bluuebunny/crossref_metadata_2025 huggingface dataset:
385-P: MDSC-Mediated Neutrophil Extracellular Traps–Based Targeting of Diabetic Vasculopathy—Dapagliflozin for Vascular Remodeling in Diabetic Nephropathy
Authors: CHEN KEYU , GAO ZEZHENG , WANG HAN , CHENG TANG , LI XIUYANG
Published: June 2024

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide, and its pathogenetic mechanism is closely associated with vascular endothelial dysfunction. Myeloid-derived suppressor cells (MDSCs) recently have been found to be participated in diabetic microangiopathy, especially DN, which can promote beneficial vascular remodeling by releasing neutrophil extracellular traps (NETs) and removing senescent vascular endothelium. Therefore, targeting MDSC-NETs may also be an important mechanism for dapagliflozin to ameliorate DN. Focusing on this mechanism, based on the KKay mice model of spontaneous DN, we combined phenotyping and electron microscopy to obtain the evidence that dapagliflozin was effective in ameliorating urine albumin creatine ratio and the structural damage of glomerular vascular endothelium.Then through immunohistochemistry, flow cytometry, quantitative cytokine antibody array, metabolomics, proteomics, and other multi-omics correlation analyses, to find that dapagliflozin significantly increased M-MDSC and PMN-MDSC levels in the peripheral blood of KKay mice. Dapagliflozin was found to improve glomerular endothelial function and hemodynamics by NETs-formatting, leukocyte transendothelial migration, complement and coagulation cascades, VEGF-JAK-STAT3 pathway, and reduced vascular-related pro-inflammatory cytokines such as CCL4, IL-22, IL23, TREM-1, CCL17, IGFBP5, and TGFb1. Meanwhile, dapagliflozin regulates the metabolism of amino acids and phospholipids represented by L-glutamine and phosphatidylcholine in renal tissues, attenuates the metabolic inflammatory state of glomerular endothelium, and promotes vascular repair and remodeling.

Disclosure

K. Chen: None. Z. Gao: None. H. Wang: None. T. Cheng: None. X. Li: None.
4-OR: Fat Contents in Pancreatic Body and Liver Are Synergistic Risk Factors for Impaired Glucose Regulation in PCOS
Authors: SHAN CHANG , YU JIE , ZHU YU-CHEN , ZHAO JIAN , WANG LI-HUI , LI YU-SHAN , LIN SI-YU , LIU WEI , LU QING , TAO TAO
Published: June 2024

Introduction & Objective: Women with polycystic ovary syndrome (PCOS) are more prone to glucose metabolic abnormalities, which is thought to be related to increased visceral adiposity. This study aimed to evaluate the relationship between fat deposition in the pancreas and liver and glucose metabolism in PCOS.

Methods: This study included 160 women with PCOS diagnosed according to the Rotterdam 2003 criteria between April 2019 and September 2022. All participants underwent the anthropometric and biochemical assessments including an oral glucose tolerance test. Magnetic resonance imaging-proton density fat fraction was used to measure fat deposition in the pancreas and liver.

Results: Pancreatic interlobular fat volume, pancreatic body fat content and liver fat content were significantly higher in PCOS with diabetes than normal glucose tolerance (P < 0.05). Increased pancreatic body fat [OR 2.21 (95% CI 1.01 - 4.85), P = 0.047] and hepatic average fat [OR 2.92 (95% CI 1.13 - 7.51), P = 0.026] were independently associated with higher risks for impaired glucose regulation (IGR). Patients with high pancreatic body fat and high hepatic average fat had increased risk for IGR after multiple confounding adjustments [OR 5.49 (95% CI 1.63 - 18.47), P = 0.006]. Combining pancreatic body fat and hepatic average fat with age, BMI, WHR, TG and FAI, the AUC for predicting IGR in PCOS was 0.789 with a sensitivity of 0.713 and a specificity of 0.800.

Conclusion: Fat contents in the pancreatic body and liver are synergistic risk factors for IGR in PCOS.

Disclosure

C. Shan: None. J. Yu: None. Y. Zhu: None. J. Zhao: None. L. Wang: None. Y. Li: None. S. Lin: None. W. Liu: None. Q. Lu: None. T. Tao: None.

Funding

National Natural Science Foundation of China (82170807, 82370797); the Natural Science Foundation of Shanghai (12ZR1417800); the Shanghai Sailing Program (21YF1425300); the National Nature Promotion Project, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine (RJTJ23-ZD-005); the Bethune Charitable Foundation (J202103E006); the Shanghai Medical and Health Development Foundation (SHMHDF DMRFP_II_10) and the Medical Guidance Science and Technology Support Projects of Shanghai Municipal Science and Technology Commission (18411968700).
416-P: Variability of Metabolic Risk Factors for Kidney Function Decline in Diabetes Compared with Nondiabetes—A Cluster Analysis of Community-Based Prospective Cohort Study
Authors: RYANG SOREE , MI KIM JEONG , IM MYUNGSOO , KIM DOOHWA , AH YOON SANG , KIM JINMI , SOO KIM SANG
Published: June 2024

Introduction & Objective: We aimed to identify different patterns of estimated glomerular filtration rate (eGFR) trajectories depending on diabetes status using long-term prospective cohort and to find the association and variability between risk factors, and patterns of eGFR trajectories.

Methods: At baseline, 2,084 participants were recruited from the Korean Genome and Epidemiology Study, followed up for 10 years. We divided participants into two groups based on their diabetes status. We used clustering trajectory analysis to identify different eGFR trajectory patterns and used logistic regression to identify association between trajectories and variability of chronic kidney disease (CKD) risk factors.

Results: We identified four distinct patterns of eGFR trajectories. About 4% of participants were belonged to rapid eGFR decline cluster, with more rapid decline rate compared to nondiabetes group. In diabetes group, systolic blood pressure (sBP) was associated with rapid eGFR decline at cross-sectional and longitudinal analysis (OR 2.58 [95% CI 1.07-6.23], p=0.035 and 3.34 [95% CI 1.03-6.02], p=0.043).

