bluuebunny/crossref_metadata_2025_split huggingface dataset:
1437-P: How Has Changing the Diagnostic Criteria Impacted Perinatal Outcomes for Those NOT Diagnosed with GDM?
Authors: MELONCELLI NINA J.L. , BARNETT ADRIAN G. , DE JERSEY SUSAN J. 
Published: June 2019

In 2015, more than 90% of Australian antenatal care providers transitioned to the IADPSG recommendations for screening and diagnosing GDM. In the Australian state of Queensland, this resulted in 34% more women being diagnosed with GDM. Based on the increased number of women being treated for GDM, we hypothesized that perinatal outcomes, commonly associated with GDM, should decrease for pregnant women without GDM. We used routinely collected perinatal data of over 124,000 women to examine the difference in perinatal outcomes in the year before (2014) and after (2016) state-wide policy was changed for diagnosing GDM. Logistic regression was used to estimate the odds ratio and 95% confidence intervals for the risk of developing selected perinatal outcomes in women without GDM. Despite 34% more women being diagnosed and treated for GDM, there was a statistically significant increase in the year after the changes to the diagnostic criteria for women without GDM for: pregnancy-induced hypertension (OR 1.10, 95% CI 1.03 - 1.16), large-for-gestational (OR 1.37, 95% CI 1.17 - 1.60), small-for-gestational age infants (OR 1.75, 95% CI 1.59 - 1.92) and neonatal hypoglycaemia (OR 1.23, 95% CI 1.15 - 1.30). There was a decrease in respiratory distress (OR 0.93, 95% CI 0.88 - 0.98). Our results add to the growing body of evidence that changing diagnostic criteria has had little impact on outcomes for women GDM and in our study, the outcomes for women without GDM appeared to have worsened. Although our study design does not allow us to examine why this negative shift has occurred, we hypothesize that the additional resources required for treating women with GDM may have been provided at the expense of women without the condition. We question whether changing the diagnostic criteria was the correct choice for our population, given the increase in costs of treatment and recommend further research on potential harms in both the GDM and non-GDM populations.

Disclosure
N.J.L. Meloncelli: None. A.G. Barnett: None. S.J. de Jersey: None.
1442-P: Incidence and Risk Factors for Type 2 Diabetes among the Offspring of Long-Lived Individuals: The Long Life Family Study
Authors: MILJKOVIC IVA , CVEJKUS RYAN , AN PING , THYAGARAJAN BHARAT , BOUDREAU ROBERT , ZMUDA JOSEPH M. 
Published: June 2019

Centenarians and their offspring appear to have a reduced risk of type 2 diabetes (T2D) compared to similarly aged controls. We determined the incidence of and potential risk factors for T2D among the offspring of probands and their spouses (mean age =60 years; SD=8 years), in the Long Life Family Study (LLFS), a multicenter cohort study of two-generation families with a clustering of healthy aging and exceptional survival. Incident T2D was defined as fasting serum glucose ≥126 mg/dl, or HbA1c of ≥6.5%, or self-reported with doctor diagnosis of T2D, or the use of antidiabetic medication during a mean follow-up 7.9 ± 1.1 years. Among nondiabetic offspring (n=1585) and spouses (n=495) at study entry, 58 (3.7%) and 19 (3.8%) developed incident T2D, respectively. By comparison, 5.1% of comparable aged nondiabetics developed T2D in the Framingham Offspring Study. At Visit 1, BMI, waist circumference, and fasting serum triglycerides were positively, whereas HDL-C and adiponectin were inversely associated with incident T2D among offspring in LLFS (all P&lt;0.05 for all using logistic GEE with intra-family correlations). Similar associations were observed in their spouses (P&lt;0.05 for all). Additionally, we observed that among spouses serum interleukin 6 and insulin-like growth factor 1 concentrations were positively associated with incident T2D (P&lt;0.05 for both). All associations were independent of age, sex, field center, alcohol intake, hours of walking, and BMI or waist circumference (in models with metabolic and inflammation biomarker predictors). The current study suggests that offspring of long-living individuals in the LLFS and their spouses may share a similar, low risk for developing T2D as compared to the general population. Our findings also raise the possibility that distinct risk factors may contribute to T2D risk among offspring of long-lived individuals compared to their spouses.

