bluuebunny/crossref_metadata_2025_split huggingface dataset:
1112-P: Prevalence of Testing for Blood Glucose among Adults with Overweight or Obesity in the U.S.
Authors: CHEN YU , LUNDEEN ELIZABETH A. , KOYAMA ALAIN , KOMPANIYETS LYUDMYLA , ANDES LINDA J. , BENOIT STEPHEN R. , IMPERATORE GIUSEPPINA , ROLKA DEBORAH B. 
Published: May 2022

An estimated 13% of all U.S. adults aged ≥18 years have diabetes, and 34.5% meet criteria for having prediabetes. Screening adults at high risk for prediabetes and diabetes may allow earlier detection, diagnosis, and treatment, thereby improving health outcomes. The U.S. Preventive Services Task Force (USPSTF) recommends screening every three years for abnormal blood glucose in adults aged 40-70 years who have overweight or obesity (this recommendation was updated to adults aged 35-70 years in August of 2021) . Using IQVIA Ambulatory Electronic Medical Records (EMR) via the IQVIA E360 platform, we aimed to estimate the proportion of adults aged 40-70 years with overweight or obesity who received a test for blood glucose in a 3-year period from 2016-2019. We defined overweight or obesity based on body mass index (BMI of 25-29.9 kg/m2 and ≥30 kg/m2, respectively) calculated using measured height and weight. Receipt of a blood glucose test was defined as having a hemoglobin A1c or fasting plasma glucose measured, as recommended by USPSTF. Our analysis identified adults aged 40-70 years with overweight or obesity in 2016 (the index year) and without preexisting diabetes, defined using a modified SUPREME-DM algorithm for EMR data[1]. We included adults who were present in the dataset for at least two years before their index BMI in 2016 (to exclude those with prevalent diabetes) and three years after the index BMI, during which we examined the occurrence of blood glucose testing. Among 1,360,095 adults who had overweight or obesity, 33.4% received a test for blood glucose in 2016-2019. The testing rate was 28.7% among adults with overweight and 37.3% among adults with obesity. Our findings could help inform clinical and public health promotion efforts to improve screening for blood glucose levels among adults with overweight or obesity. Future studies may identify factors associated with receiving timely blood glucose screening.
[1]https://pubmed.ncbi.nlm.nih.gov/25515167/

Disclosure
Y.Chen: None. E.A.Lundeen: None. A.Koyama: None. L.Kompaniyets: None. L.J.Andes: None. S.R.Benoit: None. G.Imperatore: None. D.B.Rolka: None.
1129-P: Rising Prevalence of Type 2 Diabetes in the Young in Southern India
Authors: NANDITHA ARUN , SUSAIRAJ PRISCILLA , RAGHAVAN ARUN , SATHEESH KRISHNAMOORTHY , VINITHA RAMACHANDRAN , NAIR DHRUV , SNEHALATHA CHAMUKUTTAN , RAMACHANDRAN AMBADY 
Published: May 2022

This ancillary analysis (STRIDE-I study) compares the prevalence ratio (PR) of type 2 diabetes (T2DM) in persons aged ≤40 and &gt;40 years in 20 and 2016 in Southern India. In 2016, prevalence of T2DM, generalized and abdominal obesity increased in both groups (Table 1) . Hypertension and dyslipidaemia were higher among the older and younger population respectively. Higher intake of fat and protein increased the total calorie consumption in both groups. Sedentary time increased in the younger group in 2016. Poisson regression analysis (Table 2) showed an increase in the PR in 2016 in both groups. However, the increase was significantly higher in the younger group (30%) when compared to the older group (10%) .

