bluuebunny/crossref_metadata_2025_split huggingface dataset:
1527-P: Race/Ethnic-Specific Association between BMI and Incident Type 2 Diabetes (T2DM): Evidence from the Multiethnic Study of Atherosclerosis
Authors: RODRIGUEZ LUIS A. , BRADSHAW PATRICK T. , SHIBOSKI STEPHEN , FERNANDEZ ALICIA , VITTINGHOFF ERIC , HERRINGTON DAVID M. , DING JINGZHONG , KANAYA ALKA M. 
Published: June 2019

Objective: We evaluated whether the longitudinal association between BMI and 10-year risk of developing T2DM occurred at lower BMI points among Chinese Americans, Hispanics, and African Americans compared to whites.
Research Design and Methods: We used data from the Multi-Ethnic Study of Atherosclerosis (2000-2013), a cohort of adults ages 45-85 without cardiovascular disease at baseline. Incident T2DM was defined as fasting glucose ≥126 mg/dL and/or use of a diabetes medication. We used multivariable Weibull regressions adjusting for age, sex, education, dietary quality (Alternative Healthy Eating Index and kcal/day), and exercise to estimate the association between BMI and incident T2DM by race/ethnicity. BMI was modelled with a 3-knot restricted cubic spline to capture non-linear associations.
Results: Among 4,541 participants without prevalent T2DM, 557 incident T2DM cases occurred in a median 9.1 years of follow-up. The corresponding BMI points and their respective 95% CIs for a 10% risk of T2DM over 10 years were 22.2 (20.4, 24), 24.5 (21, 28), 25.5 (24.2, 26.8) and 28 (26.5, 29.5) for Chinese-Americans, Hispanics, African Americans, and whites, respectively.
Conclusion: Race/ethnic minority groups develop T2DM at lower BMI compared to whites. Our findings support the ADA-recommended BMI≥23 for Asians and BMI≥25 for other groups for T2DM screening.

Disclosure
L.A. Rodriguez: None. P.T. Bradshaw: None. S. Shiboski: None. A. Fernandez: None. E. Vittinghoff: None. D.M. Herrington: None. J. Ding: None. A.M. Kanaya: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (F31DK115029)
1528-P: The Utility of MODY Probability Calculator in Polish Patients with Diabetes
Authors: HOHENDORFF JERZY , ZAPALA BARBARA , SOLECKA IWONA , UCIEKLAK DAMIAN , LUDWIG-SLOMCZYNSKA AGNIESZKA , MATEJKO BARTłOMIEJ , MROZINSKA SANDRA , MALECKI MACIEJ , SZOPA MAGDALENA 
Published: June 2019

MODY accounts for 1-2% of all diabetes cases. There are more than 20 genes linked with MODY. Unfortunately, ca. 90% of MODY cases are misdiagnosed as type 1 or type 2 diabetes. A proper diagnosis of the type of diabetes is crucial for the use of a tailored treatment. Next-generation sequencing (NGS) enables simultaneous testing of a set of genes responsible for MODY. However, this method is still not reimbursed in many countries and patients' selection for testing should be performed preciously. In 2012, an easy-to-use tool have been developed in Exeter, UK, to support the identification of cases appropriate for genetic testing in the British population. The aim of the study was to assess the utility of MODY Probability Calculator (MODY-PC) in Polish patients.
We have performed a retrospective analysis of 152 probands who were qualified for genetic testing between 2006 and 2018. Patients were recruited for MODY testing according to the classical clinical guidelines that include early age of diagnosis (≤35 years) and a positive, multigenerational family history. If Sanger sequencing for most likely gene was negative, NGS of a set of 28 genes was performed. MODY Probability was calculated on the website: www.diabetesgenes.org.
The study group consists of 64 GCK-, 37 HNF1A-MODY and 51 NGS-negative patients. The mean positive predictive value (PPV) was 66,6±17,7, 46,7±27,3 and 53,3±26,3% for GCK-, HNF-MODY and NGS-negative, respectively. The optimal statistical cut-off point to distinguish between MODY and NGS-negative patients was 58% (AUC: 0,568, 95% CI: 0,47-0,67). In such settings, in the analyzed group sensitivity and specificity was 64,4% and 49,0%, respectively. When using cut-off point of PPV for genetic testing of 25% sensitivity was 87,1% and specificity 17,6%.
In the analyzed group of probands that were qualified for genetic testing based on clinical features the use of MODY-PC would not substantially improve patients' selection process for genetic testing. Further improvement of MODY-PC is desirable.

