bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Target HbA1c Change in Pediatric Participants in the T1D Exchange Clinic Registry
Authors: WOOD JAMIE , BOYLE CLAIRE , QUINN MARYANNE , WONG JENISE C. , HALLER MICHAEL J. , NELSON BRYCE A. , HALLER MICHAEL J. , SCHATZ DESMOND , TAMBORLANE WILLIAM V. , FOX LARRY , PRAHALAD PRIYA , CORATHERS SARAH , MAAHS DAVID M. , ALONSO GUY T. , DESALVO DANIEL J. , PAUL WADWA R. , DIMEGLIO LINDA 
Published: June 2018

In 2014, the American Diabetes Association lowered its recommended HbA1c target for children with type 1 diabetes (T1D) from &lt;8.5% for &lt;6 years, &lt;8.0% for 6-&lt;13 years, and &lt;7.5 for 13-&lt;18 years to &lt;7.5% for all ages. To determine if HbA1c changed in response, we compared two cross-sectional cohorts of T1D participants in the United States aged &lt;18 years with T1D duration ≥1 year from the T1D Exchange Clinic Registry. The first cohort (PRE) were participants who enrolled between 2010 and 2012 (n=11,788). The second cohort (POST) were participants with an update between 2016 and 2017 (n=9,234). For each age group, mean HbA1c was compared between the cohorts using a linear regression model adjusted for age, T1D duration, and socioeconomic status (SES). A comparison of the cohorts can be found in Table 1. Demographic and SES characteristics were similar between the cohorts. More participants in the POST cohort were using insulin pumps and CGMs. Mean HbA1c was similar between the two cohorts for those &lt;6 years, though more participants in the POST cohort met the current HbA1c target. For the 6-&lt;13 and 13-&lt;18 age groups, those in the POST cohort had higher mean HbA1c, with fewer meeting the current HbA1c target (p&lt;0.01). Thus, despite the lowering of HbA1c targets, glycemic control remains suboptimal in this population.

Disclosure
J. Wood: None. C. Boyle: None. M. Quinn: None. J.C. Wong: Research Support; Self; Dexcom, Inc.. Other Relationship; Self; Tidepool Project. M.J. Haller: None. B.A. Nelson: Speaker's Bureau; Self; Dexcom, Inc.. M.J. Haller: None. D. Schatz: None. W.V. Tamborlane: Consultant; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Medtronic MiniMed, Inc., Novo Nordisk Inc., Sanofi, Takeda Pharmaceuticals U.S.A., Inc.. L. Fox: None. P. Prahalad: None. S. Corathers: None. D.M. Maahs: Advisory Panel; Self; Insulet Corporation. Consultant; Self; Abbott. Research Support; Self; Medtronic, Bigfoot Biomedical, Dexcom, Inc., Insulet Corporation, Roche Diabetes Care Health and Digital Solutions. G.T. Alonso: None. D.J. DeSalvo: Consultant; Self; Dexcom, Inc.. Speaker's Bureau; Self; Insulet Corporation. R. Wadwa: Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; Dexcom, Inc., Xeris Pharmaceuticals, Inc., Novo Nordisk Inc., MannKind Corporation, Bigfoot Biomedical. L. DiMeglio: Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; Dexcom, Inc., Medtronic, Sanofi, Caladrius Biosciences, Inc., Janssen Research & Development, Xeris Pharmaceuticals, Inc., Sanofi.
Higher Weekly Physical Activity in T1D Pediatric Patients Is Associated with Improved Target Glucose Levels—Findings from Six Months of Fitbit-Monitored Activity
Authors: BARNES TIMOTHY L. , WATSON DAVID A. , GANDRUD LAURA M. 
Published: June 2018

