bluuebunny/crossref_metadata_2025_split huggingface dataset:
175-OR: Effect of Hyperketonemia on Cardiac Efficiency in Patients with Heart Failure and Type 2 Diabetes
Authors: SOLIS-HERRERA CAROLINA , QIN YUEJUAN , HONKA HENRI , MOODY ALEXANDER , CLARKE GEOFFREY D. , TRIPLITT CURTIS L. , CERSOSIMO EUGENIO , DEFRONZO RALPH A. 
Published: May 2022

Mechanism (s) responsible for the cardiac benefits of SGLT2 inhibitors remain unknown.
Aim: To examine the effect of increased ketone concentration (with infusion of beta-hydroxybutyrate [BOHB]) on left ventricular (LV) function and myocardial glucose uptake (MGU) Methods: Two groups (12 per group) of T2DM with HFrEF (&lt;45%) were studied. Group I (Age=60; BMI=32 kg/m2; A1c = 7.7%) received randomly a 6-hr BOHB infusion (Prime =1.5 mg/kg.min, then 0.75 mg/kg.min) or 6-hr HCO3 infusion (control) . Group II (Age=57; BMI=32 kg/m2; A1c=7%) received a 3-hr BOHB infusion at a higher rate. A cardiac MRI was performed before and after each infusion. Additionally, Group I underwent a PET study with 18FDG
Results: Groups I and II achieved plasma ketone levels of 1.2 and 2.6 mmol/L respectively. In both groups, the BOHB infusion significantly (P&lt;0.05) increased CO, stroke volume (SV) , and ejection fraction (EF) ; the increase in EF was greater in Group II vs. Group I (&lt;0.001) (Figure 1) . NaHCO3 infusion had no effect on CO, SV, or EF. Myocardial glucose uptake was not altered by BOHB
Conclusion: In patients with T2DM and HFrEF, increased plasma ketones significantly increases LV function and may be dose-dependent. These findings support the hypothesis that plasma ketones can provide an additional fuel for the heart, without interfering myocardial glucose metabolism and may be used therapeutically to improve cardiac function in HFrEF.

Disclosure
C.Solis-herrera: Speaker's Bureau; Novo Nordisk. Y.Qin: None. H.Honka: None. A.Moody: None. G.D.Clarke: None. C.L.Triplitt: Consultant; Bayer AG, Speaker's Bureau; Eli Lilly and Company, Novo Nordisk. E.Cersosimo: Research Support; AstraZeneca. R.A.Defronzo: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Intarcia Therapeutics, Inc., Novo Nordisk, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Speaker's Bureau; AstraZeneca.

Funding
Merck and Co and The Max and Minnie Tomerlin Voelcker Foundation and
18-OR: Discontinuation of Renin Angiotensin System Inhibitor and Cardiovascular-Renal Events in Advanced Diabetic Kidney Disease
Authors: SHI MAI , YANG AIMIN , LAU ERIC S.H. , WU HONGJIANG , ZHANG XINGE , FAN BAOQI , KONG ALICE P. , LUK ANDREA , MA RONALD C. , CHAN JULIANA C. , CHOW ELAINE 
Published: May 2022

Introduction: Whether angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) should be discontinued in advanced diabetic kidney disease (DKD) remains controversial. We examined the association of discontinuation of ACEi/ARBs when estimated glomerular filtration rate (eGFR) reached &lt;30 ml/min/1.73m2 with risk of death, major adverse cardiovascular events (MACE) , and end-stage-kidney-disease (ESKD) defined as dialysis and/or eGFR &lt;15/ml/min/1.73m2 in Chinese patients with type 2 diabetes (T2D) .
Methods: We performed a prospective analysis of a register including 11,323 patients stratified by continuation of ACEi/ARBs within 6 months of reaching eGFR &lt;30 ml/min/1.73m2 in 2002-2018 followed up until 2019. We used Cox model with time-dependent exposure and covariates to estimate the hazard ratio (HR) of outcomes in the overlap propensity score weighted cohort.
Results: Of 11,323 ACEi/ARBs users with new-onset eGFR&lt;30 ml/min/1.73m2, 2,055 (18.5%) discontinued ACEi/ARBs within 6 months whereas 9,268 (81.5%) had continuation of ACEi/ARBs. During a mean follow-up of 4.3 years, 13.5% and 28.4% had incident MACE and ESKD respectively, and 36.2% died. Compared to ACEi/ARBs continuation, discontinuation of ACEi/ARBs was associated with higher risk of MACE (HR=1.26, 95% CI: 1.15-1.39) and ESKD (HR=1.26, 95% CI: 1.14-1.40) , and neutral risk of death (HR=0.96, 95% CI: 0.89-1.04) . Results were consistent when modeling ACEi/ARBs as a time-dependent exposure using a marginal structural model.
Conclusions: Discontinuation of ACEi/ARBs was associated with increased risk of cardiovascular-renal events in support of their continued use in patients with advanced DKD.

