bluuebunny/crossref_metadata_2025_split huggingface dataset:
1652-P: The Association between Long-Term HbA1c Variability, Blood Pressure, Cholesterol, and Body Weight in Type 2 Diabetes: Subanalysis of ABC Study
Authors: MINATO SOICHIRO , MATSUTANI DAISUKE , TSUJIMOTO YUKI , KAYAMA YOSUKE , SAKAMOTO MASAYA , NISHIKAWA MASAKO , UTSUNOMIYA KAZUNORI 
Published: June 2019

Aim: Visit-to-visit variability (VVV) of HbA1c was reported to be the risk of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM). However, factors related to VVV of HbA1c remain unclear. This study is first examined relationship between VVV of HbA1c and various parameters including VVV of blood pressure (BP), low-density lipoprotein-cholesterol (LDL-C), and body mass index (BMI).
Material and Methods: Analyzed were 4,678 patients with T2DM throughout Japan (38 hospitals). The inclusion criteria were patients whose HbA1c, BP, LDL-C, and BMI were measured 12 or more times during the 24-month period. VVV of HbA1c, BP, LDL-C, and BMI were evaluated using the coefficient of variation (CV). This study is sub-analysis of ABC trial (UMIN000034231).
Results: Mean age of participants was 61.3 ± 9.4 years (mean ± SD) and HbA1c was 57.2 ± 13.5 mmol/mol (7.4 ± 1.2%). Table shows univariate correlate and multiple regression analysis of HbA1c CV. HbA1c CV was correlated with HbA1c baseline, SBP CV, LDL-C CV, and BMI CV. In the multiple regression analysis, HbA1c baseline, LDL-C, and BMI CV were the strongest predictors of HbA1c CV.
Conclusion: VVV of HbA1c was strongly correlated with VVV of LDL-C and BMI, and HbA1c baseline in patients with T2DM. A large-scale clinical trial needs to be conducted to clarify factors affecting VVV of HbA1c.

Disclosure
S. Minato: None. D. Matsutani: None. Y. Tsujimoto: None. Y. Kayama: None. M. Sakamoto: None. M. Nishikawa: None. K. Utsunomiya: None.
1659-P: A Systematic Review of Trends in All-Cause Mortality among People with Diabetes
Authors: CHEN LEI , ISLAM RAKIBUL M. , WANG JOANNA , HIRD THOMAS R. , PAVKOV MEDA E. , GREGG EDWARD W. , TABESH MARYAM , KOYE DIGSU , HARDING JESSICA L. , SACRE JULIAN W. , BARR ELIZABETH L. , MAGLIANO DIANNA J. , SHAW JONATHAN E. 
Published: June 2019

Some studies have reported falling mortality among populations with diabetes, but the consistency of this trend is unclear. We systematically reviewed studies published from 1980-2017 reporting all-cause mortality across 2 time-periods in people with diabetes. A total of 35 studies were found, providing data on 56 sex-specific or total populations with diabetes or type 2 diabetes. All studies were from high-income countries. Mortality declined in 80% of populations with diabetes in the 1980s, 53% in the 1990s, and 85% from 2000 onwards (Table). Falling mortality in diabetes occurred in 87% of Europid populations and in 10% of non-Europid populations. Of 25 populations with age-specific data, mortality declined in 29% of populations aged &lt;40 years and in &gt;60% of populations aged &gt;55 years. Of 37 populations that reported on those with and without diabetes, greater or similar mortality reduction was observed among those with diabetes than without diabetes in 70% of populations.
In conclusion, mortality has declined in the majority of Europid populations with diabetes since 1980. However, most non-Europid and most younger populations show no such declines.

Disclosure
L. Chen: None. R.M. Islam: None. J. Wang: None. T.R. Hird: None. M.E. Pavkov: None. E.W. Gregg: None. M. Tabesh: None. D. Koye: None. J.L. Harding: None. J.W. Sacre: None. E.L. Barr: None. D.J. Magliano: None. J.E. Shaw: Advisory Panel; Self; Abbott, Merck Sharp & Dohme Corp. Speaker's Bureau; Self; AstraZeneca, Mylan, Roche Diabetes Care, Sanofi-Aventis.

