bluuebunny/crossref_metadata_2025 huggingface dataset:
1295-P: Economic Evaluation of Drug Combination Strategy for Type 2 Diabetes in China
Authors: GU SHUYAN , SHEN YI , SHI LIZHENG , DONG HENGJIN
Published: June 2019

Introduction: There are multiple antidiabetic drugs for type 2 diabetes in China, which vary in efficacy and cost. Chinese guideline recommends a stepwise escalation treatment strategy in diabetes care which consists of 3 therapy lines; and using combination therapy of antidiabetic drug + metformin (MET) for patients failed on MET. This study aims to develop 10 alternative drug combination strategies and compare their cost-effectiveness.

Method: Based on Chinese guideline, 8 classes of antidiabetic drugs were included: 1st line drug (MET), 2nd line drug (α glycosidase inhibitor=AGI, sulfonylurea=SU, glinide=NIDE, DPP-4 inhibitor=DPP-4I, thiazolidinedione=TZD), 3rd line drug (insulin=INS, GLP-1 receptor agonist=GLP-1RA); 10 drug combination strategies were developed: use MET as 1st therapy line, one of the five 2nd line drug + MET as 2nd therapy line, one of the two 3rd line drug + MET as 3rd therapy line. From societal perspective, Cardiff model was used to estimate cost-effectiveness of 10 drug combination strategies vs. non-drug treatment. Clinical data on Chinese patients were obtained from systematic literature review and meta-analysis of 325 studies. Costs were obtained from claims database study of 1164 patients. Utilities were obtained from EQ-5D survey of 868 patients. Simulation was 40 years. Discount rate was 3%. Sensitivity analysis was performed.

Result: All drug combination strategies were cost saving (increase QALYs but save costs) vs. non-drug treatment. Ranking strategies by considering incremental QALY and cost, strategy 5b (MET, MET+NIDE, MET+INS) was optimal, followed by strategy 6b (MET, MET+NIDE, MET+GLP-1RA), strategy 3b (MET, MET+SU, MET+INS), strategy 1b (MET, MET+AGI, MET+INS), strategy 4b (MET, MET+SU, MET+GLP-1RA), strategy 2b (MET, MET+AGI, MET+GLP-1RA), strategy 7b (MET, MET+DPP-4I, MET+INS), strategy 10b (MET, MET+TZD, MET+GLP-1RA), strategy 8b (MET, MET+DPP-4I, MET+GLP-1RA), strategy 9b (MET, MET+TZD, MET+INS).

Conclusion: Strategy 5b is worthy of clinical use.

Disclosure

S. Gu: None. Y. Shen: None. L. Shi: None. H. Dong: None.
1299-P: The Paediatric Diabetes Service in England and Wales—An Improvement Journey
Authors: PENG MEGAN FENGMEI , WARNER JUSTIN , ROBINSON HOLLY , MUSZYNSKA KASIA , EARDLEY SUE , CAMPBELL FIONA M.
Published: June 2019

The clear trajectory of improvement in paediatric diabetes outcomes in England and Wales since 2009 can be traced to a co-ordinated national programme of support for the 173 multi-disciplinary teams that care for 29,153 children and young people with diabetes and their families. With the introduction of a Best Practice Tariff in England by the Department of Health in 2011 and the National Paediatric Diabetes Audit (NPDA) alongside formation of 11 regional networks and an overarching national network, there has been a marked reduction in national median HbA1c levels from 73mmol/mol in 2009 to 64mmol/mol in 2017. To maintain momentum towards achieving further improvement and build on existing progress demonstrated by the NPDA and Patient Reported Experience Measures, a new way to engage teams and their host organisations has been developed. A National Children and Young People’s Diabetes Quality Programme encompassing peer review, self-assessment and quality improvement collaborative has been established to close the audit loop and provide teams with the support and tools to identify, design and analyse their own interventions specific to the needs of the children and young people they care for. The aim is to drive sustainable development of paediatric diabetes services in England and Wales and help bring transformative improvements to the wellbeing and care of children and young people with diabetes and their families for the future.

Disclosure

M.F. Peng: None. J. Warner: None. H. Robinson: None. K. Muszynska: None. S. Eardley: None. F.M. Campbell: None.
130-LB: Comparative PK and PD of the Rapid-Acting Insulin Aspart Product SAR341402, NovoLog, and NovoRapid in Subjects with T1D
Authors: KAPITZA CHRISTOPH , NOSEK LESZEK , LEHMANN ANNE , SCHMIDER WOLFGANG , ROTTHAEUSER BAERBEL , NOWOTNY IRENE K.
Published: June 2019

SAR341402 (SAR-Asp), NovoLog (NN-Asp-US) and NovoRapid (NN-Asp-EU) are rapid-acting insulin aspart products.

Exposure (PK) to and activity (PD) of SAR-Asp (T) NN-Asp-US (R1) and NN-Asp-EU (R2) were compared in a single-center, randomized, double-blind, 3-treatment, 3-period, crossover, euglycemic clamp study. Thirty male T1D subjects (22-59 years) were randomized to receive 0.3 U/kg T, R1 and R2 in separate periods; 29 subjects completed all 3 treatment periods. PK and PD (Glucose Infusion Rate, GIR) by euglycemic clamp were assessed up to 12 hours.

Mean concentration and body weight standardized GIR vs. time profiles for T, R1 and R2 were similar. Exposure to and activity of T, R1 and R2 were similar between treatments, as the 90% CIs for the treatment ratios for the primary and main secondary PK and PD endpoints were within the predefined acceptance range (0.80-1.25) (Table). Within-subject variability of exposure and activity was low across the 3 clamps, indicating high day-to-day reproducibility in clamp performance, irrespective of the individual product. Adverse events were similar for T, R1 and R2. No safety concerns were noted in laboratory, vital signs, or ECG data.

In summary, this study demonstrated similar insulin aspart exposure profiles and PD activity for SAR-Asp to NN-Asp-US and NN-Asp-EU and between NN-Asp-US and NN-Asp-EU, rendering SAR-Asp a biosimilar/follow-on product.

