bluuebunny/crossref_metadata_2025_split huggingface dataset:
1700-P: Optimizing Data Cleaning Methods for Remotely Collected Electronic Weight Measurements
Authors: DAREDIA SAHER , SMITH BRIDGETTE P. , SERRATO BANDERA HILLARY , MILLMAN ANDREA , QUESENBERRY CHARLES , FERRARA ASSIAMIRA , BROWN SUSAN D. 
Published: June 2023

Background: Digital smart scales transmit weight measurements collected outside of clinical settings to medical and research teams. Statistical packages such as SAS %TPF (TrueProfileFinder) can ensure weights belong to persons of interest instead of others who may use the scale; however, validation is required.
Methods: We obtained 32,917 remotely collected weights from 222 postpartum participants using BodyTrace scales in the Pregnancy, Environment, and Lifestyle Study-2 (PETALS-2). To assess the SAS %TPF macro's performance, we applied 18 combinations of its three modifiable parameters (number of observations in a moving window, importance of weights from clinic visits, and prediction band) to a random subsample (N=16). In parallel, two manual reviewers independently classified weights as ‘belonging’ or ‘not belonging’ to participants; Cohen's κ ≥0.91 confirmed adequate interrater agreement. Outputs from the 18 models were then compared to the manual review.
Results: As hypothesized, adjusting parameters impacted the macro's ability to identify weights truly belonging to participants (percent true calls). Prediction band, the predicted range for new observations based on a linear regression model, was the only parameter associated with macro performance. A prediction band of 15 lbs. was associated with a 2.71% (95% CI: 0.16%, 5.25%) increase in percent true call and 5.57% (95% CI: 1.77%, 9.38%) increase in sensitivity vs. a band of 10 lbs. Percent true call for a prediction band of 15 lbs. was 2.95% higher, but non-significant (p=0.18) vs. a band of 20 lbs. A prediction band of 15 lbs. was highly accurate (&gt;97% true call) and sensitive (&gt;98%).
Conclusion: Weight is often assessed in interventions for glycemic control and diabetes prevention. Precise data cleaning can increase accuracy of unsupervised, remotely collected measurements. Clinicians and researchers using smart scales can apply this data cleaning method to identify SAS %TPF macro parameters that maximize accuracy.

Disclosure
S.Daredia: None. B.P.Smith: None. H.Serrato bandera: None. A.Millman: None. C.Quesenberry: None. A.Ferrara: None. S.D.Brown: None.

Funding
National Institutes of Health (R01HL142996)
1702-P: Altered Gene Expression Signatures following COVID-19 Infections and/or mRNA Vaccination in Human Adipose Tissue
Authors: KRUPKA SONTJE , BLÜHER MATTHIAS , KLÖTING NORA 
Published: June 2023

Obesity is associated with an increase in morbidity and mortality from Coronavirus disease- 2019 (COVID-19). Adipose tissue (AT) demonstrates high expression of angiotensin-converting enzyme 2 (ACE2), a host cell entry factor of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 has been shown to infect AT, where it continues to proliferate, thereby contributing to local inflammation. Since visceral AT inflammation may play a role in the pathogenesis of type 2 diabetes, we investigated the molecular and histological AT signatures after a Covid-19 infection and/or mRNA vaccination. We investigated 54 paired subcutaneous (SC) and visceral adipose tissue (VAT) biopsies from the Leipzig Obesity BioBank in subgroups based on positive versus negative SARS-CoV-2 infection as well as mRNA vaccination status in comparison to BMI and age matched controls obtained before appearance of Covid-19 (N=27). We compared gene expression signatures by RNA-Sequencing analyses, morphology changes in AT as well as circulating inflammation markers across the groups. In relation to a Covid-19 infection, we find a distinct gene expression signature and morphology in AT suggesting that SARS-CoV-2 affects AT and may mediate the disease course. In this context, inflammation of AT, but also an altered secretion profile from AT could link obesity to its metabolic complications, but also to long Covid-19 disease courses.

