bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of First-Trimester Fasting Plasma Glucose with Gestational Diabetes Mellitus and Adverse Pregnancy Outcomes
Authors: LI PING , LIN SHUO , LI LING , CUI JINHUI , FAN JIANHUI
Published: June 2018

This study aims to evaluate the usefulness of a fasting plasma glucose (FPG) at the first trimester in predicting gestational diabetes mellitus (GDM) and the association between FPG and adverse pregnancy outcomes in Chinese women. Medical records of 2112 singleton pregnant women were collected from the third affiliated hospital of Sun Yat-Sen University, Guangzhou, China, from January 2016 to June 2017. FPG was measured at 9-13+6 weeks and 75 g oral glucose tolerance test (OGTT) was performed at 24-28 weeks in each subject. The International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria was used for diagnosing GDM. Among 2112 subjects, 224 (10.6%) subjects were diagnosed with GDM. The area under ROC curve (AUC) for FPG in predicting GDM was 0.63 (95% CI 0.61- 0.65) and the optimal cutoff value 4.5 mmol/L (sensitivity 64.29% and specificity 56.45%) (Figure 1). Higher first-trimester FPG increased the incidences of GDM, large for gestational age (LGA) and assisted vaginal delivery and/or cesarean section (all P > 0.05). These results suggested FPG at first trimester could be used to predict GDM and higher first-trimester FPG was associated with adverse pregnancy outcomes.

Disclosure

P. Li: None. S. Lin: None. L. Li: None. J. Cui: None. J. Fan: None.
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<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>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<0.001) compared with 7,5± 3,9 kg loss in COMBI group (P<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<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-<0.5=small, ≥0.5-<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 (<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<0.001). The receiver operating characteristic AUC was almost identical for the DPTRS and DPTRS60 (both 0.81, p<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 <180 mg/dl at diagnosis. Of 172 with a 1 hour glucose <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 <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 <180 mg/dl ensures a very low risk for T1D before the next routine monitoring visit. Moreover, most 1 hour glucose values are <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.
Ileum-Specific Transgenic Expression of Human Chimeric Intestinal Alkaline Phosphatase (IAP) Attenuates Western Diet (WD)–Induced Barrier Dysfunction and Glucose Intolerance
Authors: HE HONGLIANG , GHOSH SIDDHARTHA S. , YANNIE PAUL J. , WANG JING , GHOSH SHOBHA
Published: June 2018

Intestinal epithelial cell derived IAP dephosphorylates/detoxifies bacterial endotoxin LPS in the gut lumen. We have earlier demonstrated that improvement of intestinal barrier function was accompanied by an increase in IAP activity. Herein, we developed IAP transgenic mice where expression of human chimeric IAP is under the control of intestine specific villin promoter. As shown in Panel A, compared to non-transgenic wild type (WT) littermates, IAP expression (identified by c-myc tag) was noted in colon, ileum jejunum and duodenum of IAP-transgenic (IAPTg) mice. IAP was almost uniformly expressed along the length of the ileum (Panel B) and while IAP activity reduced from proximal P1 segment to distal P9 segment in WT mice, this activity was maintained in the IAPTg mice (Panel C). Dietary challenge with WD impaired glucose tolerance in WT mice and this intolerance was attenuated in IAPTg mice (Panels D and E). Significant decrease in fecal zonulin, a marker for intestinal barrier dysfunction, in WD fed IAPTg mice (Panel F) and a corresponding decrease in translocation of oral 4kDa FITC dextran to plasma (Panel G) suggests that IAP overexpression improves intestinal barrier function. Thus, targeted increase in IAP activity represents a novel strategy to improve WD induced intestinal dysfunction and glucose intolerance.

Disclosure

H. He: None. S.S. Ghosh: None. P.J. Yannie: None. J. Wang: None. S. Ghosh: None.
Simple Screening for Glucose Intolerance Based on Myoinositol Levels in Self-Collected Urine Samples at Home
Authors: TAKAKADO MISAKI , TAKATA YASUNORI , KAWAMURA RYOICHI , OSAWA HARUHIKO
Published: June 2018

Background: Urinary myoinositol (UMI) is a molecule with a structure similar to D-glucose. In the presence of hyperglycemia, reabsorption of MI in the renal tubules is inhibited by urinary glucose (UG), resulting in high concentrations of MI excreted into the urine. Unlike UG, UMI is highly stable at room temperature (RT) for over a week. Therefore, we conducted a study to establish a simple screening method for glucose intolerance (GI) based on UMI levels in self-collected pre- and postprandial urine samples at home.

