bluuebunny/crossref_metadata_2025 huggingface dataset:
377-P: Assessing the Counterregulatory Response to Hypoglycemia with Amitriptyline
Authors: MUSIC MEGAN B. , THOMPSON ANDREA , ILES ASHLEY , MARKSBURY ASHLEE R. , PATEL BANSI , SCHOEDER LILY A. , WOOTEN MASON , BECKNER ZACH , DEVORE MICAH H. , MACON ERICA L. , FISHER SIMON J.
Published: June 2024

Introduction & Objectives: Our laboratory previously demonstrated a beneficial effect of amitriptyline, a serotonin and norepinephrine reuptake inhibitor, in preventing impaired hypoglycemic counterregulation. We wished to extend these findings to a diabetic animal model.

Methods: Streptozotocin (STZ, 65 mg/kg IP) diabetic 10-week-old male Sprague Dawley rats were randomized to 3 groups: STZ+RS (n=7, RS=recurrent saline controls), STZ+RH (n=6, RH=recurrent hypoglycemia), and STZ+AMP+RH (n=8, AMP=amitriptyline 10 mg/kg, IP). After 3-days preconditioning, animals underwent a hyperinsulinemic (50mU/kg/min) hypoglycemic (~45 mg/dL) clamp.

Results: In response to hypoglycemia, peak epinephrine levels were blunted in STZ+RH (299±51 pg/ml) compared to STZ+RS (1084±916, p<0.01 vs STZ+RS), and did not improve significantly in STZ+AMP+RH (482±227, p=NS vs STZ+RH). Similarly, the glucagon response to hypoglycemia demonstrated a blunted response with STZ+AMP+RH (see Figure).

Conclusion: The beneficial effects of amitriptyline in restoring the counterregulatory response to hypoglycemia that were initially observed in nondiabetic model seem to be attenuated in the insulin deficient diabetic rodent model. It is concluded that chronic diabetes abrogates the beneficial effects of serotonin and norepinephrine reuptake inhibitors on the sympathoadrenal and counterregulatory responses to hypoglycemia.

Disclosure

M.B. Music: None. A. Thompson: None. A. Iles: None. A.R. Marksbury: None. B. Patel: None. L.A. Schoeder: None. M. Wooten: None. Z. Beckner: None. M.H. Devore: None. E.L. Macon: None. S.J. Fisher: None.
387-P: Finerenone Attenuates Kidney GLP-1 Receptor Downregulation in Mice with Comorbid Diabetes
Authors: TIN TRAN DUC , HONG LISA Y.Q. , KAUR HARMANDEEP , YEUNG EMILY S.H. , ADVANI SUZANNE L. , LIU YOUAN , NAGARJUN BATCHU SRI , ADVANI ANDREW
Published: June 2024

Introduction & Objective: Several new treatments have recently been shown to have kidney protective benefits in people with diabetes. Because these treatments were developed in parallel, at the time of their clinical trial participation many individuals were not receiving concurrent treatment with other therapies subsequently also found to have kidney protective benefits. Accordingly, it is unclear whether treatments recently shown to slow kidney function decline will have additive or redundant effects when used in combination. Here, we examined the effects of the mineralocorticoid receptor antagonist finerenone on kidney GLP-1 receptor (GLP-1R) expression levels in mice with comorbid diabetes.

Methods: Mice were fed a high fat diet and received a single intraperitoneal injection of streptozotocin 12 weeks into high fat diet feeding (DM-HFD mice). After 24 weeks, animals were fed high fat diet containing finerenone (100mg/kg diet) for a further 2 weeks. Kidney GLP-1R localization and expression were analyzed by RNAscope in situ hybridization and qRT-PCR.

Results: Blood glucose, HbA1c and systolic blood pressure were unaffected by 2-week treatment of DM-HFD mice with finerenone. GLP-1R mRNA was detectable in vascular smooth muscle cells of kidney arterioles, and also present in juxtaglomerular apparatus cells, being sparse or absent in other kidney cells. Kidney GLP-1R mRNA levels were reduced in DM-HFD mice and this reduction was negated by finerenone (GLP-1R:RPL13A mRNA (fold) control 1.02±0.22, DM-HFD 0.67±0.09 (p<0.05 vs. control), DM-HFD + finerenone 1.10±0.34 (p<0.01 vs. DM-HFD)).

Conclusion: Kidney GLP-1R expression is diminished in aged mice with comorbid diabetes. This reduction is negated by treatment with the mineralocorticoid receptor antagonist finerenone. Both GLP-1R agonism and finerenone have demonstrated kidney protective benefits in people with diabetes. The present findings lend mechanistic support for the additive potential of combination therapy.

Disclosure

D. Tran: None. L.Y.Q. Hong: None. H. Kaur: None. E.S.H. Yeung: None. S.L. Advani: None. Y. Liu: None. S. Batchu: None. A. Advani: None.
392-P: Gemigliptin Attenuates TGF-ß-Induced Renal Fibrosis by Inhibiting the TGF-ß/Smad3 Signaling Pathway through the Upregulation of FGF21 Expression
Authors: JUNG GWONSOO
Published: June 2024

Aim: Fibroblast growth factor 21 (FGF21), a well-known regulator of metabolic disorders, exhibits the potential to prevent renal fibrosis by negatively regulating the transforming growth factor β (TGF-β)/Smad3 signaling pathway. Gemigliptin, known as a dipeptidyl peptidase-4 inhibitor, is frequently utilized in the management of patients with type 2 diabetes. However, the protective effects of gemigliptin on renal fibrosis, particularly concerning its potential to upregulate the expression of fibroblast growth factor 21, remains incompletely understood. The purpose of this study was to investigate the gemigliptin’s renoprotective effects against TGF-β-induced renal fibrosis by enhancing the expression of fibroblast growth factor 21 in the cultured human proximal tubular epithelial cell line, HK-2.

Methods: HK-2 cells were maintained with keratinocyte-free medium according to the supplier’s recommendations, and exposed to the indicated doses of TGF-β, FGF21, and gemigliptin for 24 h. To elucidate the effect of FGF21, knockdown experiments were conducted by transfecting HK-2 cells with small interfering RNA targeting the fibroblast growth factor 21 for 24 h.

