication, especially using lifetime risk predictions, may play an important role in interventions to motivate YOD self-management.

Disclosure

M. Abraha: None. J. Senga: None. C.H. Yu: None. B.R. Shah: None. C. Ke: Advisory Panel; Sanofi. Speaker's Bureau; AstraZeneca.

Funding

Novo Nordisk Network for Healthy Populations, Sunnybrook Program to Access Research Knowledge (SPARK) for Black and Indigenous Students
1851-LB: “You feel isolated. You’re kind of in over your head”—Experiences of Caregivers of Aging People with Diabetes
Authors: MOORE KELLY , STUCKEY-PEYROT HEATHER L. , HUGHES ALLYSON S.
Published: June 2024

Type 1 diabetes (T1D) is becoming more prevalent in the aging U.S. population due to treatment advancements resulting in people with T1D living longer and more people being diagnosed with T1D as adults. Unfortunately, resources to care for aging people with T1D are sparse. This dearth of information may further exacerbate age related health disparities. In this study, we characterized the impact of caring for aging people with diabetes from the caregiver’s perspective. This qualitative study included 12 participants who were family members or professional caregivers who support aging people with T1D. Using an interview guide, semi-structured interviews were conducted. Interviews were transcribed and a codebook was developed to guide thematic analysis. Two coders independently coded the transcripts and then met to compare codes and confirm consensus. Three themes emerged from the data: 1. Lack of training and education for the aging T1D population, 2. Caregiver frustration, worry, and burden, and 3. Lack of community amongst aging people with T1D and their caregiver. Participants wished they knew more about how to provide effective diabetes care. Each caregiver described feeling frustrated towards the unpredictable nature of T1D or described feeling worried about hypoglycemic episodes. While participants were not outright in stating they felt burdened, each caregiver made some form of physical or emotional sacrifice which made an impact on their life. They reported caregiving difficulties and successes as well as the impact caregiving has had on work life, mental health, and physical health. Participants also expressed an interest in creating a community of caregivers to discuss the challenges of caring for an aging person with T1D similar to those for parents of children with T1D. This data provides insight into the challenges caregivers face when caring for aging people with T1D. More support and resources are needed specifically for caregivers of aging people with diabetes.

Disclosure

K. Moore: Consultant; Biocomposites LLC. H.L. Stuckey-Peyrot: None. A.S. Hughes: None.
1857-LB: Improvement of Liver Steatosis by Mazdutide in Chinese Participants with Overweight or Obesity—An Exploratory Analysis of GLORY-1
Authors: JI LINONG , JIANG HONGWEI , ZHANG YAWEI , LV LINGCHUN , GU JIEYU , LIU ZIHAN , WANG YANQI , DENG HUAN , QIAN LEI
Published: June 2024

Introduction & Objective: To explore the effect of mazdutide, a once-weekly GLP-1 and glucagon receptor dual agonist, on liver steatosis.

Methods: In the GLORY-1 phase 3 trial (NCT05607680), 610 Chinese adults with a BMI of 28 kg/m2 or more, or 24 kg/m2 or more and at least one weight-related comorbidity were randomly assigned 1:1:1 to receive once-weekly, subcutaneous mazdutide 4 mg, mazdutide 6 mg or placebo for 48 weeks. A subpopulation of participants had MRI scan and liver fat content (LFC) measurement by MRI-proton density fat fraction (MRI-PDFF). Change from baseline at week 48 in LFC was an exploratory endpoint of the study.

Results: In participants with baseline LFC of 5% or more and 10% or more, treatment with mazdutide 4 mg or 6 mg for 48 weeks led to marked and dose-dependent reductions in LFC. Of note, a mean relative reduction of 80.2% was achieved with mazdutide 6 mg among participant with baseline LFC of 10% or more. In participants with baseline LFC of 5% or more, compared with placebo, substantially more participants with mazdutide 4 mg and 6 mg achieved ≥30% relative reduction in LFC, ≥50% relative reduction in LFC and normalization of LFC (<5%) at week 48 (Figure).

Conclusion: In Chinese adults with overweight or obesity and liver steatosis, mazdutide 4 mg and 6 mg provides robust reductions in LFC.

