bluuebunny/crossref_metadata_2025_split huggingface dataset:
19-OR: Glycemic Control Differences between Individuals with Accurately and Inaccurately Provider-Perceived Literacy and Numeracy
Authors: LOGENDRAN RASHECA , CRISTELLO ANGELICA , DUBOIS JULIEN , FRIEDMAN BRANDON S. , MAYER-DAVIS ELIZABETH J. 
Published: June 2020

Little is known about provider accuracy in assessing health literacy and numeracy of individuals with diabetes and the effect of incorrect assessment on patient outcomes. We conducted a clinic-based study (121 patients, 12 providers) to explore whether there was a discrepancy between patient-actual and provider-perceived literacy and numeracy levels among those (≥18yrs) with type 1 (n=59), type 2 (n=57), and unknown (n=5) diabetes, and to test whether this discrepancy was associated with worse HbA1c. We used multiple linear regression to compare mean HbA1c of patients whose providers overestimated, underestimated, and correctly estimated literacy and numeracy. Literacy was assessed by The Rapid Estimate of Adult Literacy in Medicine-Short Form and numeracy by the Diabetes Numeracy Test. Based on a directed acyclic graph and comparison of precision and bias of multiple models, the final models were adjusted for insurance (public/private), race (white/other), and education (≤high school/≥some undergraduate/≥some postgraduate).
Providers incorrectly identified 33.3% of patients’ literacy and 55.5% of numeracy. Providers overestimated 15.7% of patients’ literacy and 47.1% of numeracy. Providers underestimated 2.5% of literacy and 15.7% of numeracy. Mean Hb1Ac was 8.1%. Patients whose provider incorrectly perceived their literacy and numeracy score had, respectively, an HbA1c that was on average 0.9% (p=0.01) and 0.6% (p=0.05) higher than those whose scores were correctly perceived. Further, patients with overestimated numeracy had a 0.9% higher HbA1c than those whose high numeracy was correctly identified (p=0.001). These findings suggest providers might benefit from accurate knowledge of patients’ numeracy and literacy so that appropriate information can be communicated. Future research is needed to test effects of changing provider communication to minimize overestimation of patient numeracy and literacy levels.

Disclosure
R. Logendran: None. A. Cristello: None. J. DuBois: None. B.S. Friedman: None. E.J. Mayer-Davis: None.
1902-P: Insulin Pulses Do Not Inhibit Glucagon Secretion in Nondiabetic Humans
Authors: LAURENTI MARCELLO C. , MAN CHIARA DALLA , VARGHESE RON T. , RIZZA ROBERT A. , MATVEYENKO ALEKSEY , COBELLI CLAUDIO , VELLA ADRIAN 
Published: June 2020

Type 2 diabetes (T2DM) is characterized by defects in insulin secretion and glucagon suppression. It has been assumed that defective glucagon secretion arises due to impaired insulin secretion. Indeed, prior work suggests that pulsatile insulin secretion has an inverse relationship with post-prandial glucagon secretion. However, more recent data suggest that dysregulation of glucagon secretion in prediabetes occurs early, and independently, of changes in insulin secretion. During a series of experiments examining the mechanisms underlying prediabetes, we studied 29 nondiabetic subjects (age = 44 ± 2, BMI 28 ± 1 Kg/m2). Hepatic vein catheterization allowed sampling of insulin and glucagon at 2 minute intervals during fasting and during a hyperglycemic clamp (150mg/dL). Mean insulin concentrations rose from fasting (33 ± 1 vs. 144 ± 2 pmol/L, p&lt;0.01) while glucagon was suppressed (96 ± 1 vs. 62 ± 1 ng/L, p&lt;0.01) during the clamp. A cross-correlation analysis of the two hormones showed, on average, a small in-phase coordination between insulin and glucagon pulses during fasting, which inverted during hyperglycemia (0.2 ± 0.1 vs. -0.4 ± 0.1, p&lt;0.01). Subsequently, Cross-Approximate Entropy (Cross-ApEn), a technique for comparing synchronicity between two time series, was used to evaluate their interaction. This showed a moderate level of synchronicity, unaffected by glucose concentrations, whether calculated using glucagon as the template to assess pattern reproducibility in insulin concentration (0.78 ± 0.03 vs. 0.76 ± 0.03, fasting vs. hyperglycemia), or when using insulin as the template for the glucagon pattern (0.78 ± 0.02 vs. 0.76 ± 0.03, fasting vs. hyperglycemia). The values of Cross-ApEn did not differ between the two scenarios, suggesting the interaction between the two hormones is not driven by either. Overall these data suggest that, on a minute-to-minute basis, direct control and secretion of glucagon is not mediated (or restrained) by insulin.

