bluuebunny/crossref_metadata_2025 huggingface dataset:
1401-P: Universal vs. Selective Screening for Hyperglycemia First Diagnosed during Pregnancy, Including Early Hyperglycemia: Diagnostic and Prognostic Value in 4,518 Women
Authors: COSSON EMMANUEL , VICAUT ERIC , BANON DORIAN SANDRE , CUSSAC-PILLEGAND CAMILLE , BAUDRY CAMILLE , VALENSI PAUL , CARBILLON LIONEL
Published: June 2019

The aim of the study was to evaluate the prevalence of hyperglycemia first diagnosed during pregnancy (Hgly), including gestational diabetes mellitus appearing early (eGDM) or after 22 weeks of gestation (GDM) or diabetes in pregnancy (DIP) and their prognosis whether women had risk factors (RFs) for Hgly or not. We included the women without known diabetes who had in our department (2012-2016) a universal screening (first: FPG measurement in early pregnancy, with immediate care without any further screening in women with eGDM or early DIP; second: OGTT after 22 WG in the other women). We considered 4 mutually exclusive groups of women according to the presence of Hgly and of RFs according to our national guidelines (maternal age ≥ 35 years or pregravid overweight or family history of diabetes or personal history of Hgly or of macrosomic infant). We considered a predefined composite endpoint (preeclampsia or large for gestational age infant or shoulder dystocia). We included 4518 women, of whom 23.5% had Hgly (eGDM 10.4%, GDM 12.2% and DIP 0.9%) and 71.1% had ≥1 RF. The four groups were: Hgly-RF- (n=1144), Hgly-RF + (n=2313), Hgly+RF - (n=163), Hgly+RF+ (n=898). Hgly was more frequent in those with RFs (OR 2.7 [95% CI 2.3-3.3]). The incidence of the composite criterion differed (p<0.0001) across groups: Hgly-RF- 6.3%; Hgly+RF- 8.6%; Hgly-RF + 13.2%; Hgly+RF+ 17.1% (Hgly effect p<0.05, RFs effect <0.001, interaction Hgly.RF p=0.94) and increased with the number of RFs (no RF: 6.3%/1: 10.8%/2: 14.7%/3: 28.0% and 4-5: 25.0%; p<0.0001). Our observational study shows that a selective screening during pregnancy leads to misdiagnose 15.3% of HGly and that the women with treated Hgly but no RF have however a very good prognosis. On the contrary, women with RFs have a poor prognosis whatever their glycemic status, suggesting that early management for women with overweight -the only modifiable RF here- might be useful to improve outcomes.

Disclosure

E. Cosson: Board Member; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., LifeScan, Inc., Lilly Diabetes, Medtronic, Merck Sharp & Dohme Corp., Novartis France, Novo Nordisk A/S, Roche Diagnostics France, Sanofi. Research Support; Self; Air Liquide, Lilly Diabetes, Novo Nordisk A/S, Roche Diagnostics France, Roche Foundation, Sanofi. E. Vicaut: Consultant; Self; Abbott, Bristol-Myers Squibb Company, Lilly Diabetes, Novartis France, Pfizer Inc., Pierre FABRE, Roche Pharma. D. Sandre Banon: None. C. Cussac-Pillegand: None. C. Baudry: None. P. Valensi: None. L. Carbillon: None.

Funding

Lilly France; Roche Diagnostics France
1434-P: Definition of Hypertriglyceridemia during Pregnancy: A Search on the Cutoffs
Authors: CHEN SAIGE , LI HUNG-YUAN
Published: June 2019

Objective: A high plasma triglyceride (TG) concentration during pregnancy is associated with adverse pregnancy outcomes. It is important to define a cutoff to initiate interventions. Since it remains unknown if there is a threshold, our aim is to explore the cutoff values of plasma TG in the first and second trimesters.

Research Design and Methods: A prospective cohort study was conducted which included 837 pregnant women. Fasting plasma TG were measured in the first and second trimesters and were divided into seven categories according to its percentile, respectively. The presence of adverse pregnancy outcome was defined if anyone of the following condition developed, including gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), preeclampsia, preterm delivery, and large for gestational age (LGA).

Results: For the relationship between plasma TG and adverse pregnancy outcomes, there was a threshold between the highest and the second-highest categories in the first and second trimesters. The adjusted odds ratios (95% confidence interval) of adverse pregnancy outcomes for the 7 categories were 1, 0.75 (0.28-1.96), 1.46 (0.59-3.59), 1.83 (0.74-4.51), 1.19 (0.48-2.95), 1.11 (0.43-2.86), and 3.34 (1.35-8.25) for plasma TG in the first trimester, and 1, 1.81 (0.82-4.02), 2.07 (0.94-4.57), 2.50 (1.15-5.46), 2.19 (1.00-4.80), 2.14 (0.97-4.71), and 3.53 (1.62-7.69) for plasma TG in the second trimester. Using the threshold as the cutoff values, women with high plasma TG concentrations in the first trimester or second trimesters were associated with increased risk for adverse pregnancy outcomes (≥150 mg/dL in the first trimester, OR 2.75, 95% CI 1.45-5.24, p = 0.002; ≥246 mg/dL in the second trimester, OR 1.78, 95% CI 1.11-2.85, p = 0.017).

Conclusions: There are inflection points for plasma TG in the first and second trimesters. The risk of adverse pregnancy outcomes increase significantly if plasma TG exceed this point, which may also be a cutoff to initiate interventions in the future.

