bluuebunny/crossref_metadata_2025_split huggingface dataset:
2255-PUB: 5-Year SLGT2-inh Treatment in Uncontrolled Elderly Diabetic Patients: Safety, Efficacy, and Durability
Authors: TRESCOLI CARLOS , PALASI PILAR , PLATERO PATRICIA , TRESCOLI-GARCIA ANA , ESPINOSA BORJA , VERCHER MANUEL 
Published: June 2020

SLGT-2 inh have cardiovascular and renal protection effect. Elderly diabetic patients are more prone to cardiovascular events but are frailer with more comorbidities and more prone to SLG2-inh adverse effects. These patients are not represented in RCT as they not fulfil inclusion criteria.
Aim: Evaluate long term safety and efficacy of adding SGLT2 inhibitors to Elderly DM2 patients with uncontrolled glycemia in real life experience.
Method: We studied 72 Elderly DM2 patients treated with SGLT2 inhibitors for more than 5 years in our Health Department. Efficacy, Safety and Durability data was collected from our computerized Primary and Hospital Medical Records at baseline and after 5 years.
Results: Patients’ basal data: mean age: 71,6 years, 42% women, mean period diabetes: 12,5 years. Prevalence Hypertension 79%, Dyslipidemia 81% Obesity 51% and previous cardiovascular events 42%. Antidiabetic Treatment: Metformin (78%), SU (31%) Gliptines (37%) Pioglitazone (12%), GLP-1A (13%) and Insulin (36%). Results Before and After 5-year SGLT2 inh Treatment: HbA1c. 8,5 vs. 7,2% (p &lt; 0,05); (38% maintained HbA1c &lt; 7.5%) Weight: 90.9 vs. 86.7 kg (p&lt; 0,05); Systolic BP: 133.2 vs. 128.6 mmHg (P&lt; 0,05) Albumin-Creatinine ratio (ACR): 58,7 vs. 36,2 mg/g (p&lt; 0,05) There were no statistical significant changes in e-GFR, microalbuminuria, lipid profile and hematocrit. No falls, volume depletion, severe hypoglycemia or ketoacidosis were recorded. 17% were treated for urinary-genital infections and half of them withdraw SLGT2i. 22% had a new non-fatal cardiovascular events and 6% heart failure hospitalization. There was a 17% mortality mainly due to neoplasic causes.
Discussion: 5-year SGLT2 inh. treatment in Elderly DM2 patients was safe and effective as in RCT. They had a significant maintained reduction in HbA1c, weight, systolic BP and ACR. Genito-urinary infection, although not frequent, was the main cause of withdraw.

Disclosure
C. Trescoli: None. P. Palasi: None. P. Platero: None. A. Trescoli-Garcia: None. B. Espinosa: None. M. Vercher: None.
2257-PUB: The Prevalence of Sarcopenia in Chinese Type 2 Diabetes Patients
Authors: HE QINGHUA , GUO LIXIN 
Published: June 2020

Objective: To examine the prevalence of sarcopenia in type 2 diabetes (T2DM) patients and to clarify the associated risk factors.
Methods: T2DM patients aged 50 years or older were included from nine research centers. Body composition was measured by bioimpedance analysis. Sarcopenia was defined by low muscle strength coexisted with low muscle mass. Low muscle strength was determined by grip strength below the lower quintile of the same sex subjects, the cutoff was below 29.5kg in men and 21.2kg in women. Low muscle mass was determined by the appendicular skeletal muscle index (ASMI) below the lower quintile of the homogeneity, same sex and healthy young group, the cutoff value was 7.18kg/m2 in men and 5.73kg/m2 in women.
Results: (1)A total of 1125 participants including 586 males(52%) and 539 females(48%) was analyzed. The average age was (62.6±8.3) years, BMI was (25.8±3.4) kg/m2, the diabetes duration was [10.36(5.32, 16.15)] years, FPG was (8.4±2.5)mmol/l, and HbA1c was (8.1±1.8)%. There were no statistical differences between male and female. (2)The detection rate of low muscle mass was 14.0%, male was significantly higher than female(18.3% vs. 9.3%); (3)The detection rate of low grip strength was 36%, male was significantly higher than female (50.3% vs. 20.4%);(4) The prevalence of sarcopenia in all participants was 8.5%, male was significantly higher than female (12.8% vs. 3.9%). (5)Logistic regression analysis showed men, low BMI, aging, high HbA1c were risk factors associated with sarcopenia. The risk of sarcopenia increased obviously in patients older than 75 years old(OR=4.992, 95%CI 2.448-10.179) or whose HbA1c was over 10%(OR=3.563, 95%CI 1.526-8.322).
Conclusion: T2DM was associated with increased risk of sarcopenia. Low BMI, aging, high HbA1c were risk factors associated with sarcopenia in T2DM.