Disclosure
M.C. Laurenti: None. C. Dalla Man: Research Support; Self; Sanofi-Aventis Deutschland GmbH. R.T. Varghese: None. R.A. Rizza: None. A. Matveyenko: None. C. Cobelli: None. A. Vella: Advisory Panel; Self; vTv Therapeutics, Zealand Pharma A/S. Research Support; Self; Novo Nordisk A/S, Xeris Pharmaceuticals, Inc.

Funding
National Institutes of Health (DK78646, DK116231)
1904-P: Metabolomic Fingerprints after Metabolic Surgery: The STAMPEDE Trial
Authors: DANTAS WAGNER S. , AXELROD CHRISTOPHER L. , HARI ADITHYA , KASHYAP SANGEETA , SCHAUER PHILIP , KIRWAN JOHN P. 
Published: June 2020

Introduction: Metabolic surgery (MS) results in durable resolution of hyperglycemia in ∼50% of patients with type 2 diabetes (T2D). Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) account for more than 90% of all metabolic surgeries, and both have been demonstrated to have greater efficacy when compared to intensive medical and lifestyle therapy (IMT) to improve glycemic control. However, a subset of patients following MS exhibit inadequate weight loss, poor glycemic control, or both. Thus, the purpose of this study was to identify novel biomarkers of biochemical resolution of T2D following IMT and MS.
Methods: Plasma samples from ninety patients (49.9±7.6 years, 57.7% female) randomly assigned to receive either IMT (n=30), RYGB (n=30) or SG (n=30) were retrospectively analyzed and quantified by untargeted metabolomic analysis using UPLC-tandem mass spectrometry at baseline (PRE) and 24 months (POST) of treatment.
Results: We identified 384 metabolites altered by RYGB, SG and IMT treatment. 2-hydroxybutyrate was significantly decreased following all 3 interventions with a greater decrease in SG and RYGB at POST (p≤0.05). Pyruvate was significant lower in the IMT and RYGB group (p≤0.05), but not in SG at POST (vs. PRE). Markers of fatty acid metabolism, including acetylcarnitine and 3-hydroxybutyrate (BHBA), were also decreased following the SG intervention (p≤0.05). Several primary and secondary bile acid metabolites were significantly increased after RYGB compared to SG.
Conclusion: We identified a novel metabolomic fingerprint characterizing the longer-term adaptations to IMT, RYGB, and SG. Notably, the metabolomic profile of both RYGB and SG procedures were distinct, suggesting that the roughly equivalent weight loss is achieved by divergent mechanisms.

Disclosure
W.S. Dantas: None. C.L. Axelrod: None. A. Hari: None. S. Kashyap: Other Relationship; Self; GI Dynamics Inc. P. Schauer: Advisory Panel; Self; GI Dynamics Inc. Consultant; Self; Ethicon US, LLC, Medtronic. Research Support; Self; Ethicon US, LLC, Medtronic. J.P. Kirwan: None.

Funding
Ethicon
1907-P: Using Human Genetics to Test the Disease Consequences of Varying Testosterone Levels in Men and Women
Authors: RUTH KATHERINE S. , DAY FELIX , TYRRELL JESS , MURRAY ANNA , ONG KEN , FRAYLING TIM , PERRY JOHN 
Published: June 2020