Disclosure
J. Hohendorff: Other Relationship; Self; Abbott, Ascensia Diabetes Care, Novo Nordisk A/S, Sanofi-Aventis. B. Zapala: None. I. Solecka: None. D. Ucieklak: None. A. Ludwig-Slomczynska: None. B. Matejko: Research Support; Self; Roche Diabetes Care. Other Relationship; Self; Ascensia Diabetes Care. S. Mrozinska: Other Relationship; Self; EGIS Polska. M. Malecki: Advisory Panel; Self; Abbott Laboratories, AstraZeneca, Bioton, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi-Aventis. Speaker's Bureau; Self; Merck & Co., Inc. M. Szopa: None.

Funding
Polish Diabetes Association (2016 to M.S.); Jagiellonian University Medical College (K/ZDS/006219 to M.S.), (K/ZDS/005596 to M.M.)
153-LB: Pharmacokinetics, Pharmacodynamics, and Tolerability of Single- and Multiple-Dose of Janagliflozin, a Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor, in Healthy Chinese Subjects
Authors: LIU HONGZHONG , SONG LING , XIAO XINHUA , JIANG JI , HU PEI , LIU DONGYANG 
Published: June 2019

Objectives: Janagliflozin (JGZ) is a novel SGLT2 inhibitor for the treatment of type 2 diabetes mellitus (T2DM) by inhibiting renal glucose reabsorption and increasing urinary glucose excretion. The purposes of the studies were 1) to investigate the PK, PD, and tolerability of JGZ in healthy Chinese subjects, 2) to provide a guidance for the selection of dosing regimens in further clinical studies.
Methods: Two randomized, double-blind, placebo-controlled studies were sequentially conducted, including one single-ascending dose (SAD) study and one multiple-ascending dose (MAD) study. In the SAD study, 56 subjects were randomized to receive 10, 25, 50, 100, 200, 300, or 450 mg JGZ or placebo. In the MAD study, 42 subjects were randomized to receive 50, 100, 200 mg JGZ or placebo as loading dose on Day 1, and then 25, 50, 100 mg JGZ or placebo once-daily from Day 2 to Day 14. The blood and urine samples were collected at prespecified time points, and the PK parameters, PD response exhibited in 24 h urinary glucose excretion (UGE), and tolerability were assessed.
Results: JGZ was readily absorbed with Tmax being 2.0∼4.5 h. The mean steady-state T1/2 was about 26∼30 h. The plasma exposure of JGZ increased in a roughly dose-dependent manner. The mean 24 h UGE ranged from about 18∼85 g in SAD study, with a dose-dependent increasing trend. The mean 24 h UGE were approximately 40, 43, and 50 g at steady state with 25, 50, and 100 mg JGZ, respectively, indicating no significant increase over the dose range of 25 to 100 mg. The adverse events in both studies were mostly mild with no serious adverse event or adverse event leading to discontinuation.
Conclusions: In healthy Chinese subjects, JGZ was generally well tolerated and had favorable PK and PD profiles supporting a once-daily dosing regimen. The present studies suggest JGZ 25 and 50 mg could be the clinically recommended doses, which need to be further investigated in T2DM patients.