Disclosure

C. Kapitza: Research Support; Self; ADOCIA, Biocon, Boehringer Ingelheim Pharmaceuticals, Inc., Dance Biopharm Holdings Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, MedImmune, Mylan, Nestlé, Nordic Bioscience, Novo Nordisk A/S, Poxel SA, Sanofi-Aventis, Wockhardt, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. L. Nosek: None. A. Lehmann: Employee; Self; Sanofi-Aventis Deutschland GmbH. W. Schmider: Employee; Self; Sanofi. B. Rotthaeuser: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. I.K. Nowotny: Employee; Self; Sanofi-Aventis Deutschland GmbH. Stock/Shareholder; Self; Sanofi.

Funding

Sanofi
1309-P: Utilizing a Clinical Decision Support System for Hypoglycemia Management
Authors: GIBBS JACQUELYN R. , BERGER KIMBERLY , FALCIGLIA MERCEDES
Published: June 2019

Per American Diabetes Association guidelines, every hospital should adopt a hypoglycemia management protocol and all episodes of hypoglycemia should be documented in the medical record and tracked. Chart audit findings at a large urban acute care hospital revealed that nurses were not always compliant with documentation and/or adherence to the hypoglycemia treatment protocol. Thus, a quality improvement (QI) project was implemented to improve documentation compliance and adherence to the treatment protocol.

A clinical decision support system (CDSS) was embedded into the electronic health record (EHR) to enable the treatment protocol to be visible to nurses at the point of care and a hypoglycemia flow sheet was implemented for documentation. Retrospective chart reviews (n=150) were conducted prior to and after implementation of the QI project to determine if the CDSS and flow sheet were associated with changes in compliance. Chart review evaluated the number of episodes were interventions were documented utilizing the required method and if the hypoglycemia treatment protocol was followed, not followed, or unclear.

The CDSS was associated with improvements in both documentation compliance, (72 to 87%) and adherence to the treatment protocol for hypoglycemia, (54 to 69%). There was a statistically significant relationship between the type of documentation utilized (pre-implementation vs. post implementation) and whether or not the treatment protocol was followed, not followed, or unclear (p=0.0003).

Incorporating a CDSS into the EHR may help nurses comply with management of hypoglycemia and its documentation. Hypoglycemia during hospitalization poses a risk to patient safety, therefore additional strategies should be explored to further improve adherence to hypoglycemia treatment protocols.

Disclosure

J.R. Gibbs: None. K. Berger: None. M. Falciglia: None.
1310-P: Outcomes Before and After Implementation of a Comprehensive Multidisciplinary Cardiovascular Diabetes Program among Patients with Diabetes Undergoing Coronary Artery Bypass Grafting (CABG)
Authors: SIRAJ ELIAS S. , NELSON AARON , BRUSH JOHN E. , ULLAL JAGDEESH , LAMICHHANE RAJAN , SHEEHAN BRYNN E.
Published: June 2019

Background: Most studies demonstrating the benefit of perioperative glycemic control in patients undergoing CABG have primarily focused on inpatient glucose management protocols only. Our study evaluated outcomes before and after implementation of an innovative, comprehensive cardiovascular diabetes program in patients with diabetes undergoing CABG.

Methods: In March 2015, Sentara Heart Hospital and Eastern Virginia Medical School implemented a Multidisciplinary Cardiovascular Diabetes Program. The inpatient aspect focuses on patient education and optimizing glycemic control with the use of Glucommander, an electronic glucose management system. Representatives from endocrinology, cardiology and cardiothoracic surgery meet monthly to review outcomes and develop policy. Patients return for a visit with the surgical and endocrine teams 1-2 weeks after discharge, followed by cardiac rehabilitation. Our retrospective study was designed to compare clinical outcomes for the period of 2 years pre- and 2 years post-implementation of the program. Data from 1013 patients (444 pre; 569 post) were extracted from the Society of Thoracic Surgeons CABG database and the EPIC electronic health record.

Results: After implementation of the program, the frequency of blood glucose values <70 mg/dl was reduced by 42% (from 1.52% to 0.89%; p < 0.001) and the length of stay (LOS) decreased from 12.4 days to 11.2 days (p = 0.026). Multiple regression analyses showed the post-implementation period was associated with shorter LOS and reduced hospital charges. Poor glycemic control, infections and cardiovascular complications had a negative effect on LOS, readmissions and hospital charges.

Conclusion: The implementation of a comprehensive, multidisciplinary program for patients with diabetes undergoing CABG resulted in significantly less hypoglycemia, shorter LOS and reduced hospital charges.

Disclosure

E.S. Siraj: Advisory Panel; Self; Sanofi. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc. A. Nelson: None. J.E. Brush: None. J. Ullal: None. R. Lamichhane: None. B.E. Sheehan: None.

Funding

EVMS-Sentara Healthcare Analytics and Delivery Science Institute
132-OR: Effects of Dapagliflozin, an SGLT2 Inhibitor, on Hepatic Steatosis and Fibrosis Evaluated by Transient Elastography in Patients with Type 2 Diabetes and Nonalcoholic Fatty Liver Disease
Authors: ASO YOSHIMASA , JOJIMA TERUO , IIJIMA TOSHIE , USUI ISAO
Published: June 2019

Objective: To investigate the effects of dapagliflozin on liver steatosis and fibrosis evaluated in patients with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD).

Research Design and Methods: In a randomized, active-controlled, open-label trial, 57 patients with type 2 diabetes and NAFLD were randomized to a dapagliflozin (5 mg/day) group (n=33) or to the control group (n=24) and were treated for 24 weeks. Hepatic steatosis and fibrosis were assessed by using a transient elastography (FibroScan) to measure the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), respectively.