Physical activity (PA) in T1D patients has been linked to improved cardiovascular and psychosocial health. Glycemic control has been reported as a benefit of PA, but it remains difficult to assess ’real-life’ PA in T1D pediatric patients.
In a novel study, we examined the relationship between weekly Fitbit-measured PA and blood glucose (BG) in 1patients over 6 months. BG was measured via home meters. Using generalized linear mixed effects regression we examined the association between weekly PA measures—steps and hours of moderate to vigorous PA (MVPA)—and weekly summaries of BG levels in, below, and above target range (70-140 mg/dL).
On average, patients took 56K steps/week and had a weekly BG measurement of 221 mg/dL. In regression models, as PA increased, patients tended to have significantly lower mean BG levels and more BG measurements in target range. Thus, an increase in 10K steps was associated with a 3.1 mg/dL drop in BG levels and a 6% increase in the odds of a target range BG (see Table). An additional hour of MVPA was associated with a 2.3 mg/dL drop in BG levels and a 4% increase in the odds of a target BG measurement. PA was also associated with being below the target range.Generalized linear mixed effects regression models examining relationship between weekly PA and BG levels1 (n=105)Average BG measurement% BG measurement between 70-140 mg/dL% BG measurement below 70 mg/dL% BG measurement above 140 mg/dLβ (95% CI)2OR (95% CI)3OR (95% CI)3OR (95% CI)3Steps (per 10K)-3.1 (-4.4, -1.8)1.06 (1.05, 1.07)1.06 (1.03, 1.08)0.94 (0.93, 0.95)Hours of MVPA-2.3 (-3.6, -1.0)1.04 (1.03, 1.05)1.03 (1.01, 1.05)0.96 (0.95, 0.97)1 Adjusted for baseline HbA1c, baseline BMI (z-score), age group, sex, treatment group.2 Beta is the fixed effects linear regression coefficient for the specified PA measurement.3 OR is the odds ratio of the indicated event for each unit increase of PA.
This study provides evidence for the positive effects of PA on BG among pediatric T1D patients, providing a further impetus for promoting PA among this population.

Disclosure
T.L. Barnes: None. D.A. Watson: None. L.M. Gandrud: Consultant; Self; UnitedHealth Group.
Clinical Islet Transplantation Outcomes Are Comparable in Obese Type 1 Diabetes Recipients
Authors: LAM ANNA , POTTER KATHRYN J. , FORBES SHAREEN , IMES SHARLEEN , MALCOLM ANDREW J. , HAQQ ANDREA , SHAPIRO A.M. JAMES , SENIOR PETER A. 
Published: June 2018

Many clinical islet transplant programs have body mass index (BMI) and/or weight based thresholds for eligibility. Large subjects may require higher islet mass to reliably achieve insulin independence. However, for long term graft function and protection from hypoglycemia, data supporting a BMI based exclusion is lacking.
Methods: Subjects undergoing islet transplantation at a single center, between 1999 and 2017 were included. Graft survival as measured by C-peptide positivity from last CIT was compared between recipients with BMI&lt;30 kg/m2 (n=237, 24.8±2.8 kg/m2) and BMI &gt;30 kg/m2 (n=24, mean±SD 31.9±2.1 kg/m2) pre-transplant.
Results: Apart from BMI and weight (BMI&lt;30 vs. BMI&gt;30, 70.9±11.3 kg vs. 82.8±9.5 kg; P&lt;0.05) there were no difference between groups in terms of baseline recipient characteristics, including in daily insulin dose (0.58±0.16 U/kg vs. 0.59±0.18 U/kg; P=0.34). Both groups received similar total number of islet infusions (2.4±0.9 and 2.3±0.6, p=0.6), total islet equivalents (1 053 022±471 532 vs. 1 182 498±366 368, P=0.19) and total islet equivalents per recipient body weight (15 208±6 373 IE/kg vs. 14 120±5 041 IE/kg, P=0.42). Long term C-peptide survival was not different between groups (P=0.18).
Conclusion: T1D patients with BMI&gt;30 appear to have similar islet mass requirements and graft survival compared to those with BMI&lt;30. This likely reflects careful selection of smaller (weight &lt;90 kg), insulin sensitive (&lt;0.6 U/kg) subjects with only class I obesity. Given the prevalence of obesity in T1D, future studies should evaluate the roles of obesity, weight and insulin sensitivity to ensure rational and equitable access to transplantation.