Disclosure
A.Nanditha: None. P.Susairaj: None. A.Raghavan: None. K.Satheesh: None. R.Vinitha: None. D.Nair: None. C.Snehalatha: None. A.Ramachandran: None.
1153-P: Association of Extracellular Matrix Remodeling Biomarkers with Complications of Type 2 Diabetes
Authors: MØLLER ALEXANDRA , BOJER ANNEMIE S. , GENOVESE FEDERICA , SØRENSEN MARTIN H. , GÆDE PETER , KARSDAL MORTEN A. , MADSEN PER L. , RASMUSSEN DANIEL G. 
Published: May 2022

Background: Persons with diabetes have a high risk of complications related to the micro- and macrovascular circulation. One of the pathological processes involved in these complications is the onset of abnormal extracellular matrix (ECM) remodeling in different organs, leading to fibrosis. The quantification of ECM remodeling may identify patients that are at higher risk for adverse outcomes.
Method: We measured biomarkers of collagen type III (PRO-C3) and VI (PRO-C6) formation and MMP-mediated degradation of type I (C1M) , III (C3M) , and IV (C4M and Tumstatin; TUM) in serum from 267 persons with T2DM from the CMR in T2DM study (NCT02684331) . Myocardial fibrosis (LGE) and ECV were determined by gadolinium-contrast CMR. Serum samples from 79 healthy controls were measured for comparison.
Results: Levels of all biomarkers were significantly elevated in persons with T2DM compared to healthy controls (all P&lt;0.0001) . Some of the markers were associated with complications, PRO-C6 levels were: significantly elevated in patients with hypertension compared to persons without known CVD (P&lt;0.0001) ; could discriminate patients with CKD - eGFR &lt; 60 ml/min/1.73m2 with an AUC of 0.83 (P&lt;0.001) ; were significantly increased in patients with ischemic LGE (P&lt;0.05) , suggesting an association of PRO-C6 with fibrosis; and in a multiple linear regression analysis, higher PRO-C6 levels were significantly associated with higher HbA1c (r=0.15, P=0.0397) , lower eGFR (r=−0.41, P&lt;0.0001) , higher proANP (r=0.24, P=0.0005) , and higher ECV (r=0.24, P=0.0006) . PRO-C3 levels were significantly elevated in patients with CKD compared to non-CKD, and levels of C3M and C4M increased significantly with presence of albuminuria.
Conclusion: Biomarkers of ECM remodeling, particularly PRO-C6, may identify persons with active pro-fibrotic processes at risk for complications related to T2DM. The potential of the biomarkers to predict adverse outcomes will be investigated once follow-up data have been collected.

Disclosure
A.Møller: None. A.S.Bojer: None. F.Genovese: Employee; Nordic Bioscience A/S, Stock/Shareholder; Nordic Bioscience A/S. M.H.Sørensen: None. P.Gæde: Advisory Panel; AstraZeneca, Research Support; Novo Nordisk. M.A.Karsdal: Employee; Nordic Bioscience A/S, Nordic Bioscience A/S, Nordic Bioscience A/S. P.L.Madsen: None. D.G.Rasmussen: Employee; Nordic Bioscience A/S.
121-OR: Alternate-Day Fasting Combined with Endurance Exercise for the Treatment of Fatty Liver Disease
Authors: EZPELETA MARK , GABEL KELSEY , VARADY KRISTA , LIN SHUHAO , CIENFUEGOS SOFIA 
Published: May 2022

