bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal Assessment of Disordered Eating Behavior (DEB) Risk in Teens with Type 1 Diabetes (T1D)
Authors: CECILIA-COSTA RAQUEL , GUO ZIJING , HARRINGTON KARA R. , VOLKENING LISA , LAFFEL LORI M.
Published: June 2018

DEBs in T1D are associated with poor glycemic control and development of diabetes complications. We assessed progression of risk for DEBs over 18 months in 169 teens, ages 13-17, with T1D. Teens completed the Diabetes Eating Problem Survey-Revised (DEPS) every 6 months. Teens were categorized by DEB risk: low, DEPS<10; moderate, DEPS 10-19; high, DEPS≥20.

At baseline, teens (54% male) were 14.9±1.3 (M±SD) years old and had T1D for 7.4±3.7 years; 37% were overweight/obese. A1c was 8.5±1.0%; 68% were pump treated. Baseline DEB risk assessment included 60% at low risk, 27% at moderate risk, and 12% at high risk. Initial DEB risk was highly predictive of DEB risk after 18 months (Figure). Most teens (66%) stayed at their same risk level, 14% improved, and 20% progressed. In a multivariate mixed model predicting DEPS scores over 18 months, female sex (p=.0002), overweight/obesity (p=.0004), less frequent BG monitoring (p=.0008), and higher A1c (p=.003) significantly and independently predicted higher DEPS scores.

Without intervention, DEB risk appears to remain relatively stable in teens with T1D. Therefore, it is important to prevent onset of DEBs, potentially by targeting teens who are female and overweight/obese as well as teens who are less adherent (e.g., few BG checks/day) and have rising A1c levels. Identifying DEB risk may permit early intervention and prevention of progression to clinical eating disorders.

Disclosure

R. Cecilia-Costa: None. Z. Guo: None. K.R. Harrington: None. L. Volkening: None. L.M. Laffel: Consultant; Self; Eli Lilly and Company, Novo Nordisk Inc., Sanofi US, MannKind Corporation, Roche Diagnostics Corporation, Dexcom, Inc., Insulet Corporation, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Johnson & Johnson Diabetes Institute, LLC..
Associations of Well-Being and Perceived Stress with Diabetes Control and Self-Care Behavior in Adolescents with Type 1 Diabetes
Authors: ADDALA ANANTA , CHAN RANDALL , WEIGENSBERG MARC
Published: June 2018

Background: Psychosocial determinants of health are thought to play a significant role in type 1 diabetes (T1D) management. Higher rates of stress have also been shown to result in poorer health outcomes. The role that self-perceived well-being, stress, and barriers to diabetes care have in T1D outcomes is less well known.

Methods: At routine clinic visits, patients with known T1D completed a self-reported survey packet consisting of Perceived Stress Scale-4 (PSS), Diabetes Distress Scale-2 (DDS), and Global Well-Being Scale (GWB), as well as a novel barriers-to-care survey we developed. Inclusion criteria included all T1D patients older than 13 years of age (n=49); the instrument was administered to all participants recruited. Multivariate linear regression analysis assessed correlations between objective data (HgA1c and blood glucose checks per day) and the four self-reported measures.

Results: GWB scale was inversely correlated with HgA1C (R2=0.111; p=0.04) and positively correlated with glucose checks per day (R2=0.211; p=0.001). PSS scale was positively correlated with HgA1C (R2=0.109; p=0.04) and DDS was inversely correlated with glucose checks per day (R2=0.103; p=0.01). Increasing numbers of barriers trended toward positive correlation with HgA1C and inverse correlation with glucose checks per day but did not reach statistical significance.

Conclusion: Patient-reported markers of well-being and stress were predictive of home glucose monitoring frequency and glycemic control. The associations between HgA1C as well as glucose monitoring with well-being suggest that attention to assessing and optimizing positive psychological states may be valuable in achieving improved diabetes outcomes in adolescents with T1D.

Disclosure

A. Addala: None. R. Chan: None. M. Weigensberg: None.
Racial Ethnic Disparities in Diabetes Youth Participating in Diabetes Summer Camps
Authors: VALENZUELA JESSICA M. , MARTIN MEGAN T. , RECORDS SAM , O'NEAL KELLY , MUELLER KELLY , WOLF RISA M.
Published: June 2018

Background: Diabetes camps are beneficial for campers, including increases in diabetes knowledge, glycemic control and psychological functioning. Racial/ethnic minority youth are likely to have poorer disease management and glycemic control, more complications, and are often managed with less intensive, less technologically advanced regimens. We hypothesized that racial/ethnic minority youth with type 1 diabetes (T1D) would have reduced participation in diabetes summer camps.

Methods: We reviewed de-identified data from 5033 campers with T1D who participated in a network of 46 ADA-affiliated summer camps during the 2017 season. We performed t-tests and chi-square analysis to analyze the demographic characteristics of white vs. non-white campers.

Results: Campers with T1D came from all over the U.S. (49 states), 68.4% were return campers, 55% were female, ages ranging from 4-18 (m =11.7 ±2.8). Of campers, 73.2% were on insulin pump regimens. Camps cost $0 to $1400 (Day Camps M=$158.83 ± $103.69, Residential Camps M=$622.73 ± $274.26). Campers identified as caucasian (83.9%), black (4.8%), Hispanic (3.9%), Asian/Pacific Islander (2.7%), and Multiracial (3.9%). We compared ethnicity data to the 2009 SEARCH data from children and adolescents where T1D prevalence was 72% in caucasians, 9% black, 15% Hispanic and 2% Asian/Pacific Islander. Camper demographics were significantly different than the general population of children with T1D (p<0.001). Racial/ethnic minority status was associated with type of camp attended (day vs. residential), and minority campers were less likely to be on insulin pump therapy.

Conclusions: Children of ethnic minorities with diabetes are underrepresented in diabetes camps nationwide compared to the prevalence of diabetes in each minority group as described by the SEARCH study. This highlights the need to assess barriers to camp attendance in these communities and to design outreach programs to increase minority youth participation in the diabetes camp experience.

