bluuebunny/crossref_metadata_2025_split huggingface dataset:
133-LB: High Hypoglycemia Risk Patients with T2D on First-Generation Basal Insulins (BI) in the U.S. Have a Lower Risk of Hypoglycemia after One Year following Switch to Insulin Glargine 300 U/mL (Gla-300) vs. First-Generation BIs (DELIVER - High Risk)
Authors: SULLIVAN SEAN D. , FREEMANTLE NICK , MENON ARJUN A. , GUPTA RISHAB , WU JASMANDA , NICHOLLS CHARLIE , WESTERBACKA JUKKA , BAILEY TIMOTHY S. 
Published: June 2019

DELIVER - High Risk study compared long-term clinical outcomes for patients with T2D and high hypoglycemia risk on first-generation BIs who were switched to Gla-300 or other first-generation BIs (other switchers). Electronic medical record data from the PHIE database were used. Eligible patients (age &gt;18 years) had ≥1 criterion for high hypoglycemia risk (age &gt;64 years; basal-bolus insulin use; renal impairment; uncontrolled baseline A1C; sulfonylurea use; atherosclerotic cardiovascular disease; history indicating high risk, including ≥1 severe hypoglycemic episode (prior 12 months). Endpoints were A1C reduction from baseline to 9-12 months, attainment of A1C goals (&lt;7.0%; &lt;8.0%), and hypoglycemia (based on ICD-9-CM codes or blood glucose ≤70 mg/dL) at 12 months. In a propensity score-matched comparison of Gla-300 vs. other switchers (Table), mean A1C reduction from baseline and attainment of A1C goals were comparable. Significantly fewer Gla-300 vs. other switchers experienced inpatient/ED-related hypoglycemia. For T2D patients at high hypoglycemia risk in a real-world setting, Gla-300 was associated with a significantly lower risk of hypoglycemia than switching to other BIs, 1 year after switching, while delivering similar glycemic control.

Disclosure
S.D. Sullivan: Research Support; Self; Sanofi. N. Freemantle: Advisory Panel; Self; Sanofi. Research Support; Self; Akcea Therapeutics, Allergan, AstraZeneca, Ipsen Biopharmaceuticals, Inc., Sanofi, Takeda Pharmaceutical Company Limited. Speaker’s Bureau; Self; Sanofi. A.A. Menon: None. R. Gupta: None. J. Wu: Employee; Self; Sanofi US. C. Nicholls: Employee; Self; Sanofi. J. Westerbacka: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. T.S. Bailey: Advisory Panel; Self; Abbott. Consultant; Self; Capillary Biomedical, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk Inc., Sanofi. Research Support; Self; Abbott, Ascensia Diabetes Care, Becton, Dickinson and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Calibra Medical, Capillary Biomedical, Inc., Companion Medical, Dance Biopharm Holdings Inc., Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, GlySens Incorporated, Kowa Pharmaceutical Europe Co. Ltd., Lexicon Pharmaceuticals, Inc., Medtronic, Novo Nordisk Inc., POPS! Diabetes Care, POPS! Diabetes Care, Sanofi, Senseonics, vTv Therapeutics, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. Speaker’s Bureau; Self; Abbott, MannKind Corporation, Medtronic, Novo Nordisk Inc., Sanofi US, Senseonics.

Funding
Sanofi
1331-P: OGTT Glucose-Response-Curve (GRC) in Islet Cell Antibody-Positive (Ab+) vs. -Negative (Ab-) Obese Youth Clinically Diagnosed with Type 2 Diabetes (CDX-T2D)
Authors: KIM JOON YOUNG , GEBARA NOUR , TFAYLI HALA , BACHA FIDA , ARSLANIAN SILVA A. 
Published: June 2019