Background: Approximately 65% of individuals with obesity have nonalcoholic fatty liver disease (NAFLD) . The primary treatment for NAFLD is regulating weight per diet and exercise. Alternate day fasting (ADF) has been shown to improve body composition and cardiometabolic risk factors in animals. This is the first human trial to compare the effects of ADF plus endurance exercise, ADF alone, endurance exercise alone versus a no intervention control, on body weight and metabolic disease risk factors in participants with obesity and NAFLD.
Methods: Subjects with obesity and NAFLD (n = 48) were randomized to 1 of 4 groups for 12 weeks:1) ADF (600 kcal “fast day”, alternated with an ad libitum intake “feast day”) ,2) exercise (endurance exercise 5 times/week for 60 min/d) ,3) combination (ADF + exercise) ,or 4) control (usual diet) .
Results: Body weight was reduced (P &lt; 0.05) in the ADF group (-5.3 ± 1.0 %) and combination group (-4.9 ± 0.6 %) , but not the exercise group (-1.9 ± 0.6 %) , versus controls (-0.3 ± 1.2 %) . ALT was reduced (P &lt; 0.05) in the combination group (-29 ± 9%) , but not in the ADF group (-9 ± 8%) , exercise group (1 ± 3%) , versus controls (17 ± 10%) . No significant changes were observed for liver fat, body composition, AST, lipid markers, or glucoregulatory factors. Subjects in the ADF and combination groups were adherent with the fast day energy goal (600 kcal) at week 12 (ADF: 548 kcal; combination: 657 kcal) . Subjects in the exercise and combination groups were adherent with attending the 5 workout sessions per week (exercise: 79% attendance; combination: 83% attendance) .
Conclusion: These preliminary findings suggest that combination of ADF plus exercise and ADF alone may be effective non-pharmacological therapies to reduce body weight and ALT. However, neither combination intervention nor ADF alone have had any effect on liver fat, metabolic risk factors, or glucoregulatory factors such as insulin.

Disclosure
K. Gabel: None. K. Varady: None. S. Cienfuegos: None.

Funding
NIH/NIDDK (R01DK119783-03)
1251-P: Aß Classification Defines Four Distinct Forms of Diabetes in Children
Authors: TOSUR MUSTAFA , DEEN SAIMA , UYSAL SERIFE , ASTUDILLO MARCELA , JAHOOR FAROOK , HAGOPIAN WILLIAM , ORAM RICHARD A. , REDONDO MARIA J. , BALASUBRAMANYAM ASHOK 
Published: May 2022

A comprehensive classification accounting for the heterogeneity of pediatric diabetes is lacking. The Aβ classification system, based on islet autoantibody status (A+ or A-) and preserved beta-cell functional reserve (β+ or β-) , was used successfully to define variable phenotypes in adults with Ketosis-prone Diabetes. We set out to investigate the utility of the Aβ classification system in children with new-onset diabetes. “A+” was defined as the presence of ≥1 islet autoantibodies (GAD65, ICA512, insulin or ZnT8 autoantibodies) and "β+" as random C-peptide level ≥0.6 ng/mL at diagnosis. We calculated T1D genetic risk score 2 (T1D GRS2) for each participant, and compared clinical characteristics at diabetes onset and T1D GRS2 between the groups. The study cohort (n=76) was 50% female, 29% non-Hispanic white, 46% Hispanic, 22% non-Hispanic black, and 3% Other. The mean age was 11.7 years and the mean BMI was 58.3%ile. Aβ classification at diagnosis defined the following groups: A+β- (34%) , A+β+ (30%) , A-β+ (33%) and A-β+ (3%) . Results are summarized in Table 1.
The Aβ classification system defines phenotypically and genetically distinct diabetes groups in children with new-onset diabetes. This classification system may be useful in clinical settings as well as the design of clinical trials.

Disclosure
M.Tosur: Advisory Panel; Provention Bio, Inc. S.Deen: None. S.Uysal: n/a. M.Astudillo: None. F.Jahoor: None. W.Hagopian: Research Support; Janssen Research & Development, LLC. R.A.Oram: Consultant; Janssen Research & Development, LLC, Research Support; Randox R & D. M.J.Redondo: Advisory Panel; Provention Bio, Inc. A.Balasubramanyam: None.