Funding
Centers for Disease Control and Prevention
1662-P: Comparison of Anthropometric and Metabolic Parameters among Africans Living in America
Authors: AHMED ALI , SIRAJ ELIAS S. , DUBOSE CHRISTOPHER , MUGENI REGINE , HORLYCK-ROMANOVSKY MARGRETHE F. , ADUWO JESSICA Y. , WILLIAMS KEVIN JON , SUMNER ANNE E. 
Published: June 2019

Differences in anthropometric and metabolic parameters among people of African, European, South Asian, and other origins are well described in the literature. In addition, we and others have reported that many of these parameters are different when comparing African Americans with Africans who recently moved to the U.S. In contrast, reports comparing African populations of various ethnicities and geographic areas are still lacking. The black sub-Saharan populations of Africa show variation in culture, cuisine, language, ethnicity and genetics. The Africans-in-America cohort was established to evaluate the cardiometabolic status of Africans living in the United States who self-identify as healthy. Our goal was to compare anthropometric and metabolic parameters in 419 African-born blacks currently living in Washington, DC. The African regions of origin were West 53% (222/419), Central 21% (89/419), and East 26% (108/419). The Table below shows key findings among the three groups. The prevalence of previously undiagnosed diabetes and prediabetes in the entire cohort was 6.2% and 31.5% respectively. Compared with West and Central Africans, East Africans had higher % body fat, plasma TG, MCV and eGFR but lower systolic BP, vitamin B12, frequency of variant hemoglobin and serum albumin. Further studies will be needed to understand the underlying reasons for these findings, their meaning and long-term consequences.

Disclosure
A. Ahmed: None. E.S. Siraj: Advisory Panel; Self; Sanofi. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc. C. DuBose: None. R. Mugeni: None. M.F. Horlyck-Romanovsky: None. J.Y. Aduwo: None. K. Williams: Advisory Panel; Self; Gemphire Therapeutics Inc. Stock/Shareholder; Self; Gemphire Therapeutics Inc., Hygieia. A.E. Sumner: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Minority Health and Health Disparities; National Institutes of Health Clinical Center
1667-P: Hemoglobin Glycation Index Is Associated with Nonalcoholic Fatty Liver Disease in Healthy Population
Authors: YOO JEE HEE , LEE WOO JE , PARK JOONG-YEOL , LEE JIWOO , KANG YU MI , JUNG CHANG HEE , CHO YUN KYUNG , PARK CHEOL-YOUNG 
Published: June 2019

Aims: Hemoglobin glycation index (HGI), which quantifies interindividual variations in glycated hemoglobin (HbA1c), is known to be associated with diabetic complications and metabolic diseases. However, information on the association between HGI and nonalcoholic fatty liver disease (NAFLD) in healthy population, especially in Asian population is limited.
Methods: A total of 14,465 subjects without diabetes who underwent liver ultrasonography during routine health examination were enrolled and stratified in quartiles according to HGI levels.
Results: The prevalence of NAFLD significantly increased with HGI quartiles (24.8%, 29.7%, 32.6% and 40.6% in the 1st, 2nd, 3rd, and 4th HGI quartiles, respectively; p-value&lt;0.001). As compared with the lowest HGI quartile group, the highest HGI quartile group had worse metabolic parameters including body weight, waist circumference, body mass index and lipid profiles. In the multiple logistic regression analysis adjusted for multiple factors, the odds ratio of having NAFLD was 1.564 (95% CI: 1.350-1.813, p &lt;0.001) in the highest HGI quartile group.
Conclusions: Elevated HGI levels are independently associated with prevalence of NAFLD in a healthy Asian population.