The OGTT-GRCs [Incessant Increase (IIn), Monophasic (Mph), and Biphasic (Bph)] reflect insulin sensitivity (IS) and β-cell function (BCF), being worse in the former and best in the latter. Accordingly, the prevalence of these GRCs differ in diabetic and nondiabetic individuals (Table). While islet cell Ab- obese youth CDX-T2D have worse IS, Ab+ youth have severe impairment in BCF [Diabetes 58: 2009]. Here, we examined the prevalence of OGTT-GRC patterns, clamp-measured IS, and BCF in obese Ab+ (GAD65 and IA2) vs. Ab- youth CDX-T2D. The dominant GRC was IIn in Ab+ and Mph in Ab- youth while Bph was scarce in both (Table). In Ab+ youth, 1st- (32.5 ± 5.6 vs. 40.2 ± 8.0 µU/mL, p=0.13) and 2nd-phase insulin (39.6 ± 8.6 vs. 62.8 ± 12.2 µU/mL, p=0.04), were 20% and 40% lower in IIn vs. the other two combined. In Ab-, while 1st- (67.3 ± 19.1 vs. 122.4 ± 28.3 µU/mL, p=0.049) and 2nd-phase insulin (110.3 ± 31.4 vs. 171.6 ± 28.6 µU/mL, p=0.054) were lower in IIn vs. Mph, overall BCF was less impaired than in Ab+ youth. IS did not differ by GRC type in either group but was lower in Ab- vs. Ab+ irrespective of GRC type. The prevalence of IIn-GRC is 3-fold higher in Ab+ vs. Ab- obese youth CDX-T2D, and the prevalence in Ab- youth is similar to that in the TODAY study (Table). The higher prevalence of IIn-GRC in Ab+ obese youth signifies the severe insulin deficiency characteristic of type 1 diabetes.

Disclosure
J. Kim: None. N. Gebara: None. H. Tfayli: Other Relationship; Self; Sanofi. F. Bacha: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases, Pediatric Diabetes Consortium. Other Relationship; Self; AstraZeneca, Jaeb Center for Health Research. S.A. Arslanian: None.

Funding
Eunice Kennedy Shriver National Institute of Child Health and Human Development (K24-HD01357, R01HD27503 to S.A.A.); National Center for Advancing Translational Sciences (UL1TR000005); National Center for Research Resources (UL1RR024153)
1333-P: Increased Spare Respiratory Capacity in Circulating Cells and Decreased Serum Antioxidant Defense Mechanisms in Obese Children
Authors: CARVALHO EUGENIA , ROSE SHANNON , COTTER MATTHEW , BENNURI SIRISH C. , DELHEY LEANNA M. , GOODE GRACE A. , BEEBE ALEXANDRIA , BØRSHEIM ELISABET 
Published: June 2019

With increasing rates of childhood obesity, diagnoses of insulin resistance and type 2 diabetes (DM) in children is on the rise. Mitochondrial dysfunction is associated with insulin resistance and DM, therefore bioenergetics profiling of circulating cells may serve as a marker for mitochondrial dysfunction in insulin resistant subjects. The advantage of this biomarker is that others currently in use may not exhibit alterations until symptoms are already present.
Mitochondrial bioenergetics (Seahorse XF96) was measured in peripheral blood mononuclear cells (PBMCs) and platelets. Levels of oxidative stress, post-translational modifications of protein tyrosine residues, 3-Nitrotyrosine and 3-Chlorotyrosine, reduced (GSH) and oxidized (GSSG) glutathione, as well as whole-body D31-palmitate oxidation were also assessed in healthy lean (HL; n=18), and overweight/obese (OW/OB; n=29) (BMI ≥85th percentile) 5-9 years old children.
While maximal respiration was not different, the reserve capacity (RC) was increased in OW/OB compared to HL subjects in PBMC (45,6±4,7 vs. 32,1±7.7; p=0.05) and platelet (65,3±3.7 vs. 31,2±6,7; p=0.001). Importantly, 20% of these children already presented HbA1c levels above 6.5%. Moreover, 3-Chlorotyrosine was elevated (52,0±3,1 vs. 40,7±1,8; p=0.05), while GSH/GSSG and cysteine/cysteine (intracellular, extracellular redox buffers, respectively) tended to be decreased. Palmitate oxidation is being quantified.
RC is a critical component of the cell’s bioenergetics and can be used during increases in energy demand. Our results suggest significant metabolic adjustments to an excess in substrate availability and already compromised antioxidant defenses in 5-9 year old OW/OB children. Oxidative stress and damage occur when antioxidant defense mechanisms fail to counter-balance and control reactive oxygen species generated from endogenous oxidative metabolism or from pro-oxidant environmental exposures.