Conclusion: There was a difference in rate of kidney function decline according to diabetes status. Among CKD risk factors, sBP was important risk factor for rapid eGFR decline aspect baseline and variability in diabetes.

Disclosure

S. Ryang: None. J. Kim: None. M. Im: None. D. Kim: None. S. Yoon: None. J. Kim: None. S. Kim: None.

Funding

Korean Diabetes Association and National Research Foundation of Korea (2019F-8)
422-P: Ferritin and COVID-19 among Dialysis Patients with Diabetes
Authors: QUANDELACY TALIA , HU MING , WANG YUEDONG , KOTANKO PETER , CONWAY REBECCA B.
Published: June 2024

Early in the COVID-19 pandemic, severe hyperferritinemia, independent of inflammation, manifested as a laboratory characteristic prognostic of poor COVID-19 outcomes, including death. To determine the association between ferritin and COVID-19 infection, hospitalization and mortality in dialysis patients w/ diabetes, we followed 114,881 in-center hemodialysis patients w/ diabetes from January 2020 to March 2022. For incident COVID infection, average ferritin levels from one year to two weeks prior to RT-PCR determined COVID-infection (days-365,-14) were used as baseline. Change in ferritin was defined as the difference between the baseline average and two weeks prior average (-14,0) to the PCR positive test date. For non-infected patients, a PCR test date was randomly chosen. Logistic regression assessed the association of ferritin and change in ferritin w/ COVID-19 infection, hospitalization and mortality, adjusting for age, sex, race, vaccination status, vintage, and lab values. During follow-up, the cumulative incidence or COVID-19 was 23%; in the infected, 33% of the population was hospitalized and 11% died. In multivariable adjusted analysis, higher baseline ferritin (p<0.01) and change in ferritin (p<0.001) were linked w/ increased risk of COVID-19 infection. However, in the infected, neither baseline (p=0.13) nor change in ferritin (p=0.07) were linked w/ hospitalization. Positive change in ferritin, but not baseline ferritin (p=0.85), showed a trend towards an increased mortality risk (p=0.06). Other significant clinical risk factors were lower hgb (p<0.001) for COVID-19, higher baseline NLR (p<0.05) and not being vaccinated (p<0.001) for hospitalization, and higher neutrophil to lymphocyte ratio (<0.001) for mortality. Our data suggest baseline and rise in ferritin are associated w/ risk of COVID-19 but show a weaker relationship w/ hospitalization and death. NLR, which is also indicative of inflammation, is a stronger risk factor for hospitalization and mortality in patients w/ diabetes.

Disclosure

T. Quandelacy: None. M. Hu: None. Y. Wang: None. P. Kotanko: Other Relationship; Fresenius Medical Care. R.B. Conway: None.
424-P: Persons with Type 2 Diabetes Who Had Macroalbuminuria Prior to Impaired Glomerular Filtration Exhibited Increased Arteriolar Hyalinosis
Authors: SUZUKI AKIHIKO , MORIYA TATSUMI , MATSUBARA MADOKA , HAYASHI AKINORI , MIYATSUKA TAKESHI
Published: June 2024

There is a certain number of people with diabetes who have decreased GFR without albuminuria. Diabetic kidney disease is comprehensive concept including typical and atypical diabetic nephropathy including such cases. However, it is still unknown which histological parameters precisely predict increased albuminuria or reduced GFR in persons with type 2 diabetes. To address this, we hypothesized that index of arteriolar hyalinosis (IAH) could be a predictor for onset of macroalbuminuria and eGFR<60 mL/min/1.73 m2 (chronic kidney disease, CKD) during early diabetic nephropathy. The subjects consisted of 34 persons with type 2 diabetes (22 men; age, 46±9 years; eGFR 92.4±18.2 mL/min/1.73 m2, 17 normoalbuminuria, 17 microalbuminuria) who underwent percutaneous renal biopsy. These subjects were divided into 3 groups, onset of macroalbuminuria in advance (MA; n=9), onset of eGFR<60 in advance (G; n=8) and no onset of CKD (C; n=17) during the observation period (19±6 year). Light and electron microscopy-based morphometric analyses were performed to quantitatively evaluate glomerular and interstitial structural changes. There was no difference in age, sex, duration of diabetes, HbA1c, eGFR, blood pressures at the baseline among 3 groups. Urinary albumin was significantly increased in MA than G and C groups (p=0.034, 0.001, respectively). The IAH was significantly larger in MA (1.95±0.70) than G (1.41±0.44, p=0.049) and C (1.37±0.49, p=0.014) groups while other histological parameters did not reach significant extent. The logistic analysis indicated that IAH score and urinary albumin are associated with MA (p=0.028 and p=0.015, respectively). Multiple regression analysis revealed that arteriolar hyalinosis (p=0.042) and urinary albumin (p=0.025) were associated with MA group.

In conclusion, persons with type 2 diabetes having macroalbuminuria prior to reduced GFR tend to have arteriolar hyalinosis at the baseline.

Disclosure

A. Suzuki: None. T. Moriya: None. M. Matsubara: None. A. Hayashi: None. T. Miyatsuka: None.
427-P: Influence of Blood Pressure Management on the Renal Outcome in Patients Treated with SGLT2 Inhibitors and GLP1 Receptor Agonist
Authors: KOBAYASHI KAZUO , TOYODA MASAO , KAWANAMI DAIJI , TAMURA KOUICHI
Published: June 2024

Background: Both sodium glucose co-transporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP1Ras) showed robust evidences for not only cardiovascular but also renal outcomes and the combination treatment of these drugs is increasing in clinical practice. We previously reported that the preceding drug did not influence the renal outcomes in patients with these combination treatments. We also reported the importance of post blood pressure (BP) management for the renal outcomes in SGLT2i-treated patients, however, it is poorly surveyed in patients with the combination treatment.