Results: Treatment of FGF21 effectively prevented TGF-β-induced renal fibrosis by attenuating TGF-β/Smad3 signaling pathway. Similarly, Gemigliptin showed protective effects against TGF-β-induced renal fibrosis by mitigating TGF-β/Smad3 signaling, which is achieved through the upregulation of FGF21 expression. However, the protective effects of gemigliptin were blocked when FGF21 expression was knockdowned in TGF-β-treated HK-2 Cells.

Conclusion: These results indicate that gemigliptin has the potential to confer protective effects against TGF-β-induced renal fibrosis by elavating FGF21 expression levels in the cultured human proximal tubular epithelial cells.

Disclosure

G. Jung: None.

Funding

National Research Foundation of Korea (RS-2023-00252005)
411-P: Extended Generalized Metabolic Fluxes (GMF) Based Digital Twins for Predicting CKD
Authors: SURIAN NAVEENAH , BATAGOV ARSEN , WU ANDREW , LAI WEN B. , DALAN RINKOO
Published: June 2024

Introduction: CKD is a prominent complication in diabetes patients. Our regulatory-approved digital twin model, HealthVector Diabetes (HVD), leverages generalized metabolic fluxes (GMF) to predict CKD within a 3-year timeframe using common biochemical and physiological parameters. HVD achieved an accuracy of 0.86 in our clinical validation studies. In this study, we aim to explore the expanded use case of HVD when incorporating specialized input parameters related to vascular dysfunction for the prediction of CKD.

Methods: A preliminary investigation involved collecting follow-up records from a previous T2DM clinical trial. Eligible patients had to be CKD-negative at baseline according to eGFR and ACR criteria and have either eGFR or ACR follow-up readings within 3 years from baseline. A total of 20 input parameters, including specialized ones (carotid intima-media thickness (CIMT), logarithmic reactive hyperemia index (lnRHI), pulse wave velocity (PWV), oxidized low density lipoprotein (ox-LDL), haptoglobin, ferritin, reactive oxygen metabolites (ROM), biological antioxidant potential (BAP), high sensitivity C-reactive protein (hs-CRP)), were gathered at baseline to calculate the GMF for predicting future CKD within 3 years.

Results: We identified 193 eligible patients based on our inclusion and exclusion criteria, with 22 developing CKD within 3 years. Extending HVD for prediction resulted in an AUC-ROC of 0.90.

Conclusion: The extension of our regulatory-approved software as a medical device digital twin model, HealthVector Diabetes continues to perform well. It accurately predicts CKD within 3 years with 90% accuracy using specialized inputs assessing vascular dysfunction.

Disclosure

N. Surian: Employee; Mesh Bio Pte. Ltd. A. Batagov: Employee; Mesh Bio. A. Wu: Employee; Mesh Bio. W.B. Lai: Employee; MESH BIO PTE LTD. R. Dalan: None.
425-P: Retrospective Analysis of Glycemic Profiles and Variabilities Using Continuous Glucose Monitoring in Elderly People with Type 2 Diabetes Undergoing Hemodialysis
Authors: HAYASHI AKINORI , MATOBA KENTA , SUZUKI AKIHIKO , MIYATSUKA TAKESHI
Published: June 2024

People with type 2 diabetes undergoing hemodialysis (T2HD) exhibit distinct glycemic profiles. The details of glycemic profiles in elderly people with T2HD, however, remain unclear. Sensor glucose levels (SGLs) were analyzed using continuous glucose monitoring (CGM) in 116 subjects with T2HD, investigating differences in clinical parameters and CGM metrics between elderly group (≥ 65 years) and non-elderly group (< 65 years). For retrospective analysis, 55 in elderly group (39 males, age 72 years, HbA1c 6.3%, glycated albumin (GA) 22.5%) and 61 in non-elderly group (41 males, age 52 years, HbA1c 6.7%, GA 19.8%) were selected. Among these, 30 (54.6%) in elderly group and 48 (78.7%) in non-elderly group were on insulin therapy (p=0.0057). While no difference was observed in HbA1c between the two groups, GA was significantly higher in elderly group (p=0.0401). Mean and SD of SGL showed no difference between the two groups, but %CV was significantly higher in elderly group (30.0±7.6% vs 37.0±7.7%, p=0.0357). There was no disparity in time in range (TIR, 70-180 mg/dL), time below range (TBR, < 70 mg/dL), and time above range (TAR, > 180 mg/dL). However, TBR (< 54 mg/dL) was significantly higher in elderly group (0.63±0.19[SE]% vs 0.32±0.18[SE]%, p=0.0499). In elderly group, 30.9% experienced all-cause hypoglycemia, and 27.3% experienced hemodialysis-induced hypoglycemia, compared to 31.2% and 16.4% in non-elderly group.

In conclusion, although there was no difference in HbA1c and mean SGL between the two groups, glycemic variability and the incidence of severe hypoglycemia were significantly higher in the elderly group.

Disclosure

A. Hayashi: None. K. Matoba: None. A. Suzuki: None. T. Miyatsuka: None.

Funding

JSPS KAKENHI(22K15674), Grants for young researchers from Japan Association for Diabetes Education and Care (2021-YNG-028)
430-P: Development and Internal Validation of Machine-Learning Algorithms for Diabetic Kidney Disease Model of People with Type 2 Diabetes Mellitus
Authors: ZHANG LIN
Published: June 2024

Objective: This study aims to establish DKD early screening model through different machine learning algorithms according to the clinical characteristics and biological indicators of type 2 diabetes patients, and compare its predictive value for DKD.

Methods: We selected 74,982 type 2 diabetes patients hospitalized in Beijing Tongren Hospital from 2013 to 2022. The collected-data included common clinical characteristics and biological indicators. 625 DKD cases was diagnosed with the increase of urine microalbumin or the decrease of eGFR and diabetes retinopathy, and 1336 cases were diagnosed as Non-DKD. Establish DKD early screening models through 7 machine learning algorithms: Deep Neural Network(DNN), RF, SVM, XGBoost, GMB, DRF, Naive Bayes.