Disclosure
E. Carvalho: None. S. Rose: None. M. Cotter: None. S.C. Bennuri: None. L.M. Delhey: None. G.A. Goode: None. A. Beebe: None. E. Børsheim: None.

Funding
National Institute of General Medical Sciences (P20GM109096)
1336-P: Health-Care Utilization in T2D Youth in the Pediatric Diabetes Consortium (PDC)
Authors: KLINGENSMITH GEORGEANNA J. , CHENG PEIYAO , GAL ROBIN L. , BEAULIEU LINDSEY C. , KOLLMAN CRAIG , ADAMS RAMON L. , HANNON TAMARA S. , LOOPER LISA M. , TAMBORLANE WILLIAM V. 
Published: June 2019

Background: Youth with T2D experience barriers to obtaining diabetes care. We evaluated whether healthcare utilization (HCU) was associated with glycemic outcomes in youth with T2D.
Methods: We evaluated annual HCU in 1,324 T2D PDC youth by diabetes duration up to 13 years post diagnosis. Medical record and self-reported HCU data were collected at enrollment and annually. Frequency of diabetes related inpatient admissions, Emergency Department (ED), urgent care, Diabetes Management (DM), Registered Dietician (RD) visits, and 911 calls were collected.
Results: After adjusting for age, gender, diabetes duration, and annual visits, those with ≥1 admission/year, regardless of admission reason, (16%) had a higher A1c vs. those without admission, 8.8 vs. 8.4% (p=0.002). Those with ≥2 DM office visits/year (75%) had lower A1c vs. those with 0-1 visits, 8.4 vs. 8.8% (p=0.001). BMI and A1c did not differ by number of RD visits (p=0.63 and 0.39 respectively); RD visits/year decreased over time.
Conclusions: In T2D youth, hospitalizations and &lt;2 DM office visits/year are associated with higher A1c. Frequencies of ED and inpatient admissions for T2D are stable following the first year of T2D diagnosis. Only 24-38% of T2D youth had 4 DM visits/year while ∼50% have ≥3 visits a year, even with long T2D duration. Methods to improve follow-up care are needed to improve outcomes in youth with T2D.

Disclosure
G.J. Klingensmith: Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Pharmaceutical Company Limited. Research Support; Self; Novo Nordisk Foundation. Stock/Shareholder; Spouse/Partner; Dexcom, Inc. P. Cheng: None. R.L. Gal: None. L.C. Beaulieu: None. C. Kollman: None. R.L. Adams: None. T.S. Hannon: Advisory Panel; Self; Eli Lilly and Company. L.M. Looper: None. W.V. Tamborlane: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic MiniMed, Inc., Novo Nordisk Inc., Sanofi, Takeda Pharmaceutical Company Limited.

Funding
Boehringer Ingelheim; Novo Nordisk; Takeda Pharmaceutical Company Limited
1338-P: Lipoprotein Insulin Resistance Scores Decrease after a Lifestyle Intervention among Obese Adolescents with Prediabetes
Authors: RENTERIA-MEXIA ANA M. , OLSON MICAH , CONNELLY MARGERY A. , VEGA-LÓPEZ SONIA , WILLIAMS ALLISON , SHAIBI GABRIEL Q. 
Published: June 2019

