bluuebunny/crossref_metadata_2025_split huggingface dataset:
140-OR: Inhibition of Serotonin 2c Receptor Internalization Potentiates Lorcaserin Effect on Body Weight Loss
Authors: HE YANG , LIU HAILAN , XU YONG 
Published: June 2020

As a body weight management medicine, lorcaserin, a selective agonist of serotonin 2C receptor (5-HT2CR) which is a G protein-coupled receptor, fails to maintain its effect on body weight loss after a long term administration. Thus, it is necessary to find a way to strengthen its effect on obesity treatment. It has been reported that the effect of lorcaserin on body weight loss is by activating Pro-opiomelanocortin (POMC) neurons in the arcuate nucleus (ARH). However, how POMCARH neuron activity changes after long term lorcaserin treatment remains unknown. In the present study, we found that POMCARH neurons cannot maintain its sensitivity to further lorcaserin stimulation after a long term lorcaserin treatment. By using in vitro electrophysiology recording and c-Fos immunostaining in the brain slice from control mice, we found that acute lorcaserin application significantly increased POMCARH neuron activity. However, this activation effect significantly decreased in mice with lorcaserin administration for consecutive 20 days. By in vivo fiber photometry calcium recording, we found that lorcaserin significantly increased POMCARH neuron activity in vivo at first day, but this activation effect decreased after 10 days lorcaserin treatment and almost disappeared after 20 days lorcaserin treatment. We further showed that this desensitization of POMCARH neurons to lorcaserin stimulation is mainly due to a beta-arrestin-mediated excessive internalization of 5-HT2C receptor in POMCARH neurons. Barbadin, a novel selective β-arrestin/adaptor protein 2 interaction inhibitor, maintains POMCARH neuron sensitivity to further lorcaserin stimulation by blocking prolonged lorcaserin-induced aberrant 5-HT2C receptor internalization. Co-treatment with barbadin also prolongs lorcaserin’s effect on body weight loss and food intake reduction in mice. Overall, our results may provide a potential strategy for facilitating obesity treatment by lorcaserin.

Disclosure
Y. He: None. H. Liu: None. Y. Xu: None.
1400-P: Rural/Urban Residence and Race/Ethnicity Differences in All-Cause Mortality Trends among Medicare Beneficiaries with Diabetes, 2001-2016
Authors: BULLARD KAI M. , ANDES LINDA J. , SAYDAH SHARON , ROLKA DEBORAH B. , MERCADO CARLA , IMPERATORE GIUSEPPINA , BENOIT STEPHEN R. 
Published: June 2020

To examine rural/urban and racial/ethnic differences in all-cause mortality from 2001-2016 among older U.S. adults with diabetes, we used Medicare claims data linked to the National Death Index. We identified beneficiaries aged ≥67y who were enrolled in fee-for-service (FFS) plans with diabetes. Rural/urban residence was based on the 2016 Medicare core-based statistical area classification. Race/ethnicity was classified as: non-Hispanic white (NHW), non-Hispanic black (NHB), Asian/Pacific Islander (API), and Hispanic (HISP). Rates were age-/sex-standardized to the 2001 FFS population. From 2001 to 2016, there were absolute declines in mortality in all rural/urban and racial/ethnic subgroups (all p&lt;0.001; Figure). By 2016, mortality rates were higher among rural residents (vs. urban) for all racial/ethnic groups (rate ratios: NHW [1.07 (1.06-1.08)]; NHB [1.05 (1.03-1.08)]; API [1.20 (1.09-1.32)], HISP [1.09 (1.05-1.13)]). Reductions in mortality were relatively consistent among rural HISP and API residents (p-trend&lt;0.05); while rates plateaued after 2007 for NHW and after 2011 for NHB rural residents. Among urban residents, reductions in mortality slowed (NHB [2010]; API [2007]) or stalled (NHW [2009]; HISP [2010]) at varying times. Future research may be helpful in addressing mortality disparities in this diverse, aging population.