Result: DNN were established for different feature dimensions: D0: blood routine, AUC=0.6911; D1: blood routine, DBP, SBP, WHR, AUC=0.7919; D2 : D1 dataset, biochemical indicators, AUC=0.8517. Evaluating the accuracy of the model, AUC of DNN is 0.902, while other algorithms have AUC between 0.81 and 0.88.

Conclusion: The best prediction result is D2 dataset, which is the most effective combined with biochemical indicators to predict DKD; The single blood routine index also has important value in predicting the development of DKD. DNN is the the best model compared to other machine learning algorithms.

Disclosure

L. Zhang: None.
447-P: Type 2 Diabetes Is Not a Coronary Artery Disease Risk Equivalent—Long-Term Results from a Prospective Cohort Study on Patients Who Underwent Coronary Angiography
Authors: PLATTNER THOMAS , LARCHER BARBARA , MADER ARTHUR , VONBANK ALEXANDER , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H.
Published: June 2024

Type 2 Diabetes (T2DM) and pre-existing coronary artery disease (CAD) are strong and independent risk factors for cardiovascular events, and data from large cohort studies suggest that the cardiovascular risk conferred by T2DM in the absence of CAD is equivalent to that conferred by CAD in the absence of T2DM. However, because the presence of CAD in these studies was defined clinically rather than by visualization, unrecognized subclinical CAD in T2DM patients may have biased results. We therefore prospectively investigated patients with T2DM and nondiabetic subjects in whom the baseline CAD state was diagnosed angiographically. We recorded cardiovascular events over a follow-up period of 22 years in a large cohort of 1819 patients undergoing coronary angiography for the evaluation of established or suspected stable CAD. From our patients, 595 had neither significant CAD nor T2DM (CAD-/T2DM-), 171 had T2DM but not significant CAD (CAD-/T2DM+), 701 had significant CAD but not T2DM (CAD+/T2DM-) and 352 had both T2DM and significant CAD (CAD+/T2DM+). The incidence of cardiovascular events was lowest in CAD-/T2DM- patients (24.7%). Compared to this group it was significantly higher in CAD-/T2DM+ patients (36.1%; p<0.001) and in CAD+/T2DM- patients (50.8%; p<0.001) and highest (p=0.001) in CAD+/T2DM+ patients, in whom it was higher than in CAD-/T2DM+ (p<0.001) or CAD+/T2DM- (p=0.001) patients. Importantly, CAD+/T2DM- patients were at a significantly higher risk of cardiovascular events than CAD-/T2DM+ patients (p<0.001). In Cox regression analysis the risk increase conferred by CAD was higher (adjusted (HR 2.35 [1.92-2.89]; p<0.001) than that conferred by T2DM (adjusted HR 1.54 [1.33-1.78]; p< 0.001). From our long term results we conclude that angiographically diagnosed CAD is a stronger predictor of future cardiovascular events than T2DM. T2DM is not a CAD risk equivalent.

Disclosure

T. Plattner: None. B. Larcher: None. A. Mader: None. A. Vonbank: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None. C.H. Saely: None.
457-P: Association of System Inflammation Index with Risk of Cardiovascular Mortality among Individuals with Type 2 Diabetes
Authors: LI HAN , GUO WENWEN , LI YIXUAN , ZENG TIANSHU ,   ESQ., KONG WEN
Published: June 2024

Introduction & Objective: This study aimed to examine the associations of system inflammation index, including system inflammation response index (SIRI) and system immune-inflammation index (SII), with cardiovascular mortality in adults with type 2 diabetes (T2D).

Methods: This analysis included 2,954 individuals from the National Health and Nutrition Examination Survey (NHANES) 1999-2010. Cardiovascular mortality was ascertained by linkage to National Death Index (NDI) records through 31 December 2019. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: During an average of 12.4 years of follow-up, 248 cardiovascular disease (CVD) deaths occurred. After multivariate adjustment, per one-unit increment in SIRI was significantly associated with a 16% higher risk of cardiovascular mortality (P <0.0001) in a dose-response manner (P non-linear = 0.26). However, the association between SII and CVD deaths exhibits a J-shaped relationship (P non-linear = 0.03) and When extreme level of SII was compared, the multivariate-adjusted HR was 1.81 (95% CI 1.11, 2.95) for CVD deaths (P trend = 0.017).

Conclusion: Higher SIRI and very high SII were linearly associated with elevated risk of cardiovascular mortality among individuals with T2D.

Disclosure

H. Li: None. W. Guo: None. Y. Li: None. T. Zeng: None. W. Kong: None.

Funding

National Natural Science Foundation of China (Grant No. 81974107); Bethune-Merck Diabetes Research Foundation (Grant No. G-X-2019-056);
463-P: Remnant Cholesterol as a Predictor of Major Cardiovascular Events in Cardiovascular Disease Patients with Differing Glycemic State
Authors: DREXEL HEINZ , PLATTNER THOMAS , LARCHER BARBARA , MADER ARTHUR , VONBANK ALEXANDER , ELSNER PASCAL , LEIHERER ANDREAS , MUENDLEIN AXEL , SAELY CHRISTOPH H.
Published: June 2024

