bluuebunny/crossref_metadata_2025_split huggingface dataset:
554-P: Dapagliflozin and Measures of Cardiovascular Autonomic Function in Patients with Type 2 Diabetes
Authors: ANG LYNN , KIDWELL KELLEY M. , REISS JACOB , DILLON BRENDAN R. , MIZOKAMI-STOUT KARA R. , LEONE VIRGINIA A. , POP-BUSUI RODICA 
Published: June 2020

Beneficial effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular outcomes in patients with type 2 diabetes (T2D) have been reported. We hypothesized that these benefits may be due to modulatory effects on the sympathetic/parasympathetic imbalance through blunting of the expected compensatory increase in heart rate associated with lowering blood pressure. We aimed to evaluate the effect of dapagliflozin (DAPA) on measures of cardiovascular autonomic neuropathy (CAN) in patients with T2D. We performed a pilot, randomized, 2-period crossover clinical trial comparing 12 weeks of glucose lowering intervention with DAPA versus glimepiride on measures of CAN [cardiovascular autonomic reflex tests (CARTs) and heart rate variability (HRV)] assessed at baseline and end of each drug period. Signed rank tests and mixed models were used to evaluate the differences in CARTs and HRV indices from baseline to 12 weeks between each drug period. Preliminary data are presented for forty-one participants with T2D on metformin monotherapy (mean age 57±8 years, mean diabetes duration 7±6 years, mean HbA1c 7.8±1.3%) at baseline. Although there were no significant differences in indices of CAN in each drug period, there was a trend for higher expiration and inspiration ratio on DAPA compared to glimepiride (mean change 0.02±0.10; p=0.07). We found significant or near significant interactions between sex and treatment for the root mean square of the differences of successive RR intervals (rmsSD) (p=0.021) and Valsalva ratio (p=0.06) in women on DAPA versus glimepiride compared with men. In women, the mean 12-week change for both measures on DAPA was larger than the mean change on glimepiride, whereas in men, the mean 12-week change was larger on glimepiride than DAPA. These preliminary short-term data suggest that DAPA may have beneficial effects on measures of CAN particularly in women with T2D. These findings need to be confirmed in larger prospective studies with longer follow-up.

Disclosure
L. Ang: None. K.M. Kidwell: None. J. Reiss: None. B.R. Dillon: None. K.R. Mizokami-Stout: None. V.A. Leone: None. R. Pop-Busui: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Consultant; Self; Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca. Other Relationship; Self; American Diabetes Association.
557-P: Gastric Electrical Neurostimulation Combined with Pyloroplasty for Refractory Diabetic Gastroparesis Improves Subjective and Objective Outcomes
Authors: BRIGHT TAMIS , SAROSIEK IRENE , SHANKER AARON , DAVIS BRIAN R. , PADILLA OSVALDO , DIAZ JESUS R. , ESPINO KARINA , MCCALLUM RICHARD M. 
Published: June 2020

Background: Gastric electrical stimulation (GES) improves symptoms in diabetic gastroparesis (DM GP) refractory to medical therapies but does not increase gastric emptying (GE). This study investigates the clinical outcomes of GES combined with pyloroplasty (PP) to improve GE as well as the pathophysiological characteristics of the responding patients.
Methods: Overall 39 DM (13 type I) GP patients with 16.6 (range 3-50) years of DM had GES with PP. Antral and pyloric biopsies were assessed for interstitial cells of Cajal (ICC) status. Depletion of ICC was defined as &lt;10 cells/HPF. GE scintigraphy (normal &lt;60% retention at 2h or &lt;10% at 4 h) was performed, and GP total symptoms score (TTS) of vomiting, nausea, early satiety, bloating, fullness and epigastric pain was assessed with a 5-point Likert scale pre and post-surgery.
Results: The 39 patients, (23F) mean age 45 (25-83) years, mean 5.2 years of GP symptoms, were enrolled. TSS improvement after mean follow up of 17 (1-42) months post-surgery was 62% (19.1±3.4) vs.(7.6±6.2), while almost 70% of patients improved TTS by ≥60%. GE at 2h improved from 77% to 45%, and from 55% to 20% at 4h while 47% completely normalized their GE. Both DM1 and DM2 patients responded with improved TSS and GE. Antral ICC were depleted in 28% of DM GP with a mean number of 12 (±5.2)/HPF, while 70% of patients had &lt;10 pyloric ICC with mean 7.4(±5.0)/HPF. Patients with &lt;10 pyloric ICC had a 64% improvement in TSS vs. 41% if pyloric ICC was ≥10/HPF.
Conclusion: DM GP patients treated by combining GES and PP show significant symptomatic improvement with accelerated and often normalized GE. Patients with depleted pyloric ICC were the most improved, emphasizing the key role of the pylorus in GP, and explains why adding PP to GES addresses the specific pathophysiological challenges in severe diabetic GP.

