bluuebunny/crossref_metadata_2025_split huggingface dataset:
1265-P: The Role of Health System Penetration Rate in Estimating Prevalence of Type 1 Diabetes (T1D) in Children and Adolescents Using Electronic Health Records (EHR)
Authors: LI PIAOPIAO , LYU TIANCHEN , BIAN JIANG , GUO YI , SHENKMAN ELIZABETH , DONAHOO WILLIAM T. , GUO JINGCHUAN , SHAO HUI 
Published: May 2022

This study aimed to develop a novel method that can accurately estimate the prevalence of T1D in children and adolescents using EHR data. T1D cases among individuals &lt;= 18 years old were identified from the OneFlorida EHR (2018-2020) using a computable phenotype algorithm we have developed. The T1D prevalence was estimated at the zip code level, with numerator being the total T1D cases and the denominator being the number of residents in each zip code area extracted from the census data. The observed health system penetration rates (HSPR) in 20 were estimated as a ratio of total patients who visited the healthcare systems in the OneFlorida network (2018-2020) to the total number of residents in each zip code area in 2019. We applied a joint-point regression to determine the cutoff thresholded where the observed HSPR can produce accurate prevalence estimation. The cutpoint value of 72.0% for the observed HSPR was identified, and the trend line between prevalence and HSPR plateaued in areas with HSPR&gt;72% (slope=0.002, figure) . The estimated T1D prevalence in 20 was 0.243%, which is similar to that of estimated by SEARCH (0.255%) . Our algorithm provides a critical tool for developing a EHR-based diabetes surveillance system in the US.

Disclosure
P.Li: None. T.Lyu: None. J.Bian: None. Y.Guo: None. E.Shenkman: None. W.T.Donahoo: None. J.Guo: None. H.Shao: Board Member; BRAVO4HEALTH, LLC.

Funding
U18DP006512 CDC/NIDDK
127-OR: Diabetic Foot Ulcers in Remission: Cyclical-Pressure Topical Wound Oxygen Therapy Significantly Reduces DFU Related Hospitalizations and Amputations over a 12-Month Period
Authors: GAROUFALIS MATTHEW G. 
Published: May 2022

Purpose: The purpose of this real-world evidence (RWE) cohort study was to evaluate whether utilization of Cyclical-Pressure Topical Wound Oxygen (TWO2) therapy had any impact on the incidence of Diabetic Foot Ulcer (DFU) related hospitalizations and amputations over a 12-month period in patients with hard to heal Diabetic Foot Ulcers (DFU)
Methods: An IRB approved retrospective review of deidentified DFU patient medical records was conducted at 2 US Veterans Affairs Medical Centers in Illinois and Virginia, which included demographic information on wound characteristics, clinical characteristics, neuropathy, cardiovascular disease (CVD) , peripheral vascular disease (PVD) , pain level and kidney disease etc.
Results: Within the unmatched cohorts of 202 DFU patients (91 TWO2, 1NO TWO2) there was an 88% reduction in hospitalizations and 71% reduction in amputations over the 12-month period for the patients treated with TWO2 therapy compared to those that did not receive TWO2 therapy. After propensity score matching was conducted, which minimizes the effects of confounding by achieving more balanced covariates in the absence of a randomized study, resulting in matched cohorts of 140 DFU patients (70 TWO2, 70 NO TWO2) , 82% fewer TWO2 patients were hospitalized) and 73% fewer TWO2 patients had amputations, compared to those who did not receive TWO2 therapy (p &lt; 0.0001, p = 0.00 respectively) .
Conclusions: This large RWE study demonstrates that TWO2 therapy positively impacts patient’s quality-of-life and the costs associated with treating their DFU by forcing them into remission, resulting in significantly reduced rates of amputations and hospitalizations.

Disclosure
M.G.Garoufalis: None.
128-OR: Income-Related Disparities in Medical Expenditures in U.S. Adults with Diabetes
Authors: WANG YU , SHAO HUI , IMPERATORE GIUSEPPINA , HOLLIDAY CHRISTOPHER S. , ZHANG PING 
Published: May 2022