Disclosure
H. Liu: Research Support; Self; XuanZhu Pharma Co., Ltd., Jinan, Shandong, China. L. Song: Research Support; Self; XuanZhu Pharma Co., Ltd., Jinan, Shandong, China. X. Xiao: None. J. Jiang: Research Support; Self; XuanZhu Pharma Co., Ltd., Jinan, Shandong, China. P. Hu: Research Support; Self; XuanZhu Pharma Co., Ltd., Jinan, Shandong, China. D. Liu: Research Support; Self; XuanZhu Pharma Co., Ltd., Jinan, Shandong, China.

Funding
XuanZhu Pharma Co., Ltd.
153-OR: Early Progression to Diabetes or Regression to Normal Glucose Tolerance among People with Impaired Glucose Tolerance Affects Long-Term Outcomes: Thirty-Year Follow-Up of Da Qing Diabetes Prevention Study
Authors: CHEN YANYAN , ZHANG PING , WANG JINPING , GONG QIUHONG , AN YALI , GREGG EDWARD , BENNETT PETER H. , LI GUANGWEI 
Published: June 2019

Responses to lifestyle interventions in people with impaired glucose tolerance (IGT) may differ during the intervention phase: some progress to diabetes, some regress to normal glucose tolerance (NGT) and some retain IGT. Whether these different responses to intervention influence subsequent outcomes is uncertain. In 1986, 576 persons with IGT in Da Qing, China, were randomized to control or intervention (diet, exercise, diet plus exercise) groups for a six-year lifestyle intervention. In 1992, of 540 participants who completed the intervention, 252 (46.7%) had progressed to diabetes, 174 (32.2%) regressed to NGT, and 114 (21.1%) remained as having IGT. In 2016, we conducted a 30-year follow-up study to assess the intervention effect on CVD events, defined as the first occurrence of non-fatal or fatal stroke, myocardial infarction or heart failure, and composite microvascular complications, defined as the first occurrence of severe retinopathy, nephropathy or neuropathy. We compared the difference in those outcomes between the three groups. The 30-year cumulative incidence of CVD was 65.6% (95% CI 58.7-71.5) in the participants with diabetes, 46.1% (95% CI 48.0-53.8) in those with NGT, and 50.6% (95% CI 40.5-59.9) in those with IGT. The corresponding incidence of microvascular complications was 44.3% (95% CI 36.8-51.4), 23.1%, (95% CI 15.7-31.4), and 31.2% (95% CI 21.1-41.7). Adjusting for age and sex, those who had developed diabetes had significantly higher risks than those who had reverted to NGT for both CVD (HR = 1.57, 95% CI 1.18-2.07, P = 0.002) and composite microvascular complications (HR = 2.53, 95% CI 1.62-3.93, P &lt; 0.0001). Our results indicate that delaying the development of diabetes in people with IGT is likely to reduce the incidence of both macro and microvascular adverse outcomes.

Disclosure
Y. Chen: None. P. Zhang: None. J. Wang: None. Q. Gong: None. Y. An: 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)
1534-P: Relationship between Metabolic Syndrome Score and Insulin Resistance
Authors: ABBASI FAHIM , REAVEN PETER , KNOWLES JOSH 
Published: June 2019

Metabolic syndrome (MS) identifies previously unrecognized individuals at risk for diabetes and cardiovascular disease. Although MS is defined as requiring ≥3 of 5 categorical factors, a continuous MS score (using race/ethnicity modified Z-scores) has been proposed to better predict outcomes and track changes with interventions. As insulin resistance (IR) may link the 5 MS factors and their risk to outcomes, we hypothesized that MS score may reflect IR and its change with different therapies. We therefore determined MS score and IR by steady-state plasma glucose (SSPG) during the Insulin Suppression Test in persons without diabetes at baseline (n=611) and before and after 3 interventions: weight loss (WL; n=29), pioglitazone (PIO; n=32), and atorvastatin (ATR; n=36). Baseline MS score correlated (r value) with SSPG (0.58), similar to the correlations of BMI with SSPG (0.54) and MS score (0.55). MS score and SSPG, respectively, correlated with HDL-C (-0.63 vs. -0.33), triglycerides (TG; 0.82 vs. 0.38), systolic BP (0.38 vs. 0.22), fasting glucose (0.46 vs. 0.38), and TG/HDL-C ratio (0.87 vs. 0.42); P&lt;0.01 for all. After WL and PIO, SSPG and MS score decreased (P&lt;0.05). In contrast, after ATR, SSPG increased (P&lt;0.05), but MS score decreased (P&lt;0.01). The change (Δ) in MS score did not correlate with ΔSSPG in any of the groups, but strongly correlated with ΔTG/HDL-C ratio: WL (r=0.94), PIO (r=0.92), and ATR (r=0.79).
In conclusion, MS score correlates modestly with SSPG, but strongly with TG and TG/HDL-C ratio. Changes in MS score in response to IR-modifying therapies do not appear to reflect changes in IR but rather changes in TG. This may limit use of MS score to evaluate change in IR or disease risk.