Disclosure
T. Bright: None. I. Sarosiek: None. A. Shanker: None. B.R. Davis: None. O. Padilla: None. J.R. Diaz: None. K. Espino: None. R.M. McCallum: None.
567-P: The Neutrophil-to-Lymphocyte Ratio as a Biomarker of Diabetic Retinopathy: A Cross-Sectional Study
Authors: LI MEI , TANG XIXIANG , TAN YING , NIE YUANPENG , LI HAICHENG , CHEN YANMING 
Published: June 2020

Aims: Diabetic retinopathy (DR) is one of the most prevalent complications, which causes visual impairment and vision loss in diabetic patients. It has been demonstrated that inflammation plays an important role in DR. Accumulating evidence suggests that the neutrophil-to-lymphocyte ratio (NLR) is a novel potential marker for determining the inflammatory state. We aimed to evaluate the correlation between the NLR and DR.
Methods: We performed a cross-sectional study involving 1658 patients with type 2 diabetic mellitus (T2DM) at the Third Affiliated Hospital of Sun Yat-sen University from January 2016 to December 2018. All these subjects underwent stereo fundus photography taken by a 45° Non-Mydriatic Fundus Camera (CR6-45NM, Canon, Tokyo, Japan) through undilated pupils, and physical examinations including body mass index (BMI), systolic and diastolic blood pressures (SBP and DBP). Laboratory tests were also performed to determine the levels of fasting plasma glucose (FPG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), serum creatinine (Scr), blood urea nitrogen (BUN), and glycosylated hemoglobin A1c (HbA1c). The NLR was calculated based on the absolute numbers of neutrophils and lymphocytes.
Results: 214 of the patients had DR. The age, DM duration, NLR, SBP were significantly higher in patients with DR compared with patients without DR (p &lt; 0.01). After the adjustments by multivariable analyses, the NLR was still significantly associated with DR (P=0.048, OR=1.088, 95% CI=1.001-1.182).
Conclusion: Our finding reveals that higher NLR values are a reliable biomarker for the occurrence of DR.

Disclosure
M. Li: None. X. Tang: None. Y. Tan: None. Y. Nie: None. H. Li: None. Y. Chen: None.

Funding
Research and Development Plans in Key Areas of Guangdong Province (2019B020227003); National Natural Science Foundation of China (81770826); National Key Research and Development Program of China (2017YFA0105803)
576-P: Association between Carbohydrate Antigen 125 and Diabetic Retinopathy in People with Type 2 Diabetes
Authors: YANG GUANGRAN 
Published: June 2020

