bluuebunny/crossref_metadata_2025_split huggingface dataset:
2116-P: MAFA S64F Missense Mutation Causes Islet Beta-Cell Aging and Senescence
Authors: CHA JEEYEON , WALKER EMILY M. , TONG XIN , GUO MIN , LIU JIN HUA , YU SOPHIA , IACOVAZZO DONATO , MAUVAIS-JARVIS FRANCK , FLANAGAN SARAH E. , KORBONITS MARTA , STAFFORD JOHN M. , STEIN ROLAND 
Published: June 2020

A missense mutation of the pancreatic islet-enriched transcription factor MAFA (S64F) was identified in patients characterized by familial diabetes or insulinomatosis, with males more prone to diabetes. This variant converts the normally unstable MAFA protein to be unusually stable. A heterozygous germline mouse model expressing this variant (S64F MafA Het) mimics the sex-dependent phenotype in humans: Het males have impaired glucose tolerance while Het females have hypoglycemia. Het males also showed increased MafA protein stability preceding glucose intolerance (Figure 1) and upregulation of genes involved in aging/senescence (Figure 2). These results implicate accelerated aging/senescence in islet β-cell dysfunction in males with the S64F MAFA mutation. Future studies will evaluate the broader significance of these processes in diabetes.

Disclosure
J. Cha: None. E.M. Walker: None. X. Tong: None. M. Guo: None. J. Liu: None. S. Yu: None. D. Iacovazzo: None. F. Mauvais-Jarvis: None. S.E. Flanagan: None. M. Korbonits: None. J.M. Stafford: None. R. Stein: None.

Funding
National Institutes of Health (T32DK007061, F32DK109577, R01DK090570); JDRF (3-PDF-2019-738-A-NDK109577)
2147-PUB: Change in Matrix Metalloproteinase Activity Is Associated with Zinc Level in the Development of Renal Changes in a Diabetic Preclinical Model
Authors: TAO ANH , MCQUILTY ROBERT , SUTANTO SURYA S. , BAN LINDA A. , TWIGG STEPHEN M. , MCLENNAN SUSAN 
Published: June 2020

Zinc is required for activation of Matrix Metalloproteinases (MMPs). Circulating zinc levels are decreased in diabetes1 and decreased activity of some MMPs is associated with the development of diabetic nephropathy (DN). The association between MMP activity and zinc in the development of DN has not been investigated and was examined in a preclinical model in this study. In this study, diabetic (DM: STZ: 3x 65mg/kg) male BALB/c mice were euthanized after 5, 10 and 30wks of diabetes. Age-matched mice acted as controls. At termination, kidneys, plasma and urine were collected for histopathology, measurement of biochemical parameters, total MMP activity using a broad spectrum MMP fluorogenic substrate and zinc level by ICPMS. In DM mice, blood glucose levels were increased at 5, 10 and 30wks (P&lt;0.01) as were kidney/body weight (P&lt;0.05) and urinary albumin/creatinine ratios (P&lt;0.05). After 5wks of diabetes histopathological changes were evident and albumin/creatinine ratio increased (P&lt;0.05). Urinary MMP activity was decreased (P&lt;0.001) at 5wks and preceded a decrease in kidney and plasma MMP activity at 10 and 30wks (both P&lt;0.05). DM decreased plasma but not urinary zinc levels at 10 and 30wks (both P&lt;0.05). In DM mice, the kidney MMP activity correlated positively with plasma MMP activity (r=0.3774, P&lt;0.03) and diabetes duration. Plasma zinc correlated with plasma MMP activity (r=-0.77, P=0.04) but only at 30wks. These results suggest an association between plasma MMP activity and zinc but only after a long duration of diabetes. The early decrease in urinary total MMP activity suggests it may have utility as a marker of early kidney disease. Whether this is so for human kidney disease is currently not known and requires further study. 1 Chabosseau and Rutter, Archives of Biochemistry and Biophysics (2016).