Disclosure
I. Miljkovic: None. R. Cvejkus: None. P. An: None. B. Thyagarajan: None. R. Boudreau: None. J.M. Zmuda: None.

Funding
National Institute on Aging
1446-P: Fall Risk in Individuals with Type 2 Diabetes: The Look AHEAD Study
Authors: LEE PEARL G. , POKHREL KESHAV P. , HERMAN WILLIAM H. 
Published: June 2019

Over one quarter of adults ≥65 years of age with diabetes report falling in the preceding 2 years. We hypothesized that participants in the Look AHEAD intensive lifestyle intervention (ILI) would have fewer falls compared to those who received diabetes support and education (DSE) only. The Look AHEAD study randomly assigned participants (aged 45-76 years) with type 2 diabetes and body mass index (BMI) ≥25 kg/m2 to ILI (diet and physical activity to induce ≥7% of initial weight) or DSE. We compared baseline characteristics of participants who reported 0, 1, or 2+ falls at year 8, by intervention group, and built multinomial logistic regression models to predict falls. Older adults with diabetes randomly assigned to the ILI compared to those in the DSE were less likely to fall 2 or more times at 8-year follow-up in the Look AHEAD study (β= -0.18, p = 0.01).

Disclosure
P.G. Lee: Advisory Panel; Self; T1D Exchange. Other Relationship; Self; Sanofi. K.P. Pokhrel: None. W.H. Herman: Consultant; Self; Janssen Scientific Affairs, LLC. Consultant; Spouse/Partner; Nestlé. Other Relationship; Self; Merck Sharp & Dohme Corp.
1459-P: Comparative Cardiovascular Safety and Effectiveness of Linagliptin in Routine Care: Final Results from a 5-Year Post-Marketing Monitoring Program
Authors: PATORNO ELISABETTA , GOPALAKRISHNAN CHANDRASEKAR , MAHESRI MUFADDAL , BRODOVICZ KIMBERLY G. , BARTELS DOROTHEE , MEYERS ANDREA , BARBERIO JULIE , LIU JUN , SCHNEEWEISS SEBASTIAN 
Published: June 2019

Real world data on the cardiovascular (CV) safety and effectiveness of linagliptin (LINA) complement trial data from CARMELINA, which showed CV safety, and CAROLINA (results pending). As part of a 5-year (05/2011-12/2016) post-marketing monitoring program, using 2 large insurance claims databases, we assessed the risk of a composite CV (cCV) outcome (hospitalization for myocardial infarction, stroke, unstable angina, or coronary revascularization). We identified three 1:1 propensity score (PS)-matched cohorts of type 2 diabetes mellitus patients who initiated linagliptin or a comparator [other DPP-4is (n=39,834 pairs), pioglitazone (PIO; n=29,646 pairs), or sulfonylureas (SU; n=25,285 pairs). We estimated pooled HR and 95% CI controlling for over 180 baseline characteristics. After PS-matching, patient characteristics were similar (Table 1) and mean follow-up was 0.8 years. LINA had a similar risk of the cCV outcome compared to other DPP-4is [HR (95% CI) = 0.90 (0.80-1.02)] and PIO [HR (95% CI) = 0.99 (0.86-1.13)], but was associated with a reduced risk compared to SU [HR (95% CI) = 0.77 (0.66-0.90)] (Table 1). Results were robust across numerous sensitivity analyses. These real-world data show that LINA has reassuring effectiveness and safety on a cCV outcome compared to other DPP-4is and PIO, and is associated with a decreased risk compared to SU.