Disclosure

L. Ji: None. H. Jiang: None. Y. Zhang: None. L. Lv: None. J. Gu: None. Z. Liu: Employee; Innovent Biologics. Y. Wang: Employee; Innoventbio. H. Deng: Employee; Innovent. L. Qian: Employee; Innoventbio.
186-OR: Longitudinal Effect of Diabetes Fatalism on Clinical Outcomes and QOL in AA with Type 2 Diabetes Mellitus
Authors: IREGBU SANDRA C. , WALKER REBEKAH J. , EGEDE LEONARD E.
Published: June 2024

High diabetes fatalism scores (DFS) strongly correlate with poor glycemic control in individuals with type 2 diabetes (T2D). Although relationships between diabetes fatalism (DF) and outcomes have been established in cross-sectional data, gaps remain regarding its longitudinal effect on clinical outcomes and quality of life (QOL). This study used results from an RCT to examine the longitudinal impact of DF on clinical outcomes and QOL in African Americans (AA) with T2D. Data were collected from AA adults (n=200) with poorly controlled T2D (HbA1c ≥8%) randomly assigned to one of two groups and received 12 sessions of telephone-delivered diabetes knowledge/skills training or usual care. HbA1c, systolic blood pressure, diastolic blood pressure, physical health-related (PCS), and mental health-related (MCS) QOL were measured at baseline, 3-, 6-, 9-, and 12 months. DF was also measured at all time points with a validated 12-item DFS. DF was investigated using validated scoring of the entire scale and the emotional distress subscale. Longitudinal mixed models with random effects were run for each of the five outcomes, adjusting for treatment, time, treatment-by-time interaction, and baseline scores of the outcome of interest. Participants were primarily female and unemployed. A statistically significant negative relationship was found between the total DFS and MCS over time (β= -0.01, 95% CI -0.17, -0.03). There was also a significant longitudinal relationship between the emotional subscale of the DFS and HbA1c (β=0.02, 95% CI 0.004, 0.04); PCS (β= -0.16, 95% CI -0.27, -0,06), and MCS (β= -0.23, 95% CI -0.34, -0.11). Higher diabetes fatalism is associated with lower MCS over time. Higher scores on the emotional distress subscale of DFS are associated with higher HbA1c, lower PCS, and lower MCS over time. This study establishes that the effect of diabetes fatalism on diabetes outcomes is persistent over time, and the emotional distress component is particularly detrimental to diabetes outcomes over time.

Disclosure

S.C. Iregbu: None. R.J. Walker: None. L.E. Egede: None.
1872-LB: Therapeutic Potential of HM15275, a Novel Long-Acting GLP-1/GIP/GCG Triple Agonist, in Animal Models of Heart Failure
Authors: YE BYEONGJIN , KIM WONKI , MYEONG LEE SEON , KIM JEONG A. , KIM EUNSEON , BAE SUNGMIN , HYUN LEE SANG , YOUNG CHOI IN
Published: June 2024

Introduction & Objective: Obesity significantly increases the risk of cardiovascular death and is a leading cause of heart failure with preserved ejection fraction (HFpEF). Considering these outcomes, the purpose of this study is to evaluate whether HM15275, a novel long-acting GLP-1/GIP/GCG triple agonist, could alleviate heart failure (HF)-related symptoms in various animal models of HF.

Methods: To investigate therapeutic effects of HM15275 in HF animal models, we used the monocrotaline (MCT)-induced HF rat model to induce HF caused by pulmonary arterial hypertension (PAH), which is one of the major contributing factors to HF. Second, isoproterenol (ISO)-induced HF mouse model was used to induce HF with cardiac dilation and ventricular dysfunction through the increase in cardiac hypercontractility. Finally, we used a high fat diet (HFD) + nitrol-arginine methyl ester (L-NAME) mouse model of HFpEF, induced by obesity and hypertension. HM15275 was administrated for 2 to 5 weeks after model induction. Semaglutide (SMG) and tirzepatide (TZP) were used as comparative control.

Results: In three HF animal models, HM15275 significantly improved cardiac hypertrophy (-66.5% in MCT-induced HF model, -12.6% in ISO-induced HF model, -28.8% in HFD + L-NAME model) compared to other incretin drugs, SMG and TZP. Interestingly, HM15275 significantly improved exercise capacity (+313.9%) and arterial oxygen saturation (+13.8%) and reduced myocardial fibrosis and cardiomyocytes size compared to SMG and TZP in MCT-induced HF rat model. Also, in HFD + L-NAME mouse model, HM15275 remarkably changed multiple biomarkers of cardiovascular risk, including body weight, blood glucose, levels of lipids, and physical limitations.

Conclusion: HM15275 significantly improved exercise intolerance, cardiac hypertrophy, and fibrosis in HF murine models, compared to SMG and TZP, supporting that it could be a novel therapeutic option for HF patients.