Relatively little is known about diabetes-related medical costs across income groups, yet such information can assist efforts to reduce income-related diabetes disparities. Using data from the 2017-20 Medical Expenditure Panel Survey, we estimated medical expenditures (total and by service category [inpatient, outpatient, and drug]) in adults with diabetes, overall and by income level (&lt;125% of federal poverty level (FPL) , ≥125% and &lt;200% FPL, ≥200% and &lt;400% FPL, ≥400% FPL) . We also identified factors that contribute to the differences (education, health insurance, marital status, physical and mental health) by constructing a concentration index (CI) (an inequality measure with values ranging from -1 to 1 with 0 indicating no disparity) and conducting a decomposition analysis which quantifies the contribution to CI by factor. We estimated crude and adjusted medical expenditures by income group, controlling for age, sex, and race/ethnicity. All expenditures were adjusted to 20 US dollars. Persons with incomes &lt;125% FPL had significantly higher health medical expenditures in total and across all service categories than the other three income groups (P&lt;0.05) . After adjustments, the lowest income group spent $2828 more per person per year than the other three income groups (P&lt;0.05) while no significant differences in expenditures were found among the other three groups. The estimated CI value was -0.022, indicating expenditures more concentrated in the lower income group About a half (49.1%) of the disparity was explained by higher public insurance coverage (28.6%) and poorer physical (13.3%) and mental (7.2%) health status. Diabetes-related medical expenditures are disproportionately concentrated among low-income group. Improving physical and mental health for low-income populations may help to reduce the disparity in medical expenditures of diabetes.

Disclosure
Y.Wang: None. H.Shao: Board Member; BRAVO4HEALTH, LLC. G.Imperatore: None. C.S.Holliday: None. P.Zhang: None.
1292-P: Differential Glycaemic Effects of Recombinant IL-9 across Species Highlight Translational Challenges for Immunometabolic Phenotypes
Authors: GUO TINGQING , STRAARUP ELLEN MARIE , CHRISTENSEN JOSEFINE LINDROOS , BOLT GERT , NØRBY PEDER LISBY , ZHE WANG , PEDERSEN THOMAS A. , FERRERAS MERCEDES , SASS-ØRUM KRISTIAN , FREDERIKSEN KLAUS S. 
Published: May 2022

In the present study, IL-9 was initially identified as a strong regulator of blood glucose in diabetic db/db mice through a hydrodynamic gene delivery screening effort. IL-9 belongs to the common gamma-chain binding cytokine family and has classically been linked to asthma and type 2 immune responses. Alongside the very clear dosing effects of mouse IL-9 on fasting blood glucose, the more classical effects of IL-9, including IL-5 plasma increases and eosinophilia, were also observed in the db/db mice. An expansion of epididymal white adipose tissue macrophages was shown with IL-9-, but not IL-5 dosing. Inhibition of endogenous IL-5, with an anti-IL5 mAb, attenuated the IL-9 effects on eosinophils but not macrophages. Interestingly, suppression of glucagon levels following IL-9 dosing was a general observation in several diabetic mouse studies. The addition of anti-IL-5 mAb to IL-9 dosing did not affect glucagon levels in the db/db mouse model, and an association between eosinophil/macrophage changes and blood glucose could not be established. To examine the translation of these interesting IL-9 effects to higher species, a recombinant protracted human IL-9 dosed to low streptozotocin induced diabetic mini-pigs (2-week study) , showed increased numbers of circulating eosinophils, but no significantly reduced levels of glucagon or plasma glucose. Finally, an 11-week treatment study in type 2 diabetic cynomolgus monkeys was performed. Eosinophilia was observed as an indicator of IL-9 receptor engagement, but several glycaemic parameters and glucagon levels were unaffected throughout the study. Conclusion: The pronounced glycaemic effects observed for IL-9 in a diabetic mouse model was not found in diabetic minipigs and non-human primates highlighting the complexity and need for further studies of the translation of immuno-metabolic phenotypes.

Disclosure
T.Guo: Employee; Novo Nordisk A/S. K.S.Frederiksen: Employee; Novo Nordisk A/S. E.Straarup: Employee; Novo Nordisk A/S. J.Lindroos christensen: Employee; Novo Nordisk A/S. G.Bolt: Employee; Novo Nordisk A/S. P.Lisby nørby: Employee; Novo Nordisk A/S. W.Zhe: Employee; Novo Nordisk A/S. T.A.Pedersen: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. M.Ferreras: Employee; Novo Nordisk A/S. K.Sass-ørum: Employee; Novo Nordisk A/S.
1293-P: Diabetes Management at the Time of Renal Transplantation
Authors: GRIFF MEGAN , CRAWLEY SVITLANA , ROWLAND ANN , SEGGELKE STACEY A. , HAWKINS R. MATTHEW , WANG CECILIA C. LOW 
Published: May 2022