Disclosure
A. Lam: None. K.J. Potter: None. S. Forbes: None. S. Imes: None. A.J. Malcolm: None. A. Haqq: None. A. Shapiro: Consultant; Self; Viacyte, Inc., Protokinetix. P.A. Senior: Consultant; Self; Abbott, AstraZeneca. Research Support; Self; AstraZeneca, Prometic Life Sciences Inc., Novo Nordisk Inc., Sanofi. Consultant; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc., Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Speaker's Bureau; Self; AstraZeneca, Merck & Co., Inc., Abbott. Research Support; Self; Viacyte, Inc..
Parental Hypoglycemia Fear and Adoption of Pump Therapy in Youth with New-Onset Type 1 Diabetes (T1D)
Authors: YOUNGKIN ERIN M. , MAJIDI SHIDEH , NOSER AMY , STANEK KELLY R. , FINCH JONATHAN H. , CLEMENTS MARK A. , PATTON SUSANA R. 
Published: June 2018

Objective: Hypoglycemia Fear (FH) is common in parents of young children with T1D and related to poor child glycemic control. We explored if T1D device adoption near onset relates to parental FH.
Methods: In a prospective study of 5-9 year-olds with new onset T1D (mean age 7.4±1.3 years, mean T1D duration 4.6±3.3 months), parents completed the FH Survey at baseline (T1) and 6 (T3) and 12 (T5) months post-baseline. We recorded pump start dates for youth during the same 12 months.
Results: Between T1 and T3, 44 youth (45%) initiated pump therapy. Between T3 and T5, 12 (13%) started a pump. Forty-one youth never started a pump (42%). Despite pump status, parents reported moderate FH Worry at T1 (32.2±11.2), which increased between T1 and T3 (38.0±11.3, p=0.052) and plateaued between T3 and T5 (38.4±12.3, p=0.45). There was no difference in T1 FH Worry among the 44 parents of youth who started a pump between T1 and T3 and those not on a pump. At T3, FH Worry trended higher in the 12 parents whose child started a pump between T3 and T5 than the 85 parents of youth either already on a pump or not on one (p=0.059). At T5, the 12 parents whose child started a pump between T3 and T5 reported significantly higher FH Worry than the other parents (p=0.048).
Conclusions: Parents of 5-9 year-olds with new onset T1D report moderate FH in the first year of T1D. Our results suggest that initiating pump therapy may not reduce parental FH.
Table.Longitudinal measures of hypoglycemia fear and relation to initiation of insulin pump therapyNT1 (Baseline)T3 (6 months)T5 (12 months)Average Age (years)977.5 ± 1.4Gender (%F)10056 (56.0%)Pump Start (%)1000 (0%)44 (44.0%)12 (12.0%)FH Worry (total)8532.7 ± 11.738.0 ± 11.338.2 ± 12.1FH Worry (pump start T1-T3)4433.1 ± 11.135.9 ± 10.738.0 ± 12.3FH Worry (pump start T3-T5)1233.3 ± 12.743.7 ± 11.644.6 ± 7.98**p value &lt;0.

Disclosure
E.M. Youngkin: None. S. Majidi: None. A. Noser: None. K.R. Stanek: None. J.H. Finch: None. M.A. Clements: Speaker's Bureau; Self; Medtronic. Advisory Panel; Self; Glooko, Inc.. S.R. Patton: None.
Establishing a Clinically Meaningful Cut-Point for the PAID-PR (Problem Areas in Diabetes-Parent Revised) Survey
Authors: TINSLEY LIANE J. , COMMISSARIAT PERSIS V. , VOLKENING LISA , ANDERSON BARBARA , KATZ MICHELLE , LAFFEL LORI M. 
Published: June 2018