Disclosure
E. Patorno: Research Support; Self; National Institute on Aging. Other Relationship; Self; Boehringer Ingelheim International GmbH. C. Gopalakrishnan: None. M. Mahesri: None. K.G. Brodovicz: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. D. Bartels: Employee; Self; BI X GmbH, Boehringer Ingelheim International GmbH. A. Meyers: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. J. Barberio: None. J. Liu: None. S. Schneeweiss: Consultant; Self; Aetion, WHISCON, LLC.

Funding
Boehringer Ingelheim
1460-P: Predicting Atherosclerotic Cardiovascular Disease (ASCVD) Risk in Veterans with Diabetes
Authors: RAGHAVAN SRIDHARAN , HO YUK-LAM , POSNER DANIEL , VASSY JASON L. , GAGNON DAVID R. , PHILLIPS LAWRENCE S. , WILSON PETER W. 
Published: June 2019

Estimating ASCVD risk in patients with diabetes could guide intensity of risk factor treatment, but existing risk calculators (2013 ACC/AHA ASCVD pooled cohort equations [PCE] and RECODe risk equations [RECODe]) have not been evaluated in a contemporary American population with diabetes. Using validated phenotyping algorithms, we evaluated prediction models for the development of a composite “hard” ASCVD outcome (non-fatal myocardial infarction, non-fatal stroke, cardiovascular death) over 5 years in 184,823 diabetic U.S. Veterans without baseline ASCVD receiving primary care in the VA 2002-2007 (2.4% women, 19.5% black, mean age 61 years, 9851 ASCVD events). We compared discrimination using the C-statistic and calibration using the Greenwood-Nam-D’Agostino test (GND) of the PCE variables (sex, age, race, cholesterol, blood pressure [BP], smoking status, BP medications, statin treatment, and aspirin), RECODe, and a series of models using PCE variables with VA sample-specific coefficients. Models with PCE variables and VA-specific coefficients had better discrimination (C=0.642) than the PCE (C=0.582) or RECODe (C=0.633). Successive addition of hemoglobin A1c, estimated glomerular filtration rate, diabetes medications, and statin therapy improved the model (full model, C=0.669), with only minimal enhancement by semisupervised variable selection using LASSO (C=0.672). The C-statistic of the full model was similar in those &lt;60 or ≥60 years old, but predicted risk was higher for black than for white patients, and for men than for women. The full model also had improved calibration (GND p=0.82) compared to the PCE and RECODe (p&lt;0.0001 for both; higher p indicates better calibration).
Conclusion: Health system-specific tailoring of prediction equations provides improved discrimination and calibration compared to existing models. This risk predictor could be embedded in the electronic health record and used to guide intensification of treatment aimed to improve ASCVD outcomes.

Disclosure
S. Raghavan: None. Y. Ho: None. D. Posner: None. J.L. Vassy: None. D.R. Gagnon: None. L.S. Phillips: Advisory Panel; Self; Janssen Pharmaceuticals, Inc. Research Support; Self; AbbVie Inc., GlaxoSmithKline plc., Kowa Pharmaceutical Europe Co. Ltd., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Pfizer Inc. Stock/Shareholder; Self; Diasyst Inc. Other Relationship; Self; Diasyst Inc., Janssen Pharmaceuticals, Inc. P.W. Wilson: None.

Funding
U.S. Department of Veterans Affairs; American Heart Association
1468-P: Cause-Specific Mortality over 30 Years among Chinese with Newly Diagnosed Diabetes: The Da Qing IGT and Diabetes Study
Authors: AN YALI , ZHANG PING , WANG JINPING , GONG QIUHONG , ZHANG BO , CHEN YANYAN , GREGG EDWARD , BENNETT PETER H. , LI GUANGWEI 
Published: June 2019