Method: A retrospective study was conducted in 418 patients who were treated with both SGLT2i and GLP1Ra. The progression of the albuminuria stage, the eGFR decline of ≥30%, or both were defined as the renal composite outcome. The cut off value of post-treatment mean arterial pressure (post-MAP) were calculated using receiver ROC curve analysis. The patients were divided into two groups by the cut-off value and propensity score (PS) matching method was performed for comparisons between the two groups.

Results: The calculated cutoff value of post-MAP was 87.3 mmHg and the patients were divided into two groups: 281 patients in post-MAP≥87.3 group and 137 patients in post-MAP<87.3 group. Of the 111 PS-matched patients in each group, the renal composite outcome after the combination treatment was observed in 38 patients (34.2%) in post-MAP≥87.3 group, which was significantly higher than in 18 patients (17.1%) in post-MAP<87.3 group (p=0.005). The progression of albuminuria stage was significantly more frequent in post-MAP≥87.3 group (23.4%) than post-MAP<87.3 group (8.1%) (p=0.004), however no significant difference was observed for the eGFR decline of ≥30%.

Conclusion: Poor BP management after combination treatment of SGLT2i and GLP1Ra treatment worsened the renal composite outcomes, especially the progression of albuminuria stage.

Disclosure

K. Kobayashi: None. M. Toyoda: None. D. Kawanami: None. K. Tamura: None.
434-P: Type 2 Diabetes Rather than the Presence of Significant Coronary Stenoses Is Associated with Quality of Life in Angiographied Coronary Patients
Authors: RATZ MAGDALENA , VOGEL JOHANNES , ELSNER PASCAL , PLATTNER THOMAS , VONBANK ALEXANDER , MADER ARTHUR , LARCHER BARBARA , LEIHERER ANDREAS , MUENDLEIN AXEL , FRICK MATTHIAS , DREXEL HEINZ , SAELY CHRISTOPH H.
Published: June 2024

Chronic medical conditions such as type 2 diabetes (T2DM) or coronary artery disease (CAD) and their treatment have a crucial impact on patients’ daily life. The EQ-5D-5L questionnaire is a validated and widely used tool to measure the health-related quality of life (HRQL). We investigated and compared the HRQL in patients with or without T2DM and CAD. We included 481 consecutive patients undergoing coronary angiography for the evaluation of established or suspected stable CAD in a tertiary care setting in Central Europe. Patients’ HRQL was measured using the EQ-5D-5L, comprising the EQ index calculated from the domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. A response rate of 88.1% was achieved. From our patients, 166 (34.5%) had T2DM according to ADA criteria, and 254 (52.8%) had significant CAD with stenoses ≥50% at angiography. Patients with T2DM showed significantly lower EQ index values than patients without T2DM (0.891 [IQR=0.783-0.970]) vs. 0.943, [IQR=0.861-1.0], p=0.002)). Regarding the different dimensions of the questionnaire, patients with T2DM reported to have significantly more problems with anxiety and depression (p=0.002) and mobility (p<0.001) than nondiabetic patients. EQ index values in contrast did not differ significantly between patients with vs. those without significant CAD. Accordingly, in analysis of covariance T2DM (F=7.38, p=0.007) but not significant CAD (F=1.74, p=0.183) predicted EQ index values after adjustment for age, sex and body-mass-index. We conclude that T2DM rather than the presence of significant CAD is associated with quality of life in angiographied coronary patients.

Disclosure

M. Ratz: None. J. Vogel: None. P. Elsner: None. T. Plattner: None. A. Vonbank: None. A. Mader: None. B. Larcher: None. A. Leiherer: None. A. Muendlein: None. M. Frick: None. H. Drexel: None. C.H. Saely: None.
459-P: Association of Intraoperative Mean Glucose with Clinical Outcomes in Patients with Acute Ischemic Stroke Treated by Mechanical Thrombectomy
Authors: WENG JIAHAO , ZHENG XUEYING , LUO SIHUI , ZHOU YONGWEN , ZHANG HONGQIANG , WANG XULIN , SHI JIE , WENG JIANPING , WANG CHAOFAN , ZHANG FENG , ZHANG PAN , XIA YUE , SUN WEN
Published: June 2024

Introduction & Objective: Poststroke hyperglycemia is common and associated with adverse outcomes for patients with acute ischemic stroke (AIS). However, the evidence of glucose level during mechanical thrombectomy (MT) are limited. This study aimed to investigate the association between intraoperative glucose level based on continuous glucose monitoring (CGM) system and clinical outcomes.

Method: In this single-center, retrospective and observational study, we consecutively included AIS patients treated by MT within 24 hours from symptom onset. All subjects received a CGM system iPro2® when they arrived at the interventional room. Clinical outcomes included in-hospital mortality, in-hospital neurological improvement and deterioration, 3-month function independence and mortality. Logistic regression estimated the association between intraoperative mean glucose and outcomes.

Results: A total of 123 AIS patients [women: 50 (40.65%), median age: 71 (60-78), diabetes: 25 (20.33%)] were included. During MT therapy, the median period of glucose monitoring was 1.04 hours, and the median mean glucose level was 6.87 mmol/L. Mean glucose was independently related to in-hospital mortality (OR 1.539, 95% CI 1.078-2.315, p = 0.026), 3-month mortality (OR 1.418, 95% CI 1.019-2.048, p = 0.048) and functional independence (OR 0.695, 95% CI 0.493-0.931, p = 0.023) after adjusting for potential confounders. There was no association of intraoperative mean glucose with in-hospital neurological improvement (OR 0.876, 95% CI 0.695-1.090, p = 0.242) and neurological deterioration (OR 1.159, 95% CI 0.909-1.499, p = 0.244).

Conclusion: Among AIS patients who received MT treatment, intraoperative mean glucose was associated with in-hospital mortality, 3-month adverse neurological function and mortality.

