bluuebunny/crossref_metadata_2025_split huggingface dataset:
27-LB: Prevalence and Severity of Diabetic Retinopathy in African Americans with End-Stage Kidney Disease
Authors: EGEOLU MICHELLE , MANISHIMWE EXAUCEE , ZABALA ZOHYRA E. , MOAZZAMI BOBAK , CALEON RAMONCITO L. , GALINDO RODOLFO J. , NAVARRETE JOSE E. , GERGES AMANY Y.G. , PENG LIMIN , UMPIERREZ GUILLERMO E. 
Published: May 2022

Background and Methods: This cross-sectional study determined the prevalence of diabetic retinopathy (DR) in non-Hispanic African Americans (AA) with end-stage-kidney disease (ESKD) and their impact on quality of life. A total of 95 adults with type 1 (n= 10) and type 2 (n= 85) on dialysis diabetes were assessed for DR using portable hand-held (Optomed Aurora) with artificial intelligence report with AEYE Diagnostic System (AEYE-DS) , visual acuity using a Snellen chart, and social determents of health, and standardized questionnaires (Kidney Disease Quality of Life (KDQoL) , depression screening (Patient health Questionaire-9) and food insecurity.
Results: Among the 95 participants (female 51%, mean age 59.5 ±12.3 years, duration of diabetes (DM) 18.2 ± 12.0 years and duration of dialysis 4.5±3.6 years) . A total of 55% of patients had a diagnosis of (DR+) , who had a longer duration of DM (18.8±9.5 vs. 15.8±12.2 years, p=0.20 and shorter duration of dialysis (3.6±2.7 vs. 5.9±5.0 years compared to DR negative (DR-) , p=0.09. Kidney Disease Quality of Life score on symptoms/problems related to ESKD and greater effect of kidney disease in daily life were lower compared to the general US, AA population with ESKD, p &lt;.0001) . DR+ had worse physical health (p: 0.09) , greater rate of severe vision impact on quality of life (p= 0.01) , similar rates below the federal poverty level per household income (25% vs. 30%) , non-statistically significantly higher Ph-Q9 depression (6.9±5.3 vs. 4.8±4.1, p=0.16) , and food insecurity scores compared to without DR (1.07±1.51 vs. 0.83±1.56, p=0.33) . Overall, the prevalence of diabetic retinopathy was 55% based on the AEYE artificial intelligence system. Diabetic retinopathy was associated with poor quality of life and physical health, higher rates of poverty, and greater impact of vision impairment on quality of life compared to DR negative. Our preliminary finding highlights the increased disease burden of DR in AAs with ESKD, indicating an alarming gap in care.

Disclosure
M. Egeolu: None. G. E. Umpierrez: Research Support; AstraZeneca, Dexcom, Inc., Novo Nordisk. E. Manishimwe: None. Z. E. Zabala: None. B. Moazzami: None. R. L. Caleon: None. R. J. Galindo: Advisory Panel; Sanofi, WW International, Inc., Research Support; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk. J. E. Navarrete: None. A. Y. G. Gerges: None. L. Peng: None.
27-OR: Fatty Acid Uptake and Metabolism in Human Adipose Tissue Is Decreased upon Consuming an Isocaloric High–Saturated Fat Diet and Partially Genetically Determined
Authors: KRUSE MICHAEL , OST ANNE-CATHRIN , HORNEMANN SILKE , HOFFMANN DANIELA , FRAHNOW TURID , BUSJAHN ANDREAS , PFEIFFER ANDREAS F. 
Published: May 2022