Remnant cholesterol has attracted interest as a marker of cardiovascular event risk. The power of remnant cholesterol to predict major cardiovascular events (MACE) in patients with differing fasting glucose state is unclear and is addressed in the present study. We prospectively recorded MACE including cardiovascular death, non-fatal myocardial infarction and non-fatal stroke in a high-risk cohort of 1787 patients with cardiovascular disease,1472 had angiographically proven coronary artery disease and 315 had sonographically proven peripheral artery disease, over a mean follow-up period of 10.7±5.0 years. At baseline, remnant cholesterol significantly increased from patients with NFG (n=690) over those with IFG (n=505) to those with T2DM (n=592; 19±21 mg/dl, 24±23 mg/dl and 26±24 mg/dl, respectively; ptrend<0.001). During follow-up, 719 of our patients suffered MACE; the incidence of MACE in subjects with NFG, IFG and T2DM was 37.8%, 34.4% and 49.1%, respectively, ptrend<0.001.Remnant cholesterol in the total study population predicted MACE (standardized adjusted HR 1.17 [1.09-1.27], p<0.001) in Cox regression models adjusting for age, sex, hypertension, smoking, body mass index and LDL cholesterol and also after additional adjustment for the baseline glycemic state (HR=1.15 [1.07-1.23], p<0.001). In subgroup analyses, standardized adjusted HR were 1.19 [1.05-1.35], p=0.005), 1.12 [0.96-1.30], p=0.146) and 1.15 [1.02-1.29], p=0.025) in patients with NFG, IFG and T2DM, respectively. An interaction term remnant cholesterol by glycemic state was not significant (p=0.363), indicating that the glycemic state did not significantly impact the power of remnant cholesterol to predict MACE. From our data we conclude that remnant cholesterol is a predictor of MACE in CVD patients irrespective of the baseline glycemic state.

Disclosure

H. Drexel: None. T. Plattner: None. B. Larcher: None. A. Mader: None. A. Vonbank: None. P. Elsner: None. A. Leiherer: None. A. Muendlein: None. C.H. Saely: None.
473-P: Hyperglycemia Increases the Biomechanical Response in Endothelial Cells
Authors: SCHELLER STEPHEN , STEWARD ROBERT
Published: June 2024

Introduction and Objective: Cardiovascular disease (CVD) is a common complication associated with diabetes. Hyperglycemia can lead to vascular changes resulting in endothelial dysfunction. While many studies have shown the molecular mechanisms by which hyperglycemia affects the vasculature, few studies have looked at how hyperglycemia affects the structure and mechanical function of the vasculature. We hypothesized that hyperglycemia will change the biomechanical response of endothelial cells.

Methods: Human Umbilical Vein Endothelial Cells (HUVECs) were cultured in media with normal glucose (5.0mM) or media with high glucose (13.9mM) for 8 days. To determine the biomechanical response, we used traction force microscopy and monolayer stress microscopy to measure cell-cell intercellular stresses and cell-substrate contractile forces (tractions) on day 8.

Results: Cells exposed to high glucose for 8 days had average normal intercellular stresses, maximum shear intercellular stresses, and tractions that were on average 121%, 22%, and 37%, respectively, higher compared to cells in normal glucose for 8 days.

Conclusion: A glucose level of 13.9mM (hyperglycemia) increased endothelial intercellular stresses and contractile forces compared to control. These results show that in addition to the molecular changes commonly seen in the vasculature after recurrent periods of hyperglycemia, there are also biomechanical changes occurring in the endothelial cells. Future studies are needed to determine if the biomechanical response of HUVECs can be recovered after a return to a euglycemic state.

Disclosure

S. Scheller: None. R. Steward: None.
476-P: Investigating C-Fiber Activation and Pain Sensitivity in Diabetic Sensorimotor Neuropathy with Transcutaneous Electrical Nerve Stimulation
Authors: ELDESOUKY OMAR , SEEBAUER LUKAS , RUKWIED ROMAN , CARR RICHARD , ROSHAN MANI , SULAJ ALBA , TSILINGIRIS DIMITRIOS , KOPF STEFAN , FLEMING THOMAS H. , SCHMELZ MARTIN , SZENDROEDI JULIA , KENDER ZOLTAN
Published: June 2024

Introduction & Objective: We aimed to assess C-fiber excitability via transcutaneous-electrical nerve stimulation (TENS) in diabetic sensorimotor neuropathy (DSPN) and its association with epidermal innervation and quantitative sensory testing. Pain perception was evaluated in glucose-tolerant humans (n=14) and patients with type 2 diabetes: no-DSPN (n=15), possible-DSPN (n=21), probable-DSPN (n=19), and confirmed-DSPN (n=11). Subsequent analysis compared patients with positive (n=17) and negative symptoms (n=16).

Methods: Slow depolarizing transcutaneous currents of low-intensity with 4 Hz sinusoidal stimulation profile and single 500 ms half sine wave pulses were used to stimulate C-fibers. Pain perception quantified using (0-10)-Numeric-Rating-Scale, detection/pain thresholds and pain-change-dynamics were assessed.

Results: Confirmed-DSPN had diminished pain perception (1.72±0.50 vs 4.98±0.46), elevated detection (0.19±0.04 vs 0.05±0.01) and pain thresholds (0.28±0.04 vs 0.1±0.01) and reduced pain habituation compared to the control group. Elevated pain perception (pos:7.32±0.72 vs neg:3.81±0.98) and lowered detection/pain thresholds (pos:0.24±0.04 vs neg:0.13±0.03) were shown in the positive symptoms group compared to the negative symptoms group (p<0.05). Over 50% of patients with DSPN experience elevated pain with electrical stimuli in regions with reduced heat pain sensitivity, while less than 6% show similar responses in areas with diminished mechanical pain sensitivity indicating axonal degeneration.

Conclusions: Our results suggest that DSPN proceeds via differential transductional disruption towards denervation. TENS results, influenced by positive symptoms, confirm C-fibers' role for the clinical burden of DSPN. TENS offers further insights into DSPN's natural course, aiding high-risk patient identification and guiding interventions.