Disclosure

J.M. Valenzuela: None. M.T. Martin: None. S. Records: None. K. O'NEal: None. K. Mueller: None. R.M. Wolf: None.
PKC Modulates sFlt1 Production by Human Placental Trophoblasts in Response to Oxidized LDL
Authors: CHOW REBECCA P. , ZHAO JIAWU , YU JEREMY
Published: June 2018

Preeclampsia (PE) is a leading cause of maternal and perinatal mortality and mortality, and its prevalence is 4 fold higher in women with diabetes than those without: the underlying mechanism is unclear. The anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt1) plays a key role in PE pathogenesis. Evidence suggests that PKC activation, which is associated with the development of diabetic vascular complications, may mediate the enhanced sFlt1 release in non-trophoblast cells. We aimed to determine the role of PKC in the regulation of sFlt1 expression in placental trophoblasts, and whether diabetic conditions upregulate sFlt1 expression via the PKC pathway. Human trophoblasts HTR8/SVneo were treated in three separate experiments with PKC activator phorbol-12-myristate-13-acetate (PMA), or diabetes stimuli ’heavily oxidized, glycated’ low-density lipoproteins (HOG-LDL) vs. native LDL ± high glucose (30 mM), over 24h, with or without PKC inhibitor GF109203X (GX). Both sFlt1 mRNA expression (RT-PCR) and protein release (ELISA) were measured. Compared to the control, PMA (5 nM) increased sFlt1 mRNA expression (2.5 fold, p<0.001) and protein release (383.8 ± 27.4 vs. 118.3 ± 21.3 pg/ml, p<0.001) in trophoblasts; these effects were entirely abrogated by the pre-treatment with 5 uM GX for mRNA expression (by 54%, p<0.001) and protein release (115.5 ± 20.9 pg/ml, p<0.001) vs. PMA-treated cells. Similarly, HOG-LDL (50 µg/ml) increased sFlt1 mRNA expression (3.7 fold, p<0.001) and protein release (126.4 ± 16.3 vs. 55.1 ± 2.4 pg/ml, p<0.001), and the both effects were partially abolished by GX (by 33-37%, p<0.05). High glucose did not significantly affect sFlt1 expression, or alter the effect of HOG-LDL. The data suggest that modified lipoproteins may promote PE development in women with diabetes, at least in part via PKC-mediated upregulation and release of sFlt1. These findings provide new insights into disease mechanisms, and may lead to new targets for prevention and treatment of PE.

Disclosure

R.P. Chow: None. J. Zhao: None. J. Yu: None.
A Three-Way Accuracy Comparison of the Dexcom G5, Abbott Freestyle Libre Pro, and Senseonics Eversense CGM Devices in an Outpatient Study of Subjects with Type 1 Diabetes
Authors: JAFRI RABAB Z. , BALLIRO COURTNEY A. , EL-KHATIB FIRAS , MAHENO MICHELE , HILLARD MALLORY A. , O'DONOVAN ALEXANDER J. , SELAGAMSETTY RAJENDRANATH , ZHENG HUI , DAMIANO EDWARD , RUSSELL STEVEN J.
Published: June 2018

There are no published studies directly comparing the accuracy of continuous glucose monitoring (CGM) devices in the outpatient setting. We tested the performance of the Dexcom G5, Abbot Freestyle Libre Pro, and Senseonics Eversense (an implantable CGM approved in Europe) during a 6-week, free-living, outpatient bionic pancreas study involving 23 subjects with type 1 diabetes who wore all 3 devices concomitantly. The primary outcome was the mean absolute relative difference (MARD) vs. plasma glucose (PG) values measured with the Nova Biomedical StatStrip Xpress meter that was also used for calibrations according to the manufacturer's instruction (except for Libre Pro that is not calibrated). We compared PG values with CGM readings when they were available from all 3 CGMS in the 5 minutes preceding the PG values (n=829 sets). Since the Libre Pro records readings every 15 minutes, we also did a two-way comparison between the G5 and the Eversense that allowed a higher number of comparisons (n=2277 sets). Statistical significance was determined using a repeated measurements model fitted with the generalized estimating equation method. All 3 CGM systems produced higher average MARDs than during in-clinic studies. However, since all three CGM systems were worn by the same individuals and used the same meter for calibration and as comparator, we were able to directly compare their performance under real-world conditions. In the 3-way comparison Eversense achieved the lowest nominal MARD (14.8%) followed by Dexcom G5 (16.3%) and Libre Pro (18.0%) (Eversense vs. Libre Pro p=0.004, other comparisons p=NS). In the 2-way comparison the MARD difference between Eversense (15.1%) and G5 (16.9%) was statistically significant (p=0.008). We found that the point accuracy of the Eversense was significantly better than two other CGM systems. The Eversense CGM system may be useful to provide glucose values to artificial pancreas devices.

Disclosure

R.Z. Jafri: None. C.A. Balliro: None. F. El-Khatib: Stock/Shareholder; Self; Beta Bionics. Employee; Self; Beta Bionics. M. Maheno: None. M.A. Hillard: None. A.J. O'Donovan: None. R. Selagamsetty: None. H. Zheng: None. E. Damiano: Other Relationship; Self; Beta Bionics. S.J. Russell: Other Relationship; Self; Beta Bionics, Novo Nordisk Inc.. Advisory Panel; Self; Companion Medical, Tandem Diabetes Care, Inc., Unomedical a/s. Research Support; Self; Beta Bionics, Zealand Pharma A/S, MITRE Corporation.
High Maternal DHA Levels in Hawaiian Women Decrease Insulin Resistance
Authors: ALVARADO FERNANDA , TSAI PAI-JONG , MINIUM JUDI , CATALANO PATRICK , O'TIERNEY-GINN PERRIE
Published: June 2018