Disclosure
F. Abbasi: None. P. Reaven: Advisory Panel; Self; Boston Heart Diagnostics. Research Support; Self; AstraZeneca, Novo Nordisk Inc. J. Knowles: None.

Funding
Doris Duke Charitable Foundation
1537-P: Impact of Obesity on Outcomes of Diabetic Ketoacidosis: A Nationwide Analysis
Authors: MUDGAL MAYURI , GOEL AKSHAY 
Published: June 2019

Background: Obesity is associated with better outcomes in diseases like myocardial infarction and heart failure, a phenomenon known as obesity paradox. However, the effect of obesity on healthcare outcomes after admission for diabetic ketoacidosis (DKA) has not been well characterized.
Objective: We aimed to explore the impact of obesity and morbid obesity on outcomes in patients hospitalized with DKA.
Methods: The National Inpatient Sample database for the year 2016 was queried. All admissions with a principal diagnosis of DKA were identified. Obesity (BMI 30-40 kg/m2) and morbid obesity (BMI &gt;40 Kg/m2) were identified using their appropriate validated ICD-10 codes. Statistical analysis was performed using STATA. The Odds ratio adjusted for age and gender was calculated for obesity and morbid obesity respectively.
Results: The study included 210,455 hospitalizations with a principal diagnosis of DKA. Out of these, 19,341 (9.19%) were obese and 7,640 (3.63%) were morbidly obese. Obese DKA patients had a longer length of stay (3.79 vs. 3.14 days, p&lt;0.001) and higher hospitalization costs ($34,643 vs. $28,976; p&lt;0.001) compared to their non-obese counterparts. There was no significant difference in the adjusted in-hospital mortality rates in DKA patients with and without obesity (0.52% vs. 0.38%, adjusted odds ratio 1.25, p=0.34). However, DKA patients who were morbidly obese had increased mortality compared to those without morbid obesity (0.72% vs. 0.38%, adjusted odds ratio 1.85, p=0.04).
Conclusion: DKA patients with obesity have a longer length of stay and higher hospitalization costs, but similar inpatient mortality rates compared to those without obesity. Morbid obesity is associated with increased mortality in DKA patients.

Disclosure
M. Mudgal: None. A. Goel: None.
154-OR: Metabolomic Profiling and Diabetes Risk in U.S. Hispanics/Latinos: Hispanic Community Health Study/Study of Latinos
Authors: CHAI JIN CHOUL , LI JUN , YU BING , ISASI CARMEN , KHAMBATY TASNEEM , HORN LINDA VAN , VIDOT DENISE C. , CASTANEDA SHEILA , BOERWINKLE ERIC , QI QIBIN 
Published: June 2019