Disclosure

S. Chen: None. H. Li: None.
1445-P: Physical Activity and Insulin Resistance in Midlife Women: 17-Year Longitudinal Associations in SWAN
Authors: BADON SYLVIA E. , GABRIEL KELLEY PETTEE , KARVONEN-GUTIERREZ CARRIE A. , STERNFELD BARBARA , LEE JENNIFER , GOLD ELLEN , WAETJEN ELAINE , HEDDERSON MONIQUE
Published: June 2019

Insulin resistance increases starting in midlife due to decreasing estrogen production and other aging-related factors. Higher intensity physical activity (PA) has the potential to attenuate rising insulin resistance; however, longitudinal associations of PA and insulin resistance have not been studied in midlife women. We used data from the Study of Women’s Health Across the Nation (SWAN, N=3,230), a cohort study with up to 17 years of follow-up, to estimate longitudinal associations of higher intensity PA with insulin resistance. Women reported PA using the Kaiser Physical Activity Survey at 7 study visits (V0, V3, V5, V6, V9, V12, V13). We used the sports and exercise physical activity index score (range: 1-5) to assess leisure-time moderate to vigorous intensity PA (MVPA). SWAN measured glucose and insulin in blood collected at 8 study visits (V0, V1, V3-V7, V12, V13). We used generalized estimating equations to estimate the adjusted longitudinal associations of MVPA with homeostatic model assessment of insulin resistance (HOMA-IR) overall, by baseline body mass index (BMI) category, and by race/ethnicity. Women were 46 (SD=3) years old at baseline. Forty-seven percent were non-Hispanic white; 28% black; 9% Japanese; 8% Chinese, and 8% Hispanic. Each additional one-unit increase in reported MVPA was associated with an average 0.2 unit lower HOMA-IR (95% CI: -0.3, -0.1) over time. Associations differed by baseline BMI (interaction P<0.001). Reported MVPA was associated with a 0.1 lower HOMA-IR (95% CI: -0.1, -0.02) in normal weight women, a 0.2 lower HOMA-IR (95% CI: -0.3, -0.1) in overweight women, and a 0.4 lower HOMA-IR (95% CI: -0.6, -0.1) in obese women. MVPA was not associated with HOMA-IR in underweight women (mean difference=0.0; 95% CI: -0.1, 0.1). Associations did not differ by race/ethnicity (interaction P=0.39). Our findings support longitudinal associations of MVPA with lower insulin resistance in midlife women, with the strongest associations in obese women.

Disclosure

S.E. Badon: None. K. Pettee Gabriel: None. C.A. Karvonen-Gutierrez: None. B. Sternfeld: None. J. Lee: None. E. Gold: None. E. Waetjen: None. M. Hedderson: None.

Funding

National Institutes of Health; U.S. Department of Health and Human Services; National Institute on Aging; National Institute of Nursing Research; Office of Research on Women’s Health (U01NR004061, U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495); National Center for Research Resources; National Center for Advancing Translational Sciences (UCSF-CTSI UL1RR024131)
1452-P: Association between Aging and Insulin Resistance and Secretion in a General Nondiabetic Population
Authors: FUJITA TOMOYUKI , DAIMON MAKOTO , MURAKAMI HIROSHI , MIZUSHIRI SATORU , MATSUHASHI YUKI , OSONOI SHO , MURABAYASHI MASAYA , TAKAHASHI KAZUHISA , NISHIYA YUKI
Published: June 2019

Objective: Aging is one of the risks for abnormal glucose tolerance or diabetes. Although association between age and, insulin secretion and resistance has been reported in various cross sectional studies, few studies evaluated changes of insulin resistance and secretion along with aging.

Research Design and Methods: Among participants of the population-based Iwaki study of Japanese, those participated consecutively from 2014 to 2017 and were nondiabetic were included in this study (Men/Women: 200/294; Age: 21-90 (54.2 ± 13.5)). The effects of aging on homeostasis model assessment indices for insulin resistance (HOMA-R) and β-cell function (HOMA-β) were examined.

Results: During the 3-year periods, HOMA-R significantly increased (p<0.0001), while HOMA-β significantly decreased (p<0.0001). Repeatedly measures ANOVA with adjustments for possible confounding and/or intermediating factors showed that the increase in HOMA-R became insignificant after adjustment with factors related to adiposity such as BMI and leptin (p=0.564), while the decrease in HOMA-β stayed significant even after such adjustments (p=0.046). Despite the facts, stepwise multiple regression analysis showed significant association of leptin not only with increases in HOMA-R (p=0.022) but also with decreases in HOMA-β (p =0.003).

Conclusion: Insulin resistance increases along with aging probably due to a simultaneous adiposity, while insulin secretion decreases along with aging at least in part independently of such adiposity. However, the association between leptin and decreases in HOMA-β may suggest that adiposity of β-cells may be in part blamed for the decreases. Further, leptin may be a marker to predict those at risk of decreasing insulin secretion. We are now examining such association in details in consideration with blood metabolites and amino acids levels.

Disclosure

T. Fujita: None. M. Daimon: None. H. Murakami: None. S. Mizushiri: None. Y. Matsuhashi: None. S. Osonoi: None. M. Murabayashi: None. K. Takahashi: None. Y. Nishiya: None.
1475-P: Aortic Valve Sclerosis and Diabetes Mellitus Are Independent Predictors of All-Cause Mortality in a Large Surgical Myocardial Revascularization Cohort
Authors: MYASOEDOVA VERONIKA ALEXANDROVNA , GENOVESE STEFANO , CAVALLOTTI LAURA , BONOMI ALICE , GRIPARI PAOLA , CAMPODONICO JENESS , VALERIO VINCENZA , RONDINELLI MAURIZIO , SONGIA PAOLA , PEPI MAURO , ALAMANNI FRANCESCO , POGGIO PAOLO
Published: June 2019

Background: Studies on the association between aortic valve sclerosis (AVSc) and diabetes in patients with coronary artery disease (CAD) are lacking.In this retrospective observational study, we evaluated the association of AVSc with diabetes and to assess the risk of all-cause mortality in patients referred to isolated coronary artery bypass surgery (CABG).

Methods: Echocardiograms obtained at the baseline from 2’327 patients undergoing CABG between 2006 and 2016 in a single center were assessed. The follow-up was carried out through a regional registry. Hazard ratios (HR) were adjusted for clinical factors [i.e., sex, age, previous myocardial infarction, ejection fraction (EF), dyslipidemia, and kidney function].