Disclosure
S.Krupka: None. M.Blüher: Advisory Panel; Boehringer Ingelheim Inc., Lilly, Novo Nordisk, Consultant; Novo Nordisk Foundation, Speaker's Bureau; Amgen Inc., AstraZeneca, Bayer Inc., Daiichi Sankyo, Novartis, Sanofi-Aventis Deutschland GmbH. N.Klöting: None.
1704-P: Efficacy and Safety of Tirzepatide for Weight Loss—A Meta-analysis of Randomized Controlled Trials
Authors: MESQUITA YASMIN L.L. , CALVI IZABELA P. , MARQUES ISABELA R. , CRUZ SARA A. , PADRAO EDUARDO M.H. , CARDOSO RHANDERSON , MOURA FILIPE , RAFALSKIY VLADIMIR V. 
Published: June 2023

Tirzepatide (TZP) is a new dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved for type 2 diabetes and shown to have substantial efficacy on weight loss. We performed a meta-analysis to assess the efficacy and safety of TZP for weight loss. We searched PubMed, Cochrane and Embase up until July 2022 for RCTs comparing TZP with placebo for the co-primary endpoints of absolute and percent change in weight. Mean difference (MD) and odds ratios (OR) were utilized, respectively, for continuous and binary outcomes. Of 397 search results, 6 studies were included, with 4036 participants. Pooled analysis showed that TZP 5 mg, 10 mg, and 15 mg were more effective than placebo, with MD in body weight change ranging from -7.7 kg (95% CI -11.0, -4.4; p &lt; 0.001) to -11.8 kg (95% CI -17.4, -6.2; p &lt; 0.001) - Figure 1A. The MD in percent change in weight ranged from -8.1% (95% CI -11.0, -5.2; p &lt; 0.001) to -12.4% (95% CI -17.2, -7.5; p &lt; 0.001) - Figure 1B. Adverse events were more frequent with TZP compared with placebo, especially with the 15 mg dose, with respect to nausea (OR 4.2; 95% CI 2.4, 7.5; p &lt; 0.001), vomiting (OR 7.0; 95% CI 4.3, 11.4; p &lt; 0.001), and diarrhea (OR 2.8; 95% CI 1.6, 4.9; p &lt; 0.001). The results support that TZP leads to a significant reduction in body weight and may be a valuable therapeutic option for weight management, despite an increase in gastrointestinal side effects.

Disclosure
Y.L.L.Mesquita: None. I.P.Calvi: None. I.R.Marques: None. S.A.Cruz: None. E.M.H.Padrao: None. R.Cardoso: None. F.Moura: None. V.V.Rafalskiy: None.
171-OR: Diagnosing GDM in Pregnancy—Closing the Door after the Horse Has Bolted?
Authors: YAJNIK CHITTARANJAN S. , BANDYOPADHYAY SOUVIK , BHALERAO ABOLI A. , BHAT DATTATREY , PHATAK SANAT , WAGH RUCHA H. , YAJNIK PALLAVI C. , OTIV SUHAS R. , COYAJI KURUS J. , FALL CAROLINE 
Published: June 2023

RCTs of GDM treatment reduces adverse pregnancy outcomes but not long-term offspring diabesity which is influenced by genetic and epigenetic programming. The vital window for programming is pre- and immediate post-conceptional, strongly influenced by maternal nutrition and metabolism. Diagnosing GDM later in the pregnancy systematically misses this window. Metabolic-endocrine abnormalities of ‘GDM’ are detectable years before pregnancy (Catalano 2013; Han 2016). There is little data to track the life course evolution of pregnancy hyperglycaemia. Pune Maternal Nutrition Study (1993) has serial glycemic and BMI data on girls born in the cohort at 6, 12 and 18 years, in pregnancy and post-delivery. By 2020, pregnancy data (28-wks gestation) was available on 170. They were 21-years old, BMI 22 kg/m2, twenty had GDM (IADPSG). We compared serial data of Q4 of fasting plasma glucose (FPG, N=44, ‘hyperglycemic’) with 126 ‘normoglycemic’. Figure shows that hyperglycemic girls had higher FPG and BMI at 6, 12 and 18-years and continued to remain so post-delivery. Our data shows that pregnancy glycemia reflects life course glycemia. Diagnosing ‘GDM’ in pregnancy ignores exposure of ova and young conceptus to an abnormal metabolic milieu, failing to prevent periconceptional programming of diabesity. There is an urgent need to reconsider strategies about GDM diagnosis and treatment to curtail the escalating epidemic of diabesity in the young.