Metabolomic profiling offers the potential to reveal metabolic pathways relevant to the development of diabetes and improve diabetes risk prediction. We examined serum metabolite profiles and their relationships with incident diabetes in Hispanic Community Health Study/Study of Latinos (HCHS/SOL). This analysis included 2010 participants (224 incident diabetes cases, 1786 control) without prevalent diabetes at baseline, aged 18-76 years with 60% female, from six Hispanic/Latino background groups in the HCHS/SOL. We profiled 624 metabolites from 8 metabolomic super-pathways. Survey Poisson regression was used to examine the associations of baseline metabolites with incident diabetes. After correcting for multiple testing (false-positive discovery rate), 134 metabolites were significantly associated with incident diabetes. For the 134 significant metabolites, network analysis identified multiple topological modules comprised of amino acids and lipids, such as BCAA metabolites, glycine, serine and threonine metabolites, sphingolipids and ceramides, monoacylglycerol and, diacylglycerol, associated with diabetes risk (Table). This study identified multiple metabolite modules related to diabetes risk in a large cohort of U.S. Hispanics/Latinos and provide new insights to metabolic pathways in the development of diabetes.

Disclosure
J. Chai: None. J. Li: None. B. Yu: None. C. Isasi: None. T. Khambaty: None. L. Van Horn: None. D.C. Vidot: None. S. Castaneda: None. E. Boerwinkle: None. Q. Qi: None.
1544-P: High Risk of Adverse Drug Reaction (ADR) in Older Adults with Type 1 Diabetes (T1D)
Authors: TOSCHI ELENA , SLYNE CHRISTINE , ATAKOV-CASTILLO ASTRID , SIFRE KAYLA , DUFOUR ALYSSA B. , CARL SAM , GREENBERG JORDAN , MUNSHI MEDHA 
Published: June 2019

The three most common drugs with high risk of ADR in older adults are insulin, anticoagulants, and opioids. As all older adults with T1D are already on insulin, we evaluated how frequently they were on other medications with high risk of ADR. In addition we assessed age-related factors associated with poor outcomes including hypoglycemia risk, and compared with younger cohort with T1D.
Methods: The T1D Exchange Clinic network database was used to evaluate older≥65 years) adults with T1D and compare them with younger (18-35 years) cohort on and frequency of severe hypoglycemia (SH) within prior 3 month, ED visit for SH and use of anticoagulants, opiates drugs.
Results: We analyzed data from 569 older (72±5 years) and 2835 younger (23±5 years) adults with T1D. The results are shown in the Table. Overall 8% of older adults had fall within past 6 months, and 11% had an episode of lost consciousness.
Conclusion: Older adults with T1D are vulnerable to ADR due to polypharmacy. The risk of poor outcomes is exacerbated by presence of multiple comorbidities, higher hypoglycemia unawareness, and greater number of severe hypoglycemia ep Conclusion: Older adults with T1D are vulnerable to ADR due to polypharmacy. The risk of poor outcomes is exacerbated by presence of multiple comorbidities, higher hypoglycemia unawareness, and greater number of severe hypoglycemia episodes.

Disclosure
E. Toschi: Advisory Panel; Self; Lexicon Pharmaceuticals, Inc. C. Slyne: None. A. Atakov-Castillo: None. K. Sifre: None. A.B. Dufour: None. S. Carl: None. J. Greenberg: None. M. Munshi: Consultant; Self; Lilly Diabetes, Sanofi.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases
1545-P: The Association between Type 2 Diabetes and Pain Severity in People with Localized Osteoarthritis: A Retrospective Study
Authors: ALENAZI AQEEL M. , OBAIDAT SAKHER M. , ALSHEHRI MOHAMMED , GRAY COREY M. , ALOTHMAN SHAIMA , RUCKER JASON L. , WAITMAN LEMUEL R. , KLUDING PATRICIA 
Published: June 2019

