bluuebunny/crossref_metadata_2025_split huggingface dataset:
1576-P: Correlation Analysis between Insulin Sensitivity, Branched-Chain Acid, and Adiponectin Levels in Japanese Individuals with Varying Degrees of Glucose Tolerance
Authors: AMANO ERI , YOSHIMURA KUMIKO , FUNAKOSHI SHOGO , HIRANO SEIKI , OHMI SATOKO , TERADA YOSHIO , FUJIMOTO SHIMPEI 
Published: June 2020

Recent researches have revealed an association between circulating branched-chain acid (BCAA) and obesity and insulin resistance. In addition, experiments using rodents have revealed that adiponectin (APN) regulates the systemic BCAA level by affecting its catabolism. However, the influence of glucose intolerance on the relationship between BCAA and insulin sensitivity (IS) and between APN and BCAA in humans is unknown. Hence, we aimed to investigate these associations in individuals with varying degrees of glucose tolerance. Based on the data of 75g OGTT in 75 Japanese individuals without diabetic medication [age:65±11 (mean±SD); BMI: 24.9±3.8], individuals were classified into the normal, impaired glucose tolerance, and diabetes (DM) group (n=25 in each group). Matsuda index (MI) was calculated as an index of IS. Normally-distributed loge-transformed (ln-) values were used for MI and APN. Fasting BCAA was assayed using an enzymatic method. In analysis of total individuals using stepwise regression analysis, BMI (β=-0.477, p&lt;0.0001) and BCAA (β=-0.243, p=0.0195) are significant factors for predicting ln-MI. Furthermore, BMI, ln-APN, age, and sex are significant factors for predicting BCAA. In multiple regression analysis, using ln-MI as a dependent variable and BMI and BCAA as independent variables in each group, BCAA was negatively and significantly correlated with ln-MI only in the DM group, but not in the other groups [DM: β of BMI =-0.325, β of BCAA =-0.465 (p=0.02), R2=0.509]. In multiple regression analysis, using BCAA as a dependent variable and BMI and ln-APN as independent variables in each group, ln-APN was negatively and significantly correlated with BCAA in all the groups. In conclusion, BCAA was negatively correlated with IS independent of BMI, especially in individuals with DM. APN was negatively correlated with BCAA, independent of glucose tolerance.

Disclosure
E. Amano: None. K. Yoshimura: None. S. Funakoshi: None. S. Hirano: None. S. Ohmi: None. Y. Terada: None. S. Fujimoto: None.
1583-P: Decreased Serum 1,5-Anhydroglucitol Level Is Associated with Development of Abnormal Glucose Metabolism or Metabolic Syndrome in Male Japanese: Tokushima Cohort Study
Authors: HATA AKIKO , AKI NANAKO , ICHIHARA TAKAKO , TAMURA AYAKO , MINAGAWA TAKAKO , KUWAMURA YUMI , FUNAKI MAKOTO 
Published: June 2020

Serum 1,5-anhydroglucitol (1,5-AG) is a useful clinical indicator for short-term glycemic control status, which exhibits a rapid decrease if blood glucose levels are poorly controlled in diabetic patients. Interestingly, some cross-sectional studies have suggested that serum 1,5-AG level decreases even before the onset of type 2 diabetes. Thus, the aim of the present study was to examine whether there is an association between a decrease in serum 1,5-AG level and the incidence of abnormal glucose metabolism (AbGM) or metabolic syndrome (MetS) in Japanese in a prospective cohort study. We here report a prospective occupational-based cohort study, which was conducted during 2010-2017 in Japan. Briefly, 1) 837 male workers without AbGM and 2) 843 male workers without MetS aged over 20 years were followed up prospectively. AbGM was defined as either: 1) fasting plasma glucose ≥ 110 mg/dl, 2) HbA1c ≥ 6.0% or 3) medication for hyperglycemia. In multivariate analysis after adjusting for age, BMI, smoking habit, alcohol intake, regular exercise and estimated glomerular filtration rate, the HR of developing MetS was 1.81 [95%CI: 1.12 to 2.92, P=0.01] in the lowest quartile of baseline serum 1,5-AG, compared with the highest quartile. In addition, the incidence and multivariate-adjusted HR of AbGM or MetS also increased with decreasing quartile of serum 1,5-AG (P for trend for both &lt;0.05). Our findings suggest that a decrease in serum 1,5-AG level is a predictive marker for the future onset of AbGM or MetS in male Japanese.