Circulating testosterone and SHBG levels are associated with type 2 diabetes (T2D). These associations differ between sexes and by total and bioavailable testosterone. For example, in UK Biobank a 1-SD raised bioavailable testosterone is associated with lower risk of T2D in men (OR=0.90 [0.88,0.92]) but higher risk in women (OR=1.24 [1.20,1.29]). Genetic studies provide more robust tests of causality and have indicated that higher circulating SHBG is protective of T2D (OR=0.92 [0.88,0.96], Perry et al 2010), but were limited to few genetic variants. In this study we aimed to: i) expand the set of genetic variants associated with circulating testosterone; ii) separate variants into clusters representing SHBG or direct testosterone effects; and iii) perform Mendelian Randomisation studies to better understand the potential causal effects of SHBG and testosterone on T2D and related traits. We used genome-wide analyses of sex hormones from 425,097 UK Biobank participants. We identified 2,571 genome-wide significant (P&lt;5x10-8) associations (vs. 17 pre-2019). The genetics of testosterone levels were very different between men and women (genetic correlation ∼0). To identify variants with specific testosterone-increasing effects independent of SHBG, we used a hierarchical-clustering strategy. In men, 122 loci were associated with higher testosterone in a dose-response manner with no effect on SHBG, with 241 such signals in women. We found that SHBG and testosterone levels can influence T2D and related traits. A genetically determined 1-SD higher testosterone increased the risk of T2D (OR=1.37 [1.22,1.53]) and polycystic ovary syndrome (OR=1.51 [1.33,1.72]) in women, but reduced T2D risk in men (OR=0.86 [0.76,0.98]). Using clustered variants suggested that diabetes effects were primarily mediated by testosterone in men. Our findings provide insights into the disease impacts of testosterone and highlight the importance of sex-specific analyses of diabetes.

Disclosure
K.S. Ruth: None. F. Day: None. J. Tyrrell: None. A. Murray: None. K. Ong: None. T. Frayling: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi, Servier. Research Support; Self; GlaxoSmithKline plc. J. Perry: None.

Funding
European Research Council (SZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERC); UK Wellcome Trust/Royal Society (104150/Z/14/Z); UK Wellcome Trust/Global Challenge Research Fund (SBF004\1079); Medical Research Council UK (MC_UU_12015/1, MC_UU_12015/2)
191-OR: A Web-Based Lifestyle Intervention to Reduce Postpartum Weight Retention in Women with Recent Gestational Diabetes: The Balance after Baby Intervention Trial
Authors: NICKLAS JACINDA M. , SKURNIK GERALDINE , ROCHE ANDREA T. , SCHULTZ CLAIRE , SURESH KRITHIKA , SEELY ELLEN W. 
Published: June 2020

Women with gestational diabetes (GDM) have a 30-70% risk for developing type 2 diabetes. Although women with a GDM history can decrease their risk for type 2 diabetes through weight loss and physical activity, few evidence-based programs exist to help decrease their risk in the postpartum period. Women with recent GDM were randomized at ∼6 weeks postpartum to a web-based 12-month lifestyle intervention program or to a control website. We measured weight and administered behavioral questionnaires at 6 weeks, 6 months, and 12 months postpartum. Our study included 181 women (mean 33±5.3 years; 48% White, 22% Asian, 17% African-American, 13% other race, with 35% Hispanic). 31% of women reported household incomes &lt;$35,000 per year. The mean BMI at the baseline study visit was 31 ± 6 kg/m2. Using a mixed effects model, at 12 months, women randomized to the intervention lost 1.4 kg vs. +1.1 kg in the control group (difference between groups -2.6 kg, 95% CI: -6.8 to +1.6, p=0.23). Retention at 12 months was over 85%. In a pre-planned subgroup analysis by ethnicity, non-Hispanic women in the intervention lost significantly more weight than non-Hispanic controls at 12 months (difference between groups of -5.8 kg, 95% CI: -10.9 to -0.6 kg, p=0.03). On the other hand, no significant weight difference between the intervention and control groups was seen at 12 months in Hispanic women (+2.9 kg, 95% CI: -3.2 to 9.1 kg, p=0.35). At 12 months postpartum, the Balance after Baby intervention program was associated with significant postpartum weight loss among non-Hispanic women, but not among Hispanic women. The Balance after Baby intervention program holds promise for decreasing diabetes risk factors in women with recent GDM. Analysis of the behavioral data may help explain the difference in weight outcome by ethnicity, and help guide future optimization of the intervention for Hispanic women.