Obesity prevalence during pregnancy (PG), a significant risk factor for metabolic inflammation and subsequent increase in insulin resistance (IR), has increased ∼ 35% in the last 20 years. Offspring of obese (OB) women are at a higher risk of metabolic dysfunction. Omega-3 fatty acids such as DHA have been shown to decrease IR in animals, though the effects of DHA in PG women are unclear. We hypothesize that high plasma DHA levels are associated with lower IR in PG women in an environment of high omega-3 intake (Hawaii), but differ in metabolic effect in OB vs. lean (LN) women. We evaluated 54 healthy, normal glucose tolerant women and their offspring at term elective C-section in Honolulu. We grouped subjects according to their pre-PG BMI into LN and OB. We measured maternal plasma insulin, glucose, C-reactive protein (CRP), and DHA concentration (gas chromatography/mass spectrophotometry) and calculated the homeostatic model assessment for IR (HOMA-IR). As expected, IR was higher in OB women (Table 1). Maternal DHA was negatively correlated with maternal HOMA-IR (R2= 0.25 p = 0.001), and CRP (R2=0.15 p= 0.004) among all women. These correlations persisted for OB women: HOMA-IR (R2=38 p=0.0007), CRP (R2=0.20 p=0.01); but not for LN women. High maternal DHA is associated with lower inflammation and IR in OB PG women at term. We speculate that high pre-PG omega-3 intake has a significant metabolic impact on insulin sensitivity, especially in OB women.Table 1Lean (BMI: 16-24.9 kg/m2 n=29)Obese (BMI>30, n=26)P.valueGestational Age at delivery (wks)38.8 ± 0.639.1 ± 0.40.088Pre-Pregnancy BMI (kg/m2)21.1 ± 2.236.8 ± 6.9<0.0001DHA (µmol/L)453 ± 187347 ± 1200.02HOMA IR1.1 ± 0.82.4 ± 1.4<0.0001CRP (ng/mL)5180 ± 2688 7859 ± 23180.0005Birth Weight (kg)3.3 ± 0.43.5 ± 0.40.04

Disclosure

F. Alvarado: None. P. Tsai: None. J. Minium: None. P. Catalano: None. P. O'Tierney-Ginn: None.
Is Gestational Weight Gain Associated with Change in Ectopic Lipid Stores?
Authors: VESCO KIMBERLY , LEO MICHAEL C. , FRANCISCO MELANIE , BAETSCHER ERIC , ROONEY WILLIAM , MARSHALL NICOLE E. , PURNELL JONATHAN Q.
Published: June 2018

Background: In nonpregnant adults, increased ectopic lipid stores [intrahepatic (IHL), intramyocellular (IMCL)] are associated with increased risk of diabetes mellitus and nonalcoholic fatty liver disease. While the amount of weight gained during pregnancy is significantly associated with the amount of weight retained after delivery, it is unclear whether weight gain during pregnancy is correlated with increased IHL or IMCL stores; thus, predisposing women with postpartum weight retention to increased risk of diabetes and NAFLD.

Methods: We evaluated 36 women with an enrollment BMI between 18.5 and 38 kg/m2 at a mean (min-max) of 15.6 weeks (12.9-17.3) gestation and again at 34.2 (32.1-37.7) weeks gestation. Women with pregestational diabetes and multifetal pregnancies were excluded. Participants underwent 1H magnetic resonance spectroscopy to assess IHL and IMCL content, and air displacement plethysmography to assess body weight, percent (%) body fat, fat mass, and lean mass.

Results: The participants were primarily white (89%) with mean age of 30.4 years. Table shows mean, standard deviation (SD), and Pearson’s correlation coefficients for all measures.

Conclusion: Gestational weight gain tracks closely with increase in fat mass during pregnancy, but is not significantly correlated with change in IHL or IMCL stores.able. Means, standard deviations, and Pearson’s correlation coefficients for weight and total and ectopic fat measures at early pregnancy and from early to late pregnancy.MeasureEarly pregnancy Mean (SD)Mean change (SD) from early to late pregnancyCorrelation of change with weight changeWeight (kg)72.2 (10.3)10.4 (3.2)--BMI (kg/m2)25.2 (3.4)3.6 (1.1)--Body fat (%)33.6 (6.5)-0.6 (3.0).38*Fat mass (kg)24.8 (7.6)3.1 (3.1).70*Lean mass (kg)47.5 (5.1)7.4 (2.4).40*IHL (% water peak)0.5 (0.2)0.1 (0.2)-.12IMCL (% water peak)0.9 (0.4)0.2 (0.5)-.25*p<.05

Disclosure

K. Vesco: None. M.C. Leo: None. M. Francisco: None. E. Baetscher: None. W. Rooney: None. N.E. Marshall: None. J.Q. Purnell: Advisory Panel; Self; Novo Nordisk Inc..
Subclinical Inflammation and Lymphocytes in Subcutaneous and Visceral Adipose Tissue—The Influence of Pregnancy and Gestational Diabetes Mellitus
Authors: CINKAJZLOVA ANNA , ANDERLOVÁ KATEřINA , SIMJAK PATRIK , LACINOVÁ ZDENA , KLOUCKOVA JANA , KRATOCHVILOVA HELENA , KREJCI HANA , MRAZ MILOS , HALUZIK MARTIN , KRSEK MICHAL
Published: June 2018

Obesity and type 2 diabetes mellitus are accompanied by low-grade inflammation and changed immune cell composition in adipose tissue. However, little is known about subclinical inflammation in gestational diabetes mellitus (GDM). The aim of our study was to analyse lymphocyte populations in subcutaneous (SAT) and visceral adipose tissue (VAT) together with systemic levels and mRNA expression of selected inflammatory markers in these depots and placenta. Thirty-seven pregnant females - 21 with GDM (GDM group) and 16 without GDM (P group) - were included into the study. Blood samples were taken in 28th-32th and 36th-38th gestational week and 6-12 months after delivery and SAT, VAT and placental samples were obtained during delivery. Lymphocytes were assessed as percent of CD45+ cells measured by flow cytometry. In both groups CD45+ lymphocytes were higher in VAT compared to SAT (19.2 ± 2.2 vs. 6.5 ± 0.7%, p<0.001 for GDM and 18.3 ± 3.4 vs.7.8 ±1.6, p=0.0for P, respectively). In GDM group T helper (CD4+) cells were higher in SAT compared to VAT (37.6 ± 2.4 vs. 28.6 ± 2.6%, p=0.019), resulting in a higher ratio of CD4+/CD8+ cells. Similarly, the amount of B (CD19+) and NKT (CD16/56+CD3+) cells was higher in SAT relative to VAT in GDM group, but not in P group. In contrast, NK (CD15/56+CD3-) cells were increased in VAT compared with SAT in GDM group (17.9 ± 3.1 vs. 9.1 ± 1.3%, p=0.015), while no difference was seen in P group. CRP levels did not differ between GDM and P group, while TNF-α concentrations were higher in GDM throughout the study (7.92 ± 0.69 vs. 4.59 ± 0.61 pg/ml, p=0.001). Placental mRNA expression of IL-10 and IL-8 was elevated in GDM vs. P group with no difference between SAT and VAT depots. Taken together GDM is associated with increased systemic TNF-α levels and changed lymphocyte content in different adipose tissue depots. These changes could be in part responsible for increased risk of complications for both mother and child during and after pregnancy.

