bluuebunny/crossref_metadata_2025_split huggingface dataset:
Free Thyroxin T4 in Early Pregnancy and Risk of Gestational Diabetes Mellitus
Authors: LI PING , LIN SHUO , LI LING , OUYANG LIPING , FAN JIANHUI 
Published: June 2018

Our study aims to evaluate the correlations between thyroid hormone levels in early pregnancy and the incidence of gestational diabetes mellitus (GDM). A total of 2112 pregnant women were recruited from our hospital, Guangzhou, China, from June 2016 to June 2017. Fasting plasma glucose (FPG), Thyrotropin (TSH), free T4 (FT4), and thyroid peroxydase antibody (TPO-Ab) were measured at 9-14 weeks’ gestation (first trimester) and 75-g OGTT (24-28 weeks’ gestation) were performed in each subject. Diagnosis of GDM was made by the IADPSG guideline (2010). All subjects had median age of 30 years (interquartile range:27-34 years). Two hundred and twenty four subjects (10.6%) were diagnosed as GDM. GDM women had older age and higher FPG(P&lt;0.05). The level of free T4 (FT4) in GDM women was similar than that in non-GDM women (16.45±3.42pmol/L and 16.80±3.46 pmol/L, respectively, P=0.152). No difference was observed in the levels of TSH and TPO-Ab between GDM women and non-GDM women (all P&gt;0.05). The prevalence of GDM in subjects among different quartiles of FT4 levels were 11.9%, 11.5%, 9.5% and 9.5% from the first to fourth quartile (P=0.429,χ2=2.766). By using logistic regression, FT4 in the first trimester odds ratios for GDM were not significant: OR 0.970 [95% CI 0.931-1.011] (unadjusted) and 0.960[95% CI 0.920-1.002] (adjusted for age, TSH, TPO-Ab). Our results indicated the level of FT4 in the first trimester may not have strong correlation with incidence of GDM.

Disclosure
P. Li: None. S. Lin: None. L. Li: None. L. Ouyang: None. J. Fan: None.
GLP-1 Receptor Agonist Liraglutide Increased IVF Pregnancy Rates in Obese Women with PCOS and Previous Poor Response to First-Line Reproductive Treatments
Authors: JANEZ ANDREJ , JENSTERLE MOJCA 
Published: June 2018

Objective: GLP-1 has been investigated in regulation of reproductive system in animal models. Current observations suggest that it directly regulates kisspeptin and GnRH expression and that ovaries express GLP-1 mRNA.
Aim: To evaluate the impact of low dose liraglutide in combination with metformin compared to metformin alone on IVF pregnancy rate (PR) and cumulatively PR (IVF and spontaneous) in infertile obese women with PCOS who had been previously poor responders regarding weight reduction with lifestyle modification and resistant to first line reproductive treatments.
Design/Participants/Methods: A prospective randomized open-label study was conducted with 28 infertile obese PCOS patients (aged 31,07±4,75 years, BMI 36,7±3,5 kg/m2, mean ± SD). They were assigned to metformin (MET) 1000 mg BID or combined MET 1000 mg BID and low dose liraglutide 1.2 mg QD s.c. (COMBI) for 12 weeks. Ovarian stimulation protocol was started after 4-week medication free period.
Results: Patients in MET lost on average 7,0±6,0 kg (P&lt;0.001) compared with 7,5± 3,9 kg loss in COMBI group (P&lt;0.001), with no significant between-treatment difference (P=0,103). All treatment interventions resulted in significant reduction of visceral adipose tissue as assessed by DXA and reduction of HOMA-IR (p&lt;0.001), with no significant difference regarding the treatment employed. After intervention, PR per ET was significantly higher in COMBI (85,7%) compared with MET (28,6%) (P=0.03). Moreover, cumulatively PR in time frame of 12 months in COMBI was 69,2% compared to 35,7% in MET.
Conclusion: Short-term preconception intervention with low dose liraglutide as an add on to metformin was superior to metformin alone in increasing PR per ET and cumulative PR in infertile obese PCOS, despite comparable weight reduction in both arms. Potential direct crosstalk between GLP-1 and reproductive system needs further exploration.