The goal of this retrospective review was to characterize the glycemic status and antihyperglycemic treatments in persons with diabetes (PwD) undergoing renal transplant and to determine whether use of intravenous insulin infusion (IVI) is associated with clinical outcomes. A retrospective review of all adult patients undergoing renal transplantation at a single tertiary referral center from January 1 - December 31, 20 was performed.
Results: Of the 292 patients who underwent renal transplantation, 1 (34.6%) had a diagnosis of diabetes. Pre-transplant treatment for diabetes included insulin in 61 (60.4%) , non-insulin medications in (10.9%) , and both insulin and non-insulin medications in 5 PwD (4.9%) . Twenty-four PwD (23.8%) were not taking medications for diabetes. While hospitalized 65 (64.4%) PwD received IVI while the remainder received SC insulin (SCI) . The pooled daily mean point of care (POC) glucose on postoperative day (POD) 0 through POD 3 was not significantly different between IVI vs. SCI (164.5 vs. 165.3mg/dL, p=0.91) . ICU admission occurred in 7 (10.8%) IVI and 8 (22.5%) SCI (OR 0.42, 95% CI 0.14-1.28) . Fourteen (21.5%) IVI and 5 (13.9%) SCI underwent dialysis during hospitalization (OR 1.70, 95%CI 0.56-5.19) . Readmission within 30 days occurred for 17 (26.6%) IVI and 12 (33.3%) SCI (OR 0.53, 95% CI 0.22-1.27) .
Discussion: While pre-transplant treatment of diabetes varied, most PwD undergoing renal transplantation were placed on IV insulin for management of hyperglycemia post-transplant. Insulin infusion was not associated with significant differences in pooled daily mean blood glucose. Significant differences in clinical outcomes were not identified between those treated vs. not treated with insulin infusion, but this could be due to the relatively small sample size. More research is needed to understand how diabetes care can be improved in hospitalized PwD undergoing renal transplantation.

Disclosure
M.Griff: None. S.Crawley: None. A.Rowland: None. S.A.Seggelke: None. R.Hawkins: None. C.C.Low wang: Employee; CPC Clinical Research, Research Support; CellResearch Corporation, Virta Health Corp.
1300-P: Novel Insulin Modified Oral Glucose Tolerance Test Improves the Estimation of Insulin Sensitivity and Glucose Effectiveness
Authors: STEFANOVSKI DARKO , PICCININI FRANCESCA , ADER MARILYN , KABIR MORVARID , BERGMAN RICHARD N. 
Published: May 2022

Estimating insulin resistance from the oral glucose tolerance test (OGTT) has long been a challenge in diabetes research and practice. Because the time courses of glucose and insulin during the OGTT are similar in shape, the estimates of insulin sensitivity per se may be corrupted by other metabolic responses such as insulin release or glucose absorption. We have previously shown insulin injection during the intravenous test yields accurate values of insulin sensitivity (SI) and glucose effectiveness (SG) . Here we examine an analogous approach during the OGTT - in which exogenous insulin is administered during the test. Methods: For 100 simulated subjects (NGT: n=25, IGT: n=25, T2D: n=25, T1D: n=25) , glucose and insulin data were calculated using Dalla Man Mixed Meal Simulator. For each simulated subject, several protocols were examined by varying the time of insulin bolus (30, 60, or 90 min) and the dose of the bolus (0, 0.01, 0.02, or 0.03 IU/kg) . The resulting 3600 simulated datasets were analyzed with Dalla Man’s OGTT model to estimate SI. Results: When adjusted for the dose of insulin, the time of the dose did not significantly impact the estimation of SI. The 0.IU/kg insulin dose resulted in significantly (P&lt;0.001) better estimates of SI when compared to the three other doses. Unique estimates of SG were obtained only without and with insulin dose of 0.IU/kg. There was no difference (P=NS) between the quality of SG estimates with these two doses. Conclusions: An intravenous insulin bolus of 0.IU/kg given at 60 min during the OGTT will enable accurate and precise estimations of both SI and SG.

Disclosure
D.Stefanovski: None. F.Piccinini: Employee; Medtronic. M.Ader: None. M.Kabir: None. R.N.Bergman: Consultant; Fractyl Health, Inc., Novo Nordisk, Research Support; AstraZeneca, Janssen Research & Development, LLC.
1307-P: Leptin Action in the Nucleus of the Solitary Tract
Authors: BRUCE KYLA , LI ROSA J.W. , LIM YUMI , YUE JESSICA T. , LAM TONY K. 
Published: May 2022