Disclosure
A. Hata: None. N. Aki: None. T. Ichihara: None. A. Tamura: None. T. Minagawa: None. Y. Kuwamura: None. M. Funaki: None.

Funding
Tokushima Prefecture
1586-P: Five-Year Risk of Hepatobiliary Disease in Type 2 Diabetes: The Fremantle Diabetes Study Phase II
Authors: DAVIS WENDY A. , DAVIS TIMOTHY 
Published: June 2020

Nonalcoholic fatty liver disease (NAFLD) is estimated to coexist in 30-64% of people with type 2 diabetes (T2D). Several risk scores use clinical/laboratory data to screen for NAFLD. Although not developed for diabetes, some include it as a binary variable. The prognostic value of a high score in T2D is unknown. We therefore aimed to i) identify prevalent/5-year incident hepatobiliary biliary disease (HBD) in community-based people with T2D, ii) evaluate available NAFLD risk scores to predict 5-year incident HBD, and iii) if none performed acceptably, develop a novel prognostic risk score. Detailed data from the Fremantle Diabetes Study Phase II (FDS2) cohort and validated linkages were used to identify ICD coded hospitalizations/cancer registrations for/with HBD and deaths from/with HBD. Of 1,499 FDS2 T2D participants recruited in 2008-2011, 204 (13.6%) had prevalent HBD and 94 (7.3%) of the remaining 1295 had a first HBD event during 5,979 person-years’ follow-up to the event, death from non-HBD causes (124 (9.6%)), or census at 5 years, whichever came first (incidence rate 16 (95% CI 13-19)/1,000 person-years). The discrimination of available NAFLD risk scores for prediction of 5-year incident HBD was weak (AUC 0.51 to 0.61). In a novel competing risk regression equation, Aboriginality, eGFR &lt;30 and ≥90 ml/min/1.73m2, ln(AST/ALT), ln(GGT), ln(platelets), and ln(alpha-2-macroglobulin) independently predicted 5-year incident HBD. Discrimination (AUC (95% CI): 0.70 (0.64-0.76), calibration (Hosmer-Lemeshow test, P=0.07) and accuracy (Brier score 0.06 (range 0-0.96)) were acceptable. For a 10% risk cut-off, sensitivity was 38%, specificity 89%, PPV 20% and NPV 95%. This FDS2-derived prognostic risk equation for incident HBD may facilitate selection of people with T2D who would benefit from intensified management aimed at preventing the adverse outcomes of NAFLD.

Disclosure
W.A. Davis: Advisory Panel; Spouse/Partner; Lilly Diabetes, Merck Sharp & Dohme Corp., Novo Nordisk A/S. Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Spouse/Partner; Lilly Diabetes, Merck Sharp & Dohme Corp., Mylan, Novo Nordisk A/S, Sanofi-Aventis. Other Relationship; Self; Proteomics International. Other Relationship; Spouse/Partner; Proteomics International. T. Davis: Advisory Panel; Self; Lilly Diabetes, Merck Sharp & Dohme Corp., Novo Nordisk A/S. Speaker’s Bureau; Spouse/Partner; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; Lilly Diabetes, Merck Sharp & Dohme Corp., Mylan, Novo Nordisk A/S, Sanofi-Aventis. Other Relationship; Self; Protemics International. Other Relationship; Spouse/Partner; Protemics International.