Methods: First, to diagnose GI, we performed a 75gOGTT at the hospital in 115 volunteers without a past history of diabetes (DM). Within a week, each volunteer collected urine samples before and 2h after consuming the test meal (500kcal, energy bar) at home, and these samples were shipped to a single laboratory at RT. UMI was measured using an enzymatic method.

Results: To assess the usefulness of UMI for screening GI (IGT+DM), we performed statistical analyses using receiver-operating characteristic (ROC) curve. It revealed that the area under the curve of ROC (AUCROC) for 2h-postprandial UMI/creatinine (Cr) was 0.74 for diagnostic accuracy of GI (IGT+DM). The optimal cut-off was 27 mg/gCr with a sensitivity of 60%, and a specificity of 81%. For diagnostic accuracy of DM, AUCROC for 2h-postprandial UMI/Cr was 0.83, with a sensitivity of 80%, and a specificity of 74% at the cut-off value of 27 mg/gCr.

Conclusions: UMI measurement of urine samples self-collected at home may be a non-invasive, inexpensive, and valuable screening method for GI. This strategy may be suitable for subjects in area with limited access to medical care including developing countries, and could be the first step towards further medical examinations such as blood glucose (OGTT when required), and HbA1c.

Disclosure

M. Takakado: None. Y. Takata: None. R. Kawamura: None. H. Osawa: None.
Differential Effects of Birth Weight on Early-Onset Type 2 Diabetes in Adolescents and Young Adults
Authors: OLAIYA MUIDEEN T. , SINHA MADHUMITA , HANSON ROBERT L. , KOBES SAYUKO , NELSON ROBERT , KNOWLER WILLIAM C.
Published: June 2018

Background: Type 2 diabetes mellitus (T2DM) is increasingly diagnosed in adolescents and young adults. However, the impact of birth weight (BW) on this early onset T2DM is not well quantified.

Methods: A longitudinal study of Southwestern American Indians, aged ≥ 5 years, was conducted from 1965-2007. Subjects who had a recorded BW and at least one research exam that included an OGTT were followed until they developed T2DM or their last exam before the age of 40 years, whichever came first. Age-sex-adjusted incidence rate of T2DM was computed and Poisson regression models were used to estimate the effect of BW on the incidence of T2DM, adjusted for sex, BMI z-score (fitted as time-varying), and maternal variables, such as the presence of diabetes during pregnancy. The effect of BW on T2DM was non-proportional over time, and in some regression models, the effect was non-linear (quadratic). Therefore, all analyses were stratified by decade of age at follow-up and BW was analyzed as quintiles.

Results: Among 4,275 subjects (52% females, median BW 3.45 kg), there were 728 incident cases of T2DM over a median follow-up of 20.6 years (7.5 cases per 1000 person-years). Incidence rates, stratified by decade of age at follow-up, were greater in females and in older age groups. In multivariable regression analyses, the effect of BW on T2DM risk varied by age group, showing a quadratic (U-shaped) effect at 10-19 years (P<0.05) and a negative linear effect at older age intervals (20-29 years, P=0.015; 30-39 years, P<0.001). We could not reliably estimate risk at 0-9 years because of few cases. Female sex, greater BMI z-score, and the presence of maternal diabetes in pregnancy added to the effect of BW on T2DM risk in all age groups.

Conclusions: Both low and high BWs increased the risk of T2DM in adolescence, but only the effect of low BW persisted into young adulthood. Effects of female sex, accelerated growth, or being the offspring of a diabetic pregnancy added to the effect of BW on the risk of early onset T2DM.