Disclosure
A. Tao: None. R. McQuilty: None. S.S. Sutanto: None. L.A. Ban: None. S.M. Twigg: Advisory Panel; Self; Abbott, AstraZeneca, Sanofi. Speaker’s Bureau; Self; Abbott, AstraZeneca, Novo Nordisk Inc., Roche Diabetes Care, Sanofi. S. McLennan: None.
2164-PUB: Community Expansion of Peer Support for Diabetes Management in Shanghai
Authors: LIU YUEXING , TANG PATRICK Y. , QIAN YIQING , COUFAL MUCHIEH M. , FISHER EDWIN B. , JIA WEIPING 
Published: June 2020

Peer support can be effective but dissemination is a challenge. In the context of the Shanghai Integration Model linking specialty/hospital with primary/community care, trained volunteer peer leaders (PLs) based in 9 Community Health Centers (CHCs) implemented peer support. Results included improved glycemic control and reduced BMI, diabetes distress and depression, each more pronounced among those with poorer baseline status. Benefit varied however according to CHCs’ ability to organize peer support. Dissemination needs to recruit additional agencies to support CHCs. Accordingly, a current phase includes additional government and citizen-led organizations in an additional 12 of Shanghai’s 240 communities. District-level and sub-district or community health staff work with each community’s CHC as well as citizen led Community Self Management Groups (&gt; 5,000 in Shanghai) and government affiliated, local Residential Committees. Reports through regular monitoring and meetings with CHC and community staff during the first 8 months (May-December, 2019) indicate CHC and community staff work together in a complementary manner. CHC staff take responsibility for diabetes education (e.g., teaching 6 basic diabetes education modules) and designing activities. Community staff organize or facilitate activities, e.g., the 6 modules, cooking events, discussion groups, or recreational activities that provide a sense of solidarity among those with diabetes. District-level staff coordinate key responsibilities, integrate resources, organize large-scale activities, and train community level groups. Other community organizations include, e.g., an NGO in one district with extensive experience in community services. Across the 12 communities, an average of 6.33 PLs have been trained not including community groups that lead activities. Communities have held an average of 14.08 classes drawing from the 6 diabetes education modules.

Disclosure
Y. Liu: None. P.Y. Tang: Research Support; Self; Merck Foundation. Y. Qian: None. M.M. Coufal: None. E.B. Fisher: Research Support; Self; Merck Foundation, Sanofi China. W. Jia: None.

Funding
Shanghai Municipal Grants (GWIV-3.1 to W.J.); Shanghai 6th People’s Hospital (YNLC201812 to Y.L.); Shanghai Municipal Health Commission (20194Y0141 to Y.L.); Merck Foundation; Sanofi China; Michigan Center for Diabetes Translational Research; National Institute of Diabetes and Digestive and Kidney Diseases (P30DK092926)
2167-PUB: Effect of Low-Available Carbohydrate Diet Containing Okara and Konjac on Blood Glucose Levels in Spontaneous Diabetic Torii Fatty Rats
Authors: SURUGA KOHEI , TOMITA TSUYOSHI , KOBAYASHI MASAKAZU , MITSUI TADAHIKO , KADOKURA KAZUNARI 
Published: June 2020

Background: The ADA and Diabetes UK reported the efficacy of low-carbohydrate diets (LCD) in medical nutrition therapy for blood glucose and lipid management. However, following an LCD may be difficult for many people with diabetes, especially those who consume noodles regularly. To remedy this, we developed a low-available carbohydrate noodle (LACN) using a by-product of Soybean (Glycine max) processing (commonly called “okara”) and Amorphophallus konjac (commonly called Konjac). In this initial study, the effects of the LACN (Figure A) on blood glucose levels (GL) were investigated in Spontaneously Diabetic Torii fatty rats (SDT-fr).
Methods: Male, 5-week-old SDT-fr were allocated into two groups based on diet; Group I was fed standard chow (SC) as a control group (n = 6), while Group II was fed SC with 50% LACN (n = 6). The animals were allowed free access to food for 28 days.
Results: The plasma GL in the LACN group (Group II) were significantly lower than those in the control group (Figure C), in which body weight (BW) gain was observed (Figure B). Our results, in concurrence with other papers, provide evidence that BW increase in Group II was associated with increase in lean body mass, and that the change in muscle mass of SDT-fr was mainly caused by the LACN intake.
Conclusions: LACN might be useful for patients with diabetes or celiac disease who wish to maintain a noodle-based diet.