Funding
Texas Children's Pilot Award
130-LB: Linagliptin vs. Sitagliptin for Type 2 Diabetes Inpatient Glycemic Management and Cardiovascular Outcomes—Is There a Difference between DPP-4 Inhibitors?
Authors: BARAKAT SAMI , HABIB HELEN A. , CHUN CATHERINE , OH ERIN 
Published: May 2022

Background: Oral DPP-4 inhibitors provide adjunctive therapy to insulin in hospitalized patients with blood glucose (BG) &lt; 400 mg/dL. Results from trials comparing sitagliptin or linagliptin to basal-bolus insulin showed mixed results, with no head-to-head comparison between sitagliptin and linagliptin. The aim of this study is to provide new evidence on their comparative efficacy and safety.
Methods: This was a retrospective, single-center, observational study of hospitalized general medicine and surgery adult patients with type 2 diabetes. Patients who received at least 2 doses of linagliptin or sitagliptin between January and December 2019 were assigned to either arms. Primary endpoint was the difference in mean daily BG. Secondary endpoint was a composite of 3-point major adverse cardiac events (MACE) and heart failure (HF) hospitalization. Safety endpoints included the number of hypoglycemic events (BG &lt; 70 mg/dL) and the appropriateness of dosing based on eGFR.
Results: A total of 100 patients were included. The mean daily BG was similar in the linagliptin arm (167.6 ± 43.5 mg/dL) compared to the sitagliptin arm (162.1 ± 37.5 mg/dL) (p=0.5) . In a subgroup analysis, patients who received linagliptin plus correctional insulin had more BG readings within the range of 140-180 mg/dL (50% vs. 36%, p=0.2) . The composite of 3-point MACE and HF hospitalization was similar between both arms. Hypoglycemia occurred more frequently with linagliptin versus sitagliptin (4 vs. 1 event, p=0.2) . Only 70% of sitagliptin orders were appropriately dosed based on eGFR.
Conclusion: There was no difference between linagliptin and sitagliptin in regards to mean daily BG and cardiovascular outcomes. However, there were numerically more BG readings within range with linagliptin. Our results favor the utilization of linagliptin in the inpatient setting considering it does not require renal dose adjustments.

Disclosure
S. Barakat: None. H. A. Habib: None. C. Chun: None. E. Oh: None.
1306-P: In Vivo Downregulation of Pancreatic Amylin in Diabetic Mice Improves Recognition Memory
Authors: VISWANATHAN VELMURUGAN GOPAL , VERMA NIRMAL , WINFORD EDRIC D. , KOTIYA DEEPAK , RADULESCU LAURA E. , LEIBOLD NOAH , CHEN KUEY C. , DESPA SANDA , HILL DEMITRIUS A. , MUEHLBAUER MICHAEL , BAIN JAMES R. , DESPA FLORIN 
Published: May 2022

Hypersecretion of amylin, a β-cell hormone that regulates satiation, is common in individuals with prediabetes and is associated with pancreatic amyloid deposition and type-2 diabetes. Evidence has emerged that increased circulating levels of amyloid-forming human amylin may potentially impair brain function. Because mouse amylin is non-amyloidogenic, we generated transgenic mice with conditional pancreatic expression of amyloid-forming human amylin to study how in vivo knockdown of human amylin expression influences brain function during the development of type-2 diabetes. Males and females were fed a high-fat diet starting at 3 months of age to induce amylin hypersecretion and glucose dysregulation. Males developed hyperglycemia at 5 months of age, whereas females showed glucose dysregulation 3-4 months later. At 5 months of age, human amylin-expressing male mice were randomly assigned to either amylin downregulation (by peritoneal tamoxifen injection) or control (maintained amylin expression) groups (n = 10/group) . Two months later, we assessed brain function with a novel object recognition test and performed comparative non-targeted metabolomics and global RNA-seq analyses of hippocampal tissue. Mice with downregulated human amylin showed enhanced recognition memory index (p &lt; 0.001) and lower blood glucose levels (p &lt; 0.001) compared to those that continued to express human amylin. This was associated with increased hippocampal levels of glycolysis metabolites, including lactic acid (p &lt; 0.01) , glucose-6-phosphate (p = 0.06) , and fructose (p = 0.07) . Hippocampal gene-expression patterns between the two mouse groups revealed extensive compensatory changes in gene expression related to glucose metabolism.
In conclusion, amylin downregulation in diabetic mice improves systemic glucose homeostasis and memory. Molecular processes associated with improved memory involve increased hippocampal glycolytic fluxes and compensatory gene expression.