CD36 transports fatty acids (FA) into adipocytes and is increased in white adipose tissue (WAT) in obesity. In rodents, however, it was shown that CD36 knock out is protective for diet induced adiposity. In humans a hypocaloric high fat diet decreased CD36 gene expression in WAT. This study investigated the response of gene expression of FA uptake and metabolism in sub cutaneous WAT after a sudden switch from a healthy isocaloric low fat diet to an isocaloric high fat diet (HF) in healthy human twins. 35 monzyogotic and dizygotic healthy pairs of twins (women and men, age 18 - 70) were investigated for 12 weeks. An isocaloric diet rich in carbohydrates (55% carbohydrates, 30% fat, 15% protein, LF) was applied for 6 weeks, followed by an isocaloric diet rich in saturated fat (40% carbohydrates, 45% fat, 15% protein, HF) for another 6 weeks. Body weight (BW) , BMI, serum FA and gene expression of CD36, PDK4, PGC1α and CPT1α by qPCR were analyzed after the LF period, after one week (HF1) and at the end (HF6) of the HF period. BW did not change during the study. Serum FA were unchanged at HF1 but decreased at HF6 by 18% (P&lt;0.compared to LF) . Gene expression of CD 36 was strongly decreased by 33% at HF1 and by 26% at HF6, respectively, compared to LF (both P&lt;0.001) . A significant decrease of gene expression of PDK4 by 18% was observed at HF1 and by 27% at HF6 (both P&lt;0.0compared to LF) . Gene expression of PGC1α and CPT1α were not changed at HF1 but decreased both at HF6 by 14% (both P&lt;0.0compared to LF) and were highly heritable: 64% for PGC1α and 48% for CPT1α. Gene expression was positively correlated with BMI for CD36 at HF1 and for PDK4 at LF, HF1 and HF6 (P&lt;0.05) . These data indicate that gene expression of transport (CD36) and re-esterification (PDK4) of FA are not only dependant on the amount of nutritional fat, but also on energy content. Moreover, expression of genes controlling mitochondrial (PGC1α) and FA (CPT1α) metabolism appear to be genetically determined.

Disclosure
M.Kruse: None. A.Ost: None. S.Hornemann: None. D.Hoffmann: None. T.Frahnow: None. A.Busjahn: None. A.F.Pfeiffer: None.

Funding
German Federal Ministry of Education and Research (0315424)
276-OR: Impaired Glucagon-Mediated Suppression of VLDL-TG Secretion in Individuals with MAFLD
Authors: HEEBØLL SARA , RISIKESAN JEYANTHINI R. , GRONBAEK HENNING , SØNDERGAARD ESBEN , NIELSEN SØREN 
Published: May 2022

Background: Individuals with Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) have both elevated triglyceride and glucagon levels, although glucagon suppresses the very-low-density lipoprotein-triglyceride (VLDL-TG) secretion in lean individuals. Therefore, we hypothesized that the glucagon-mediated suppression of VLDL-TG secretion is impaired in MAFLD, with greater impairment in individuals with steatohepatitis (MASH) than individuals with simple steatosis (MAFL) .
Methods: 28 participants were included in the study (seven overweight control subjects (CON) , patients with MAFL, and with MASH) . We performed a somatostatin-clamp with replacement doses of growth hormone, insulin (0.2 mU/kg/min) and glucagon to suppress endogenous hormone production. Participants were studied during low-dose glucagon infusion (0.65 ng/kg/min, t=0─270 min, LowG) followed by a high-dose glucagon infusion (1.5 ng/kg/min, t=270─450 min, HighG) . We used 14C-labeled VLDL-TG and 3H-labeled glucose tracers to evaluate VLDL-TG secretion and endogenous glucose production (EGP) .
Results: HighG suppressed VLDL-TG secretion compared to LowG in all groups, but with a greater reduction in VLDL-TG secretion in CON than in the MAFLD groups (CON 36% (±SD 19%) ; MAFL 10% (±SD 8%) ; MASH 13% (±SD 16%) , p&lt;0.01) . Thus, the suppression was similarly mitigated in both MAFLD groups. This led to insignificant reductions in plasma VLDL-TG, TG and VLDL-TG oxidation rates in the CON group, in contrast to stable or increasing values in the MAFLD groups (CON vs. MAFLD delta-values, p&lt;0.01, p=0.02 and p=0.04) , respectively) . EGP was similar in all groups throughout the LowG period and rose similarly when increasing glucagon infusion rate.
Conclusions: Patients with MAFLD, MAFL as well as MASH, have an impaired glucagon-mediated suppression of VLDL-TG secretion which is a probable contributing factor to the dyslipidemia and the increased cardiovascular risk observed in individuals with MAFLD. NCT04042142

Disclosure
S.Heebøll: None. J.R.Risikesan: None. H.Gronbaek: Other Relationship; ARLA, Research Support; AbbVie Inc., Intercept Pharmaceuticals, Inc., Speaker's Bureau; AstraZeneca, Novartis AG. E.Søndergaard: None. S.Nielsen: None.