Disclosure

B. Ye: None. W. Kim: None. S. Lee: None. J.A. Kim: None. E. Kim: None. S. Bae: None. S. Lee: None. I. Choi: None.
1874-LB: PG-102, a Bivalent GLP-1R/GLP-2R Agonist, Protects ß-Cell Mass and Enhances Glycemic Control in Obese db/db Mice, Showing Superiority over Semaglutide, Tirzepatide, and Retatrutide
Authors: WON KIM SAE , YANG SANG-IN , SUNG YOUNGCHUL
Published: June 2024

PG-102, a first-in-class heterodimeric Fc fusion protein, simultaneously targets GLP-1R and GLP-2R. In this study, we assess the efficacy of PG-102 against established comparators - semaglutide, tirzepatide, and retatrutide - in severely hyperglycemic, obese db/db mice. Based on our dose response findings, we chose 30 nmol/kg as the optimal PG-102 dose for maintaining normoglycemia in subsequent comparative studies. Strikingly, at the same dosage and regimen, PG-102 surpassed all comparators in reducing blood glucose and HbA1c levels. It was also worth noting that PG-102 was uniquely capable of achieving and sustaining normoglycemia at the end of the study. Histopathological and immunohistochemical analysis of pancreatic islets revealed that PG-102 treatment led to the largest islet mass with the highest percentage of insulin-positive β-cell area along with the lowest percentage of glucagon-positive α-cell area among the treatment groups. We also observed reduced macrophage infiltration into pancreatic islets and peri-pancreatic adipose tissue. These results demonstrate that PG-102’s superior glycemic control may be due to a combination of better protection of β-cell and reduction in islet inflammation. Collectively, our study provides the rationale for advancing the clinical investigation of PG-102.

Disclosure

S. Kim: Employee; ProGen. Co., Ltd. S. Yang: Employee; Progen. Y. Sung: Advisory Panel; Progen Co., Ltd.
1882-LB: Efficacy and Safety Outcomes with Once-Weekly Insulin Icodec vs. Once-Daily Insulin Degludec in Type 1 Diabetes According to Glycemic Variability—ONWARDS 6 Post Hoc Analysis
Authors: IRACE CONCETTA , BEGTRUP KAMILLA , FRAGÃO MARQUES MARIANA , WATT SARA K. , KLONOFF DAVID C.
Published: June 2024

Introduction & Objective: ONWARDS 6 assessed the efficacy and safety of once-weekly insulin icodec (icodec) vs once-daily insulin degludec (degludec) in adults with type 1 diabetes (T1D). This post hoc analysis evaluated the impact of glycemic variability on efficacy and safety outcomes.

Methods: Outcomes were assessed across coefficient of variation (CV) subgroups (≤36% and >36%) based on CGM data from week 0-2.

Results: Estimated change in A1C with icodec vs degludec from baseline to week 26 was similar regardless of CV subgroup. In both arms, a numerically higher proportion of people with CV ≤36% vs CV >36% achieved A1C <7.0% at week 26. Estimated rate ratios (icodec/degludec) of combined clinically significant or severe hypoglycemia and CGM-based clinically significant hypoglycemic episodes were similar regardless of CV subgroup (Table). In both arms, hypoglycemia rates were numerically lower for people with CV ≤36% vs CV >36%. Time below range (<70 mg/dL and <54 mg/dL) during weeks 22-26 in the CV ≤36% subgroup was below recommended targets (<4% and <1%, respectively) and comparable between arms.

Conclusion: Similar to degludec, when used as part of a basal-bolus regimen in T1D, once-weekly icodec may offer a lower risk of hypoglycemia for people with low glycemic variability (CV ≤36%) than for those with high glycemic variability (CV >36%).

Disclosure

C. Irace: Board Member; Abbott, Roche Diabetes Care, Novo Nordisk, Medtronic. K. Begtrup: Employee; Novo Nordisk A/S. M. Fragão Marques: None. S.K. Watt: Employee; Novo Nordisk. D.C. Klonoff: Consultant; Afon Technology Ltd, Better Therapeutics, Inc, Glucotrack, LIfecare, Nevro Corp., Novo Nordisk, Samsung, Thirdwayv Inc.

Funding

Novo Nordisk A/S
1885-LB: Status of Irrational Prescription of Oral Antidiabetic Drugs (OADs) Based on eGFR in Elderly Type 2 Diabetes Patients and the Related Affecting Factors
Authors: LI TINGZHI , SHAO YUAN , LUO WEN , ZHU JINGJING , LIU ZHIGU , XU WEN , ZENG LONGYI
Published: June 2024

Objective: To explore the current status of irrational prescription of OADs in elderly T2D patients based on eGFR and the related affecting factors.