Objective: Carbohydrate antigen 125 was reported to be related with incident type 2 diabetes risk and coronary artery calcification. However, little was known about its role in diabetic retinopathy. This study was to analyze the relationship between carbohydrate antigen 125 and diabetic retinopathy in type 2 diabetes.
Method: Type 2 diabetes people hospitalized in the department of Endocrinology without a history of tumor from March 2018 to February 2019 were enrolled. Diabetic retinopathy was diagnosed on the results of fundus photography. Serum carbohydrate antigen 125 was measured. People with cataract, other retina diseases, neoplastic diseases, cancers, hepatic failure and renal failure were excluded.
Results: All the people were divided into two groups based on the results of fundus photography. There were 177 people with diabetic retinopathy and 291 people without diabetic retinopathy. There was no significant difference in age, body mass index, fasting glucose, and lipid profiles between the diabetic retinopathy group and nondiabetic retinopathy group (p&gt;0.05). There was significantly different in gender, duration of diabetes, hypertension, HbA1c, and urinary albumin excretion rate (p&lt;0.05). Diabetic retinopathy people had higher carbohydrate antigen 125 compared to people without diabetic retinopathy (9.75±6.14U/ml, 8.11±4.04U/ml, respectively, p&lt;0.05). Logistic analysis showed that carbohydrate antigen 125 was associated with diabetic retinopathy after adjusting gender, duration of diabetes, HbA1c, hypertension, triglyceride, urinary albumin excretion rate and other confounding variables (adjusted OR=1.059, p&lt;0.05).
Conclusions: In this study, diabetic retinopathy had higher carbohydrate antigen 125 compared with people without diabetic retinopathy. Carbohydrate antigen 125 might be associated with diabetic retinopathy in type 2 diabetes. Further large-scale studies are needed to confirm this association.

Disclosure
G. Yang: None.

Funding
National Natural Science Foundation of China (81471009); Beijing Health System, Health and Technical Personnel of High Level Plan (2014-3-013); Capital’s Funds for Health Improvement and Research (2016-2-2054, 2020-026285-000005)
578-P: A Loss-of-Function Mutation of NRG4 Contributes to the Pathogenesis of NAFLD and Insulin Resistance
Authors: HU CHENG , LI YANGYANG 
Published: June 2020

Neuregulin 4 (Nrg4), as an adipose tissue-enriched endocrine factor, participates in adipocyte-to-hepatocyte communication which elicits beneficial metabolic effects in NAFLD. We identified a mutation of NRG4 by whole exome sequencing in 151 severe obese subjects and exome array in a community-based population of 2388 subjects. Nrg4 R44H mutation carriers have increased visceral fat area, abnormal liver function and hyperlipidemia. Then we hypothesized that the mutation would affect the function of Nrg4 and accelerated the development of NAFLD. Compared with Nrg4 WT mice, Nrg4 R44H mice gained more weight, accompanied by significantly increased fat mass and lipid accumulation in the liver upon HFD feeding. In vitro, we found that Nrg4 WT activated ErbB4 and stimulated the STAT5 signaling pathway and decreased transcriptional activation of srebp1c. As we hypothesized, the primary hepatocytes treated with Nrg4 R44H purified protein didn’t showed the same activation of cell signaling as Nrg4 WT. In order to reveal the potential mechanisms of loss-of-function of Nrg4 R44H, we performed surface plasmon resonance (SPR) experiments to test the binding affinity of purified Nrg4 and ErbB4 proteins. The SPR results showed Nrg4 WT bind to ErbB4 with an affinity of 2.20uM, while Nrg4 R44H showed no binding. Taken together, these results suggested Nrg4 WT prevented HFD-induced NAFLD and alleviated insulin resistance, and demonstrated Nrg4 R44H lost its ability to bind to the receptor ErbB4, thus losing its physiological function.

Disclosure
C. Hu: None. Y. Li: None.
579-P: Dyslipidemia in Type 2 Diabetic Mice Is Improved by Targeting Smad3 with a Smad3 Inhibitor SIS3
Authors: HE HUIJUN , HUANG XR , MA RONALD C. , LAN HY 
Published: June 2020