Disclosure

O. Eldesouky: None. L. Seebauer: Other Relationship; Springer Medizin Verlag GmbH. R. Rukwied: None. R. Carr: None. M. Roshan: None. A. Sulaj: None. D. Tsilingiris: None. S. Kopf: Speaker's Bureau; Lilly Diabetes, Bayer Inc. T.H. Fleming: None. M. Schmelz: Consultant; Lilly GmbH, Merz Therapeutics, Bayer Inc., Medtronic GmbH. J. Szendroedi: None. Z. Kender: None.
487-P: In Vivo Vasculogenic Tissue Reprogramming and Rescue of Diabetic Ischemic Tissue
Authors: MOHANTY SUJIT K. , SINGH KANHAIYA , KUMAR MANISHEKHAR , VERMA SUMIT S. , ROY SASHWATI , SEN CHANDAN K. , GNYAWALI SURYA C. , YODER MERVIN C.
Published: June 2024

Our recent work reported on the identification of the vasculogenic fibroblast (VF) that is capable of generating new blood vessels during tissue repair (Pal et al. Nat Com, 2023). While VF are physiologic and injury-inducible, inducible VF generation is blunted under conditions of diabetes. We report that such barrier may be overcome by the induction of fibroblast Etv2, Fli1 and Foxc2 (EFF) using tissue nanotransfection (TNT) technology (PMIDs: 28785092, 34837085, 35819852). To understand the mechanisms underlying VF function and significance, we developed EFFfl/fl COL1A2creER mice. In these mice, EFF regions in fibroblasts (COL1A2+ cells) are induced in response to tamoxifen. To gain insight into the significance of VF in vivo, hind limb ischemia (HLI) studies were performed. Significant overexpression of EFF was noted in laser capture dissected dermal fibroblast tissue elements of tamoxifen treated HLI mice (n=6, P < 0.05). Tamoxifen treatment enhanced hindlimb perfusion, as determined by laser speckle perfusion imaging (Perimed Inc.), in HLI mice (n=7, P < 0.05). This rescue was associated with increased abundance of COL1A2+VWF+ VF as compared to control (EFFfl/fl) (n=7, P<0.05). These favorable rescue findings were reproduced in diabetic (db/db) mice subjected to HLI (n=7, P<0.05).

In conclusion, vasculogenic reprogramming in vivo is capable rescuing ischemic tissue under both nondiabetic and diabetic conditions.

Disclosure

S.K. Mohanty: None. K. Singh: None. M. Kumar: None. S.S. Verma: None. S. Roy: None. C.K. Sen: Consultant; SouthWest Technologies. Board Member; VisopalExo. Consultant; Vomaris Inc. S.C. Gnyawali: None. M.C. Yoder: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (DK136814, DK128845, DK135447, DK125835); Department of Defense (W81XWH-21-1-0033, W81XWH-22-1-0146)
489-P: Vitamin D Deficiency's Role in Increasing Large-Fiber Neuropathy Risk in Elderly Type 2 Diabetics
Authors: FEI SIJIA , FAN JINGWEN , PAN QI
Published: June 2024

Background: Previous research has linked Vitamin D deficiency (VDD) with diabetic peripheral neuropathy (DPN), yet the specific relationship between serum vitamin D levels and the extent of large and small fiber neuropathies in elderly patients with type 2 diabetes mellitus (T2DM) remains unclear.

Methods: In this single-center cross-sectional study, 257 elderly T2DM patients were enrolled. To achieve balance in age, sex, and duration of diabetes among study participants, propensity score matching was employed. VDD was identified with serum 25-hydroxyvitamin D (25(OH)D) concentrations below 20 ng/ml. Electromyograms were utilized to evaluate large nerve fiber lesions, while skin conductance measurements were used for assessing small nerve fiber lesions.

Results: In this study, DPN patients exhibited significantly lower serum 25(OH)D levels compared to non-DPN patients [15.05 vs. 18.4 ng/ml, P=0.018]. VDD was identified as an independent risk factor for DPN (odds ratio = 0.959, P = 0.049) in multivariate logistic regression analysis. Spearman's correlation showed that nerve latencies negatively correlated with vitamin D levels, while nerve velocities and amplitudes showed a positive correlation. The group with VDD had longer nerve latencies and motor-evoked potential latencies, yet no significant correlation was found between serum 25(OH)D levels and electrochemical skin conductance.

Conclusions: VDD is independently associated with a higher risk of DPN. VDD may promote the development of DPN by affecting large nerve fibers.

Keywords: diabetic peripheral neuropathy, elderly, propensity score matching, type 2 diabetes mellitus, vitamin D

Disclosure

S. Fei: None. J. Fan: None. Q. Pan: None.

Funding

National Natural Science Foundation of China (Grant No. 82270881)
49-PUB: Body Mass Index, Dietary Intake, Diet Quality, and Pubertal Status of a Cohort of Children with Clinical Partial Remission of Type 1 Diabetes
Authors: HUERTA-SAENZ LINA , VLIEM MCKAYLA , BENAVIDES-VASQUEZ JORGE A. , DENG ELEN , LUGONE CHELSEA , PETERSEN KRISTINA
Published: June 2024

Objective: Some children with type 1 diabetes (T1D) develop a transient recovery phase of beta cell function after diagnosis, also called partial remission (PR). Our aim is to describe the body mass index (BMI), dietary intake/quality, and glycemic metrics of children with clinical PR of T1D one year after diagnosis and explore associations with pubertal stage.

Methods: Children aged 1-17 yo with T1D diagnosis ≥1 year, at least 1 positive T1D antibody, receiving care at the Penn State Pediatric Diabetes Clinic and with PR (defined by an insulin dose-adjusted HbA1C index [IDAA1C] ≤9 were included. Dietary intake was assessed by a single 24-hour recall (ASA24®). Diet quality was assessed by the Healthy Eating Index (HEI-2015). Data were reported as median ± interquartile ranges (IQR), frequencies and percentages. Comparisons by pubertal stage were performed using the Fisher’s exact and Wilcoxon rank-sum tests (p=0.05).

Results: We identified 21 remitters: 62% M, 10.9 ± 3.96 yo, 71% White, 57% pump users, and 90% private insurance. T1D duration= 29 ± 18 months, HbA1C= 6.06 ± 0.53%, blood glucose= 137.9 ± 19.56 mg/dL, IDAA1C= 8.06 ± 0.94, and 95% were on CGMs. BMI at diagnosis vs. enrollment= 18.63 ± 4.54 kg/m2 and 16.6 ± 2.92 kg/m2; and 62% were prepubertal at diagnosis. Most participants had healthier BMI at diagnosis vs. enrollment: 73.7% vs. 57.1% (p<0.05). Dietary intake = 1792 ± 347.2 kcal; carbohydrates (CHO) = 40.1 ± 8.2%, fats 41.9 ± 8.05%, protein 17.7 ± 5.8%, CHO intake = 188.4 ± 59.5 g/day. HEI-2015 = 58 ± 12.6. Pre-pubertal participants had higher rates of overweight/obesity at enrollment than at diagnosis (p=0.0135).