Results: Overall, AVSc was present in 1’116 (39.7%) and diabetes in 840 patients (29.9%). Diabetic patients showed a significant higher AVSc prevalence compared to nondiabetic patients (44 vs. 38%, respectively; p=0.005).In 5 years follow-up, 479 deaths (20.6%) for any cause were registered. Independent predictors of all-cause mortality were age (p<0.001), EF (p<0.001), AVSc (p=0.02), and diabetes (p=0.004).We stratified the patients into three groups: A) no-diabetes and no-AVSc; B) diabetes or AVSc; C) diabetes and AVSc. The mortality rate was 18.6% in group A, 20.8% in group B, and 26.5% in group C. Group B and C had a significant increased overall mortality risk with a HR of 1.4 (p=0.04) and 2.1 (p<0.001), respectively, when compared to group A. The HR of group C was also significantly higher than group B (HR=1.5; p=0.03).

Conclusions: Our findings indicate that: 1) AVSc is associated with diabetes; 2) AVSc and diabetes are independently associated with all-cause mortality in patients undergoing CABG; and 3) patients with both clinical conditions have the highest mortality rate. These data improve risk stratification in patients undergoing surgical myocardial revascularization.

Disclosure

V.A. Myasoedova: None. S. Genovese: Advisory Panel; Self; Novartis Pharmaceuticals Corporation, Sanofi. Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Hikma Pharmaceuticals. Speaker's Bureau; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk A/S, Takeda Pharmaceutical Company Limited. L. Cavallotti: None. A. Bonomi: None. P. Gripari: None. J. Campodonico: None. V. Valerio: None. M. Rondinelli: Consultant; Self; Sanofi. Speaker's Bureau; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp., Takeda Pharmaceutical Company Limited. P. Songia: None. M. Pepi: None. F. Alamanni: None. P. Poggio: None.

Funding

Fondazione Gigi e Pupa Ferrari ONLUS
151-OR: Technosphere Insulin Provides Better Early Postprandial Glucose Control than Subcutaneous Rapid-Acting Analog
Authors: GRANT MARSHALL L. , POMPILIO FRANK , SHARMA GAURAV , KRUEGER JOHN A. , KENDALL DAVID M. , ZAVERI NADIA
Published: June 2019

In a recent study (STAT, NCT03143816), patients with type 1 diabetes mellitus (T1DM) treated with Technosphere Insulin (TI) demonstrated better early postprandial glucose (PPG) control than those on subcutaneous (SC) insulin aspart. The average daily dose of TI in patients who took TI as directed in the protocol was twice that of aspart (40.5 vs. 20.6 units). Despite the higher dose, the TI group experienced less time in hypoglycemia than the aspart group. These results prompted a retrospective analysis of mixed-meal tolerance tests (MMTTs) conducted in T1DM to further evaluate the 2:1 dosing ratio.

In study MKC-TI-009 (NCT00308308), patients with T1DM underwent 1 to 3 MMTTs. A total of 1326 PPG profiles were evaluable: 674 MMTTs from 261 patients on SC aspart and 652 MMTTs from 264 patients on TI. On average, the area under the PPG excursion curve (PPGE AUC) decreased with increasing dose, and the mean (SE) ratio of the aspart slope to the TI slope was 2.1 (0.3), consistent with the results of STAT. This was confirmed when doses of TI 8, 16, and 24 units were compared with mean (SE) aspart doses of 4 (1), 8 (1), and 12 (1) units, respectively (Figure).

The PPGE curves confirm the earlier onset and shorter duration of TI, while the tendency to drop below baseline in the late postprandial period reflects the longer duration of action of SC aspart. The timing of hypoglycemia (levels 1 and 2) follows the pattern of PPGEs.

Disclosure

M.L. Grant: Employee; Self; MannKind Corporation. Stock/Shareholder; Self; MannKind Corporation. F. Pompilio: Employee; Self; MannKind Corporation. Stock/Shareholder; Self; Amgen Inc., MannKind Corporation. G. Sharma: Employee; Self; MannKind Corporation. J.A. Krueger: Employee; Self; Eli Lilly and Company, MannKind Corporation. Stock/Shareholder; Self; Eli Lilly and Company. D.M. Kendall: Employee; Spouse/Partner; Amgen Inc. Employee; Self; MannKind Corporation. Stock/Shareholder; Self; MannKind Corporation. N. Zaveri: Employee; Self; MannKind Corporation. Stock/Shareholder; Self; Becton, Dickinson and Company.

Funding

MannKind Corporation
1518-P: Serum Dihomo-γ-Linolenic Acid Levels Predict Glycemic Control Deterioration in Type 2 Diabetes Patients after Discharge from Admission
Authors: SUNOUCHI TAKASHI , TSURUTANI YUYA , TAKIGUCHI TOMOKO , SAITO JUN , NISHIKAWA TETSUO
Published: June 2019

The measurement of serum polyunsaturated fatty acid (PUFA) levels in type 2 diabetes (T2DM) patients may be useful for evaluating not only the dietary habits, but also metabolic abnormalities, as high dihomo-γ-linolenic acid (DGLA) levels or low arachidonic acid (AA)/DGLA ratios are associated with obesity-related abnormalities. However, the impact of PUFA levels on glycemic control remains unknown. This retrospective study analyzed the association between serum PUFA levels and glycemic control one year after discharge from admission. Data from 480 T2DM patients admitted to our hospital from 2011 to 2016 were analyzed. Patients with renal dysfunction (eGFR < 30 mL/min/1.73 m2) or insulin deficiency [fasting C-peptide (CPR) < 0.5 ng/mL or two-hour postprandial CPR < 1.0 ng/mL] were excluded. Patients achieving < 7.0% glycated hemoglobin (HbA1c) at one year after discharge were defined as achievers, and the others, as non-achievers. Multiple baseline factors, including the PUFA levels between the two groups were analyzed. Of 480 patients, 206 were achievers and 274 were non-achievers. The achievers were younger (59.4±12.8 vs. 62.0±13.7 years, p = 0.0188), and had a higher two-hour postprandial CPR (4.98±2.46 vs. 4.26±2.10 ng/mL, p = 0.002), lower DGLA level (36.2±15.6 vs. 39.8±13.5 μg/mL, p = 0.002), and higher AA/DGLA ratio (6.09±2.39 vs. 5.12±1.73, p <0.001) than non-achievers, while the body mass index, HbA1c at admission, fasting CPR, omega-3 PUFA levels between the groups did not differ. The two-hour postprandial CPR and DGLA levels (or AA/DGLA ratios) also showed significant associations in the multivariate logistic regression model. Sensitivity analyses excluding the patients ≥ 75 years old or those treated with insulin showed similar results. Our results show that high DGLA levels and low AA/DGLA ratios, as well as decreased postprandial insulin secretion are predictors of glycemic control deterioration after discharge from admission.