Disclosure

J. Weng: None. X. Zheng: None. S. Luo: None. Y. Zhou: None. H. Zhang: None. X. Wang: None. J. Shi: None. J. Weng: None. C. Wang: None. F. Zhang: None. P. Zhang: None. Y. Xia: None. W. Sun: None.

Funding

Clinical Medical Research Transformation Project of Anhui Province (Grant No. 202204295107020026).
46-OR: Palmitic Acid Coordinates Impaired Adipose Tissue ICOShigh Treg Immunosuppression and Systemic Metabolic Disturbance during Obesity
Authors: SU WEITONG , CUI AOYUAN , HUANG MENGYAO , LIN JING , DING DONG , ZHENG ZENGPENG , JIANG YANG , CAI GENXIANG , LI WENJING , WEI SHUANG , SHEN JIAXIN , FANG XIA , WEN JIAN , HUO YANLING , WEI XIAOYI , LI LIANJIA , LIU ZHAN , QIAN KEYU , ZHAO JIUXIANG , LI YU
Published: June 2024

Treg cells serve essential roles in immunological tolerance and tissue homeostasis remodeling. However, the precise mechanism by which Treg cells specifically regulate the immune response in adipose tissue during obesity remains largely unexplored. Here we show that Foxp3, the master transcription factor of Treg cells, is negatively regulated by CREBZF, which mediates the immunosuppression of Treg cells in visceral adipose Treg cells. We found that CREBZF was dramatically induced in Treg cells from visceral adipose tissue (VAT) of obese subjects and epididymal adipose tissue (eWAT) of mice. Interestingly, palmitic acid (PA), but not insulin or lactate, promotes the expression of CREBZF in Treg cells. Treg cell-specific CREBZF deficiency significantly attenuated high-fat high sucrose (HFHS) diet-induced obesity, hyperglycemia and insulin resistance. Moreover, CREBZF deletion exhibited ameliorated inflammation and hypertrophic morphology in eWAT and enhanced systemic energy expenditure. Furthermore, obesity induced Treg cells loss, impaired Foxp3 expression and IL-10 production were reversed by CREBZF deletion in Treg cells from eWAT of mice, suggesting a key role of CREBZF in regulating the stability and immunosuppression of Treg cells. Mechanistically, single-cell transcriptomic analysis has identified a ICOShigh Treg cell subset, which is distinct from previously characterized adipose Treg cell populations and exhibited enhanced immunosuppressive function and more accumulation in CREBZF-deficient mice. Importantly, expression levels of CREBZF are negatively correlated with Foxp3 in VAT of obese human and eWAT of mice. Collectively, these studies uncover a specific adipose ICOShigh Treg subpopulation, which plays crucial roles in palmitic acid-induced immunosuppression restriction and systemic metabolic disorders.

Disclosure

W. Su: None. A. Cui: None. M. Huang: None. J. Lin: None. D. Ding: None. Z. Zheng: None. Y. Jiang: None. G. Cai: None. W. Li: None. S. Wei: None. J. Shen: None. X. Fang: None. J. Wen: None. Y. Huo: None. X. Wei: None. L. Li: None. Z. Liu: None. K. Qian: None. J. Zhao: None. Y. Li: None.

Funding

National Key R&D Program of China (2019YFA0802502), National Natural Science Foundation of China (81925008), Shanghai Science and Technology Commission (19140903300)
461-P: Metabolic Profile Alterations in Patients with Obstructive Sleep Apnea and Type 2 Diabetes
Authors: TUNA KUBRA , CHAGANI FATIMA , DANYLUK ALEXANDRIA , KESSLER ALEEZA T.F. , HADIGAL SUSHEELA , LEEY JULIO A.
Published: June 2024

The co-occurrence of Obstructive Sleep Apnea (OSA) in individuals with Type 2 Diabetes (T2D) is well-established. Several studies have shown that T2D patients with moderate to severe OSA exhibit a more unfavorable glycemic profile. In this retrospective analysis, we conducted a chart review of 147 patients with T2D who had a sleep study. Within this cohort, 115 patients (78%) were categorized within the OSA group based on sleep study results, while 32 (28%) were classified in the no-OSA group. Both groups were similar in age, diabetes duration, and the presence of micro and macrovascular complications. Hypertension, higher BMI, and increased neck circumferences was more prevalent in the OSA group. Hemoglobin A1c (HbA1c) levels were similar prior to the initiation of sleep therapy (7.6% vs. 7.7%, P=0.8), patients who commenced positive airway pressure (PAP) therapy exhibited notable improvements in HbA1c levels, with values of 7.1% at one month (P=0.06) and 7.0% at three months post-therapy initiation from 7.6% (P=0.01). Importantly, the OSA and no-OSA groups demonstrated similar levels of serum glucose, lipid profiles, and FIB-4 scores. In summary, our findings suggest that individuals with coexisting OSA and T2D exhibit a constellation of unfavorable metabolic indicators, including increased body weight (246.5±60.2 vs 201.5±50.1 lbs, P = 0.00006 p<0.01), increased complexity of diabetes, and increased incidence of fatty liver disease. The application of PAP therapy appears promising in terms of enhancing glycemic control, even in the short term. Given the marked prevalence of concurrent OSA and T2D, it is imperative to establish more effective treatment strategies for these individuals, who are predisposed to a higher risk of metabolic and cardiovascular diseases.

