bluuebunny/crossref_metadata_2025_split huggingface dataset:
2269-PUB: Correlation between Serum Uric Acid Level in Adult Males and Their Fasting Blood Glucose Level in the Time of 1.5 Years
Authors: WANG YAN 
Published: June 2020

Objective: Investigating the correlation between serum uric acid (SUA) level in adult males and their fasting blood glucose (FBG) level in the time of 1.5 years.
Methods: Retrospective analysis based on two physical examinations including laboratory tests held at the Beijing Hospital during the period from 2014 to 2018, on 2337 adult males who work on non-physical jobs. Mean age was 61.6±13.3 at the first exam and 63.1±13.3 at the second exam. The two exams were held in the same season with an interval of 1-2 years (average 1.5). Results were collected from questionnaire, physical exams, and laboratory tests including levels of SUA, FBG, Hemoglobin Subunit Alpha 1, total cholesterol, triglycerides, LDL-c, HDL-c, creatinine, etc. During the first exam, no diabetes mellitus, gout, hepatic and renal insufficiency or malignant tumor was found, and all participants showed FBG &lt; 7.0 mmol/L. Data were divided into 4 groups based on SUA levels obtained from the two exams. Group 1 (296 participants, 12.7%): SUA ≥ 420umol/L in both exams. Group 2 (458 participants, 19.6%): SUA ≥ 420umol/L in one exam while 240 ≤ SUA &lt; 420umol/L in the other one. Group 3 (1479 participants, 63.3%): 240 ≤ SUA &lt; 420umol/L in both exams. Group 4 (104 participants, 4.4%): SUA&lt;240umol/L.
Results:1. A total of 136 participants (5.8%) showed FBG ≥ 7.0 mmol/L at the second exam, among which 29 (9.8%) belong to group 1, 40 (8.7%) belong to group 2, 65 (4.4%) belong to group 3, and 2 (1.9%) belong to group 4 (X2 24.000,P 0.000). 2. Risk analysis: Compared to group 4, the risk of individuals having FBG≥7.0mmol/L was 5.539 (95%CI 1.298-23.637) for group 1, 4.880 (95%CI 1.160-20.527) for group 2, and 2.344 (95%CI 0.566-9.712) for group 3.
Conclusions: The Hyperuricemia in adult males, especially those with Chronic Hyperuricemia, is correlated to the increase of FBG in the time of 1.5 years. Hyperuricemia is potentially a predictor of FBG increase in adult males, and clinical diagnosis of diabetes is required for those having FBG≥7.0mmol/L.

Disclosure
Y. Wang: None.
2273-PUB: Long-Term Incidence Rates of Complications in Patients with Type 2 Diabetes in Sweden
Authors: SVENSSON ANN-MARIE , FRANZÉN STEFAN , KLOK ROGIER M. , WEISS TRACEY , RAJPATHAK SWAPNIL , ELIASSON BJORN 
Published: June 2020

While it is known that patients with type 2 diabetes mellitus (T2DM) are at an elevated risk of developing several complications, there are limited data on incidence of these diabetic complications based on extended follow-up time following diagnosis of T2DM. We conducted an observational database study among newly diagnosed T2DM patients using the National Diabetes and other registries in Sweden. We calculated the incidence rates (IR) for several diabetic complications as number of events per person years with 95% exact Poisson confidence intervals. A total of 100,878 persons with new diagnosis of T2DM were included; average age (SD) was 62.6 (12.5) years, and 42.7% was female. The mean follow-up time was 5.5 years with the maximum follow up of 17 years. The Figure below shows the cumulative incidence of different complications from time of diagnosis as well as the IR of these complications. The cumulative incidence for the different diabetic complications shows a steady increase over time.

Disclosure
A. Svensson: None. S. Franzén: None. R.M. Klok: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. T. Weiss: Employee; Self; Merck & Co., Inc. S. Rajpathak: Employee; Self; Menarini Group. B. Eliasson: Consultant; Self; Amgen, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk A/S, Sanofi.
2275-PUB: Demographic Profile and Severity of Premature Ejaculation among Person with Type 2 Diabetes Mellitus Attending a Tertiary Care Hospital of Bangladesh
Authors: AHMED MOHAMMAD A.U. 
Published: June 2020