Disclosure

T. Sunouchi: None. Y. Tsurutani: Research Support; Self; Astellas Pharma Inc. T. Takiguchi: None. J. Saito: None. T. Nishikawa: None.
1524-P: Discordance between A1C and Glucose for the Diagnosis of Prediabetes in a Filipino-American Population
Authors: MERCADO MARIA ELIZABETH P. , KIM SARAH , EVA MARIA C , LA PAZ CUTIONGCO DE , SEIELSTAD MARK , PAZ-PACHECO ELIZABETH , MURPHY ELIZABETH
Published: June 2019

Discordance between A1C and fasting glucose (FBG) or oral glucose tolerance glucose (OGTT) in the detection of dysglycemia has been observed in multiracial and multiethnic populations. In most instances, A1C under detected diabetes or prediabetes compared to glucose tests. To determine the relationship between FBG, OGTT and A1C for the diagnosis of prediabetes in a Filipino American population we studied 154 self-reported nondiabetic adult subjects from the Filipino Health study living in the U.S. > 3 year. Mean age 42 ± 18 y, BMI 25.8 ± 3.8, 58% female, and 67% with a family history of diabetes. Using ADA criteria, 5 subjects met the diagnosis of diabetes (4 by A1C and 1 by OGTT, the later subject is not included in Table 1) while 61 (40%) had prediabetes. Prevalence of prediabetes was only 6.5% by FBG and 7.1% by OGTT. However, the prediabetes prevalence was 36% by A1C. Kruskal Wallis was used to test the difference in insulin resistance by HOMA-IR and insulin between HbA1C categories. Subjects with an A1C of 5.7-6.4% (41 of whom had normal FBG and OGTT) were significantly more insulin resistant than those with an A1C < 5.7%. This suggests A1C may be a more sensitive test of abnormal glucose regulation in a Filipino population living in the U.S. than FBG or OGTT. Outcome studies assessing progression to diabetes will be needed to confirm this hypothesis.

Disclosure

M.P. Mercado: None. S. Kim: None. E.C. Cutiongco de la Paz: None. M. Seielstad: None. E. Paz-Pacheco: None. E. Murphy: None.

Funding

Philippine-California Advanced Research Institutes
156-LB: Assessment of Treatment Patterns in a Real-Life Setting with Dapagliflozin or DPP-4 Inhibitors as Add-On Therapy in Uncontrolled T2DM Patients That Failed on Other Regimens
Authors: ESPINOZA-PERALTA DIEGO , SILVA ALEJANDRA I. , COLLADO JUAN G. , ROGEL-MANZANARES JORGE D.
Published: June 2019

Mexico is one of the three countries in America with the highest prevalence (14.4%) of DM. Providing medical care to uncontrolled T2DM patients who failed antidiabetic treatment (ADT) is challenging. We designed a retrospective study to assess the response to dapagliflozin (Dapa) or DPP-4-inhibitors (DPP-4i) as add-on therapy in uncontrolled T2DM patients who had previous ADT.

Objectives: Compare subjects with ≥5% improvement of the weighted sum of the composite variable (HbA1c, body weight (BW) and blood pressure (BP)) by the end of the 24-week observation period.

Inclusion Criteria: T2DM subjects ≥18 years old with failure to any ADT and HbA1c% ≥7 that started Dapa or DPP-4i as add-on to other antidiabetic drugs from August 2014 to November 2017.

Statistical Methods and Analysis: A propensity score matching model (nearest neighbor algorithm) was used, the covariates included were prior ADT, TC, LDL-c, HbA1c, BW, SBP and age.

Results: Of 1379 subjects, 131 met statistical matching criteria. Subjects with Dapa had a significant improvement (>5%) in the composite variable compared to DPP-4i (60.3% vs. 34.3%, p<0.01). Significant results were shown in BMI (-0.36 (-1.04 to 0.40) vs. 0 (-0.62 to 0.78), p<0.01), weight (-1 (-3 to 1) vs. 0 (-1.69 a 2), p<0.001), glucose (-8 (-39 to 24) vs. -1 (-22 to 16), p<0.01) and HbA1c (-0.89 (-1.44 to -0.38) vs. -0.12 (-0.82 to 0.46), p<0.01). Logistic Regression Model (LRM) was carried out to identify if the improvement at Dapa group was independent to the confusion factors. LRM confirmed that the improvement in the primary outcome was dependent of the type therapy, regardless of age, BMI, triglyceride, HDL and LDL cholesterol levels and ADT at the beginning of the study (Dapa OR 4.23 IC 95% 2.46-7.29, p<0.001).

Conclusion: T2DM Mexican patients who have failed to previous antidiabetic therapies showed significant decrements of HbA1c, glucose, weight and blood pressure levels with the use of Dapa.

Disclosure

D. Espinoza-Peralta: None. A.I. Silva: Employee; Self; AstraZeneca. J.G. Collado: None. J.D. Rogel-Manzanares: None.
1588-P: Regression to Normal Glucose Regulation in American Indians and Alaska Natives of a Diabetes Prevention Program
Authors: PRATTE KATHERINE A. , JOHNSON ANN , BEALS JANETTE , BULLOCK ANN , MANSON SPERO M. , JIANG LUOHUA
Published: June 2019

Objectives: To evaluate whether regression from impaired glucose regulation (IGR) to normal glucose regulation (NGR) after one year of a lifestyle intervention reduces diabetes risk in American Indians and Alaska Natives (AI/ANs). Additionally, we sought to identify predictors for regression to NGR and understand possible mechanisms for the association between NGR and future diabetes risk.