Disclosure

K. Tuna: None. F. Chagani: None. A. Danyluk: None. A.T.F. Kessler: None. S. Hadigal: None. J.A. Leey: None.

Funding

National Institutes of Health (UL1TR001427)
475-P: Peroxisome Proliferator-Activated Receptor Delta (PPARδ)—A Key Modulator in the Pathogenesis of Diabetes Mellitus and Mycobacterium Tuberculosis Comorbidity
Authors: ALSAEED HALEMAH , ALMULLA FAHD , AHMAD RASHEED , ALRASHED FATEMA
Published: June 2024

The interplay between lipid metabolism and immune response in macrophages plays a pivotal role in various infectious diseases, notably tuberculosis (TB). Herein, we illuminate the modulatory effect of heat-killed Mycobacteria tuberculosis (HKMT) on macrophage lipid metabolism and its implications on the inflammatory cascade. Our findings demonstrate that HKMT potently activates the lipid scavenger receptor, CD36, instigating lipid accumulation. While CD36 inhibition mitigated lipid increase, it unexpectedly exacerbated the inflammatory response, marked by elevated CCL2 secretion. Intriguingly, this paradoxical effect was linked to an upregulation of PPARδ, distinct from its PPAR counterparts. Functional analyses employing PPARδ modulation revealed its central role in regulating both lipid dynamics and inflammation, suggesting it as a potential therapeutic target. Moreover, peripheral blood mononuclear cells (PBMCs) from diabetic individuals, a demographic at amplified risk of TB, exhibited heightened PPARδ expression and inflammation, further underscoring its pathological relevance. Targeting PPARδ in these cells effectively dampened the inflammatory response, offering a promising therapeutic avenue against TB, especially for those with diabetes.

Disclosure

H. AlSaeed: None. F. Almulla: None. R. Ahmad: None. F. Alrashed: None.

Funding

Kuwait Foundation for the Advancement of Sciences (RA CB-2023-017)
491-P: Transplantation of Dental Pulp Stem Cells Ameliorates Diabetic Muscle Atrophy and Inflammation and Improves Diabetic Peripheral Neuropathy
Authors: NARUSE KEIKO , OMI MAIKO , HATA MASAKI , NAKAMURA NOBUHISA , MIYABE MEGUMI , SASAJIMA SACHIKO , OZAKI REINA , OZAWA SHOGO , TAKEBE JUN , MATSUBARA TATSUAKI
Published: June 2024

Objectives: Diabetic peripheral neuropathy is associated with neurogenic muscle atrophy. The development of successful therapies for nerve damage and muscle atrophy must be needed for patients with DPN. In this study, we investigated the effects of dental pulp stem cell (DPSC) transplantation on skeletal muscles in streptozotocin (STZ)-induced diabetic rats.

Methods: DPSCs were isolated and expanded from dental pulp of 6-wk old Sprague-Dawley rats. Cultured DPSCs were transplanted into the unilateral hindlimb skeletal muscles of normal and streptozotocin-induced diabetic rats. Four weeks after DPSC transplantation, the impacts of DPSC transplantation on hindlimb skeletal muscles and peripheral nerves were examined.

Results: Diabetic rats showed significant decreased the muscle fiber cross-sectional area and increased the CD68-positive inflammatory cell infiltration in gastrocnemius muscles, which were ameliorated by DPSC transplantation. Gene expression analyses revealed that DPSC transplantation increased PGC1α and suppressed atrogin-1 and TNF-α in diabetic skeletal muscles. DPSC transplantation significantly ameliorated decreased-FGF2 gene expression with the improvement of motor and sensory nerve conduction velocities in diabetic rats.

Conclusions: We identiﬁed that DPSC transplantation into hindlimb skeletal muscle could ameliorate diabetic muscle atrophy and inflammation and improve diabetic peripheral neuropathy.

Disclosure

K. Naruse: None. M. Omi: None. M. Hata: None. N. Nakamura: None. M. Miyabe: None. S. Sasajima: None. R. Ozaki: None. S. Ozawa: None. J. Takebe: None. T. Matsubara: None.
50-OR: Metabolic Dysfunction Attenuates D-dopachrome Tautomerase (DDT) Expression in the Heart—A Key Mechanism Exacerbates Myocardial Post-ischemic Injury
Authors: LI LISHA , QI YADAN , CUI NI , LENG LIN , WU HONG , BUCALA RICHARD , QI DAKE
Published: June 2024

Metabolic abnormalities affect clinical recovery and long-term survival in patients with acute myocardial infarction, but the underlying mechanisms remain unclear. D-dopachrome tautomerase (DDT) in cardiomyocytes protects the heart from injury during hypoxia-ischemia in mice. Our present study found that metabolic dysfunction induced by high fat diet (HFD) was associated with reduced cardiac DDT expression and aggravated cardiac injury following ischemia-reperfusion. Supplementation of DDT prior to ischemia decreased post-ischemic injury in these hearts, suggesting that DDT reduction is an important mechanism regulating post-ischemic cardiac injury associated with metabolic dysfunction. Among all the major fatty acid species in HFD, high palmitic acid (PA) triggered the expression and activation of protease activated receptor 2 (PAR2), which upregulated the transcriptional factors, CREB1 and FOXO1 leading to downregulation of DDT expression in the heart. PAR2 stimulated ERK phosphorylation, thereby upregulating CREB1 phosphorylation. Attenuation of CREB by siRNA significantly decreased FOXO1 expression and accumulation in the nucleus, thereby reducing cardiac DDT expression. Accordingly, PAR2 deficient mice exhibited normal ERK and CREB phosphorylation and DDT levels in the heart following HFD and reversed cardiac function recovery following reperfusion. Overall, our data reveal for the first time a novel role for DDT in mediating myocardial ischemia-reperfusion injury associated with metabolic dysfunction.

Disclosure

L. Li: None. Y. Qi: None. N. Cui: None. L. Leng: None. H. Wu: None. R. Bucala: None. D. Qi: None.

Funding

This study was supported by National Sciences and Engineering Research Council of Canada (NSERC: RGPIN-2017-04542) and Canadian Institutes of Health Research (CIHR Project Grant: PJT-156116).
504-P: Prevalence and Risk Factors of Diabetic Retinopathy in South Korea’s Population
Authors: LEE MIN-KYUNG , HAN KYUNGDO , KWON HYUK-SANG
Published: June 2024

Introduction & Objective: Diabetic retinopathy is a long-term microvascular complication of diabetes, and its prevalence has increased over recent years worldwide. The purpose of this study is to provide national representative statistics on the epidemiology and risk factors of diabetic retinopathy in Korean diabetic patients.