Purpose of the Study: Dyslipidemia is one of the diabetic complications which is relevant to the disorder of interaction between glucose and lipid metabolism. In our preliminary studies, we found that Smad3 is the key pathogenic mediator in db/db mice. Metabolic symptoms in diabetes are improved in Smad3KO-db/db mice. Thus, we hypothesized that Smad3 is a therapeutic target for treatment of dyslipidemia in type 2 diabetes.
Methods: db/db mice were treated with Smad3 inhibitor SIS3 at the age of 4 weeks at the dose of 2.5mg/kg bw/day by intra peritoneal injection for 8 weeks. Control group db/db mice were treated with SIS3 solvent only. Molecules and cytokines involved in lipid metabolism were examined by Realtime-PCR, Western blotting, immunohistochemistry, ELISA for in vivo and in vitro experiments. The mechanism of Smad3 signaling interfering lipid metabolism was studied by Chip-sequencing and RNA sequencing.
Summary of the results: Blood high density lipoprotein (HDL) level was up regulated while low density lipoprotein (LDL) level and triglycerides were down regulated in Smad3 KO mice, which showed Smad3 is one of the main regulators in lipid metabolism. SIS3 treated mice showed significantly improved glycemia, lipidemia. Insulin sensitivity was ameliorated in SIS3 treatment group compared with control group. SIS3 treated Hepg2 cells and AML12 cells showed lower lipid absorbance than control group. RNA sequencing revealed that differentially expressed genes (DEGs) in concentrations of apolipoproteins A1 (ApoA1) was notable enriched in liver of Smad3KO mice, which also showed APOA1 has direct binding site with Smad3. We subsequently found that APOA1 was negatively regulated by Smad3 signaling therefore influence the lipid metabolism in type 2 diabetes.
Conclusion: Smad3 is a pathogenic mediator of diabetic metabolism. Treatment of type 2 diabetic mice with Smad3 inhibitor SIS3 improves lipidemia by enhancing the activity of DEGs in APOA1.

Disclosure
H. He: None. X. Huang: None. R.C. Ma: Advisory Panel; Self; AstraZeneca. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Tricida Inc. H. Lan: None.
58-LB: Barriers to Technology Use for Underserved Communities with Type 1 Diabetes
Authors: WALKER ASHBY F. , CUTTRISS NICOLAS , HALLER MICHAEL J. , FILIPP STEPHANIE L. , YABUT KATARINA , ANEZ-ZABALA CLAUDIA , HOOD KOREY K. , ROQUE XANADU , NARANJO DIANA , AULISIO GINA , ADDALA ANANTA , LOOK SYDNEY , GURKA MATTHEW J. , MAAHS DAVID M. ,   PROJECT ECHO DIABETES WORKING GROUP
Published: June 2020

Disparities in the use of CGMs and insulin pumps in T1D based on socioeconomic status (SES) and race/ethnicity are pronounced. However, systematic reports of perspectives from patients in vulnerable communities are limited. To better understand barriers, focus groups were conducted in Florida and California with adults with T1D. Selection criteria included hospitalization for DKA, HbA1C &gt;9%, or receiving care at a Federally Qualified Health Center. A total of 16 focus groups were conducted in English or Spanish with 86 adults (Table 1). Transcript themes and pre-focus group demographic survey data were analyzed. In order of frequency, barriers to diabetes technology included: (1) provider-level (overtly blocked/discouraged by provider) (2) system-level (financial barriers related to coverage) and (3) individual-level (difficulty with use or preference issues). In Florida there was less technology use overall (38% had used CGMs in FL, 63% in CA; 43% had used pumps in FL, 69% in CA) and significant differences in pump use by SES (P=0.02 in FL, P=0.08 in CA) and race/ethnicity (P=0.01 in FL, P=0.80 in CA). In California there were significant differences in CGM use by race/ethnicity (P=0.05 in CA, P=0.56 in FL) and education level (P=0.02 in CA, P=0.90 in FL). These findings provide novel insights and demonstrate the need for multi-level interventions and further research on variations in technology use based on geographic location.

Disclosure
A.F. Walker: None. N. Cuttriss: None. M.J. Haller: Advisory Panel; Self; SAB Biotherapeutics, Inc. S.L. Filipp: None. K. Yabut: None. C. Anez-Zabala: None. K.K. Hood: Research Support; Self; Dexcom, Inc. Speaker’s Bureau; Self; LifeScan, Inc., MedIQ. X. Roque: None. D. Naranjo: None. G. Aulisio: None. A. Addala: None. S. Look: None. M.J. Gurka: None. D.M. Maahs: Advisory Panel; Self; Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk A/S. Consultant; Self; Abbott, Sanofi. Research Support; Self; Bigfoot Biomedical, Dexcom, Inc., Roche Diabetes Care, Tandem Diabetes Care.