Conclusion: Most remitters had lower BMI percentiles at diagnosis, but those who were pre-pubertal increased their BMI significantly during the course of the disease.

Disclosure

L. Huerta-Saenz: None. M. Vliem: None. J.A. Benavides-Vasquez: None. E. Deng: None. C. Lugone: Speaker's Bureau; Dexcom, Inc. Employee; Dexcom, Inc. Speaker's Bureau; Sanofi. K. Petersen: None.

Funding

The project described was partially supported by the National Center for Advancing Translational Sciences, Grant KL2 TR002015 to Pennsylvania State University - KL2 ESI award to Dr. Huerta-Saenz. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
496-P: Early-Onset Diabetes Increase the Risk of Referable and Sight-Threatening Diabetic Retinopathy
Authors: MENG CHUCHEN , MA YUHANG , WANG YUFAN
Published: June 2024

Objective: This study aimed to investigate the influence of early-onset type 2 diabetes on the risk of developing diabetic retinopathy (DR), referable diabetic retinopathy (referable DR), and sight-threatening diabetic retinopathy (STDR).

Method: A total of 6847 individuals with type 2 diabetes were included. Individuals diagnosed with type 2 diabetes at or before the age of 40 are defined as having early-onset T2DM. Logistic regression and interaction analysis were used to assess the risk of DR, referable DR, and STDR in early versus late-onset diabetes. Kaplan-Meier analysis and cox regression analysis were employed to measure the relationship between incidences of retinopathy and early-onset diabetes in 1507 patients without DR at baseline.

Results: The early-onset group exhibited a higher prevalence of any DR, referable DR, and STDR with a diabetic duration exceeding 5 years (all P<0.05).After adjusting for confounding factors, early-onset diabetes showed a significant association with an increased risk of referable DR and STDR (P=0.02 and P=0.03, respectively), with an interaction based on diabetes duration (P for interaction = 0.01 and P for interaction = 0.02 respectively).In follow-up analysis, the early-onset group had a significantly higher cumulative incidence of referable DR in terms of diabetes duration compared to the late-onset group (12.21% vs 9.8%, P=0.03).The multivariable-adjusted hazard ratios for referable DR in early-onset diabetes were 3.25 (95% CI 1.11-9.47) relative to the late-onset group, only in patients with a duration over 10 years.

Conclusions: Early-onset diabetes increased the risk of referable and sight-threatening DR, especially in those with diabetes duration over 10 years. Enhanced retinal screening and comprehensive diabetes manangement are vital for individuals with early-onset diabetes.

Disclosure

C. Meng: None. Y. Ma: None. Y. Wang: None.

Funding

National Key Research and Development Program of China (2021YFC2501600, 2021YFC2501601)
538-P: Multilevel Behavioral Drivers of Type 2 Diabetes Disparities in the United States—An Integrative Review
Authors: OWOLABI EYITAYO O. , DIAZ MONICA , BRAXTON MORGAN , GODFREY TIMIAN , SINGH MANTEJ , RASCON ALIRIA M. , SHAIBI GABRIEL Q.
Published: June 2024

Introduction: Type 2 diabetes (T2D) disproportionately impacts minority populations. The National Institute of Minority Health and Health Disparities (NIMHD) Research Framework identifies drivers of health disparities across multiple levels and domains. This study synthesized evidence on the behavioral drivers of T2D disparities among minority populations in the US and categorized them across individual, interpersonal, community, and societal levels.

Methods: Relevant articles were retrieved from PubMed, CINAHL, PsycINFO, and Scopus. Eligible studies, defined as studies published between 2017 and 2023 that report glycemic measures or differences in T2D prevalence or related outcomes for US minority populations were abstracted and summarized descriptively.

Results: Of the 108 included studies, 28 (26%) addressed behavioral drivers or strategies for addressing T2D disparities, the majority of which were at the individual level 20 (71%), 7(25%) at the community level, and 1(4%) at the interpersonal level. Individual-level drivers included physical activity, dietary practices, dysfunctional eating, sleep quality and duration, health-seeking behavior, and coping strategies such as anxiety, stress, depression, or distress. The interpersonal-level factors were emotional and maternal abuse. The identified community-level interventions to improve T2D outcomes included lifestyle interventions, self-management education, and interventions aimed at improving resilience. No identified behavioral factors at the societal level.

Conclusions: This review identified a persistent focus on individual-level behavioral drivers of T2D disparities. Given the clear evidence that disparities in T2D are the result of upstream factors, more studies are needed at the interpersonal, community, and societal levels to inform comprehensive interventions and policies aimed at reducing T2D disparities.

Disclosure

E.O. Owolabi: None. M. Diaz: None. M. Braxton: None. T. Godfrey: None. M. Singh: None. A.M. Rascon: None. G.Q. Shaibi: None.
541-P: Medicare’s Initial or Annual Wellness Visits and Participation of Diabetes Self-Management Education and Support among Medicare Beneficiaries with Type 2 Diabetes
Authors: PENG NG BOON , LAMANNA JACQUELINE B. , HAWKINS GEORGIANNE T. , TOWNE SAMUEL D. , PARK CHANHYUN
Published: June 2024