Disclosure
C.S.Yajnik: None. C.Fall: None. S.Bandyopadhyay: None. A.A.Bhalerao: None. D.Bhat: None. S.Phatak: None. R.H.Wagh: None. P.C.Yajnik: None. S.R.Otiv: None. K.J.Coyaji: None.

Funding
UK Wellcome Trust (038128/Z/93, 059609/Z/99, 079877/Z/06/Z, 098575/B/12/Z, 083460/Z/07/Z); Medical Research Council, UK (MR/J000094/1); Department of Biotechnology, Government of India (BT/PR-6870/PID/20/268/2005); KEM Hospital Research Centre
1712-P: Serum miRNA-1 Levels as a Potential Marker for Myocardial Steatosis in Normal Weight and Obese/Overweight Diabetic Individuals—A Pilot Study
Authors: PALANISAMY SRIKANTH , PARLATAN UGUR , OZEN MEHMET , KARIM ASMA H. , AKIN DEMIR , DEMIRCI UTKAN , PALANIAPPAN LATHA 
Published: June 2023

Of the 37 million Americans with type II diabetes, a substantial proportion have a normal body mass index (BMI). These populations suffer a disproportionately high burden of mortality; the development of diabetic cardiomyopathy (DCM) is likely a contributor. Myocardial steatosis, a known consequence of diabetes, is a significant part of DCM's pathogenesis; unfortunately, there is no feasible way to screen patients for steatosis. Exosomal microRNAs (miRNAs) are a promising biomarker for this purpose. However, no study has evaluated miRNA signatures in normal-weight patients with diabetes. Serum samples of obese/overweight and normal-weight diabetic subjects were obtained via IMPACT and STRONG-D clinical trial protocols respectively. Exosomes were extracted using the ExoTIC (exosome total isolation chip) platform. MiRNA-1 levels from extracellular vesicles were quantified using RT-qPCR and compared via unpaired student's two-tailed t-test. A total of 8 samples (4 normal-weight and 4 overweight/obese) were analyzed. Overall, the obese cohort had a mean age of 63.7 vs. 57.2 for the normal-weight cohort. The obese cohort had a mean BMI of 29.7 vs. 23.1 for the normal weight cohort. Both cohorts were composed of 75% men and 25% women. The obese cohort had a mean hemoglobin A1c of 7.2% vs. 8.0% in the normal-weight cohort. Serum miRNA-1 levels were significantly higher in normal-weight diabetic subjects (p = 0.0004). In this pilot study, patients with diabetes of a normal weight had significantly higher levels of serum miRNA-1, implying that they may have more myocardial steatosis and possibly, more cardiac dysfunction. This pathophysiologic difference could help explain the significant morbidity and mortality that diabetic patients of a normal weight suffer. Further directions for our study include the complete quantification of both miRNA-1 and miRNA-133a among our entire cohort, as well as assessment of echocardiographic parameters.

Disclosure
S.Palanisamy: None. U.Parlatan: None. M.Ozen: None. A.H.Karim: None. D.Akin: None. U.Demirci: None. L.Palaniappan: None.

Funding
National Institutes of Health (1R18DK096394-01A1, 2R01DK081371-06A1)
1716-P: Real-World Outcomes Using Medication and Intensive Lifestyle Intervention to Treat Obesity and Improve Diabetes at Scale
Authors: BOYD KIM , MEDEIROS KAELEN L. , KRAMER DANIEL , CELIO CHRISTINE , RYAN DONNA H. , KENYON ISABELLE 
Published: June 2023