Research Design and Methods: Data from participants enrolled from 2006 to 2009 in the Special Diabetes Program for Indians Diabetes Prevention Program with IGR at baseline and an oral glucose tolerance test (OGTT) at year 1 were analyzed (N = 1443). Based on OGTT results, participants were classified into four categories: NGR; isolated IFG (iIFG); isolated IGT (iIGT); or both IFG and IGT (IFG/IGT). Cox regression models were used to estimate the subsequent diabetes risk (year 1 to year 3) by year 1 glucose status. Mediation analysis was employed to estimate the proportions of the association between year 1 glycemic status and diabetes risk explained by specific factors.

Results: Those who reverted to NGR at year 1 (38%) had lower diabetes risk than those with sustained IGR (adjusted hazard ratio (HR) = 0.28, 95% CI: 0.12-0.67). Compared to the NGR group at year 1, IFG/IGT carried the highest risk of developing diabetes with an adjusted HR of 4.72 (95% CI: 1.84-12.07), followed by the iIGT group (HR=3.26, 95% CI: 0.96-11.12; p-value=0.059) and the iIFG group (HR=3.13, 95% CI: 1.27-7.31). The lower risk associated with regression to NGR was explained by both baseline risk factors and differences in weight loss. Metformin use, weight loss, and increase in exercise were modifiable risk factors associated with a higher odds of regression to NGR.

Conclusions: AI/AN patients with prediabetes who reverted to NGR had a reduced risk of developing type 2 diabetes over the next two years; modifiable risk factors explained a major proportion of risk reduction associated with NGR.

Disclosure

K.A. Pratte: None. A. Johnson: None. J. Beals: None. A. Bullock: None. S.M. Manson: None. L. Jiang: None.

Funding

Indian Health Service (HHSI242200400049C to S.M.M.); National Institute of Diabetes and Digestive and Kidney Diseases (1P30DK092923 to S.M.M), (R21DK108187 to L.J.)
16-OR: Contributions of Chronic Kidney Disease and Cardiovascular Disease to Medical Costs of Type 2 Diabetes
Authors: NICHOLS GREGORY A. , USTYUGOVA ANASTASIA V. , DERUAZ-LUYET ANOUK , BRODOVICZ KIMBERLY G.
Published: June 2019

Medical costs of type 2 diabetes (T2D) are driven by the presence of microvascular and macrovascular complications. We compared annual costs of T2D patients with and without chronic kidney disease (CKD) and cardiovascular disease (CVD). We used the electronic medical records of Kaiser Permanente Northwest to identify 37,684 patients with T2D with an eGFR in 2016 or 2017. We grouped them according to presence of CKD (2 eGFR <60mL/min/1.73m2), CVD (ischemic heart disease, stroke or heart failure), or both. We used 1 year of follow-up data to compare the annual outpatient, inpatient, emergency, pharmaceutical, and total medical care costs (2017 USD) between the four groups adjusted for age, sex, and non-white race. Of the 37,684 total patients, 16% had CKD without CVD, 12% (n=4,596) had CVD without CKD, 11% (n=4,089) had both, and 61% had neither. Patients with neither CKD nor CVD incurred adjusted total costs of $7,582 (Table). Costs were significantly higher in total and for all components among patients with CKD without CVD, and higher still among those with CVD without CKD. When both CKD and CVD were present, total, inpatient and emergency costs were approximately the sum of costs which each condition existed alone, CKD and CVD each approximately double annual medical costs, but the combination of the two conditions increases costs nearly 4-fold, underscoring the need for preventive therapies.

Disclosure

G.A. Nichols: Research Support; Self; Amarin Corporation, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Scientific Affairs, LLC., Merck Sharp & Dohme Corp. A.V. Ustyugova: Employee; Self; Boehringer Ingelheim International GmbH. A. Deruaz-Luyet: Employee; Self; Boehringer Ingelheim International GmbH. Employee; Spouse/Partner; Medtronic, Sanofi. K.G. Brodovicz: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc.

Funding

Boehringer Ingelheim
160-LB: Effect of Sodium-Glucose Cotransporter 2 Inhibitors on Hemodynamic and Metabolic Cardiovascular Markers in Patients with Type 2 Diabetes Mellitus
Authors: SATHAVARODOM NATTAPOL
Published: June 2019

Background: Sodium glucose co-transporter 2 (SGLT2) inhibitors could early reduce cardiovascular (CV) and heart failure (HF) risk in patients with type 2 diabetes mellitus (T2DM) in recent CV outcome trials. We hypothesized that benefit of SGLT2 inhibitors would be early on both hemodynamic and metabolic CV markers.

Objectives: The goal of this study was to examine the effects of empagliflozin or dapagliflozin on CV markers. Factors associated beneficial CV marker changes were determined.

Material and Method: This prospective study included 60 patients with T2DM, In ASCVD group (n = 18), all patients received empagliflozin (n = 18). In non-ASCVD groups (n = 42), they were allocated to received either empagliflozin or dapagliflozin. The study assessed the change in serum N-terminal pro-B-type natriuretic peptide (NT-proBNP), apolipoprotein B (apo B), and highly sensitive C-reactive protein (hsCRP) from baseline to 4, and 26 weeks.

Results: Median change of NT-proBNP from baseline after receiving SGLT2 inhibitors were -11.1 (-30.4, -1.3) pg/mL, and -11.5 (-30.4, -1.5) pg/mL at weeks 4, and 26, respectively (all p <0.05). Although, median change of body weight (BW) were initially -0.77 (-1.11, -0.44) kg and -1.65 (-2.3, -1.01) kg at the end of the study, both apo B and hsCRP were not statistically changed. We found that baseline NT-proBNP >125 pg/mL could predict beneficial in hemodynamic in CV marker changes with sensitivity 58.3%, specificity 96.6%, positive predictive value 87.5%, negative predictive value 84.8% and accuracy 85.4%.