Methods: We conducted a cross-sectional study using the Korea National Health and Nutrition Examination Survey between 2017 and 2020. Participants aged ≥40 years who diagnosed with diabetes mellitus were analyzed. The prevalence of diabetic retinopathy during the entire period was estimated using the weighted percentage as mean and standard error. We also assessed adjusted risk factors for diabetic retinopathy using the logistic regression models.

Results: Among a total of 2,221 subjects (mean age, 60.8 years; 56.85% male subjects), 451 subjects had diabetic retinopathy, and the overall weighted prevalence of diabetic retinopathy was 20.64±1.06%. The prevalence of diabetic retinopathy tended to increase with higher HbA1c levels and longer duration of diabetes (P for trend <0.001). The adjusted odd ratios for incident diabetic retinopathy were 1.348 (95% CI 0.893-2.037), 2.012 (95% 1.385-2.922), 2.799 (95% CI 1.777-4.408), 3.406 (95% CI 1.971-5.886), and 5.85 (95% CI 3.273-10.457) for HbA1c levels of 6.5-6.9%, 7.0-7.9%, 8.0-8.9%, 9.0%-9.9% and ≥10.0%, respectively. And they were 1.499 (95% CI 0.992-2.267), 2.066 (95% 1.385-3.082), 20.396 (95% CI 1.542-3.724), and 3.622 (95% CI 2.386-5.498) for non-awareness, diabetes duration of <5 years, 5-10 years, 10-15 years, and ≥10 years, respectively.

Conclusion: The prevalence of diabetic retinopathy was estimated to increase in patients with poor control and long duration of diabetes. Hyperglycemia and diabetes duration are determinants for diabetic retinopathy in Korea's population.

Disclosure

M. Lee: None. K. Han: None. H. Kwon: None.

Funding

The National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2021R1A2C2013890 and 2022R1F1A061069)
511-P: Serum Tsukushi Is Associated with HDL Dysfunction in Type 2 Diabetes and Nonalcoholic Fatty Liver Disease
Authors: TAN KATHRYN C.B. , LAM SUM , LUI DAVID T. , YI FONG HO , WONG YING , SHIU SAMMY , HO LEE CHI
Published: June 2024

Introduction & Objective: Tsukushi (TSK) is a recently identified hepatokine and animal studies have suggested that TSK can affect systemic cholesterol homeostasis. Gain- and loss-of-function experiments in mice showed that TSK reduced circulating HDL-cholesterol (HDL-C). We therefore investigated whether TSK was associated with HDL-C and HDL function in type 2 diabetes with co-existing non-alcoholic fatty liver disease (NAFLD).

Methods: Vibration‑controlled transient elastography was performed in 565 subjects with type 2 diabetes. The degree of hepatic steatosis and fibrosis was reflected by controlled attenuation parameter (CAP) and liver stiffness (LS) respectively, and the presence of NAFLD was defined as CAP ≥248 dB/m. Serum TSK was measured by ELISA. Cholesterol efflux capacity (CEC), an indicator of HDL function, was determined by measuring the efflux of [3H]-cholesterol from RAW264.7 macrophages to apolipoprotein B-depleted serum.

Results: NAFLD was present in 430 subjects (76%). The age, proportion of male subjects and duration of diabetes were comparable between those with and without NAFLD. However, individuals with NAFLD had higher BMI (p<0.01) and serum TSK levels [97.0 ng/ml (63.8 - 136.3) versus 81.5 ng/ml (57.8 - 119.4) respectively, p<0.01], lower HDL-C (p<0.01) and CEC (18.0 ± 4.9% versus 19.1 ± 5.9% respectively, p<0.05) than those without NAFLD. Serum TSK correlated with HDL-C (r = -0.19, p<0.01) and with CEC (r = -0.16, p<0.01). Linear regression analysis showed that TSK, HDL-C and the use of thiazolidinediones were significant and independent determinants of CEC, in a model also consisting of age, sex, smoking, BMI, and the use of various anti-diabetic agents and lipid lowering therapy.

Conclusion: elevated TSK level was associated with reduced HDL-C, and HDL dysfunction with impaired CEC in type 2 diabetes and co-existing NAFLD.

Disclosure

K.C.B. Tan: None. S. Lam: None. D.T. Lui: None. H. Fong: None. Y. Wong: None. S. Shiu: None. C. Lee: None.
512-P: The Effect of Remnant Cholesterol on the Onset of Diabetes Mellitus
Authors: KANAMOTO AYUMI , MIYAKE TERUKI , FURUKAWA SHINYA , MATSUURA BUNZO , YOSHIDA OSAMU , MIYAZAKI MASUMI , SHIOMI AKIHITO , NAKAGUCHI HIRONOBU , HIROOKA MASASHI , ABE MASANORI , HIASA YOICHI
Published: June 2024

Remnant cholesterol (Rem-C) is the cholesterol content found in triglyceride-rich lipoproteins, which are produced in the metabolic process of VLDL and chylomicrons. REM-C is associated with an increased risk of cardiovascular disease and is a target of lipid-lowering therapies. Conversely, insulin resistance is linked to increased levels of Rem-C. However, the effect of Rem-C levels on the onset of diabetes mellitus (DM) has not been adequately clarified. Therefore, this study aims to examine the association between Rem-C levels and the onset of diabetes. We reviewed the records of 13,044 nondiabetic individuals (6,499 males, 6,545 females) who underwent health check-ups at least twice, with a median age of 44 (IQR 37-51) years. The observation period spanned 5.86 (0.60-16.92) years. DM onset was determined based on HbA1c≧6.5% or fasting plasma glucose≧126mg/dL. Four hundred sixty subjects developed DM. In univariate analysis, an increase in Rem-C significantly raised the risk of DM onset (HR: 1.017, 95% CI: 1.014-1.019). Similar results were obtained in multivariate analysis (adjusted HR: 1.009, 95% CI: 1.005-1.013), adjusting for gender, age, body mass index, systolic blood pressure, fasting blood glucose, alanine aminotransferase, creatinine, family history of diabetes, and smoking history.