Welcome to Medicare and Annual Wellness Visits (AWV) provide opportunities for providers to engage beneficiaries in health promotion-related discussions. Diabetes self-management education and support (DSMES) facilitates beneficiary competence in complex technical skills, critical decision-making, and coping behaviors required to achieve individualized blood glucose goals. Although covered by Medicare, DSMES utilization is low. Increasing AWVs may help improve DSMES participation by older adults. Using the 2020 national sample of the Medicare Current Beneficiary Survey Public Use File, a survey-weighted multivariable logit model, adjusting for socio-demographics and comorbidities, was performed to estimate predictive margins for comparing the prevalence of participating in DSMES among beneficiaries aged ≥65 years with type 2 diabetes (n=1,837). Of beneficiaries, 50.9% self-reported participation in DSMES. Beneficiaries with AWV were 7.2% [95%CI=1.2%, 13.1%] more likely to participate in DSMES. Beneficiaries with lower educational attainment (less than high school, -18.9% [-26.4, -11.4] and high school, -10.0% [-15.8, -4.4]) were less likely to participate in DSMES than those with a college education. Beneficiaries with lower incomes (less than $25,000, -14.4% [-21.5, -7.4]) were also less likely to participate in DSMES. Beneficiaries of Other race (-15.1% [-22.9, -7.4]) were less likely to participate in DSMES than non-Hispanic White beneficiaries. About half of study beneficiaries with type 2 diabetes, representing almost 4 million older adults, did not access DSMES services. AWV was significantly associated with DSMES participation. Disparities in DSMES participation were observed by race, income, and education. Implementation efforts from both provider and beneficiary perspectives to improve the use of AWV and DSMES among at-risk beneficiaries should be considered.

Disclosure

B. Ng: None. J.B. LaManna: None. G.T. Hawkins: None. S.D. Towne: None. C. Park: None.
543-P: Characterizing Predictors of Receipt of Diabetes Self-Managment Education in the United States
Authors: MONTERO ALEX R. , NAM JOON
Published: June 2024

Introduction& Objective: ADA recommends DSMES in general and at critical time points, such as hospital admission - a care transition. The National Health and Nutrition Examination Survey (NHANES) has asked about receipt of care from providers of DSME (nurse educators / dieticians) since 2005. Our aim was to characterize predictors of receipt of DSMES services with a focus on health system factors in NHANES, a nationally representative sample of the U.S. population.

Methods: This cross sectional study utilized NHANES 2005-2018 limited to those self-reporting diabetes and age ≥ 30. Our primary outcome was ever receipt of DSMES. Predictors of interest were insurance, current PCP, and recent hospital admit. Analyses used Student T-test, Chi square, and logistic regression as appropriate. All analyses were done in SAS and used weighting/sampling to account for the complex survey design of NHANES.

Results:4612 met eligibility. Those with A1C ≥ 9.0 were more likely to be younger; male of non-Hispanic black race/ethnicity (NHB); and on insulin. In multivariable analyses high A1C, NHB race/ethnicity, age ≤ 65, presence of PCP, and hospital admit were positively associated with DSME. Receipt of DSME has been decreasing over time.

Conclusion: Health system factors such as presence of PCP and recent hospital admit were positively associated with receipt of DSMES but insurance status was not associated with DSMES.

Disclosure

A.R. Montero: None. J. Nam: None.
550-P: Utilization of an Electronic Clinical Decision Support Tool by Health Care Providers for Hospital Glycemic Management in a Large Academic Center
Authors: MILLER THEODORE J. , MAREBOINA MANVITA , GONG JASON , KEARCHER KALEN , ORR MELISSA , PICHARDO-LOWDEN ARIANA
Published: June 2024

Introduction: Sequelae of dysglycemia include infections and non-infectious complications, longer hospitalizations, and added hospital expenditure. Clinical Decision Support (CDS) is linked to optimization of glycemic control and shorter hospital stay. However, knowledge about clinicians’ responsiveness to CDS for diabetes care is limited.

Objective: This study aims to evaluate response to an inpatient electronic health record (EHR) CDS tool that detects gaps in glycemic care in real-time, and offers notifications containing evidence-based management recommendations.

Methods: We conducted abstractions of 65 patients’ charts with notifications delivered to providers related to persistent hyperglycemia, hypoglycemia or near hypoglycemia, or insulin sliding scale monotherapy. We calculated the proportion of response to CDS recommendations.

Results: Insulin reduction after alerts for or near hypoglycemia (≤80 mg/dL) or hypoglycemia risk (81-100 mg/dL) was 0% and 16.7% respectively. Insulin was initiated (50%) or increased (33%) after notifications for hyperglycemia (180 mg/dl x 2) in patients with diabetes, and initiated (60%) for stress hyperglycemia. After alerts for sliding scale monotherapy, insulin was initiated (53%) or stayed the same (55%).

Conclusions: There were variable reactions to CDS prompts. Even though our program is characterized by a standardized process that presents evidence-based real-time recommendations in the context of practice, uses a knowledge-promoting approach, and delivers automated prompts in the EHR, the overall response was noted to be limited. This phenomenon is likely multifactorial and requires closer investigation. CDS programs can benefit from careful assessment of users’ engagement, notification burden, and implementation strategies. Further, assessment of programs’ design to foster adoption of guidelines and evidence-based recommendations is warranted.

Disclosure

T.J. Miller: None. M. Mareboina: None. J. Gong: None. K. Kearcher: None. M. Orr: None. A. Pichardo-Lowden: None.

Funding

National Institute Of Diabetes And Digestive And Kidney Diseases of the National Institutes of Health Award Number: R01DK130992
590-P: Nutrition Able—A Lecture-Based Intervention to Increase Childhood Health Literacy of Nutrition Labels in Bexar County
Authors: BOLTE JEFFERY
Published: June 2024

Intro: Nutrition Able aims to teach food scarce Bexar County middle/high school students how to read a nutrition label via lectures at Southside and Southwest ISD. Notably, Southside ISD is a food desert.

Methods: Our team gave lectures and administered a pre-survey. Following the pre-survey, a lecture was given. Afterwards, an identical post-survey was administered. The anonymous survey consisted of 7 multiple-choice questions about calories, macronutrients, calories/serving, macronutrient content, fiber, protein, and diabetes/obesity prevention. We collected demographics at the students’ discretion- height, weight, sex, grade, age, and family history of obesity/diabetes (FH).