Disclosure
K. Suruga: None. T. Tomita: None. M. Kobayashi: None. T. Mitsui: None. K. Kadokura: None.
2178-PUB: Validating a New Classification Method for SMBG Logging Habits in Real-World Data
Authors: BIVEN RICHARD P. , WREDE JAN , BANKOSEGGER RAFAEL P. , KOBER JOHANNA , PETERSEN BETTINA , RINGEMANN CHRISTIAN , HUSCHTO TONY 
Published: June 2020

Objective: Assessing diabetes therapy performance in Real World Data (RWD) is difficult as the data quantity of SMBG measurements shows strong variability. In a previous study, we proposed a new metric, Gkn/N ⇔ n out of N days :|SM BG| ≥ k, which ensures data quality so patients with skewed SMBG values or highly motivated users are not overrepresented. The classification separates users by logging habits, e.g., G1 ≅ 1 log a day . The aim of this study is to validate our metric with CGM data and determine if more logs a day increase metrics accuracy.
Method: We analyzed 299 users of a data set with CGM and SMBG logs . The inclusion criteria was 70% CGM logs for 1 month with associated SMBG logs. Each user was classified into a G-group. The distribution was biased to the G4-G5 groups. Therefore, users were randomly selected and had logs randomly removed to create lower G-group users, providing an equal distribution. The percent errors of the users’ mean BG, standard deviation (SD), and tests-in-range (TIR) between the SMBG and CGM logs were analyzed. With random sampling the analysis was repeated and mean results used.
Results: Results had G1 users with the largest error in all metrics tested (Mean Error:BG =8%, SD =15.4%, TIR =17.5%). The error did not substantially decrease as the logs increased (correlating to a higher G-groups). Because differences were not apparent in the mean BG, SD, or TIR;t-tests were performed for each group to determine statistical differences from the other groups based on BG or SD error. The only G-group to be statistically different (p&lt;0.05) was G1 from all higher groups.
Conclusion: Results allow separating users into two groups. The error between G2 and all higher logging groups was not significant, implying metric accuracy does not increase with more logs. The validation allows the use of metrics based on mean BG or SD to a larger portion of users while limiting the bias on users’ logging habits. Further analyses are necessary to compare values from each G-class with clinically reported metrics.

Disclosure
R.P. Biven: None. J. Wrede: None. R.P. Bankosegger: Employee; Self; mySugr. J. Kober: Employee; Self; mySugr. B. Petersen: Employee; Self; Roche Diabetes Care. C. Ringemann: Employee; Self; Roche Diabetes Care. T. Huschto: Employee; Self; Roche Diabetes Care.
2186-PUB: Comparison of Insulin Degludec (IDeg)/Insulin Aspart (IAsp) Coformulation Therapy Twice Daily with Free Combination of GLP-1 Receptor Agonist Liraglutide plus Insulin Degludec in Tochigi: IDEAL Trial
Authors: ASO YOSHIMASA , JOJIMA TERUO , SAKURAI SHINTARO , IIJIMA TOSHIE , TOMARU TAKUYA , USUI ISAO 
Published: June 2020