Disclosure
V.Gopal viswanathan: None. M.Muehlbauer: None. J.R.Bain: Other Relationship; CardioEphEx, LLC. F.Despa: None. N.Verma: None. E.D.Winford: None. D.Kotiya: None. L.E.Radulescu: None. N.Leibold: None. K.C.Chen: None. S.Despa: None. D.A.Hill: None.

Funding
National Institutes of Health NS116058, AG057290, AG053999
1319-P: Gabra5 Plays a Sexually Dimorphic Role in POMC Neuron Activity and Glucose Balance
Authors: PEI ZHOU , HE YANLIN , HE YANG , XU YONG , WANG CHUNMEI 
Published: May 2022

Pro-opiomelanocortin (POMC) neurons are important for body weight and glucose balance. The inhibitory tone to POMC neurons is mediated primarily by GABA receptor complex. However, the detailed mechanisms and functions of GABA receptors are not well understood. We found that α5 subunit of GABA receptor complex, Gabra5, is highly expressed in POMC neurons. To explore the function of Gabra5 in POMC neurons, we deleted Gabra5 specifically from mature POMC neurons using the CRISPR-Cas9 strategy. Body weight and food intake were not affected in either male mice or female mice by the deletion of Gabra5 from POMC neurons. We found that the deletion of Gabra5 caused a significant increase in the firing frequency and rest membrane potential, and a decrease in the amplitude of mIPSC in male POMC neurons. However, the deletion of Gabra5 just modestly decreased the frequency of mIPSC in female POMC neurons. Consistently, loss of Gabra5 from POMC neurons significantly improved the glucose tolerance in male mice but not in female mice. These results revealed a sexually dimorphic role of Gabra5 in POMC neuron activity and glucose balance, independent of body weight control.

Disclosure
Z.Pei: None. Y.He: None. Y.He: None. Y.Xu: None. C.Wang: None.

Funding
National Institutes of Health (KDK119471)
132-OR: Trends in Total Payments, Net Payments, and Rebates for a 30-Day Supply of Glucose-Lowering Drugs (GLDs) from 2010–2017
Authors: DING YAO , SHI LIZHENG , LIN YILU , SHAO HUI 
Published: May 2022

The rapid increase in total payments for GLDs may not reflect the change in actual economic burden, because a growing portion of the total payments were returned to the payers in the form of manufacturer rebates. This study explored trends in rebates for GLDs from 2010-17. We defined total payments as the retail amount the pharmacy received, including two components:1) rebates, the estimated proportion of the total payments retroactively passed through to pharmacy benefit managers and the payers; and2) net payments, the net spending for the GLDs. We used data from the 2010-17 Medical Expenditure Panel Survey to estimate the total payments including out-of-pocket payments, and data from the SSR Health and Medicaid programs to estimate the net payments and rebates. Four high-cost GLDs were included in this study: basal insulin, bolus insulin, GLP-1 Receptor Agonists (GLP-1RA) , and SGLT2 inhibitors (SGLT2i) . Costs were adjusted to 2017 U.S. dollars. While the total payments for a 30-day supply of bolus insulin, basal insulin and GLP-1RA increased by almost 200% from 20 to 2017, the rebates increased by more than 300%, attenuating the increase in net payments. By 2016-17, rebates accounted for 59%, 54%, 37%, and 49% of total payments for bolus insulin, basal insulin, GLP-1RA, and SGLT2i, respectively (Figure 1) . Our study is the first to quantify rebates for GLDs by class from a payer’s perspective.