Disclosure
J.M. Nicklas: None. G. Skurnik: None. A.T. Roche: None. C. Schultz: None. K. Suresh: None. E.W. Seely: None.

Funding
Centers for Disease Control and Prevention (HHSD2002013M53968B); National Institutes of Health (1K23HL133604); Colorado National Center for Advancing Translational Sciences (UL1TR001082, UL1TR001102)
1911-P: The Physiological Role of GLP-1 in Regulating Pancreatic Inflammation in a Sepsis Model
Authors: DAVIS ELLEN M. , HUTCH CHELSEA , KIM KI-SUK , MAERZ BASMA , LEHRKE MICHAEL , SANDOVAL DARLEEN A. 
Published: June 2020

Patients who have diabetes mellitus (both type 1 and type 2) have increased susceptibility to sepsis. Among the hormones that are altered by sepsis, there is an increase in the glucoregulatory peptide glucagon-like peptide-1 (GLP-1), and in animal models there is a specific increase in pancreatic-produced GLP-1 vs. glucagon. While the function of GLP-1 during sepsis is unknown, GLP-1 agonists have recently been of interest as an anti-inflammatory agent. We hypothesized that GLP-1 increases are necessary for dampening pancreatic inflammatory responses to sepsis in lean and HFD-fed mice. To model sepsis, we administered 100ng/g lipopolysaccharide (LPS) to C57BL/6 mice who had been fed HFD or chow for 12 weeks. We found that compared to vehicle treatment, LPS significantly increased plasma levels of GLP-1 in both HFD and chow-fed mice, but plasma GLP-1 was significantly higher and plasma glucose was significantly lower in HFD compared to chow-fed mice. To determine whether GLP-1 specifically regulated pancreatic inflammation, 24 hours after LPS we used flow cytometry to isolate pancreatic immune cells from chow-fed mice devoid of GLP-1 (GcgΔNull) and wild type (WT) mice. In chow-fed mice, we found approximately 20% more CD45+ cells in WT LPS treated mice compared to vehicle, and a similar percentage of CD45+ cells in LPS treated GcgΔNull mice compared to WT. In contrast, LPS administration to HFD-fed GcgΔNull mice, resulted in increased F4/80 positive cells compared to WT mice. Taken together, these data suggest that Gcg peptides are necessary to blunt LPS-induced inflammation in the pancreas and that GLP-1 physiologically regulates tissue inflammation. Future studies will determine whether the increased GLP-1 in HFD-fed mice is due to an increased inflammatory state or a decreased effectiveness of GLP-1.

Disclosure
E.M. Davis: None. C. Hutch: None. K. Kim: None. B. Maerz: None. M. Lehrke: Research Support; Self; Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Novo Nordisk A/S. Other Relationship; Self; Amgen, AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novo Nordisk A/S. D.A. Sandoval: Research Support; Self; MedImmune, Novo Nordisk A/S.
1921-P: Nonalcoholic Steatohepatitis in Mice with Hepatocyte-Specific Deletion of Mitochondrial Fission Factor
Authors: TAKEICHI YUKINA , MIYAZAWA TAKASHI , SAKAMOTO SHOHEI , SAKAMOTO RYUICHI , NOMURA MASATOSHI , OGAWA YOSHIHIRO 
Published: June 2020