Background: As of 2014 worldwide about 9% (87 million) of the adult population have DM. Premature ejaculation (PE) is three times more common among them and diabetic patient experience the problem 10 to 15 years earlier than nondiabetic person.
Objective: It was aimed to find out premature ejaculation among patients with type 2 DM attending in a tertiary care hospital of Bangladesh.
Methods: This descriptive cross sectional study was conducted in the outpatient department of BIRDEM general hospital from July 2017 to June 2018. Total 225 adult respondents were recruited from diagnosed type 2 DM patients as per ADA 2016 criteria. A face to face interview was conducted with the help of premature ejaculation diagnostic tool (PEDT).
Result: Mean age of respondents 39.13 yrs±12.52 and age range was (21-65) years. Most of the respondents were married (73.3%). Among the study population, the prevalence of PE was 55.6%. Mean age of patients having PE was 38.36±8.89 year and age group of 21-30 years had higher incidence rate. Mean age of severe PE (within 15 sec) was found 41.17+_ 9.17 year and age group of 31-40 years had higher incidence rate. Among PE patients, 72% were married. Almost equal PE patients were from rural and urban habitat. Almost half PE patients (48%) had severe PE (within 15 seconds). Almost half of PE patients (48%) were suffering from type 2 DM for more than 10 years. PE was significantly higher (p&lt;.001) among patients with poor glycaemic control (HbA1c&gt;7).
Conclusion: PE is highly prevalent sexual dysfunction among type 2 DM patients, most of the times which remain under diagnosed and untreated. Large scale multi centered study would help to generalize as well as address the issue in a country like Bangladesh.

Disclosure
M.A.U. Ahmed: None.
2278-PUB: Longitudinal Progression of Diabetes Mellitus in Wolfram Syndrome
Authors: RAY MARY KATHERINE , HERSHEY TAMARA , CHEN LING , WHITE NEIL H. , MARSHALL BESS A. 
Published: June 2020

Wolfram Syndrome (WFS) is a rare, genetic, neurodegenerative disorder with associated features of diabetes mellitus (DM), diabetes insipidus, deafness, and optic atrophy. In order to design intervention studies, concrete markers of disease progression are required. DM in WFS is believed to be due to endoplasmic reticulum stress-induced failure of insulin secretion. Therefore, progressive loss of insulin production may be a viable marker of disease progression. The purpose of this study was to examine progression of DM, measured by beta-cell function, in WFS patients over time. N=44 (25F/19M) participants with genetically confirmed WFS attended the Washington University Wolfram Research Clinic from 2010-2019. A mixed meal tolerance test was administered to assess beta cell function (i.e., C-peptide). A hierarchical random coefficients model was used to relate C-peptide as a function of DM duration. Most patients (91%) had DM at time of study enrollment (N=39) or developed DM during the study (N=1). There was a significant association between C-peptide and DM duration, such that C-peptide decreased over time (F= 39.44, p=&lt;0.0001). Given the high prevalence and easily dated onset of DM in WFS, deterioration in C-peptide could potentially be used as a biomarker to assess disease progression in intervention trials for WFS, particularly in those with duration of DM &lt; 10 years as they may be less likely to experience a C-peptide floor effect.

Disclosure
M. Ray: None. T. Hershey: None. L. Chen: None. N.H. White: None. B.A. Marshall: None.

Funding
Washington University (HD070855, U54HD087011); Clinical and Translational Science Award (UL1RR024992); National Institute on Drug Abuse (5T32DA007261-27); Diabetes Research Center (DK020579); Snow Foundation, George Decker and Julio V. Santiago Pediatric Diabetes Research Fund; Mallinckrodt Institute of Radiology; McDonnell Center for Systems Neuroscience
2280-PUB: Cluster of Metabolic Disorders Increases Risk of Cancer in Chinese Patients with Type 2 Diabetes
Authors: ZHANG LEI , YANG YUXIU , MENG WEI , WANG JUN , CHEN SHUFANG , DONG YANHU 
Published: June 2020