Conclusion: We demonstrated that SGLT2 inhibitors had early beneficial effect in hemodynamic CV marker. Furthermore, SGLT2 inhibitors didn’t have detrimental effect on both atherogenic lipoprotein particle and inflammatory CV markers. Measurement of NT-proBNP level might enhance CV risk stratification and guide introduction of SGLT2 inhibitors in both ASCVD and non-ASCVD patients with T2DM.

Disclosure

N. Sathavarodom: None.
1652-P: The Association between Long-Term HbA1c Variability, Blood Pressure, Cholesterol, and Body Weight in Type 2 Diabetes: Subanalysis of ABC Study
Authors: MINATO SOICHIRO , MATSUTANI DAISUKE , TSUJIMOTO YUKI , KAYAMA YOSUKE , SAKAMOTO MASAYA , NISHIKAWA MASAKO , UTSUNOMIYA KAZUNORI
Published: June 2019

Aim: Visit-to-visit variability (VVV) of HbA1c was reported to be the risk of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM). However, factors related to VVV of HbA1c remain unclear. This study is first examined relationship between VVV of HbA1c and various parameters including VVV of blood pressure (BP), low-density lipoprotein-cholesterol (LDL-C), and body mass index (BMI).

Material and Methods: Analyzed were 4,678 patients with T2DM throughout Japan (38 hospitals). The inclusion criteria were patients whose HbA1c, BP, LDL-C, and BMI were measured 12 or more times during the 24-month period. VVV of HbA1c, BP, LDL-C, and BMI were evaluated using the coefficient of variation (CV). This study is sub-analysis of ABC trial (UMIN000034231).

Results: Mean age of participants was 61.3 ± 9.4 years (mean ± SD) and HbA1c was 57.2 ± 13.5 mmol/mol (7.4 ± 1.2%). Table shows univariate correlate and multiple regression analysis of HbA1c CV. HbA1c CV was correlated with HbA1c baseline, SBP CV, LDL-C CV, and BMI CV. In the multiple regression analysis, HbA1c baseline, LDL-C, and BMI CV were the strongest predictors of HbA1c CV.

Conclusion: VVV of HbA1c was strongly correlated with VVV of LDL-C and BMI, and HbA1c baseline in patients with T2DM. A large-scale clinical trial needs to be conducted to clarify factors affecting VVV of HbA1c.

Disclosure

S. Minato: None. D. Matsutani: None. Y. Tsujimoto: None. Y. Kayama: None. M. Sakamoto: None. M. Nishikawa: None. K. Utsunomiya: None.
1659-P: A Systematic Review of Trends in All-Cause Mortality among People with Diabetes
Authors: CHEN LEI , ISLAM RAKIBUL M. , WANG JOANNA , HIRD THOMAS R. , PAVKOV MEDA E. , GREGG EDWARD W. , TABESH MARYAM , KOYE DIGSU , HARDING JESSICA L. , SACRE JULIAN W. , BARR ELIZABETH L. , MAGLIANO DIANNA J. , SHAW JONATHAN E.
Published: June 2019

Some studies have reported falling mortality among populations with diabetes, but the consistency of this trend is unclear. We systematically reviewed studies published from 1980-2017 reporting all-cause mortality across 2 time-periods in people with diabetes. A total of 35 studies were found, providing data on 56 sex-specific or total populations with diabetes or type 2 diabetes. All studies were from high-income countries. Mortality declined in 80% of populations with diabetes in the 1980s, 53% in the 1990s, and 85% from 2000 onwards (Table). Falling mortality in diabetes occurred in 87% of Europid populations and in 10% of non-Europid populations. Of 25 populations with age-specific data, mortality declined in 29% of populations aged <40 years and in >60% of populations aged >55 years. Of 37 populations that reported on those with and without diabetes, greater or similar mortality reduction was observed among those with diabetes than without diabetes in 70% of populations.

In conclusion, mortality has declined in the majority of Europid populations with diabetes since 1980. However, most non-Europid and most younger populations show no such declines.

Disclosure

L. Chen: None. R.M. Islam: None. J. Wang: None. T.R. Hird: None. M.E. Pavkov: None. E.W. Gregg: None. M. Tabesh: None. D. Koye: None. J.L. Harding: None. J.W. Sacre: None. E.L. Barr: None. D.J. Magliano: None. J.E. Shaw: Advisory Panel; Self; Abbott, Merck Sharp & Dohme Corp. Speaker's Bureau; Self; AstraZeneca, Mylan, Roche Diabetes Care, Sanofi-Aventis.

Funding

Centers for Disease Control and Prevention
1662-P: Comparison of Anthropometric and Metabolic Parameters among Africans Living in America
Authors: AHMED ALI , SIRAJ ELIAS S. , DUBOSE CHRISTOPHER , MUGENI REGINE , HORLYCK-ROMANOVSKY MARGRETHE F. , ADUWO JESSICA Y. , WILLIAMS KEVIN JON , SUMNER ANNE E.
Published: June 2019

Differences in anthropometric and metabolic parameters among people of African, European, South Asian, and other origins are well described in the literature. In addition, we and others have reported that many of these parameters are different when comparing African Americans with Africans who recently moved to the U.S. In contrast, reports comparing African populations of various ethnicities and geographic areas are still lacking. The black sub-Saharan populations of Africa show variation in culture, cuisine, language, ethnicity and genetics. The Africans-in-America cohort was established to evaluate the cardiometabolic status of Africans living in the United States who self-identify as healthy. Our goal was to compare anthropometric and metabolic parameters in 419 African-born blacks currently living in Washington, DC. The African regions of origin were West 53% (222/419), Central 21% (89/419), and East 26% (108/419). The Table below shows key findings among the three groups. The prevalence of previously undiagnosed diabetes and prediabetes in the entire cohort was 6.2% and 31.5% respectively. Compared with West and Central Africans, East Africans had higher % body fat, plasma TG, MCV and eGFR but lower systolic BP, vitamin B12, frequency of variant hemoglobin and serum albumin. Further studies will be needed to understand the underlying reasons for these findings, their meaning and long-term consequences.

