bluuebunny/crossref_metadata_2025 huggingface dataset:
1357-P: Real-World Glycemic Profiles and Insulin Use Patterns of 9,914 Pediatric and Adolescent Patients with Type 1 Diabetes Using the Omnipod® Insulin Management System with Cloud-Based Data Management
Authors: LAYNE JENNIFER E. , ZHENG YIBIN , HE JIALUN , JANTZ JAY , BENJAMIN ERIC , LY TRANG T.
Published: June 2019

This observational study characterized glycemic profiles and treatment patterns of a large cohort of pediatric and adolescent patients with T1D using the Omnipod® Insulin Management System (Insulet Corp., Acton, MA) with integrated BG meter (Abbott Diabetes Care Inc., Alameda, CA) and data management system (Glooko, Mountain View, CA). From January 2015 through September 2018, usage data from the pump system were uploaded to the data management system and matched via device serial number to a second database of self-reported demographic data and de-identified. BG and insulin data from ≥3 months of system use per patient were analyzed. Demographics, glycemic profiles and insulin use of pediatric and adolescent patients with T1D (n=9,914) stratified by age group <6 y (n=499), 6 to <12 y (n=3,560) and 12 to <18 y (n=5,855) are reported in the Table. Mean glucose was 192±32, 190±31 and 201±39 mg/dL and bolus frequency per day was 7.5±2.8, 6.4±2.2 and 5.3±2.1 in the <6 y, 6 to <12 y and 12 to <18 y groups, respectively. These real-world data from a large cohort of youth with T1D demonstrate that use of a tubeless insulin pump was associated with BG levels that compare favorably to large registries including the T1D Exchange. These data also highlight important management patterns including frequent bolusing with Omnipod® System use.

Disclosure

J.E. Layne: Employee; Self; Insulet Corporation. Y. Zheng: Employee; Self; Insulet Corporation. Stock/Shareholder; Self; Insulet Corporation. J. He: Employee; Self; Insulet Corporation. J. Jantz: Employee; Self; Insulet Corporation. Employee; Spouse/Partner; Insulet Corporation. E. Benjamin: Employee; Self; Insulet Corporation. T.T. Ly: Employee; Self; Insulet Corporation.

Funding

Insulet Corporation
1365-P: Metabolic Control Three Years after Diagnosis in Children with T1D: Is DKA at Onset or HbA1c at Onset Closer Associated with Third Year HbA1c? Data from the International Pediatric Diabetes Registry SWEET
Authors: PICCINI BARBARA , SCHWANDT ANKE , ARSLANOGLU ILKNUR , CARDONA-HERNANDEZ ROQUE , COUTANT REGIS , JEFFERIES CRAIG A. , KIM JAE HYUN , KORDONOURI OLGA , LIMBERT CATARINA , PREIKSA ROMUALDAS TOMAS , LYCKÅ AUSTE PUNDZIUTE , RAMI-MERHAR BIRGIT , RICHMOND ERICK , SAVOVA RADKA , TODOROVIC SLADJANA , VEEZE HENDRIK J. , TONI SONIA ,   FOR THE SWEET REGISTRY
Published: June 2019

Objective: To establish if DKA at onset or HbA1c at onset is closer associated with metabolic control three years after diagnosis in a large, heterogeneous, international T1D cohort.

Methods: Data were collected from the international diabetes registry SWEET. 1420 T1D children (54% boys; 994 from Northern Europe, 341 from Southern Europe, 85 from America/Canada), diagnosed before 18 years, with documented clinical presentation and HbA1c at onset and follow-up data available were included. Patients were grouped according to presentation at onset: DKA with coma, DKA without coma and no DKA; and HbA1c at onset: low (HbA1c <10%), medium (10-<12%) and high (≥12%). To adjust for age at onset, gender and region, linear regression models were applied (adjusted means with 95% CI). Vuong test was employed to compare the association between third year HbA1c and both HbA1c at onset and presentation at onset.

Results: Median age at T1D onset was 9.1 [Q1; Q3: 5.8; 12.2] years. DKA with coma was present in 6% of children, DKA without coma in 37% and no DKA in 57%. No significant differences were found in third year HbA1c between DKA with coma 7.7 (7.4;8.0)%, DKA without coma 7.5 (7.4;7.6)% and no DKA group 7.6 (7.5;7.7)% [adjusted means (95% CI)]. Third year HbA1c was lower (7.4 (7.3;7.5)%) in low HbA1c compared to high HbA1c at onset group (7.7 (7.6;7.8)%, p<0.01). In the medium HbA1c group, third year HbA1c was 7.5 (7.4;7.6)% (no differences). Comparing the model with HbA1c at onset groups vs. the model with presentation at onset groups, the model with HbA1c at onset was closer associated with the third year HbA1c (p=0.02).

Conclusions The high percentage of DKA at T1D onset is still a concern worldwide. The level of HbA1c at onset was more closely associated with long term T1D control than the DKA at onset. Early T1D diagnosis, preventing high HbA1c at onset as well as DKA at onset, is important for long term metabolic control.

Disclosure

B. Piccini: None. A. Schwandt: None. I. Arslanoglu: None. R. Cardona-Hernandez: None. R. Coutant: None. C.A. Jefferies: None. J. Kim: None. O. Kordonouri: None. C. Limbert: None. R. Preiksa: None. A. Pundziute Lyckå: None. B. Rami-Merhar: Speaker's Bureau; Self; Eli Lilly and Company, Medtronic, Menarini Group, Roche Diabetes Care. E. Richmond: None. R. Savova: None. S. Todorovic: None. H.J. Veeze: Consultant; Self; Medtronic MiniMed, Inc. S. Toni: None.
1366-P: Effect of Substance Use on Type 1 Diabetes (T1D) Pancreas Histopathology
Authors: BRUGGEMAN BRITTANY S. , CAMPBELL-THOMPSON MARTHA , POSGAI AMANDA L. , ATKINSON MARK A. , SCHATZ DESMOND , JACOBSEN LAURA M.
Published: June 2019