Aims: The study aimed to investigate the relationship between metabolic syndrome (MS) and risk of cancer in patients with type 2 diabetes (T2DM).
Methods: We enrolled 6587 patients with T2DM who were hospitalized in Qingdao Endocrine and Diabetes Hospital from Feb 2005 to Jan 2016. According to the number of MS component each patient had, they were divided into isolated T2DM, T2DM plus 1 component,2 components, 3 components and 4 components, respectively. The IDF Worldwide Definition of the Metabolic Syndrome was applied. Information on the diagnosis of cancer was obtained by matching ICD-10 codes recorded in local Healthcare medical records database. Prevalence of cancer was compared using Chi-square test. Logistic regression model was used to evaluate risk of cancer associated with MS.
Results: The prevalence of cancer was 4.2% among 6587 patients with T2DM. Female patients had higher prevalence than did male in total or in the MS subgroup. The prevalence of cancer were 3.8%, 3.9%, 3.8%, 5.1% and 5.0% in isolated DM, T2DM plus 1 component of MS, T2DM plus 2, T2DM plus 3 and T2DM plus 4 components, respectively (P for trend &lt;0.05). Compared with those with less than 3 components, T2DM plus 3 or 4 components had increased risk of having cancer (OR=1.32, 95% CI: 1.04-1.69). Among T2DM patients who had more than 3 components of MS, a specific cluster of increased waist, elevated triglycerides (TG) and decreased High-Density Lipoprotein Cholesterol (HDL-C) was associated with the highest prevalence of cancer (10.7%), followed by 8.3% in T2DM patients plus hypertension, elevated TG and decreased HDL-C and 3.2% in T2DM patients plus hypertension, increased waist and elevated TG (χ2=26.6, P&lt;0.05).
Conclusions: A cluster of metabolic disorders consisting of increased waist, elevated TG and decreased HDL-C seems to be oncogenic among Chinese patients with T2DM. For patients in combination with 3 or 4 MS components, it is important to conduct early cancer screening and prevention.

Disclosure
L. Zhang: None. Y. Yang: None. W. Meng: None. J. Wang: None. S. Chen: None. Y. Dong: None.
2285-PUB: Hippocampal Transcriptomic Changes Due to High-Fat Diet in Prediabetic Mice
Authors: ELZINGA SARAH , HENN ROSIE , O’BRIEN PHILLIPE D. , GUO KAI , EID STEPHANIE , RUMORA AMY E. , HINDER LUCY M. , HAYES JOHN M. , MENDELSON FAYE , FELDMAN EVA L. , HUR JUNGUK 
Published: June 2020

The metabolic syndrome, prediabetes, and type 2 diabetes are increasingly common conditions worldwide, which predispose patients to the development of significant complications in both the central and peripheral nervous systems. Recently, our integrated lipidomics and transcriptomics study revealed an important role for lipid signaling pathways in peripheral nerves of mouse models of prediabetes and type 2 diabetes. While these data point to possible mechanisms of nerve damage peripherally, less is known about damage due to prediabetes and diabetes in the brain. This is of particular interest as growing evidence indicates that these conditions negatively affect cognition. Therefore, we performed RNA-Seq on hippocampi, a major site of learning and memory in the brain. Samples were isolated from a model of prediabetes and cognitive decline, wherein mice are fed a 60% high-fat diet (HFD). We identified various differentially expressed genes (DEGs) due to HFD, particularly after 11 wks (n=886), with fewer after 19 wks (n=111). Pathway analysis showed enrichment of pathways previously identified in the peripheral nervous system in response to HFD, including inflammatory and MAPK signaling pathways. Of interest, ∼31% of DEGs due to 11 wks of HFD overlapped with DEGs due to age (control animals only, comparing 19 to 11 wks of diet). These overlapping DEGs included genes such as fatty acid elongase 6 and hyccin (leukodystrophy protein FAM126A), which have roles in lipid metabolism and myelination, respectively. Enrichment analysis revealed multiple metabolic and protein processing pathways, such as oxidative phosphorylation and the proteasome. These data suggest that, like the peripheral nervous system, HFD effects similar pathways in the brain and may accelerate age-related gene expression changes in the hippocampus. However, more robust studies are needed to fully understand the influence of HFD on possible premature brain aging and how gene expression changes may contribute to cognitive decline.

Disclosure
S. Elzinga: None. R. Henn: None. P.D. O’Brien: None. K. Guo: None. S. Eid: None. A.E. Rumora: None. L.M. Hinder: None. J.M. Hayes: None. F. Mendelson: None. E.L. Feldman: Consultant; Self; Novartis Pharmaceuticals Corporation. J. Hur: None.

Funding
Program for Neurology Research and Discovery (T32DK007245, T32DK101357); National Institutes of Health (R24DK082841)
2286-PUB: Profiling MicroRNA (miRNA) and Metabolic Disease Association by Using Diffusion Model
Authors: HU PENGWEI , KUANG ZEMIN , HE TIANTIAN , HUANG YUAN , TANG ZEFANG , LI SHAOCHUN , MEI JING 
Published: June 2020