Despite its growing prevalence in China, the extent to which diabetes leads to excess mortality and its underlying causes are ill-defined. Six-hundred and six persons with newly diagnosed diabetes (NDD) and a comparison group of 494 with normal glucose tolerance (NGT) were identified in 1986 by screening 110,660 adults aged 25-74 years who agreed to participate in The Da Qing IGT and Diabetes study. A follow-up study of the original study participants was conducted in 2016. We compared death rates and causes of death between the two groups during 30 years of follow-up. Four-hundred and forty (71.7%) participants with NDD and 153 (31.0%) with NGT died. Overall mortality (rates/1,000 person-years + 95% CI) were much higher in those with NDD than with NGT, 40.8 (35.6-46.5) vs.15.8 (13.0-19.1) in men (P&lt; 0.0001), and 30.4 (26.4-34.9) vs. 6.9 (5.0-9.3) in women (P&lt;0.0001). Earlier age at diagnosis of diabetes was significantly related to the relative risk of death (RR (+95% CI)), 5.0 (2.9-8.6) in those diagnosed at age 25∼39y, 3.2 (2.3-4.4)] at 40∼49y, and 2.8 (2.1-3.6) at 50∼74y. Cardiovascular disease (CVD) was the predominant cause of death in those with diabetes (66.5% in men and 62.8% in women), almost half of which was due to stroke (52.1% in men and 40.6% in women). After age-sex adjustment, the NDDs had significant increased mortality from CVD (RR 3.9 [95% CI, 2.9-5.2]), renal failure (RR 15.6 [95% CI, 6.3-38.9]), infection (RR 4.2 [95% CI, 2.0-8.5]), and cancer (RR 1.5 [95% CI, 1.0-2.3]).
In conclusion, diabetes is associated with substantially increased risks of death in Chinese adults, especially from CVD, renal failure, infection and cancer. Earlier age at diagnosis leads to greater relative risk of death.

Disclosure
Y. An: None. P. Zhang: None. J. Wang: None. Q. Gong: None. B. Zhang: None. Y. Chen: None. E. Gregg: None. P.H. Bennett: Consultant; Self; World Health Organization. Stock/Shareholder; Self; Becton, Dickinson and Company, Eli Lilly and Company, Pfizer Inc., UnitedHealth Group Inc. Other Relationship; Self; American Diabetes Association, Centers for Disease Control and Prevention, European Association for the Study of Diabetes, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. G. Li: None.

Funding
Centers for Disease Control and Prevention/Chinese Center for Disease Control and Prevention (5U19GH000636-05)
147-LB: PATAS, an Adipocyte-Targeted Peptide Approach to Treat Type 2 Diabetes and Associated Comorbidities
Authors: MARION VINCENT 
Published: June 2019

Studying rare genetic disorders, associating type 2 diabetes, is a valuable approach to decipher disease origins as a specific causal gene can be linked to the diabetic phenotype. Understanding the related protein functions favors the discovery of new pathways, hence the design of new therapies. We focused on an ultra-rare genetic disorder, the Alström syndrome, associated with severe early-onset type 2 diabetes, obesity, steatosis and generalized fibrosis and for which a unique gene is consistently found mutated in ALMS patients, ALMS1 gene. Combining clinical, multiomics and in vivo mouse data, we discovered that ALMS1 regulates the ultimate steps of insulin signaling in the adipocyte, controlling fusion of GLUT4 sorting vesicles with the plasma membrane. ALMS1 binds to αPKC in the GLUT4 sorting vesicles vicinity and, under insulin stimulus, releases αPKC to trigger GLUT4 plasma membrane entry and glucose absorption. ALMS1 inactivation specifically inhibits adipocyte’s glucose absorption. In mice, the diabetic, steatotic and fibrotic phenotypes were linked to switching adipocyte energy tropism from glucose to lipids corelated with fatty acid transporters’ upregulation like FATP2 in the adipocyte; also observed in ALMS patients’ adipocytes. This change in fuel source in the adipocyte is the underlying cause for the observed metabolic disorders in vivo; primarily mediated through lipid signaling. Insulin-independent glucose absorption was achieved in normal adipocytes using a cell-penetrant, stapled peptide termed PATAS that targets ALMS1/αPKC protein interaction and in vivo can restore physiological adipocyte’s glucose energy tropism. Several in-house and outsourced experiments have demonstrated that PATAS administration significantly improves glucose intolerance, fasting blood glucose levels, liver steatosis and fibrosis in different mouse and rat models thereby making PATAS a potential novel drug to treat type 2 diabetes and its associated complications.