Results: To date, we have reached 432 students from 6th-12th grade. There were improvements in pre-/post-survey scores (2.47 vs. 3.31, P<<<.05), median (2 vs. 3), and mode (2 vs. 4). Positive FH predicted higher BMI (23.6 vs. 21.8, P=.003). Those with a positive FH reported their BMI more frequently (OR 1.63, CI 1.0-2.6).Predictors of better pre-survey scores include negative FH (2.65 vs. 2.42, P=.066), male sex (2.62 vs. 2.30, P=.01), and overweight or greater BMI (2.72 vs. 2.33, P=.01). Predictors of larger improvements in pre/post surveys include reporting BMI (0.93 vs. 0.60, P=.058), positive FH (.92 vs. .73, P=.16), and female sex (0.96 vs. 0.71, P=.092) - with large improvements in overweight girls(+1.4), healthy weight girls(+1.2), obese girls(+1.08) and obese boys(+1.0). The only predictor of higher post-survey scores was overweight girls scored better than overweight boys (4.03 vs. 3.1, P=.03).

Conclusion: Nutrition Able improves health literacy. Negative FH, male sex, and overweight/obese BMI are predictors of higher pre-survey scores. Overweight/obese BMI, positive FH and female sex are predictors of higher pre-/post-survey improvement. There were no material predictors of post-survey score. Nutrition Able effectively reaches those in need.

Disclosure

J. Bolte: None.

Funding

University of Texas Health Science Center Community Service Learning Grant
602-P: Relationships between Diagnosis Duration, Motor Proficiency, and Physical Fitness in Youth with Type 1 Diabetes
Authors: THRASHER BRAD J. , WINTERGERST KUPPER A. , SKETCH AMY E. , FRYE CAROLINE , OLAJUYIGBE TOLUWANIMI G.
Published: June 2024

Introduction & Objective: Individuals with T1D encounter unique challenges regarding physical activity, glucose control, and chronic health conditions. Understanding the connection between diagnosis duration, motor proficiency (MP), physical fitness, and glycemic control is crucial for optimizing health and quality of life. The purpose of this study was to examine the relationships between diagnosis duration, MP, and physical fitness in pediatrics and young adults with T1D enrolled in a clinical sports & activity program (CSAP).

Methods: Data were collected from individuals with T1D enrolled in a CSAP, aged 6-21, receiving care at the Wendy Novak Diabetes Institute. Participants underwent assessments for MP, grip strength (GS), sit and reach (SR), body composition, resting metabolic rate (RMR), and cardiorespiratory fitness (VO2max). Data were analyzed using Spearman’s correlation test.

Results: Data were analyzed for 37 participants (14.1± 3.5 years; male, n=22, 59.5%, white, n=34, 91.9%). Positive correlations were seen between percent body fat (BF) and GS (rs = -0.382, p <0.05), BF and VO2max (rs =-0.507, p <0.05), BF and vertical jump (VJ; rs =-0.608, p<0.05), RMR and GS (rs =0.791 p<0.05), RMR and VJ (rs =0.615, p<0.05), VJ and MP composite (rs =0.495, p<0.05), GS and VJ (rs =0.619, p<0.05), and MP composite and diagnosis duration (rs = 0.393, p<0.05).

Conclusion: MP composite scores were found to still be high in individuals with T1D even years after diagnosis. Improved physical fitness shows improved markers in cardiorespiratory fitness. Future research should continue to assess motor proficiency and physical fitness as duration of diagnosis increases.

Disclosure

B.J. Thrasher: None. K.A. Wintergerst: None. A.E. Sketch: None. C. Frye: None. T.G. Olajuyigbe: None.
62-PUB: Diabetes Control and Complications in Men vs. Women in India—Three-Year Results of LANDMARC Trial
Authors: DAS ASHOK K. , THACKER HEMANT , CHAWLA MANOJ S. , GOPALAKRISHNAN UNNIKRISHNAN AMBIKA , KUMAR WANGNOO SUBHASH , MENON SHALINI K. , GADEKAR ARVIND , CHODANKAR DEEPA
Published: June 2024

Glycemic control, therapy trends, and diabetes complications were evaluated in LANDMARC, a prospective observational 3-year study (CTRI/2017/05/008452), of participants with T2D on ≥2 antihyperglycemic medications. This subgroup analysis included 6222 participants, comprising 3517 men and 2705 women. The mean (SD) duration of T2D was 8.72 (5.8) years in men and 8.42 (5.4) years in women. At baseline, 1935 (75.4%) men and 1412 (74.4%) women had HbA1c ≥ 7%, which dropped to 1298 (63.0%) men and 1046 (63.8%) women at 3-year. The mean HbA1c, FPG, and PPG improved from baseline to 3-year in both genders (Table). The mean (SD) basal insulin dose reduced from 24.1 (19.1) U at baseline to 23.3 (16.3) U at 3-year in men and from 24.4 (18.7) U at baseline to 23.8 (16.2) U at 3-year in women. At 3-year, the most common macrovascular complication was myocardial infarction in men and peripheral vascular disease in women. Neuropathy was the most common microvascular complication in both genders at 3-year (Table). Hypertension and dyslipidemia were the most common CV risk factors reported at 3-year in both genders. This pivotal understanding of anthropometry, glycemic parameters, complications, and CV risk factors among genders may help strategize future diabetes management practices in India.

Disclosure

A.K. Das: Other Relationship; Sanofi. H. Thacker: Other Relationship; Merck Sharp & Dohme Corp., Novartis India, Sanofi. M.S. Chawla: Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Advisory Panel; Biocon. Speaker's Bureau; Biocon. Advisory Panel; Eris Lifesciences Ltd. Speaker's Bureau; Eris Lifesciences Ltd. Advisory Panel; Torrent Pharmaceuticals Ltd. Speaker's Bureau; Torrent Pharmaceuticals Ltd. Advisory Panel; USV Private Limited, Lupin Pharmaceuticals, Inc. A. Unnikrishnan: Speaker's Bureau; Sanofi. Other Relationship; Novo Nordisk. Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim, Abbott, Intas Pharmaceuticals Ltd. Research Support; Torrent Pharmaceuticals Ltd. S. Wangnoo: None. S.K. Menon: Employee; Sanofi. A. Gadekar: None. D. Chodankar: Employee; Sanofi.

Funding

Sanofi