Disclosure

A. Cinkajzlova: None. K. Anderlová: None. P. Simjak: None. Z. Lacinová: None. J. Klouckova: None. H. Kratochvilova: None. H. Krejci: None. M. Mraz: None. M. Haluzik: None. M. Krsek: None.
The Association of Pregnancy Number and Outcome with Mortality in Type 1 Diabetes
Authors: COSTACOU TINA , RUBINSTEIN DEBRA , ORCHARD TREVOR J.
Published: June 2018

Women with type 1 diabetes are at greater risk of adverse pregnancy outcomes and complications compared with the general population. Whether the number and outcome of pregnancies predict mortality risk, however, is not well studied. We thus assessed this hypothesis among women with childhood-onset type 1 diabetes. Female participants (n=325, mean age 28 and duration 19 years) of the Pittsburgh Epidemiology of Diabetes Complications (EDC) study, a prospective investigation of childhood onset type 1 diabetes, were selected for study. Pregnancy data were available for 320 women (98.5%). During 25 years of follow-up, 25.9% died (n=83). Excluding women (n=4) with twin pregnancies, no differences were observed in the proportion having been pregnant or in the number of pregnancies by mortality status. However, among those with at least one pregnancy (and adjusting for the total number of pregnancies), deceased were more likely to have had fewer live births and induced abortions but a greater number of spontaneous abortions and stillbirths (all p≤0.05). In multivariable Cox models adjusting for traditional baseline risk factors, having ever been pregnant was associated with a borderline inverse mortality risk (HR=0.65, p=0.07). In addition, among women with at least one pregnancy, adjusting (among other risk factors) for the total number of pregnancies, ≥ 2 spontaneous abortions (HR=3.5, p=0.03); ≥ 2 stillbirths (HR=9.1, p=0.02); and ≥ 2 occurrences of any adverse pregnancy outcome (i.e., tubal/ectopic pregnancies, spontaneous abortions, stillbirths; HR=3.9, p=0.007) were associated with an increased risk of death. Women whose pregnancy outcomes were all spontaneous abortions were at tenfold increased risk for mortality (p=0.004) whereas those with all preterm births were 76% less likely to die (HR=0.24, p=0.06).

In conclusion, adverse pregnancy outcomes among women with type 1 diabetes are associated with a greater mortality risk even after adjustment for traditional risk factors and diabetes control.

Disclosure

T. Costacou: None. D. Rubinstein: None. T.J. Orchard: None.
Comparison of Cardiometabolic Risk Factors in Offspring of Diabetic Mothers (ODM) and Nondiabetic Mothers (ONDM) in India
Authors: WAGLE SONALI S. , KUMARAN KALYANARAMAN , LADKAT RASIKA , BHAT DATTATRAY , YAJNIK PALLAVI C. , YAJNIK CHITTARANJAN S.
Published: June 2018

Background: Maternal diabetes is a risk factor for obesity and glucose intolerance in the child, and contributes to the escalating epidemic of diabesity. This could have both a genetic and fetal programming basis. Only sparse data is available in India. We followed children born to diabetic and nondiabetic mothers 2-26 years after delivery to assess their cardio-metabolic risk factors.

Methods: Of 861 women diagnosed and treated for diabetes in pregnancy (1986-2014), we traced 346 and studied 200 children (ODM). We also studied 177 children of nondiabetic mothers (ONDM), matched for age, gender and socioeconomic status. We measured anthropometry, body composition (DXA) and a capillary blood glucose (<10y, 119 ODM, 93 ONDM) or a 1.75g/kg OGTT with venous blood (>10y, 81 ODM, 84 ONDM). Overweight+obesity was diagnosed by IOTF (≤18y) or WHO criteria (>18y). Glucose tolerance was classified by the ADA 2014 criteria. We compared cardio-metabolic risk factors in ODM and ONDM by calculating age and gender specific SD scores (reference ONDM).

Results: Three (4%) ODM were known diabetic (diagnosed at 16, 14 and 23y, 2 receiving OHA and 1 insulin), one was diagnosed on testing. ODM had higher BMI, skinfolds, body fat percent, and circulating glucose, insulin, total and LDL cholesterol, and triglyceride concentrations. ODM had higher HOMA-IR and pulse rate but lower disposition index (HOMA-β/HOMA-IR) and diastolic blood pressure. Prediabetes (IFG+IGT) (37 vs. 20%, p=0.005) and overweight+obesity (24 vs. 15%, p=0.014) were more common in ODM compared to ONDM.

Conclusions: We confirm elevated risk of obesity, adiposity, diabetes and other cardio-metabolic risk factors in children of Indian diabetic mothers. Despite following the current standards of practice for GDM management, the offspring continue to have high risk of diabesity. This suggests a need for reevaluation of current standards of care which overlook the peri-conceptional window of fetal programming.

Disclosure

S.S. Wagle: None. K. Kumaran: None. R. Ladkat: None. D. Bhat: None. P.C. Yajnik: None. C.S. Yajnik: None.
Maternal Postprandial Triglycerides in the Home Setting
Authors: BARRETT HELEN L. , DEKKER MARLOES NITERT , DE JERSEY SUSAN J. , D'EMDEN MICHAEL C. , CALLAWAY LEONIE , DAVID MCINTYRE H.
Published: June 2018

Background and Aims: Elevated maternal triglycerides (TG) have been associated with adverse pregnancy outcomes including an increased risk of preeclampsia and macrosomia. Maternal TG are primarily measured in the fasting state and at single time points during pregnancy. Temporal and prandial changes in TG levels during pregnancy are not well described. The purpose of this study was to examine flux of capillary glucose and TG in late pregnancy, how they are influenced by high and low fat meals, and whether they relate to infant body composition.