Background: MiRNAs play an important role in complex human diseases, and the identification of disease and miRNA associations can accelerate drug development, individualized diagnosis, and treatment of diseases. From a miRNA perspective, the molecular mechanisms of many complex diseases, such as metabolic disease, are not fully understood. However, experimentally exploring the relationship between miRNA and disease is expensive and time-consuming. The purpose of this study was to examine whether the computational model could infer related miRNAs for metabolic disease.
Methods: miRNA and disease can construct a bipartite graph according to their associations. Here, we propose a novel graph-based two-way diffusion model to reconstruct the bipartite graph and then transform the prediction task into a matrix to complete the problem. The underlying assumption made by our model is that miRNA or diseases that are highly similar to each other tend to have similar correlations and vice versa. We calculate the miRNA similarities for all the miRNAs by use MiRNA functional similarity and miRNA Gaussian similarity. We also calculate the semantic similarity and Gaussian similarity for all the diseases. Access to a miRNA expression, our model can infer its correlation with each metabolic disease.
Results: To assess the predictive model, we used the HMDD V3.2 database, which included 35,547 miRNA-disease association entries consisting of 1,206 miRNA and 893 diseases identified from the literature. The results show that the prediction model can achieve AUCs of 0.916 based on 5-fold cross-validation. We took type 2 diabetes mellitus as a target for miRNA prediction, 9 out of the top 10 predicted potential miRNA were confirmed by literature (e.g., hsa-mir-205).
Conclusions: We can use the model to select the most likely miRNA targets that specific metabolic diseases would associate with. It is anticipated that our model would become a practical tool for the clinical metabolic diagnosis and lab experiments.

Disclosure
P. Hu: None. Z. Kuang: None. T. He: None. Y. Huang: None. Z. Tang: None. S. Li: None. J. Mei: None.

Funding
National Natural Science Foundation of China (61702424)
2288-PUB: Ameliorating Type 1 Diabetes in Mice via Implantation of APA Microencapsulated Human Stem Cell–Derived Islets
Authors: GUO LIXIN , PAN QI , SONG YIZHE , CAO YIZHAO , OU ZHENSHENG , CHEN XIAOFENG , LI WENJIA , TANG XINFA 
Published: June 2020

Objective: Human pluripotent stem cells derived islets (SC-islets) provide a promising alternative source for beta cell replacement therapies for type 1 diabetes, while facing immune-rejection risks. Recent studies show that alginate-poly-L-lysine-alginate (APA) microcapsules have potentials to overcome the need for immunosuppression in allogeneic transplantation. In this study, APA encapsulated SC-islets were implanted into type 1 diabetes immune-competent mice models, to explore their ability to treat diabetes.
Method: First, we optimized differentiation method, SC-islets’ ratio of mature β cells and in vitro glucose response were measured; SC-islets encapsulated with APA were implanted into the intraperitoneal space of C57BL/6 STZ-induced diabetic mice (n=8), and blood glucose levels were further monitored.
Result: After optimization, SC-islets mature β cells (NKX6.1+/C-peptide+) reach 43.72 ± 1.62% (previous data was 21.01± 4.07%), and C-peptide positive cells increased from 34.93 ± 10.05% to 60.86 ± 1.15%. The SC-islets also included α or Δ cells, and responded to multiple sequential high-glucose challenges (insulin secreted ranged 2.10-3.27 μIU/103 cells). Then APA encapsulated SC-islets were implanted into the intraperitoneal space of diabetes mice. The fasting blood glucose decreased to normal level (3.70 ± 0.93 mM) on day 1 post-transplant, and the blood glucose maintained normal for 11 days. Similarly, random blood glucose returned to normal levels (11.01 ± 4.63 mM) on day 7 post-transplant.
Conclusion: Optimized SC-islets had a higher proportion of mature β cells and improved glucose response functions. The in vivo results showed that SC-islets in APA microcapsules can rapidly ameliorate hyperglycemia in diabetic mouse, while the duration time need further improvement through inhibiting fibrosis in alginate microspheres. Our results indicate that microencapsulated allogeneic SC-islets have potentials to treat diabetes.

Disclosure
L. Guo: None. Q. Pan: None. Y. Song: None. Y. Cao: None. Z. Ou: None. X. Chen: None. W. Li: None. X. Tang: None.
2289-PUB: Comparison of GalT-KO Porcine Islet Xenograft Survival between Microcapsule against Hypoxia and Microcapsule against Fibrosis in Diabetic Mice Model
Authors: LEE EUN YOUNG , YANG YEOREE , CHO YUNJUNG , LEE SEUNG-HWAN , CHO JAE-HYOUNG , YOON KUN-HO 
Published: June 2020