Funding
Independent Research Fund Denmark (9039-00177B and -00278B) and Aase og Ejnar Danielsens Fond
289-OR: Automated Insulin Delivery Use among 12,065 T1D Exchange Registry Participants
Authors: LIU JINGWEN , MILLER KELLEE , KELLY CAITLIN , CHAPMAN KATHERINE S.M. , PETER MEGAN , FINAN DANIEL , NGUYEN HUYEN , LAFERRIERE KELSIE , LEON CAROLINA , WOLF WENDY 
Published: May 2022

Use of automated insulin delivery (AID) in people with type 1 diabetes (T1D) has increased in recent years. We analyzed data from the T1D Exchange Registry - an online longitudinal study following adults and children with T1D - to describe characteristics of AID use and its association with self-reported HbA1c, occurrence of diabetic ketoacidosis (DKA) symptoms, and occurrence of severe hypoglycemia events (SHE) . Of 12,065 participants (69.5% female, 87.5% non-Hispanic White, mean age 37.9 yrs, mean T1D duration 19.9 yrs) , 26.4% reported using AID, 43.6% using insulin pump without AID, and 30.0% using multiple daily injections (MDI) . Private insurance was reported in 77.4% of AID users, 74.9% pump without AID, and 66.3% MDI. Among the 3,185 AID users, 50.6% used predictive low glucose suspend (PLGS) features, including Medtronic 640G and Tandem Basal-IQ; 49.4% used hybrid closed-loop (HCL) , including DIY looping, Medtronic Auto Mode, and Tandem Control-IQ. Average HbA1c was lower in AID users than those using MDI and pump without AID; Incidence of SHE was lower among HCL users compared with PLGS users and AID users compared with MDI users (Table 1) . These cross-sectional real-world data support findings of previous clinical studies showing significant improvements in HbA1c with AID use, with HCL use providing additional protection against SHE.

Disclosure
J.Liu: None. W.Wolf: None. K.Miller: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc. C.Kelly: None. K.S.M.Chapman: None. M.Peter: None. D.Finan: None. H.Nguyen: None. K.Laferriere: None. C.Leon: None.
291-OR: Using the Performance in Exercise and Knowledge (PEAK) Guidelines Incorporated in a Smartphone-Based Decision Support System Improves Glucose Outcomes during Free-Living Exercise
Authors: WILSON LEAH M. , JACOBS PETER G. , GUILLOT FLORIAN H. , TYLER NICHOLE S. , KUSHNER TAISA , ESPINOZA ALEJANDRO Z. , MOSQUERA-LOPEZ CLARA M. , PINSONAULT JOSEPH , DODIER ROBERT , OGANESSIAN SOS M. , BRANIGAN DEBORAH , GABO VIRGINIA , EOM JAE H. , YOUSSEF JOSEPH EL , WINTERS-STONE KERRI , CASTLE JESSICA R. 
Published: May 2022

DailyDose is a smart-phone decision support system developed at Oregon Health & Science University that uses Dexcom G6 CGM and Medtonic’s InPen. The app calculates insulin doses using CGM value and trend, insulin-on-board, carbohydrate amount, and exercise information. Insulin dosing and carbohydrate intake recommendations before and after exercise are adjusted according to the 2017 consensus statement by Riddell et al. known as the PEAK Guidelines. Twenty-four adults with T1D, using multiple daily injections of insulin at baseline, completed a two-week run-in period then used the DailyDose intervention for 8 weeks. Participants completed 3 at-home exercise sessions per week, one aerobic exercise video and two other sessions of their choice. We examined the impact of the use of PEAK guidelines on glucose outcomes during exercise comparing 176 exercise sessions done during run-in and 471 sessions done during the intervention period. Glucose outcomes were assessed from start of exercise to 4 hours after the start or until either a meal was consumed, insulin dosed or new exercise session initiated. Mixed effects analysis was used to determine significance of the intervention on glucose outcomes. The nadir of the glucose was lower for the run-in compared with the intervention (120.6 vs. 130.9 mg/dL, P=.012) . Change in glucose from the start of exercise to the nadir was 58.0 for the run-in versus 46.9 for the intervention period (P=.016) . Time in hyperglycemia (&gt;180mg/dL) during the exercise periods trended toward being lower during the intervention (43.8% run-in, 35.0% intervention, P=.059) , as did time in range of 70-180 mg/dL, (54.2% run-in, 62.2% intervention, P=.081) . There was no difference in time in hypoglycemia. Data suggest that use of PEAK within a decision support app can help prevent more severe glucose drops during and after exercise with a trend toward improving time in range.

