bluuebunny/crossref_metadata_2025_split huggingface dataset:
1506-P: Breast Cancer as a Risk Factor for New Diabetes
Authors: SHAH REEMA , GERSTEIN HERTZEL , KOMJÁTHIN SZÉPLIGETI SZIMONETTA , SÔRENSEN HENRIK T. , THOMSEN REIMAR W. 
Published: June 2019

While diabetes is an important risk factor for breast cancer, less is known regarding whether a breast cancer diagnosis is associated with increased risk of subsequent diabetes. We therefore assessed the effect of a breast cancer diagnosis on incident diabetes, using population-level data from Danish healthcare registries during 2005-2016. Our study population comprised 33,909 women aged &gt;50 years with new-onset breast cancer and 313,998 comparison cohort members matched by age and the breast cancer diagnosis date (index date) from the general population, all with no prior history of cancer or diabetes. Women with breast cancer and their comparison cohort members were followed for up to 12 years, to ascertain a first occurrence of glucose-lowering drug treatment or hospital-diagnosed diabetes. The hazard of breast cancer for subsequent diabetes was computed using Cox proportional hazard models, adjusting for a range of comorbidities and medications. Mean age at baseline was 66.0 in cancer patients and 65.8 in the comparison cohort. The rate of developing diabetes was 15% greater in breast cancer patients than in the comparison cohort during the first year after breast cancer diagnosis/index date (adjusted hazard ratio [aHR] 1.15, 95% confidence interval [CI] 1.01-1.30). During total follow-up (median 5.2 years), the diabetes rate was 23% greater in women with breast cancer (aHR 1.23, 95% CI 1.16-1.30), corresponding to 8.4 new cases of diabetes per 1000 women per year vs. 6.8 among comparison cohort members. Breast cancer patients were more likely to be treated with an insulin-based regimen (4.8%) compared to comparison cohort members (2.1%). Our findings suggest that breast cancer is an important risk factor for diabetes. Breast cancer patients may benefit from targeted screening for diabetes and counseling regarding risk factor modification.

Disclosure
R. Shah: None. H. Gerstein: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Sanofi. S.K. Szépligeti: None. H.T. Sôrensen: None. R.W. Thomsen: None.
1511-P: Trend in the Prevalence of Diabetes between 2002-2009 in Populations in Qingdao, China
Authors: ZHANG LEI , GAO WEIGUO , WANG NA , WANG JUN , YIN XIAOYAN , ZHU YAMEI , DONG YANHU 
Published: June 2019

The current study aims to determine the secular trend of prevalence of type 2 diabetes and prediabetes and risk factors for diabetes from 2002 to 2009. We conducted 3 population-based surveys for diabetes in individuals aged 35-74 years in Qingdao in 2002, 2006 and 2009, respectively, with random-sampling approach. The sample size was 1792, 4549 and 4310 in 2002, 2006 and 2009, respectively. We performed a questionnaire-based survey to collect general information. All participants underwent standardized 2-h 75-g oral glucose tolerance tests (OGTTs). The 1999 WHO diagnostic criteria for diabetes and prediabetes was applied. Age-standardized prevalence of diabetes was calculated. Multiple non-conditional logistic regression were applied to analyze the risk factors for diabetes, taking diabetes as the dependent variable. In 2002, the age-standardized prevalence of diabetes was 12.32%, the corresponding prevalence was 16.57% and 18.01%, respectively, in 2006 and 2009. The prevalence of diabetes increased from 2002 to 2009 (p&lt;0.05). The age-standardized prevalence of prediabetes in 2002, 2006 and 2009 was 16.18%, 24.56% and 28.25%, respectively (P for trend &lt; 0.05). Multiple non-conditional logistic regression analysis showed that the risk factor for diabetes were age, waist, systolic blood pressure (SBP), total cholesterol, triglyceride, and family history of diabetes in both 2002 and 2006. The risk factor for diabetes included age, waist, SBP, total cholesterol, triglyceride, and family history of diabetes in 2009. High density lipoprotein cholesterol was negatively associated with increased risk for diabetes. The prevalence of diabetes and prediabetes in Qingdao increases from 2002 to 2009, implying an epidemic of diabetes in this area. The common risk factors contributing to the increasing trend are age, waist, SBP, total cholesterol, triglyceride, and family history of diabetes.