Funding
National Health and Medicine Research Council of Australia (513781, 1042231, 1126886)
159-OR: Vitamin E Treatment Reduces Severe Hypoglycemia-Induced Fatal Cardiac Arrhythmias in Type 1 Diabetic Rats
Authors: RENO CANDACE M. , OXSPRING MILAN B. , BAYLES JUSTIN , HOLIDAY IVANA , HUANG YIQING , FISHER SIMON J. 
Published: June 2020

Severe hypoglycemia can lead to fatal cardiac arrhythmias. Our studies have shown that diabetes, per se, increases the risk of hypoglycemia-induced mortality in rats. It was hypothesized that excess oxidative stress, associated with diabetes, increases the heart’s susceptibility to hypoglycemia-induced fatal arrhythmias. To test this hypothesis, Sprague Dawley rats were made diabetic (streptozotocin 65 mg/kg) and randomized to two treatment groups: 1) antioxidant Vitamin E (400 mg/kg/day; n=18) or 2) control (vehicle, n=16) injected subcutaneously over 8 days. Then, rats underwent hyperinsulinemic (0.4 units/kg/min) severe hypoglycemic (10-15 mg/dl) clamps for 3 hours with continuous electrocardiogram recording. Confirming its antioxidant properties, Vitamin E treatment significantly reduced oxidative stress in the heart 3.3-fold versus controls (Figure). As compared to hypoglycemia-induced mortality of 38% in controls, Vitamin E treatment significantly reduced mortality to 6% (p&lt;0.05; Figure). Additionally, Vitamin E treatment reduced 3rd degree heart block (6%) vs. control (46%; Figure). Overall, these results suggest that 1) oxidative stress in diabetes increases the heart’s susceptibility to hypoglycemia-induced arrhythmias, and 2) Vitamin E treatment reduces oxidative stress and reduces both cardiac arrhythmias and mortality to insulin-induced severe hypoglycemia.

Disclosure
C.M. Reno: None. M.B. Oxspring: None. J. Bayles: None. I. Holiday: None. Y. Huang: None. S.J. Fisher: None.

Funding
National Institutes of Health (5T32DK091317, R01NS070235); JDRF (3-APF-2017-407-A-N)
160-LB: T1D Technology Uptake in Massachusetts Schools: Preliminary Data Gathering
Authors: QUINN MARYANNE , PETTENGILL CAITLIN M. , AFZALI JEAN , TOULOUSE SHANYN , AFZALI JEAN , MELCHIONDA LAURIE A. , LINEHAN ANN , CONNOLLY JILL 
Published: June 2020

As length of hospital stay at T1D diagnosis declines, clinicians must innovate to manage pediatric T1D care. Concurrently, insulin pump and continuous glucose monitor (CGM) use has increased in Massachusetts (MA) youth.
Objectives: To report school nurse assessments of: 1. time MA school nurses coordinate parent-student T1D care; 2. prevalence of IP and CGM use in MA schools.
Methods: Questionnaires were emailed to 1330 licensed school nurses in March 2019; 327 (25%) submitted data on 576 students, i.e., student/RN = 1.76.
Demographics: School Nurses: The School Health Unit in the Commonwealth of MA is divided into 5 regions: Western, Central, MetroWest/Boston, Northeast and Southeast. 93% of questionnaires were answered by public school nurses; 94% of nurses work in 1 school and 5% in 2 schools; 67% of schools have 1 FTE, 31% have 2 FTE and 3% have ≥3 FTE nurses;33% attended a T1D continuing education course in the past year.
Demographics: Students: ages 3 to 18 years, enrolled in pre-school-grade 12; 29% receive free, reduced or universal free school lunch; 4% speak English as a 2nd language; 67% have a 504 plan, 19% an Individualized Education Plan, and 79% an Individualized Health Care Plan. Attendance, Tardiness and Early Dismissal: School year 2018 - 2019: 12% of students were reported absent ≥10% of days; 8% were reported tardy ≥10% of days due to home T1D management; and 10% were dismissed early due to T1D
management concerns at school. No student was dismissed from school via ambulance.
Technology: 50% wear an insulin pump and 96% were reported to monitor glucose at school. Of those, 32% monitor interstitial and capillary glucose, 30% monitor only interstitial glucose and 37% monitor only capillary glucose. Four percent do not monitor glucose at school.
Communication: School nurse respondents spend 4.3 minutes/student/day communicating w a student’s parent/guardian. Massachusetts school nurses have ~7 hours/day to assist T1D-affected youth and the data supports most students see a school nurse daily.