Introduction: Overweight and obesity impact &gt;200 million Americans, driving rates of diabetes and cardiometabolic disease. To address this, we established a digital metabolic health company to provide medically-supervised obesity treatment at scale.
Methods: Treatment: GLP-1 receptor agonist medications combined with a proprietary intensive lifestyle intervention. Data analysis: Individuals who reached 12 months in the core program and a subset who continued to 18 months were analyzed for weight change, metabolic labs (baseline and 12mo) and patient-completed questionnaires (baseline, 6, and 12mo).
Results: The cohort included 2,643 patients. At baseline, 3.9% had type 2 diabetes, and 22.8% had prediabetes. Average weight loss at 12, 15 and 18 months was 15.58% (n=2,397), 15.97% (n=1,319) and 15.82% (n=569). Average weight loss for patients with diabetes or prediabetes at 12, 15 and 18 mo was 16.22% (n=299), 16.60% (n=233), and 15.57% (n=133). Patients with diabetes saw average improvements of -1.42 percentage points for HbA1c and -14.05 units for insulin; for patients with prediabetes, these were -0.45 reduction to HbA1c and -7.05 for insulin. 72.9% of patients with abnormal HbA1c levels at baseline were normal at 12 months. Positive changes were also seen for other metabolic markers and for patient-reported outcomes.
Discussion: Results from 2,643 enrollees in a new digital metabolic health program demonstrate robust and sustained weight loss through 18 months. For those with diabetes or prediabetes, there was significant weight loss, reduction in HbA1c and insulin with categorical improvement to diabetes status in 80.5%, improvements to other metabolic markers, and positive changes to health behaviors. These results offer great promise in addressing the obesity epidemic and reversing diabetes.

Disclosure
K.Boyd: Employee; Calibrate Health, Inc. K.L.Medeiros: Employee; Calibrate Inc. D.Kramer: Employee; Calibrate Health, Inc. C.Celio: None. D.H.Ryan: Advisory Panel; Altimmune, Wondr Health, YSOPIA, Zealand Pharma A/S, Consultant; Amgen Inc., Boehringer Ingelheim Inc., Carmot Therapeutics, Inc., Epitomee, Lilly, Other Relationship; Calibrate, Gila, IFA Celtic, Scientific Intake,, real appeal, Scientific Intake, Xeno Bioscience, Novo Nordisk. I.Kenyon: None.
1721-P: Patients with Metabolic Syndrome Are at Risk of Renal Outcome in CKD Stages 1-4 Regardless of Diabetes
Authors: LIN HUGO Y.H. , CHANG KAI-TING 
Published: June 2023

Metabolic syndrome (MetS) is a cluster of risk factors predicting cariometabolic disease. MetS was associated with renal outcome in some studies. However, the effect of MetS seemed loss after the adjustment of proteinuria, late CKD stage or diabetes in advanced CKD. Whether MetS predicts renal outcome in established CKD is unknown. We investigated the prognostic effects of MetS in 2500 patients with CKD stage 1-4. 66.9% and 49.2% patients had MetS and DM, respectively. The MetS score was positively associated with proteinuria (p&lt;0.001), inflammation (p=0.001), and nutrition markers (p&lt;0.001). In fully-adjusted Cox regression model, hazard ratio (HR) (95% confidence interval) of MetS for composite renal outcome in DM and non-DM subgroup was 1.56 (1.15-2.12) (p&lt;0.05) and 1.31 (1.02-1.70) (p&lt;0.05), respectively, while that for all-cause mortality was 1.00 (0.71-1.40) and 1.27 (0.92-1.74). Blood pressure is the most important component of MetS for clinical outcomes (1.50 (1.08-2.08) (p&lt;0.05)). In a 2 by 2 matrix, compared with non-MetS non-DM group, MetS DM group (HR: 1.62 (1.31-2.02) (p&lt;0.05)) and MetS non-DM group (HR:1.33 (1.05-1.69) (p&lt;0.05)) had higher risks for composite renal outcome, while MetS DM group had higher risk for all-cause mortality (HR: 1.43 (1.09-1.88) (p&lt;0.05)). In conclusion, MetS could predict renal outcome in CKD stage 1-4 patients independent of diabetes.

Disclosure
H.Y.H.Lin: None. K.Chang: None.