Disclosure
M.Shi: None. J.C.Chan: Board Member; Asia Diabetes Foundation, Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Celltrion, Merck Sharp & Dohme Corp., Roche Diabetes Care, Viatris Inc., Research Support; Applied Therapeutics, AstraZeneca, Eli Lilly and Company, Hua Medicine, Servier Laboratories, Stock/Shareholder; GemVCare Ltd. E.Chow: Research Support; Hua Medicine, Medtronic, Powder Pharmaceuticals Inc., Speaker's Bureau; Novartis AG, Sanofi. A.Yang: None. E.S.H.Lau: None. H.Wu: None. X.Zhang: None. B.Fan: None. A.P.Kong: Advisory Panel; Abbott, Kyowa Kirin Co., Ltd., Other Relationship; AstraZeneca, Novo Nordisk, Research Support; Boehringer Ingelheim, Speaker's Bureau; AstraZeneca, Bayer, Eli Lilly and Company, Sanofi, Stock/Shareholder; Aptorum Group Limited. A.Luk: None. R.C.Ma: Other Relationship; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; AstraZeneca, Bayer AG, Novo Nordisk A/S, Pfizer Inc., Tricida, Inc.
182-OR: Clinical Effects of SGLT2 Inhibitors in HNF1A-Diabetes (MODY3) : A Case Series
Authors: MAAGENSEN HENRIK , HAEDERSDAL SOFIE , KROGH JESPER , HANSEN TORBEN , KNOP FILIP K. , VILSBØLL TINA 
Published: May 2022

Mutations in hepatocyte nuclear factor 1-alpha (HNF1A) cause HNF1A-diabetes (or maturity-onset diabetes of the young type 3 (MODY3)) . Treatment of HNF1A-diabetes is primarily based on sulphonylureas (SU) and secondarily insulins, glucagon-like peptide 1 receptor agonists (GLP1-RA) and dipeptidyl peptidase-4 inhibitors (DPP4i) . Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are effective glucose-lowering agents, cause body weight loss and protect from chronic kidney disease, heart failure and major adverse cardiovascular events. The utility of SGLT2i in patients with HNF1A-diabetes is unknown. Here, we describe a case series of five patients with HNF1A-diabetes treated with SGLT2i. Patient characteristics (median [range]) : age: 52 [35; 68] years; men/women: n=4/1; diabetes duration: 23 [9; 55] years; age at diabetes onset: 18 [13; 44] years; HbA1c: 6.9 [6.0; 7.4]% (52 [42; 57] mmol/mol) ; body weight: 92.3 [65.5; 95.1] kg; BMI: 25.6 [23.8; 29.4] kg/m2. At baseline, patients were treated with SU (n=5) , insulin (n=3; total daily dose: 15 [6; 25] IE divided into 1-4 injections/day) , DPP-4i (n=3) , GLP1-RA (n=2) , metformin (n=1) . All patients were started on empagliflozin mg QD. Follow-up was 1.5 [0.7; 1.8] years (total 6.2 patient years) . After three to six months of SGLT2i therapy, HbA1c was 6.1 [5.5; 7.5]% (43 [37; 59] mmol/mol) and had decreased in four patients (HbA1c change: -0.5 [-1.3; 0.7]% (-5 [-14; 8] mmol/mol)) , while body weight had decreased in all patients (change: -3.4 [-5.9; -1.5] kg) . During SGLT2i treatment, insulin was fully ceased in two patients and insulin dose was reduced from 15 IE/day to 3 IE/day in one patient. No serious adverse events were reported. Our data suggest that SGLT2i is safe, have glucose-lowering effects and is well-tolerated in HNF1A-diabetes, but randomized controlled trials are needed.