Disclosure
L.M.Wilson: n/a. S.M.Oganessian: None. D.Branigan: None. V.Gabo: None. J.H.Eom: None. J.El youssef: None. K.Winters-stone: None. J.R.Castle: Advisory Panel; Insulet Corporation, Novo Nordisk, Zealand Pharma A/S, Stock/Shareholder; Pacific Diabetes Technologies. P.G.Jacobs: Other Relationship; Pacific Diabetes Technologies, Research Support; Dexcom, Inc. F.H.Guillot: Stock/Shareholder; Pacific Diabetes Technologies. N.S.Tyler: None. T.Kushner: Consultant; Tandem Diabetes Care, Inc. A.Z.Espinoza: None. C.M.Mosquera-lopez: None. J.Pinsonault: None. R.Dodier: None.

Funding
The Leona M. and Harry B. Helmsley Charitable Trust (Grant 2018PG-T1D001) , OHSU Medical Research Foundation, Supplies provided by Dexcom
296-OR: Single-Cell Multiomic Analysis of the Human Pancreas in Type 1 Diabetes
Authors: MELTON REBECCA , BEEBE ELISHA , ZENG CHUN , MILLER MICHAEL T. , WANG GAOWEI , MCGRAIL CAROLYN , MUMMEY HANNAH , KUSMARTSEVA IRINA , ATKINSON MARK A. , PREISSL SEBASTIAN , SANDER MAIKE , GAULTON KYLE J. 
Published: May 2022

The cis-regulatory programs of specific cell types in the pancreas that are affected in type 1 diabetes (T1D) are poorly understood. Single cell technology enables detailed interrogation of genomic profiles of cell types within a heterogeneous tissue, and when applied to samples across disease states can reveal cell type-specific changes in disease. In this study we applied single nucleus RNA-seq (snRNA-seq) and single nucleus ATAC-seq (snATAC-seq) , as well as paired multiome (snRNA-seq+snATAC-seq) , to cryopreserved whole pancreas samples from 34 donors including 13 control, 9 T1D autoantibody positive (Aab+) , 7 early T1D (1&lt; yr) and 5 late T1D donors in the nPOD biorepository. Clustering of 313,078 gene expression and 342,863 accessible chromatin profiles after extensive processing and filtering resolved pancreatic endocrine, exocrine, immune, stellate, glial and endothelial cell types, as well as known and novel cell sub-types for example REG1A+ acinar cells and MUC5b+ ductal cells. There were marked changes in the abundance of many cell types and sub-types across disease states, including a significant reduction in beta cells and increase in immune cell populations in T1D compared to control. Differential analysis of gene expression and cis-regulatory element (cCRE) activity in each cell type revealed changes in early and late T1D, as well as in T1D Aab+. In beta cells, 2 and 2,177 genes and 1,080 and 9,177 cCREs had differential activity in early and late T1D, respectively, and early and late T1D genes in beta cells were enriched for distinct molecular processes related to interferon gamma signaling and cell death. Intersecting differential beta cell cCREs with comprehensive T1D genetic fine-mapping revealed 13 T1D signals where candidate variants mapped in a differential beta cell cRE of which were proximal to a differentially expressed gene, such as at the GLIS3 locus. Together these results provide insight into the role of cis-regulatory programs in beta cells and other pancreatic cell types in T1D.