Disclosure
Q. He: None. L. Guo: None.
2258-PUB: Impact of Cardiovascular (CV) Risk Factors during the Initial 6 Months of the First Large-Scale Longitudinal Nationwide Study on Management and Real-World Outcomes of Diabetes in India (LANDMARC)
Authors: GHOSH ROMIK , DAS ASHOK K. , JOSHI SHASHANK , MITHAL AMBRISH , KUMAR K.M. PRASANNA , KALRA SANJAY , UNNIKRISHNAN AMBIKA GOPALAKRISHNAN , THACKER HEMANT , SETHI BIPIN , MOHANASUNDARAM SENTHILNATHAN , MENON SHALINI K. , NAIR ARJUN , RAIS NADEEM , WANGNOO SUBHASH KUMAR , CHOWDHURY SUBHANKAR , ZARGAR ABDUL H. 
Published: June 2020

Impact of cardiovascular (CV) risk factors in participants with T2D during the first 6-months of observational period were examined in this 3 year prospective study (LANDMARC; CTRI/2017/05/008452). CV risk factors (rate of hypertension, dyslipidemia, albuminuria, and family history of premature coronary disease) at baseline (V1) and 6 months (Visit 2 [V2]) were assessed and compared between subgroups. Overall, &gt;50% of the participants who had A1C data available, had CV risks at both V1 (2385/4479; 53.2%) and V2 (2422/4479; 54.1%). More than half of the participants with obesity (BMI ≥25 kg/m2) had CV risks at V1 (2305/4150; 55.5%) and V2 (2340/4150; 56.4%). On comparing the insulin (N=1548) vs. insulin naïve (N=4688) subgroups, a higher proportion of participants on insulin had CV risks than those who were insulin naïve (V1: 60.1% vs. 50.1%; V2: 60.8% vs. 50.9%). At V2, hypertension and dyslipidemia were more predominant in those with BMI ≥23 kg/m2 than &lt;23 kg/m2, with A1C ≥ 7% than &lt;7%, and in men than women (Table). In India, CV risks may be increased in people with T2D who are overweight, have suboptimal glycemic control, or are men. The real-world trend of CV risks may offer insights and direction for risk factor modifications and treatment adjustments.

Disclosure
R. Ghosh: Employee; Self; Sanofi. A.K. Das: Advisory Panel; Self; Novo Nordisk A/S, Sanofi. S. Joshi: Advisory Panel; Self; Novo Nordisk A/S, Roche Pharma, Sanofi. A. Mithal: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Johnson & Johnson, Lilly Diabetes, Novo Nordisk A/S. K. Kumar: None. S. Kalra: Advisory Panel; Self; Eli Lilly and Company. Speaker’s Bureau; Self; Novo Nordisk A/S, Sanofi-Aventis. A. Unnikrishnan: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. Speaker’s Bureau; Self; Eli Lilly and Company, Ipca Laboratories, Merck Sharp & Dohme Corp., Novartis AG. H. Thacker: None. B. Sethi: None. S. Mohanasundaram: Employee; Self; Sanofi. S.K. Menon: None. A. Nair: Employee; Self; Sanofi. N. Rais: None. S. Wangnoo: None. S. Chowdhury: Advisory Panel; Self; Novo Nordisk A/S. A.H. Zargar: None.