Disclosure
K.M. Bullard: None. L.J. Andes: None. S. Saydah: None. D.B. Rolka: None. C. Mercado: None. G. Imperatore: None. S.R. Benoit: None.
1403-P: Glycemic Control Levels Are Not Major Determinants of Accumulation of AGE
Authors: MIZUSHIRI SATORU , DAIMON MAKOTO , MURAKAMI HIROSHI , KAMBA AYA , MURABAYASHI MASAYA , NISHIYA YUKI 
Published: June 2020

Objective: Chronic hyperglycemia increases glycation as well as oxidization, and, thus, facilitates production of advanced glycation end products (AGEs), whose accumulation is involved in the pathophysiology of diabetic complications. Although association between AGE and insulin resistance has been reported thoroughly, association between AGE and insulin secretion has not been well examined, especially in relation with age.
Research Design: Among participants of the population-based Iwaki study of Japanese held in 2014, those who attended the Iwaki study consecutively in 2014 and 2015 were enrolled in this study (n=518; model A), and we excluded fasting blood glucose levels &lt;63 and &gt;140 to calculate HOMA-β and IR (n=489; model B). We used skin autofluorescence as AGE, and also measured blood levels of Pentosidine and urine albumin-to-creatinine ratio.
Results: 1. AGE levels significantly increased from 1.93±0.52 to 1.97±0.44 (p=0.014) in the 1 year period.
2. Regression analysis showed correlations between ∆AGE (change in AGE in the 1 year period) and age, BUN, FPG and log10uACR in model A, and, age, log10uACR, and log10HOMA-ß in model B. However, these correlations became none-significant after adjustment for multiple factors mentioned above as well as factors representing glucose control levels such as HbA1c, except for age in models A and B, respectively.
3. Subjects were stratified into tertiles (mildly, moderately, rapidly progress) based on their ∆AGE, Logistic analysis revealed the aging is a significant risk for the accumulation of AGE (rapidly progress) (OR: 1.02. 95%CI: 1.01-1.03). ROC analysis showed the age of 60 as an optimal cut-off value for determining the risk subjects for the increase in AGE (OR: 1.74, 95%CI: 1.20-2.51).
Conclusions: The accumulation of AGEs may increase with increasing speed, which becomes rapid over the age of 60 independent of glycemic levels, uACR and HOMA-ß, indicating that not glycemic control levels but aging per se is a major contributor for AGE accumulation.

Disclosure
S. Mizushiri: None. M. Daimon: None. H. Murakami: None. A. Kamba: None. M. Murabayashi: None. Y. Nishiya: None.
1404-P: Association with Insulin Resistance and Sarcopenia: The Korean Frailty and Aging Cohort
Authors: CHOE HUN JEE , KIM KYUHO , OH TAE JUNG , CHOI SUNGHEE , PARK KYONG SOO , JANG HAK CHUL 
Published: June 2020

Introduction: Previous studies demonstrated that older adults with diabetes had lower skeletal muscle mass, strength, and physical function compared with those without diabetes. The aim of this study is to evaluate the effect of hyperglycemia and insulin resistance in the progression of sarcopenia in older adults with diabetes.
Methods: The Korean Frailty and Aging Cohort Study is a multicenter prospective study with a baseline examination measured in 2016-2017. Longitudinal analysis was conducted with the 2018 follow up data. The difference of muscle related variables over the two years was evaluated for both genders and stratified by the presence of diabetes and insulin resistance.
Results: Among the 1,515 participants with baseline and two-year follow-up examination on skeletal muscle mass, strength, and function, 327 (21.6%) had diabetes mellitus at baseline. Participants showed decline in ASM, ASM/height2, ASM/body mass index (BMI), gait speed, and Timed Up and Go (TUG) test regardless of diabetes status over the two years (all p&lt;0.001). In men with higher HOMA-IR (≥1.11), the decline of muscle mass indices (p&lt;0.001), and TUG test (p=0.002) was significantly greater than men with lower HOMA-IR (&lt;1.11). Women with higher HOMA-IR also showed greater decline in hand grip strength (p=0.040) gait speed (p=0.035), muscle mass indices (p&lt;0.005), and TUG test (p=0.010) than women with lower HOMA-IR. None of the variables were significantly different when compared according to the baseline HbA1c level. In subjects without diabetes, the decline of muscle mass indices was significantly greater in subjects with higher HOMA-IR compared to those with lower HOMA-IR, but muscle strength and function were not affected by insulin resistance.
Conclusion: Insulin resistance shows preponderating influence over hyperglycemia in progression of sarcopenia in Korean older adults. This result suggests that insulin sensitizer might be beneficial in prevention of sarcopenia in older adults with diabetes.