Disclosure
R.Melton: None. S.Preissl: None. M.Sander: None. K.J.Gaulton: Consultant; Genentech, Inc., Stock/Shareholder; Neurocrine Biosciences, Inc., Vertex Pharmaceuticals Incorporated. E.Beebe: None. C.Zeng: None. M.T.Miller: None. G.Wang: None. C.Mcgrail: None. H.Mummey: None. I.Kusmartseva: None. M.A.Atkinson: None.

Funding
Ruth Kirschstein Institutional National Research Service Award T32 (GM008666) National Institutes of Health (DK120429)
299-OR: Molecular and Physiological Consequences of the Diabetes-Related PGC1A Gly482Ser Polymorphism
Authors: GALIPEAU MARIA , JOUVET NATHALIE , COURTY EMILIE , VANDENBEEK ROXANNE , KHAN NAVEEN P. , BOUYAKDAN KHALIL , NIAN CUILAN , IORIO CATERINA , SCOTT DANIEL D. , FARAJ MAY , OEFFINGER MARLENE , LYNN FRANCIS C. , SCREATON ROBERT A. , ALQUIER THIERRY , ESTALL JENNIFER L. 
Published: May 2022

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1A) is a nuclear transcriptional coregulator that plays a major role in the control of metabolism and mitochondrial biogenesis. We showed that a diabetes-linked single nucleotide polymorphism (SNP rs8192678) within the coding region of PPARGC1A gene (Gly482Ser) results in decreased protein stability and half-life in liver and beta-cell lines and human induced pluripotent stem cells (iPSCs) . Our mass spectrometry data suggest that degradation of the S482 variant is mediated by phosphorylation at amino acid 482 when a serine is present. A kinome screen identified three potential kinases (NEK2, MARK4 and S6K2) that can modify this site. We found that mutation of the mouse homolog at the conserved site (serine to glycine) similarly stabilized mouse PGC1A. To study the physiological consequences of this SNP, we generated whole-body homozygous glycine (G/G) , serine (S/S) and heterozygous (S/G) mice. We analyzed various metabolic parameters in male (N=10-per genotype) and female (N=8-9) mice subjected to standard chow or high fat, high fructose diet (HFHF) for 14 or 24 weeks. We found that G/G male and female mice had increased caloric intake using metabolic cages without increased body weight. Male mice on a HFHF diet carrying a glycine allele (G/G or S/G) were more resistant to insulin in an insulin tolerance test (ITT) , secreted less insulin in response to a mixed-meal challenge and had decreased glucose uptake in muscle and adipose tissue. In line in humans, non-diabetic subjects with G/G (N=20) or G/S (N=22) variants oxidize more fat while those with S/S variant (N=6) oxidize more carbohydrate over 6-hours following the ingestion of a high-fat meal (68% fat, 18% carbohydrate) .
In summary, these results demonstrate that differences in PGC1A stability associated with phosphorylation at site 482 may lead to differences in glucose and fat metabolism, which could explain the link between this SNP and metabolic diseases.

Disclosure
M.Galipeau: None. M.Faraj: None. M.Oeffinger: None. F.C.Lynn: None. R.A.Screaton: None. T.Alquier: None. J.L.Estall: None. N.Jouvet: None. E.Courty: None. R.Vandenbeek: None. N.P.Khan: None. K.Bouyakdan: None. C.Nian: None. C.Iorio: None. D.D.Scott: None.

Funding
CIHR (PJT-148771) CIHR (PJT-168853)
30-LB: Multicenter, Randomized Controlled Clinical Investigation Evaluating a Unique Micro Water Jet Technology Device Versus Standard Debridement in the Treatment of Diabetic Foot
Authors: ARMSTRONG DAVID G. , ZELEN CHARLES 
Published: May 2022