Introduction: Insulin resistance (IR) is associated with impaired lipid metabolism. The Lipoprotein Insulin Resistance Index (LP-IR) is a novel composite biomarker that estimates IR from lipoprotein particle size and concentration, and prospectively predicts type 2 diabetes (T2D) in adults. Less is known about LP-IR and T2D risk in youth. This study evaluated the effect of a lifestyle intervention on LP-IR scores in obese Latino youths with prediabetes.
Methods: Obese Latino adolescents (n=27, 15.5±1.1 years, 13 male/14 female) with prediabetes (defined as a 2-hour, post-challenge glucose ≥120 mg/dL) completed a 12-week intervention including nutrition education (one hour/week) and moderate-to-vigorous physical activity (three hours/week). Measurements at baseline and 12 weeks included anthropometrics, total, large, medium, and small lipoprotein particle concentrations (VLDL and chylomicron, LDL, and HDL), mean lipoprotein particle sizes (VLDL, LDL, HDL), lipid concentrations (total triglyceride, VLDL and chylomicron triglyceride, and HDL cholesterol), and LP-IR scores using nuclear magnetic resonance spectroscopy.
Results: After adjusting for body fat and sex, significant reductions in LP-IR scores (63.2±14.4 vs. 59.0±15.5 units, p=0.013), large VLDL and chylomicron particle concentration (9.1±7.8 vs. 7.3±6.2 nmol/L, p=0.004), total HDL particle concentration (30.2±4.3 vs. 28.3±3.9 μmol/L, p=0.013), total triglyceride concentration (144.5±91.9 vs. 122.9±77.9 mg/dL, p=0.002), as well as VLDL and chylomicron triglyceride concentration (117.5±66.7 vs. 102.0±55.7 mg/dL, p=0.020) were observed following lifestyle intervention.
Conclusion: Lifestyle intervention significantly reduces LP-IR scores and lipoprotein particle parameters in obese adolescents with prediabetes and may decrease future risk of cardiometabolic disorders through improvements in insulin resistance and lipoprotein metabolism.

Disclosure
A.M. Renteria-Mexia: None. M. Olson: None. M.A. Connelly: Employee; Self; LabCorp. S. Vega-López: None. A. Williams: None. G.Q. Shaibi: None.

Funding
National Institute on Minority Health and Health Disparities (P20MD002316, U54MD002316); Programa para el Desarrollo Profesional Docente, para el Tipo Superior, México (to A.M.R-M.)
1345-P: Presymptomatic and Clinical T1D in The U.S., Sweden, and Finland: Joint Analysis of Four Birth Cohort Studies
Authors: ANAND VIBHA , LIU BIN , GHALWASH MOHAMED , KOSKI EILEEN , NG KENNEY , DUNNE JESSICA L. , HAGOPIAN WILLIAM , LUNDGREN MARKUS , LERNMARK ÅKE , ILONEN JORMA , VEIJOLA RIITTA , REWERS MARIAN ,   FOR T1DI STUDY GROUP
Published: June 2019

Four birth-cohort studies in the U.S. (DAISY, DEWIT), Sweden (DiPiS) and Finland (DIPP) were initiated in 1990s to early 2000. General population newborns and young first-degree relatives (FDR) of T1D patients, preselected on increased HLA risk, were followed for islet autoantibodies (AAb)and T1D. We harmonized their common variables, including AAb to insulin, IA-2, GAD, or ZnT8, HLA-DR-DQ risk genotypes, socio-demographics, diet, family history, glucose/HbA1c and anthropometric measures. The combined cohort included 22,312 subjects with AAb measured in 256,243 visits (mean 11±10 per subject) at 3-12 month intervals. During follow-up, 2279 (10%) subjects developed at least one AAb, 914 (4%) multiple AAb and 603 (3%) T1D. The cumulative risk of T1D differed by the number of AAb at seroconversion (Figure). T1D developed in 26% (95% CI 24-32%) of 1AAb, 62% (55-68%) of 2AAb and 84% (75-88%) of &gt;=3AAb positive subjects in the 15y after seroconversion. T1D risk varied by HLA genotype: 40% (35-48%) in DR3/4-DQ2/8, 22% (18-31%) in DR4/x-DQ8/x and 21% (18-35%) in DR3/x-DQ2/x of 1AAb subjects and, respectively, in 82% (68-88%), 61%(50-65%)and 87% (32-98%)of 2AAb subjects. Once ≥2 AAb positive, HLA genotype was less predictive of progression to T1D. This harmonized dataset offers an unparalleled opportunity to validate and improve upon reported risk estimates for T1D development via novel analytical methods.