Recent efforts addressing the pathogenesis of T1D have benefited greatly from access to transplant-quality human pancreas samples obtained from organ donors. While alcohol use is linked to pancreatitis clinically, the effect of alcohol and other illicit substances on pancreatic histopathology in T1D is not known. Hence, we determined the influence of alcohol, marijuana, tobacco, cocaine, and other controlled substances in T1D pancreata. In total, 140 T1D organ donor pancreata [median age at T1D onset=11 (range 0-36) years, duration=12 (0-84) years, 47% female] were recovered through the Network for Pancreatic Organ donors with Diabetes (nPOD) program. Paraffin sections were stained and reviewed for insulin positivity, insulitis (≥6 CD3+ cells adjacent/within the islet in ≥3 islets/section), amyloid staining, acute (acinar cell loss, mononuclear cell infiltrate, fat necrosis, and hemorrhage) and chronic pancreatitis (acinar cell loss, mononuclear cell infiltrate, and fibrosis) as well as chronic exocrine changes (acinar atrophy, fibrosis, fatty infiltration, or periductal fibrosis). Terminal hospital records were reviewed for a history of alcohol, tobacco, marijuana, and any illicit substance use. Of 140 T1D donors, 51% had a history of alcohol use, 40% tobacco use, 29% marijuana, and 20% other illicit substances. Urine drug screening on admission was available for 74 donors with 36 positive (49%). Alcohol use was associated with histopathological features of acute pancreatitis (p<0.05) and islet amyloid deposition (p<0.05). History of cocaine use (p<0.05) as well as a positive urine drug screen (p<0.05) were associated with chronic exocrine changes. To conclude, in T1D donor pancreata, alcohol use was associated with acute pancreatitis and islet amyloid deposition while a history of cocaine use and a positive urine drug screen were associated with chronic exocrine changes. These findings should be given consideration in studies aimed at interpreting histopathologic changes in T1D pancreata.

Disclosure

B.S. Bruggeman: None. M. Campbell-Thompson: None. A.L. Posgai: None. M.A. Atkinson: None. D. Schatz: None. L.M. Jacobsen: None.

Funding

JDRF
1372-P: Impact of Distance to Pediatric Diabetes Center on Outcomes in Youth with Type 1 Diabetes
Authors: WATSON SARA , JAWAD KAHIR S. , RODRIGUEZ LUNA MANUEL A. , WINTERGERST KUPPER A.
Published: June 2019

Background: The burden of T1D includes multiple visits to an endocrinologist each year, often requiring significant travel. Youth with T1D are especially impacted as pediatric endocrinologists are primarily concentrated at academic centers in urban areas.

Objectives: To assess the impact of distance to the diabetes treatment center on diabetes outcome measures. And to determine if the prevalence of technology use for the management of diabetes differs among youth with T1D living in urban versus rural communities.

Methods: Retrospective data was collected for youth ≤ 18 years of age, with a diagnosis of T1D for ≥ 6 months, seen at the Wendy Novak Diabetes Care Center. GIS mapping was used to analyze outcome measures by distance to the treatment center. Rural-Urban Commuting Area (RUCA) Codes were assigned to identify those living in metropolitan (RUCA 1-3), micropolitan (RUCA 4-6), and rural communities (RUCA 7-10).

Results: Inclusion criteria were met by 823 youth. Of these, 710 (86.3%) were white. Current CGM use was identified for 288 (35%), and pump use by 385 (46.8%). The mean distance traveled to the center was 18 miles (S.D. 8.8-52.2). Those traveling farther distances attended fewer clinic visits (p=0.0033). Those using a CGM or an insulin pump had more visits per year (p < 0.0001 and p=0.01, respectively). Among white youth, those traveling <20 miles used CGM 1.4 times more often than those traveling ≥20 miles (p=0.0196). Those living in metropolitan areas were more likely to use a CGM than those living in micropolitan or rural areas (p=0.0383).

Conclusions: Those with a greater burden of travel to receive specialty care attended fewer visits and were less likely to use CGM technology that has important benefits in improving blood glucose management and safety for those living with T1DM. This will be important to consider when developing strategies to improve access and support for this technology.

Disclosure

S. Watson: None. K.S. Jawad: None. M.A. Rodriguez Luna: None. K.A. Wintergerst: None.

Funding

Jaeb Center for Health Research
138-LB: Digital-Tool-Supported Basal Insulin (BI) Titration: Real-World Effectiveness of My Dose Coach in India
Authors: MODI K. D. , JHA SUJEET , PANDA MANJU , RASKAR VIVEK , MITTAL DIWAKAR , GHOSH ROMIK , GRIFFEN STEVE , ABUBUCKER SAHAR , SALEH MILENA
Published: June 2019

Appropriate insulin titration is critical in helping people with T2DM meet glycemic targets, but rates of successful self-adjustment are low, highlighting a need for additional support. My Dose Coach (MDC) is an FDA-approved digital tool that combines a smartphone app for people with T2D and a web portal for healthcare professionals (HCPs). HCPs define an individualized long-acting BI dose plan, which MDC uses to give dose recommendations based on the user’s fasting blood glucose (FBG) readings and hypoglycemic event data. MDC was introduced in India in 2018.

We evaluated real-world outcomes from people with T2D in India who were registered for MDC between Sep 1 and Dec 31, 2018. FBG and BI dose were logged directly by users in the MDC app. Users who reached goal were defined as those who logged three consecutive FBG measurements within their prescribed target range during their care plan.

There were 337 people who were registered with MDC and had logged >1 FBG reading; 113 (34%) reached their FBG goal, 27 (8%) were still titrating and 197 (58%) were no longer actively using MDC (discontinued without reaching goal). Mean (SD) time to FBG target in the ‘at goal’ cohort was 25 (26.9) days. In this cohort, mean (95% CI) FBG at baseline was 165.8 (156.4, 175.1) mg/dL, which decreased to 108.0 (106.7, 109.2) mg/dL at goal (p<0.001). Mean (95% CI) BI dose increased from 16.2 (15.1, 17.4) units at baseline to 19.4 (17.6, 21.2) units at goal (p=0.012). Over the entire observation period, 35% of participants in the ‘at goal’ group experienced hypoglycemia (FBG <70 mg/dL or below individual HCP-defined cut-off of at least 70 mg/dL); mean 0.62 events.