Disclosure
H. Choe: None. K. Kim: None. T. Oh: None. S. Choi: None. K. Park: None. H. Jang: Speaker’s Bureau; Self; Daiichi Sankyo, Handok, Pfizer Inc., Takeda Pharmaceutical Company Limited.
1409-P: Diabetes Development in Adults with Cardiovascular Disease: Age Matters
Authors: CIGOLLE CHRISTINE , BLAUM CAROLINE , SZYMONIFKA JACKIE , KABETO MOHAMMED , HA JINKYUNG , ZHONG JUDY 
Published: June 2020

The epidemiology of diabetes (DM) and subsequent development of cardiovascular disease (CVD) is well-studied. Less is known about the development/course of DM in adults with preexisting CVD. We hypothesized that incidence of DM in these adults varies by age. We analyzed waves 1993-2014 of the Health and Retirement Study, a nationally-representative health survey. Our study sample included adults ≥50 years (n=27,650) not having CVD or DM at entry. Age of CVD-onset was defined as age when respondent first reported CVD diagnosis. We classified adults who developed CVD into 3 age of CVD-onset groups (years): 50-59, 60-69, ≥70. For each group, we constructed a propensity-score-matched control group of respondents not having CVD. We compared risk of developing DM for each age of CVD-onset group and its matched control. Of all respondents, 683 developed CVD at 50-59 years, 1,609 at 60-69, and 3,253 at ≥70; 22,105 never developed CVD. Adults diagnosed with CVD at 50-59 years had substantial increased risk of DM: incidence risk ratio (IRR) 1.5 (1.1, 2.0). CVD diagnosis at 60-69 years also had increased risk of DM: IRR 1.2 (1.0, 1.5). CVD diagnosis at ≥70 years had no increased risk of DM: IRR 1.1 (0.9, 1.4). (Figure) Age of CVD diagnosis differentially impacts the risk of subsequent development of DM in middle-age and older adults. The relationship between DM and CVD is complex, with the role of prevalent CVD on DM incidence/course incompletely understood.

Disclosure
C. Cigolle: None. C. Blaum: None. J. Szymonifka: None. M. Kabeto: None. J. Ha: None. J. Zhong: None.

Funding
National Institutes of Health (AG054467-01)
1417-P: Lipoprotein(a)-Associated Residual Atherosclerotic Cardiovascular Disease Risk in Patients with Cardiovascular Disease on Statin Therapy by Diabetes Status
Authors: ZHAO YANGLU , SUNG JENNIFER C. , BROWNE AURIS , WONG NATHAN D. 
Published: June 2020

Background: The relation between elevated lipoprotein(a) [Lp(a)] and future atherosclerotic cardiovascular disease (ASCVD) in those with vs. without diabetes mellitus (DM) but known cardiovascular disease (CVD) is not clear. We examined recurrent ASCVD event risk by DM status in persons with known CVD on statin therapy.
Methods: We studied 1,354 patients with and 2,005 patients without DM, all with prior CVD on statin therapy in the AIM-HIGH cohort. First and total recurrent ASCVD event rates were calculated by Lp(a) levels and the PWP model provided hazard ratios (HRs) for events over a mean follow-up of 3.3 years, adjusted for age, sex, trial treatment, LDL-C, and other risk factors.
Results: ASCVD event rates (per 1000 person years) increased with Lp(a) levels ranging from &lt;15 mg/dl to ≥70 mg/dL in non-DM: 39.7 to 74.1 for first and 48.5 to 87.3 for total recurrent events and in DM: 51.1 to 79.5 for first and 69.8 to 100.3 for total recurrent events. The Table shows HRs by Lp(a) categories for first and total recurrent ASCVD events. A higher risk for first recurrent events is noted at lower Lp(a) levels in those with vs. without DM.
Conclusions: Higher Lp(a) levels predict residual ASCVD risk. However, ASCVD event risk may occur at lower levels of Lp(a) in those with vs. without DM. Future investigations in larger cohorts are needed to confirm these findings.