Disclosure
L. Zhang: None. W. Gao: None. N. Wang: None. J. Wang: None. X. Yin: None. Y. Zhu: None. Y. Dong: None.
1523-P: Variation in Diabetes Prevalence by Sex and Weight in Middle-Aged Chinese and Filipino Adults
Authors: GU KRISTINE , GORDON NANCY P. , CHANDRA MALINI , LAU GENE , GONZALEZ JOEL R. , LO JOAN C. 
Published: June 2019

Background: Contemporary data comparing weight status and diabetes (DM) prevalence among U.S. East Asians and Filipinos are limited.
Methods: Among 23,050 Chinese and 28,201 Filipinos aged 45-64 years (mean age 55±6) with a 2016 outpatient visit in a U.S. integrated healthcare delivery system, body mass index (BMI) and DM prevalence (based on clinical diagnosis and pharmacotherapy) were ascertained. BMI was classified using Asian-specific thresholds: healthy or underweight (BMI &lt;23), overweight (23-27.4) and obese (≥27.5 kg/m2). Differences were examined by subgroups and log-binomial regression was used to examine the independent association of ethnicity and DM risk.
Results: Among Chinese women (14,871) and men (8,179) and Filipino women (18,406) and men (9,795), overweight/obesity was higher in men vs. women and Filipino vs. Chinese (Figure, BMI distribution). Obesity was highest in Filipino men (50%). DM prevalence was highest in those with obesity; however, Filipinos of both sexes had higher DM prevalence across all weight categories (Figure) compared to Chinese, with a relative risk of 1.7 (CI 1.6-1.8), adjusting for age, BMI and sex.
Conclusion: Filipino adults have substantially higher BMI and independently higher risk of DM compared to Chinese adults. While limited to adults receiving healthcare, the data highlight the need for heightened DM surveillance and targeted care in high risk ethnic populations.

Disclosure
K. Gu: None. N.P. Gordon: None. M. Chandra: None. G. Lau: None. J.R. Gonzalez: None. J.C. Lo: Research Support; Self; Amgen Inc. Research Support; Spouse/Partner; GlaxoSmithKline plc., Novartis Pharmaceuticals Corporation, Sanofi-Aventis. Research Support; Self; Sanofi-Aventis.

Funding
Kaiser Permanente Northern California
1531-P: Spontaneous Ketonuria Is Associated with Reduced Incidence of Diabetes
Authors: CHO SUNG J. , LEE INKUK , LEE SANG BAE , KANG EUN SEOK , FERRANNINI ELE , LEE YONG-HO , KIM GYURI , CHA BONG-SOO 
Published: June 2019

Objective: Ketones may be regarded as a thrifty fuel for peripheral tissues, but their clinical prognostic significance still remains unclear. We investigated the association between spontaneous fasting ketonuria and incident diabetes in conjunction with changes in metabolic parameters in a large population-based, observational study.
Research Design and Methods: We analyzed a total of 8,703 individuals free of diabetes at baseline in the Korean Genome and Epidemiology Study, a community-based, 12-year prospective study. Subjects with (n=195) or without fasting ketonuria were 1:4 matched by propensity score. Incident diabetes was defined as: fasting plasma glucose ≥126 mg/dL, 2-hour glucose ≥200 mg/dL on biennial 75g oral glucose tolerance test, or current antidiabetic medication. Using Cox regression models, hazard ratios for developing diabetes associated with the presence of ketonuria at baseline were analyzed.
Results: Over 12 years, of the 925 subjects in the propensity score matched cohort, 190 (20.5%) developed diabetes. The incidence rate of diabetes was significantly lower in subjects with spontaneous ketonuria compared to those without ketonuria (adjusted hazard ratio 0.64 [95% confidence interval=0.42-0.99]. This result was replicated in the whole cohort (HR 0.67 [95% CI: 0.46-0.98] after multivariate adjustment). During follow-up, subjects with ketonuria at baseline maintained lower 1-hour and 2-hour glucose levels, and a higher insulinogenic index during follow-up despite comparable baseline values.
Conclusions: The presence of spontaneous fasting ketonuria was significantly associated with a reduced incidence rate of diabetes, independently of metabolic parameters. Our findings suggest spontaneous fasting ketonuria is a stable phenotype and a novel signature in the modulation of glucose metabolism.