Objective: To compare the efficacy and safety of insulin degludec/insulin aspart co-formulation (IDegAsp) twice daily with free combination of basal insulin degludec and GLP-1 receptor agonist liraglutide once daily in type 2 diabetic patients inadequately controlled on insulin therapy with oral antidiabetic drugs.
Subjects and Methods: Eligible patients were randomly allocated at a 1:1 ratio to receive once-daily IDeg plus liraglutide given separately (n=24) or twice daily IDegAsp (n=28). IDeg+Lira were separately administered before breakfast. The primary endpoints were the change in HbA1c from baseline to 52 weeks of treatment, as well as the percentage of participants achieving HbA1c less than 7.0% at 52 weeks.
Results: After 52 weeks, HbA1c was decreased by 0.3% in the IDegAsp group and by 0.7% in the IDeg+Lira group. Reduction in HbA1c tended to be greater in the IDeg+Lira group than in the IDegAsp group (P=0.070). Nineteen percent of patients on IDegAsp versus 40% on IDeg+Lira achieved HbA1c&lt;7.0%. Pre-breakfast and -dinner FBP at 52 weeks were significantly lower in the IDeg+Lira group than in the IDegAsp group. A reduction in body mass index (BMI) was greater in the IDeg+Lira group than in the IDegAsp group throughout the study period. In the IDeg+Lira group, mean insulin degludec and liraglutide at 52 weeks were 15.1 U and 0.84 mg, respectively.
Conclusions: In patients with inadequately controlled type 2 diabetes on insulin and oral antidiabetic drugs, treatment with insulin degludec and liraglutide separately injections compared with IDegAsp co-formation twice daily showed no significant difference in glycemic control, but with somewhat greater reduction in HbA1c at 52 weeks, and a statistically superior weight loss.

Disclosure
Y. Aso: None. T. Jojima: None. S. Sakurai: None. T. Iijima: None. T. Tomaru: Research Support; Self; Merck & Co., Inc., Teijin Pharma Limited. I. Usui: None.
219-LB: The Hepatocyte Clock and Feeding Interdependently Control Chrono-Homeostasis of Multiple Liver Cell Types
Authors: GUAN DONGYIN , LAZAR MITCHELL A. 
Published: June 2020

Most cells in the body contain a cell autonomous molecular clock, but the requirement of peripheral clocks for circadian rhythmicity, and their effects on physiology, are not well understood. Here we show that deletion of core clock components REV-ERB alpha and β in adult mouse hepatocytes disrupted circadian rhythmicity of many liver genes, as expected, but also led to maintained and even gained rhythmicity of other genes without altering feeding behavior. The loss of REV-ERBs from hepatocytes led to an exaggerated circadian rhythm of de novo lipogenesis. Liver function is also influenced by non-hepatocytic cells, and remarkably the loss of REV-ERBs in hepatocytes remodeled the circadian transcriptomes and metabolomes of multiple cell types within the liver, indicating that hepatocytes communicated time signals to non-hepatocytic cells. Finally, alteration of food availability demonstrated strong interdependence of the cell-autonomous hepatocyte clock mechanism and non-cell-autonomous environmental change. Together these studies reveal previously unsuspected roles of the hepatocyte clock in the physiological coordination of nutritional signals and cell-cell communication controlling rhythmic metabolism.

Disclosure
D. Guan: None. M.A. Lazar: Board Member; Self; Pfizer Inc. Consultant; Self; Calico, Madrigal Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (F32DK116519)
2198-PUB: The Impact of Basal Insulin Initiation to Background Sulfonylurea Treatment on Hypoglycemia Occurrence: Evaluation of the Balkan Cohort of Dune Study
Authors: JANEZ ANDREJ , LUNDER MOJCA , JANIC MIODRAG , GRULOVIC NATASA , ZDRAVKOVIC DRAGAN , JOTIC ALEKSANDRA Z. , LALIC KATARINA , LALIC NEBOJSA 
Published: June 2020