Mitochondria are highly dynamic organelles continuously undergoing fission and fusion, referred as mitochondrial dynamics (MtD), to adapt to nutritional demand. Evidence suggested that impaired MtD leads to metabolic abnormalities such as nonalcoholic steatohepatitis (NASH)-like phenotypes, which are characterized by hepatic steatosis, inflammation and fibrosis. However, how MtD is involved in the development of NASH is poorly understood. In this study, we found mitochondrial fission factor (Mff), a critical mediator of mitochondrial fission, is upregulated in the liver from mice fed high-fat diet (HFD). To explore the role of Mff in the development of NASH, we generated liver-specific deletion of Mff (MffLiKO) mice. Histological analysis revealed that mitochondria are enlarged in the liver from MffLiKO mice fed normal chow diet (NCD), which is followed by hepatocyte apoptosis, slightly increased infiltration of inflammatory macrophages, and fibrosis. However, no lipid accumulation was observed in the liver from MffLiKO mice fed NCD. That is, only the impairment of Mff-regulated mitochondrial fission did not develop NASH-like phenotypes. On the other hand, the liver of MffLiKO mice fed HFD developed NASH-like phenotype with severer steatosis. Expression of mRNAs related to endoplasmic reticulum (ER) stress was markedly upregulated in the liver from MffLiKO mice. In addition, expression of genes related to hepatic triglyceride secretion was downregulated, with reduced hepatic triglyceride secretion in MffLiKO mice in vivo and in primary cultures of Mff-deficient hepatocytes in vitro. Interestingly, thapsigargin-induced ER stress suppressed triglyceride secretion in primary cultured hepatocytes in vitro. This study demonstrates that MffLiKO develop NASH-like-phenotypes in response to HFD and suggests that impaired MtD induces ER stress and thus reduces hepatic triglyceride secretion, which may play a role in the pathogenesis of NASH.

Disclosure
Y. Takeichi: None. T. Miyazawa: None. S. Sakamoto: None. R. Sakamoto: None. M. Nomura: None. Y. Ogawa: Research Support; Self; Mitsubishi Tanabe Pharma Corporation. Speaker’s Bureau; Self; Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation.
1925-P: Beneficial Effects of a Novel Long-Acting Glucagon Analog, HM15136, on Obesity and Obesity-Related Metabolic Disorders in Animal Models
Authors: LEE JONG SUK , LEE SEON MYEONG , CHOI JAEHYUK , PARK EUNJIN , LEE JONGSOO , LEE SANG DON , BAE SUNGMIN , KIM DAEJIN , CHOI IN YOUNG 
Published: June 2020

Obesity is a major risk factor for a number of metabolic disorders such as hyperlipidemia, glucose intolerance, and T2DM. Recent researches indicated a stimulatory effect of glucagon (GCG) on energy expenditure and appetite inhibition, suggesting the utilization of GCG as a pharmacological therapy for obesity and related metabolic disorders. In line with this, we previously observed that chronic treatment of HM15136, a novel long-acting glucagon analog, conferred efficient body weight loss (BWL) in DIO mice. Here, we further investigated the potential benefits of HM15136 in obesity-related metabolic disorders. In DIO mice, time-course change in fat mass, liver triglyceride (TG), and fasting blood glucose (FBG) was determined. Chronic treatment of HM15136 was associated with progressive BWL (-37.5% vs. vehicle (Veh) at day17) and fat mass reduction with little effect on lean mass, confirming its potent anti-obesity effect. Interestingly, despite marginal BWL at initial drug treatment period, significant reduction in blood TG (-56.5% vs. Veh at day2) and subsequent liver TG (-41.5% vs. Veh at day7) was achieved, and maintained thereafter. Moreover, the TG lowering both in blood and liver was followed by sustainable FBG lowering, suggesting that rapid depletion of lipid, the main sources for gluconeogenesis, might contribute to FBG control by HM15136. To evaluate the potential effect on post-prandial glucose control, oral glucose tolerance test (oGTT) was performed, and reduced BG level during oGTT was observed as BWL occurred. Time-dependent reduction in HOMA-IR evidenced the insulin sensitivity improvement. To our knowledge, this is the first study demonstrating the potential benefits of chronic GCG engagement in the management of BW, blood lipid, and even BG. Based on these results, HM15136 may be a novel option for the management of obesity and related metabolic disorders. Human study is ongoing for the clinical relevance of these findings.

Disclosure
J. Lee: Employee; Self; Hanmi Pharmaceutical. S. Lee: Employee; Self; Hanmi Pharmaceutical. J. Choi: Employee; Self; Hanmi Pharmaceutical. E. Park: Employee; Self; Hanmi Pharmaceutical. J. Lee: Employee; Self; Hanmi Pharmaceutical. S. Lee: Employee; Spouse/Partner; Hanmi Pharmaceutical. S. Bae: Employee; Self; Hanmi Pharmaceutical. D. Kim: Board Member; Self; Hanmi Pharmaceutical. I. Choi: Board Member; Self; Hanmi Pharmaceutical.
1928-P: ß-Casein–Derived Peptides Prevents Obesity by Activating Adipose Tissue Thermogenesis
Authors: ZHONG HONG , ZHANG XIAOXIAO , ZHANG ZHUO , CHI XIA , JI CHENBO , CUI XIANWEI 
Published: June 2020