Disclosure
J. Yoo: None. W. Lee: None. J. Park: None. J. Lee: None. Y. Kang: None. C. Jung: None. Y. Cho: None. C. Park: None.
1692-P: miR17 Overexpression or Deleting Its Target Gene Txnip Ameliorates Neural Tube Defect Formation in Diabetic Embryopathy
Authors: YANG PENGHUA , YANG PEIXIN 
Published: June 2019

microRNAs (miR) play important roles in the induction of diabetic embryopathy. Our previous studies have demonstrated that high glucose in vitro and maternal diabetes in vivo suppressed miR-17 expression. To determine whether miR17 down-regulation is involved in maternal diabetes-induced neural tube defects (NTDs) formation, we created a miR-17 transgenic (Tg) mouse line in which miR-17 specifically overexpresses in the developing neuroepithelium. miR-17 Tg male mice crossed with nondiabetic and diabetic (streptozotocin-induced type 1 diabetes) wild type (WT) female mice to generate WT and Tg embryos. Under nondiabetic conditions, there was no NTDs in both WT and Tg embryos. The NTD rate of WT embryos was 52.4% (22 out of 42 embryos) in diabetic pregnancy, whereas miR-17 overexpression in the neuroepithelium significantly reduced the NTD rate to 8.1% (3 out of 37 embryos). Txnip up-regulation is implicated in the pathogenesis of diabetes and diabetic complications. Txnip is a predicted miR-17 target genes, and miR-17 overexpression abolished maternal diabetes-increased Txnip expression. To investigate whether Txnip participates in the pathogenesis of diabetic embryopathy, the Txnip gene was deleted specifically in the neuroepithelium using the Cre-flox (f) approach by crossing Txnipf/w; nestin-cre male mice with nondiabetic or diabetic Txnipf/f female mice. Comparing to the NTD rate of 19.4% (7 out of 36 embryos) in WT embryos, embryos with conditional Txnip deletion had an NTD rate of 8.3% (1 out of 12 embryos). Our findings indicated that the miR-17-Txnip circuit is critically involved in the induction of diabetic embryopathy.

Disclosure
P. Yang: None. P. Yang: None.

Funding
American Diabetes Association (1-13-BS-220 to P.Y.); National Institutes of Health
1714-P: Absence of CYP8B1 Increases Insulin Sensitivity in Part via Modulation of the Gut Microbiome
Authors: CORLIANÒ MARIA , ZHONG SHIQI , SINGARAJA ROSHNI R. 
Published: June 2019

Disruption of a key bile acid synthesis enzyme, CYP8B1, results in the absence of cholic acid (CA), increased levels of chenodeoxycholic acid (CDCA) and improved glucose metabolism in mice. However, the mechanism by which the BAs affect glucose metabolism remains unclear. We found that the absence of CYP8B1 increases insulin sensitivity in chow-fed mice, making them phenotypically similar to antibiotic-treated wild type mice, suggesting a role for the microbiome in the beneficial effect derived from CYP8B1 depletion. The aim of this study is to determine if the gut microbiome contributes to the increased insulin sensitivity observed in the absence of CYP8B1. Ten to twelve weeks old female CYP8B1-/- and CYP8B1+/+ mice (n=8-10/group) were fed chow diet ad libitum and OGTT, ITT and GSIS were evaluated. The C2C12 mouse myotubes were exposed to either CA or CDCA, and Insr and Tgr5 levels were measured by qPCR. Moreover, 10 to 12 weeks old female CYP8B1-/- and CYP8B1+/+ mice (n=8-10/group) received a cocktail of antibiotics (1 g/L) in drinking water. Plasma bile acids were measured by GC-MS and ITT was evaluated every two weeks. CYP8B1-/- mice showed significantly increased insulin sensitivity compared to wild type littermates (p&lt;0.001) but no differences in OGTT and GSIS. In addition, the in vitro studies show that exposure of the myotubes to CDCA resulted in significant increases in Insr (t-test, p=0.009) and Tgr5 (t-test, p=0.02). We found that the alteration of the gut microbiome by antibiotics in the wild type mice abolished the difference in ITT between CYP8B1-/- and CYP8B1+/+ mice (p=0.08). Furthermore, the antibiotic-treated wild type mice displayed a significant increase in the CA:CDCA ratio (p&lt;0.0001), mimicking the bile acid pool composition of the untreated CYP8B1-/- littermates. Our results suggest that the specific microbiome composition in the absence of CYP8B1 might play a critical role in enhancing the insulin sensitivity, and therefore glucose metabolism in mice.