Funding
The Leona M. and Harry B. Helmsley Charitable Trust
584-P: Optimal Utilisation of Statins in Real-World Settings
Authors: KRISHNA SESHADRI G. , DAS SAMBIT , NK NARAYANAN , MANOHAR SUDEEP P. , BS NARENDRA , MC DEEPAK , SHAH SANJIV , AHMED AFTAB , CHAVAN MAHESH , SATHYAKUMAR SAMANTHA , KOLUKULA VAMSI K. 
Published: June 2020

Aim: The purpose of this retrospective data analysis is to assess prescription practices including appropriate use and dose of statins in patients with T2DM.
Methods: This is an observational retrospective data analysis of T2DM patients with dyslipidemia and who were on statin treatment for at least 6 months. Data for this study was obtained from EMRs of diabetes and endocrinology specialty outpatient clinics (n=35), pan India between Jan 2018 and May 2019. Patients aged &lt;40 and &gt;75 years were excluded from the analysis. Patient’s record with demographics, medical history, prescriptions (antidiabetes and statin drugs) and lab investigations data were collected.
Results: Of the total 45,205 diabetes patients, 15023(33%) were on statins. The mean age was 53.2 years, 64% were males and 36% were females. Final analysis included 4099 patients between ages 40 and 75 years on statin drugs along with antidiabetes drugs. Mean HbA1c, fasting and post-prandial blood glucose was 8.5%, 173mg/dL and 257 mg/dL, respectively. The lipid profile TC, TG, HDL, and LDL was 174mg/dL, 188 mg/dL, 41 mg/dL, and 107 mg/dL, respectively. Low-intensity statins (2539[62%]) were the most common prescriptions followed by moderate (1402[34%]) and high (158[4%]) intensity statins. Rosuvastatin (2615[64%]) was most commonly prescribed followed by atorvastatin (1302[32%]), and non-statin fenofibrate (182[4%]). 4% of the patients on low-intensity statins at the first visit moved to moderate or high dose intensity statins. In contrast, 2% of patients on moderate dose moved to low dose intensity.
Conclusion: In endocrine clinic population with 45205 patients only 33% of patients were on statins. In the population between 40 and 75, a majority were on low-intensity statins with relatively very few progressing to moderate and high-intensity statin. The low uptake of statins and low dose use indicates the need to increase awareness of appropriate patient selection and correct dose of statin use in the clinic population including referral and tertiary care clinics.

Disclosure
S.G. Krishna: None. S. Das: None. N. Nk: None. S.P. Manohar: None. N. Bs: None. D. Mc: None. S. Shah: None. A. Ahmed: None. M. Chavan: None. S. Sathyakumar: None. V.K. Kolukula: None.
593-P: Cold Atmospheric Pressure Plasma for Accelerated Wound Healing in Diabetic Foot: The Prospective, Randomized, Placebo-Controlled KPW-Trial
Authors: STRATMANN BERND , COSTEA TANIA-CRISTINA , NOLTE CATHARINA , HILLER JONAS , SCHMIDT JÖRN , REINDEL JÖRG , MASUR KAI , MOTZ WOLFGANG H. , TIMM JÜRGEN , KERNER WOLFGANG , TSCHOEPE DIETHELM 
Published: June 2020