Disclosure
V. Marion: Research Support; Self; Rhythm Pharmaceuticals, Inc. Stock/Shareholder; Self; ALMS THERAPEUTICS.
1472-P: Association between Triglycerides and Residual Cardiovascular (CVD) Risk in Patients with Type 2 Diabetes and Established CVD: An Analysis of the BARI2D Trial
Authors: PAGIDIPATI NEHA , NAVAR ANN MARIE , MULDER HILLARY , WOJDYLA DANIEL M. , PHILIP SEPHY , GRANOWITZ CRAIG B. 
Published: June 2019

Background: While hypertriglyceridemia is a known risk factor for developing CVD, whether it poses residual risk in patients with type 2 diabetes mellitus (T2DM) and established CVD is under-studied.
Methods: Using data from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial, we examined 2,307 patients with T2DM and CVD to determine the association of baseline fasting triglyceride (TG) levels with MACE (time to CV death, myocardial infarction (MI), or stroke) or CV death over a mean follow-up of 5.0 years.
Results: At baseline, the mean fasting TG was 181 mg/dl with a median (Q1, Q3) of 148 (104, 219) mg/dl. Overall, 49.3% had TG≥ 150 mg/dl (N=1,167). Compared with those with TG&lt;150 mg/dl, they were younger, more frequently Caucasian and with higher BMI. In unadjusted models, TGs were significantly associated with MACE and CV death (Table). This association did not remain after adjustment for multiple factors, including nonHDLc.
Conclusions: In this analysis of patients with T2DM and known CVD, TGs were relatively high and were associated with CV outcomes, but not when other risk factors were taken into account. Thus, while TGs are clearly a marker of those with residual high risk for CV events in T2DM, whether they specifically need to be lowered awaits well conducted clinical trials.

Disclosure
N. Pagidipati: Research Support; Self; Amarin Corporation, Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Regenerative Medical Solutions, Sanofi. A. Navar: Advisory Panel; Self; AstraZeneca, Novo Nordisk Inc. Research Support; Self; Janssen Pharmaceuticals, Inc. Other Relationship; Self; Amarin Corporation, Amgen Inc., Regeneron Pharmaceuticals, Sanofi. H. Mulder: None. D.M. Wojdyla: None. S. Philip: Employee; Self; Amarin Corporation. Stock/Shareholder; Self; Amarin Corporation. C.B. Granowitz: Employee; Self; Amarin Pharma Inc. Stock/Shareholder; Self; Amarin Pharma Inc.

Funding
Amarin Corporation
1478-P: Impact of Prior Cerebrovascular Disease (CVD) and Glucose Tolerance Status on Incident CVD in Japanese
Authors: YANAGISAWA DAICHI , FUJIHARA KAZUYA , OSAWA TAEKO , KITAZAWA MASARU , YAMAMOTO MASAHIKO , MATSUBAYASHI YASUHIRO , YAMANAKA NAUTA , KODAMA SATORU , SONE HIROHITO 
Published: June 2019