In conclusion, a high level of Rem-C is a risk factor for the onset of DM. Therefore, Rem-C may serve as a useful surrogate marker for DM onset, and interventions, such as lifestyle guidance and drug therapy, focusing on Rem-C may help suppress the onset of DM.

Disclosure

A. Kanamoto: None. T. Miyake: None. S. Furukawa: Speaker's Bureau; Lilly Diabetes, Novo Nordisk, Mitsubishi Tanabe Pharma Corporation. B. Matsuura: None. O. Yoshida: None. M. Miyazaki: None. A. Shiomi: None. H. Nakaguchi: None. M. Hirooka: None. M. Abe: None. Y. Hiasa: None.
521-P: Association between the Hepatic Steatosis and the TyG Index in a Population of Healthy Adults in Korea
Authors: BAE LEE SANG
Published: June 2024

It has been established that the triglyceride glucose (TyG) index is a reliable indicator of insulin resistance (IR), which strongly impact to development of hepatic steatosis and non-alcoholic fatty liver disease (NAFLD). However, the relation between NAFLD and the TyG index remains not fully understood. We examined and analyzed the association between NAFLD and the TyG index in a population of healthy adults in Korea.

A total of 5158 participants who visit health promotion center, underwent blood sampling and abdominal ultrasonography were analyzed in this study. Degree of hepatic steatosis and NAFLD was classified via ultrasonograpic findings.

According to changes in the TyG index, significant changes in metabolic parameters were observed. The prevalence of NAFLD also increased proportionally with the increase in the TyG index. We also performed additional exploration using HOMA-IR with logistic regression analysis. The TyG index showed more strong predictive power for prevalence of NAFLD than HOMA-IR. Comparing the lowest and highest quartiles of the TyG index and HOMA-IR, the odds ratio for NAFLD prevalence in the TyG index was 3.11 (95% CI: 2.46-3.93; P for trend <0.01), which is higher than the value of 1.82 in HOMA-IR (95% CI: 1.35-2.45; P for trend <0.01).

As a result of our study, prevalence of NAFLD showed strong association with the TyG index. Additionally, the TyG Index showed stronger predictive value for NAFLD compared to HOMA-IR.

Disclosure

S. Lee: None.
558-P: Virtual Reality to Educate Health Professional Students about the Complexity of Care in Older Adults with Type 2 Diabetes
Authors: BEVERLY ELIZABETH A. , LOVE CARRIE , LOVE MATTHEW
Published: June 2024

Introduction & Objective: Diabetes care for older adults is complex. Older adults are at increased risk for geriatric syndromes, including cognitive impairment, hearing loss, visual impairment, depression, polypharmacy, incontinence, disability, and injurious falls. To address this complexity, we created a virtual reality (VR) training for health professional students. The purpose of this single arm, pre-post-test study was to assess students’ changes in empathy, attitudes toward disability, and self-efficacy in identifying and managing elder abuse and neglect before and after participating in the VR training.

Methods: Health professional students at a large university in the Midwest were invited to participate in the VR training centered on an 80-year-old man, with a history of type 2 diabetes, a mobility disability, hearing loss, urinary incontinence, and potential dementia. Participants completed pre-post questionnaires via Qualtrics.

Results: A total of 67 health professional students participated (mean age=22.7±3.9 years, 80.6% women, 67.2% White, 20.9% Black, 9.0% Asian, 29.9% pre-medical). Surprisingly, we observed a decrease in empathy post-VR training (t=3.204, p=.002). This may reflect a potential empathy bias, such that the participants overestimated their empathy prior to the VR training but became more aware of their lack of experience in understanding different perspectives and emotions of adults with complex health issues. Next, we observed an improvement in participants’ attitudes toward disability (t= -2.799, p=.007) and an improvement in their self-efficacy to identify and manage elder abuse and neglect (t= -2.209, p=.032).

Conclusion: Findings suggest that this VR training may improve health professional students’ attitudes toward disability and self-efficacy towards identifying and managing elder abuse and neglect; more research is needed to determine its impact on empathy.

Disclosure

E.A. Beverly: None. C. Love: None. M. Love: None.

Funding

Ohio Department of Medicaid (ODM202238)
571-P: Life-Stage Specific Education for Young Adults with Diabetes—Integrating Theory into Practical Tools
Authors: JANE ROCHE MARY , SAMAI KRYSTLE , KIM STEPHANIE
Published: June 2024

Introduction: There is a lack of targeted resources to promote self-management behaviors in young adults (ages 18-30) with diabetes. Online information-seeking commonly occurs among this group for chronic disease management and support. To fill this unmet need, The Diabetes Link created an e-learning framework (“The Framework”) and utilized it to develop life-stage specific, online educational resources that result in high engagement.

Methods: The Framework incorporated Adult Learning Theory and Bloom’s Taxonomy, a model used to classify levels of educational learning outcomes, along with inputs relevant for this demographic such as resource format, length, and media type. A clinical advisory panel provided feedback to ensure materials were clinically sound and achieved learning outcomes. The Diabetes Link created four topic modules using this framework. Engagement analytics include quantitative measures of online usage.

Results: The Framework was used to develop and release materials focusing on 4 topic modules over 9 months on an online platform: Mental Health & Wellbeing, Sex & Diabetes, Relationships, and Management 101: Technology. Each topic module contains 11-20 assets, defined as videos, infographics, and peer perspectives. Each asset highlights independence, lived experiences, and practical skills. Each topic module focuses on 6-8 specific learning outcomes based on the 6 different levels of hierarchical learning, ranging from building knowledge to evaluation. From 5/11/23-12/31/23, these topic modules have reached 2228 individuals and 228 hours spent engaging with the educational resources.