Diabetic foot is a common complication of diabetes mellitus and requires specialized treatment. Cold plasma has demonstrated beneficial effects on wound infection and healing in case reports. The “Kaltplasma Wund (KPW)-Trial” aimed to analyse whether the application of cold plasma accelerates wound healing in diabetic foot compared to standard care therapy. It was a prospective, randomized, placebo-controlled, patient-blinded, bi-center trial. People with diabetes mellitus and diabetic foot WA 1B or 2B were eligible. Each wound was randomized separately. Wounds were treated additionally with cold plasma generated from inert argon gas in an atmospheric pressure plasma jet or placebo. Primary endpoints were reduction in wound size, in clinical infection and microbial load compared to beginning. Important secondary endpoints were time to significant wound reduction (&gt;10%), and to reduction of infection. Ad hoc we analysed the time to 20% wound reduction. In addition, wound dressings from 15 patients per group were analysed for expression of VEGF via ELISA. In total 65 cases were included in the study and 62 were considerable for final evaluation. Plasma therapy yielded in a significant increase of wound healing, both in total area reduction (-26.31±11.72, p=0.0248 vs. placebo) as well as time to significant wound area reduction (10% from baseline, -1.60±0.58, p=0.0085 vs. placebo). The effect was even more significant, if the reduction level was set to 20% (p&lt;0.0001). Reduction of infection and microbial load was not significantly pronounced in plasma therapy. Regarding the expression of VEGF wounds in the plasma group presented throughout the study with at most visits significant higher levels of baseline corrected VEGF than wounds randomized to placebo therapy. Cold plasma therapy revealed beneficial effects in chronic wound treatment in terms of wound surface reduction and time to wound closure independent from background infection.

Disclosure
B. Stratmann: Speaker’s Bureau; Self; AstraZeneca, Neoplas Tools GmbH. T. Costea: Other Relationship; Self; Merck Sharp & Dohme Corp. C. Nolte: None. J. Hiller: None. J. Schmidt: None. J. Reindel: None. K. Masur: None. W.H. Motz: None. J. Timm: None. W. Kerner: None. D. Tschoepe: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH. Research Support; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Neoplas tools GmbH.
596-P: Emergence of Peripheral Arterial Disease in Persons with Diabetes, Dar Es Salaam, Tanzania: A Need for Clinical and Public Health Intervention
Authors: ABBAS ZULFIQARALI G. , ARCHIBALD LENNOX K. 
Published: June 2020

Background: Surveillance data from Tanzania during the 1980s and 1990s had shown that the vast majority (&gt;80%) of foot ulcers in persons with diabetes (DM) were neuropathic in origin and not associated with peripheral arterial disease (PAD). However, over the past decade, clinicians have observed an increase in the occurrence of PAD among persons who attend DM clinics at Muhimbili National Hospital (MNH) in Dar es Salaam. We therefore carried out this study to characterize the epidemiology of PAD in a large DM population and identify risk factors.
Methods: During Jan 2014 through Dec 2018, (study-period) and following informed consent, patients who attended MNH DM clinics with foot ulcers were evaluated. We recorded detailed epidemiologic and clinical data, and outcomes. Logistic regression was performed and adjusted odds ratio (AOR) and 95% confidence intervals (CI) calculated.
Results: Of 5,687 enrolled subjects, 3,621 (65%) were male; median BMI was 26.5; median age and diabetes duration were 57 and 8 years, respectively. All patients had some degree of PN; 28% had PAD; ischemic heart disease was uncommon (0.4%). Independent factors associated with PAD included hypertension (AOR: 1.3, CI: 1.1-1.5); tobacco (AOR: 1.4, CI: 1.2-1.7); major amputation (AOR: 3.2, CI: 1.9-5.9); or death (AOR: 2.2, (1.6-3.0). Indians and Arabs were significantly more likely than ethnic Africans to have PAD (p&lt;0.01).
Conclusion: We documented a significant increase in the prevalence of PAD in DM patients in Tanzania—a problem that heretofore was not appreciated. The increase appears to be linked to hypertension and tobacco and likely reflects increasing urbanization of African communities across the African continent, more sedentary lifestyles, lack of exercise, and diet. Underscoring these risks are changes in population demography. PAD is now playing a more substantial role in the pathogenesis of DM foot ulcer in Africa than was previously thought.

Disclosure
Z.G. Abbas: None. L.K. Archibald: None.