Although both a glucose metabolism abnormality and prior cerebrovascular disease (CVD) are major predictors of CVD, few studies have compared their impact on a subsequent CVD event. Also, few studies evaluated risk of prediabetes separately from nondiabetic categories. Thus, the impact of diabetes mellitus (DM) on subsequent CVD compared to normal glucose tolerance (NGT) could have been underestimated. We analyzed a nationwide claims-based database of 290,865 participants in 2008-14. Participants were classified as having NGT, prediabetes or DM based on fasting plasma glucose, HbA1c and use of antihypoglycemic agents (185,648 with NGT; 87,867 with prediabetes; 17,350 with DM). Participants were also classified as with or without prior CVD based on ICD-10 and questionnaires (1,944 with prior CVD; 288,921 without prior CVD). Cox regression model showed that prediabetes and DM confers about 1.1- and 1.4-fold excess risk for CVD, respectively, compared to NGT without prior CVD. Prediabetes and DM does not increase risk for CVD compared to NGT with prior CVD (Table). Prior CVD confers a 4-7-fold excess risk for CVD regardless of glucose tolerance status. Hazard ratio of CVD in NGT with prior CVD was 4 times higher than in DM without prior CVD. This implies that prediabetes and DM increase CVD only in those without prior CVD. Prior CVD confers a higher risk for subsequent CVD regardless of glucose tolerance status.

Disclosure
D. Yanagisawa: None. K. Fujihara: None. T. Osawa: None. M. Kitazawa: None. M. Yamamoto: None. Y. Matsubayashi: None. N. Yamanaka: None. S. Kodama: None. H. Sone: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kowa Pharmaceutical Europe Co. Ltd., Kyowa Hakko Kirin Co., Ltd., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited.
1479-P: Predictors of Incident Hospitalization for Heart Failure in the ACE Trial Population
Authors: SCOTT CHARLES A.B. , MCMURRAY JOHN J. , RYDÉN LARS , SUN YIHONG , TENDERA MICHAL , COLEMAN RUTH L. , HOLMAN RURY R. 
Published: June 2019

Background and Aims: Heart failure (HF) is a deadly complication of type 2 diabetes but little is known about its incidence in patients with coronary heart disease (CHD) and impaired glucose tolerance (IGT). We used Acarbose Cardiovascular Evaluation (ACE) trial data to identify baseline variables predictive of incident hospitalization for HF (hHF) or HF-death during median 5.0 years follow-up in this Chinese population with CHD and IGT.
Methods: Independent predictors of hHF/HF-death were determined using a Cox proportional hazards model. Patients were censored at first hHF event, HF-death or end of follow-up. The 16 variables tested included age, gender, BMI, smoking, plasma creatinine, prior cardiovascular events, fasting and 2-hour postload glucose and HbA1c. Those with a univariate hHF association (P&lt;0.10) were considered for inclusion in the model, with P values &lt;0.05 required for retention in the multivariable model.
Results: Of the 6522 ACE participants, 6278 had no prior HF. They were mean (SD) 64.2 (8.0) years old, BMI 25.4 (3.1) kg/m2 and 73% were male. Of these, 111 (1.8%) had ≥1 episode of adjudicated hHF. Significant independent hHF/HF-death predictors were age, plasma creatinine, prior myocardial infarction (MI) and prior atrial fibrillation (AF) (Table).
Conclusion: In Chinese patients with CHD and IGT, those at higher risk of hHF/HF-death were older with higher plasma creatinine values, prior MI and prior AF.

Disclosure
C.A.B. Scott: None. J.J. McMurray: Other Relationship; Self; AbbVie Inc., Amgen Inc., AstraZeneca, Bayer AG, Bayer AG, Bristol-Myers Squibb Company, DalCor Pharmaceuticals, GlaxoSmithKline plc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Theracos, Inc., Vifor Pharma. L. Rydén: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Speaker's Bureau; Self; Bayer AG. Other Relationship; Self; Merck Sharp & Dohme Corp., Novo Nordisk A/S. Y. Sun: None. M. Tendera: Consultant; Self; Bayer AG, Servier. R.L. Coleman: None. R.R. Holman: Advisory Panel; Self; Bayer AG, Novartis AG, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Bayer AG, Merck Sharp & Dohme Corp. Other Relationship; Self; AstraZeneca, Bayer AG, GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc.