bluuebunny/crossref_metadata_2025_split huggingface dataset:
2256-PUB: Clonal Hematopoiesis of Indeterminate Potential (CHIP), Glycemic Traits, and Type 2 Diabetes (T2D) Risk
Authors: TOBIAS DEIRDRE K. , RAGHAVAN SRIDHARAN , BICK ALEXANDER , RAFFIELD LAURA , WU PEITAO , DICORPO DANIEL A. , DUPUIS JOSEE , LANGE LESLIE , ROTTER JEROME I. , KOOPERBERG CHARLES L. , MEIGS JAMES B. , MANSON JOANN E. 
Published: June 2020

Background and Objective: CHIP is the aging-related accumulation of genetic mutations in the hematopoiesis-associated genes of stem cells. CHIP was recently associated with total mortality and atherosclerotic cardiovascular disease. We tested the hypothesis that CHIP is associated with adverse glycemic traits and incident T2D risk.
Methods: This study includes a subset of n=9,704 individuals in the NHLBI Trans-omics for Precision Medicine (TOPMed) project from the Framingham Heart Study (FHS), Jackson Heart Study (JHS), Multi-Ethnic Study of Atherosclerosis (MESA) and Women’s Health Initiative (WHI). We analyzed individuals without a history of T2D, cancer, or cardiovascular disease, and collected blood for fasting glycemic traits and CHIP carrier status. CHIP was recently determined from blood DNA-derived whole genome sequencing using the CATK MuTECT2 somatic variant caller in pre-specified leukemogenic driver mutations in candidate clonal expansion genes. We are conducting multivariable linear models examining both cross-sectional associations of CHIP with glycemic traits and survival models for baseline CHIP with incident T2D, adjusting for age, sex, body mass index, smoking, cohort, and family history of diabetes.
Results: Mean (SD) age was FHS = 50 (14), JHS = 55 (13), MESA = 60 (10), and WHI = 66 (7) years. We identified n=460 (4.7%) as CHIP carriers. The most common variant was located in DNMT3A gene (60% of carriers). Among CHIP carriers, the prevalence of having CHIP present in 1 of the 4 genes previously implicated in atherosclerotic heart disease (DNMT3A, TET2, ASXL1, JAK2; Jaiswal, et al, NEJM 2017) was lowest in FHS (75%) and highest in JHS (96%). Results for CHIP in relation to glycemic traits and incident T2D (∼1,500 cases) will be presented in detail. We will additionally present the associations for gene-specific CHIP mutations.
Conclusions: These cutting-edge TOPMed data will elucidate the role of CHIP, a novel aging biomarker, in relation to T2D risk.

Disclosure
D.K. Tobias: None. S. Raghavan: None. A. Bick: None. L. Raffield: None. P. Wu: None. D.A. DiCorpo: None. J. Dupuis: Consultant; Self; Merck Sharp & Dohme Corp. L. Lange: None. J.I. Rotter: None. C.L. Kooperberg: None. J.B. Meigs: Consultant; Self; Quest Diagnostics. J.E. Manson: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (U01DK078616 to J.B.M., J.D., D.A.D., P.W.), (U01DK105554 to J.D., D.A.D.)
2259-PUB: Aging, Systolic Hypertension, Obesity, and Hyperuricemia Increase the Cardiovascular Risk in Patients with Type 2 Diabetes Mellitus in Northwest China
Authors: ZHAO QINGBIN 
Published: June 2020

Background: Diabetes has become an epidemic in developing countries. The incidence of adverse cardiovascular events is high and the control rate is low in Chinese patients with type 2 diabetes mellitus (T2DM), particularly in low-income areas of China. The aim of this study was to identify the risk factors for acute coronary syndrome (ACS) in patients with T2DM in Northwest China.
Methods: A total of 456 patients with T2DM admitted to The First Affiliated Hospital of Xi’an Jiaotong University from January 2018 to January 2019 were included in the study. Among these, 186 individuals newly diagnosed with ACS were categorized as the case group and 270 patients without ACS as the control group. Demographic characteristics and serum biomarkers between the two groups were compared using t-test or Chi-square test. Multivariate logistic regression was used to analyze the risk factors for ACS in T2DM.
Results: The proportion of elderly patients was higher in the case group than in the control group (30.65% vs. 15.56%, p &lt;0.001). Similarly, the case group had a higher proportion of patients with hypertension history (66.67% vs. 34.81%, p &lt;0.001), substandard systolic blood pressure (SBP) (44.09% vs. 21.48%, p &lt;0.001), hyperuricemia (34.41% vs. 11.11%, p &lt;0.001), and higher body mass index (BMI) (26.64 ± 3.96 vs. 24.87 ± 3.53, p &lt;0.001) compared to the control group. The multivariate logistic regression analysis showed that age ≥ 65 years, SBP ≥ 140 mm Hg, overweight or obesity, and hyperuricemia were all risk factors for ACS in T2DM, and their OR (95% CI) were 2.283 (1.371-3.802), 2.067 (1.322-3.233), 2.019 (1.501-2.716), and 3.108 (1.831-5.275), respectively.
Conclusion: Aging, systolic hypertension, obesity and hyperuricemia increase the risk of ACS in T2DM in Northwest China. Thus, weight loss and lowering of SBP and of blood uric acid levels may reduce the risk of ACS in T2DM.

Disclosure
Q. Zhao: None.

Funding
Shaanxi Province Science Technology of China (2019KW-079)
2270-PUB: Advanced Diabetes Does Not Necessarily Increase Risk of Liver Disease
Authors: MINHEM MOHAMAD A. , NAKSHABANDI AHMAD , CERASALE MATTHEW 
Published: June 2020

Objective: The association between uncontrolled diabetes mellitus (DM) and liver disease (LD) has been established. The impact of different etiologies of LD on specific DM complications (Cx) is not well known. The aim of this study is to determine if the frequency of DM complications are related to specific LD etiologies.
Methods: This is a cross-sectional study of the 2016 National Inpatient Sample database. Adult patients with type 2 DM were studied. ICD-10 CM codes were used to identify DM complications and different LD etiologies. Univariate analyses and multivariate logistic regressions were performed.
Results: 1,538,604 patients met inclusion criteria. The prevalence of DM complications was 26.9%. Based on multivariate analysis results (Table 1), kidney Cx were associated with increased viral hepatitis. Ophthalmic Cx were preferentially associated with an increased prevalence of hepatitis B but not C. Skin and circulatory Cx were associated with less reported in all LD, while neurological Cx were associated more with reported LD.
Conclusion: Among inpatients, the prevalence of DM Cx differ by LD, with more significant differences noted for patients with Hepatitis etiologies. Our analysis is limited with retrospective nature and should be supported with future prospective studies.

Disclosure
M.A. Minhem: None. A. Nakshabandi: None. M. Cerasale: None.
2274-PUB: Prevalence and Risk Factors of Sexual Dysfunction in Romanian Women with Type 2 Diabetes Mellitus and Chronic Autoimmune Thyroiditis
Authors: GHERBON ADRIANA , FRANDES MIRELA , TIMAR ROMULUS 
Published: June 2020

Background: Female sexual dysfunction (FSD) represents one of the chronic complications of diabetes, as the male sexual dysfunction, but less studied.
Objective: Assessment of the prevalence and risk factors associated with sexual dysfunction in Romanian women with type 2 diabetes mellitus (T2DM) and chronic autoimmune thyroiditis (CAT).
Material and Methods: The study sample included 132 Romanian women with T2DM and CAT. The presence of sexual disfunction was established using two validated questionnaires: Female Sexual Function Index, and Female Sexual Distress Scale-revised. CAT diagnosis was confirmed by the presence of antithyroid antibodies (antiperoxidase and antithyroglobulin antibodies).
Results: We found that 47% of women presented sexual dysfunctions: 25.8% loss of libido, 21.2% orgasm, 17.4% lubrication, 18.9% arousal, 8.3% pain, and 17.4% satisfaction problems. The analysis revealed that age was a significant risk factor for FSD, along with DM duration and CAT duration. The presence of dyslipidemia as well as a ponderal status of overweight or obese, and also the glycemic control parameters such as average glycemic level and HbA1c were significant risk factors for FSD.
Conclusions: Women with T2DM and CAT are more likely to present FSD and should be aware of additional risk factors.

Disclosure
A. Gherbon: None. M. Frandes: None. R. Timar: None.
2277-PUB: Factors Effecting Diabetes Patients’ Perception of Diet: An Extended Analysis of Facts and Fads
Authors: ERUKULAPATI RAVI S. , RM MANIKANDAN , DASH KALPANA , DAS SAMBIT , REDDY HARINI , S VENKATARAMAN , PUNJANI ARSHAD , YALAMANCHILI SANDHYA , TIPPISETTY SUREKHA , KOLUKULA VAMSI K. , KRISHNA SESHADRI G. 
Published: June 2020

Aim: To assess the awareness of dietary constituents, perception of diet in those with diabetes.
Methods: A cross-sectional, objective, qualitative questionnaire-based assessment was performed among outpatient diabetes patients who visited tertiary diabetes care centers in Metropolitan cities of India. The questionnaire was answered by diabetes patients in a simple ’Yes’ or ’No’ format about awareness of various foods. The questions were about diet, quantity that could be consumed, and myths about various food products consumed routinely. Patients’ perception of diet was categorized into ’correct’ and ’incorrect’ depending on their response to each question in a 10-point questionnaire. A score of ’1’ was given for each ’correct’ answer and ’0’ for an ’incorrect’ answer. Maximum score one can get is 10/10 and a minimum of 0/10.
Results: Total 2295 patients with diabetes were assessed. Patients included were in age range 9 to 90 years with median age of 55 years. Males, females were 62% and 38% respectively. A mean score of 3.8 and median score of 4 was achieved. 2.2% patients achieved maximum correct answer score of 9/10 and 5.9% patients had minimum score 0/10. 44.8% patients scored &lt;4, 45.3% scored 4-6 and 9.9% scored &gt;6. Socioeconomic status, education, HbA1c levels, occupation, Insulin use, duration of diabetes were the factors that contributed to better level of awareness about diet (p &lt;0.001). Age &lt;40 years, male gender, type 1 diabetes, previous diet counseling, exercise patterns, family history of diabetes, unmarried, weight &lt;40kgs, history of no alcohol usage and being non-smoker, were associated with better scores, although not statistically significant.
Conclusion: This study gives valuable insights into the lack of awareness about daily food products and the factors associated with the diet perceptions in diabetic patients. This facilitates health care providers to work on areas that could facilitate improving awareness about dietary practices in those with diabetes.

Disclosure
R.S. Erukulapati: None. M. Rm: None. K. Dash: None. S. Das: None. H. Reddy: None. V. S: None. A. Punjani: None. S. Yalamanchili: None. S. Tippisetty: None. V.K. Kolukula: None. S.G. Krishna: None.
229-OR: The Gut Microbiome in Adults with Prediabetes and Effect of Dietary Glycemic Index
Authors: UTZSCHNEIDER KRISTINA , NEUHOUSER MARIAN L. , NEWTON KATHERINE M. , BREYMEYER KARA , HULLAR MEREDITH A. 
Published: June 2020

Compositional and functional differences in gut bacteria exist between adults with normal glucose tolerance, IGT and type 2 diabetes and can change with dietary factors. We compared the gut microbiome between adults with impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and IFG+IGT and evaluated the impact of dietary glycemic index (GI) on the gut microbiome. The study enrolled 53 adults (mean±SEM: age 53.0±1.4 y, BMI 32.5±0.9 kg/m2) with IFG (n=20), IGT (n=10) or both IFG+IGT (n=23). Stool samples were collected in RNAlater after 2 weeks on a control, moderate GI diet (GI 55-58) and again after a 4 week dietary intervention of a low GI (GI&lt;35, n=18) or high GI diet (GI&gt;70, n=18 on placebo and n=17 on the antioxidant N-acetyl-cysteine 1200 mg po BID). Diets had the same macronutrient composition (55%carbohydrate/30% fat/15% protein) but more fiber in the LGI (65.1±2.2 g/d) vs. HGI diet (25.8±0.8 g/d). The stool microbiome was analyzed using 16S rRNA gene sequencing (V1-V3).
Results: α diversity was significantly higher in IGT vs. IFG+IGT (7.2±0.08 vs. 7.0±0.06, p&lt;0.05). Linear regression analysis adjusted for age, sex, BMI, race and sequencing plate showed 3 genera differed across groups on the control diet: Fusicatenibacter (p=0.01) and Lachnospiraceae UCG-008 (p=0.02) were lower in IGT vs. IFG+IGT; Oxalobacter was reduced in IFG (p=0.04) and enriched in IGT (p=0.004) vs. IFG+IGT. After 4 weeks on LGI or HGI diets α diversity did not differ and NAC had no effect on the microbiome. Adjusted regression analysis showed only the genus Anaerostipes differed, being higher in the LGI group (p&lt;0.0001).
Conclusions: Differences in microbiota were observed between IGT and IFG+IGT. These associations may contribute to poorer metabolic function in IFG+IGT, but would need further testing to determine cause and effect. The LGI diet was associated with higher Anaerostipes, a butyrate producing bacteria with beneficial anti-inflammatory effects. This may be related to the higher fiber content of the LGI diet.

Disclosure
K. Utzschneider: Other Relationship; Self; Medtronic. M.L. Neuhouser: None. K.M. Newton: None. K. Breymeyer: None. M.A. Hullar: None.

Funding
National Institutes of Health (R01DK092568, P30DK017047, UL1TR002319, P30CA015704, KL2TR002317, TL1TR002318)
2297-PUB: The Shape of Glucose Response Curve during Oral Glucose Tolerance Tests (OGTT) and Long-Term Near-Normoglycemia Remission in African Americans Presenting with Hyperglycemic Crises
Authors: COTTEN LUCIA , STEFANOVSKI DARKO , OLADEJO OMOLADE , UMPIERREZ GUILLERMO E. , VELLANKI PRIYATHAMA 
Published: June 2020

Approximately 70% of obese African American (AA) patients with new-onset diabetic ketoacidosis (DKA) and severe hyperglycemia (SH) achieve near-normoglycemia remission (defined as HbA1c &lt;7%, fasting blood glucose [BG]&lt; 130 mg/dl, and off insulin for 1 month) with intensive insulin treatment. The shape of glucose response curve during OGTT has been shown predictive of future glycemic failure and beta(β)-cell function in adolescents with diabetes and adults. Biphasic (Bφ) curves showing better glycemic control and β-cell function compared to monophasic (Mφ) or incessant rise (IR) curves. We hypothesize that in AA patients with new-onset DKA and SH, Bφ shape at remission is associated with lower hyperglycemia relapse compared to Mφ or IR curves. Seventy AA patients underwent a 75g two-hour OGTT after near-normoglycemia remission and at end of study (median follow-up, 392 days). Insulin sensitivity (Si, oral minimal model) and β-cell function (AUCi: incremental area under the curve of insulin), and disposition index (Di= Si x AUCi) were compared among the different OGTT response curves. Hyperglycemia relapse-free survival (fasting BG &gt; 130 mg/dl, 2 random BG &gt; 180 mg/dl or HbA1c &gt; 7%) was calculated with Kaplan-Meier curve. At remission, initial OGTT showed 56% of patients with Mφ, 16% with Bφ, and 29% with IR curve shape. Baseline characteristics did not differ. Even though, more patients in the Bφ group (88%) sustained remission than the Mφ (57%) and IR (53%), hyperglycemia relapse-free survival did not differ by curve shape (log rank, p=0.26). On initial OGTT, Si (p=0.09), AUCi (p=0.12) and Di (p=0.06) did not differ between curve shapes. At last OGTT, Si (p=0.43), AUCi (0.47) and Di (p=0.22) did not differ. In obese AA patients with new-onset DKA and SH, the shape of the glucose response curve during OGTT does not predict long-term glycemic control or β-cell function.

Disclosure
L. Cotten: None. D. Stefanovski: None. O. Oladejo: None. G.E. Umpierrez: None. P. Vellanki: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.

Funding
National Institutes of Health (K08DK0830361, K23DK113241-01A1, UL1TR002378, 1P30DK111024-01)
2304-PUB: Increased Glucagon Expression in Diabetes: The Role of miR-320a
Authors: JO SEONGHO , XU GUANLAN , JING GU , SHALEV ANATH 
Published: June 2020

Glucagon, secreted from the α-cells of pancreatic islets, plays an important, yet underappreciated role in glucose homeostasis. As the major counter-regulatory hormone to insulin, it helps maintain normal blood glucose levels and prevent life-threatening hypoglycemia. However, while the regulation of glucagon has been shown to be perturbed in subjects with diabetes leading to inadequately high levels and worsening of the hyperglycemia, the molecular mechanisms involved in this abnormal regulation are still unknown. We therefore first investigated the possibility that microRNAs might be involved in the regulation of glucagon expression. Indeed, analysis of the glucagon 3’UTR revealed two potential miR-320a binding sites in human and one potential site in mouse and rat, respectively. In addition, we performed luciferase reporter assays and found that miR-320a directly binds to the 3’ UTR of the human glucagon gene. To further determine the role of miR-320a in the regulation of glucagon gene expression, we performed gain and loss of function studies with miR-320a in αTC1-6 cells. Glucagon gene expression was reduced in response to miR-320a overexpression, whereas inhibition of miR-320a upregulated glucagon gene expression. Interestingly, consistent with its role in the regulation of glucagon, miR-320a is more highly expressed in α-cells than beta cells and its expression was decreased by high glucose. Moreover, this was associated with an increase in glucagon gene expression in mouse αTC 1-6 cells as well as human islets. Finally, these findings are not only consistent with the results in response to high glucose, but also demonstrate the pathophysiological relevance of this phenomenon. Taken together, our data suggest that reduced miR-320a expression may contribute to the increase in glucagon gene expression in type 2 diabetes. These findings indicate for the first time that glucagon gene expression is under the control of a microRNA and provide novel insight into the abnormal regulation of glucagon in diabetes.

Disclosure
S. Jo: None. G. Xu: None. G. Jing: None. A. Shalev: None.
231-OR: Phase I Study Investigating the PD, PK, and Safety of AT247 in Comparison with Novorapid and Fiasp
Authors: PIEBER THOMAS R. , AUGUSTIN THOMAS , MAGNES CHRISTOPH , GERRING DAVID J. , JEZEK JAN , HOWELL SARAH J. , ZAKRZEWSKI LEON , LAWRENCE FIONA J. , SVEHLIKOVA EVA 
Published: June 2020

Background: AT247, an ultra-rapid acting formulation of insulin aspart designed for faster absorption following s.c. injection, will lead to better postprandial glycaemic control and is key to the development of closed-loop pump systems.
Method: Plasma glucose and serum insulin concentrations were measured in 19 adult male participants with T1DM following a single s.c. dose (0.3 U/Kg) of insulin in a randomised, double-blind, cross over euglycaemic clamp study.
Results: Data presented as median; range. AT247 had a faster onset of glucose lowering effect than NovoRapid® and Fiasp® (onset of action: 17; 12-30 vs. 37; 20-88 vs. 23;16-50 mins). The early glucose lowering effect was greater for AT247 than NovoRapid® and Fiasp® (AUCGIR 0-60min: 212; 63-465 vs. 49; 0-303 vs. 91; 11-300 mg/kg; GIR=glucose infusion rate) (Fig 1A). Similarly, greater initial insulin exposure was seen for AT247 compared to NovoRapid® and Fiasp® (AUC Insulin 0-60min: 111; 48-205 vs. 41; 12-147 vs. 66; 25-188 mU*h/L). In addition, offset of exposure occurred earlier for AT247 than NovoRapid® and Fiasp® (time to late 50% Cmax Insulin: 173; 89-414 vs. 212; 106-389 vs. 221;106-441 mins). (Fig 1B). Comparisons are statistically significant with p&lt;0.05. No safety signals were detected for AT247.
Conclusion: AT247 has a superior (left-shifted) time-action and time-concentration profile as compared to both NovoRapid® and Fiasp®.

Disclosure
T.R. Pieber: Advisory Panel; Self; ADOCIA, Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker’s Bureau; Self; Novo Nordisk A/S, Roche Diagnostics K.K. T. Augustin: None. C. Magnes: None. D.J. Gerring: None. J. Jezek: None. S.J. Howell: None. L. Zakrzewski: None. F.J. Lawrence: None. E. Svehlikova: None.
2314-PUB: The Uric Acid Is Differentiated by Thyroid Hormones Levels in Obese Patients with Acanthosis Nigricans
Authors: ZHANG JUNYI , LI GUIFANG , CHENG XIAOYUN , WANG XINGCHUN , JAYACHANDRAN MUTHUKUMARAN , HUANG YUEYE , QU SHEN 
Published: June 2020

Purpose: To investigate the serum levels of uric acid (UA) in obese acanthosis nigricans (AN) patients with different thyroid hormones (THs) levels within the normal range.
Methods: We investigated 834 obese patients (385 females and 449 males) with euthyroid function in the department of endocrinology of shanghai 10th people’s hospital from 2011 to 2019 with the median age of 29 years (interquartile range 22-36 years) for this study. 343 patients were diagnosed of AN. The cut-offs for thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) were 2mIU/L, 16mIU/L and 5mIU/L, respectively.
Results: In male obese patients, AN patients with high TSH and FT4 had higher levels of UA compared to those with high TSH and low FT4 (523.20±120.98 vs. 477.56±86.92umol/L, P=0.036) and showed a correlation with fasting C-peptide (FCP) (r=0.330, P=0.029). The TSH, FT3, and FT4 alone did not showed any predictive value in male patients. In female patients, high FT3 was associated with higher levels of UA (388.47±100.95 vs. 366.33±82.40umol/L, P=0.019). However, the predictive value of FT3 in female was obtained only in low TSH subgroup (low TSH+ high FT3 vs. low TSH+ low FT3, P=0.033) not in high TSH patients. The levels of fasting insulin, 2h-insulin, FCP, 2h C-peptide, total cholesterol, triglyceride and testosterone were in correlation with higher UA levels in female obese patients with low TSH and high FT3(all P&lt;0.05).
Conclusion: The metabolic characteristics of UA are found to differ in obese patients with euthyroid function, in which AN plays an important role for male obese patients with high TSH and high FT4. But in the case of female, a combination of THs instead of AN showed it’s unique in UA metabolism.

Disclosure
J. Zhang: None. G. Li: None. X. Cheng: None. X. Wang: None. M. Jayachandran: None. Y. Huang: None. S. Qu: None.

Funding
National Key Research and Development Program of China (2018YFC1314100); National Natural Science Foundation of China (81970677); Shanghai Pujiang Program (2019PJD040); Effect of ApoC3 High Expression on Islet Cells and Related Molecular Mechanism (03.05.18.002)