Managing type 1 diabetes (T1D) in youth can create substantial family distress and affect diabetes care efforts. The current study aimed to establish a cut-point on the PAID-PR, a previously validated measure of diabetes distress in parents of youth with T1D.
The 18-item PAID-PR has shown construct validity with BGM frequency, A1c, and measures of diabetes-specific family conflict (DSFC) and general quality of life (QoL). Higher PAID-PR scores (range 0-100) indicate more diabetes distress. We applied a standard approach to identify a meaningful cut-point: scores ≥75th percentile of the distribution of PAID-PR scores obtained from 2 large clinic samples. Cutoff score was confirmed by convergent validity, including demographics, diabetes data from youth, and parent reported psychosocial measures (DSFC and QoL).
The sample included 527 parents of youth with T1D. Youth (50% male, 84% white) were aged (M±SD) 14.0±2.5 years with T1D duration 6.3±3.6 years; 86% were from 2-parent families. Youth checked BG 5.3±2.5 x/day; A1c was 8.4±1.1% and 69% were pump-treated. PAID-PR score was 43.3±18.5 (range 0-92, IQR 31-56). Analyses determined a cut-point of 56. Youth whose parents scored in the upper quartile vs. lower 3 quartiles were similar with respect to sex and racial distributions, age, percent 2-parent families, T1D duration, and BG checks/day. There were significant differences in A1c (8.6±1.2 vs. 8.3±1.1%) and pump use (60 vs. 71%) (p&lt;.01 for both) between youth whose parents were in the upper vs. lower 3 quartiles of the PAID-PR. Parents in the upper quartile vs. lower 3 quartiles reported more DSFC and poorer youth QoL (p&lt;.001 for both).
As youth-onset T1D may engender diabetes distress in families, pediatric diabetes teams recognize the need to identify parents experiencing extreme symptoms. A cut-point of 56 on the PAID-PR appears to identify families in need of additional medical and psychological support in order to improve biomedical and psychosocial outcomes.

Disclosure
L.J. Tinsley: None. P.V. Commissariat: None. L. Volkening: None. B. Anderson: Advisory Panel; Self; Sanofi-Aventis. M. Katz: 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..
Effects of Modified Lipoproteins on Human Trophoblast Cells-A Role in Preeclampsia in Pregnancies Complicated by Diabetes
Authors: MCLEESE REBECCA H. , ZHAO JIAWU , YU JEREMY , BRAZIL DEREK , LYONS TIMOTHY 
Published: June 2018

Preeclampsia (PE) complicates 2-8% of pregnancies worldwide. In women with diabetes, the risk for PE is substantially increased by approximately 4 fold. Evidence indicates that an increased release of two anti-angiogenic factors, soluble fms-like tyrosine kinase (sFlt-1) and soluble endoglin (sEng) from placental trophoblasts into the maternal circulation promotes endothelial dysfunction associated with PE. In this study, we investigated sFlt-1 and sEng release from the human placental trophoblast cell line, HTR8/SVneo, in response to modified lipoproteins and/or elevated glucose. HTR8/SVneo cells were exposed to native low-density lipoprotein (N-LDL) vs. ’highly-oxidized glycated’ LDL (HOG-LDL) (50 µg protein/ml) for 24h, with and without pre-treatment with 30mM glucose for 72h. The mRNA expressions of sFlt-1 isoforms (sFlt-1-i13, sFlt-1-e15a), endoglin and MMP-14 were measured by RT-PCR, and levels of sFlt-1 and sEng in cell supernatant were determined by ELISA. Compared with N-LDL, HOG-LDL increased the mRNA expression of sFlt-1-i13 (2.0 fold, p&lt;0.05), sFlt-1-e15a (1.9 fold, p&lt;0.01), endoglin (1.5 fold, p&lt;0.05) and MMP-14 (1.8 fold, p&lt;0.05). HOG-LDL increased the levels of sFlt-1 and sEng proteins in the supernatant (2.9 fold, p&lt;0.and 3.6 fold, p&lt;0.01, respectively). High glucose alone had no significant effect on sFlt-1 and sEng expressions; however, pre-treatment of high glucose potentiated the effects of HOG-LDL: the supernatant levels of sFlt-1 and sEng were increased by 1.5 fold and 1.8 fold, respectively, compared to HOG-LDL treatment alone (p&lt;0.for both). Exposure of trophoblasts to modified lipoproteins (which accumulate in the tissues of patients with diabetes due to vascular leakage) may contribute to the development of PE in diabetes, which is amplified by the presence of high glucose. These findings may explain, in part, the high risk of PE in women with diabetes.