Disclosure
S.J. Cho: None. I. Lee: None. S. Lee: None. E. Kang: None. E. Ferrannini: None. Y. Lee: None. G. Kim: None. B. Cha: None.
1536-P: Parametric Survival Analysis of Complications from Type 1 Diabetes
Authors: BARBOSA CAROLINA , MACK NICOLE , BOBASHEV GEORGIY , KING GRANT A. , LIU YIYAN , HILSCHER RAINER , NEUWAHL SIMON , HOERGER THOMAS J. 
Published: June 2019

Aim: To develop novel models of the risk of fatal and non-fatal complications for individuals with type 1 diabetes (T1D). Models used two 30 years’ follow-up studies: Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) and Epidemiology of Diabetes Complications (EDC).
Method: Models were developed for: Microalbuminuria, Macroalbuminuria, End-Stage Renal Disease, Impaired Glomerular Filtration Rate, Non-proliferative Diabetic Retinopathy, Proliferative Diabetic Retinopathy, Clinically Significant Macular Edema, Ketoacidosis, Hypoglycemia, Ulcers, Diabetic Peripheral Neuropathy, Amputations, Cardiovascular (CVD) Major Adverse Cardiac Event (MACE), CVD non-MACE, Death after CVD MACE, Death after CVD non-MACE, and Death with no history of CVD. Each model considered 44 risk factors, including demographics, time-varying clinical measures, and other T1D complications. Bivariate associations, followed by stepwise regression, were used for variable selection. Interval-censored Weibull and Gompertz survival models were chosen for non-fatal and fatal complications, respectively. Final models combined optimal statistical prediction and expert knowledge for model interpretability.
Results: All models included age, gender, diabetes duration, and HbA1C, with HbA1c significantly increasing the risk of most complications. Across all models, the highest predictor of a complication was history of another complication(s). Blood pressure (e.g., systolic, diastolic), pulse rate, and lipid variables (e.g., triglycerides, LDL, HDL, total cholesterol) were significantly predictive of most complications. Cumulative hazard plots comparing predicted and actual hazards indicated good accuracy of prediction for all models.
Conclusion: Our risk equations highlight the importance of accounting for the time-varying nature of many risk factors and the impact that history of diabetes complications has on a different complication.

Disclosure
C. Barbosa: None. N. Mack: None. G. Bobashev: None. G.A. King: None. Y. Liu: None. R. Hilscher: None. S. Neuwahl: None. T.J. Hoerger: Research Support; Self; Sanofi.

Funding
Centers for Disease Control and Prevention
154-LB: Accelerating Clinical Development of Janagliflozin, a Novel Antidiabetic Drug, Using Model-Informed Drug Development Strategy
Authors: LIU DONGYANG , SONG LING , WANG XIAOXU , LIU XU , CAO FANGRUI , LIU HONGZHONG , DING YANHUA , XIAO XINHUA , JIANG JI , HU PEI 
Published: June 2019