Most participants who continuously used MDC were able to successfully titrate BI and achieve target FBG. These data are very encouraging, showing the potential for simple digital titration tools, in appropriately selected people with T2D, to engage users in their own care, decrease the HCP burden and accelerate FBG target achievement in a resource-limited setting.

Disclosure

K.D. Modi: None. S. Jha: None. M. Panda: None. V. Raskar: Advisory Panel; Self; Sanofi. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Sanofi. D. Mittal: None. R. Ghosh: Employee; Self; Sanofi. S. Griffen: Employee; Self; Sanofi. S. Abubucker: None. M. Saleh: Employee; Self; Sanofi-Aventis Deutschland GmbH.

Funding

Sanofi
1380-P: Multiplex Detection of T1D-Associated Autoantibodies by High-Quantum-Efficiency FRET
Authors: METZ ANGELINA A. , ARSHAM ANDREW M. , LASER DANIEL J. , DROITCOUR AMY D.
Published: June 2019

We have developed a homogeneous time-resolved Förster Resonance Energy Transfer (TR-FRET) assay for rapid, no-wash multiplexed detection of T1D-associated autoantibodies from small volumes (5-10 μL) of patient plasma or serum. In our assay, separate pools of recombinant antigen are labelled with either a long-lived high-quantum-efficiency terbium cryptate FRET donor or a small-molecule flurophore FRET acceptor, generating potent FRET pairs. With the mean distance between the tips of the two epitope binding regions approximately 12-13 nm and the distance between the edges of each epitope binding arm on the order of 3.5 nm, the pairs are brought into signaling proximity when the twin binding arms of immunoglobulin bind a donor and an acceptor. We used terbium’s tightly banded multi-peak luminescence with large stokes shift and long millisecond-scale lifetime under 350 nm excitation to engineer the assay for detection of four T1D targets at clinically relevant concentrations—GAD 65, IA-2, ZnT8 and insulin—along with a fifth pair as an internal control. We report on the assay’s impressive performance with clinical samples, including the development and implementation of a high-performance crosstalk correction algorithm. The assay described here functions identically in both commercial plate readers and in point-of-care systems, a key feature for highly consistent test results.

Disclosure

A.A. Metz: Employee; Self; Wave 80 Biosciences, Inc. A.M. Arsham: Consultant; Self; Wave 80 Biosciences. D.J. Laser: Board Member; Self; Wave 80 Biosciences. A.D. Droitcour: Employee; Self; Wave 80 Biosciences.

Funding

Type 1 Diabetes Foundation
139-LB: Haptoglobin Phenotype and Levels in Type 2 Diabetes and Effects of Fenofibrate
Authors: JANUSZEWSKI ANDRZEJ S. , YOUNG HAYDEN K. , LI LIPING , OCONNELL RACHEL L. , LYONS TIMOTHY , KELLY CLARE B. , SULLIVAN DAVID , SCOTT RUSSELL , KEECH ANTHONY C. , JENKINS ALICIA
Published: June 2019

Background: Haptoglobin (Hp) is a plasma protein with anti-oxidant, anti-inflammatory and pro-angiogenic properties. Based on the Hp gene alleles there are three Hp phenotypes (1-1, 2-1 and 2-2). In diabetes, Hp-2 is associated with substantially increased risk of cardiac and renal damage relative to Hp-1. AIMS: To evaluate 1) associations between Hp phenotype and levels; and 2) effects of fenofibrate vs. placebo on Hp levels.

Methods: A substudy of 180 adults with type 2 diabetes (T2D) (50% females) from the FIELD trial. Average age was 60±6 years, BMI 30.4±5.1 kg/m2 and HbA1c 6.8±1.3%. Plasma (citrate) samples were evaluated at baseline, after 6-weeks daily 200 mg co-micronised fenofibrate (end of active run-in) and 2-years after randomisation to fenofibrate or placebo.

Results: Hp phenotype 1-1 was detected in 19%, Hp 2-1 in 48% and Hp 2-2 in 33% subjects. Hp levels at baseline were 1.44±1.10, 1.31±0.49 and 0.99±0.46 mg/mL in type 1-1, 2-1 and 2-2 respectively (all p<0.0001). In Hp type 2-2 baseline Hp levels correlated with HbA1c (r=0.35, p=0.005), BMI (r=0.30, p=0.02) and HDL-C (r=0.29, p=0.02). No such correlations were observed for Hp type 1-1 and 2-1. After 6-weeks fenofibrate Hp levels dropped by 22.3, 19.9 and 17.7% in type 1-1. 2-1 and 2-2 respectively (all p<0.0001; difference between types p=ns.). After 2-years of fenofibrate vs. placebo Hp levels in the placebo group had increased back to baseline values whereas Hp levels in the fenofibrate group remained reduced similar to 6-weeks levels. In Hp 1-1 subjects Hp levels dropped after 6-weeks fenofibrate in 94% of subjects, in Hp 2-1 - in 92% and in Hp 2-2 only in 73% of subjects (difference between phenotypes: p=0.002).

Conclusions: Hp levels differ by Hp phenotype in T2D adults. Fenofibrate lowers Hp levels in all phenotypes, however the effect is significantly attenuated in Hp 2-2.

Disclosure

A.S. Januszewski: None. H.K. Young: Other Relationship; Self; Medtronic. L. Li: None. R.L. OConnell: None. T. Lyons: None. C.B. Kelly: None. D. Sullivan: None. R. Scott: None. A.C. Keech: None. A. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc.