Disclosure
M. Corlianò: None. S. Zhong: None. R.R. Singaraja: None.
1721-P: Effect of the TCF7L2 Variant rs7903146 T Allele on the Incretin Effect in Individuals with Normal Glucose Tolerance or Type 2 Diabetes
Authors: MATHIESEN DAVID S. , LUND ASGER B. , HANSEN KATRINE BAGGE , JUNKER ANDERS , IDORN THOMAS , HORNUM MADS , JONSSON ANNA , HANSEN TORBEN , VILSBØLL TINA , BAGGER JONATAN I. , KNOP FILIP K. 
Published: June 2019

Background and Aim: The T allele of TCF7L2 rs7903146 is a common genetic variant associated with type 2 diabetes. The mechanisms underlying this association are not fully understood, but diminished incretin-induced insulin secretion has been suggested. We undertook this study to evaluate the effect of the TCF7L2 rs7903146 T allele on the incretin effect in normal glucose tolerant individuals and patients with type 2 diabetes.
Methods: The incretin effect was assessed by relating the difference in integrated beta cell secretory responses to oral glucose tolerance test (OGTT) and isoglycemic intravenous glucose infusion (IIGI) to the response during OGTT in 36 normal glucose tolerant individuals (of whom 12 had the risk-conferring variant rs7903146 (TC/TT)) and 20 patients with type 2 diabetes (10 with TC/TT). Homeostatic model assessment (HOMA) was used to estimate insulin resistance.
Results: No differences in incretin effect estimates between risk allele carriers and non-carriers in the two groups were observed. Normal glucose tolerant individuals with rs7903146 displayed higher C-peptide levels in the fasting state (P=0.029) as well as during OGTT (P=0.029) and IIGI (P=0.015) compared to normal glucose tolerant non-carriers. Normal glucose tolerant risk allele carriers were more insulin resistant compared to normal glucose tolerant non-carriers (P=0.042). No detectable differences in glucose metabolism were found between risk allele carriers and non-carriers in the type 2 diabetes group.
Conclusions: The TCF7L2 rs7903146 T allele was not associated with reduced incretin effect in these relatively small cohorts of normal glucose tolerant individuals and patients with type 2 diabetes. Insulin resistance rather than beta cell secretory defects distinguished the normal glucose tolerant risk allele carriers examined here, from the normal glucose tolerant non-carriers.

Disclosure
D.S. Mathiesen: None. A.B. Lund: None. K.B. Hansen: None. A. Junker: None. T. Idorn: Employee; Self; Novo Nordisk A/S. M. Hornum: None. A. Jonsson: None. T. Hansen: None. T. Vilsbøll: None. J.I. Bagger: None. F.K. Knop: Advisory Panel; Self; AstraZeneca, MedImmune, Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk A/S, Sanofi. Consultant; Self; Amgen Inc., Carmot Therapeutics, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker's Bureau; Self; AstraZeneca, MedImmune, Merck Sharp & Dohme Corp., Mundipharma, Norgine, Novo Nordisk A/S.

Funding
Novo Nordisk Foundation (NNF17OC0029370)
1729-P: Circadian Patterns of Autoimmune Components in the Blood of Persons with Type 1 Diabetes: Implications for the Timing of Blood Sampling
Authors: BELI ELENI , DIMEGLIO LINDA , WOERNER STEPHANIE , EVANS-MOLINA CARMELLA , MCGRAIL KIERAN M. , WASSERFALL CLIVE , ATKINSON MARK A. , BEAM CRAIG 
Published: June 2019