Disclosure

M.T. Olaiya: None. M. Sinha: None. R.L. Hanson: None. S. Kobes: None. R. Nelson: None. W.C. Knowler: None.
Metabolic Syndrome and Prediabetes Fail to Detect a High Prevalence of Early Insulin Resistance—The PREMIER Study
Authors: CISTOLA DAVID P. , DWIVEDI ALOK K. , ARD JAMY D.
Published: June 2018

The PREMIER Study was a multi-center randomized controlled trial of lifestyle interventions in 810 nondiabetic subjects with elevated blood pressure. At baseline, one half of the cohort met the criteria for metabolic syndrome (MetS) and one third met the fasting glucose criterion for prediabetes (PreD). The purpose of the current analysis of PREMIER data was to quantify the sensitivity of the MetS criteria and cut points for detecting hyperinsulinemia and insulin resistance, defined here as fasting insulin ≥ 12 μIU/mL based on prior calibration against the euglycemic clamp. Insulin showed statistically significant bivariate correlations with 4 of the 5 MetS criteria in decreasing order of strength: waist circumference, fasting glucose, HDL-cholesterol and fasting triglycerides. By contrast, systolic and diastolic blood pressure, and total- and LDL-cholesterol did not correlate with fasting insulin. Logistic regression revealed that each MetS criterion, except blood pressure, had an independent contribution to hyperinsulinemia, even after correcting for age, race and gender. Receiver operator characteristic curves showed that the harmonized MetS cut points were non-optimal for detecting hyperinsulinemia. Specifically, the fasting triglyceride and glucose cut points were too high, while those for waist circumference were too low. Using the criteria for MetS and hyperinsulinemia, the subjects were divided into four metabolic subtypes. The subtype with hyperinsulinemia but not MetS represented 14.7% (95% CI 12.4-17.5) of the cohort. The prevalence of individuals with hyperinsulinemia that did not meet the criteria for MetS or PreD was surprisingly high at 12.7% (95% CI 10.3-15.1). This subtype is an important target for early intervention and diabetes prevention, but was not detected in this population using the current criteria for MetS or PreD. New screening strategies and metabolic health measures are needed to improve outcomes for diabetes prevention.

Disclosure

D.P. Cistola: None. A.K. Dwivedi: None. J.D. Ard: Consultant; Self; Nestlé. Research Support; Self; Nestlé, VIVUS, Inc..
The Visceral Adiposity Index Is a Significantly Stronger Predictor of Incident Diabetes in Men than in Women
Authors: SAELY CHRISTOPH H. , VONBANK ALEXANDER , HEINZLE CHRISTINE , ZANOLIN DANIELA , LARCHER BARBARA , MADER ARTHUR , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ
Published: June 2018

The visceral adiposity index (VAI) is a validated tool for the evaluation of visceral adiposity, using waist circumference, serum triglycerides, age and gender to diagnose this metabolic abnormality. We aimed at investigating the power of the VAI to predict diabetes incidence in men and in women. We prospectively recorded diabetes incidence in a large consecutive cohort of 1282 patients undergoing coronary angiography for the evaluation of established or suspected coronary artery disease who did not have diabetes at baseline. The VAI was calculated according to the Amato formula; diabetes was diagnosed according to ADA criteria. At baseline, the VAI score did not differ significantly between men (n=845) and women (230±199 vs. 238±239; p=0.247). Prospectively, 133 patients newly developed diabetes during a follow-up period of 3.7±0.9 years; diabetes incidence did not differ significantly between men and women (13.3 vs. 9.8%; p=0.093. The VAI significantly predicted incident diabetes in men but not in women both univariately (standardized odds ratios (ORs) of 1.71 [1.40-2.10]; p<0.001 and 1.09 [0.81-1.49]; p=0.565, respectively) and after multivariate adjustment (standardized adjusted ORs 1.56 [1.24-1.97]; p<0.001 and 1.[0.75-1.46]; p=0.790, respectively). An interaction term VAI x gender was statistically significant (p=0.017), indicating that the VAI was a significantly stronger predictor of diabetes incidence among men than women. We conclude that the VAI is a significantly stronger predictor of diabetes incidence in men than in women.

Disclosure

C.H. Saely: None. A. Vonbank: None. C. Heinzle: None. D. Zanolin: None. B. Larcher: None. A. Mader: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None.
Clinical Importance of One-Hour Plasma Glucose in Relation to Diabetes and Metabolic Syndrome in an Obese Population
Authors: HAVERALS LIEN , VAN DESSEL KRISTOF P.S. , VERRIJKEN AN , DIRINCK EVELINE L. , PEIFFER FRIDA W. , GAAL LUC VAN , BLOCK CHRISTOPHE DE
Published: June 2018

Introduction: Type 2 diabetes mellitus (T2DM) is increasingly prevalent and associated with increased morbi/mortality. In Caucasian obese subjects we investigated a possible link between 1-hour plasma glucose (1HrPG), diabetes and the metabolic syndrome (MetS).