Funding
Sanofi India Limited
2267-PUB: 1,5-Anhydroglucitol X Glycated Hemoglobin A1c/100: A Potential Biomarker for Islet ß-Cell Function in Type 2 Diabetes Mellitus
Authors: MA XIAOJING , SU HANG , SHEN YUN , HE XINGXING , YING LINGWEN , ZHU WEI , WANG YUFEI , BAO YUQIAN , ZHOU JIAN 
Published: June 2020

Aims: The goals of the current study were to explore the level of and changes in the AH index (AHI, defined as 1,5-anhydroglucitol × glycated hemoglobin A1c/100) associated with different glucose metabolism statuses, and to evaluate the islet function and insulin sensitivity of type 2 diabetes mellitus (T2DM) patients with different AHI levels.
Methods: A total of 3562 individuals were enrolled in the study. According to the 2010 American Diabetes Association (ADA) diagnostic criteria, 1697 subjects were diagnosed as T2DM. The disposition index (DI) was defined as the product of insulin sensitivity-related indexes and islet secretion function.
Results: The overall AHI level was 1.0 (0.7-1.3), while the AHI level of the T2DM group was 0.8 (0.5-1.2), which was significantly lower than that of the normal glucose tolerance group and the impaired glucose regulation group [both AHI 1.2 (0.9-1.5), and P &lt; 0.01]. The T2DM group was further divided into four subgroups according to the quartile of AHI level. The results demonstrated that the homeostasis model assessment of insulin resistance (HOMA-IR) decreased with the increase of AHI level (P for trend &lt; 0.01). However, other parameters [i.e., HOMA of β-cell function (HOMA-β), insulin generation index, insulin sensitivity index, and DI] increased while AHI level increased (all P for trend &lt; 0.01). Multivariate logistic regression illustrated that the odds ratios for a low DI for increasing levels of AHI were 1.00, 0.22 (0.16-0.29), 0.16 (0.11-0.22), and 0.09 (0.06-0.13), respectively, showing a decreasing trend (P for trend &lt; 0.01).
Conclusion: AHI could reflect the changes in the trend of glucose metabolism disorder and the function of islet β cells to some extent. The lower AHI was associated with worsening of the glucose metabolism disorder in recent years, and the islet β-cell function was correspondingly poor.

Disclosure
X. Ma: None. H. Su: None. Y. Shen: None. X. He: None. L. Ying: None. W. Zhu: None. Y. Wang: None. Y. Bao: None. J. Zhou: None.
2283-PUB: Metformin Treatment and Prostate Cancer Risk: Cox Regression Analysis with Time-Dependent Covariates of 150,000 Men with Incident Diabetes Mellitus
Authors: DANKNER RACHEL , MURAD HAVI , AGAY NIRIT , OLMER LIRAZ , FREEDMAN LAURENCE S. 
Published: June 2020

Background: There is conflicting evidence regarding the association between metformin use and prostate cancer risk in diabetic men.
Objective: We investigated the association of metformin treatment, as a time dependent exposure, with prostate cancer incidence, in a population-based cohort of T2D incident men, while accounting for major time related biases, time-dependent confounding by glucose levels, and for use of other diabetes medications.
Methods: During 2002-2012, we followed a cohort of 145,617 incident diabetic men aged 21-87 years insured in the largest health maintenance organization in Israel. We used a discrete form of the weighted cumulative exposure to metformin to evaluate its association with prostate cancer incidence. This was implemented in a time-dependent covariate Cox model, adjusting for age, ethnic background, and socioeconomic status. Other diabetes medications were not found to be strongly associated with prostate cancer. To account for time- dependent confounding by glucose levels, we used Propensity Score weighting for receiving metformin at each time-point.
Results: There were 1,592 prostate cancer events occurring over a total of 910,000 person-years. We found a positive association of prostate cancer with metformin exposure in the previous year (hazard ratio (HR) for 1 defined daily dose = 1.66; 95%CI 1.23, 2.24), but a negative association with metformin exposure in the previous 2-7 years (HR=0.57; 95%CI 0.32, 1.02).
Conclusion: Our results do not support a clear causal effect of metformin treatment on the incidence of prostate cancer. The positive association with metformin given in the previous year could be due to reverse causation of the cancer raising glucose levels and causing increased prescription of metformin. The negative association with metformin given 2-7 years previously is of borderline statistical significance and requires further research.