Disclosure
V. Anand: None. B. Liu: None. M. Ghalwash: None. E. Koski: None. K. Ng: None. J.L. Dunne: None. W. Hagopian: Research Support; Self; Novo Nordisk A/S. M. Lundgren: None. Å. Lernmark: None. J. Ilonen: None. R. Veijola: None. M. Rewers: None.

Funding
JDRF
1348-P: Celiac Disease in Children with T1D Varies among the World: An International, Cross-Sectional Study of 39,425 Patients from the SWEET Registry
Authors: TACZANOWSKA ANNA , SCHWANDT ANKE , AMED SHAZHAN , SVENSSON JANNET , SZYPOWSKA AGNIESZKA , KANAKA-GANTENBEIN CHRISTINA , TOTH-HEYN PETER , KREPEL VOLSKY SARIK 
Published: June 2019

Comorbid celiac disease (CD) may affect the course of type 1 diabetes (T1D). We aimed to compare T1D children with and without CD. This study is based on the SWEET (Better control in Pediatric and Adolescent diabeteS:Working to crEate cEnTers of Reference) database. We included 39 425 patients aged ≤18 y. Regression models adjusted for demographics were applied to compare outcomes. CD was present in 1 804 subjects (4.6%). Prevalence of CD differed among regions: 1.9% Asia/Middle East, 4.3% Northern Europe, 5.1% Southern Europe, 5.3% North America/Canada and 6.1% Australia/New Zealand. Girls were diagnosed with CD significantly more often than boys (p&lt; 0.01). Children with CD were younger at diabetes onset (p&lt; 0.001), also when boys and girls were separately analyzed. CD subjects were significantly shorter (p= 0.002) and had lower BMI-SDS (p&lt; 0.001) (Fig). HbA1c was lower in patients with CD (p&lt; 0.001), even after adjustment for pump use (Fig). Across regions, gender differences in CD prevalence were not shown in Northern Europe and Asia/Middle East. HbA1c was lower in CD patients in Southern Europe and North America/Canada. In contrast, in Asia/Middle East, HbA1c was significantly higher among CD patients (p&lt;0.001). No difference was found in Northern Europe. The frequency, anthropometric as well as metabolic consequences of CD in T1D children differs around the world.

Disclosure
A. Taczanowska: None. A. Schwandt: None. S. Amed: None. J. Svensson: Advisory Panel; Self; Janssen Pharmaceuticals, Inc., Medtronic. Speaker's Bureau; Self; Novo Nordisk A/S, Sanofi-Aventis. Stock/Shareholder; Self; Novo Nordisk A/S. A. Szypowska: None. C. Kanaka-Gantenbein: None. P. Toth-Heyn: None. S. Krepel Volsky: None.
1350-P: Safety and Pharmacokinetics of Technosphere Insulin in Pediatric Patients
Authors: GRANT MARSHALL L. , KRUEGER JOHN A. , FINEMAN MARK , SHARMA GAURAV , POMPILIO FRANK , KENDALL DAVID M. 
Published: June 2019

Technosphere Insulin (TI) is an ultra-rapid, short-acting inhaled insulin that provides glycemic control in patients with diabetes. This ongoing, 2-part, open-label, interventional study aims to assess the efficacy and safety of TI in children aged 4 to 17 years with type 1 diabetes mellitus (T1DM) who are on a stable regimen of basal-bolus insulin therapy. Part 1 is a single-arm study that includes evaluation of insulin pharmacokinetics (PK) after a single prandial dose of TI (4, 8, or 12 units), followed by a 4-week titration period. Approximately 46 patients will be enrolled across 3 age cohorts: cohort 1 (13-17 years), cohort 2 (8-12 years), and cohort 3 (4-7 years). As of August 16, 2018, 15 patients had enrolled in cohort 1, 14 had received at least 1 dose, and 8 completed the titration period. Overall, 50% of the safety population (n=14) was female, mean duration of T1DM was 6.2 years, mean age was 15 years, and mean body mass index was 22.4 kg/m2. Initial PK results from cohort 1 demonstrated insulin metabolism similar to that in adult patients receiving TI. Insulin concentrations rapidly increased in the first 30 minutes after TI treatment and returned to baseline by 120 minutes for the 4-, 8-, and 12-unit doses. Mean postprandial glucose levels decreased within 1-hour postdose for the 8- and 12-unit dose groups. Seven patients developed treatment-related cough of mild (6 events) or moderate (1 event) severity. Seven patients experienced a total of 41 hypoglycemic events, but no patient required the assistance of another person to administer corrective carbohydrates. No clinically relevant declines in pulmonary function were reported. Two patients discontinued the study due to adverse events (cough, diabetic ketoacidosis). These data will help determine the appropriate age range for inclusion and recommended dosing for part 2, which will be a 1-year efficacy and safety study.