Disclosure

A. Ahmed: None. E.S. Siraj: Advisory Panel; Self; Sanofi. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc. C. DuBose: None. R. Mugeni: None. M.F. Horlyck-Romanovsky: None. J.Y. Aduwo: None. K. Williams: Advisory Panel; Self; Gemphire Therapeutics Inc. Stock/Shareholder; Self; Gemphire Therapeutics Inc., Hygieia. A.E. Sumner: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Minority Health and Health Disparities; National Institutes of Health Clinical Center
1667-P: Hemoglobin Glycation Index Is Associated with Nonalcoholic Fatty Liver Disease in Healthy Population
Authors: YOO JEE HEE , LEE WOO JE , PARK JOONG-YEOL , LEE JIWOO , KANG YU MI , JUNG CHANG HEE , CHO YUN KYUNG , PARK CHEOL-YOUNG
Published: June 2019

Aims: Hemoglobin glycation index (HGI), which quantifies interindividual variations in glycated hemoglobin (HbA1c), is known to be associated with diabetic complications and metabolic diseases. However, information on the association between HGI and nonalcoholic fatty liver disease (NAFLD) in healthy population, especially in Asian population is limited.

Methods: A total of 14,465 subjects without diabetes who underwent liver ultrasonography during routine health examination were enrolled and stratified in quartiles according to HGI levels.

Results: The prevalence of NAFLD significantly increased with HGI quartiles (24.8%, 29.7%, 32.6% and 40.6% in the 1st, 2nd, 3rd, and 4th HGI quartiles, respectively; p-value<0.001). As compared with the lowest HGI quartile group, the highest HGI quartile group had worse metabolic parameters including body weight, waist circumference, body mass index and lipid profiles. In the multiple logistic regression analysis adjusted for multiple factors, the odds ratio of having NAFLD was 1.564 (95% CI: 1.350-1.813, p <0.001) in the highest HGI quartile group.

Conclusions: Elevated HGI levels are independently associated with prevalence of NAFLD in a healthy Asian population.

Disclosure

J. Yoo: None. W. Lee: None. J. Park: None. J. Lee: None. Y. Kang: None. C. Jung: None. Y. Cho: None. C. Park: None.
1692-P: miR17 Overexpression or Deleting Its Target Gene Txnip Ameliorates Neural Tube Defect Formation in Diabetic Embryopathy
Authors: YANG PENGHUA , YANG PEIXIN
Published: June 2019

microRNAs (miR) play important roles in the induction of diabetic embryopathy. Our previous studies have demonstrated that high glucose in vitro and maternal diabetes in vivo suppressed miR-17 expression. To determine whether miR17 down-regulation is involved in maternal diabetes-induced neural tube defects (NTDs) formation, we created a miR-17 transgenic (Tg) mouse line in which miR-17 specifically overexpresses in the developing neuroepithelium. miR-17 Tg male mice crossed with nondiabetic and diabetic (streptozotocin-induced type 1 diabetes) wild type (WT) female mice to generate WT and Tg embryos. Under nondiabetic conditions, there was no NTDs in both WT and Tg embryos. The NTD rate of WT embryos was 52.4% (22 out of 42 embryos) in diabetic pregnancy, whereas miR-17 overexpression in the neuroepithelium significantly reduced the NTD rate to 8.1% (3 out of 37 embryos). Txnip up-regulation is implicated in the pathogenesis of diabetes and diabetic complications. Txnip is a predicted miR-17 target genes, and miR-17 overexpression abolished maternal diabetes-increased Txnip expression. To investigate whether Txnip participates in the pathogenesis of diabetic embryopathy, the Txnip gene was deleted specifically in the neuroepithelium using the Cre-flox (f) approach by crossing Txnipf/w; nestin-cre male mice with nondiabetic or diabetic Txnipf/f female mice. Comparing to the NTD rate of 19.4% (7 out of 36 embryos) in WT embryos, embryos with conditional Txnip deletion had an NTD rate of 8.3% (1 out of 12 embryos). Our findings indicated that the miR-17-Txnip circuit is critically involved in the induction of diabetic embryopathy.

Disclosure

P. Yang: None. P. Yang: None.

Funding

American Diabetes Association (1-13-BS-220 to P.Y.); National Institutes of Health
1714-P: Absence of CYP8B1 Increases Insulin Sensitivity in Part via Modulation of the Gut Microbiome
Authors: CORLIANÒ MARIA , ZHONG SHIQI , SINGARAJA ROSHNI R.
Published: June 2019

Disruption of a key bile acid synthesis enzyme, CYP8B1, results in the absence of cholic acid (CA), increased levels of chenodeoxycholic acid (CDCA) and improved glucose metabolism in mice. However, the mechanism by which the BAs affect glucose metabolism remains unclear. We found that the absence of CYP8B1 increases insulin sensitivity in chow-fed mice, making them phenotypically similar to antibiotic-treated wild type mice, suggesting a role for the microbiome in the beneficial effect derived from CYP8B1 depletion. The aim of this study is to determine if the gut microbiome contributes to the increased insulin sensitivity observed in the absence of CYP8B1. Ten to twelve weeks old female CYP8B1-/- and CYP8B1+/+ mice (n=8-10/group) were fed chow diet ad libitum and OGTT, ITT and GSIS were evaluated. The C2C12 mouse myotubes were exposed to either CA or CDCA, and Insr and Tgr5 levels were measured by qPCR. Moreover, 10 to 12 weeks old female CYP8B1-/- and CYP8B1+/+ mice (n=8-10/group) received a cocktail of antibiotics (1 g/L) in drinking water. Plasma bile acids were measured by GC-MS and ITT was evaluated every two weeks. CYP8B1-/- mice showed significantly increased insulin sensitivity compared to wild type littermates (p<0.001) but no differences in OGTT and GSIS. In addition, the in vitro studies show that exposure of the myotubes to CDCA resulted in significant increases in Insr (t-test, p=0.009) and Tgr5 (t-test, p=0.02). We found that the alteration of the gut microbiome by antibiotics in the wild type mice abolished the difference in ITT between CYP8B1-/- and CYP8B1+/+ mice (p=0.08). Furthermore, the antibiotic-treated wild type mice displayed a significant increase in the CA:CDCA ratio (p<0.0001), mimicking the bile acid pool composition of the untreated CYP8B1-/- littermates. Our results suggest that the specific microbiome composition in the absence of CYP8B1 might play a critical role in enhancing the insulin sensitivity, and therefore glucose metabolism in mice.