Background: Optimal glycemic control and proper basal insulin initiation timing when non-insulin treatment becomes insufficient is critical in type 2 diabetes mellitus (T2DM). The DUNE study investigated the effectiveness and safety of newly initiated basal insulin in T2DM patients compared to those who already received insulin. The impact of background therapy with sulfonylureas (SU) on insulin dose and hypoglycemia occurrence was also explored.
Methods: The DUNE study was a 12-week, prospective, single-arm, observational study of adults with T2DM. The present sub-analysis included the patients from the Balkan region (Slovenia and Serbia). The first group (n=83) included patients with newly initiated basal insulin and the second group (n=94) included patients who were already treated with basal insulin for up to 12 months. Patients also received other non-insulin antihyperglycemic drugs.
Results: The proportion of patients receiving SUs was higher in the group with newly initiated basal insulin (72.3% vs. 55.3%; p&lt;0.001). Basal insulin treatment included NPH or 1st generation basal insulin analogues (BIA) (98.8% vs. 1.2% for newly initiated basal insulin and 83% vs. 17% for already initiated basal insulin), due to local reimbursement policy. Daily insulin doses were lower in newly initiated basal insulin group (11.7±5.58U vs. 18.6±9.18U; p&lt;0.001), the difference remained significant also after 12 weeks of observation (17.5±11.8U vs. 22.6±10.69U; p&lt;0.01). A trend towards higher hypoglycemia occurrence in the newly initiated basal insulin group was observed, despite the lower insulin dose, but with higher percentage of treatment with SUs as a background treatment.
Conclusions: Continuation of SUs in T2DM patients, both newly initiated and already initiated with basal insulin therapy (NPH or first-generation insulin analog), should be considered with caution due to the potentially enhanced effect on the risk of hypoglycemia.

Disclosure
A. Janez: None. M. Lunder: None. M. Janic: None. N. Grulovic: None. D. Zdravkovic: None. A.Z. Jotic: None. K. Lalic: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim, Merck, Novo Nordisk, Sanofi. N. Lalic: None.
2200-PUB: Application of Data Envelopment Analysis in Health Economic Evaluation of Insulin Pump Treatment during Perioperative Period
Authors: SONG WEI , WEN JIANXUAN , ZHAO LING , FAN GUANJIE , LUO MENG , LIANG JIAJIAN , ZHANG JINMING , YANG CAIFENG , WANG QIUPING , GAO ZHIJUAN , MA LIU 
Published: June 2020

Objective: To evaluate the effect of insulin pump on perioperative patients with type 2 diabetes and the role of health economics by applying data envelopment analysis (DEA).
Method: This retrospective study involved 639 patients with type 2 diabetes undergoing surgery in Guangdong Provincial Hospital of Traditional Chinese Medicine from January 2009 to November 2017. All patients were treated with insulin during the perioperative period. They were divided into a insulin pump group for diabetes (perioperative blood glucose control with insulin pump, 369 cases) and a Non-insulin pump group (perioperative blood glucose control with subcutaneous insulin injection, 270 cases). Data Envelope analysis was applied to compare the input indicators of the two groups to total cost and total length of hospital stay. The output indicators of the two groups were blood glucose control time before surgery, mean fasting blood glucose, blood glucose in the first sky after surgery, days of antibiotic use, and hospital stay after surgery.
Result: In the aspect of comparison of scale efficiency, the efficiency values of the pump set in the C2R model and BC2 model are better than those of the unused pump set. In Another aspect of the relaxation variables, the higher the surgical level, the closer the pump group is to the ideal state compared with the non-pump group, in terms of improving average fasting blood glucose, antibiotic use days, preoperative blood glucose control time, first day postoperative fasting blood glucose, and postoperative hospitalization days.
Conclusion: Insulin pump can quickly and stably control blood glucose levels and shorten the length of hospital stay during the perioperative period of type 2 diabetes patients. It is suggested that the application of insulin pump in perioperative period may have better benefits and is worthy of clinical promotion.