Funding

Sydney Medical School Foundation; National Health and Medical Research Council of Australia
139-OR: GIP Regulates Fatty Acid and Glycerol Synthesis in Human Adipocytes
Authors: MILLIGAN PAUL L. , ROTH KENNETH D. , HU HAITAO , MOYERS JULIE , RUAN XIAOPING , ROELL WILLIAM C. , REGMI AJIT
Published: June 2019

Activation of GIP (glucose-dependent insulinotropic peptide) receptor (GIPR) in combination with GLP-1 receptor has demonstrated reduced adiposity and bodyweight in mice. Although the incretin action of GIP in pancreatic beta cells is well characterized, its regulation of adipose tissue metabolism are incompletely understood. Using differentiated human adipocytes we demonstrated GIP suppression of insulin stimulated [14C] glucose and [14C] acetate incorporation into the cellular lipid fraction suggesting GIP/insulin co-regulation of de novo lipogenesis. To further investigate these findings, we employed an NMR and mass spec strategy. Briefly, human adipocytes were differentiated then incubated with [13C] glucose or [13C] acetate overnight in the presence GIP, insulin, GIP + insulin, or control followed by lysate preparation for mass spec and NMR analysis. Isotope label incorporation in lysate fatty acids were determined by HPLC-MS detection of base-hydrolyzed lipids. GIP significantly reduced incorporation of labeled acetate and labeled glucose in fatty acids, both in the presence and absence of insulin. Sample analysis by NMR demonstrated a GIP regulated increase in glycerol production from labeled glucose both in the presence and absence of insulin with little to no acetate incorporation into glycerol under all conditions tested. These findings demonstrate GIP signaling in adipocytes reduces de novo fatty acid synthesis while increasing glycerol formation. This suggests a model whereby GIP suppresses generation of new fatty acids from substrate but enhances appropriate storage capacity of dietary fatty acids by increasing production of glycerol required for triglyceride generation. Further studies will be required to elucidate this potential benefit of GIP to improve nutrient partitioning.

Disclosure

P.L. Milligan: Employee; Self; Eli Lilly and Company. K.D. Roth: Employee; Self; Eli Lilly and Company. H. Hu: None. J. Moyers: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. X. Ruan: Employee; Self; Eli Lilly and Company. W.C. Roell: Employee; Self; Eli Lilly and Company. A. Regmi: Employee; Self; Eli Lilly and Company.
1392-P: The Potential Role of Placental α2-Adrenergic Receptors in the High Risk of Preeclampsia in Diabetes
Authors: CHOW REBECCA P. , ZHAO JIAWU , CURTIS TIM , LYONS TIMOTHY , YU JEREMY
Published: June 2019

Preeclampsia is a life-threatening complication of pregnancy that occurs four times more frequently in the presence of maternal diabetes. The anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt1), released from the placenta, plays a crucial role in PE development. Alpha 2-adrenoceptor (A2AR) dysfunction has been reported in diabetes, and is implicated in the development of vascular complications. Furthermore, A2AR agonist antihypertensive agents are frequently used to treat patients with preeclampsia, whether they have a disease-modifying role is unclear. We hypothesized that A2AR dysfunction could underlie up-regulation of placental sFlt1 expression, thus ‘driving’ preeclampsia in diabetes. We treated cultured human trophoblasts (HTR8/SVneo) with a stressor often present in the diabetic vasculature, ‘heavily oxidized, glycated’ low-density lipoproteins (HOG-LDL), vs. native LDL (at 100 µg protein/ml) with or without the A2AR agonist, clonidine, and antagonist, yohimbine (24h; both drugs at 10 μM and 100 μM). We determined α2A-, α2B- and α2C-AR mRNA expression (RT-PCR) and immunostaining; sFlt1 mRNA expression and protein release (ELISA); and cell viability (Cell Counting Kit-8 assay). Experiments were repeated three times independently. We found that all three A2AR subtypes were expressed in human trophoblasts. HOG- vs. N-LDL increased sFlt1 mRNA expression (2.0-fold, p<0.001) and protein release (2.5-fold, p<0.01), but neither clonidine nor yohimbine had any effect at either dose. Neither HOG- nor N-LDL altered A2AR expression or cell viability. Overall, the data confirm that modified lipoproteins may promote PE development in women with diabetes via upregulation and release of sFlt1, but do not provide clear evidence that A2ARs are implicated in this process. Further work will investigate whether A2ARs may be modified by other stressors of diabetes, and whether they may affect non-sFlt1 mechanisms for PE.

Disclosure

R.P. Chow: None. J. Zhao: None. T. Curtis: None. T. Lyons: None. J. Yu: None.
1395-P: Maternal Exercise during Pregnancy Affects Offspring Adiposity through One Carbon Metabolism Cycle
Authors: BOONPATTRAWONG NICHA , MEHRAN ARYA , LAHER ISMAIL , DEVLIN ANGELA M.
Published: June 2019

Maternal obesity during pregnancy can adversely affect adult offspring adiposity and insulin resistance. The goal of this study was to determine if maternal exercise mitigates the adverse effects of maternal obesity on offspring health. Female (C57BL/6NJ) mice were fed from weaning a control diet (10%kcal fat; MC n=18) or western diet (45% kcal fat; MW n=15) to induce excess adiposity. After 13 weeks, the mice were bred and maintained on the diets, with (E) and without (S) access to a running wheel (exercise), throughout pregnancy and lactation. Offspring were weaned onto the control diet and fed for 13 weeks; male offspring were studied. Offspring from MWE dams had greater (p<0.05) retroperitoneal and mesenteric adipose tissue than offspring from MWS dams. This was not observed in offspring from dams fed the control diet. Offspring from exercised dams had lower glucose-stimulated insulin secretion compared to those from sedentary dams, independent of maternal diet. No differences in glucose and insulin tolerance were observed. One carbon metabolism is required for several physiological processes including DNA synthesis, amino and lipid metabolism, and the generation of methyl groups. Disturbances in one carbon metabolism occur in obesity. We hypothesized that maternal exercise mitigates the adverse effects of maternal obesity on offspring adiposity through changes in one carbon metabolism. MCE offspring had lower serum total homocysteine (6.3μmol/L) compared to MCS offspring (9.4μmol/L). This was not observed in the offspring from western diet-fed dams. Offspring from western diet-fed dams had higher hepatic methylenetetrahydrofolate reductase (Mthfr) mRNA expression compared to offspring from control diet-fed dams. Offspring from dams that exercised also had higher hepatic Mthfr mRNA; the highest expression was observed in MWE offspring. The findings from this study suggest that one carbon metabolism may play a role in developmental programing of offspring adiposity.