Disclosure
Y. Zhao: None. J.C. Sung: Employee; Self; Novartis Pharmaceuticals Corporation. A. Browne: Employee; Self; Novartis Pharmaceuticals Corporation. N.D. Wong: Advisory Panel; Self; Esperion Therapeutics, Inc. Research Support; Self; Amarin Corporation, Amgen, Boehringer Ingelheim Pharmaceuticals, Inc., Novartis AG, Novo Nordisk Inc. Speaker’s Bureau; Self; Amarin Corporation, Sanofi.
1422-P: Different Diagnostic Criteria for Diabetes and Risk of Cardiovascular Disease in the Greenland Inuit
Authors: BYBERG STINE , TVERMOSEGAARD MARIA , DÍAZ LARS , SENFTLEBER NINNA K. , LARSEN CHRISTINA V.L. , RØNN PERNILLE F. , BJERREGAARD PETER , PEDERSEN MICHAEL L. , JØRGENSEN MARIT E. 
Published: June 2020

Introduction: Diabetes prevalence in Greenland is high and increasing. Diabetes can be diagnosed by different criteria; currently HbA1c levels ≥ 48 mmol/mol, fasting plasma glucose (FPG) ≥ 7.0 mmol/l and/or two-hour plasma glucose (2hPG) ≥ 11.1 mmol/l after an oral glucose tolerance test (OGTT). We compared the risk of cardiovascular disease (CVD) by different diagnostic criteria, in the Greenland Inuit. Methods: Participants included in the population-based Inuit Health in Transition (IHIT) study in Greenland (2005-2010), had HbA1c, FPG and 2hPG levels measured at entry. We followed participants in the Danish and Greenlandic health registers for a composite endpoint of non-fatal and fatal CVD until 31/12-2017. Participants with known diabetes (n=77) and previous CVD (n=140), were excluded. We compared incidence rates for different diagnostic criteria, adjusted for various clinical and sociodemographic confounders in separate Poisson regressions, using multiple imputations for missing data and split follow-up into 1-year age-bands to account for a non-constant effect of age.
Results: We included 2,898 adult participants, with 246 CVD events and 366 deaths during follow-up. In the crude analyses, incidence rate ratios (IRR) of CVD were highest among participants diagnosed by HbA1c (IRR:2.69; 95%CI (1.66-4.34)), followed by participants diagnosed by FPG (2.04 (1.27-3.27)), and both FPG and 2hPG (1.96 (1.31-2.94)), compared with normoglycemia. The IRR for all three diagnostic criteria were attenuated after confounder adjustment (HbA1c 1.14 (0.70-1.88); FPG: 0.81 (0.50-1.30); FPG and 2hPG: 0.78 (0.51-1.18)).
Conclusions: IRR of CVD were highest among participants diagnosed by HbA1c in the crude analyses. None of the diagnostic criteria were associated with CVD after adjustment, especially for age. Future studies will investigate other diabetes related complications, competing risks from death, and interactions with genetic variants in the Greenland population.

Disclosure
S. Byberg: None. M. Tvermosegaard: None. L. Díaz: None. N.K. Senftleber: None. C.V.L. Larsen: None. P.F. Rønn: Research Support; Self; Amgen, Danish Diabetes Academy. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. P. Bjerregaard: None. M.L. Pedersen: None. M.E. Jørgensen: Research Support; Self; Amgen, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi-Aventis. Stock/Shareholder; Self; Novo Nordisk A/S.
1423-P: The Association of the American Heart Association’s Life’s Simple 7 with Self-Reported Health, Diabetes, and Adiposity in African American Males
Authors: ABOAGYE-MENSAH EMMANUELA B. , AZAP ROSEVINE A. , ODEI JAMES B. , GRAY DARRELL M. , NOLAN TIMIYA S. , ELGAZZAR RANA , WHITE DEVEONNE L. , GREGORY JOHN H. , JOSEPH JOSHUA 
Published: June 2020