Objective: Type 2 diabetes (T2D) has been associated with osteoarthritis (OA). However, research related to the impact of T2D on pain severity is limited. The purpose of this study was to examine the association between T2D and pain severity in people with localized OA (LOA) (e.g., OA restricted to only one or two joints), and to explore the association between glycosylated hemoglobin (A1c) level and pain severity in people with LOA and T2D.
Methods: A retrospective review of data from a tertiary medical center was performed. Records were selected based on diagnoses codes for LOA using international classification of disease 9th and 10threvisions. Index date was set as the first diagnosis date. Pain severity, measured by a 0 to 10 numeric rating scale, was obtained and linked to the index date. T2D was defined as having two diagnostic codes for T2D or using insulin. A1c was obtained for patients with T2D within six months of the index date. Covariates of age, sex, depression, hypertension, dyslipidemia, and medications (+/- 90 days of the index date) were included in linear regression analysis. Alpha level was 0.05.
Results: Data from 819 patients (mean age = 65.08±9.77, 54.3% women) included 671 patients with LOA only (n=671) and 148 patients with LOA+T2D. T2D was significantly associated with increased pain severity (B=1.08, 95% CI 0.23 -1.93, p=0.013) after controlling for covariates. For patients with LOA+T2D with data for A1C (n=87), higher A1c was significantly associated with increased pain severity (B=0.33, 95% CI 0.01 -0.64, p=0.045) after controlling for medications.
Conclusion: This study found that T2D was associated with higher pain severity in people with LOA, and that poorer glycemic control was associated with higher pain severity in people with LOA+T2D. Only T2D was associated with pain that exceeded the clinically meaningful difference (&gt;1 score). Clinicians should consider T2D as a factor in the management of pain in people with LOA.

Disclosure
A.M. Alenazi: None. S.M. Obaidat: None. M. Alshehri: None. C.M. Gray: None. S. Alothman: None. J.L. Rucker: None. L.R. Waitman: None. P. Kluding: None.
155-OR: Are the American Diabetes Association Screening Guidelines Appropriate for the Racial/Ethnically Diverse U.S. Population? Evidence from the Multiethnic Study of Atherosclerosis
Authors: RODRIGUEZ LUIS A. , BRADSHAW PATRICK T. , SHIBOSKI STEPHEN , FERNANDEZ ALICIA , HERRINGTON DAVID M. , DING JINGZHONG , KANAYA ALKA M. 
Published: June 2019

Objective: Current ADA screening guidelines recommend screening adults with a BMI ≥25 (or ≥23 for Asian Americans) who have at least one risk factor (e.g., belonging to a race/ethnic minority group, hypertension, dyslipidemia, physical inactivity) for diabetes. We determined if these guidelines are appropriate when applied to a multi-ethnic cohort of adults free of diabetes at baseline.
Research Design and Methods: We used data from the Multi-Ethnic Study of Atherosclerosis (exams 1-5 every 1.5 to 3 years between 2002-2013). Incident cases of diabetes were defined as fasting glucose ≥ 126 mg/dL and/or use of any diabetes medication. We used multivariable Weibull regression adjusting for age, sex, education, diet, exercise, hypertension, and dyslipidemia to estimate the differential association between BMI and incident diabetes by race/ethnicity.
Results: Among 4,541 MESA participants without prevalent diabetes, 1,860 were white, 539 Chinese American, 1,167 African American, and 975 Hispanic. In a median 9.1 years of follow-up, 557 new cases of diabetes occurred (166 in whites, 66 in Chinese Americans, 169 in African Americans, and 156 in Hispanics). Incidence rates were 11.4 (95% CI 9.8 to 13.2), 15.9 (12.5 to 20.3), 19.9 (17.1 to 23.1) and 22 (18.8 to 25.7) per 1,000 person-years among whites, Chinese Americans, African Americans and Hispanics, respectively. The race/ethnic-specific BMI for participants without any additional diabetes risk factors, compared to whites with a BMI of 25 and one or more diabetes risk factor was 29.2 in whites, 22.8 in Chinese Americans, 26.2 in African Americans and 25.4 in Hispanics.
Conclusions: Our findings show that the current American Diabetes Association diabetes screening guidelines are appropriate for the ethnically and racially diverse populations, and suggest that a higher BMI cut point, such as 29, may be appropriate for screening whites without other risk factors.

Disclosure
L.A. Rodriguez: None. P.T. Bradshaw: None. S. Shiboski: None. A. Fernandez: None. D.M. Herrington: None. J. Ding: None. A.M. Kanaya: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (F31DK115029)