Disclosure
H.Maagensen: None. S.Haedersdal: None. J.Krogh: None. T.Hansen: None. F.K.Knop: Advisory Panel; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi, ShouTi, Zucara Therapeutics, Consultant; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Pharmacosmos A/S, Sanofi, ShouTi, Zealand Pharma A/S, Zucara Therapeutics, Research Support; AstraZeneca, Novo Nordisk, Sanofi, Zealand Pharma A/S, Speaker's Bureau; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Stock/Shareholder; Antag Therapeutics. T.Vilsbøll: Consultant; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Gilead Sciences, Inc., GlaxoSmithKline plc., Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk, Sun Pharmaceutical Industries Ltd.
183-OR: Overcoming Immunological Barriers for “Off-the-Shelf” iPSC-Derived Islets
Authors: HU XIAOMENG , WHITE KATHY , OLROYD ARI G. , DEJESUS ROWENA , DOMINGUEZ ANTONIA , DOWDLE WILLIAM E. , CHU ELAINE Y.L. , FRIERA ANNABELLE , YOUNG CHI , WELLS FRANK , MCGILL TREVOR , RUKSTALIS MICHAEL , GATTIS CORIE , BASCO RONALD , MILLMAN JEFFREY R. , SCHREPFER SONJA 
Published: May 2022

Improved differentiation protocols allow large-scale generation of induced pluripotent stem cell (iPSC) -derived islets. In order to make allogeneic “off-the-shelf” islets clinically useful and avoid rejection absent immunosuppression (IS) , they need to evade host immune responses, a property we refer to as being “hypoimmune.” Rhesus macaque (NHP) iPSCs were engineered to knock-out function of MHC class I and II and overexpress CD47 (HIP iPSCs) . HIP iPSCs and unedited iPSCs (wt iPSCs) were transduced to express luciferase and transplanted IM into four allogeneic NHPs per group. There was a strong IFN-γ ELISpot T cell response 1 week after wt iPSC transplantation, and increased production of wt-iPSC specifc IgM antibodies (Ab) and IgG Abs. At all time points tested (up to 12 weeks) , PBMCs killed wt iPSCs via direct and Ab-mediated cellular cytotoxicity. Furthermore, serum from NHPs killed wt iPSCs via complement-dependent cytotoxicity. In contrast, NHPs that received HIP iPSCs showed no measurable immune response against HIP iPSCs at all time points. After 6 weeks, NHPs initially receiving wt iPSCs were injected with HIP iPSCs. Although the NHPs maintained their strong immune response against wt iPSCs, they did not mount any response against HIP iPSCs. NHPs receiving HIP iPSCs first developed a strong cellular and Ab-response against the subsequently injected wt iPSCs but continued to have no reactivity against HIP iPSCs. Bioluminescence imaging in vivo revealed rejection of all wt iPSC grafts in both groups within 2-3 weeks after transplantation, while all HIP iPSC grafts survived the study period of 16 weeks. As a step to extending these studies to human iPSCs, we created human HIP iPSCs. We were able to differentiate these human HIP iPSCs into functional HIP islet cells that evaded host immune responses. This work suggests that HIP modifications do not impact islet cell differentiation or function. These data support the development of allogeneic HIP islets for the treatment of patients with T1DM.

Disclosure
X.Hu: None. F.Wells: None. T.Mcgill: Employee; Sana Biotechnology Inc. M.Rukstalis: Employee; Sana Biotechnology Inc. C.Gattis: None. R.Basco: None. J.R.Millman: Consultant; Sana Biotechnology Inc., Other Relationship; Sana Biotechnology Inc., Vertex Pharmaceuticals Incorporated, Research Support; Sana Biotechnology Inc., Stock/Shareholder; Salentra Biosciences. S.Schrepfer: Other Relationship; Sana Biotechnology Inc. K.White: None. A.G.Olroyd: None. R.Dejesus: None. A.Dominguez: Employee; Sana Biotechnology Inc. W.E.Dowdle: Employee; Sana Biotechnology Inc., Stock/Shareholder; Sana Biotechnology Inc. E.Y.L.Chu: None. A.Friera: None. C.Young: Employee; Sana Biotechnology Inc.
187-OR: Declines in ß-Cell Glucose Responsiveness Correlate with Loss of Glucose Metabolism during T1D Pathogenesis
Authors: HUBER MOLLIE , RUPNIK MARJAN SLAK , DROTAR DENISE M. , HILLER HELMUT , BEERY SR., MARIA , KUSMARTSEVA IRINA , ATKINSON MARK A. , PHELPS EDWARD , MATHEWS CLAYTON E. 
Published: May 2022