Disclosure
R.H. McLeese: None. J. Zhao: None. J. Yu: None. D. Brazil: None. T. Lyons: None.
Enrichment of miR-126 Boosts the Therapeutic Effects of Endothelial Progenitor Cells Derived Exosomes on Ischemic Stroke in Diabetic Mice
Authors: WANG JINJU , PAN QUNWEN , LIU HUA , ZHAO BIN , YANG YI , MA XIAOTANG , BIHL JI 
Published: June 2018

We have demonstrated that endothelial progenitor cell (EPCs) have therapeutic effects on ischemic stroke in diabetic mice and that microRNA (miR)-126 modulates the function of EPC through vascular endothelial growth factor receptor 2 (VEGFR2) pathway in cell culture studies. Here, we determined the effects of EPC-released exosomes (EPC-EXs) on ischemic stroke in diabetic mice and tested whether miR-126 enriched EPC-EXs (EPC-EXsmiR126) could have enhanced efficacy. Type 2 diabetic mice subjected to filament-induced focal ischemic stroke were intravenously administrated with vehicle, or PKH26 labelled EPC-EXs or EPC-EXsmiR-126. The neurological deficit score (NDS), cerebral blood flow (CBF), infarct volume, cerebral microvascular density (MVD), cell death, angiogenesis and neurogenesis, and levels of miR-126, VEGFR2 and cleaved caspase-3 were measured. We found: 1) Injected EPC-EXs merged with brain endothelial cells, neurons and astrocytes dominantly in the peri-infarct area; 2) EPC-EXsmiR126 were more effective than EPC-EXs in decreasing NDS, ischemic damage and cell death, and increasing CBF and MVD on both day 2 and 14, and in promoting angiogenesis and neurogenesis on day 14; 3) These effects were accompanied with down-regulated cleaved caspase-3 on day 2 and prolonged VEGFR2 up-regulation till day 14. The data suggest that transfusion of EPC-EXsmiR126 has enhanced therapeutic efficacy on ischemic stroke in diabetic mice by attenuating acute injury and promoting neurological function recovery.

Disclosure
J. Wang: None. Q. Pan: None. H. Liu: None. B. Zhao: None. Y. Yang: None. X. Ma: None. J. Bihl: None.
Long-Term Function of Islet Allografts Transplanted on the Omentum Using a Biological Scaffold
Authors: BAIDAL DAVID , RICORDI CAMILLO , BERMAN DORA M. , PILEGGI ANTONELLO , ALVAREZ GIL ANA M. , PADILLA NATHALIA , CIANCIO GAETANO , LINETSKY ELINA , ALEJANDRO RODOLFO 
Published: June 2018

The liver is the preferred site for islet transplantation (ITx) but not ideal due to limitations affecting engraftment.
We evaluated the safety and efficacy of ITx in the omentum using a resorbable biological scaffold in 3 subjects with type 1 diabetes and negative C-peptide. Islets were combined with autologous plasma and thrombin to generate a biologic scaffold and layered laparoscopically on the omentum. Induction was with anti-thymocyte globulin and etanercept. Maintenance was with mycophenolate sodium and tacrolimus. Demographics, islet dose and metabolic data are shown in the Table.Subject #Age (years)Duration T1DM (years)BMI (Kg/m2)IEQ†/KgMMTT‡ Stimulated Glucose (mg/dl)/C-peptide (ng/ml)Insulin dose U/Kg/day (Units/day)HbA1c%6 months12 months24 monthsPre-ITxLatestPre-ITxLatest1432621.511,386181/3.32277/1.79317/0.490.62 (33)0.14 (7)6.85.32321625.39,635372/0.88374/0.65332/0.52*0.45 (31)0.45 (30)5.75.6346422412,648277/2.47--0.45 (20)0.2 (11)6.36.3* 18 months Post-ITx † IEQ= islet equivalents ‡ MMTT = mixed meal tolerance test
Subject 1 was insulin independent for 15 months and maintains stable glycemic control. Subject 2 had marginal graft function with persistence of severe hypoglycemia (SH) and then underwent intrahepatic ITx resulting in insulin independence. Subject 3 had a 55% reduction in insulin dose and maintains excellent glycemic control.
Our initial experience demonstrates feasibility and safety of ITx on the omentum. Graft function persisted throughout follow-up (6-24 months) resulting in improved glycemic control and absence of SH (subjects 1 and 3).
Results suggest a significant loss of islets early post-ITx followed by gradual functional decline similar to intrahepatic ITx. Strategies to improve oxygen delivery and neo-vascularization and minimize immunosuppression are needed to improve long-term outcomes at this site.