Conclusion: The Diabetes Link has developed an e-learning framework that enables age appropriate online content development. Adoption of The Framework has resulted in high engagement above industry standards. The four topic modules will be tested in a pilot study to measure the relevance and impact of materials on young adults with diabetes.

Disclosure

M. Roche: None. K. Samai: None. S. Kim: Consultant; Signos, Inc.

Funding

Novo Nordisk
584-P: A Case Study Approach to Explore Barriers Associated with Uncontrolled Diabetes among Patients Receiving Care at Health Centers in the U.S. Virgin Islands
Authors: SHEEN JULIA
Published: June 2024

Introduction & Objective: The prevention and control of diabetes is a significant public health issue in the U.S. Virgin Islands (VI). This study explored the barriers associated with uncontrolled diabetes among Federally Qualified Health center patients in the VI.

Methods: This study followed a case study method of qualitative inquiry. The novelty of this study lies in its exploration of a critical public health concern within a specific and often neglected subset of the U.S. healthcare system, the VI. Existing literature focusing on diabetes prevention and control in the VI is both infrequent and sparse. Subsequently, this study addressed a major gap in the literature, about the barriers associated with uncontrolled diabetes in the VI and particularly among health center patients.

Results: It found that the overarching barriers associated with uncontrolled diabetes among patients receiving care at health centers in the VI, from the patient, provider and executive director’s perspectives included the following: (1) the social determinants of health; (2) lack of family support; (3) lack of medication adherence; (4) culture; (5) lack of access to care; (6) mental and social issues; (7) lack of patient knowledge about diabetes, and (8) lack of exercise and inability to maintain a healthy diet.

Conclusion: This study had several implications for future research, for example it presented an opportunity to explore cultural factors and patient adherence to lifestyle measures; the use of naturopathic remedies in the treatment of diabetes and emergency preparedness related to hurricanes and its impact on patients with type 2 diabetes. There were also policy implications related to healthcare provider shortages, the use of community health workers in the support of patients with type 2 diabetes and the need for the establishment of standards of care for the treatment of patients with diabetes across the lifespan.

Disclosure

J. Sheen: None.
586-P: Enhancing Diabetes Prevention through Lifestyle Modifications in Idaho
Authors: RANI RAVEEN
Published: June 2024

Introduction & Objective: In response to the escalating diabetes epidemic, the U.S. National Diabetes Prevention Program encourages lifestyle modifications among individuals at high risk of diabetes. Nationally, these interventions, aimed at causing a modest 5-7% body weight reduction, led to a remarkable 58%decline in type 2 diabetes risk among participants. This study objective was to evaluate the impact of lifestyle changes on obesity and diabetes incidence among high-risk individuals in Idaho.

Methods: This study analyzed data collected from University of Idaho Extension DPRP-enrolled participants. We enrolled 226 participants at high risk of diabetes in a year-long program focused on promoting lifestyle modifications. Inclusion criteria encompassed individuals aged 18 or older with a Body Mass Index (BMI) of ≥24 kg/m² (≥22 kg/m² for Asian individuals) and a recent blood test indicating prediabetes or a history of gestational diabetes mellitus (GDM). Using paired t-tests, we analyzed the changes in final BMI (31.4851 kg/m²) compared to initial BMI(32.5775 kg/m²) and physical activity changes among participants.

Results: The analysis revealed a statistically significant decrease in final BMI by an average of 1 kg/m²among participants. Furthermore, a notable increase in physical activity levels was observed among those that completed the year-long program, characterized by an average increase of 98minutes per week.

Conclusion: The study showcased a significant decrease in BMI, affirming the effectiveness of DPRP lifestyle intervention program.

Disclosure

R. Rani: None.
592-P: The Association of the Timing and Magnitude of Peak Physical Activity with Cardiometabolic Health Outcomes in People with Diabetes
Authors: ALOZAIRI EBAA S. , ALKANDARI JUMANA , ALSAEED DALAL , IRSHAD MOHAMMAD , ALESMAEEL BATOOL C. , ABDALLA MOHAMED , ABDULLAH MARIAM A. , GRAY STUART R.
Published: June 2024

Introduction & Objective: To investigate the association of the timing and magnitude of peak physical activity with cardiometabolic outcomes, such as glycated haemaglobin (HbA1c) and body mass index (BMI), in people with type 1 and type 2 diabetes.

Methods: We recruited 810 people with type 1 diabetes and 1381 people with type 2 diabetes to the study. Participants wore a wrist-worn accelerometer for a 7 day and the start time of the most active 5 hours (M5time) and the acceleration (physical activity) performed in this 5 hour period (M5value) quantified. Outcome variables recorded were HbA1c, total cholesterol, HDL cholesterol, LDL cholesterol, waist circumference and BMI. Associations were assessed by linear regression after adjustment for sex, age and total (24 hour) physical activity levels.

Results: In people with type 1 diabetes the M5 time was no associated with any of the outcome variables, but the M5value was associated with HbA1c (β-coefficient [95%CI], -0.19[-0.05,-0.32], p-value 0.005), HDL cholesterol (0.004,[0.001,0.007], p-value 0.016) and LDL cholesterol (-0.008[-0.001,-0.016], p-value 0.034). In people with type 2 diabetes both the M5time 0.45[0.05,0.85], p-value 0.028) and M5value (-0.23[-0.03,-0.43], p-value 0.032) were associated with HbA1c. No other associations were observed.

Conclusions: A greater amount of physical activity during the peak activity time was associated with better glycaemic control in people with type 1 and 2 diabetes, even after adjusting for total physical activity levels. Performing peak physical activity levels earlier in the day was also associated with better glycaemic control, only in people with type 2 diabetes.

Disclosure

E.S. Alozairi: None. J. AlKandari: None. D. Alsaeed: None. M. Irshad: None. B.C. Alesmaeel: None. M. Abdalla: None. M.A. Abdullah: None. S.R. Gray: None.

Funding

Kuwait Foundation for the Advancement of Sciences (KFAS), Kuwait