Disclosure

N. Boonpattrawong: None. A. Mehran: None. I. Laher: None. A.M. Devlin: None.

Funding

Canadian Institutes of Health Research
1409-P: Using Fasting Venous Plasma Glucose (FVPG) to Stratify Risk in Women with Gestational Diabetes (GDM)
Authors: MCINTYRE DAVID , GIBBONS KRISTEN S. , MADSEN LENE R. , MA RONALD C. , SACKS DAVID A. , TAM WING H. , CATALANO PATRICK
Published: June 2019

Powe et al described variable “defects” (defined as parameter values <25th centile for non GDMs) in OGTT derived insulin secretion (Isecr) and sensitivity (Isens) estimates in GDM. They reported that pregnancy complications relate primarily to low Isens. To explore applicability to routine OGTT data, an analogous but simplified analysis was undertaken, classifying IADPSG GDM women according to FVPG < or ≥ 75th centile for non GDM women (cut-off 4.6 mmol/L - near the cohort mean (SD) of 4.5(0.4) mmol/L). Our multi-ethnic cohort included a diverse group of 6128 untreated women from 5 centers in the blinded epidemiologic HAPO study. Analyses compared outcome frequencies (LGA, excess neonatal (NN) adiposity, NN hypoglycemia, NN hyperinsulinemia, preterm birth, primary C section) with non GDM women and between GDM-FVPG groups using χ2 tests and logistic regression analyses adjusted for maternal age, height, smoking, FH diabetes, BMI at OGTT visit and ethnicity (Table 1). The 25% of GDM women with FVPG < 4.6 mmol/L were at much lower risk of adverse outcomes. Although “mechanistic” classification considering Isecr and Isens may offer insights for treatment, a simpler classification by FVPG performs better and appears simpler for routine use. A modified “two-step” approach for detection and classification of pregnancy hyperglycemia, using FVPG as the first step, deserves consideration.

Disclosure

D. McIntyre: None. K.S. Gibbons: None. L.R. Madsen: None. R.C. Ma: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Research Support; Self; AstraZeneca, Bayer AG, Pfizer Inc. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; AstraZeneca. D.A. Sacks: None. W.H. Tam: None. P. Catalano: None.

Funding

National Institutes of Health
1415-P: Gestational Diabetes Mellitus after Delivery: The Need for Continued Vigilance
Authors: KAUL PADMA , SAVU ANAMARIA , MOORE LINN E. , YEUNG ROSEANNE O. , RYAN EDMOND A.
Published: June 2019

Despite guideline recommendations, there are currently limited data on the extent and yield of repeat postpartum glucose testing of women with gestational diabetes mellitus (GDM). Accordingly, we examined these issues in a large population-based cohort of women in Alberta, Canada, who gave birth between 10/01/2008-06/30/2013, were diagnosed with GDM, and followed-up until 12/31/2015 (n=10520). The study population included the 4625 (44%) women who underwent glucose testing within 6 months (m) after delivery. Laboratory data were used to identify rates of repeat testing between 6-18 m postpartum. Diabetes Canada thresholds were used to identify women who converted to diabetes mellitus (DM). A total of 211 (4.6%) women had overt DM, i.e., DM within 6 m of delivery. Among 4414 women with GDM who had a normal glucose test within 6 m, 1656 (37.5%) underwent repeat testing between 6-18 m. Of these, 77 (4.6%) were diagnosed with DM. This latter group was older, more likely multiparous, had higher rates of gestational hypertension and C-section, more likely to have been on insulin therapy during pregnancy, and had the highest rates of large for gestational age (LGA) babies (Table). While early postpartum glucose screening is likely to identify women with overt diabetes, continued monitoring, despite initial normal screens, is necessary to ensure early detection of DM and other chronic disease in women with GDM.

Disclosure

P. Kaul: None. A. Savu: None. L.E. Moore: None. R.O. Yeung: Advisory Panel; Self; Sanofi. Consultant; Self; Novo Nordisk Inc. Research Support; Self; AstraZeneca. Speaker's Bureau; Self; Novo Nordisk Inc., Sanofi. E.A. Ryan: None.

Funding

Canadian Institutes of Health Research
1421-P: Associations of Sleep Disturbances Before and During Early Pregnancy with Increased Risk of Gestational Diabetes
Authors: BADON SYLVIA E. , XU FEI , FERRARA ASSIAMIRA , HEDDERSON MONIQUE M.
Published: June 2019

Women with sleep disturbances before or during pregnancy may be at high risk for gestational diabetes (GDM) due to poor sleep-related increases in insulin resistance. To estimate associations of habitual snoring and other sleep disturbances before and during early pregnancy with GDM risk, we combined data collected as part of two prospective pregnancy cohort studies at Kaiser Permanente Northern California that used the same sleep questionnaires (N=3,646, 2011-2018). In early pregnancy (7-22 weeks gestation) participants self-reported snoring frequency in the 12 months before becoming pregnant and since becoming pregnant. Snoring most or some of the time was considered habitual snoring. Participants also reported if they had trouble falling asleep in early pregnancy. Three hundred four (8%) women were diagnosed with GDM based on laboratory glucose values meeting the Carpenter and Coustan criteria. Forty-four percent of women reported habitual snoring prior to pregnancy and 45% in early pregnancy. Thirty-one percent of women reported trouble falling asleep in early pregnancy. In logistic regression models adjusted for maternal age, race/ethnicity, pre-pregnancy BMI, and parity, habitual snoring prior to pregnancy was associated with a 33% greater odds of GDM (OR [95% CI]: 1.33 [1.00, 1.77]) compared to no snoring. Habitual snoring in early pregnancy was not statistically significantly associated with GDM (1.14 [0.84, 1.53]). Trouble falling asleep in early pregnancy was borderline significantly associated with greater GDM risk (1.27 [0.98, 1.66]). Our findings suggest that snoring prior to pregnancy and other sleep disturbances during early pregnancy are associated with greater risk of GDM. Studies with objective measures of sleep are needed to confirm these findings and prior to designing interventions to reduce sleep disturbances to decrease risk for GDM.