Disclosure
M. Quinn: Advisory Panel; Self; Dexcom, Inc. C.M. Pettengill: None. J. Afzali: None. S. Toulouse: None. J. Afzali: None. L.A. Melchionda: None. A. Linehan: None. J. Connolly: None.
1603-P: Changes in Age- and Gender-Specific All-Cause Mortality Rates and Ratios in People with T2DM in Hungary between 2001-2016: A Nationwide Cohort Study
Authors: JERMENDY GYORGY , KISS ZOLTAN , ROKSZIN GYÖRGY , FÁBIÁN IBOLYA , WITTMANN ISTVAN , KEMPLER PETER 
Published: June 2020

T2DM is associated with a higher risk of all-cause mortality; however, detailed analyses of age- and gender-specific subgroups are rare. The aim of the study was to analyze the changes of age- and gender-specific all-cause mortality rates and ratios (excess risk) in T2DM subjects (aged &gt;40 years) in Hungary between 2001 and 2016. We used the central database of the National Institute of Health Insurance Fund. Annual all-cause mortality rates and ratios (T2DM/non-T2DM) were determined in males/females and in different age-groups (41-50, 51-60, 61-70, &gt;71 years). Age-adjusted values were used for evaluating standardized mortality rates. Among pharmacologically treated T2DM subjects we found 117,700 and 329,845 males, 232,143 and 391,382 females in 2001 and 2016, respectively. Standardized all-cause mortality rate was higher in males than females in 2001 (4540/100,000 vs. 3365/100,000) which decreased to 4125/100,000 in males (change: -11.8%, p&lt;0.0001) and to 2977/100,000 in females (change: -9.2%; p=0.0558) in 2016. The standardized all-cause mortality ratio was higher in females (1.39) than in males (1.13) in 2001. We found a significant increase (8.35%; p=0.0272) in standardized mortality ratios in our cohort between 2001 and 2016 which was higher in males (11.44%; p=0.0096) than females (2.78%; p=0.3288). We observed the most pronounced increase in all-cause mortality ratios between 2001 and 2016 in age-groups of 41-50 and 51-60 years in both genders (change varied from 54.2% to 101.8%; p&lt;0.05) which was due to distinct tendencies in changes of mortality curves (more impressive decrease in non-T2DM subjects than in T2DM patients). Pharmacologically treated T2DM subjects in lower age-groups (41-60 years) had the highest increase in all-cause mortality ratios between 2001 and 2016 in Hungary. These data indicate that younger patients with T2DM need special attention for improving long-term outcomes.

Disclosure
G. Jermendy: None. Z. Kiss: None. G. Rokszin: None. I. Fábián: None. I. Wittmann: None. P. Kempler: None.

Funding
Hungarian Diabetes Association (2019)
1608-P: Life Years Lost Associated with Prediabetes in a 40-Year Follow-Up Study
Authors: RAPOPORT MICHA , CHETRIT ANGELA , NOVIKOV ILIA , CANTRELL DROR , DANKNER RACHEL 
Published: June 2020