Disclosure
R. Dankner: None. H. Murad: None. N. Agay: None. L. Olmer: None. L.S. Freedman: None.
2290-PUB: Donor HLA-DR4 Positivity and Islet Transplantation Outcomes
Authors: CHAVEZ CARMEN , FUENMAYOR VIRGINIA , BAIDAL DAVID , ALVAREZ ANA M. , PADILLA NATHALIA , RICORDI CAMILLO , ALEJANDRO RODOLFO 
Published: June 2020

Islet transplantation (ITx) has demonstrated efficacy in improving glycemic control and abolishing severe hypoglycemia in patients affected with type 1 diabetes (T1D). Several factors account for graft loss and recurrence of autoimmunity has been suggested as a contributor to graft failure but remains controversial. We hypothesized that ITx recipients of HLA DR4+ donors could be at increased risk for recurrence of autoimmunity, as DR4+ is a well-known risk factor for T1D.
We evaluated 50 ITx recipients transplanted at the Diabetes Research Institute, University of Miami, who have been followed from 2000 to 2019. Out of the 50 subjects, 7 received islet after kidney transplantation and 43 islet transplantation alone. Subjects received an average of 2 islet infusions from 1 to 5 donors. The data was analyzed using Kaplan-Meier Survival Curves, along with log-rank and Wilcoxon tests statistics.
No significant association was found between Donor DR4+ and islet transplant outcomes (&gt;0.05). However, our study is limited by the small sample size, use of multiple donors as well as differences in immunosuppression regimens and use of GLP-1 analogs and DPP-4 inhibitors which may have affected outcomes.
Our data suggests that donor DR4+ is not associated with transplantation outcomes in our study cohort. Further studies are required to validate these findings.

Disclosure
C. Chavez: None. V. Fuenmayor: None. D. Baidal: None. A.M. Alvarez: None. N. Padilla: None. C. Ricordi: None. R. Alejandro: None.

Funding
Diabetes Research Institute Foundation; State of Florida; JDRF; The Leona M. and Harry B. Helmsley Charitable Trust; University of Miami Clinical and Translational Science Institute
2292-PUB: Luminescent Assays Quantitate the Biology of Peptide Hormones
Authors: VIDUGIRIENE JOLANTA , LEIPPE DONNA M. , VALLEY MICHAEL 
Published: June 2020

The interest in metabolic diseases like diabetes, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), continues to increase due to their growing impact on cell health. To facilitate studies and uncover novel drug targets, there is a significant need to develop disease relevant in vitro cellular models and robust, easy to use detection technologies. Here we demonstrate that luminescent assays coupling specific dehydrogenases to the production of NAD(P)H and generation of light can be used to study insulin biology and its effects on key metabolic pathways. Insulin stimulated glucose uptake was measured in 3T3-L1 MBX adipocytes with 10-fold assay window and the expected pharmacology using a glucose uptake assay. Using a glycerol detection assay, we showed 4-fold increase in lipolysis upon isoproterenol stimulation that was suppressed by insulin. Effects of insulin on gluconeogenesis was studied by measuring glucose production in liver microtissues, which are also a useful model for NAFLD studies and measurement of steatosis using a triglyceride assay. This assay does not require organic extraction and has the sensitivity required for quantitative triglyceride detection using low cell numbers (&lt;1000 cells/per well). Pancreatic islets are critical for regulated glucose homeostasis and measuring hormone production and secretion is the most direct method for assessing the quality and function of islets. To facilitate those studies, we developed bioluminescent, in solution, no wash insulin and glucagon immunoassays that are significantly more rapid and cost-effective than current commonly used approaches. The assays show high sensitivity and wide dynamic range (10 pM to 8 nM for insulin and 0.5 pM to 1 nM for glucagon) and are amenable to miniaturization making them well suited for rapid measurements of large numbers of samples that are generated, for example, in perifusion or high throughput screening experiments.