Disclosure
W. Song: None. J. Wen: None. L. Zhao: None. G. Fan: None. M. Luo: None. J. Liang: None. J. Zhang: None. C. Yang: None. Q. Wang: None. Z. Gao: None. L. Ma: None.
2206-PUB: Efficacy of Fixed-Dose Combination of Empagliflozin and Linagliptin in Addition to the Ongoing Treatment in Type 2 Diabetes: Real-World Observational Study
Authors: GUPTA ABHINAV , KHALSE MANEESHA , BHARGAVA AMIT 
Published: June 2020

Empagliflozin (SGLT2 inhibitor) and linagliptin (DPP-4 inhibitor) is a Fixed Dose Combination (FDC) with limited real-world evidence. We assessed the efficacy of this novel FDC in the real world Indian setting by analyzing the mean change in 12-week values of the glycemic (HbA1c and FPG) and extra-glycemic parameters (SBP, DBP, eGFR and body weight) as compared to the baseline values at the point of initiation of FDC in 498 patients. (Table). The patients enrolled were independently naïve to both DPP IV inhibitor and SGLT2 inhibitor therapy. Unpaired t test and ANOVA were utilised for statistical analysis. The mean age was 61 years (SD ± 7.6). The ongoing treatment in 20% (n=100), 43% (n=214), 38% (n=189), 26% (n=127) were metformin (M), combination of M and sulfonylureas (SU), combination of M, SU and voglibose, and insulin, respectively. The mean change in HbA1c, FPG, SBP, DBP, eGFR and body weight was -1.1%, -45 mg/dl, -12 mmHg, -5 mmHg, 5 mL/min/1.73m2, -5 kg (p&lt;0.0001), respectively. 23.9 % patients (n=119) achieved HbA1c &lt; 7%. 36.8% (n=183) patients achieved FPG reductions ≥100mg/dl. Six patients reported clinically evident hypoglycaemia which was managed symptomatically. There was a meaningful change and a substantial quantum of improvement in glycemic, metabolic and renal parameters. The results need to be validated through a long-term larger study.

Disclosure
A. Gupta: None. M. Khalse: None. A. Bhargava: None.
221-LB: Association between Muscle Strength and Advanced Fibrosis in Nonalcoholic Fatty Liver Disease: Korean Nationwide Survey
Authors: KANG SUNYOUNG , MOON MIN KYONG , KOO BO KYUNG 
Published: June 2020

Background: We investigated the association between muscle strength and the prevalence of advanced fibrosis among individuals with nonalcoholic fatty liver disease (NAFLD) using a nationwide cross-sectional survey.
Methods: Individuals, 20 to 79 years of age, from the Korean National Health and Nutrition Examination Surveys (KNHANES) from 2014 to 2016 were selected (n = 14,861), with sample weights applied. Muscle strength was quantified as the hand grip strength (HGS) divided by the body mass index (BMI); low muscle strength (LMS) was defined as the lowest quartile (Q1) of the HGS/BMI scores for our sample population. NAFLD was defined by hepatic steatosis index (HSI) &gt;36 (NAFLDHSI). The highest quartile of NAFLD fibrosis score (NFS) (FibrosisNFS) was used to define advanced fibrosis.
Results: In a crude analysis, LMS was associated with the increased prevalence of NAFLDHSI (OR 3.62, 95% CI 3.25-4.03), which remained significant even after adjustment for age, sex, obesity, and insulin resistance (OR 1.69, 95% CI 1.30-2.18). Even in those without obesity, individuals with LMS had a higher prevalence of NAFLDHSI compared to those without LMS (OR 1.93, 95% CI, 1.42-2.63). Among individuals with NAFLDHSI (n = 3,320), LMS was also associated with the presence of advanced fibrosis (FibrosisNFS) even after adjustment for age, sex, obesity, and insulin resistance (OR 1.68, 95% CI 1.09-2.58).
Conclusion: Muscle strength is independently associated with NAFLD and advanced fibrosis.

Disclosure
S. Kang: None. M. Moon: None. B. Koo: None.