Materials and Methods: Women in the third trimester of pregnancy completed 4 days of home capillary glucose and TG monitoring (4 times a day (fasting and two hours post each meal)). Using the Roche Accutrend Plus meter. Each woman consumed an isocaloric high fat (41%) and a low fat (25%) breakfast meal on different days during the study period. Area under the curve (AUC) for the capillary glucose and TG measures after the standardized meals was calculated using trapezoidal approximation. AUC for women with and without GDM was compared for each meal and metabolic measure. Infant body fat % was measured by air displacement plethysmography.

Results: To date, thirteen women, 7 with GDM and 6 normoglycaemic have completed the study. Median capillary glucose levels: fasting 5.0 (95% CI 4.6-5.2) mmol/L and postprandial 6.0 (95% CI 5.7-6.2) mmol/L. Median capillary TG: fasting 3.3 (95% CI 2.9-3.8) mmol/L and postprandial 3.6 (95% CI 3.2-3.8) mmol/L. Mean infant body fat % 10.6 (SD4.9)%. There were no significant differences in capillary glucose or triglycerides between the meals although capillary glucose trended higher with the low fat meal. GDM status did not affect the AUC glucose or AUC triglycerides for either meal.

Conclusion: This study demonstrates that capillary triglycerides can be monitored at home in a similar fashion to capillary glucose. Capillary triglyceride levels were not related to infant anthropometry and did not vary significantly with meal fat content. Recruitment is ongoing.

Disclosure

H.L. Barrett: None. M. Dekker: Speaker's Bureau; Self; Abbott. Other Relationship; Self; Nestlé. S.J. de Jersey: None. M.C. d'Emden: Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company, Boehringer Ingelheim GmbH. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Sanofi, Novo Nordisk A/S, Novartis Pharmaceuticals Corporation. L. Callaway: None. H. McIntyre: Speaker's Bureau; Self; Novo Nordisk Inc.. Research Support; Self; Danish Diabetes Academy.
Maternal Metabolites during Pregnancy Are Associated with Newborn Outcomes
Authors: KADAKIA RACHEL , NODZENSKI MICHAEL , TALBOT OCTAVIOUS , KUANG ALAN , BAIN JAMES R. , MUEHLBAUER MICHAEL , ILKAYEVA OLGA , O'NEAL SARA K. , LOWE LYNN P. , METZGER BOYD E. , SCHOLTENS DENISE , LOWE WILLIAM ,   HAPO STUDY COOPERATIVE RESEARCH GROUP
Published: June 2018

The maternal metabolome serves as a proxy for the fetus’s metabolic environment, but its impact on newborn outcomes is largely unknown. To address this, we determined the association of maternal metabolites with newborn adiposity and hyperinsulinemia in a multiethnic cohort of mother-newborn dyads. Targeted and nontargeted metabolomics assays were performed on fasting and 1 hour serum samples from 1600 mothers in four ancestry groups (Northern European, Afro-Caribbean, Mexican-American, and Thai) who participated in the Hyperglycemia and Adverse Pregnancy Outcome Study, underwent an OGTT at ∼28 weeks gestation, and whose newborns had anthropometric measurements at birth. Maternal metabolite-newborn phenotype associations were investigated using 1) per-metabolite analyses within and across ancestries and 2) network analyses to identify interconnected metabolites associated with phenotypes. Meta-analyses demonstrated more associations of maternal 1 hour vs. fasting metabolites with newborn outcomes. At fasting, maternal triglycerides, valine, pyruvate, and acylcarnitine (AC) C20 were associated with newborn birthweight, cord C-peptide, and/or sum of skinfolds (SSF). At 1 hour, several amino acids (AAs), ACs, fatty acids (FA), and lipid metabolites were associated with one or more of these same outcomes in models adjusted for maternal BMI or glucose. For example, the branched-chain amino acid valine and its carnitine ester AC C4/Ci4 were associated with cord C-peptide at 1 hour independent of maternal BMI or glucose. Network analyses revealed clusters of fasting ACs, AAs, FA and lipid metabolites associated with cord C-peptide and SSF, with the addition of branched-chain and aromatic amino acids at 1 hour. Maternal metabolites during pregnancy, particularly 1 hour post glucose, are associated with fetal adiposity and hyperinsulinemia, independent of maternal BMI and glycemia, and provide insight into the interrelationship between maternal metabolism and newborn size.

Disclosure

R. Kadakia: None. M. Nodzenski: None. O. Talbot: None. A. Kuang: None. J.R. Bain: None. M. Muehlbauer: None. O. Ilkayeva: None. S.K. O'Neal: None. L.P. Lowe: None. B.E. Metzger: None. D. Scholtens: None. W. Lowe: None.
Maternal Central Obesity and Birth Size—A Mendelian Randomization Analysis
Authors: HUANG TAO , GENG TINGTING
Published: June 2018

Background: Observational studies have illustrated that maternal central obesity is associated with birth size,including of birth weight, birth length and head circumference, but the causal nature of these associations remains unclear.

Objective: To test the causal effect of maternal central obesity on birth size and puberty height growth using a Mendelian randomization (MR) analysis.

Methods: We performed two-sample MR using summary-level genome-wide public data from the Genetic Investigation of Anthropometric Traits (GIANT) Consortium and the Early Growth Genetics Consortium (EGG). Thirty-five single nucleotide polymorphisms (SNPs), 25 SNPs and 41SNPs were selected as instrumental variables for waist-to-hip ratio adjust BMI (WHRadjBMI), waist circumference adjust BMI (WCadjBMI) and hip circumference adjust BMI (HIPadjBMI), respectively to test the causal effects of maternal central obesity on birth size and puberty height using an inverse-variance-weighted approach.

Results: In this MR analysis, we found no evidence between genetic instrumental variables for waist circumference (WC)or waist-to-hip ratio (WHR) and the outcomes. We observed one standard deviation (SD) increase in hip circumference (HC) was associated with a 0.392 SD increase in birth length (p=1.1×10-6) and a 0.168 SD increase in birth weight (p=7.1×10-5), respectively.In addition, higher genetically predicted maternal HP was strongly associated with the puberty heights (0.835 SD, p=8.4×10-10). However,HP was not associated with head circumference(p=0.172).