Disclosure
J. Vidugiriene: None. D.M. Leippe: None. M. Valley: None.
2298-PUB: Estradiol Protects Female ApoE KO Mice against Nonalcoholic Steatohepatitis
Authors: MOREIRA GABRIELA V. , MATOS SANDRO L. , CAMARGO FELIPE N. , ARAUJO LAYANNE , MURATA GILSON M. , CARVALHO CARLA R.O. , CAMPOREZ JOAO PAULO 
Published: June 2020

Lifestyle and increased consumption of high fat diets contribute greatly to the development of obesity, insulin resistance, type 2 diabetes (DM2), and cardiovascular diseases, which are less prevalent in young women than in men of the same age or postmenopausal women. One of the consequences of the Western lifestyle and high fat diet is Nonalcoholic Fatty Liver Disease (NAFLD) and its aggressive form, Nonalcoholic Steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular cancer (HCC) and is rapidly becoming the leading cause for end-stage liver disease or liver transplantation. Therefore, we evaluated if female mice were protected against Western Diet (WD)-induced NASH in apolipoprotein E (ApoE) KO animals. Female ApoE KO mice ovariectomized (OVX) or sham operated (SHAM) were fed a WD for 7 weeks. Whole-body fat was increased by ∼65% (P&lt;0.001) in OVX mice associated with an increase of glucose intolerance of by ∼75% (P&lt;0.01) and increased hepatic triglycerides (TAG) by 130% (P&lt;0.01) compared with SHAM mice. OVX mice also displayed increased plasma ALT (∼130, P&lt;0.001) and AST (∼65%, P&lt;0.05) compared with SHAM mice. These data were associated with increased hepatic inflammation in OVX mice, demonstrated by an increased of F4/80 of by ∼70% (P&lt;0.01). Hepatic fibrosis was also increased in OVX mice by ∼80% (P&lt;0.001) compared with SHAM mice. Estradiol treatment of OVX mice reversed some of these effects, reducing whole-body fat (P&lt;0.01), glucose intolerance (P&lt;0.01), and hepatic TAG content (P&lt;0.001). Taken together, these data support the hypothesis that estradiol protects OVX mice from WD-induced NASH and glucose intolerance, by protecting female mice against hepatic steatosis, inflammation and fibrosis.

Disclosure
G.V. Moreira: None. S.L. Matos: None. F.N. Camargo: None. L. Araujo: None. G.M. Murata: None. C.R.O. Carvalho: None. J. Camporez: None.

Funding
Fundação de Amparo a Pesquisa do Estado de São Paulo (2018/04956-5)
2309-PUB: Postprandial Thermogenesis Is Reduced in Obesity
Authors: VOSSELER ANDREAS , FRITSCHE LOUISE , HUMMEL JULIA , DANNECKER CORINNA , STEFAN NORBERT , BIRKENFELD ANDREAS L. , HAERING HANS-ULRICH , FRITSCHE ANDREAS , WAGNER ROBERT , HENI MARTIN 
Published: June 2020

Background and Aims: Postprandial thermogenesis is thought to be important for the control of metabolism. This process could be reflected by minute changes in body temperature after glucose load. In this study, we measured body temperature before and its change during a glucose challenge and investigated the relationships with anthropometric and glycemic traits.
Methods: We prospectively studied 383 volunteers (251 females, 132 males) with a mean age of 46.6 (SD ± 16) years and a BMI of 27.9 kg/m2 (SD ± 5.9). All participants underwent a 75 g oral glucose tolerance test (OGTT) and repeated bilateral measurements of intra-auricular temperature at time points 0, 30 and 120 minutes during the OGTT using a tympanic thermometer (Covidien Genius 2).
Results: Baseline temperature was 0.17°C lower in males compared to females (p = 0.001) and inversely associated with age (p &lt; 0.0001). During the OGTT, there was a significant increase in body temperature (0.18 ± 0.34°C). This response was present in females and males. BMI was negatively associated with the increase of temperature during the OGTT (p = 0.0147). Participants with higher BMI displayed higher fasting temperatures, but less increase of temperature during the OGTT. Body temperature was not associated with glycemia, insulin sensitivity or insulin secretion, neither in females nor males.
Conclusions: There is a robust increase in body temperature during a glucose load that can be captured by intra-auricular temperature measurements. We did not detect any associations of the body temperature with glucose metabolism, arguing against a major contribution of the variability of body temperature in the pathogenesis of diabetes. However, the rise in temperature in response to oral glucose is reduced in obesity and might therefore be involved in body weight regulation.