Disclosure

S.E. Badon: None. F. Xu: None. A. Ferrara: None. M.M. Hedderson: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (T32DK11668401 to S.E.B.)
1425-P: A Translational Diabetes Prevention Program (DPP)-based Lifestyle Intervention in Women with GDM Improves Postpartum Lifestyle Behaviors
Authors: HEDDERSON MONIQUE M. , BROWN SUSAN D. , FENG JUANRAN , QUESENBERRY CHARLES , FERRARA ASSIAMIRA
Published: June 2019

Women with GDM are 7 times more likely to develop type 2 diabetes later in life than parous women without GDM. Thus, interventions to improve lifestyle behaviors among women with GDM are urgently needed. In a randomized controlled trial, we tested a DPP-based intervention to help women with GDM make long-term healthy lifestyle changes and manage weight after pregnancy. Of 352 participants, 178 were randomized to standard care and 174 were randomized to a lifestyle intervention of individual sessions with a coach trained in motivational interviewing, which provided specific diet, physical activity and weight goals. The intervention consisted of a pregnancy phase (1 in-person session and 2 telephone sessions), an early postpartum phase (2 in-person sessions and 11 telephone sessions up to 6 months postpartum), and a late postpartum phase (6 maintenance newsletters up to 12 months postpartum). Participants were followed from pregnancy (shortly after GDM diagnosis) to 24 months postpartum. On average, over the 24-month postpartum period, women in the intervention reported greater reductions in daily total energy intake (mean changes [95% CI]: 103.5 [-206.8 to -0.2] kcal) and percent of calories from fat (-1.6 [-2.7 to -0.4]) than women in standard care. Women in the intervention also reported greater increases in MET hours/week of moderate-intensity sports activity at 6 months postpartum (1.98 [-0.24 to 4.20]); however, this difference did not persist at 24 months postpartum (1.00 [-1.64 to 3.65]). On average, over the 24-month postpartum period, there was no difference between conditions in mean weight change (-0.09 [-1.12 to 0.94] kg). A 12-month, translational DPP-based intervention delivered primarily via telephone improved diet and physical activity, but did not impact weight, at 24 months postpartum.

Disclosure

M.M. Hedderson: None. S.D. Brown: None. J. Feng: None. C. Quesenberry: None. A. Ferrara: None.

Funding

National Institutes of Health
1427-P: Plasma Phospholipid MUFA Biomarkers and Gestational Diabetes Mellitus: A Longitudinal Study in a Multiracial Cohort
Authors: TSOI KIT YING , ZHU YEYI , WU JING , SUN QI , LI MENGYING , HINKLE STEFANIE , AJJARAPU APARNA , MA RONALD C. , ZHANG CUILIN
Published: June 2019

Previous studies on circulating monounsaturated fatty acids (MUFAs) and the risk of gestational diabetes (GDM) are limited although MUFAs have been implicated outside of pregnancy in glucose homeostasis. The aim of this study was to prospectively investigate levels of total and individual MUFAs (16:1n-7c, 18:1n-9, 20:1n-9, 24:1n-9) in plasma phospholipids in relation to risk of GDM. This was a case-control study nested in the NICHD Fetal Growth Studies-Singletons (2009-2013), a prospective study of 2,802 low risk pregnant women. A total of 107 GDM cases were ascertained using the Carpenter and Coustan criteria, and 214 non-GDM controls were selected on a 1:2 ratio and individually matched on age, race/ethnicity, and gestational week (GW) of blood collection. Blood samples were collected at GW 10-14, 15-26, 23-31 and 33-39. Spearman’s correlation coefficient was used to assess the association of circulating MUFAs with indices of glucose homeostasis (e.g., insulin, C-peptide, and HOMA-IR). Conditional logistic regression models adjusted for risk factors of GDM including pre-pregnancy BMI were used to assess the associations of circulating MUFAs with subsequent GDM risk. Total MUFAs (p=0.015) and 18:1n-9 (p=0.012) were significantly lower in GDM cases than controls at GW 15-26. 16:1n-7c was significantly higher in GDM cases than controls at GW 10-14 (p=0.008) and 15-26 (p=0.048). Total MUFAs and 18:1n-9 at GW 15-26 were significantly associated with a lower GDM risk; the adjusted ORs (95% CIs) comparing highest vs. lowest quartiles were 0.15 (0.05-0.44) and 0.14 (0.05-0.45), respectively. Total MUFAs and 18:1n-9 at GW10-14 were inversely correlated with insulin, HOMA-IR, c-peptide at GW 15-26. No significant associations were observed for other individual MUFAs at GW 10-14 or 15-26 with GDM risk.

In conclusion, higher plasma concentrations of MUFAs, especially 18:1n-9, at GW 15-26 were prospectively related to a reduced risk of GDM.

Disclosure

K. Tsoi: None. Y. Zhu: None. J. Wu: None. Q. Sun: Consultant; Self; Emavant Solutions GmbH. M. Li: None. S. Hinkle: None. A. Ajjarapu: None. R.C. Ma: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Research Support; Self; AstraZeneca, Bayer AG, Pfizer Inc. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; AstraZeneca. C. Zhang: None.

Funding

Eunice Kennedy Shriver National Institute of Child Health and Human Development; American Recovery and Reinvestment Act (HHSN275200800013C, HHSN275200800002I, HHSN27500006, HHSN275200800003IC, HHSN275200800014C, HHSN275200800012C, HHSN275200800028C, HHSN275201000009C, HHSN275201000001Z)
1433-P: Does Physician Counseling Regarding Lifestyle Choices Impact Postpartum Visit Attendance among Pregnant Women with Diabetes?
Authors: MANIN EMILY , HERRICK CYNTHIA J. , DUCKHAM HILLARY E. , WOOLFOLK CANDICE L. , CARTER EBONY B.
Published: June 2019

Objective: To determine whether physician lifestyle counseling during prenatal care for patients with diabetes is associated with increased attendance at postpartum visit.

Study Design: We performed a retrospective cohort study of pregnant women with type 1, type 2 and gestational diabetes who received prenatal care at Barnes-Jewish Hospital from June 2009- December 2017. Medical records were reviewed to determine whether the physician documented counseling the patient regarding exercise, diet, weight gain, and whether the patient saw a diabetes educator for at least one visit during the course of prenatal care. Logistic regression was used to identify the association between physician counseling and 6-week postpartum visit attendance after controlling for age, race, employment, education, number of prenatal visits, delivery complications, and delivery mode.