Objectives: To accelerate clinical development of Janagliflozin (JANA), an active inhibitor of sodium-glucose cotransporter 2 (SGLT2), using model-informed drug development (MiDD) strategy.
Methods: Firstly, after receiving the SAD PK and PD (change from baseline in urinary glucose excretion, ∆UGE) profiles in healthy subjects (HS), a PK/PD model was developed and optimized by MAD data in HS. Secondly, we projected PK/∆UGEc/FPG/HbA1c profiles based on HS data using the established quantitative relationship between HS and T2DM patients, where ∆UGEc, FPG corrected ∆UGE, was a novel translational biomarker. Thirdly, the predicted PK/PD profiles were confirmed in a 2-week MAD study in T2DM patients and the dose-HbA1c relationship in T2DM patients after 6-month treatment was predicted.
Results: The predicted PK/PD profiles of JANA in T2DM patients were within 2-fold of the observed data. Prediction performance was showed in Figure 1 and a Phase III trial was allowed after the 2-week MAD study.
Conclusion: This MiDD strategy exhibited a good capability to accelerate early phase clinical development of JANA after confirmation from short-term clinical trials.

Disclosure
D. Liu: Research Support; Self; XuanZhu Pharma Co., Ltd., Jinan, Shandong, China. L. Song: Research Support; Self; XuanZhu Pharma Co., Ltd., Jinan, Shandong, China. X. Wang: Research Support; Self; XuanZhu Pharma Co., Ltd., Jinan, Shandong, China. X. Liu: Research Support; Self; XuanZhu Pharma Co.Ltd,Jinan,Shandong,China. F. Cao: Research Support; Self; XuanZhu Pharma Co., Ltd., Jinan, Shandong, China. H. Liu: Research Support; Self; XuanZhu Pharma Co., Ltd., Jinan, Shandong, China. Y. Ding: None. 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.

Funding
XuanZhu Pharma Co., Ltd.
1543-P: Trends in U.S. Diabetes Care Management, 1999-2016
Authors: MERCADO CARLA , BULLARD KAI M. , ALI MOHAMMED K. , IMPERATORE GIUSEPPINA , SAYDAH SHARON , GREGG EDWARD 
Published: June 2019

Clinical guidelines and national programs recommend control of ABCS risk factors [glycohemoglobin (A1c), Blood pressure, Cholesterol, and Smoking] to reduce diabetes-related comorbidities and mortality. We investigated changes in meeting the ABCS goals (A1c &lt;8.0%, blood pressure (BP) &lt;140/90 mmHg, non-HDL cholesterol &lt;160 mg/dL, and current non-smoker) among U.S. adults with diagnosed diabetes (DM). Proportion and changes of adults aged ≥18 years with DM and who met each and all ABCS goals were estimated using data on 5,534 participants from the National Health and Nutrition Examination Survey, 1999-2016. In U.S. adults with DM from 1999-2004 to 2011-2016, there was an increase in the proportion meeting the goals of: BP (67% to 73%, p=0.003), non-HDL cholesterol (59% to 77%, p&lt;0.001), and current non-smoking (74% to 81%, p&lt;0.001). However, meeting the A1c goal increased (p=0.001) from 70% in 1999-2004 to 78% in 2005-2010 then decreased (p=0.004) to 71% in 2011-2016 (A1c goal 1999-2004 versus 2011-2016, p=0.53). The proportion of adults with diabetes meeting all four ABCS risk factors goals significantly increased from 18% in 1999-2004 to 32% in 2011-2016 (p&lt;0.001). Control of risk factors for DM complications has improved during 1999-2016 with about a 15% point increase of U.S. adults with DM meeting all four ABCS risk factors goals. Thus, long-term improvements in ABCS appear to be continuing with the exception of A1c levels.