Disclosure
D. Baidal: None. C. Ricordi: None. D.M. Berman: Stock/Shareholder; Self; Pfizer Inc. A. Pileggi: Stock/Shareholder; Self; Converge Biotech, Inc.. Stock/Shareholder; Spouse/Partner; Converge Biotech, Inc. A.M. Alvarez Gil: None. N. Padilla: None. G. Ciancio: None. E. Linetsky: None. R. Alejandro: None.
Family History of Diabetes Delays Fetal Brain Activity
Authors: SCHLEGER FRANZISKA , WALTER LAURA , HENI MARTIN , BRUCKER SARA Y. , HAERING HANS-ULRICH , FRITSCHE ANDREAS , PREISSL HUBERT 
Published: June 2018

Introduction: We have previously shown that fetuses of mothers with gestational diabetes mellitus (GDM) and insulin resistance exhibit a prolongation of fetal auditory evoked brain responses (fAER) compared to fetuses of normal glucose tolerant (NGT) women during an oral glucose tolerance test (OGTT). This implies that maternal metabolism may program the fetal brain. We asked whether a positive family history of type 2 diabetes (FHD) without metabolic programing also impacts fetal brain activity. We therefore investigated brain activity in fetuses of NGT mothers with positive FHD.
Methods: A 75g OGTT was administered to healthy pregnant women. Glucose and insulin levels were measured after 0, 60 and 120 minutes. Each blood extraction was preceded by magnetoencephalographic recordings of fAER. From a group of 151 participants, a sub-sample of 53 women, 38 with a negative and 15 with a positive FHD (at least one first- or second-degree relative) was selected based on the following inclusion criteria: no GDM, BMI 18.5-30 kg/m², no preterm birth, no change in fetal position, at least two fMEG with detectable fetal responses.
Results: There were no significant differences in age, BMI at delivery, weight gain during pregnancy and gestational age between the groups. Maternal glucose levels and insulin sensitivity determined by glucose and insulin measurements during the OGTT were not significantly different. Manova with gestational age as covariate showed a significant interaction between measurement timepoint and FHD on fAER latency (F(2)=4.96, p=0.009). Fetuses of mothers with positive FHD had a prolonged fAER (273±109ms) compared to fetuses of mothers with negative FHD (218±67ms) at 60 minutes during the OGTT (F(1)=5.21, p=0.027).
Discussion: In addition to the previously shown influence of maternal metabolism on fetal brain activity, a positive maternal FHD also appears to delay fetal brain activity. This can be due to the genetic or environmental influence which is linked to a positive FHD.

Disclosure
F. Schleger: None. L. Walter: None. M. Heni: Research Support; Self; Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Boehringer Ingelheim GmbH, Merck Sharp & Dohme Corp., Novo Nordisk Inc.. S.Y. Brucker: None. H. Haering: None. A. Fritsche: Advisory Panel; Self; Sanofi-Aventis Deutschland GmbH, Novo Nordisk A/S, Eli Lilly and Company, Boehringer Ingelheim GmbH. H. Preissl: None.