Results: Of 638 patients in the cohort, 319 (50%) were documented to have received lifestyle counseling from their physician: 82 (26%) on exercise, 277 (87%) on diet, and 100 (31%) on recommended gestational weight gain. Most patients (87%) saw a diabetes educator. Demographic characteristics were similar between women who received lifestyle counseling and those who did not. Seventy-three percent of patients attended the 6-week postpartum visit and women with documentation of lifestyle counseling were nearly twice as likely to attend as those without (aOR 1.87; 95% CI 1.18-2.98). There were no differences in postpartum visit attendance based on consultation with a diabetes educator.

Conclusion: Physician documentation of lifestyle counseling for pregnant women with diabetes is associated with improved rates of postpartum visit attendance, but documentation of counseling remains low. Further study is needed to determine the content/quality of physician lifestyle counseling and its impact on pregnancy and postpartum outcomes among women with pregnancies complicated by diabetes.

Disclosure

E. Manin: None. C.J. Herrick: Stock/Shareholder; Spouse/Partner; Cardinal Health. H.E. Duckham: None. C.L. Woolfolk: None. E.B. Carter: None.

Funding

Robert Wood Johnson Foundation (74250)
1436-P: Gestational Diabetes Pregnancy by Pregnancy
Authors: GIULIANI CHIARA , BITTERMAN OLIMPIA , AMOROSI FRANCESCA ROMANA , FESTA CAMILLA , NAPOLI ANGELA
Published: June 2019

Gestational diabetes mellitus (GDM) is a risk factor for GDM in next pregnancies.The aims of this observational study are to measure GDM recurrence rate in post index pregnancy of women with prior GDM and to compare maternal and neonatal outcomes and pancreatic beta cells function in two consecutive pregnancies.

Methods: Longitudinal observational study in 68 women with GDM in index pregnancy (G1), followed by a post index pregnancy (G2) and normal glucose tolerance in-between [G1 vs. G2: age 32,1±4,6 vs. 35,5±4,7 years, BMI 24,5 (19,2-42,7) vs. 24,7 (17,5-42,2) kg/m2, ns]. GDM diagnosis according to IADPSG criteria. Statistics: SPSS.

Results: significantly earlier first visit gestational age in G2 [17 (6-36) weeks] than in G1 [28,5 (8-35) weeks] (p<0,001). GDM recurrence rate was 85,3% (n58) 3,32±1,8 years after index pregnancy: of these women, n31 (45,6%) [36.5±4 years; BMI 24.7 (19.3-42.1) Kg/m2] developed GDM in early pregnancy (16-18 weeks), while n27 (39,7%) [35.66±4 years; BMI 25.26 (17.6-42.2) Kg/m2] at the end of second trimester (24-28 weeks). Women who reported a negative OGTT at both time-points (n10, 14,7%) [33.7±5.5 years; BMI 20.45 (17.5-25.4) Kg/m2;] showed a significantly lower BMI (p<0,0015) and a higher disposition index (p=0.07) than those with positive OGTT. In women who did not relapse GDM, no significant inter-pregnancy weight gain was observed and GDM diagnosis in G1 was performed by post-load OGTT points. Lower 24-28thOGTT post load blood glucose levels and AUCglucose were found in G2 (p<0,02, Wilcoxon). No pancreatic beta cells function deterioration was recorded in post index pregnancy. We found a lower rate of cumulative neonatal adverse outcomes in G2 (30,2% in G1 vs. 25,7% in G2, p<0,04) and a reduced maternal hypertension rate even though it did not reach the level of significance (4vs8).

Conclusions: GDM relapsed in the majority of women with previous GDM with no weight gain between pregnancies and no pancreatic function deterioration. However, a normal OGTT in second pregnancy was found in normoweight women.

Disclosure

C. Giuliani: None. O. Bitterman: None. F. Amorosi: None. C. Festa: None. A. Napoli: None.
1437-P: How Has Changing the Diagnostic Criteria Impacted Perinatal Outcomes for Those NOT Diagnosed with GDM?
Authors: MELONCELLI NINA J.L. , BARNETT ADRIAN G. , DE JERSEY SUSAN J.
Published: June 2019

In 2015, more than 90% of Australian antenatal care providers transitioned to the IADPSG recommendations for screening and diagnosing GDM. In the Australian state of Queensland, this resulted in 34% more women being diagnosed with GDM. Based on the increased number of women being treated for GDM, we hypothesized that perinatal outcomes, commonly associated with GDM, should decrease for pregnant women without GDM. We used routinely collected perinatal data of over 124,000 women to examine the difference in perinatal outcomes in the year before (2014) and after (2016) state-wide policy was changed for diagnosing GDM. Logistic regression was used to estimate the odds ratio and 95% confidence intervals for the risk of developing selected perinatal outcomes in women without GDM. Despite 34% more women being diagnosed and treated for GDM, there was a statistically significant increase in the year after the changes to the diagnostic criteria for women without GDM for: pregnancy-induced hypertension (OR 1.10, 95% CI 1.03 - 1.16), large-for-gestational (OR 1.37, 95% CI 1.17 - 1.60), small-for-gestational age infants (OR 1.75, 95% CI 1.59 - 1.92) and neonatal hypoglycaemia (OR 1.23, 95% CI 1.15 - 1.30). There was a decrease in respiratory distress (OR 0.93, 95% CI 0.88 - 0.98). Our results add to the growing body of evidence that changing diagnostic criteria has had little impact on outcomes for women GDM and in our study, the outcomes for women without GDM appeared to have worsened. Although our study design does not allow us to examine why this negative shift has occurred, we hypothesize that the additional resources required for treating women with GDM may have been provided at the expense of women without the condition. We question whether changing the diagnostic criteria was the correct choice for our population, given the increase in costs of treatment and recommend further research on potential harms in both the GDM and non-GDM populations.