Purpose: Immune populations and cytokines are known to exhibit distinct circadian ("daily") variations. We sought to characterize circadian-related immune variation in persons with type 1 diabetes (T1D) to ascertain whether sampling of peripheral immune biomarkers should be timed with circadian patterns
Methods: We enrolled 10 adults (6 female) volunteers between 18 and 40 years of age, with T1D diagnosed for at least 12 months and free of other diseases. Subjects were admitted to the Research Center and had blood collections performed every 4 hours over a 24-hour period. Samples were processed and aliquoted after each draw. Flow cytometric analyses of central memory, regulatory, naïve T- and B-cells, monocytes and NK cell frequencies were performed in 200μl. Circadian variation patterns were characterized with fitted cosine curves using COSINOR analysis.
Results: Significant circadian patterns were identified for CD4 and CD8 T cells, T regulatory cells (T regs), Natural killer T cells (NKT), Dendritic Cells (DC) and B cells in T1D subjects. All populations except of NKT cells peaked during the night with peak levels estimated to occur respectively at (24:00 hour [95% CI]); CD4 0030 [2396,0040]; CD8 0106 [2358,0014]; T regs 2349 [2395,0005]; NKT 1527 [1217,1819]; DC 0070 [2392,0008]; B cells 0111 [2382,0014].
Conclusion: Clinical studies of immune interventions meant to influence immune populations should sample these populations at consistent times of day, and likely at peaks, or nadirs, in order to have the greatest range for therapeutic effect to be demonstrated. For B-cell reduction interventions (such as Rituximab), our study indicates the best time for PBMC sampling would be around midnight. For therapies targeting immune cell expansion, e.g., Treg expansion, the sampling may be better at nadir, where the increase will be the greatest- i.e., approximately noon.

Disclosure
E. Beli: None. L. DiMeglio: Research Support; Self; Amgen Inc., Caladrius Biosciences, Inc., Janssen Research & Development, Medtronic, Sanofi. Other Relationship; Self; Dexcom, Inc. S. Woerner: None. C. Evans-Molina: None. K.M. McGrail: None. C. Wasserfall: None. M.A. Atkinson: None. C. Beam: None.

Funding
JDRF International (3-SRA-2015-7-M-RJDRF, 3-APF-2017-396-A-N)
1737-P: Prevalence of Autoimmune Diseases in Longstanding Diabetes: Results from the Canadian Study of Longevity in Type 1 Diabetes
Authors: CARDINEZ NANCY , LOVBLOM LEIF ERIK , ORSZAG ANDREJ , CHERNEY DAVID , PERKINS BRUCE A. 
Published: June 2019

Objective: Type 1 diabetes (T1D) predisposes to higher lifetime autoimmune (AI) disease risk; the magnitude of this risk is not known with certainty. To approximate lifetime risk, we aimed to determine the prevalence of AI diseases in those exceeding 50 years T1D duration, as well as to explore sex-specific differences and associations with complications.
Methods: Descriptive analysis of the Canadian Study of Longevity in T1D, a nationwide questionnaire study initiated in 2013 that recruited 374 T1D participants with duration &gt;50 years. The questionnaire collected diabetes management variables, general medical history with a focus on AI disease, and diabetes-related complications. Clinical and laboratory data were obtained from primary care providers. The χ2-test and Student’s t-test were used for simple comparisons.
Results: The 374 participants with longstanding T1D had median age of 66 [59, 71] years, T1D duration 53 [51, 58] years and HbA1c 7.5±1.0%. AI diseases were reported in 184/374 (49.3%). Thyroid disease was most prevalent, 154/374 (41.2%) reported thyroid disease or was prescribed thyroid hormone replacement therapy. Addison’s disease or prescribed glucocorticoid and mineralocorticoid therapy was reported in 5/374 (1.3%). Autoimmune polyendocrine syndrome type 2 (APS-2), defined by the presence of thyroid disease, Addison’s disease and T1D, was present in 3/374 (0.8%). We observed a sex-specific difference in AI disease prevalence (34.6 females vs. 14.8% in males; p&lt;0.0001), driven by the difference in thyroid disease (29.5 females vs. 11.5% males, p&lt;0.0001). No difference in HbA1c was observed (7.5±1.1 vs. 7.6±1.0%, p=0.62). There was a trend toward lower CAD prevalence among those with AI disease (12.1 vs. 16.9%, p=0.05).
Conclusions: We estimate that in a population with longstanding T1D, the lifetime risk of AI disease approaches half, driven primarily by the presence of autoimmune thyroid disease, and with greater risk in females.