Background: The prevalence of prediabetes is gradually increasing and its association with life years lost (LYL) is yet to be determined.
Objective: to examine LYL associated with prediabetes as compared to normoglycemia, by age, sex, country of origin, smoking status, BMI, and blood pressure, using data of the Israel Study of Glucose Intolerance, Obesity and Hypertension (GOH) 40-year follow-up.
Methods: The population of the current study included 2,844 men and women (mean age 52±8.2 years) who underwent OGTT and anthropometric measurements, during 1976-1982, and were followed for mortality until May 2019. Normoglycemia, Prediabetes and diabetes were defined according to fasting plasma glucose, 2-hour post OGTT plasma glucose, reporting of having diabetes or use of antidiabetes medications. By the end of follow-up 27.7% remained alive and multiple imputation procedures were used for missing mortality dates.
Results: At baseline, 35.8%, 48.8% and 15.4% individuals were found with normoglycemia, prediabetes, and diabetes, respectively. Using multiple regression mixed models, the average difference in LYL associated with prediabetes as compared to normoglycemia was 4.3 years (95%CI 3.3-5.2; p&lt;0.001). LYL were higher in prediabetic women than in prediabetic men 4.4 (95%CI 3.0-5.7) vs. 3.3 (95%CI 1.9-4.8). These differences persisted mainly in individuals younger than 60 years, with BMI&lt;25 kg/m2, never smokers, and normotensives at baseline. Significant reductions of 9.9 years (95%CI 8.6-11.2) were observed for diabetes as compared to prediabetes and 14.2 years on average (95%CI 12.8-15.5) as compared to normoglycemic individuals.
Conclusions: This study reveals that life expectancy of middle-aged individuals with prediabetes is more than 4 years shorter than of normoglycemic individuals. As expected, diabetes was associated with the greatest LYL in this long-term cohort study.

Disclosure
M. Rapoport: None. A. Chetrit: None. I. Novikov: None. D. Cantrell: None. R. Dankner: None.
161-LB: Neurodevelopmental Outcomes of Infancy-Onset Diabetes
Authors: MCCAULEY MARY , DENSON ANNA M. , LETOURNEAU-FREIBERG LISA R. , SCOTT MEGAN N. , GREELEY SIRI ATMA W. 
Published: June 2020

Background: Infancy-onset diabetes is largely monogenic before 6 months of age, whereas autoimmune type 1 diabetes is more likely from 6-12 months of age. As the most common neonatal diabetes, patients with KATP channel mutations exhibit a spectrum of neurodevelopmental disability that is largely related to brain expression of mutated channels. It is not known how glycemic dysregulation of any type of early-onset diabetes may affect brain development.
Methods: Subjects included from UChicago Monogenic Diabetes Registry with diabetes diagnosed under a year of age currently aged 4-20 years and unaffected sibling controls. Known KATP channel mutations or other rare causes affecting brain development were excluded. Measures of intellectual function (IF), executive function (EF), visual motor integration (VMI) and academic achievement (AA) were utilized (Table 1). A two-sample t-test was conducted comparing each group assuming unequal variance.
Results: Comprehensive testing was completed for those with infancy-onset diabetes and siblings (Table 1). There were no significant differences on any measure, though mean scores trended lower in the affected group.
Conclusion: Our findings show no difference in IF, EF, VMI, AA in children diagnosed with diabetes in infancy compared to their unaffected siblings. Our conclusions are limited due to a small sample size; differences may be subtle and require a larger sample size to be identified.

Disclosure
M. McCauley: None. A.M. Denson: None. L.R. Letourneau-Freiberg: None. M.N. Scott: None. S.W. Greeley: None.

Funding
American Diabetes Association (1-17-JDF-008 to S.A.W.G.); National Institute of Diabetes and Digestive and Kidney Diseases (R01DK104942, P30DK0205950); National Center for Advancing Translational Sciences (UL1TR002389)
1620-P: Metabolites Associated with Insulin Resistance in Women with and without Type 1 Diabetes
Authors: SNELL-BERGEON JANET K. , SCHAUER IRENE E. , BERGMAN BRYAN C. , NADEAU KRISTEN J. , CREE-GREEN MELANIE , KESHAWARZ AMENA , PYLE LAURA 
Published: June 2020