Disclosure
C. Mercado: None. K.M. Bullard: None. M.K. Ali: None. G. Imperatore: None. S. Saydah: None. E. Gregg: None.
1548-P: High Prevalence of Glaucoma and Cataract with Uncommon Diabetic Retinopathy in Haitian Youth with Diabetes
Authors: BAPTISTE EDDY JEAN , LARCO PHILIPPE , CHARLES LARCO MARIE-NANCY , VON OETTINGEN JULIA E. , ROCOURT FRANCOISE , HUDICOURT BRIGITTE , MOISE KEDDY , PAUL RODOLPHE , CHARLES RENE 
Published: June 2019

Aim: Data on glaucoma and cataract in Afro-Caribbean youth with diabetes are scarce. We sought to determine the prevalence of ocular complications and their risk factors in a group of Haitian youth with diabetes.
Methods: A cross-sectional study was conducted on youth aged 0-25 years with insulin-treated diabetes from one diabetes clinic in Haiti. We performed on both eyes visual acuity, Ishihara test, tonometry by Goldmann applanation, corneal pachymetry, slit lamp, refraction, gonioscopy, dilated fundoscopy and retinography, Humphrey visual field (VF), and spectral domain optical coherence tomography (Cirrus SD-OCT). We carried out Michigan Neuropathy Screening Instrument and neurothesiometer tests, and measured hemoglobin A1c (HbA1c), fasting lipid profile, and spot urinary albumin-to-creatinine ratio (UACR) twice 6 weeks apart. Primary open-angle glaucoma (POAG) was based on characteristic changes in: 1- optic disc, 2- retinal nerve fiber layer/combined macular ganglion cell and inner plexiform layers, 3- VF. Possible, suspected and overt POAG were diagnosed in the presence of 1, ≥ 2 and ≥ 2 criteria plus visual acuity loss, respectively.
Results: We enrolled 51 patients: Age 18.4 ± 4.7 y, male 52.9%, diabetes duration 5.0 ± 3.2 y, HbA1c 11.2 ± 2.9%, normal lipid profile. Background diabetic retinopathy (DR), cataract, diabetic peripheral neuropathy, and increased UACR were found in 2.0%, 13.7%, 29.4%, and 7.8%, respectively. No color vision impairment was detected. Intraocular pressure was 17.3 ± 3.7 (R) and 17.1 ± 2.8 (L) mmHg. Ocular hypertension was found in 5.9%. POAG was overt in 3.9% and suspected in 17.7%. On regression analyses, none of the studied variables predicted POAG or cataract.
Conclusion: POAG and cataract are common and precocious in Haitian youth with diabetes, without detectable risk factors. DR is uncommon. Comprehensive eye examination with VF and OCT when available is suggested early after diabetes diagnosis.

Disclosure
E. Jean Baptiste: None. P. Larco: None. M. Charles Larco: None. J.E. von Oettingen: None. F. Rocourt: None. B. Hudicourt: None. K. Moise: None. R. Paul: None. R. Charles: None.
1556-P: Gender Differences in Glycemic Control, Microvascular and Macrovascular Complications in Hospitalized Patients with Diabetes
Authors: PATEL NEETI , PINKHASOVA DIANA , DONIHI AMY , FRENCH ESRA KARSLIOGLU , SIMINERIO LINDA M. , DELISI KRISTIN , HLASNIK DEBORAH S. , KORYTKOWSKI MARY T. 
Published: June 2019