Disclosure
A. Vosseler: None. L. Fritsche: None. J. Hummel: None. C. Dannecker: None. N. Stefan: None. A.L. Birkenfeld: None. H. Haering: None. A. Fritsche: None. R. Wagner: Advisory Panel; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Novo Nordisk A/S. Other Relationship; Self; Eli Lilly and Company. M. Heni: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi. Speaker’s Bureau; Self; Novo Nordisk A/S.

Funding
German Federal Ministry of Education and Research (01GI0925)
231-LB: Importance of Intestinal Environment and Cellular Plasticity of Beta Cells in the Development of Post-Pancreatectomy Diabetes
Authors: BOUCHI RYOTARO , FUKUDA TATSUYA , TAKEUCHI TAKATO , AMO-SHIINOKI KIKUKO , TANABE KATSUYA , TANIZAWA YUKIO , YAMADA TETSUYA , OGAWA YOSHIHIRO 
Published: June 2020

To elucidate the pathogenesis of post-pancreatectomy diabetes (PPDM), we carried out a prospective observational study in patients without diabetes undergoing partial pancreatectomy, investigating the effects of gut microbiota, incretins, and short-chain fatty acids (SCFAs) on postsurgical glucose metabolism. In addition, we analyzed histologically the resected pancreas to investigate whether increased cellular-plasticity and expansion of the islets could predict the development of PPDM. Forty-eight patients without diabetes, who underwent either pancreatoduodenectomy (PD) (n=20) or distal pancreatectomy (DP) (n=28), were included. To assess the post-surgical glucose metabolism, 75-g oral glucose tolerance test (OGTT) was performed every 6 months. Microbiome composition and SCFAs in feces were examined before and 6 months after the surgery. We also underwent immunostainings of insulin, glucagon, and ALDH1A3 (a progenitor cell marker) in the resected pancreatic samples obtained from patients following DP. During the follow-up (median 2.50 years), 2 out of 18 patients with PD and 16 out of 28 patients with DP developed PPDM. Microbiota shifted to a higher relative abundance of Proteobacteria after PD. After PD, fecal butyrate and plasma GLP-1 concentrations were significantly increased, which were not increased after DP. In all patients, postsurgical change in butyrate was strongly correlated with increased GLP-1 secretion. In DP patients, expansion of both α- and β-cell areas in the resected pancreas were significantly associated with the development of PPDM, and HR (95% CI) of ALDH1A3 positive cells (%) for PPDM was 1.127 (1.000-1.270). This study demonstrates that incidence of PPDM is much lower after PD than that after DP, which may be explained by marked changes in intestinal environment after PD. On the other hand, high cellular-plasticity and expansion of the islets in the resected pancreas can predict the development of PPDM after DP.

Disclosure
R. Bouchi: None. T. Fukuda: None. T. Takeuchi: None. K. Amo-Shiinoki: None. K. Tanabe: None. Y. Tanizawa: None. T. Yamada: Research Support; Self; Astellas Pharma Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD, Novartis Pharma K.K., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Y. Ogawa: Research Support; Self; Mitsubishi Tanabe Pharma Corporation. Speaker’s Bureau; Self; Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation.

Funding
Ministry of Education, Culture, Sports, Science and Technology of Japan (15K19507); Japan Foundation for Applied Enzymology; Takeda Science Foundation; AstraZeneca