Results: At baseline, LSM was positively correlated with several markers and scoring systems for liver fibrosis in a total of 57 patients with T2D and NAFLD. In week 24, CAP showed a significant decrease from 314±61 to 290±73 dB/m (P=0.0424) in the dapagliflozin group, while there was no significant change in the control group. In addition, LSM tended to decrease from 9.49±6.05 kPa to 8.01±5.78 kPa in the dapagliflozin group. In 14 patients from this group with LS values ≥8.0 kPa, indicating significant liver fibrosis, LSM decreased significantly from 14.7±5.7 to 11.0±7.3 kPa (P=0.0158). Furthermore, serum alanine aminotransferase and γ-glutamyltranspeptidase levels decreased in the dapagliflozin group, but not in the control group, and visceral fat mass was significantly reduced in the dapagliflozin group.

Conclusions: Based on these findings, the SGLT2 inhibitor dapagliflozin improves liver steatosis in parallel with a decrease of liver enzymes in patients with type 2 diabetes and NAFLD, and attenuates liver fibrosis in only patients with significant liver fibrosis. (UMIN000022155)

Disclosure

Y. Aso: Research Support; Self; Ono Pharmaceutical Co., Ltd. T. Jojima: None. T. Iijima: None. I. Usui: None.
1326-P: Metformin Increases GLP-1 Concentrations and Improves Glycemia in Youth with Type 2 Diabetes
Authors: CRAVALHO CELESTE K. , MEYERS ABBY G. , MABUNDO LILIAN , COURVILLE AMBER B. , BERNSTEIN SHANNA , DAI YUHAI , WALTER MARY , CHACKO SHAJI , HAYMOND MOREY W. , CHUNG STEPHANIE T.
Published: June 2019

Metformin is the only approved oral agent for youth with type 2 diabetes (T2D), but its mechanism of action remains controversial. Recent data suggests a primary role for the entero-insular instead of the gluconeogenic pathway, but there is no data in youth, in whom metformin efficacy is ∼50%. Our objectives were to: (1) compare incretin concentrations, glucagon-like 1 peptide (GLP-1) and gastric inhibitory polypeptide (GIP) in 12 youth with T2D not on metformin to 10 healthy age and BMI-matched controls, and (2) determine the change in incretins and gluconeogenesis (GNG) after 3 months of metformin in 8 youth with T2D. Intact GLP-1 and total GIP were measured at 0 and 2-hour during a 75g OGTT and basal GNG (2H20) and glucose production (6,62H2glucose) measured after an overnight fast. Compared to controls, youth with T2D before metformin had higher HbA1c and glucose levels and lower fasting and 2-hour GLP-1 (P<0.05 Table). After metformin, HbA1c decreased and fasting GLP-1 increased but there was no change in BMI, GNG or glucose production (P>0.1 Table). Post-metformin GLP-1 was comparable to levels in controls (P>0.1). There was no difference in GIP between youth with and without T2D and no change with metformin. Overall, improved glycemic control with short-term metformin in youth was associated with increased GLP-1 concentrations independent of changes in BMI and GNG supporting an entero-insular mechanistic pathway.

Disclosure

C.K. Cravalho: None. A.G. Meyers: None. L. Mabundo: None. A.B. Courville: None. S. Bernstein: None. Y. Dai: None. M. Walter: None. S. Chacko: None. M.W. Haymond: Advisory Panel; Self; Daiichi Sankyo Company, Limited, Zealand Pharma A/S. Stock/Shareholder; Self; Xeris Pharmaceuticals, Inc. Other Relationship; Self; AstraZeneca. S.T. Chung: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases
1327-P: Baseline Characteristics of Latino Youth with Prediabetes: The Preventing Diabetes in Latino Youth Cohort
Authors: OLSON MICAH , KONOPKEN YOLANDA P. , CASTRO FELIPE G. , HU HOUCHUN H. , KELLER COLLEEN , PATRICK DONALD L. , WILLIAMS ALLISON , AYERS STEPHANIE , KNOWLER WILLIAM C. , PIMENTEL JANIEL , PENA ARMANDO , SOLTERO ERICA G. , SHAIBI GABRIEL Q.
Published: June 2019

Background: Latino youth are disproportionately impacted by type 2 diabetes (T2D). Prediabetes is an intermediate stage in the pathogenesis of T2D and represents a critical opportunity for prevention in adults. In youth and adults, prediabetes is identified by HbA1c, fasting glucose, and/or 2-hour glucose (2HrGluc). In youth, it is not well-characterized whether prediabetes by each criterion confers a similar metabolic profile. The objective of this study is to compare baseline characteristics of prediabetic Latino youth enrolled in a randomized, controlled diabetes prevention trial based on hyperglycemic status.

Methods: Participants were selected for the following inclusion criteria: 1) Latino ancestry, 2) Age 12-16 years, 3) BMI ≥ 95th percentile for age and sex, and 4) Prediabetes defined as HbA1c ≥ 5.7% and < 6.5%, fasting glucose ≥ 100 and < 126 mg/dL, or 2HrGluc ≥ 120 and < 200 mg/dL after an OGTT.

Results: Ninety-four youth (age 13.5±1.4 years, 59 male/35 female) met inclusion criteria with 25% eligible by HbA1c, 45% by 2HrGluc, and 30% based on more than one criterion. No participant met eligibility by fasting glucose alone. Those who met eligibility by more than one criterion were more likely to be exposed to gestational diabetes in utero (19.2%) compared to 2HrGluc (7.9%) or HbA1c (0%) groups, P=0.04. The multiple eligibility group also exhibited higher hepatic fat fraction by MRI (11.9%) compared to 2HrGluc (7.6%) and HbA1c (6.6%) groups, P=0.055. There were no statistically significant differences between eligibility groups in body fat percentage, BMI percentile, diabetes family history, liver enzymes, or lipid profiles.

Conclusion: These data suggest that obese Latino adolescents with prediabetes according to more than one criteria were more likely to be exposed to hyperglycemia in utero and exhibit higher liver fat content. Whether prediabetes criteria are associated with a differential response to lifestyle intervention will be tested in this clinical trial.

Disclosure

M. Olson: None. Y.P. Konopken: None. F.G. Castro: None. H.H. Hu: None. C. Keller: None. D.L. Patrick: None. A. Williams: None. S. Ayers: None. W.C. Knowler: None. J. Pimentel: None. A. Pena: None. E.G. Soltero: None. G.Q. Shaibi: None.