Gender differences have been described for glycemic control and prevalence of diabetes related complications in the outpatient setting but have not been examined in the hospitalized population. To address this, we investigated gender differences in demographics, glycemic control and variability (GV), macrovascular and microvascular complications, and admission diagnosis in non-critically ill hospitalized patients with a secondary diagnosis of diabetes recruited for the Readmission and Comprehension of Diabetes Education at Discharge (ReCoDED) Study. To date, 111 men and 87 women have been recruited, with the majority having type 2 DM (86 vs. 79%). Participants age (men vs. women) was 60.6 ± 11.7 vs. 57.6 ± 11.8 years, BMI 32.2 ± 8.4 vs. 32.1 ± 10.6 kg/m2, systolic (SBP) 136 ± 26 vs. 127 ± 23 mmHg, diastolic (DBP) 77 ± 13 vs. 75 ± 14 mmHg, HbA1c 8.0 ± 2.3 vs. 8.3% ± 2.5%, and DM duration 14.5 ± 10.4 vs. 14.1 ± 11.6 years. Race, education, and employment were similar. Men had more retinopathy (23 vs. 16%) and nephropathy (40 vs. 28%), but not neuropathy (60 vs. 63%). Women had a lower prevalence of CAD (49 vs. 36%), but a similar prevalence of CHF (37 vs. 37%), stroke (15 vs. 18%), and PVD (18 vs. 17%). The most frequent admission diagnoses were CVD (37 vs. 22%) and infection (10 vs. 19%). Mean blood glucose (BG) (198 ± 51 vs. 200 ± 54 mg/dl), GV (177 ± 80 vs. 182 ± 112 mg/dl), frequency of hypoglycemia (BG &lt; 70 mg/dl) and hyperglycemia (BG &gt;250 mg/dl) were similar in the 48 hours prior to discharge. Length of stay was 7.8 ± 6.9 vs. 8.3 ± 7.4 days.
In summary, this gender-based description of glycemic control and prevalence of diabetes-related complications in an inpatient population demonstrates that hospitalized women with DM have fewer microvascular complications, a lower prevalence of CAD but a similar prevalence of CHF, stroke and PVD when compared to men, despite similar BMI and DM duration. These findings will be examined as a risk factor for hospital readmissions in this ongoing study.

Disclosure
N. Patel: None. D. Pinkhasova: None. A. Donihi: None. E. Karslioglu French: None. L.M. Siminerio: None. K. Delisi: None. D.S. Hlasnik: None. M.T. Korytkowski: None.
1559-P: Differential Effects of Type 1 (T1D) and Type 2 Diabetes (T2D) on the Growth Hormone (GH)-Insulin-Like Growth Factor (IGF) Axis in Youth
Authors: SNELL-BERGEON JANET K. , REUSCH JANE E.B. , BAUMGARTNER AMY D. , CREE-GREEN MELANIE , NADEAU KRISTEN J. 
Published: June 2019

T1D and T2D are characterized by hyperglycemia and insulin resistance (IR), but in T1D the IR occurs even in the absence of metabolic syndrome features. The loss of β-cell insulin secretion in T1D results in lower portal and thus hepatic insulin concentrations in T1D than in T2D or nondiabetic (non-DM) individuals, affecting the GH-IGF axis, as exogenous insulin is subcutaneously delivered in T1D. In this study, we examined how the GH-IGF axis differs by diabetes type, and how it relates to IR. This study included youth (mean age 15±2 years, 37% female) with T1D (n=16), T2D (n=27) and non-DM controls (n=38). A morning fasting blood sample was obtained to measure GH, IGF-1, and IGF binding proteins (IGF BP-1, 2 and 3). Hyperinsulinemic euglycemic clamps were performed to measure glucose infusion rate (GIR), an estimate of skeletal muscle IR, and serum free fatty acid (FFA) suppression. GH, IGF BP-1 and IGF BP-2 were higher in T1D compared to non-DM youth (Figure). Higher IGF BP-3 was associated with lower GIR (more muscle IR) in all youth, but lower IGF BP-1 and 2 were associated with lower GIR in non-DM youth only. Higher GH, IGF BP-1 and IGF BP-3 were associated with less FFA suppression (more adipose IR) in T1D youth only. The GH-IGF-1 axis is altered and is differentially correlated to IR in T1D versus T2D. These data provide clues regarding the unique phenotype of IR in T1D.

Disclosure
J.K. Snell-Bergeon: None. J.E.B. Reusch: Board Member; Self; American Diabetes Association. Other Relationship; Self; Merck & Co., Inc. A.D. Baumgartner: None. M. Cree-Green: None. K.J. Nadeau: None.

Funding
American Diabetes Association (7-13-CD-10 to J.K.S-B.)