Obesity and diabetes are characterized by a disruption in energy balance and glucose homeostasis in association with leptin resistance. Leptin action in the hypothalamus regulates glucose levels and body weight, but whether other brain regions facilitate leptin action remain unclear. Here, we investigate whether the nucleus of the solitary tract (NTS) of the brainstem is a crucial site for leptin action in regulating glucose homeostasis in 3d high-fat (HF) -fed male rats, as recent studies report leptin activates leptin receptor in the NTS to regulate feeding. In this study, we performed brain stereotaxic bilateral surgery targeting the NTS followed one week later by catheterization of the left carotid artery and right internal jugular vein for infusion/sampling purposes. Rats that attained &gt;90% of presurgical weight received 3d of Lard oil enriched HF diet and were fasted 4-6 hr before undergoing a 2min pancreatic (basal insulin) -euglycemic clamp studies together with tracer glucose infusion to assess glucose metabolism independent of changes in plasma insulin and glucagon levels. Leptin (91.7 ng/uL at 0.33 ul/hr) or saline was infused into the NTS throughout the duration of the clamp studies. Correct placement of the NTS catheter was verified by infusion of bromophenol blue dye through the brain cannula. For the first time, we found that leptin vs. saline infusion into the NTS markedly increased the exogenous glucose infusion [lep: 4.6±0.2 vs. sal: 1.3±0.4 mg/kg/min; p&lt;0.005; n=12, 5] required to maintain euglycemia [lep: 137.5±2.2 vs. sal: 145±3.1 mg/dl; p&gt;0.05; n=12, 5], during the clamps. The drop in plasma glucose levels was due to an inhibition of glucose production [lep: 4.9±0.1 vs. sal: 8.4±0.7 mg/kg/min; p&lt;0.01; n=12, 5], but not an increase in glucose uptake [lep: 10.4±0.5 vs. sal: 9.7±0.3 mg/kg/min; p&gt;0.05; n=12, 5]. These findings demonstrate that the NTS mediates leptin action on glucose homeostasis. Future studies are needed to investigate the NTS leptin signaling cascade in glucose homeostasis in obesity and diabetes.

Disclosure
K.Bruce: None. R.Li: None. Y.Lim: None. J.T.Yue: None. T.K.Lam: None.

Funding
Canadian Institutes of Health Research Foundation Grant (FDN-143204)
1309-P: Central Mechanisms of Pollution-Induced Metabolic Disease
Authors: DEBARBA LUCAS K. , KOSHKO LISA , JAYARATHNE HASHAN M. , YI ZHENGPING , KLUEH ULRIKE , SADAGURSKI MARIANNA 
Published: May 2022

There is growing evidence linking exposure to volatile organic compounds (VOC) in ambient air with metabolic disease in humans. Benzene is a prominent VOC present in water, food, detergents, vehicle exhaust, tobacco smoke, and e-cigarettes. However, a direct link between exposure to VOC and metabolic homeostasis is not yet established. We performed a meta-analysis and found a positive association between exposure to VOC and metabolic impairments. Using a highly controlled mouse exposure system, we have recently demonstrated that chronic exposure of mice to VOC induces neuroinflammation and insulin resistance predisposing to T2D. To establish a timeline for the onset of VOC-triggered metabolic effects, we monitored glucose changes of exposed mice using continuous glucose monitoring (CGM) system. Surprisingly, we detected significant changes in glycemic control of male mice starting at day 4 of exposure. Further, mice exhibited impaired parameters of energy homeostasis within 6h of exposure. This was associated with activation of hypothalamic gliosis via stimulation of the NF-κB signaling and dysregulation of hypothalamic insulin signaling, contributing to blunted responses to glucose stimulation in glucose-sensing neurons. To determine the role of the central inflammatory mechanism in VOC-induced metabolic imbalance, we genetically ablated NF-κB signaling in microglia using Cx3cr1creERΔIKK mice. Selective inhibition of microglial NF-κB signaling completely restored hypothalamic insulin signaling, astrocytes activation, and hypothalamic glucose-sensing, consequently protecting from whole-body metabolic imbalance induced by VOC exposure. Importantly, this effect was mediated via hypothalamic ER stress response. Collectively, our data provide evidence that neuroinflammatory responses precede and mechanistically contribute to whole-body metabolic imbalance and identify air pollution-induced cellular and molecular targets in the hypothalamus that lead to metabolic disease.

Disclosure
L.K.Debarba: n/a. L.Koshko: None. H.M.Jayarathne: None. Z.Yi: None. U.Klueh: Research Support; Dexcom, Inc. M.Sadagurski: None.