Disclosure
M.L. Grant: Employee; Self; MannKind Corporation. Stock/Shareholder; Self; MannKind Corporation. J.A. Krueger: Employee; Self; Eli Lilly and Company, MannKind Corporation. Stock/Shareholder; Self; Eli Lilly and Company. M. Fineman: Consultant; Self; MannKind Corporation. Employee; Self; Elcelyx Therapeutics, Inc. Stock/Shareholder; Self; Elcelyx Therapeutics, Inc. G. Sharma: Employee; Self; MannKind Corporation. F. Pompilio: Employee; Self; MannKind Corporation. Stock/Shareholder; Self; Amgen Inc., MannKind Corporation. D.M. Kendall: Employee; Spouse/Partner; Amgen Inc. Employee; Self; MannKind Corporation. Stock/Shareholder; Self; MannKind Corporation.

Funding
MannKind Corporation
1359-P: Improving Transition Readiness in Teens with Type 1 Diabetes (T1D): Feasibility Results of a Pilot RCT
Authors: GARVEY KATHARINE , DEAN TAYLOR , CHRISTENSEN SINEAD , RICE KRISTEN , RICH VIRGINIA B. , TERRIO SHANNON , LAFFEL LORI M. 
Published: June 2019

Suboptimal preparation for transition to adult care has been associated with adverse outcomes in youth with T1D. There is need for innovative curricular approaches acceptable to teens in order to optimize transition preparation and engagement. To create a feasible transition education model, we conducted 6 focus groups with teens and young adults with T1D (N=41) and 3 parent groups (N=23). Participants desired facilitated peer group education while maintaining 1:1 individualized T1D care. The Self-Management, Adherence and Readiness for Transition in T1D (SMART T1D) curriculum was derived from focus group themes and refined by a T1D Teen Advisory Committee (N=20) prior to packaging as 3 modules. Session topics included self-advocacy/adherence, T1D science education, and transition planning. Pediatric nurse specialists trained in motivational interviewing delivered SMART T1D in evening sessions over ∼9 months. Feasibility was assessed in a pilot RCT. Teens (N=40, 50% male, 85% white) with T1D were randomized to SMART T1D (N=20) or an attention control group (N=20) receiving 3 educational electronic newsletters, with both groups maintaining routine T1D care. Teens had mean±SD age 15.7±1.2 years, T1D duration 6.4±3.9 years, A1c 9.5±1.2%; 63% pump users. During the 1-year pilot RCT, we conducted 17 groups, with 1-6 teens in attendance/group (mean, median, mode=3/group); 15/20 teens attended 3 sessions, 2 attended 2 sessions, 3 attended 1 session. Review of 3 newsletters was confirmed by 19/20 controls. Only 3 teens withdrew (1 intervention, 2 control). Intervention feedback was very positive; 88% endorsed agree/strongly agree for recommending groups to other teens and 65% endorsed increased interest in transition information. Negative feedback related to scheduling/traveling to group sessions. SMART T1D was feasible and acceptable to most (95%) teens with T1D; future multi-center studies can assess portability, generalizability, and alternative virtual delivery models.

Disclosure
K. Garvey: None. T. Dean: None. S. Christensen: None. K. Rice: None. V.B. Rich: None. S. Terrio: None. L.M. Laffel: Advisory Panel; Self; Lilly Diabetes, Novo Nordisk A/S, Roche Diabetes Care, Sanofi. Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Janssen Pharmaceuticals, Inc., UpToDate.

Funding
National Institutes of Health