Features of type 1 diabetes (T1D) include loss of first-phase insulin secretion in response to glucose, declining c-peptide, and glucose intolerance; indicating β cell dysfunction. Here, we investigate the mechanisms of this dysfunction with the hypothesis that immune dysregulation during the early stages of T1D development impacts β cell dysfunction in pathways affecting glucose metabolism. The live pancreas tissue slice (LPTS) model is ideal for the study of T1D pathogenesis due to its preservation of the pancreatic environment. LPTS were generated from organ donors without diabetes or autoantibodies (ND, n=9) , donors positive for one or more autoantibodies without a diagnosis of T1D (AAb+, n=6) , and donors with T1D (T1D, n=4) . Imaging studies were conducted to assess the impact of T cell infiltration on β cell function through Ca2+ imaging and slice perifusion. Islets from ND and AAb+ donors had no insulitis and exhibited Ca2+ responses to both high glucose (HG) and potassium chloride (KCl) . A majority of β cell+ islets in tissue from donors with T1D had infiltrating T cells with several having insulitis. Islet HG response from donors with T1D was heterogenous (∼50% failed to respond) while all T1D islets exhibited responses to KCl. Insulin secretion was significantly higher in LPTS from ND donors than in donors with T1D (p=0.0079) . To determine the basis for this loss of function, we assessed transcriptomics of islets within these cohorts. When comparing gene expression levels in islets from ND versus T1D, significant differences were observed in genes involved in glycolysis (GAPDH, p=3.27x10-21) , the citric acid cycle components (OGDH, p=1.88x10-18) , and the electric transport chain (F1FoATP synthase, p=2.69x10-13) . The decreased expression of glucose metabolism genes during T1D development along with the loss of β cell function in LPTS demonstrates β cell dysfunction before their demise and may be a contributory mechanism towards the pathogenesis of disease.

Disclosure
M.Huber: None. M.Slak rupnik: None. D.M.Drotar: None. H.Hiller: None. M.Beery: None. I.Kusmartseva: None. M.A.Atkinson: None. E.Phelps: Research Support; Immunocore, Ltd. C.E.Mathews: None.

Funding
National Institutes of Health (5T32DK108736-03) National Institutes of Health (PO1 AI42288)
190-LB: Vaspin—A Novel Predictor of Type 2 Diabetes Risk
Authors: WANG HARRY , CHONG MICHAEL , PERROT NICOLAS , FEINER JAMES , HESS SIBYLLE , YUSUF SALIM , GERSTEIN HERTZEL C. , PARE GUILLAUME , PIGEYRE MARIE 
Published: May 2022

Vaspin (visceral adipose tissue-derived serpinA12) is an adipokine suspected to be involved in type 2 diabetes (T2D) pathogenesis, linking obesity and T2D. We sought to assess epidemiological and genetic associations of vaspin with T2D and related variables.
We assessed the relationship of body-mass index (BMI) and waist-hip ratio (WHR) and plasma vaspin concentration, along with the relationship between plasma vaspin and adiposity-related variables and T2D in (i) a case-cohort within the Prospective Urban and Rural Epidemiology (PURE) prospective multi-country study (N=10,052) , and (ii) the Outcome Reduction with Initial Glargine Intervention (ORIGIN) Trial (N=7,840) of participants with dysglycemia. We next investigated the predictive value of vaspin for T2D risk. All models adjusted for age, sex, and ethnicity. Using two-sample Mendelian randomization (MR) , we analyzed if genetically higher vaspin is causal for T2D. The MR analysis used 34 independent genetic variants (linkage disequilibrium r2&lt;0.1) associated with vaspin concentration in PURE (N=3,513) , estimating their effect on BMI-adjusted T2D risk in the DIAGRAM (DIAbetes Genetics Replication And Meta-analysis) consortium (N=898,130) .
In PURE, a 1 unit increase in BMI and WHR was associated with a 0.01 SD (95% CI 0.01 - 0.02; P = 2.04x10−15) and 0.45 SD (95% CI, 0.21 - 0.70; P = 2.87 × 10−4) increase in plasma vaspin respectively. A 1 SD increase in plasma vaspin was associated with higher triglycerides (0.09 mmol/L; 95% CI, 0.07 - 0.12, P = 4.08x10−13) . Directionally-consistent associations were observed in ORIGIN. A 1 SD increase in plasma vaspin was associated with a 19% increase in incident T2D risk in PURE (HR, 1.19; 95% CI, 1.12 - 1.26; P = 6.36x10−8) and a 16% increase in prevalent T2D in ORIGIN (OR, 1.16; 95% CI, 1.07 - 1.25; P = 2.17x10−4) . Sensitivity analyses showed vaspin's specificity for T2D. Genetically-higher vaspin was associated with increased BMI-adjusted T2D risk (OR, 1.02; 95% CI, 1.00 - 1.03; P = 5.46x10−3) .
Our data suggests that vaspin is a predictor for T2D risk, a modest causal factor for T2D development, and might represent a potential T2D therapeutic target.