Disclosure
A. Janez: None. M. Jensterle: None.
Frailty and Health Care Utilization among Community-Dwelling Older Patients with Diabetes Mellitus
Authors: PRIYADARSHNI SHIVANI , NELLURI SRUTHI , RAHAMAN ZUBAIR , MINTZER MICHAEL J. , DANG STUTI , VALENCIA WILLY MARCOS , RUIZ JORGE G. 
Published: June 2018

Frailty is a state of vulnerability to stressors resulting in higher morbidity, mortality and healthcare utilization in older adults. Frailty impact on healthcare utilization in patients with T2DM is not well characterized. The aim of this study was to determine in a community cohort of older patients (65 years and older) with type 2 diabetes mellitus (T2DM) whether frailty is associated with healthcare utilization. Community dwelling Veterans with T2DM underwent frailty assessment with the validated 5-item FRAIL Scale (frail ≥ 3; pre-frail 1-2; robust 0 points) between January 2016 and December 2017. At one year follow-up, we aggregated data on patients with a least one primary care visit, hospitalization and/or ER visit. Binomial logistic regression was used to examine the association between frailty and emergency department (ED) visits or hospitalizations. Among 868 patients (mean age 74 ± 7 years, 98% men), 31% were robust, 36% prefrail, and 33% frail. Over a mean follow-up period of 274 ± 90 days, 1221 primary care visits, 396 ED visits, and 219 hospitalizations occurred. Frailty was associated with an increased risk for ED visits (odds ratio: 1.73, 95% CI 1.19-2.52) and an increased risk for hospitalizations (odds ratio: 3.88, 95% CI 1.18-8.22). The population-attributable risk associated with frailty was 51% for ED visits and 40% for hospitalizations.
In conclusion, frailty is a strong predictor of ED visits and hospitalizations in older patients with T2DM. As frailty is a potentially treatable condition, it should be part of the clinical evaluation of patients with T2DM.

Disclosure
S. Priyadarshni: None. S. Nelluri: None. Z. Rahaman: None. M.J. Mintzer: None. S. Dang: None. W. Valencia: None. J.G. Ruiz: None.
Cognitive Impairment and Glycemic Status among U.S. Adults
Authors: CASAGRANDE SARAH , COWIE CATHERINE C. 
Published: June 2018

Several studies have shown that cognitive impairment is a complication of diabetes, however, this association has not been assessed in an older, nationally representative U.S. sample. This study determined the association between diabetes and cognitive function overall and by participant characteristics among adults age ≥60 years in the 2011-2014 National Health and Nutrition Examination Surveys (N=1,552). Participants had diabetes if they reported a physician diagnosis of diabetes, had an A1c ≥6.5%, or fasting plasma glucose ≥126 mg/dL. Cognitive function was assessed by three tests: Consortium to Establish a Registry for Alzheimer’s Disease Word Learning subtest (CERAD W-L), which measures the ability to learn new verbal information; the Animal Fluency test, which measures executive function; and the Digit Symbol Substitution Test (DSST), which measures working memory. The standardized effect size (Cohen’s d; value ≥0.2-&lt;0.5=small, ≥0.5-&lt;0.8=moderate, ≥0.8=large) for each cognitive test was determined for those with diabetes vs. those without diabetes. Overall, adults with diabetes performed consistently lower on the cognitive assessments compared to those without diabetes. The overall effect size was moderate for the CERAD W-L and DSST assessments (Cohen’s d range -0.44 to -0.51), and was small for the Animal Fluency score (Cohen’s d = -0.33) for those with diabetes vs. those without. For the CERAD W-L, the effect size was greatest (≥ -0.50) for youngest ages (60-69 years), non-Hispanic Asians, never smokers, those with normal weight, and no hypertension, compared to counterparts. For the DSST assessment, the effect size was greatest (≥ -0.50) for those age 60-69 years, Mexican Americans, females, former or never smokers, those who did not consume alcohol, those who exercised, those with hyperlipidemia, and those without hypertension.
In conclusion, diabetes was associated with a lower ability to learn new verbal information and poorer working memory but had less of an effect on executive function.