Hypoxia and fibrosis are one of the most important obstacles for encapsulated islet transplantation. Previously, we have developed alginate-based microcapsules improving fibrosis (alginate-chitosan) or hypoxia (alginate-perfluorodecalin) and proved their effects. In this study, we compared long-term graft survival of encapsulated islet with microcapsule against fibrosis or hypoxia in diabetic mice model, using 1,3-galactosyltransferase gene-knockout (GalT-KO) pigs. Islets were isolated form GalT-KO pigs and then encapsulated with alginate-chitosan or alginate-perfluorodecalin microcapsule. To magnify graft survival gap between different microcapsules, marginal dose of islets were transplanted into streoptozotocin-induced diabetic mice intraperitoneally. Blood glucose level were measured for a year. Intraperitoneal glucose tolerance test (IPGTT) was performed at 6 and 12 months after transplantation. In the alginate-chitosan group, the blood glucose level of diabetic mice decreased after encapsulated islet transplantation. However, blood glucose level increased again within two months in 3 out of 4 mice. In the alginate-perfluorodecalin group, the blood glucose level of diabetic mice decreased after transplantation and maintained normoglycemia more than 6 months. Although blood glucose level tended to increase 6 months after transplantation, it remained below 300 mg/dL by one year. The area under curve (AUC) of IPGTT was similar between two groups at baseline. At 6 months after transplantation, AUC of IPGTT in alginate-perflourodecalin group lower than AUC of alginate-chitosan group. At one year after transplantation, microcapsules were retrieved. Dithizone stain was positive in most retrieved islet and fibrosis was minimal in both groups.
In conclusion, microcapsule against hypoxia showed a longer xenograft survival than microcapsule against fibrosis in diabetic mice.

Disclosure
E. Lee: None. Y. Yang: None. Y. Cho: None. S. Lee: None. J. Cho: None. K. Yoon: None.

Funding
Cooperative Research Program for Agriculture Science and Technology Development (PJ01345301); Rural Development Administration, Republic of Korea
229-LB: Plasma Lactate and Muscle Aerobic Substrate Oxidation: Does Elevated Lactate Precede Obesity?
Authors: BROSKEY NICHOLAS T. , JONES TERRY E. , YANG ZHEN , KHANG NKAUJYI , ZHENG DONGHAI , TANNER CHUCK J. , CORTRIGHT RONALD N. , HOUMARD JOSEPH A. , DOHM LYNIS 
Published: June 2020

Background: The incidence of metabolic diseases is rising and there is a dire need for early detection of risk in order to implement prevention. Fasting plasma lactate concentrations have been shown to be elevated in individuals with obesity and predictive of the development of T2D. An elevated lactate concentration is the product of a shift to glycolysis and a possible reduction in oxidative capacity. However, it is unknown if there are associations between lactate and oxidative capacity in healthy individuals that may predispose them to metabolic disease.
Aim: The aim of this study was to determine if fasting lactate concentrations were linked with a reduction in skeletal muscle oxidative capacity in a young healthy population.
Methods: Young (age 22 ± 0.5; N=30) lean (BMI (22.4 ± 0.4 kg/m2) women were screened for fasting plasma lactate. Subjects underwent assessments of body composition, aerobic capacity (VO2 peak), skeletal muscle oxidative capacity via near infrared spectroscopy (NIRS) and fasting glucose and insulin were measured for calculating HOMA-IR. Fatty acid oxidation rate was also determined in a subset of samples from skeletal muscle biopsies (vastus lateralis).
Results: The women were insulin sensitive (HOMA-IR 1.1 ± 0.1) and had a mean fasting lactate of 0.9 ± 0.1 mmol/L. Time till exhaustion on the VO2 peak test was inversely associated with lactate (R2 = 0.20, p=0.05). Likewise, the rate of deoxygenated hemoglobin (NIRS) (R2 = 0.23, p=0.03) and skeletal muscle fatty acid oxidation (R2 = 0.72, p=0.004) were also inversely associated with fasting lactate. Lactate was inversely correlated with HDL:LDL (R2 = 0.57, p=0.02) and positively correlated with waist:hip (R2 = 0.52, p=0.02).
Conclusion: Plasma lactate was inversely related to skeletal muscle oxidative capacity and with metabolic parameters that are risk factors for obesity and T2D. Fasting plasma lactate may thus be a biomarker for identifying healthy individuals at risk for metabolic diseases.

Disclosure
N.T. Broskey: None. T.E. Jones: None. Z. Yang: None. N. Khang: None. D. Zheng: None. C.J. Tanner: None. R.N. Cortright: None. J.A. Houmard: None. L. Dohm: None.

Funding
National Institutes of Health (DK56112, DK120296)