Funding

National Institutes of Health (R01DK107579P)
1335-P: Weight Status and Cardiometabolic Risk Factors among Adolescents in Japan
Authors: MORIKAWA SAKIKO Y. , FUJIHARA KAZUYA , ISHII DAI , NEDACHI RINA , ISHIZAWA MASAHIRO , ISHIGURO HAJIME , MATSUBAYASHI YASUHIRO , YAMADA TAKAHO , KODAMA SATORU , SONE HIROHITO
Published: June 2019

Pediatric obesity is associated with clustered cardiometabolic risk and the future incidence of diabetes. However, few studies have determined the effect of pediatric obesity in Asia, where obesity is less common than in Western countries. Thus, we clarified whether metabolic risk factors are associated with weight status including slight overweight and underweight among Japanese adolescents. We performed a cross-sectional analysis of 2241 Japanese adolescents (1180 boys) aged 13-14 years whose height, weight, HbA1c, blood pressure (BP), and serum lipids were measured. Participants were classified as underweight, normal weight, slightly overweight, overweight, or obese according to both the universal and Asian cutoffs of the International Obesity Task Force, which correspond to adult BMI cutoffs. The clustered cardiometabolic risk (Z-CMR) was estimated by summing standardized sex-specific Z scores of HbA1c, mean arterial pressure (MAP), and non-high-density lipoprotein cholesterol (non-HDL-C). Linear regression analysis showed that MAP (sex-specific Z score), non-HDL-C (sex-specific Z score), and Z-CMR were higher in the slightly overweight, overweight, and obese groups than in the normal weight group after adjusting for confounders. Compared with the normal weight group, the slightly overweight, overweight, and obese groups had significantly higher odds ratios (ORs) for high BP [OR = 1.38 (95% CI, 1.03-1.85); OR = 2.63 (1.77-3.91); and OR = 2.39 (1.57-3.64), respectively]. Compared with the normal weight group, underweight boys, but not girls, had a significantly lower OR for high Z-CMR [OR = 0.20 (0.05-0.84)]. Our results indicated that adolescents classified as slightly overweight had higher levels of BP, serum lipids (but not HbA1c), and clustered cardiometabolic risk than those classified as normal weight. This observation demonstrated that significant associations between weight status and cardiometabolic risk factors could be seen during adolescence even in East Asia.

Disclosure

S.Y. Morikawa: None. K. Fujihara: None. D. Ishii: None. R. Nedachi: None. M. Ishizawa: None. H. Ishiguro: None. Y. Matsubayashi: None. T. Yamada: None. S. Kodama: None. H. Sone: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kowa Pharmaceutical Europe Co. Ltd., Kyowa Hakko Kirin Co., Ltd., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited.
134-LB: Treatment Patterns and Outcomes Before and After Human Regular U-500 Insulin Initiation via Kwikpen in U.S. Veterans with Type 2 Diabetes
Authors: CHEN JIELING , FAN LUDI , JUNEJA RATTAN , BORRA SUJANA , HUANG AHONG , WANG LI
Published: June 2019

Introduction: Human regular U-500 insulin (U-500R) improves glycemic control in people with type 2 diabetes (PwT2D) inadequately controlled with high doses of other insulins. Limited evidence exists on treatment patterns and outcomes in PwT2D who initiate U-500R using a U-500R KwikPen (U500KP) in the real-world setting.

Methods: Adults with ≥2 claims for T2D and initiating U500KP (index date: 1st claim) in Veterans Health Administration data (01MAR2016-01JUN2017) were identified. Inclusion criteria included continuous enrollment and ≥1 A1C measure in 9 months of both pre- and post-index date and no U-500R use in 9 months pre-index. Treatment patterns and outcomes including observed total daily dose (TDD), A1C level, and hypoglycemia events (ICD-9 diagnosis codes, glucagon administration, blood glucose ≤70 mg/dl) per patient per year (PPPY) in 9 months pre- and post-index were compared using paired t-test and McNemar’s test. Linear Mixed Model (LMM) was used to confirm the effect of U500KP initiation on A1C, adjusting for demographics, Quan-Charlson Comorbidity Index (Q-CCI) and TDD.

Results: PwT2D who initiated U500KP were identified (n=647). Mean age was 64 years, most were white (80%) and men (97%). Mean Q-CCI score was 3.8. After initiating U500KP, mean TDD increased from 188 to 270 units. 62% of the PwT2D had a TDD ≤200 units in the pre-index period, with 27% remaining on ≤200 units post-index. After U-500R initiation, mean A1C decreased from 9.5% to 8.7% (p<0.0001). LMM confirmed this A1C decrease was significant. Hypoglycemic events PPPY increased from 4.3 to 5.3 (p<0.05).

Conclusions: Post-U500KP initiation, there is a clinically significant drop in A1C accompanied by an average increase of 1 hypoglycemic event/year. Analysis showed that most PwT2D requiring high dose insulin starting U500KP were on TDD ≤200 units pre-index. After initiation of U500KP, TDD increased by ∼80 units with 1 in 4 PwT2D continuing on TDD ≤200 units.