Methods: Overweight and obese patients were consecutively included from the obesity clinic. ROC-curves were used to compare the diagnostic sensitivity and specificity of 1HrPG vs. fasting plasma glucose (FPG), 2HrPG, and HbA1c to diagnose diabetes, using American Diabetes Association criteria.

Results: We included 2439 patients (72% female) [mean age 43±13 years, median BMI 37.3 (33.7-41.3) kg/m²]. Diabetes was diagnosed in 9.8% and prediabetes in 33.8% of subjects. Exactly 1262 (51,7%) had a 1HrPG ≥155 mg/dL. These subjects were more insulin-resistant (p<0.001), had a higher waist (p<0.001), visceral adipose tissue (VAT) (p<0.001), systolic blood pressure (p<0.001), worse lipid profile (p<0.001), and higher plasminogen activator inhibitor-1 (PAI-1) [p<0.001] than subjects with 1HrPG <155mg/dL. MetS was present in 64.1% of the subjects with 1HrPG ≥155 mg/dL vs. 42.5% of subjects with a 1HrPG <155 mg/dL (p<0.001). In the group with 1HrPG ≥155 mg/dL only 32.6% had a normal glucose tolerance (NGT) while 18.5% was diagnosed with T2DM and 48.9% had prediabetes, compared to 81.7% NGT, 0.6% T2DM and 17.7% prediabetes in subjects with a 1HrPG < 155 mg/dL (p<0.001). In the group with NGT 412 subjects (30,0%) had a 1HrPG ≥155 mg/dL. These subjects showed higher HOMA-IR (p=0.008), VAT (p<0.001), blood pressure (p<0.001), worse lipid profile (p=0.001) than those with a 1HrPG<155 mg/dl, indicating its clinical relevance. For diabetes, the ROC area under the curve for 2HrPG was 0.928, compared to 1HrPG (0.764), Hba1c (0.752) and, FPG (0.600).

Conclusion: This study supports the need for detection of subjects with higher 1HrPG values. being at risk for development of T2DM, MetS and cardiovascular disease.

Disclosure

L. Haverals: None. K.P.S. Van Dessel: None. A. Verrijken: None. E.L. Dirinck: None. F.W. Peiffer: None. L. Van Gaal: Advisory Panel; Self; Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen J & J, Merck MSD, Novo Nordisk, Sanofi and Servier/Intarcia. Speaker's Bureau; Self; Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen J & J, Merck MSD, Novo Nordisk, Sanofi and Servier/Intarcia. Research Support; Self; EU (Hepadip & Resolve consortium) and National Research Funds. C. De Block: None.
Glucose Variability of Individuals without Diabetes Using a Long-Term Continuous Glucose Monitoring System
Authors: DEISS DOROTHEE , ABTAHI TAHMID , RASTOGI RAVI , KELLEY E. L.
Published: June 2018

Background: Prior investigations regarding glucose variability in nondiabetic subjects measured by continuous glucose monitoring (CGM) have been limited to only few weeks. Little is known about what defines healthy or pathologic glycemic variability. This study investigated “normal glycemia” under daily conditions using a long-term implantable CGM system in nondiabetic adults for 90 days.

Methods: 25 adult nondiabetic participants (10 Male, 15 Female, 17 participants >45 years old) were inserted with the Eversense® CGM System (Senseonics Inc, MD). Participants were instructed to continuously wear the CGM system during the 90 day period and calibrate the system when prompted. Analysis was performed to estimate standardized measures of euglycemia (70-180 mg/dL), hypoglycemia (<54, <70 mg/dL), hyperglycemia (>180, >200 mg/dL) and glucose variability (Mean, SD, CV).