Background: African American (AA) men have the highest age-adjusted all-cause mortality rate in the U.S. and a high burden of risk factors contributing to chronic diseases. The African American Male Wellness Walk (AAMWW) seeks to reduce health disparities and promote attainment of Life’s Simple 7 (LS7) among AA males. We investigated the association of six components of the American Heart Association’s LS7 metrics: blood pressure, body weight, cholesterol, physical activity, smoking, and blood glucose with self-reported health, diabetes prevalence, body fat percentage (BF%), and family history of diabetes.
Methods: Our study included 731 AA male participants from the 2017 and 2018 AAMWWs. ANOVA and Chi-square tests analyzed continuous and categorical variables, respectively. Six metrics of LS7 developed a total cardiovascular health score, categorized by the number of ideal LS7 components as 0-2, 3, 4, 5-6. Logistic and linear regression models examined the association of LS7 with outcomes adjusted for age and insurance status.
Results: Participants with 5-6 ideal metrics compared to 0-2 had 261% higher odds of a 1 category higher self-reported health (p&lt;0.0001). Individuals with 3-6 compared to 0-2 ideal metrics had 88% lower odds of diagnosed diabetes (p&lt;0.001). Participants with 5-6 ideal metrics had a 12.2% lower body fat percentage compared to participants with 0-2 ideal metrics (p=0.0003).
Conclusion: Attainment of LS7 metrics is associated with improved self-reported health and inversely associated with diabetes prevalence and BF% among AA men in the AAMWW. Interventions targeting LS7 ideal metrics among AA men may promote health equity.

Disclosure
E.B. Aboagye-Mensah: None. R.A. Azap: None. J.B. Odei: None. D.M. Gray: Consultant; Self; Genentech, Inc. T.S. Nolan: None. R. Elgazzar: None. D.L. White: None. J.H. Gregory: None. J. Joseph: None.
1425-P: White Blood Cell Count Predicts Cardiovascular Prognosis in Type 2 Diabetic Patients with Established Coronary Artery Disease
Authors: KAWABE ATSUHIKO , NAKATANI YUKI , ONO SHOYA , MIYASHITA YASUSHI , MATSUMURA MIHOKO , BANBA NOBUYUKI , YASU TAKANORI 
Published: June 2020

Introduction and Hypothesis: White blood cell (WBC) count in healthy persons is reported to be associated with the risk of coronary artery disease (CAD) and all-cause death. The aim of our study was to determine whether WBC count predicts cardiovascular outcome, including heart failure and mortality, in consecutively registered patients with type 2 diabetes.
Methods and Results: This was a post-hoc study from the Intensive Lipid and Blood Pressure Lowering and Cardiovascular Outcome Randomized Controlled Trial in Patients with CAD and type 2 diabetes. A total of 7,608 participants (mean age 68 years, 72% men) had WBC measured at baseline and were eligible for this study. Participants were followed for a mean of 1,328 days. We used Cox proportional hazards regression model to assess the hazard ratio (HR) and 95% confidence interval (CI). Participants with WBC count in the highest quartile had an adjusted HR for all-cause death of 1.66 (95% CI, 1.33 to 2.06, Figure) compared to those in the lowest quartile (WBC &lt;5300 cells/µL). Additionally, similar findings were observed for the risk of acute myocardial infarction and heart failure; however, no significant difference was found for stroke risk (Figure).
Conclusions: In patients with CAD and type 2 diabetes, higher WBC count may have potential as a predictor for all-cause death, myocardial infarction, and heart failure but not stroke.