Disclosure

J. Chen: Employee; Self; Eli Lilly and Company. L. Fan: Employee; Self; Lilly Diabetes. Stock/Shareholder; Self; Lilly Diabetes. R. Juneja: Employee; Self; Eli Lilly and Company. S. Borra: Other Relationship; Self; STATinMED. A. Huang: Other Relationship; Self; STATinMED. L. Wang: Other Relationship; Self; STATinMED.
1347-P: Improvement in Peripheral Insulin Sensitivity (IS) with Metformin (MET) in Adolescents with Type 1 Diabetes (T1D) Is Not Mediated by Muscle Mitochondrial Change
Authors: TOMMERDAHL KALIE L. , CREE-GREEN MELANIE , BJORNSTAD PETTER , CARREAU ANNE-MARIE , REYES YESENIA GARCIA , BAUMGARTNER AMY D. , BROWN MARK S. , NEWCOMER BRADLEY , REUSCH JANE E.B. , NADEAU KRISTEN J.
Published: June 2019

T1D youth are insulin resistant and we recently demonstrated that whole-body IS improved after 3 months of MET therapy. We also found that youth with T1D and type 2 diabetes both have skeletal muscle mitochondrial dysfunction that correlated with IS, but with a unique pattern in T1D. We aimed to determine if improvement in IS in T1D youth following MET was related to improvement in mitochondrial function. Forty-nine youth aged 12-21 years with T1D participated in Effects of MEtformin on CardiovasculaR Function in AdoLescents with T1D (EMERALD), a randomized, double-blind, placebo-controlled study. Youth were randomized to 3 months of MET titrated to 1000mg BID over 4 weeks or placebo (PLA). Assessments prior to and after MET or PLA included a hyperinsulinemic euglycemic clamp (80 mU/m2/minute insulin) to evaluate IS (glucose infusion rate [GIR]) and, in a subset of youth, calf 31Phosphorus magnetic resonance spectroscopy (MRS) before, during, and after 90 sec of near-maximal isometric exercise to evaluate post-exercise muscle mitochondrial function. Change with treatment for each group was compared via t-test or Mann Whitney U, as appropriate. Twenty-two youth with pre/post MRS (n=12 MET, n=10 PLA, 16.3±2.1 years, 45% female, 91% Caucasian, BMI 25.6±3.9 kg/m2, 7.4±3.7 years T1D duration, HbA1c 8.2±1.1%) were included. GIR increased more in the MET group (MET 1.5 [1.1-2.1] vs. PLA 0.4 [-0.1-0.9] mg/kg/minute, p=0.024). There were no differences between groups in any mitochondrial measure (initial phosphocreatine [PCr] synthesis, ADP and PCr time constants, oxidative phosphorylation, maximal mitochondrial function) or the related measures of creatine kinase reaction or anaerobic glycolysis.

In summary, metformin improves peripheral IS in T1D youth, but likely not via muscle mitochondrial-mediated mechanisms. Further research is needed to understand mitochondrial dysfunction and metformin-induced improvements in IS in T1D.

Disclosure

K.L. Tommerdahl: None. M. Cree-Green: None. P. Bjornstad: Advisory Panel; Self; Horizon, XORTX. Consultant; Self; Bayer US, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company. A. Carreau: Advisory Panel; Self; Pfizer Inc. Y. Garcia Reyes: None. A.D. Baumgartner: None. M.S. Brown: None. B. Newcomer: None. J.E.B. Reusch: Board Member; Self; American Diabetes Association. Other Relationship; Self; Merck & Co., Inc. K.J. Nadeau: None.

Funding

American Diabetes Association (7-11-CD-08 to K.J.N.)
1349-P: Sociodemographic and Clinical Factors Associate with Parental Fear of Hypoglycemia: Italian Nationwide Cross-Sectional Survey
Authors: CHERUBINI VALENTINO , PJETRAJ DORINA , BONFANTI RICCARDO , MARINO MONICA , IANNILLI ANTONIO ,   ISPED, CARLE FLAVIA , GESUITA ROSARIA
Published: June 2019

Aim of this study was to evaluate the association of socio-demographic and clinical factors, including technologies used for diabetes management, and parental fear of hypoglycaemia (FOH) in parents of children (<18y) with T1D. A cross-sectional, nationwide electronic survey, supported by the Italian Society of Paediatric Endocrinology and Family Associations of children with diabetes, was conducted during September-November 2018. The Hypoglycaemia Fear Survey for Parents (HFS-P), a 25-item questionnaire, was used to assess FOH. Quintile regression analysis was performed to estimate factors associated to FOH. Out of 1450 questionnaires, 1106 (873 mothers) reported a complete HFS-P in both the worry and behavior subscales. Children median age was 11 y (IQR: 8-14), median diabetes duration 6 y (IQR: 3-10); median HbA1c 7.2% (IQR: 6.7-7.8). Glucose Sensor (including CGM and FGM) was used in 79% of patients and insulin pump in 45%. Median HFS-P worry score was 36 (IQR: 29-46), behavior score 29 (IQR: 24-33). Parental FOH was associated with parental modifiable and non-modifiable factors (Table 1). The use of insulin pump does not seem to impact worries and behaviors, while glucose sensor do influence parental behaviors. As the use of diabetes-advanced technologies is today increasingly widespread, the impact on parental FOH requires more analyses.

Disclosure

V. Cherubini: None. D. Pjetraj: None. R. Bonfanti: Advisory Panel; Self; Abbott, Lilly Diabetes, Medtronic, Novo Nordisk A/S, Roche Diabetes Care, Sanofi. M. Marino: None. A. Iannilli: None. F. Carle: None. R. Gesuita: None.
1356-P: Comparison of Serum Adipokines and Anthropometric Measures in Children with Type 1 Diabetes (T1D) and Obesity
Authors: REDONDO MARIA JOSE , GU XIANGJUN , SISLEY STEPHANIE , TOSUR MUSTAFA , SILLER ALEJANDRO F. , BONDY MELISSA , DEVARAJ SRIDEVI
Published: June 2019

Obesity or overweight occur in 40% of U.S. youth with T1D. While BMI is used to define obesity, it may not accurately reflect excess adiposity, which correlates better with metabolic dysfunction. However, it is difficult to measure adiposity without a research setting. In contrast, adipokines, which are produced by the adipose tissue, can be measured in serum. We aimed to analyze, in youth with T1D and obesity, the relationships of serum adipokines with measures of adiposity and cardiovascular risk factors.

We studied participants in the T1D Exchange Metformin Study with a serum sample obtained before randomization (n=61, mean age=8.0 years [SD=3.0], 27.9% male, 82.0% non-Hispanic white, mean BMI percentile=99.0 ([SD=1.0], mean BMI Z-score=2.7 [SD=0.78], mean % of the 95th BMI percentile (%95th BMI pctle)=134.6 [SD=20.0]). We measured serum levels of adipokines and inflammatory markers. We studied the correlations between DEXA scan-derived measures of adiposity (e.g., % body fat) with adipokines (e.g., leptin, adiponectin) or anthropometric measures (e.g., % 95th BMI pctle [recommended measure for extreme obesity], BMI-Z score).