Disclosure

M. Corlianò: None. S. Zhong: None. R.R. Singaraja: None.
1721-P: Effect of the TCF7L2 Variant rs7903146 T Allele on the Incretin Effect in Individuals with Normal Glucose Tolerance or Type 2 Diabetes
Authors: MATHIESEN DAVID S. , LUND ASGER B. , HANSEN KATRINE BAGGE , JUNKER ANDERS , IDORN THOMAS , HORNUM MADS , JONSSON ANNA , HANSEN TORBEN , VILSBØLL TINA , BAGGER JONATAN I. , KNOP FILIP K.
Published: June 2019

Background and Aim: The T allele of TCF7L2 rs7903146 is a common genetic variant associated with type 2 diabetes. The mechanisms underlying this association are not fully understood, but diminished incretin-induced insulin secretion has been suggested. We undertook this study to evaluate the effect of the TCF7L2 rs7903146 T allele on the incretin effect in normal glucose tolerant individuals and patients with type 2 diabetes.

Methods: The incretin effect was assessed by relating the difference in integrated beta cell secretory responses to oral glucose tolerance test (OGTT) and isoglycemic intravenous glucose infusion (IIGI) to the response during OGTT in 36 normal glucose tolerant individuals (of whom 12 had the risk-conferring variant rs7903146 (TC/TT)) and 20 patients with type 2 diabetes (10 with TC/TT). Homeostatic model assessment (HOMA) was used to estimate insulin resistance.

Results: No differences in incretin effect estimates between risk allele carriers and non-carriers in the two groups were observed. Normal glucose tolerant individuals with rs7903146 displayed higher C-peptide levels in the fasting state (P=0.029) as well as during OGTT (P=0.029) and IIGI (P=0.015) compared to normal glucose tolerant non-carriers. Normal glucose tolerant risk allele carriers were more insulin resistant compared to normal glucose tolerant non-carriers (P=0.042). No detectable differences in glucose metabolism were found between risk allele carriers and non-carriers in the type 2 diabetes group.

Conclusions: The TCF7L2 rs7903146 T allele was not associated with reduced incretin effect in these relatively small cohorts of normal glucose tolerant individuals and patients with type 2 diabetes. Insulin resistance rather than beta cell secretory defects distinguished the normal glucose tolerant risk allele carriers examined here, from the normal glucose tolerant non-carriers.

Disclosure

D.S. Mathiesen: None. A.B. Lund: None. K.B. Hansen: None. A. Junker: None. T. Idorn: Employee; Self; Novo Nordisk A/S. M. Hornum: None. A. Jonsson: None. T. Hansen: None. T. Vilsbøll: None. J.I. Bagger: None. F.K. Knop: Advisory Panel; Self; AstraZeneca, MedImmune, Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk A/S, Sanofi. Consultant; Self; Amgen Inc., Carmot Therapeutics, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker's Bureau; Self; AstraZeneca, MedImmune, Merck Sharp & Dohme Corp., Mundipharma, Norgine, Novo Nordisk A/S.

Funding

Novo Nordisk Foundation (NNF17OC0029370)
1729-P: Circadian Patterns of Autoimmune Components in the Blood of Persons with Type 1 Diabetes: Implications for the Timing of Blood Sampling
Authors: BELI ELENI , DIMEGLIO LINDA , WOERNER STEPHANIE , EVANS-MOLINA CARMELLA , MCGRAIL KIERAN M. , WASSERFALL CLIVE , ATKINSON MARK A. , BEAM CRAIG
Published: June 2019

Purpose: Immune populations and cytokines are known to exhibit distinct circadian ("daily") variations. We sought to characterize circadian-related immune variation in persons with type 1 diabetes (T1D) to ascertain whether sampling of peripheral immune biomarkers should be timed with circadian patterns

Methods: We enrolled 10 adults (6 female) volunteers between 18 and 40 years of age, with T1D diagnosed for at least 12 months and free of other diseases. Subjects were admitted to the Research Center and had blood collections performed every 4 hours over a 24-hour period. Samples were processed and aliquoted after each draw. Flow cytometric analyses of central memory, regulatory, naïve T- and B-cells, monocytes and NK cell frequencies were performed in 200μl. Circadian variation patterns were characterized with fitted cosine curves using COSINOR analysis.

Results: Significant circadian patterns were identified for CD4 and CD8 T cells, T regulatory cells (T regs), Natural killer T cells (NKT), Dendritic Cells (DC) and B cells in T1D subjects. All populations except of NKT cells peaked during the night with peak levels estimated to occur respectively at (24:00 hour [95% CI]); CD4 0030 [2396,0040]; CD8 0106 [2358,0014]; T regs 2349 [2395,0005]; NKT 1527 [1217,1819]; DC 0070 [2392,0008]; B cells 0111 [2382,0014].

Conclusion: Clinical studies of immune interventions meant to influence immune populations should sample these populations at consistent times of day, and likely at peaks, or nadirs, in order to have the greatest range for therapeutic effect to be demonstrated. For B-cell reduction interventions (such as Rituximab), our study indicates the best time for PBMC sampling would be around midnight. For therapies targeting immune cell expansion, e.g., Treg expansion, the sampling may be better at nadir, where the increase will be the greatest- i.e., approximately noon.

Disclosure

E. Beli: None. L. DiMeglio: Research Support; Self; Amgen Inc., Caladrius Biosciences, Inc., Janssen Research & Development, Medtronic, Sanofi. Other Relationship; Self; Dexcom, Inc. S. Woerner: None. C. Evans-Molina: None. K.M. McGrail: None. C. Wasserfall: None. M.A. Atkinson: None. C. Beam: None.

Funding

JDRF International (3-SRA-2015-7-M-RJDRF, 3-APF-2017-396-A-N)