Disclosure
S. Casagrande: None. C.C. Cowie: None.
High Performance Two-Step Model for Early Detection and Management of Type 2 Diabetes Risk in the Workplace
Authors: ZULUETA MIRELLA , DIABETES PATIA 
Published: June 2018

Background: Identification of T2D high risk individuals is key for early implementation of prevention interventions. Employers could be instrumental in reversing T2D risk for a majority of its population via improved predictive power risk detection tools.
Objective: To test the feasibility of a two-step screening model, based on the combination of a risk test score and Hb1Ac, for early detection and management of risk in an employee population.
Methodology: The model was tested in nondiabetic employees of a large employer in Mexico. As a first step, a T2D risk score was computed for each participant via a multivariate logistic regression model that integrates 16 T2D genetic variants, T2D parental history and BMI. Subjects with a risk score above certain cut points were considered medium and high-risk individuals. As a second step, medium and high-risk individuals identified in the first step were tested for levels of Hb1Ac. Subjects with Hb1Ac of ≥5.7% were recommended to join the employer’s diabetes prevention program.
Results: 5,201 of 7,480 (69.5%) employees (46% women, 54% men) aged 18-60 years and free of diabetes agreed to participate in the screening program. 5,201 samples (buccal swabs) for genotyping and corresponding data (demographics, personal and family medical history) were collected on-site at 36 branch offices from 10/2017 to 12/2017 in Mexico City, Monterrey and Guadalajara. Participants risk scores stratified as low (52%), medium (34%) or high risk (14%). Of the medium and high-risk individuals, 31% showed elevated Hb1Ac (≥5.7%), and were suggested to join the employer’s diabetes prevention program.
Conclusions: Our study initiates a data-driven discussion of how employers can radically support employee diabetes prevention and lower healthcare costs via improved predictive power tools. A two-step system, based on the combination of a risk test score and Hb1Ac, may be a useful tool for an effective identification of high risk individuals in a workplace setting.

Disclosure
M. Zulueta: Employee; Self; Patia, Patia.
Obese and Overweight Ex-smokers Live Longer Overall but Spend More Years with Type 2 Diabetes than Normal Weight Smokers
Authors: ASLLANAJ ERALDA , VOORTMAN TRUDY , GLISIC MARIJA , FRANCO OSCAR , MUKA TAULANT 
Published: June 2018

Objectives: To investigate the association between smoking status, total life expectancy and the number of years lived with and without diabetes. In addition, to examine whether total life expectancy and life expectancy with and without diabetes is different between normal-weight smokers and overweight/obese ex-smokers.
Methods: The study included 10,739 participants aged 45+ years from the population-based Rotterdam Study. We developed a multistate life table to calculate life expectancy for individuals who were (i) current, former and never smokers (reference) as well as for (ii) normal-weight current smokers (reference), overweight and obese ex-smokers.
Results: Compared to never smoker, current male smoker lived 6.6 (95% confidence interval -8.4 to -3.9) years fewer overall, of which 6.0 (-7.8 to -3.0) years fewer without diabetes and 0.6 (-1.8 to 1.3) years longer with diabetes; whereas current female smoker lived 5.1 (-8.4 to -3.9) years fewer overall of which 5.4 (-7.8 to -3.0) years fewer without diabetes and 0.3 (-1.8 to 1.3) years more with diabetes. Additionally, obese and overweight former male smoker lived 4.8 (6.1 to 8.4) and 4.0 (6.3 to 8.4) years longer than current normal-weight smoking men, of which 0.1 (-3.5 to 6.2) and 2.4 (0.7 to 6.4) years more without diabetes and, 4.7 (1.3 to 10.4) and 1.6 (1.1 to 6.0) years longer with diabetes, respectively. Among women, obese and overweight ex-smokers lived 9.2 (6.1 to 8.4) and 8.0 (6.3 to 8.4) years longer than their current normal-weight counterparts, of which 1.3 (-3.5 to 6.2) and 3.4 (0.7 to 6.4) years longer without diabetes and 7.8 (1.3 to 10.4) and 4.6 (1.1 to 6.0) years longer with diabetes, respectively.
Conclusions: We found that the benefits of quitting smoking outweigh the risk of weight gain associated with smoking cessation in terms of life expectancy and years of life lived with and without diabetes.