Funding
American Diabetes Association (1-18-JDF-063)
1311-P: Glucokinase in AGRP Neurons Is Required for Normal Insulin Secretion and Action in Female Mice
Authors: JOSIPOVIC MASA , STARICOFF EMILY O. , RICHES CHRISTINE H. , SHEPPARD LAURA , EVANS MARK 
Published: May 2022

Discrete brain areas, including hypothalamic nuclei, have been implicated in glucose homeostasis. Some contain molecular machinery capable of detecting changes in blood glucose such as glucokinase (GK) , a low affinity hexokinase important for pancreatic beta cell glucose-sensing. A subset of arcuate nucleus AGRP neurons express GK. We created GKAGRP knockout (KO) mice by crossing AGRP Cre with GK floxed mice, hypothesizing that they would display impaired gluco-regulation. Despite established sex differences in metabolic neurocircuitry, female mice are not always studied. In pilots, we found impaired glucose handling in i.p. glucose tolerance tests in older GKAGRP KO females, but not younger female, nor male mice. Here, we perform detailed phenotyping, using sequential euglycemic (with stable glucose isotope tracers) and hyperglycemic clamp studies in conscious, free moving, 19-23 week old female mice with implanted carotid artery and jugular vein catheters. As shown below, we found that GKAGRP KO females were insulin resistant with a lower dextrose infusion rate and reduced suppression of hepatic glucose production during euglycemic clamps. They also displayed reduced insulin secretory responses during hyperglycemic clamps. Our data support a sexually-dimorphic central gluco-regulatory role for AGRP neurons which requires the presence of GK to facilitate normal insulin release and action.

Disclosure
M.Josipovic: Research Support; Novo Nordisk A/S. E.O.Staricoff: Research Support; Novo Nordisk A/S. C.H.Riches: Research Support; Novo Nordisk. L.Sheppard: None. M.Evans: Advisory Panel; Pila Pharma, Zucara Therapeutics, Other Relationship; Abbott Diabetes, Dexcom, Inc., Medtronic, Novo Nordisk, Research Support; AstraZeneca, Sanofi, Speaker’s Bureau; Lilly Diabetes.

Funding
European Union’s Innovative Medicines Initiative 2 Joint Undertaking (grant agreement 777460) also supported by EFPIA, T1D Exchange, JDRF, International Diabetes Federation (IDF) , The Leona M. and Harry B. Helmsley Charitable Trust, Wellcome Trust, Medical Research Council UK and Gates Cambridge Trust.
1314-P: Activating GABAergic Neurons in the Caudal Preoptic Area Promote Energy Expenditure in Diet-Induced Obesity
Authors: BASU RASHMITA , ELMENDORF ANDREW J. , MAHLER CONNOR A. , FLAK JONATHAN 
Published: May 2022

Obesity results from the imbalance between energy intake and energy expenditure, which are tightly regulated by dynamic hypothalamic circuits. Our goal is to identify and leverage hypothalamic components that promote energy expenditure for successful weight loss. Vesicular communication by ventromedial hypothalamic nucleus (VMN) steroidogenic factor 1 (Sf1) neurons is required for maintaining body weight, due at least in part to stimulating metabolic activity in adipose tissue, but the mechanistic details are unclear. VMNSf1 neurons efferently communicate with relatively few places in the brain but the most prominent projections are in the most caudal regions of the preoptic area (cPOA) (+0.1 to -0.3mm bregma, lateral to the suprachiasmatic nucleus) . We tested the hypothesis that GABAergic cPOA neurons promote energy expenditure and weight loss by activating either GABAergic or glutamatergic neurons via hM3dq, using vGATCre (vesicular GABAergic transporter) or vGLUT2Cre (vesicular glutamatergic transporter 2) in diet-induced obese male mice. Activating vGATcPOA neurons reduced body weight and adiposity without altering food intake. Activating vGLUT2cPOA neurons reduced body weight and food intake but did not reduce adiposity. Activating vGLUT2cPOA neurons reduced core body temperature, but not vGATcPOA neurons. We are currently investigating the mechanisms for how vGATcPOA neurons reduce adiposity. Weight loss is not likely mediated by direct inhibition of vGLUT2cPOA neurons because diet induced obese male mice with CNO-initiated signaling of hM4di in vglut2cPOA neurons does not reduce adiposity or body weight. Alternatively, vGATcPOA neurons may communicate with a distinct efferent system. Indeed, vGATcPOA, but not vGLUT2cPOA, neurons project to the lateral hypothalamus and medial raphe. Future studies will reveal the functional connection between VMNSf1 neurons and vGATcPOA neurons, and the descending circuitry that promotes energy expenditure.

Disclosure
R.Basu: None. A.J.Elmendorf: Research Support; Eli Lilly and Company. C.A.Mahler: Stock/Shareholder; AstraZeneca, Pfizer Inc. J.Flak: Research Support; Eli Lilly and Company.

Funding
American Diabetes Association (17-INI-15) ; IU CDMD NIH/NIDDK (P30 DK097512)