Disclosure
A. Kawabe: None. Y. Nakatani: None. S. Ono: None. Y. Miyashita: None. M. Matsumura: None. N. Banba: None. T. Yasu: None.
1431-P: Risk of Venous Thromboembolism amongst Initiators of SGLT2 Inhibitors Compared with Other Glucose-Lowering Agents
Authors: GOPALAKRISHNAN CHANDRASEKAR , DESAI RISHI J. , KIM SEOYOUNG C. , PATORNO ELISABETTA 
Published: June 2020

The comparative safety of frequently used second-line agents to treat type 2 diabetes (T2D) with respect to the risk of venous thromboembolism (VTE) in routine care is unknown. It has been hypothesized that the diuretic effect of SGLT2 inhibitors (SGLT2i) may have an unintended impact on VTE risk by increasing blood viscosity. Using Optum Clinformatics, a large U.S. commercial health insurance claims database, we assessed the risk of an incident hospitalization for VTE within two pair-wise 1:1 propensity score (PS)-matched cohorts of patients with T2D who initiated a SGLT2i or a comparator, i.e., a GLP-1 receptor agonist [GLP-1 RA (n=59,712 pairs)], or a DPP-4 inhibitor [DPP-4i (n=50,178 pairs)] between April 2013-March 2019. We estimated hazard ratios (HR) and 95% CI controlling for over 100 baseline characteristics including common risk factors for VTE, baseline comorbidites, medication use and healthcare utilization. SGLT2i had a similar risk of VTE compared to GLP-1 RA [HR (95% CI) = 0.99 (0.68, 1.44)] and DPP-4i [HR (95% CI) = 1.01 (0.66, 1.52)] (Table 1), with incidence rates ranging between 1.1 and 1.3 events per 1,000 person-years. Results were consistent within subgroups of age, frailty and cardiovascular disease. In a large population-based study of adult patients with T2D, SGLT2i had similar risk of VTE compared to GLP-1 RA and DPP-4i, with reassuringly low absolute rates overall.

Disclosure
C. Gopalakrishnan: None. R.J. Desai: Research Support; Self; Bayer AG, Novartis AG. S.C. Kim: Research Support; Self; AbbVie Inc., Bristol-Myers Squibb. E. Patorno: Other Relationship; Self; Boehringer Ingelheim International GmbH.

Funding
National Institute on Aging (K08AG055670)
1432-P: Association between Insulin Use and Long-Term Cardiovascular Disease Outcomes in Older Adults
Authors: VISARIA AAYUSH , DHARAMDASANI TINA , WICKRAMASINGHE KAVINDYA , LO DAVID , MALHOTRA RAJ 
Published: June 2020

Introduction: Exogenous insulin therapy has been the mainstay of treatment for those with uncontrolled type 2 diabetes; however, recent literature has pointed to a lack of risk reduction for cardiovascular disease (CVD). We sought to determine the association between insulin use and major adverse cardiovascular events (MACE) among older adults with type 2 diabetes with a long-term follow-up.
Methods: A cohort of 1,084 participants &gt;50 years with type 2 diabetes from the National Health and Nutrition Examination Survey-III (1988-1994) was followed for an average 22.4 years through 2015. Subjects were divided into two groups: 1) those using insulin therapy and 2) those using oral medications only. The primary outcome was major adverse cardiovascular events (MACE), a combination of self-reported myocardial infarction, stroke, or CVD mortality. We used multivariable logistic regression, adjusting for HbA1c, demographic, metabolic, and inflammatory factors and accounting for the survey design.
Results: Among the participants, 227 (21%) regularly used insulin. Those using insulin were of similar age, more likely to be male, have similar BMI, waist circumference, blood pressure, and lipids, have higher HbA1c (8.2% vs. 7.3%, p&lt;0.01), and have significantly higher serum insulin levels (mean[SD]: 51.1[4.2] vs. 18.5[0.7], p&lt;0.001). Those taking insulin had nearly twice the adjusted odds of MACE relative to those only taking oral agents (aOR [95% CI]: 1.89 [1.11, 3.24]). When assessing individual conditions, those taking insulin had significantly increased odds of stroke, but not MI or CVD mortality (aOR [95% CI]: stroke = 3.69 [1.26, 10.78], MI = 1.41 [0.75, 2.65], CVD mortality = 1.19 [0.69, 2.06]). There was no significant dose-dependent association between insulin use and MACE.
Conclusion: Long-term insulin use may be associated with increased stroke, although no dose-dependent association was present. Increased care and assessment may be warranted in patients taking insulin.

Disclosure
A. Visaria: None. T. Dharamdasani: None. K. Wickramasinghe: None. D. Lo: None. R. Malhotra: None.