DEXA % body fat was significantly correlated with % 95th BMI pctle (r=0.494, p<0.0001) or leptin (r=0.467, p=0.0002), without statistical difference between these two correlations (p = 0.857). The correlation between % body fat and BMI Z-score was weaker (r=0.29, p=0.0270). Higher adiponectin was correlated with cardiovascular protective factors, such as lower systolic blood pressure (p=0.039) and higher HDL cholesterol (p=0.001), while neither % 95th BMI pctle nor BMI Z-score were. Children with high adiponectin (>26.5 mg/L, distribution mean) were less likely to have high CRP >6 mg/L (1.6%) vs. children with low adiponectin (23.0%, p<0.05).

Serum adipokines levels could be used as more convenient markers of adiposity than BMI measures, and potentially become therapeutic targets to improve clinical outcomes in children with T1D and obesity.

Disclosure

M.J. Redondo: None. X. Gu: None. S. Sisley: Advisory Panel; Self; Rhythm Pharmaceuticals, Inc. M. Tosur: None. A.F. Siller: None. M. Bondy: None. S. Devaraj: None.
1362-P: Puberty Changes Everything: Longitudinal Multitrajectory Modeling of Metabolic Control, Body Mass Index, and Insulin Dose among 9,239 Children with T1D from the DPV Registry
Authors: SCHWANDT ANKE , KUSS OLIVER , DUNSTHEIMER DESIREE P. , KARGES BEATE , KAPELLEN THOMAS M. , MEISSNER THOMAS , WITSCH MICHAEL , FLURY MONIKA , STRAUBINGER STEFANIE , HOLL REINHARD W. ,   DPV INITIATIVE
Published: June 2019

Worsening metabolic control, weight changes and increasing insulin dose during puberty have emerged as a challenge in diabetes care. However, individual variation is large. Data from the German/Austrian/Luxembourgian diabetes registry DPV were used to identify distinct patterns of hemoglobin A1c (HbA1c), age/sex-standardized body mass index (BMI-SDS) and daily insulin dose from childhood to young adulthood.

Longitudinal data from 9,239 participants with T1D aged 8 to 18 years with duration >=2 years and >=5 years of follow-up were analyzed. We applied group-based multitrajectory (GBMT) modeling, a generalization of the group-based trajectory approach, to identify latent groups of subjects following similar developmental curves over time across multiple variables (Nagin, 2018). The GBMT approach revealed five unique groups of heterogeneous HbA1c, BMI-SDS and insulin dose patterns over time (Fig1). Differences in age at onset, gender, migration background as well as height-SDS, insulin pump and CGM usage, frequency of SMBG and physical activity were found across all groups. The present study identified for the first time five distinct multitrajectories of HbA1c, BMI-SDS and insulin dose during puberty. This approach demonstrates that variability between individuals is obscured by statistics on central tendency.

Disclosure

A. Schwandt: None. O. Kuss: None. D.P. Dunstheimer: None. B. Karges: None. T.M. Kapellen: None. T. Meissner: None. M. Witsch: None. M. Flury: Other Relationship; Self; Pfizer Inc. S. Straubinger: None. R.W. Holl: None.

Funding

German Center for Diabetes Research; Robert Koch Institute; German Diabetes Association
1381-P: Psychological Characteristics of Caregivers Choosing Continuous Glucose Monitoring (CGM) for Their Children with Type 1 Diabetes (T1D)
Authors: ALKHALED LINA , ANN O'RIORDAN MARY , MACLEISH SARAH A. , HAZEN REBECCA A. , WOOD JAMIE R.
Published: June 2019

The objective was to explore parental reason for adding CGM to child’s T1D management and relationships with parental anxiety and stress. Prior to CGM initiation as part of routine care, the primary caregiver of a child with T1D completed validated questionnaires including Fear of Hypoglycemia Scale, State-Trait Anxiety Inventory, Problem Areas in Diabetes Scale, as well as an investigator developed questionnaire assessing primary reason for starting CGM. Participants were grouped by primary reason for starting CGM. ANOVA methods were used to compare baseline characteristics and questionnaire scores (Table 1). Results of the Global F test are reported. Half of caregivers (16/32) were starting CGM with the goal of improving glycemic control and their children had a nominally higher HbA1c than the other groups. There were no differences in demographic characteristics or scores among the groups, although a nominally higher percentage of those who chose less fear of hypoglycemia had an elevated score (>45) on the State-Trait Anxiety Inventory.

In summary, while not reaching statistical significance, results suggest that caregivers have different reasons for starting CGM in their children which may be found to be related to their emotional state in future studies with larger samples.

Disclosure

L. Alkhaled: None. S.A. MacLeish: None. R.A. Hazen: None. J.R. Wood: Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc.
1384-P: The Guided Transition of Care
Authors: LAL RAYHAN , MAAHS DAVID M. , DOSIOU CHRYSOULA , AYE TANDY , BASINA MARINA
Published: June 2019

Objective: Every year 500,000 youths in the U.S. with chronic disease need transfer to adult providers. Diabetes is a model of chronic illness that transcends age. For those with type 1 diabetes (T1D), 58% report a bad transition experience, the majority change adult providers and there is a 21% drop in clinic visits. Retrospective studies show unstructured transfers result in worse A1c. Despite the need, there is a lack of evidence-based interventions on the organization of care. Meta-analysis established engagement and retention in adult care as appropriate outcomes. Sustained continuity of care improves patient satisfaction and reduces hospital visits. We hypothesized that a physician trained in both adult and pediatric endocrinology would have greater show rates for patients transferred to adult care if he or she first provides care to the patient in the pediatric clinic. In this “guided transition” the doctor continues caring for the patient from pediatric to adult clinic.