Disclosure
H. Wang: None. M. Chong: None. N. Perrot: None. J. Feiner: None. S. Hess: Employee; Sanofi. S. Yusuf: None. H. C. Gerstein: Advisory Panel; Abbott, Eli Lilly and Company, Hanmi Pharm. Co., Ltd., Novo Nordisk, Pfizer Inc., Sanofi, Viatris Inc., Consultant; Kowa Company, Ltd., Other Relationship; DKSH, Eli Lilly and Company, Sanofi, Zuellig Pharma Holdings Pte. Ltd., Research Support; AstraZeneca, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi. G. Pare: Advisory Panel; Amgen Inc., Bayer AG, Sanofi, Research Support; Bayer AG. M. Pigeyre: n/a.

Funding
PURE biomarker study was sponsored by Bayer and CIHR. Origin (NCT00069784) and the biomarker-substudy in Origin were sponsored by Sanofi and CIHR.
192-LB: Ductal Epithelial Cells Adopt Transcriptional Features of Tolerogenic Dendritic Cells in Type 1 Diabetes
Authors: KAESTNER KLAUS H. , CONSORTIUM HPAP , VAHEDI GOLNAZ 
Published: May 2022

Type 1 diabetes (T1D) is an autoimmune disease in which immune cells destroy insulin-producing beta cells. Disease etiology is dependent on the interplay of multiple heterogeneous cell types in the pancreatic environment; however, technical constraints have thus far impeded our understanding of the initial molecular perturbations that occur during disease progression and a comprehensive identification of the pathogenic cell types in T1D. In particular, it is difficulty to safely biopsy the human pancreas of living donors, and there is significant disease progression and beta cell destruction by the time patients are clinically diagnosed with T1D. To address this, the Human Pancreas Analysis Program (HPAP) collects pancreatic tissues from deceased organ donors diagnosed with T1D and performs comprehensive molecular phenotyping. Using the full spectrum of imaging, genetic, and genomic technologies available through HPAP, we discovered that a subset of pancreatic ductal cells acquires the signature of tolerogenic dendritic cells in an apparent attempt at immune suppression in T1D donors. Single cell RNA-seq revealed a highly significant enrichment of the tolerogenic dendritic cell gene signature in ductal cells of T1D donors, including activation of interferon genes. In addition, via highly multiplexed flow CyTOF, we identified a population of ductal cells expressing dendritic cell proteins that was enriched in pancreata from T1D donors. Finally, we confirmed these results independent of islet culture via analysis of spatial features in pancreatic tissue using imaging mass cytometry. Together, our multi-modal analyses, ranging from transcriptomics to spatial proteomics, suggest that in the setting of disease, ductal cells are transcriptionally similar to tolerogenic ductal cells These results imply a previously unappreciated role of these exocrine cells in modulating immune cell activity in long-term T1D.

Disclosure
K. H. Kaestner: None. Hpap consortium: n/a. G. Vahedi: None.

Funding
NIH UC4 DK112217NIH R01CA230800Susan G. Komen CCR185472448 NIH R01HL145754NIH U01DK127768The Burroughs Wellcome FundThe Chan Zuckerberg Initiative, Penn EpigeneticsThe Sloan Foundation
193-LB: Differentiation of PTPN2 Knockout Pluripotent Stem Cells into Stem-Cell–Derived ß-Like Cells Leads to Increased Stimulation of Diabetogenic TCR T Cell Transductants
Authors: MATUSCHEK JULIA Q. , RUSS HOLGER A. , TRIOLO TAYLOR M. , MICHELS AARON W. , MCDANIEL KRISTEN , HANSEN MARIA S. , WILLIAMS SHANE , CASTRO-GUTIERREZ ROBERTO , SHILLEH ALI 
Published: May 2022