Conclusion: A genetic predisposition to higher maternal HC was causally associated with larger offspring birth weight,higher birth length, and puberty height independent of maternal BMI. However, we found no evidence of a causal association between maternal WC, WHR and birth size.

Disclosure

T. Huang: None. T. Geng: None.
Nocturnal Insulin Requirements Are Higher in Pregnant Hispanic Women with Type 2 DM
Authors: EHRIG JESSICA C. , ALLSHOUSE AMANDA A. , BARBOUR LINDA A.
Published: June 2018

T2DM is rapidly rising in pregnancy, especially in Hispanic women (HW). Classically, OBGYNs are taught to manage T2DM with a split dose NPH/Regular, especially if cost is a concern. OBGyn textbooks advise that 2/3 of total NPH be given in the am; 1/3 in pm based on historical data in Caucasians with T1DM. However, HW often display greater fasting glucoses (FBG) secondary to hepatic insulin resistance. We tested the hypothesis that more HW who are adequately controlled would require >50% of their NPH at night compared to non-Hispanic (NHW). All 667 pregnant women with T2DM at our county hospital from 2010-2016 were evaluated for inclusion (insulin treatment by 22 weeks, ≥5 prenatal visits, and ≥4/7 FBG≤95 mg/dl and A1C <6.5 by term). Our primary endpoint was tested with χ2; differences over time with generalized linear mixed-effects modeling. Inclusion criteria were met by 102 (81 HW and 21 NHW). Mean A1C decreased from baseline to term (7.7 to 5.9; 7.2 to 5.9 respectively). By term, more HW required >50% of NPH at night (51% vs. 19%, p=0.009). Fig. 1 shows at each prenatal visit, significantly more HW required >50% NPH at night (p< 0.05). Hispanic women require a higher % of NPH at night throughout gestation and at term to achieve adequate control. This novel finding questions the efficacy of traditional split dosing of NPH/Reg in HW and could lead to a change in dosing strategies and earlier FBG control, essential to improve outcomes.

Disclosure

J.C. Ehrig: None. A.A. Allshouse: None. L.A. Barbour: None.
Predicting Diabetes in the First Two Years Postpartum among Women with Recent Gestational Diabetes—The Linda-Brasil Study
Authors: CASTILHOS CRISTINA D. , LADWIG RUBEN , DREHMER MICHELE , DUNCAN BRUCE B. , FACANHA CRISTINA , SCHMIDT MARIA I.
Published: June 2018

Background: GDM is a strong risk factor for early development of diabetes. Yet, adherence to protocols for testing at postpartum is usually low. We investigated the main predictors of diabetes up to two years post-partum among women with recent GDM participating in the LINDA-Brasil cohort.

Methods: We recruited potential participants with GDM for an ongoing clinical trial of postpartum diabetes prevention, LINDA-Brasil. We ascertained diabetes by OGTT. We estimated relative risks and 95% CIs, and area under the ROC curve (AUC) for diabetes postpartum through logistic regression.

Results: We recruited 27women with GDM, of whom 1482 (55%) underwent OGTT testing postpartum. Among these, mean (SD) pre-pregnancy BMI was 30.2 (6.4) kg/m2 and mean age, 32.0 (6.3) years; 316 (21.3%) used insulin during pregnancy, an additional 314 (21.2%) oral hypoglycemic agents (OHAs). During follow-up, 163 (11%) developed diabetes. Use of insulin during pregnancy predicted a six-fold higher crude risk of developing diabetes postpartum (RR 6.7; 95% CI 4.7-9.4) and of OHAs, a two-fold risk (RR=2.0; 95% CI 1.4-2.9). The inclusion of just these two variables yielded an AUC of 0.754; adding fasting and 2h plasma glucose at the diagnosis of GDM increased it to 0.810; further addition of age and pre-pregnancy BMI increased it minimally (0.813), and age was not statistically significant. Most incident cases used insulin (59%) or OHAs alone (20%) during pregnancy, thus, 79% of all cases (sensitivity) could be identified as being at high risk just by this information. Stated as post-test probabilties, 20% of those using antidiabetic medication during pregnancy but only 4% of those not using medication developed diabetes.

Conclusions: Simple clinical or administrative information can be effectively used to prioritize screening and counselling for diabetes prevention in the initial years following pregnancy complicated by GDM.

Disclosure

C.D. Castilhos: None. R. Ladwig: None. M. Drehmer: None. B.B. Duncan: Research Support; Self; Eli Lilly and Company. Research Support; Spouse/Partner; Eli Lilly and Company. C. Facanha: None. M.I. Schmidt: Research Support; Self; Eli Lilly and Company. Research Support; Spouse/Partner; Eli Lilly and Company.
White Coat Hypertension in Early Pregnancy Is Prevalent in Women with Type 1 and Type 2 Diabetes
Authors: VESTGAARD MARIANNE , ÁSBJÖRNSDÓTTIR BJÖRG , RINGHOLM LENE , JENSEN DORTE M. , TORVIN ANDERSEN LISE LOTTE , DAMM PETER , MATHIESEN ELISABETH R.
Published: June 2018

Aim: Verifying the diagnosis of hypertension in pregnancy by home blood pressure (BP) or 24-h BP measurements is recommended (ACOG, 2013) to avoid over-treatment of white coat hypertension. In pregnancy a threshold of 140/90 mmHg measured by office BP is normally used, but in our center, we use a threshold of ≥135/85 mmHg for antihypertensive therapy in women with diabetes. The prevalence of white coat hypertension in pregnant women with diabetes is unknown. We explored the prevalence of white coat hypertension in early pregnancy in women with type 1 (T1DM) and type 2 (T2DM) diabetes.

Methods: Home BP was measured for 3 days (18 measurements in total) at median 67 gestational days (range 33-139), within a week of office BP measurement. The women were divided in groups: treated hypertension, white coat hypertension (office BP ≥135/85 mmHg and mean home BP <130/80 mmHg), true new-onset hypertension (office BP ≥135/85 mmHg and mean home BP ≥130/80 mmHg), masked hypertension (office BP <135/85 mmHg and home BP ≥130/80 mmHg) and normotension (office BP <135/85 mmHg and mean home BP <130/80 mmHg).