Funding
Ministry of Science and Technology (110-2314-B-037-068-MY3); Municipal Ta-Tung Hospital (KMTTH-110-003)
173-LB: Circulating Calprotectin Is Increased in Children with T1D and Obesity—Implications for T1D Progression and Outcome
Authors: HASAN AMAL , KOCHUMON SHIHAB P. , ALBASIRI IMAN D. , ALBELOUSHI SHAIMA , ALOZAIRI EBAA S. , ALMULLA FAHD 
Published: June 2023

Purpose: Circulating calprotectin is elevated in inflammatory disorders and is a biomarker of severity in inflammatory rheumatic and bowel diseases. Calprotectin has immunomodulatory properties that may influence the progression and outcome of inflammatory diseases. Calprotectin is elevated in children with obesity, but its levels in children with T1D co-morbid with obesity remain unexplored. We examined the levels of circulating calprotectin in children with T1D and obesity and compared these levels with those of children with normal weight as well as those with obesity and T2D or children with obesity only (no prediabetes or T2D).
Methods: Sixty-four children (aged 5-13 years) were included. Participants' characteristics included being of normal weight (body mass index, BMI &lt;85th percentile; n = 12), having obesity (BMI ≥95th percentile) with T1D (n = 4), obesity with T2D (n = 8), or having obesity without prediabetes or diabetes (n = 40). Clinical markers were assessed using established procedures on peripheral blood. The levels of calprotectin were quantified using commercially available ELISA kits.
Results: Circulating calprotectin was significantly (P = 0.0044) higher in children with T1D and obesity, as well as in children with T2D and obesity (P = 0.02), compared to healthy children with normal weight. There was no difference in calprotectin levels between children with T1D and obesity compared to those with T2D and obesity or obesity without prediabetes or diabetes.
Conclusion: Increased calprotectin in children with T1D (as well as T2D) is due to the obese state and is not further increased by having diabetes. Given the immunomodulatory properties of calprotectin, obesity in children with T1D might hasten disease progression, resulting in a worse outcome. These findings highlight the need for tailored obesity prevention in children with high risk for T1D and emphasize the importance of treatment strategies for weight management in children with T1D.

Disclosure
A. Hasan: None. S. P. Kochumon: None. I. D. Albasiri: None. S. Albeloushi: None. E. S. Alozairi: None. F. Almulla: None.

Funding
Kuwait Foundation for the Advancement of Sciences
1735-P: The Dichotomic and Timely Regulation of SerpinB13 Plays a Role in Beta-Cell Neogenesis and Pancreatic Islet Expansion
Authors: KRYVALAP YURY , MENG SHAWN Z. , HABTE RIM , CZYZYK JAN 
Published: June 2023

There has been recent emphasis on the potential role of a functional crosstalk between the exocrine and endocrine pancreas in the development of type 1 diabetes (T1D). Our interest in this was sparked by our observations that, (i) serpinB13, a protease inhibitor of cathepsin L, is expressed in mouse pancreatic ductal cells, and (ii) an antibody response to serpinB13 is associated with better clinical outcomes in mice and humans with T1D. The exact pattern of serpinB13 expression in the human pancreas has, to date, not been examined. Similarly, the exact role of serpinB13 in beta-cell biology and diabetes remains unclear. We aimed to determine the distribution of serpinB13 expression using immunochemistry on pancreatic sections obtained from nPOD. In addition, we developed a mouse serpinB13 genetic knockout model to examine the role of this serpin in regulating pancreatic islet morphology. Visiopharm software was used for an unbiased quantitative image analysis of islet size and cellularity. We found that in healthy humans, serpinB13 expression was confined to the pancreatic ducts, mimicking the pattern we observed previously in rodents. Studies of serpinB13 genetic deficiency revealed that early inhibition of serpinB13 increased the small pancreatic islet population while with time this trend reversed, and a drop in the number of pancreatic islets was observed. Our results demonstrate that serpinB13 is expressed in the exocrine epithelial compartment of the human pancreas. In addition, quite unexpectedly, serpinB13 appears to play a dual role in regulating pancreatic islet mass. More specifically, we postulate that serpinB13 initially hampers the development of additional insulin-producing cells, but with time it promotes expansion of the already formed beta cells. Thus, we propose an approach that first impedes serpinB13, followed by later administration of this serpin, which may lead to an increase in beta-cell mass and improved resistance to T1D.