Results: Out of 25 participants, 5 had inadequate data for inclusion. Analysis showed the average glucose value of the nondiabetic participants was 102 mg/dL (SD=18 and CV=0.17). Average percent time spent in hypoglycemia <54mg/dL was 0.14% and <70mg/dL was 1.5%. Time spent in euglycemia 70-180 mg/dL was 98%. Time spent in hyperglycemia >180 and >200 mg/dL was 0.17% and 0.05%, respectively. 17 participants had at least one value < 54mg/dL and 18 participants had glucose values >180mg/dL with 11 subjects with glucose values > 200mg/dL.

Conclusions: Glycemic variability recorded over extended period of time in participants without a diagnosis of diabetes showed similar results as observed by previous researchers over short duration with tight glycemic control. However, hypo- and hyperglycemic excursions are in some normoglycemic regarded individuals more frequent than suggested without CGM. Further analysis including meal challenge and fasting levels may provide guidance regarding expected values for persons without a diagnosis of diabetes and to set realistic target ranges for those with diabetes.

Disclosure

D. Deiss: Consultant; Self; Senseonics. Advisory Panel; Self; Abbott. Consultant; Self; Roche Diabetes Care Health and Digital Solutions. Advisory Panel; Self; Becton, Dickinson and Company. T. Abtahi: Other Relationship; Self; Senseonics. R. Rastogi: Employee; Self; Senseonics. E.L. Kelley: Employee; Self; Senseonics.
Exocrine Pancreatic Function as a Novel Biomarker in Pre-T1D
Authors: ROSS JAMES J. , WASSERFALL CLIVE , PERRY DANIEL J. , MCGRAIL KIERAN M. , POSGAI AMANDA L. , BRUSKO TODD M. , SCHATZ DESMOND , HALLER MICHAEL J. , ATKINSON MARK A.
Published: June 2018

Recent studies demonstrated reduced serum trypsinogen levels as well as pancreatic weight/volume in patients with type 1 diabetes (T1D) and nondiabetic/autoantibody (AAb)-positive subjects. Histological defects including increased CD8+ T cell infiltration and elevated C4d deposition have been observed in the exocrine T1D pancreas. Like trypsinogen, amylase and lipase are produced by the exocrine pancreas and serve as more common markers of exocrine function. We hypothesized that amylase and lipase levels would be lower in patients with T1D as well as in subjects with multiple (i.e., ≥2) T1D-related AAb compared with controls. To test this, serum amylase and lipase levels were determined in 70 patients with recent-onset T1D (duration <3 mo), 57 patients with established T1D (duration >3 mo), 56 single AAb positive (1AAb+) subjects, 42 multiple AAb positive (≥2AAb+) subjects, 96 AAb negative (AAb-) relatives of T1D patients, and 110 AAb- control subjects. Amylase levels, which are independent of age (r = -0.02, P = 0.7), were significantly lower in patients with T1D (mean ± SD 39.98 ± 17.8 ng/mL; P < 0.005) vs. AAb- subjects (47.40 ± 20.17 ng/mL). Lipase levels, which are positively correlated with age (r = 0.30, P < 0.0001), were significantly lower in T1D patients (25.95 ± 21.ng/mL; P < 0.001) as well as ≥2AAb+ subjects (22.59 ± 11.12 ng/mL; P < 0.001) compared with 1AAb+ individuals (37.60 ± 16.79 ng/mL). These results provide further evidence that exocrine pancreas abnormalities exist in patients with T1D and ≥2AAb+ subjects considered to have early-stage T1D with high risk of progressing to clinical diagnosis. These data also support the possibility that an inherent or acquired defect in exocrine pancreas development and/or function may contribute to disease pathogenesis, but cause and effect cannot yet be ascertained. Importantly, these exocrine pancreas enzymes may serve as biomarkers of T1D to better predict disease progression and/or stratify patients according to etiology.

Disclosure

J.J. Ross: None. C. Wasserfall: None. D.J. Perry: None. K.M. McGrail: None. A.L. Posgai: None. T.M. Brusko: Stock/Shareholder; Self; OneVax, LLC. Advisory Panel; Self; Caladrius Biosciences, Inc.. Consultant; Self; Merck & Co., Inc., Sanofi-Aventis. D. Schatz: None. M.J. Haller: None. M.A. Atkinson: Other Relationship; Self; Patent Issued.
The Progression of Hyperglycemia and Diabetes Before and After Lung Transplant
Authors: AKSHINTALA DIVYA , SCHEKER EVANA VALENZUELA , PELAEZ ANDRES , CHANDRASHEKARAN SATISH , MACHUCA TIAGO , LEEY JULIO A.
Published: June 2018

Diabetes mellitus (DM) is a frequent complication of organ transplantion . The aim of the study was to determine the incidence and prevalence of DM after Lung Transplant (LTx).