Having type 1 diabetes (T1D) at least doubles insulin resistance (IR) compared to people without diabetes, but factors explaining this increased IR remain poorly understood. We analyzed untargeted plasma metabolomics in 30 premenopausal women aged 18-45 years (15 with and 15 without T1D) who underwent a hyperinsulinemic euglycemic clamp to measure insulin sensitivity. Sparse Partial Least Squares Discriminant Analysis (sPLS-DA) was used to identify metabolites that discriminated T1D status and diabetes-specific GIR tertile. Women with T1D had a significantly lower glucose infusion rate (GIR) than women without diabetes (5.5 ± 3.2 mg/kg/min vs. 12.8 ± 5.4 mg/kg/min, p=0.0001), indicating lower insulin sensitivity. Using sPLS-DA, we identified two components that discriminated T1D status (AUC=0.84) and two components that discriminated the lowest vs. highest group-specific GIR tertile (AUC= 0.91). Metabolite pathways discriminating T1D status and lowest vs. highest GIR tertile are shown in the Table. Common pathways discriminating both T1D and GIR tertile are in bold in the Table. Plasma metabolites mainly in the amino acid and lipid metabolism pathways differed by T1D status, and both overlapping and novel metabolites distinguished IR in premenopausal women. These data provide insight into common factors influencing IR regardless of diabetes status, as well as metabolic pathways affected by T1D.

Disclosure
J.K. Snell-Bergeon: Stock/Shareholder; Self; GlaxoSmithKline plc. I.E. Schauer: None. B.C. Bergman: Consultant; Spouse/Partner; Novo Nordisk Inc., Sanofi US. Research Support; Self; Eli Lilly and Company. Speaker’s Bureau; Spouse/Partner; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc. K.J. Nadeau: None. M. Cree-Green: Advisory Panel; Self; Novo Nordisk Inc. A. Keshawarz: None. L. Pyle: None.

Funding
American Diabetes Association (7-13-CD-10 to J.K.S-B.)
1635-P: Recurrent Mosaicism in Memory T-Cells from Newly Diagnosed Patients with Type 1 Diabetes
Authors: AL-RIYAMI MAHA , MARCHAND LUC , POLYCHRONAKOS CONSTANTIN 
Published: June 2020

Type 1 diabetes (T1D) is an autoimmune disease resulting in destruction of pancreatic beta cells by infiltrating self-reactive T-cells into the islets. The concordance rate of T1D is far from 100% in monozygotic twins and in the inbred NOD mice, despite genetic identity and shared environment during the years of peak incidence. This suggests stochastic determinants such as, somatic mutations in the expanding autoantigen-specific T cell lineages, parallel to what is seen in the expanding tumor lineages in cancer.
Here, using comparative genomic hybridization (CGH), we found that ∼67% of our study subjects (newly diagnosed patients with T1D) carry somatic copy number aberrations (CNAs) in proinsulin- reactive CD3+ T cell clones. Some of the mutated genes reoccurred independently in cells from two or three different patients which is a substantial evidence for a pathogenic contribution. These include genes with T cell expression and a proliferation or regulatory function, such as IKZF1, CHD7 and SMARCA2. Moreover, we identified genes, such as SAMD1 and CASZ1 that were previously identified in T cells of diabetic NOD mice and also have a proliferative and a regulatory function. The level of TCR clonality of the tested lymphocytes shows that these somatic mutations can occur both pre- and post- to the thymic selection. CNAs in T cells involved in host defense (reaction to Tetanus Toxoid) obtained from the same patients were significantly smaller in size. Our data provide evidence of a potential role of somatic mutations in the pathogenesis of T1D and, potentially, other autoimmune diseases.

Disclosure
M. Al-Riyami: None. L. Marchand: None. C. Polychronakos: Employee; Self; MaiDa Gene Technology, Zhoushan, Zhejiang Province, China.

Funding
Canadian Institutes of Health Research (MOP-137050); Canadian Diabetes Association (OG-3-11-3429CP); Sultan Qaboos University (to M.A-R.)