Disclosure
E. Asllanaj: None. T. Voortman: None. M. GLisic: None. O. Franco: None. T. Muka: Employee; Self; Novo Nordisk A/S.
Estimating Cardiometabolic Risk Using Existing Scoring Systems
Authors: GURKA MATTHEW J. , FILIPP STEPHANIE L. , PEARSON THOMAS A. , DEBOER MARK D. 
Published: June 2018

While useful for prediction of cardiovascular disease (CVD), risk estimators such as the Framingham Risk Score (FRS) and the Atherosclerotic CVD (ASCVD) calculator have not been evaluated for prediction of incident type 2 diabetes (T2D) and progression to CVD, or for how changes in scores over time predict future risk. We evaluated these scores alongside a metabolic syndrome (MetS) severity Z-score (http://mets.health-outcomes-policy.ufl.edu), using data from 8,026 participants in the Atherosclerosis Risk in Communities (ARIC) study without T2D or CVD by Visit 2. We characterized individuals by incident T2D by V4 (mean years from V1 = 8.9), and whether they had an adjudicated CVD event by V4 ("early" CVD) or a "late" CVD event (after V4; mean total follow-up = 20.7 years). For each disease category, we estimated mean scores at V1 and changes in score, V2-V1 (Figure 1). MetS severity distinguished those developing T2D vs. not and future CVD vs. not. FRS and ASCVD distinguished CVD development in each incident T2D group, but trends were not as discernible across T2D status. We then standardized FRS and ASCVD scores to allow for comparisons of OR’s, using logistic regression to model odds of each disease category by each score, including V1 and the (V2-V1) change (OR’s in Figure 1). While CVD scores predict future CVD, MetS severity, based both on baseline levels and change in score, better predicts individuals who go on to develop T2D and further progress to CVD.

Disclosure
M.J. Gurka: None. S.L. Filipp: None. T.A. Pearson: Consultant; Self; Bayer AG. M.D. DeBoer: None.
The Extent of Severe Periodontal Disease as a Predictor of Cardiovascular Complications and Mortality in Type 1 Diabetes (T1D)
Authors: KHOUJA TUMADER , MILLER RACHEL G. , MOORE PAUL A. , ORCHARD TREVOR J. , COSTACOU TINA 
Published: June 2018

This analysis was based on 320 participants (mean age=32.1 years and duration=23.7 years) of the Pittsburgh Epidemiology of Diabetes Complications study of childhood-onset (&lt;17 years) T1D, who during 1992-94 received a comprehensive oral health exam including periodontal assessment of three facial sites (mesial, mid-cervical and distal) of the right maxillary/left mandibular or left maxillary/right mandibular quadrants and who were subsequently followed for up to 19 years to ascertain complication incidence. PD was defined as clinical attachment loss of ≥4 mm for at least 10% of the examined sites. Predictors of all-cause mortality; Hard Coronary Artery Disease (HCAD; CAD death, myocardial infarction or revascularization); and Coronary Artery Disease (CAD; HCAD but also including angina and ischemic ECG) were assessed using Cox models. In multivariable models, PD was not significantly associated with all-cause mortality (HR=1.07, 95% CI=0.48-2.37) although it was a significant predictor of both HCAD (HR=1.27, 95% CI=1.09-1.48) and CAD (HR=1.07, 95% CI=1.02-1.14). As smoking status was identified as a significant effect modifier of the PD-CAD and PD-HCAD associations, analyses were also conducted stratifying by smoking status. PD was associated with an increased risk of HCAD (HR=2.13, 95% CI= 1.26-3.61) and CAD (HR=1.27, 95% CI 1.05-1.53) only among smokers, whereas no relationship was observed among non-smokers (CAD HR=1.08, 95% CI=0.83-1.40; HCAD HR=1.18, 95% CI=0.83-1.69). PD was a significant predictor of HCAD and CAD among smokers with T1D.