Disclosure
Y.Kryvalap: None. S.Z.Meng: None. R.Habte: None. J.Czyzyk: None.
174-LB: Autoantibodies against PTM-IA2 Extracellular Domain Are Only Associated with Late Progression of Type 1 Diabetes
Authors: JIA XIAOFAN , WENZLAU JANET M. , REWERS MARIAN , MICHELS AARON W. , YU LIPING 
Published: June 2023

Background: Autoantibodies directed against the extracellular domain of IA2 (IA2ecA) with post-translationally modified (PTM) (deamidated) epitopes have been identified in new-onset T1D patients. The prevalence and timing of appearance of PTM-IA2ecA in pre-T1D individuals is evaluated in the current study.
Methods: A PTM-IA2ec protein antigen probe containing four T-cell responsive deamidated Q&gt;E peptides (aa 198-216, aa 467-482, aa 523-536 and aa 545-562) was produced. The study subjects included 269 children and 260 adults with new-onset T1D, 271 adults with LADA, 274 children with new-onset diabetes but negative for all islet autoantibodies (IAbs) (IAA, GADA, IA-2A and ZnT8A), and 222 pre-T1D children who were longitudinally followed from birth to stage 1-3 T1D. The longitudinal follow-up serum samples included samples prior to seroconversion, samples at the first appearance on an IAb and the last follow-up samples. All serum samples were tested for PTM-IA2ecA and the wide type (WT-IA2ecA) with a radio binding assay.
Results: In new-onset T1D, positivity for PTM-IA2ecA and WT-IA2ecA were 60.6% (163/269) and 19.3% (52/269), respectively in children, while significantly less in adults, 14.2% (37/260, P&lt;0.0001) and 8.8% (23/260, P=0.0007), respectively. The positivity for PTM-IA2ecA and WT-IA2ecA were only 4.1% (11/271) and 1.5% (4/271) in LADA patients, 1.5% (4/274) and 1.1% (3/274) in diabetic children who were otherwise IAb negative. In 222 longitudinally followed children with pre-T1D, only 13 were tested positive for PTM-IA2ecA and 8 positives for WT-IA2ecA, with most detected at diagnosis of stage 3 T1D.
Conclusion: Autoantibodies against either WT-IA2ec or PTM-IA2ec were not frequently seen in pre-T1D as shown in new onset T1D. These autoantibodies develop in the late stage of T1D progression with overt clinical disease.

Disclosure
X. Jia: None. J. M. Wenzlau: None. M. Rewers: Research Support; Provention Bio, Juvenile Diabetes Research Foundation (JDRF), Hemsley Charitable Trust, Dexcom, Inc., Janssen Research & Development, LLC. A. W. Michels: Stock/Shareholder; Immnomolecular Therapeutics. L. Yu: None.

Funding
National Institute of Allergy and Infectious Diseases (AI53665); National Institute of Diabetes and Digestive and Kidney Diseases (DK032083)
1746-P: The Role of Cell–Cell Junction Associated Mediator in Glucose-Stimulated Insulin Secretion of Pancreatic Islets
Authors: WANG HAO 
Published: June 2023

Glucose-stimulated insulin secretion from β cells is essential in maintaining glucose homeostasis. Cell-cell communication within the pancreatic islets, mediated by cell-cell junctions and their mediators, regulates insulin secretion dynamics and glucose homeostasis. It has been reported that Nephrin-mediated intercellular junction between β cells is implicated in the regulation of insulin secretion, however, the underlying mechanisms are not fully understood. Here, we investigated the effects of Girdin, a cell-cell junction associated mediator, on insulin release. We found that Girdin was expressed in mouse pancreatic β cells and mediated glucose-stimulated insulin secretion, especially for the second phase. Next, we demonstrated that glucose-stimulated tyrosine phosphorylation of Girdin mediated Nephrin phosphorylation by recruiting Src kinase, which leads to the endocytosis of Nephrin. Furthermore, we observed the glucose-induced Girdin/Nephrin/Src signaling induced downstream Akt phosphorylation and activated Rac1-mediated cytoskeleton reorganization, allowing insulin secretory granules to access the plasma membrane for the second-phase secretion. Finally, we found that Girdin is downregulated in the diabetic islets, and rescue of Girdin restored impaired glucose-stimulated insulin secretion. Taken together, these data provide evidence that the cell-cell junction associated mediator play important roles in fusion of insulin secretory vesicles within the cell and establish a role for Girdin in regulating this process.

Disclosure
H.Wang: None.

Funding
National Natural Science Foundation of China