Caloric intake that exceeds caloric expenditure is the main driver of obesity. Brown fat is characterized by the abundant mitochondria and could dissipate energy as heat, thus giving a feasible way to combat obesity. With the advent of GLP-1 receptor agonist in medical practice for diabetes treatment, peptide drug has been an important element in the pharmaceutical landscape. Discovery of bioactive peptide is hence increasingly appreciated. Presently, we identified an endogenous peptide, TPDHM1, from β-casein in milk. We further demonstrated its function in activating adipose tissue thermogenesis and the potential molecular mechanism involved. Our results confirmed that TPDHM1 could promote brown and white adipocytes energy metabolism both in vitro and in vivo. Chronic administration of TPDHM1 attenuated the high-fat diet induced obesity. Additionally, the insulin resistance and hyperglycemia of diabetic db/db mice were improved following TPDHM1 treatment. Mechanistically, both RNA-seq and protein microarray results revealed that the thermogenic effect of TPDHM1 is possibly mediated by p38-mitogen-activated protein kinase (p38-MAPK) signaling pathway. Inhibition of the p38-MAPK by SB203580 abolished the UCP-1 expression induced by TPDHM1. Taken together, our data suggest that TPDHM1 can potentially alleviate obesity and diabetes by stimulating energy metabolism via p38-MAPK pathways.

Disclosure
H. Zhong: None. X. Zhang: None. Z. Zhang: None. X. Chi: None. C. Ji: None. X. Cui: None.

Funding
National Natural Science Foundation of China (81770837, 81770866, 81900783)
193-LB: Diabetes Mellitus Does Not Impact Negatively on Outcomes of Hospitalizations Primarily for Systemic Lupus Erythematosus (SLE): An Analysis of the National Inpatient Sample Database
Authors: EDIGIN EHIZOGIE , SHAKA HAFEEZ , XU JING , YAP SARA ELIZABETH T. , PADILLA SORTO MARIA ELENA 
Published: June 2020

Background: Diabetes mellitus (DM) is a multisystemic disorder, known to be associated with worse outcomes of multiple conditions.
Objectives: This study aims to determine if diabetes has an impact on outcomes of hospitalizations primarily for SLE.
Methods: Data were extracted from the Nationwide Inpatient Sample (NIS) 2016 and 2017 database. The NIS was searched for SLE as the principal diagnosis for hospitalizations in 2016 and 2017, with and without DM as a secondary diagnosis, using ICD-10 codes. Adult Patients from the above groups were included. The primary outcome was inpatient mortality, while secondary outcomes were length of stay (LOS) and Total hospital charge. Multivariate logistic and linear regression analysis were used to adjust for possible confounders for the primary and secondary outcomes respectively.
Results: 20630 hospitalizations were for adult patients, who had principal diagnosis of SLE. 18560 (90.0%) of these hospitalizations had no secondary diagnosis of DM and 2070 (10.0%) had a secondary diagnosis of DM. A total of 255 inpatient mortality (1.23%) occurred in SLE hospitalizations, 35 (1.19%) of which occurred in patients with DM. The adjusted odds ratio (AOR) of inpatient mortality for SLE with DM compared to without DM was 0.554 (95% CI: 0.233 - 1.315, P=0.180). Hospitalizations with SLE and DM had a decreased adjusted mean LOS of 2.1 days (95% CI -3.0 - {-1.1}, P=0.000) compared to without DM. The adjusted mean total hospital charge for SLE and DM hospitalizations was also decreased by $24875 compared to without DM (95% CI -36154 - {-13596}, P=0.000).
Conclusions: There was no statistically significant difference in inpatient mortality of hospitalizations for SLE with DM compared to SLE without DM. Interestingly, SLE with DM hospitalizations has a shorter LOS and lower total hospital charge compared to without DM.

Disclosure
E. Edigin: None. H. Shaka: None. J. Xu: None. S.T. Yap: None. M. Padilla Sorto: None.