Methods: We conducted a prospective cohort study of patients with T1D, age 16-26 years, referred to adult T1D clinic and seen by a physician trained in adult and pediatric endocrinology. Patients were grouped based on if their referral originated from another pediatric endocrinologist or if the dual-trained physician previously saw the patient in the pediatric T1D clinic. Transfer to adult care occurred when physician and patient felt it appropriate. The primary outcome was show rate at the first and second adult visits.

Results: Of 22 patients, 9 were referred from a different pediatric endocrinologist and 13 underwent guided transition. Both groups had similar initial A1c (p = 0.54). For patients seeing a different pediatric provider, the show rate to the first and second visit was 44% compared to 100% in the guided transition group (p = 0.003). The guided transition group maintained A1c (p = 0.79).

Conclusions: The guided transition group was significantly more likely to attend adult clinic than those seeing the provider for the first time. These findings deserve broader replication.

Disclosure

R. Lal: Consultant; Self; Abbott. D.M. Maahs: Advisory Panel; Self; Novo Nordisk Inc. Consultant; Self; Abbott, Sanofi. Research Support; Self; Dexcom, Inc., Tandem Diabetes Care. C. Dosiou: None. T. Aye: None. M. Basina: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007217)
1389-P: Nontargeted Metabolomics Reveal Novel Metabolites in Small- and Large-for-Gestational-Age Infants and Their Mothers Associated with Glucose and Lipid Metabolism
Authors: LIU JIEYING , ZHAI XIAO , XIAO XINHUA , YU MIAO , ZHAO NAN , LI ZHENGYAO , FU JUNLING , DENG MINGQUN , ZHOU LIYUAN
Published: June 2019

Small-for-gestational-age (SGA) or large-for-gestational-age (LGA) infants have increased risk of type 2 diabetes mellitus in later life. The intrauterine environment provides a foundation on which chronic disease develop in adulthood, however, the molecular mechanisms still remained unsolved. We recruited 135 pregnant and their infants, and then selected 67 pairs for plasma metabolomics analysis according to the birthweight of newborns, SGA (<10th percentile, n=16), AGA (∼50th percentile, n=28) and LGA (>90th percentile, n=23). Non-targeted metabolomics were performed by UPLC-Q-TOF-MS, and the metabolites were screened by P value, fold change and VIP value in OPLS-DA model. We found a group of metabolites over-/low-expressed in both SGA and LGA groups when compared to AGA group. Cholesteryl acetate (CE) was negatively related to SGA and LGA (logistic regression, AGA=0, SGA and LGA=1) in both mothers (adj. r=-1.50, adj. p=0.03) and infants (adj. r=-1.22, adj. p=0.03). Citicoline was positively related to SGA and LGA (maternal adj. r=4.71, adj. p=0.18; fetal adj. r=0.97, adj. p=0.06). CE and citicoline were involved in glycerophospholipid metabolism (EHMN database). Dihydroxyfumaric acid (DA) reported as insulin inhibitor was over-expressed in SGA and LGA (maternal adj. r=0.72, adj. p=0.09; fetal adj. r=0.91, adj. p=0.09). Moreover, the fetal citicoline (r=-0.294, p=0.082) and CE (r=0.369, p=0.027) was associated with cord blood glucose. Fetal DA was negatively associated with HDL (r=-0.416, p=0.012) and total cholesterol (r=-0.345, p=0.039).

In conclusion, the abnormal expression of CE, citicoline and DA in SGA and LGA mothers might cause the same abnormality in fetus, and were involved in glycerophospholipid metabolism and insulin inhibition. These new findings indicated that a group of metabolites which can be passed from mother to offspring might affect the metabolic syndrome in both SGA and LGA infants.

Disclosure

J. Liu: None. X. Zhai: None. X. Xiao: None. M. Yu: None. N. Zhao: None. Z. Li: None. J. Fu: None. M. Deng: None. L. Zhou: None.

Funding

National Natural Science Foundation of China (81870579); Fundamental Research Funds for the Central Universities (3332018015)
1393-P: Alterations in the Placental Proteome in Gestational Diabetes
Authors: ASSI EMMA , D'ADDIO FRANCESCA , NASR MOUFIDA BEN , LORETELLI CRISTIAN , MAESTRONI ANNA , USUELLI VERA , MANDÒ CHIARA , ROCCHIO FRANCESCA , CORRADI DOMENICO , FOLLI FRANCO , ZUCCOTTI GIANVINCENZO , CETIN IRENE , FIORINA PAOLO
Published: June 2019

Gestational diabetes mellitus (GDM) is the most frequent metabolic complication during pregnancy, affecting 3% to 25% women, and it is associated with abnormal fetal growth. Interestingly, the mechanism behind altered fetal growth in GDM is only partially understood. In order to discover novel factors that may play a role in placental function and fetal development, we interrogated the placental proteomes of healthy (CTRL, n=5) and GDM-affected (n=5) pregnant women using an unbiased proteomic approach. We demonstrated that the placental proteome is altered in GDM, with at least 64 proteins differentially expressed to a high degree (p<0.001) in GDM as compared to CTRL. Among those, 10 proteins are strictly involved in the mother-to-fetus crosstalk. While some of these proteins (e.g., C5, KRT8 and ATPSB) primarily exert protective effects of the trophoblast both in structure and function (e.g., invasion, angiogenesis, oxidative stress, barrier, energy support), others (e.g., CPAN6, TFRC and EZR) were importantly involved in fetal development (iron, muscle differentiation, nutrients) and protection from fetal loss (anticoagulant, regulation of epithelial-to-mesenchymal transition). These alterations in the GDM placental proteome suggest that placental dysfunction may be directly responsible for abnormal fetal growth/development during GDM. Targeting these proteins may thus offer therapeutic potentials for managing and treating GDM.