Disclosure
T. Khouja: None. R.G. Miller: None. P.A. Moore: None. T.J. Orchard: None. T. Costacou: None.
Epicatechin Modulates Vasoreactivity and Mitochondrial Function in Endothelium
Authors: KELLER AMY C. , HULL SARA E. , KNAUB LESLIE , JOHNSTON ASPEN , REUSCH JANE E. 
Published: June 2018

Vascular dysfunction heralds the onset of diabetic cardiovascular disease. We have reported that vascular mitochondrial dysfunction contributes to impaired vasoreactivity in diabetes. The botanical compound -(-) epicatechin (EPICAT) is a known vasodilator. We hypothesized that EPICAT restores vasodilation by bolstering mitochondrial function in the context of high glucose via support of endothelial nitric oxide synthase (eNOS) activity and mitigation of reactive oxygen species (ROS). To test this hypothesis, we examined the impact of EPICAT on vasoreactivity ex situ and endothelial cell function in vitro. EPICAT significantly increased endothelium dependent acetylcholine-stimulated vasodilation (64.74%, p=0.002). HUVEC cells were incubated with 7 mM (normal glucose, NG) or 30 mM glucose (HG) with or without 0.1 µM EPICAT for 30 min, 2, 4-6 hours, and 24 hours. Mitochondrial superoxide was detected via electron spin resonance spectroscopy, and respiration and hydrogen peroxide were measured using Oroboros. Mitochondrial superoxide production was elevated in HG cells (2 hours=1.63 ± 0.17 µM/mg (HG) vs. 1.18 ± 0.07 µM/mg (NG), p=0.017 and 4-6 hours=1.46 ± 0.16 µM/mg (HG) vs. 1.18 ± 0.07 µM/mg (NG), p=0.09). Mitochondrial respiration was greater in cells exposed to HG for 2 hours in state 3 (23.8%) and uncoupled (14.5%), and hydrogen peroxide was higher in HG treated cells, while both metrics were unchanged after 6 hours, and respiration was decreased after 24 hours. Cells pretreated with EPICAT had elevated rates of respiration (state 3=73.4% and uncoupled=55.2%) without a commensurate increase in superoxide, and EPICAT dampened HG superoxide generation after 2 hours by 17.0%. Cells pretreated with EPICAT and exposed to HG had significantly elevated eNOS protein expression (p=0.001). Our data suggest that EPICAT potentiates vasodilation by acutely activating eNOS, leading to an increase in mitochondrial respiration while mitigating excess ROS production.

Disclosure
A.C. Keller: None. S.E. Hull: None. L. Knaub: None. A. Johnston: None. J.E. Reusch: Research Support; Self; Merck & Co., Inc.. Board Member; Self; American Diabetes Association. Research Support; Self; AstraZeneca. Other Relationship; Self; Sanofi-Aventis.
One-Hour Oral Glucose Tolerance Tests (OGTTs) for the Prediction and Diagnostic Surveillance of Type 1 Diabetes (T1D)
Authors: SIMMONS KIMBER , SOSENKO JAY , ISMAIL HEBA M. , LARSSON HELENA ELDING , STECK ANDREA 
Published: June 2018