Disclosure

N.J.L. Meloncelli: None. A.G. Barnett: None. S.J. de Jersey: None.
1442-P: Incidence and Risk Factors for Type 2 Diabetes among the Offspring of Long-Lived Individuals: The Long Life Family Study
Authors: MILJKOVIC IVA , CVEJKUS RYAN , AN PING , THYAGARAJAN BHARAT , BOUDREAU ROBERT , ZMUDA JOSEPH M.
Published: June 2019

Centenarians and their offspring appear to have a reduced risk of type 2 diabetes (T2D) compared to similarly aged controls. We determined the incidence of and potential risk factors for T2D among the offspring of probands and their spouses (mean age =60 years; SD=8 years), in the Long Life Family Study (LLFS), a multicenter cohort study of two-generation families with a clustering of healthy aging and exceptional survival. Incident T2D was defined as fasting serum glucose ≥126 mg/dl, or HbA1c of ≥6.5%, or self-reported with doctor diagnosis of T2D, or the use of antidiabetic medication during a mean follow-up 7.9 ± 1.1 years. Among nondiabetic offspring (n=1585) and spouses (n=495) at study entry, 58 (3.7%) and 19 (3.8%) developed incident T2D, respectively. By comparison, 5.1% of comparable aged nondiabetics developed T2D in the Framingham Offspring Study. At Visit 1, BMI, waist circumference, and fasting serum triglycerides were positively, whereas HDL-C and adiponectin were inversely associated with incident T2D among offspring in LLFS (all P<0.05 for all using logistic GEE with intra-family correlations). Similar associations were observed in their spouses (P<0.05 for all). Additionally, we observed that among spouses serum interleukin 6 and insulin-like growth factor 1 concentrations were positively associated with incident T2D (P<0.05 for both). All associations were independent of age, sex, field center, alcohol intake, hours of walking, and BMI or waist circumference (in models with metabolic and inflammation biomarker predictors). The current study suggests that offspring of long-living individuals in the LLFS and their spouses may share a similar, low risk for developing T2D as compared to the general population. Our findings also raise the possibility that distinct risk factors may contribute to T2D risk among offspring of long-lived individuals compared to their spouses.

Disclosure

I. Miljkovic: None. R. Cvejkus: None. P. An: None. B. Thyagarajan: None. R. Boudreau: None. J.M. Zmuda: None.

Funding

National Institute on Aging
1446-P: Fall Risk in Individuals with Type 2 Diabetes: The Look AHEAD Study
Authors: LEE PEARL G. , POKHREL KESHAV P. , HERMAN WILLIAM H.
Published: June 2019

Over one quarter of adults ≥65 years of age with diabetes report falling in the preceding 2 years. We hypothesized that participants in the Look AHEAD intensive lifestyle intervention (ILI) would have fewer falls compared to those who received diabetes support and education (DSE) only. The Look AHEAD study randomly assigned participants (aged 45-76 years) with type 2 diabetes and body mass index (BMI) ≥25 kg/m2 to ILI (diet and physical activity to induce ≥7% of initial weight) or DSE. We compared baseline characteristics of participants who reported 0, 1, or 2+ falls at year 8, by intervention group, and built multinomial logistic regression models to predict falls. Older adults with diabetes randomly assigned to the ILI compared to those in the DSE were less likely to fall 2 or more times at 8-year follow-up in the Look AHEAD study (β= -0.18, p = 0.01).

Disclosure

P.G. Lee: Advisory Panel; Self; T1D Exchange. Other Relationship; Self; Sanofi. K.P. Pokhrel: None. W.H. Herman: Consultant; Self; Janssen Scientific Affairs, LLC. Consultant; Spouse/Partner; Nestlé. Other Relationship; Self; Merck Sharp & Dohme Corp.
1459-P: Comparative Cardiovascular Safety and Effectiveness of Linagliptin in Routine Care: Final Results from a 5-Year Post-Marketing Monitoring Program
Authors: PATORNO ELISABETTA , GOPALAKRISHNAN CHANDRASEKAR , MAHESRI MUFADDAL , BRODOVICZ KIMBERLY G. , BARTELS DOROTHEE , MEYERS ANDREA , BARBERIO JULIE , LIU JUN , SCHNEEWEISS SEBASTIAN
Published: June 2019

Real world data on the cardiovascular (CV) safety and effectiveness of linagliptin (LINA) complement trial data from CARMELINA, which showed CV safety, and CAROLINA (results pending). As part of a 5-year (05/2011-12/2016) post-marketing monitoring program, using 2 large insurance claims databases, we assessed the risk of a composite CV (cCV) outcome (hospitalization for myocardial infarction, stroke, unstable angina, or coronary revascularization). We identified three 1:1 propensity score (PS)-matched cohorts of type 2 diabetes mellitus patients who initiated linagliptin or a comparator [other DPP-4is (n=39,834 pairs), pioglitazone (PIO; n=29,646 pairs), or sulfonylureas (SU; n=25,285 pairs). We estimated pooled HR and 95% CI controlling for over 180 baseline characteristics. After PS-matching, patient characteristics were similar (Table 1) and mean follow-up was 0.8 years. LINA had a similar risk of the cCV outcome compared to other DPP-4is [HR (95% CI) = 0.90 (0.80-1.02)] and PIO [HR (95% CI) = 0.99 (0.86-1.13)], but was associated with a reduced risk compared to SU [HR (95% CI) = 0.77 (0.66-0.90)] (Table 1). Results were robust across numerous sensitivity analyses. These real-world data show that LINA has reassuring effectiveness and safety on a cCV outcome compared to other DPP-4is and PIO, and is associated with a decreased risk compared to SU.

Disclosure

E. Patorno: Research Support; Self; National Institute on Aging. Other Relationship; Self; Boehringer Ingelheim International GmbH. C. Gopalakrishnan: None. M. Mahesri: None. K.G. Brodovicz: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. D. Bartels: Employee; Self; BI X GmbH, Boehringer Ingelheim International GmbH. A. Meyers: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. J. Barberio: None. J. Liu: None. S. Schneeweiss: Consultant; Self; Aetion, WHISCON, LLC.

Funding

Boehringer Ingelheim