Disclosure
N. Cardinez: None. L. Lovblom: None. A. Orszag: None. D. Cherney: Other Relationship; Self; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Prometic Life Sciences Inc., Sanofi. B.A. Perkins: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Boehringer Ingelheim International GmbH, Insulet Corporation. Research Support; Self; Boehringer Ingelheim International GmbH. Other Relationship; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Medtronic, Novo Nordisk Inc., Sanofi.

Funding
JDRF (17-2013-312)
1752-P: GDF11 Involved in Expressed MicroRNAs during GLP-1RA Inhibited Adipogenesis
Authors: XUE PENG , WANG NA , LI ZIYI , LI SHILUN , YUKUN LI 
Published: June 2019

Differentiation of bone marrow mesenchymal stem cells (BMSCs)is controlled by a vast array of mechanisms, with miRNAs-mRNAs regulation network identified widely recently. In this study, we aimed to specify the differentially expressed (DE) miRNAs after glucagon-like peptide-1 receptor agonist (GLP-1RA) administration during adipogenesis in BMSCs. MiRNAs extracted from three different groups, [the control group (C), the adipogenesis group (A), and the GLP-1RA administration group (GA)], were sent for high-throughput sequencing. We identified 5 DE miRNAs (miRNA-150-5p, miRNA-129-5p, miRNA-201-3p, miRNA-201-5p, and miRNA-214-5p) among groups. The expression of the 5 DE miRNAs were verified by the real-time RT-PCR analysis and consistent with the small-RNA sequencing data. Target genes were then predicted, and highly enriched GOs and KEGG pathway analyses indicated that they were involved in multiple biological processes concerning adipogenesis. Two of the target genes, growth differentiation factor 11 (GDF11) and cholecystokinin B receptor (CCKBR), were verified for functional study. Actually, the mRNA levels of GDF11, rather than CCKBR, was down-regulated by miRNA-150-5pand involved in GLP-1RA administration. Taken together, these results suggested for the first time that GDF11 was involved in differentially expressed microRNAs during GLP-1RA inhibited adipogenesis in primary BMSCs.

Disclosure
P. Xue: None. N. Wang: None. Z. Li: None. S. Li: None. L. Yukun: None.

Funding
Natural Science Foundation of Hebei Province (H2016206243); Department of Health of Hebei Province (361005)
1755-P: Transferrin Role in Systemic Iron Influence on Insulin Sensitivity and Adipocyte Function
Authors: LORENZO FELIPE , JAIN SHALINI , MCCLAIN DON , DAS SWAPAN K. 
Published: June 2019

Systemic iron overload is associated with decreased insulin sensitivity (Si) and diabetes. We previously characterized the genetic regulation of iron and its effect on Si in humans, which demonstrated that expression of the iron transport protein transferrin (Tf) in adipose tissue plays a role in regulating insulin sensitivity. To further characterize this effect at the tissue and cellular levels, we generated heterozygous Tf knock out (KO) mice and human adipose cells (ASC52Telo) with knock down (KD) of Tf. Heterozygous Tf KO and wild type (WT) mice were fed a 40% fat “fast-food” diets, supplemented with glucose in the water, containing either 35mg or 2000mg iron per kg chow. Fasting glucose levels were not affected in the Tf KO mice compared to WT (p=0.3889) on the low iron diet, but increased in the KO mice on 2gm/kg iron (13% increase, p=0.0511) suggesting the attenuation of the protective effect of transferrin in blood sugar regulation at high iron diet. We previously reported that adipose cells transfected with TF shRNA compared to a control vector had decreased intracellular iron and exhibited insulin resistance. We also performed mitochondrial function studies (oxygen consumption analyzed by Seahorse) in these cells. Tf KD cells exhibited decreased maximal oxygen consumption compared to controls (p:0.0004). Iron treatment of the cells augmented respiration in the control cells but worsened maximal oxygen consumption in the Tf KD cells (p=0.0011). We conclude that transferrin-mediated iron transport in adipocytes plays an important role in determining insulin sensitivity, allowing beneficial responses to high iron, namely protection from hyperglycemia and augmented mitochondrial function.

Disclosure
F. Lorenzo: None. S. Jain: None. D. McClain: None. S.K. Das: None.

Funding
U.S. Department of Veterans Affairs