Methods: Chart review of patients undergoing LTx at the University of Florida, Gainesville between 2013 and 2015. Variables such as diabetes status before and after LTx, glucose level (G) during first seven days after LTx, insulin therapy and other relevant factors were included.

Results: There were 81 LTx surgeries corresponding to 78 patients (3 had repeat LTX). Prior to LTx 14 patients had DM (5 CF), only 2 them were taking insulin, both had CF. G >200 mg/dl and <70mg/dl were observed in 71% (58/81) and 19% (16/81) patients during the first 7 days after LTx respectively. At LTx surgery discharge, 35% (29/81) were on insulin, 51% of them (15/29) on basal insulin alone or in combination. After 12m from LTx, 26 were on insulin, 69% of them (18/26) on basal insulin alone or in combination. Among those who had G>200mg/dl within the first 7 days, only 19% (11/58) had been diagnosed of DM before LTX, and 45% of them (26/58) were taking DM medications 12 months after LTx, and 65% (17/26) were using basal insulin alone or in combination.

Conclusion: Inpatient hyperglycemia is very common after LTx. Use of insulin at discharge is a strong predictor for use of insulin 12m after LTX, indicating the need for close monitoring.

Characteristic1 month BEFORE LTx12 months AFTER LTxAge (SD)50.7 (16.8)xFemale41% (34/81)xBMI23.9 (4.0)25.2 (4.2)Diabetes Mellitus18 (14/78) Dx per PMH36% (28/78) Dx per medication listAny type of Insulin14% (2/14)32% (26/81)G >200 mg/d first 7 d after LTx71% (58/81)xG <70 mg/dl first 7 d after LTx19% (16/81)x

Disclosure

D. Akshintala: None. E. Valenzuela Scheker: None. A. Pelaez: None. S. Chandrashekaran: None. T. Machuca: None. J.A. Leey: None.
Different Course of the Microvascular Complications of Diabetes Mellitus in Kidney Transplant Recipients with Posttransplant Diabetes—A Longitudinal Study
Authors: LONDERO GAI THIZÁ M. , GIARETTA LUANA S. , MANFRO ROBERTO C. , CANANI LUIS H. , LAVINSKY DANIEL , LEITAO CRISTIANE B. , BAUER ANDREA
Published: June 2018

Objective: This study assessed microvascular complications (MC) occurrence in renal posttransplant diabetes mellitus (PTDM).

Methods: Patients ≥ 5 years of PTDM were included from a cohort of 895 kidney recipients (KR) transplanted in 2000-2011. Diabetic retinopathy (DR) was evaluated by fundus photographs (FP) and optical coherence tomography (OCT). Diabetes kidney disease was evaluated by protein to creatinine ratio (PCR) and eGFR. Distal polyneuropathy (DPN) was assessed by Michigan Protocol/monofilament foot exam. Ewing protocol identified cardiovascular autonomic neuropathy (CAN). Controls were KR transplanted in the same period but without PTDM (NPTDM).

Results: After 578 weeks, 135 (15%) KR developed PTDM, 64 with PTDM ≥ 5 years. None of PTDM KR presented DR at FP but thinning of inner retinal layers was observed with OCT (Figure 1). More than 60% of PTDM KR had DPN (OR 1.55; CI 1.26-1.91; p<0.001). Frequency of CAN was similar between PTDM and NPTDM KR (p=0.26). During the 1st year and after 8.5±3.0 years of transplantation, eGFR and PCR did not differ between groups.

Conclusions: This is the first longitudinal study to assess MC in PTDM KR. A lower than expected prevalence as well as a different clinical course of the MC was observed. PTDM seems to be a unique type of DM and its consequences may be milder than expected in type 1 and type 2 DM.

Disclosure

T.M. Londero Gai: None. L.S. Giaretta: None. R.C. Manfro: None. L.H. Canani: None. D. Lavinsky: None. C.B. Leitao: None. A. Bauer: None.