Methods: Data from 219 patients over 65 years old with established T2D and treated on OADs who admitted to our department in 2023 were retrospectively analyzed. The irrational prescription was defined as the doses of OADs were not reduced or OADs were not discontinued based on eGFR level before admission. The patients were therefore divided into the rational prescription (RP) or irrational prescription (IRP) group. The clinical characteristics were compared between groups, and the related affecting factors for irrational prescription were analyzed with multivariate logistic regression model.

Results: Among these patients [mean age: 72.2 years old; mean duration of diabetes: 11.3 years; mean HbA1c: 7.8%; 46 (21%) with eGFR<60 ml/(min·1.73m2) ], the most frequently used OADs were biguanides (80.4%) and sulfonylureas (43.8%). And 37 (17%) patients were in the IRP group. Compared with the RP group, patients in the IRP group had higher serum creatinine (144.3±45.8 vs. 67.6±20.4 umol/L, P<0.001), lower eGFR [39.3±12.4 vs. 85.0±14.2ml/(min·1.73m2), P <0.001], and treated with more OADs (2.2±0.8 vs. 1.9±0.7, P<0.05). Multivariate logistic regression model showed that the number of OADs (OR: 4.14, P<0.05) and eGFR (OR: 0.802, P<0.001) were the affecting factors for irrational prescription.

Conclusions: The irrational prescription of OADs were common in elderly T2D patients. The number of OADs used and lower eGFR were the risk factors accounting for the irrational prescription in this papulation.

Disclosure

T. Li: None. Y. Shao: None. W. Luo: None. J. Zhu: None. Z. Liu: None. W. Xu: None. L. Zeng: None.
1899-LB: The Predictors and Management of Eating Disorders in Adult Patients with Type 1 Diabetes Mellitus
Authors: SASMAZER BASAK , YILDIZ MEVHIBE I. , KELES SUKRU , OGUZ SEDA H. , SENDUR SULEYMAN N. , ÜNLÜTÜRK UGUR , GÜRLEK ALPER , ERBAS TOMRIS , DAGDELEN SELCUK
Published: June 2024

Introduction & Objective: Eating disorders are a common issue in T1DM. The use of diabetes technologies in this patient group is controversial. In this study, we investigated the impact of eating disorders on the clinical course of T1DM and how insulin pumps affect treatment goals.

Methods: In a prospective, case-control study, the Diabetes Eating Problem Survey-Revised (DEPS-R) was used as a screening tool for diabetes-specific eating disorders in T1DM. A total score of ≥20 indicates a high risk for eating disorders. All patients were divided into 2 groups based on DEPS-R scores: those at high risk for eating disorders (n:42 cases, F/M: 26/16, age: 26.5 years, disease-duration: 11.5 years, HbA1c: %8.4, rates of minor hypoglycemic events >1 per week: %57.1, history of major hypoglycemic events on treatment: %11.9, hypoglycemia unawareness: %11.9) and those not at high risk (n:75 controls, F/M: 48/27, age: 29 years, disease-duration: 16 years, HbA1c: %7.5, rates of minor hypoglycemic events >1 per week: %60, history of major hypoglycemic events on treatment: %22.7, hypoglycemia unawareness: %13.3). Patients with confirmed or suspected Munchausen Syndrome were excluded. These 2 groups were compared in terms of clinical predictors, complications, and comorbidities. Patients at high risk for eating disorders using insulin pumps were compared with those not using pumps in terms of HbA1c, glycemic variability, and hypoglycemia.

Results: Younger age, shorter disease duration, and higher HbA1c are associated with a higher risk of eating disorders. When cases with DEPS-R scores ≥20 were compared as active pump users (n:13) versus MDI (n:29), pump provides lower HbA1c (%7.8 vs %9.4, p=0.005), lower major hypoglycemic events (%0 vs %17.2, p=0.302), and lower glycemic variability (0.66 vs 0.90, p=0.041).

Conclusion: When Munchausen Syndrome is excluded, we suggest with these data that insulin pump therapy is also safe and efficient for patients with high risk of eating disorders in T1DM.

Disclosure

B. Sasmazer: None. S. Keles: None. U. Ünlütürk: None. A. Gürlek: None. T. Erbas: None. S. Dagdelen: None.