Background: Proper debridement of the wound base is critical to facilitate wound granulation and closure in non-healing diabetic foot ulcers (DFUs) . A unique micro water jet device has been developed that precisely cleans acute and chronic wounds in a tissue-preserving manner while performing a precise mechanical cleaning and stimulation of the wound base to enhance granulation and healing. In this trial the device was used to treat non healing DFUs.
Methods: 85 patients were screened, and 50 patients were enrolled for the preliminary analysis, in a two arm randomized controlled trial. Diabetic foot wounds that were non-healing for at least 4 weeks, with adequate blood flow and were void of clinical infection or osteomyelitis were entered into 2 weeks of screening. Those that met all the qualifications were randomized to receive either weekly micro jet wound debridement or standard sharp debridement along with SOC wound dressing and offloading. Both groups were followed for 16 weeks. The study endpoints included healing at 16 weeks as well as percent area wound reduction (PAR) over the treatment phase of 16 weeks.
Results: At 16 weeks 72% (18/25) of the Micro Water jet treated DFUs healed compared with 40% (10/25) treated with standard sharp debridement p=0.023 (unadjusted) . Furthermore, at 16 weeks, the percent area reduction (PAR) was 86.5% (SD: 25.60) for the wounds treated with the Micro Water Jet versus 35.1% (SD: 164.47) with standard sharp wound debridement p=0.021 (unadjusted) . The safety analysis showed with regard to wound related adverse events (AE) and serious adverse events (SAE) ; 1 AE and 1 SAE occurring in the Micro Water jet group versus 9 AEs and 4 SAEs in the standard sharp debridement group.
Conclusion: The micro water jet device was able to statistically significantly close more refractory DFUs over 16 weeks, with a significant difference in wound area reduction that should be noted. Further evaluation with larger randomized controlled trials are warranted to validate these initial promising findings.

Disclosure
D. G. Armstrong: None. C. Zelen: Research Support; Geistlich Pharma, Medaxis LLC, Musculoskeletal Transplant Foundation, PolarityTE, Inc.

Funding
Medaxis LLC (A0010)
311-OR: Regulation of Brown Adipocyte Differentiation and Thermogenesis by Prostaglandin F2a
Authors: FADUMIYE ESTHER , KODANI SEAN , KIEBISH MICHAEL , BUSSBERG VALERIE , TSENG YU-HUA 
Published: May 2022

Brown adipocytes hold the potential to mitigate body fat accumulation and type 2 diabetes (T2D) via their specialized function in dissipating energy as heat, a process known as thermogenesis. To fuel their function, brown adipocytes release the bond energy of fat through lipolysis and β-oxidation; then, uncoupling cellular respiration releases this energy as physical heat. In addition to their energy-dissipating function, brown adipocytes can release factors, such as lipids, metabolites, peptides, or microRNA, to regulate metabolism. Signaling lipids have demonstrated roles in regulating thermogenesis in brown adipocytes by regulating lipid uptake and utilization. To further explore these pathways, we performed signaling lipidomics analysis in in vitro differentiated human brown adipocytes and found 15-keto-PGF2α was increased when treated with forskolin, an adenylyl cyclase activator that mimics adrenergic stimulation. Previous studies have shown PGF2α, the parent molecule of 15-keto-PGF2α, inhibits maturation, or adipogenesis, in white adipocyte cell lines by preventing the expression of key adipogenesis genes, such as PPARγ and C/EBPα. Similarly, PGF2α inhibits thermogenic gene expression in brown adipocyte cells. To explore and compare the functional activities of PGF2α and 15-keto-PGF2α, we characterized the dose-response relationship of these lipids on thermogenic gene and protein expression. We found that 15-keto-PGF2α is not as potent as PGF2α at inhibiting both thermogenic gene and protein expression. This suggests the conversion of PGF2α to 15-keto-PGF2α represents a significant signaling event to promote thermogenesis in brown adipocytes. Interestingly, carbonyl reductase 1, an enzyme that catalyzes this conversion, is regulated by treatment with the adrenergic agonist, norepinephrine, in vitro and by cold exposure in vivo. Targeting this conversion may be an attractive approach towards activating thermogenesis to mitigate obesity and T2D.

Disclosure
E.Fadumiye: None. S.Kodani: None. M.Kiebish: None. V.Bussberg: None. Y.Tseng: Consultant; Cellarity.

Funding
National Institutes of Health (R01DK122808)