Natural history studies and prevention trials for T1D use 2 hour OGTTs for two main goals: prediction and diagnostic surveillance. Although 2 hour OGTTs are reliable for these purposes, they impose time burdens and costs for research participants and staff. We thus examined whether 1 hour OGTTs are suitable for prediction and diagnostic surveillance. To assess their accuracy for prediction, we developed a 1 hour risk score similar to the Diabetes Prevention Trial-Type 1 Risk Score (DPTRS). The DPTRS utilizes log fasting C-peptide, sums of 30, 60, 90 and 120-min glucose and C-peptide, age, and log BMI. The components are the same for the 1 hour risk score (DPTRS60) and the DPTRS except that 1 hour glucose and C-peptide replace the glucose sum and C-peptide sum. Diabetes Prevention Trial-Type 1 participants were included in the analysis (n=670; age at baseline: 13.8±9.6 years; 56% male; 241 diagnosed with T1D). 1 hour glucose and C-peptide were highly predictive of T1D within the DPTRS60 model, as were log fasting C-peptide, age and log BMI (all p&lt;0.001). The receiver operating characteristic AUC was almost identical for the DPTRS and DPTRS60 (both 0.81, p&lt;0.001). To assess diagnostic surveillance, we sought to identify a 1 hour glucose threshold below which a diagnosis of T1D would be unlikely. Of 162 (among the 241 total) diagnosed by 2 hour OGTTs, only 2 (1.2%) had a 1 hour- glucose &lt;180 mg/dl at diagnosis. Of 172 with a 1 hour glucose &lt;180 mg/dl at baseline who were ultimately diagnosed, only 1 (0.6%) was diagnosed before the 6±3 month window for the next monitoring visit. 568/670 (85%) had a 1 hour glucose &lt;180 mg/dl at baseline. These findings show that 1 hour OGTTs are virtually as predictive of T1D as 2 hour OGTTs. Also, it appears that a 1 hour glucose &lt;180 mg/dl ensures a very low risk for T1D before the next routine monitoring visit. Moreover, most 1 hour glucose values are &lt;180 mg/dl. Accordingly, 1 hour OGTTs can reduce time burdens and costs for the majority of T1D natural history and prevention trial participants.

Disclosure
K. Simmons: None. J. Sosenko: None. H.M. Ismail: None. H. Elding Larsson: None. A. Steck: None.
Clinical and Socioeconomic Characteristics Associated with Ketoacidosis at Diagnosis of Type 1 Diabetes in Italian Children—Nationwide Survey, 2014–2016
Authors: CHERUBINI VALENTINO , BONFANTI RICCARDO , SKRAMI EDLIRA , FERRITO LUCIA , GESUITA ROSARIA ,   STUDY GROUP FOR DKA IN ITALY
Published: June 2018

To analyse clinical and socioeconomic factors associated with diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes (T1D) in Italy. Incident cases less than 15 years of age, were recruited during 2014-2016 from 31 paediatric centres. Age, gender, venous pH, presence of coeliac or thyroid disease, HbA1c, minority status, residence, family history of T1D and parents’ level of education were collected. DKA was defined according to ISPAD criteria. Point and 95% CI of DKA frequency were estimated. Two logistic regressions were performed to evaluate the role of clinical and socioeconomic characteristics on the risk of overall and severe DKA, considered as present vs. absent. A total of 1430 cases were evaluable. Severe and mild DKA frequencies were of 12.4% (95% CI: 10.8-14.3%) and 26.4% (95% CI: 24.1-28.7%), respectively. Females, minority status and younger children were at significant higher risk of DKA; family history of T1D and high maternal education were significantly associated with a lower risk. Despite prevention campaigns intended to reduce the DKA recently implemented, the frequency of DKA at T1D diagnosis remains high in Italy. Multiple factors affect the risk of DKA at the onset of type 1 diabetes, suggesting potential opportunity to intervene between symptom onset and development of diabetic ketoacidosis for both parents and clinicians.
Factors associated with the risk of DKA at diagnosis of type 1 diabetes in Italyoverall DKAsevere DKAOR95%CIpOR95%pAge class5-9 vs. 0-4 y0.660-45-0.970.0330.480.27-0.830.00910-14 vs. 0-4 y0.680.47-1.000.0490.620.36-1.050.073GenderMales vs. females0.730.54-0.980.0370.680.44-1.050.086Mother’s level of educationHigh vs. Low0.760.60-0.950.0170.590.42-0.830.003Family history of T1DNo vs. Yes0.430.22-0.790.0090.360.11-0.920.006Minority statusNo vs. Yes2.051.29-3.270.0021.290.60-2.600.499

Disclosure
V. Cherubini: Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; Novo Nordisk A/S, Menarini Group. R. Bonfanti: Advisory Panel; Self; Roche Diabetes Care Health and Digital Solutions, LifeScan, Inc., Abbott, A. Menarini Diagnostics, Eli Lilly and Company, Medtronic, Sanofi-Aventis, Novo Nordisk A/S. E. Skrami: None. L. Ferrito: None. R. Gesuita: None.