Disclosure

E. Assi: None. F. D'Addio: None. M. Ben Nasr: None. C. Loretelli: None. A. Maestroni: None. V. Usuelli: None. C. Mandò: None. F. Rocchio: None. D. Corradi: None. F. Folli: None. G. Zuccotti: None. I. Cetin: None. P. Fiorina: None.
1396-P: Lessons Learned from Implementing a Dietician-Led Low Risk Model of Care
Authors: MELONCELLI NINA J.L. , BARNETT ADRIAN G. , DE JERSEY SUSAN J.
Published: June 2019

Research from the U.S. and Australia indicates that individualized medical nutrition therapy provided by a Registered Dietician over a minimum of three appointments can reduce pharmacotherapy requirements for women with GDM. We used an implementation science approach to develop a dietician-led model of care for low risk GDM women. Our evaluation used a pre-post intervention comparison, with primary outcomes of pharmacotherapy use and adherence to clinical guidelines which includes the recommendation of three dietician appointments. Although there were significantly more women who received best-practice dietetic care in the post-intervention cohort, pharmacotherapy use increased (Table). However, other changes over time need to be considered when interpreting these results. Women in the post-intervention cohort were more likely to: have been diagnosed before 24 weeks; have had previous GDM; and be prescribed metformin (Table). Lessons learned included: timing of dietician appointments; ongoing facilitation of the implementation process; workforce engagement; lower targets for commencing pharmacotherapy; and increased surveillance of low-risk women, all of which may have resulted in higher pharmacotherapy conversion rates. Our results have highlighted the importance of measuring process outcomes alongside clinical outcomes and using an implementation science approach when aiming to provide best-practice care.

Disclosure

N.J.L. Meloncelli: None. A.G. Barnett: None. S.J. de Jersey: None.

Funding

Health Practitioner Research Scheme
1402-P: Functional Data Analysis Reveals Differences in Temporal Glucose Profiles Hidden by Standard Continuous Glucose Monitoring Analysis: A Secondary Analysis of the CONCEPTT Trial
Authors: SCOTT ELEANOR M. , MURPHY HELEN R. , FEIG DENICE , LAW GRAHAM
Published: June 2019

Background: The CONCEPTT randomized trial of CGM in pregnant women with type 1 diabetes showed significant improvement in pregnancy outcomes, but no difference in mean CGM glucose between those allocated to CGM vs. capillary glucose monitoring. Whilst summary statistics are recommended for the reporting of CGM data, they do not give dynamic information about the glucose profile across 24 hours.

Aim: To determine, using novel functional data analysis (FDA), if differences in the temporal glucose profile occurred in women randomized to CGM.

Methods: CGM data was available from 200 pregnant women (100 CGM intervention; 100 control) in the CONCEPTT study, at baseline, 24 and 34 weeks gestation. FDA was applied to the glucose data to generate functional glucose curves and multivariable statistical analysis applied.

Results: Despite having the same mean CGM glucose as those on capillary glucose monitoring alone 121 vs. 126 mg/dL; 6.7 vs. 7.0 mmol/l p=0.14, FDA revealed that pregnant CGM users were in fact running a significantly lower glucose (by 9-14mg/dL; 0.5-0.8 mmol/l) for a total of 8 hours a day (08.30-12.30 and 15.00-19.00).

Conclusion: Analysis of temporal glucose profiles gives key information about glucose control, missed by commonly reported CGM metrics. The women allocated to CGM ran a significantly lower glucose for 33% of the day.

Disclosure

E.M. Scott: Advisory Panel; Self; Abbott. Speaker's Bureau; Self; Abbott, Eli Lilly and Company. H.R. Murphy: Advisory Panel; Self; Medtronic MiniMed, Inc. D. Feig: Advisory Panel; Self; Medtronic. Speaker's Bureau; Self; Medtronic. G. Law: None.

Funding

JDRF; Canadian Clinical Trials Network; National Institute for Health Research
1404-P: Fasting Hyperglycemia during Pregnancy: Outcomes According to Delay of Care—An Observational Study Including 471 Women
Authors: COSSON EMMANUEL , VICAUT ERIC , BANON DORIAN SANDRE , BAUDRY CAMILLE , CUSSAC-PILLEGAND CAMILLE , VALENSI PAUL , CARBILLON LIONEL
Published: June 2019

Some guidelines, as the French one, recommend to screen early in pregnancy for hyperglycaemia first-diagnosed during pregnancy and to immediately care for high-risk women with a fasting plasma glucose level (FPG) higher than 92 mg/dL before 22 weeks of gestation (WG) (eFHG: early fasting hyperglycaemia). To date, no randomized study has shown any benefit of such a strategy. Among the women without known diabetes who delivered in our French center (2012-2016), we compared in those with eFHG the incidence of a predefined composite outcome (preeclampsia or large for gestational age infant or shoulder dystocia or neonatal hypoglycemia) by tertiles of delay of care. We performed a sensitivity analysis in the women with an early FPG ≥100 mg/dL. We included 471 women (88% with risk factor(s); 456 early gestational diabetes mellitus; 15 overt diabetes) whose delay of care was by increasing tertiles: 3.5±1.5 (T1), 9.5±2.3 (T2) and 20.1±8.8 weeks (T3). FPG (101±17/99±9/97±9 mg/dL for T1/T2/T3 respectively), rates of obesity (45/28/30%), age ≥ 35 years (42/37/26%), insulin treatment during pregnancy (63/50/38%), gestational age at insulin onset (21.7±7.1/23.5±5.2/31.0±4.8 weeks of gestation) statistically differed across tertiles. The incidence of the composite outcome was similar across tertiles in the 471 women (15.8 vs. 11.4 vs. 15.5%; p=0.45) and also in the 136 women with early FPG ≥ 100 mg/dL (13.0 vs. 7.3 vs. 22.9%; p=0.12) with however more neonatal hypoglycemia for T3 in this subpopulation (0 vs. 0 vs. 9.3%; p<0.05).This observational study shows that a long delay of care of women with FPG ≥ 100 mg/dL early in pregnancy is associated with a high rate of neonatal hypoglycemia. This stands in favor of screening for this condition which should be immediately cared for. Adjustment of our results for propensity scores is ongoing.

Disclosure

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

Funding

Lilly France; Roche Diagnostics France