Results: In total 178 (72%) out of 244 consecutive pregnant women with diabetes were included: 107 women with T1DM and 71 women with T2DM with mean age 31±5 and 34±5 years and mean BMI 27±6 and 34±5 kg/m2, respectively. Treated hypertension was present in 11 (6%). In total 20/27 (74%) of the remaining women with hypertension measured by office BP ≥135/85 mmHg had white coat hypertension (85% (12/14) of women with T1DM and 62% (8/13) in women with T2DM). Among women with office BP ≥140/90 mmHg 8/9 (89%) had white coat hypertension (home BP <135/85 mmHg). True new onset hypertension was seen in 7 (4%). One women had masked hypertension and the remaining 139 (78%) were normotensive.

Conclusion: White coat hypertension in early pregnancy is prevalent in women with T1DM and T2DM. These data support routine home BP measurement before initiating antihypertensive therapy in this population.

Disclosure

M. Vestgaard: None. B. ásbjörnsdóttir: None. L. Ringholm: None. D.M. Jensen: None. L. Andersen: None. P. Damm: Advisory Panel; Self; Novo Nordisk A/S. Other Relationship; Self; Novo Nordisk A/S. E.R. Mathiesen: Speaker's Bureau; Self; Novo Nordisk A/S. Other Relationship; Self; Novo Nordisk A/S, Novo Nordisk Foundation, Novo Nordisk A/S.
Medical Nutrition Therapy for Gestational Diabetes Mellitus (GDM) Based on Mediterranean Diet Principles
Authors: DURAN ALEJANDRA , ASSAF-BALUT CARLA , DE LA TORRE NURIA GARCIA , FUENTES MANUEL , BORDIU ELENA , VALLE LAURA DEL , BARABASH ANA M. , CUESTA MARTIN , RUBIO MIGUEL A. , CALLE ALFONSO L.
Published: June 2018

Background: Medical nutrition therapy (MNT) is the first-line therapy to achieve glycemic control in women with gestational diabetes mellitus (GDMw). It has been associated with better pregnancy outcomes. Whether MNT can make pregnancy outcomes like women without GDM remains unknown.

Objective: To assess if a Mediterranean-diet-based medical nutrition therapy (MNT) facilitates near-normoglycemia (determined by HbA1c levels) at 36-38 gestational weeks in GDMw, and observe its effects on adverse pregnancy outcomes.

Study Design: A sub-analysis of the St Carlos GDM Prevention Study. It was conducted between January-December 2015 in the Hospital Clínico San Carlos (Madrid, Spain). One thousand consecutive normoglycemic women were included before 12th gestational weeks, and 874 included in the final analysis: 177 were diagnosed with GDM (IADPSG criteria) and 697 had normal glucose tolerance. GDMw received Mediterranean diet-based MNT, with a daily intake of ≥40 ml extra-virgin olive oil and a handful of nuts (mainly pistachios).

Results: GDMw had higher HbA1c levels, fastinG insulin and HOMA-IR at 24-28 gestational weeks as compared with NGT. At 36-38 gestational weeks these values became similar. Insulin therapy was necessary in 26.6% of GDMw. Rates of macrosomia, large-for-gestational-age, pregnancy-induced hypertensive disorders, prematurity and c-sections were similar between groups. Crude RR analysis showed that GDMw had a higher risk of insufficient weight gain [2.37(1.64-3.30), P=.001], urinary tract infection [1.69(1.20-2.38), P=.005], small-for-gestational age newborns [2.05(1.29-3.24), P=.009] and neonate ICU admission [3.42(1.45-8.04), P=.006].

Conclusions: Using a Mediterranean-diet-based MNT in GDMw helps to achieve a near-normoglycemia, making most pregnancy outcomes similar to women with NGT. The higher rates of small-for-gestational-age and insufficient weight gain require further analysis.

Disclosure

A. Duran: None. C. Assaf-Balut: None. N. Garcia de la Torre: None. M. Fuentes: None. E. Bordiu: None. L. Del Valle: None. A.M. Barabash: None. M. Cuesta: None. M.A. Rubio: None. A.L. Calle: None.
Prevalence of Gestational Diabetes and Preexisting Type 2 Diabetes in a 10-Year Multistate Hospital Discharge Cohort
Authors: HERRICK CYNTHIA J. , KELLER MATTHEW , OLSEN MARGARET A.
Published: June 2018

Background: Gestational diabetes (GDM) and preexisting type 2 diabetes (T2DM) in pregnancy are important public health challenges. Our study updates previous literature, using hospital discharge data to define the trends in GDM and preexisting T2DM in multiple states over 10 years.

Methods: Utilizing a validated ICD-9 code algorithm, we defined a retrospective cohort of deliveries from the Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases (SID) for FL, NY, and NE from 2005-2014. The HCUP SID contains hospital discharge data for all hospitalizations within a year. Prevalence of GDM and preexisting T2DM were calculated by state and year. Associations with race and socioeconomic status were explored.

Results: Of 4,690,551 births in the cohort, 270,623 were complicated by GDM (5.8%) and 26,261 (0.6%) were complicated by preexisting T2DM. The prevalence of GDM increased from 4.8% in 20to 6.7% in 2014. The prevalence of preexisting T2DM increased from 0.5% in 20to 0.7% in 2014. Native Americans had the highest rates of both preexisting T2DM (0.8-1.7%) and GDM (8.0-15.1%). Preexisting T2DM was next most common among African Americans (0.7% in 20to 1.1% in 2014), and GDM was next most common among Asian/Pacific Islanders (8.1% in 20to 13.1% in 2014). Rates of preexisting T2DM were higher in the lowest income compared to the highest income zip codes (0.8 vs. 0.5% FL, 0.6 vs. 0.3% NY, 0.7 vs. 0.3% NE), with rates declining across income quartiles. Women missing income quartile data had higher rates of preexisting T2DM (0.8-0.9%). GDM did not show a similar trend with socioeconomic status.

Conclusions: The prevalence of GDM and preexisting T2DM increased between 20and 2014 with rates varying by race. Lower socioeconomic status was associated with higher rates of preexisting T2DM. We will use multivariable analysis to explore associations between GDM and preexisting T2DM and demographic, clinical, and healthcare system access variables.