Disclosure
Y.Ding: None. L.Shi: None. Y.Lin: None. H.Shao: Board Member; BRAVO4HEALTH, LLC.
1329-P: A RIPK2 Inhibitor Protects against Saturated-Fat–Induced Glucose Intolerance in Mice
Authors: TSAKIRIDIS NICOLE , IVOVIC ALEKSANDAR , RAHMAN S M NIAZUR , TAN YAO , GIACCA ADRIA 
Published: May 2022

Background: Obesity and type 2 diabetes (T2D) are associated with chronic low-grade inflammation. Elevated free fatty acids (FFAs) , as seen in obesity and T2D, can act as damage associated molecular patterns (DAMPs) activating the innate immune system. Recent studies have identified nucleotide binding oligomerization domain 1 (NOD1) , an intracellular pattern recognition receptor, can be activated by saturated fatty acids (sFA) . NOD1 activates inflammatory kinase RIPK2, leading to increased cytokine production by the innate immune system. Our study aimed to determine whether wild type mice treated with GSK583, a RIPK2 inhibitor, are protected against FFA-induced glucose intolerance.
Material and Methods: C57Bl/6J mice were surgically cannulated in their jugular veins and were infused with ethylpalmitate (EtP) for 48h, which results in increased plasma palmitate levels and mimics the elevated FFA levels seen in vivo. Furthermore, mice were also infused with EtP and GSK583 for 48h. After infusion, the mice were subjected to a hyperglycemic clamp and the glucose infusion rate was measured to assess glucose tolerance that under hyperglycemic clamp conditions, is mainly determined by the beta cell ability to compensate for FFA-induced insulin resistance.
Results: Preliminary data revealed that mice infused with EtP and GSK583 had a higher glucose infusion rate (GIR; mg/kgmin) (83+20, mean+SEM) than mice infused with EtP alone (57+4) . The EtP and GSK583 was comparable to the GIR of control (EtP vehicle infused) mice (84+7) .
Conclusions: Our data indicate that pharmacological inhibition of NOD1 signaling protects against FFA-induced glucose intolerance in mice. Targeting NOD1 may be an effective strategy for treating beta cell dysfunction in T2D.

Disclosure
N.Tsakiridis: None. A.Ivovic: None. S.Rahman: None. Y.Tan: None. A.Giacca: None.
1330-P: Longitudinal Multiyear Prospective Study in 87 Diabetic Primates: Lack of Support for a Mechanistic Basis for the Disposition Index
Authors: SHIVER LACHLAN , BELLIDO CARLOS , ROSADO ALANIS , HANSEN BARBARA C. 
Published: May 2022

Cross-sectional studies of individuals before, during, and after the development of overt type 2 diabetes (ADA definition) , as well as those in which 3 to 5 subgroups have been analyzed, typically have applied DM progression analyses using the parameters of the Disposition Index (DI) . In such correlation-based analyses, the inferences drawn do not reflect the relationships we and others have drawn from longitudinal analyses of the same data obtained within-subject across time during the development of diabetes. The problems with the DI and its interpretation have been a subject of concern for many years, but, nevertheless, its assumptions and interpretations have dominated the diabetes scientific literature. As recently noted by Arreola, et al 2022, the form of the relationship between two measures, insulin sensitivity as measured by the “gold standard” euglycemic hyperinsulinemic clamp and beta-cell responsiveness based on the intravenous glucose tolerance test induced Acute Insulin Response (AIR, 0 to min) is clearly nonlinear, and likely is not hyperbolic. In our longitudinal laboratory study of adult nonhuman primates, 87 developed overt type 2 diabetes[LS1] while under study. The laboratory provided standard monkey chow ad libitum to all individually caged Macaca mulatta rhesus monkeys throughout the study. We found that ß cell function was not a result of or associated with a decline in insulin sensitivity as measured by a euglycemic hyperinsulinemic clamp. Furthermore, hyperglycemia is clearly not the stimulus for nor cause of hypersecretion of insulin, the latter significantly preceding the development of impaired glucose tolerance followed by progression to overt DM. We conclude that the disposition index failed to predict the natural progression from normal to overt type 2 diabetes mellitus in this longitudinal data analysis, and its value is best considered only in the context of an epidemiological study using cross-sectional data.

Disclosure
L.Shiver: None. C.Bellido: None. A.Rosado: None. B.C.Hansen: None.

Funding
National Institutes of Health (NO1 AG3 1012)