Type 1 diabetes (T1D) is an autoimmune disease marked by permanent loss of insulin-producing pancreatic β cells. Genome wide association studies have identified protein tyrosine non receptor type 2 (PTPN2) as a high-risk T1D gene. PTPN2 has been classically implicated in immune cell function, but is expressed in T cells, B cells, and in pancreatic β cells. Mice with a β cell specific knock out (KO) of ptpn2 exhibit impaired function and increased susceptibility to stress induced β cell death. We hypothesized that altered PTPN2 expression in pancreatic beta cells may contribute to T1D disease development. In order to study PTPN2 in the human context we generated CRISPR/Cas9 mediated clonal PTPN2 knock out (KO) hPSCs, abolishing the functional domain of PTPN2. PTPN2 KO and WT hPSCs were differentiated into functional stem cell derived beta-like cells (sBCs) using our published protocol without significant differences in key developmental markers or insulin content. Compared to WT sBC, PTPN2 KO sBCs at steady state and under T1D stress conditions show increased expression of HLA Class I molecules important in T cell recognition. To investigate the interaction of KO or WT sBCs with diabetogenic T cells we employed an HLA-peptide-TCR matched coculture system we recently established. Using this system, we observed increased stimulation of diabetogenic TCR T cell transductants by KO sBC compared to WT. Our data provide evidence for a potential mechanism by which PTPN2, a known T1D high-risk gene may contribute to an immunogenic phenotype of β cells. Our findings suggest that dysregulation of PTPN2 expression contributes to an autoimmune response towards human β cells thus contributing to the pathogenesis of type 1 diabetes.

Disclosure
J. Q. Matuschek: None. H. A. Russ: Consultant; Eli Lilly and Company, Sigilon Therapeutics, Inc. T. M. Triolo: None. A. W. Michels: Employee; ImmunoMolecular Therapeutics, Stock/Shareholder; ImmunoMolecular Therapeutics. K. Mcdaniel: None. M. S. Hansen: None. S. Williams: None. R. Castro-gutierrez: None. A. Shilleh: None.

Funding
NIH: K12DK094712
194-OR: The Effect of Level of Spinal Cord Injury on the Prevalence of Diabetes
Authors: TRBOVICH MICHELLE , DIMAS RUDI , MADER MICHAEL J. , SALEHI MARZIEH 
Published: May 2022

Persons with spinal cord injury (SCI) develop diabetes at much higher rates than those with able bodies. Glycemic effect of SCI is exaggerated in those with higher level of injury (LOI) (e.g.: tetraplegia [TP]) compared to those with lower LOI (e.g.; paraplegia [PP]) . We hypothesized that prevalence and incidence of diabetes is higher in those with higher LOI among SCI patients. In a retrospective cohort study of veterans with spinal cord injury, from 20to 2021, electronic record data on weight, height, gender, ethnicity, level of injury (TP vs. PP) , glucose and A1C levels, and antidiabetic medications were obtained. Diabetes was defined by random glucose &gt;200 mg/dl and HbA1C&gt;6.5%. A total of 9persons with SCI were identified (440 TP/ 471 PP,48 F/863 M, age (22-90) , BMI (13.1-51.4)) . The prevalence of diabetes at the first visit among those with TP and PP was similar (21vs. 20%) . Among 728 nondiabetic subjects with SCI, 1 (34%) with TP vs. 127 (34%) with PP developed type 2 diabetes over a median period of 40m (18-93) vs. 39m (15-75) (p=0.3) . Groups were similar for age and gender distribution, but PP had greater BMI compared to TP (p&lt;0.01) . Despite similar A1C and plasma glycemia between the 2 groups at their first encounters, PP subjects had higher glycemic control estimated by A1C at the time of DM conversion or their last encounter (6.4± 1.7% vs. 6.0± 1.1%, p&lt;0.05) . Of note, a larger number of diabetic patients in this cohort did not receive any antidiabetes medications (76% in TP/ 65% in PP, p=0.09) . At the end of 20-year study period, there were a total of 72 deaths in TP patients with diabetes compared to 60 deaths in PP patients with diabetes (61% vs. 47%, p&lt;0.05) . Our findings indicate that despite greater amount of innervated lean muscle mass and lesser impaired autonomic nervous signaling in persons with PP compared to TP, rate of diabetes development and glycemic control are relatively similar among those with the high and low LOI. However, among SCI patients with diabetes those with TP had worse survival rate than PP.

Disclosure
M.Trbovich: None. R.Dimas: None. M.J.Mader: None. M.Salehi: None.