Disclosure

C.J. Herrick: Stock/Shareholder; Spouse/Partner; Cardinal Health. M. Keller: None. M.A. Olsen: Research Support; Self; Sanofi Pasteur. Consultant; Self; Pfizer Inc.. Research Support; Self; Pfizer Inc..
Sweet Transitions—Improving Outcomes for Hospitalized Patients with Diabetes
Authors: BERGER KIMBERLY , CORBIN ADELE , KAMAL PALWASHA , BACHMAN NICHOLE E. , RIDDELL LYNDSEY A. , FALCIGLIA MERCEDES
Published: June 2018

Effective diabetes care after hospitalization is commonly limited by poor care coordination. Key information from hospitalization is often not communicated to outpatient clinicians as diabetes is rarely the reason for admission. Published interventions to address this problem are limited or lack sustainable benefit. We studied the effectiveness of Sweet Transitions (ST), a program providing and coordinating diabetes care after hospitalization. Sweet Transitions enrolled patients at a 750-bed hospital with poorly controlled diabetes (A1C ≥ 9%) for visits and phone communication with a nurse practitioner and diabetes educator. The ST dyad provided education, identified barriers, adjusted medication, and coordinated care within the organization and community. An individualized plan was transferred to the clinician responsible for diabetes care. Readmissions for ST patients were compared to matched controls, and A1C was assessed before and after ST intervention. For a median of 43 days, 197 patients participated in the program (64% male, age 52 ± 0.9). In 160 patients with repeat A1C at 131 ± 7 days, A1C decreased from 12.0 ± 0.1 to 9.1 ± 0.2% (p <0.0001), and A1c decreased to ≤ 8.5% in 52%. A1C reduction was sustained in 94 patients with repeat A1C at 378 ± 5 days (12.0 ± 0.1 to 9.0 ± 0.3%, p<0.0001). There was a trend toward lower 30-day readmission rates in ST patients (11% vs. 17%, p=0.08). Readmissions were commonly elective among cardiovascular (CV) admissions (46 vs. 11%). Further analysis by admission diagnosis showed lower readmission rates in ST patients admitted for non-CV reasons vs. matched controls (8 vs. 17% p=0.02). Sweet Transitions was associated with improved glycemic control that persisted at 1 year as well as lower readmission rates. Sustained improvements at 1 year suggest effective engagement and communication at the level of patient, organization, primary care, and community. Scalability of ST’s effectiveness relies on identifying factors and processes contributing to improved outcomes.

Disclosure

K. Berger: None. A. Corbin: None. P. Kamal: None. N.E. Bachman: None. L.A. Riddell: None. M. Falciglia: None.
Mechanisms by Which Glucagon Acutely Stimulates Hepatic Mitochondrial Oxidation and Gluconeogenesis
Authors: PERRY RACHEL J. , WANG YONGLIANG , BRILL ALLISON L. , PENG LIANG , ZHANG DONGYAN , DUFOUR SYLVIE , ZHANG YE , ZHANG XIAN-MAN , NOZAKI YUICHI , CLINE GARY , EHRLICH BARBARA E. , PETERSEN KITT , SHULMAN GERALD I.
Published: June 2018

Glucagon has been suggested to be both pathogenic and protective against type 2 diabetes (T2D) reflecting our poor understanding of the molecular mechanisms by which glucagon alters hepatic metabolism. Using Positional Isotopomer NMR Tracer Analysis (PINTA) we found that acute glucagon infusion stimulates rates of hepatic gluconeogenesisin glycogen-depleted mice by promoting increases in intrahepatic lipolysis and hepatic acetyl-CoA content (75±6 vs. 101±6 nmol/g, p=0.01), pyruvate carboxylase flux (VPC, 70.9±3.9 vs. 99.9±7.1 µmol/[kg-min], p=0.008) and mitochondrial oxidation (90.0±12.9 vs. 452.1±78.3 µmol/[kg-min], p=0.001) in vivo. Each of these effects was abrogated in liver-specific Inositol Trisphosphate Receptor-I (InsP3R-I) knockout mice demonstrating that intracellular calcium signaling is necessary for these processes. Liver specific knockdown of adipocyte triglyceride lipase abolished acute glucagon stimulation of gluconeogenesis (control 70.5±2.9 vs. 103.3±3.3 µmol/[kg-min], p<0.0001 and ATGL knockdown 69.7±1.7 vs. 69.6±2.0 µmol/[kg-min], p=0.9) and VPC (control 63.3±5.0 vs. 100.0±4.8 µmol/[kg-min], p=0.0003, ATGL knockdown 58.9±4.9 vs. 59.2±3.2 µmol/[kg-min], p=0.9) in WT mice demonstrating the necessity of hepatocellular lipolysis in mediating this process. Chronic increases in plasma glucagon concentrations reversed high fat diet-induced hepatic steatosis (liver triglyceride 50.1±8.5 vs. 28.3±5.1 mg/g, p=0.04; liver membrane diacylglycerol 801±142 vs. 448±47 nmol/g, p=0.03, PKCε membrane/cytosol 1.76±0.40 vs. 0.23±0.04, p=0.0009) and glucose intolerance (GTT glucose AUC 1.44±0.vs. 1.13±0.mM-min, p=0.003, insulin AUC 226.8±18.7 vs. 90.2±11.2 nM-min, p<0.0001). These results provide new insights into glucagon biology and suggest that glucagon and InsP3R-I may be therapeutic targets to reverse nonalcoholic fatty liver disease and T2D.

Disclosure

R.J. Perry: None. Y. Wang: None. A.L. Brill: None. L. Peng: None. D. Zhang: None. S. Dufour: None. Y. Zhang: None. X. Zhang: None. Y. Nozaki: None. G. Cline: None. B.E. Ehrlich: None. K. Petersen: Research Support; Spouse/Partner; Gilead Sciences, Inc.. Advisory Panel; Spouse/Partner; AstraZeneca, Merck & Co., Inc., Novo Nordisk A/S. G.I. Shulman: Advisory Panel; Self; AstraZeneca, Janssen Research & Development, Merck & Co., Inc., Novo Nordisk Inc.. Research Support; Self; Gilead Sciences, Inc..