bluuebunny/crossref_metadata_2025_split huggingface dataset:
1157-P: Diabetic Ketoacidosis (DKA) Rates Do Not Differ by Insulin Pump Use vs. Nonuse in Teens with Type 1 Diabetes (T1D) and Executive Function (EF) Problems
Authors: VITALE REBECCA J. , VOLKENING LISA K. , LAFFEL LORI M. 
Published: June 2023

Aim: Providers may resist offering pump therapy to teens with T1D who have challenges with EF (planning, organization) due to concerns for DKA. We evaluated rates of DKA and severe hypoglycemia according to pump use in teens with and without EF problems.
Methods: Parents of teens aged 13-17 years with T1D provided proxy reports of teen EF using the Behavior Rating Inventory of Executive Function (BRIEF). Global Executive Composite (GEC) t-score ≥60 defined risk of executive dysfunction. Families reported severe hypoglycemic episodes and ER visits/hospitalizations for hyperglycemia (including DKA) every 3 months for 18 months. Incidence rates (IR) were calculated as events/100 person-years. DKA IR includes ER visits/hospitalizations for either hyperglycemia or DKA. Poisson regressions evaluated differences in IR by pump use, CGM use, and BRIEF score.
Results: 169 teens (54% male) had baseline age 14.9±1.3 years, T1D duration 7.4±3.7 years, A1c 8.5±1.0%; 69% were pump users, 41% used CGM some time during follow-up, and 31% had GEC ≥60. During 297 person-years, severe hypoglycemia IR was 38.3/100 person-years and DKA IR was 7.7/100 person-years. There were no differences in hypoglycemia IR by pump or CGM use or GEC score. There was no difference in DKA IR by CGM use while DKA IR was lower in pump users vs non-users (4.9 vs 14.0, p=.01) and in those with GEC &lt;60 vs ≥60 (4.9 vs 14.0, p=.01). Among those with GEC &lt;60, DKA IR was lower in pump users vs non-users (2.0 vs 13.7, p=.003); in those with GEC ≥60, DKA IR was similar in pump users and non-users (13.7 vs 14.4, p=.94).
Conclusion: In this sample of teens with T1D, hypoglycemia IR did not differ by pump or CGM use or EF status; in the teens with EF challenges, DKA IR was not higher in pump users vs non-users. These observations suggest that hesitation by clinicians to offer insulin pump therapy to teens with clinical suspicion of executive dysfunction due to concerns for increased DKA risk may not be warranted.

Disclosure
R.J.Vitale: None. L.K.Volkening: None. L.M.Laffel: Advisory Panel; Medtronic, Lilly Diabetes, Novo Nordisk, Vertex Pharmaceuticals Incorporated, Roche Diagnostics, Provention Bio, Inc., Consultant; Dexcom, Inc., Janssen Pharmaceuticals, Inc., Medscape.

Funding
National Institutes of Health (P30DK036836, R01DK095273); JDRF (2-SRA-2014-253-M-B); Iacocca Family Foundation
1164-P: Evaluating the Impact of Telemedicine Expansion on Access to Care for Oregon's Pediatric Type 1 Diabetes Population
Authors: MITCHELL EMILY S. , ANDREA SARAH B. , GUTTMANN-BAUMAN INES 
Published: June 2023

Background: Type 1 Diabetes (T1D) has a higher incidence in low density areas but only 1.8% of US pediatric endocrinologists are located in rural areas. The telemedicine expansion (TE) that accompanied the COVID-19 pandemic presents a novel opportunity to increase access to care for rural-residing children with T1D who may live a great distance from their provider.
Purpose: The study objective was to compare trends in visit frequency amongst our region's pediatric T1D population before and after TE by those living &lt;100 miles versus ≥100 miles from clinic (MFC) and those residing in urban versus rural areas.
Methods: We evaluated EHR data from 790 children receiving care between July 2018 - December 2021. We estimated differences in likelihood of adequately-timed monitoring care (ATMC) over time by patient CCS status using Generalized Estimating Equations.
Results: Just prior to TE, those living ≥100 MFC were 20.6% less likely to receive ATMC compared to those living &lt;100 MFC (RR 0.79; 95% CI: 0.57, 1.11). Following TE, likelihood of ATMC decreased from 31.0% to 24.0% in those living ≥100 MFC and decreased from 39.0% to 25.9% in those living &lt;100 MFC; decreases in ATMC for those living ≥100 MFC were less than for those living &lt;100 MFC (RR of interaction: 1.17; 95% CI: 0.68, 2.00). Just prior to TE, those living in rural areas were 0.1% less likely to receive ATMC (RR 1.00; 95% CI: 0.61, 1.63) compared to those living in urban areas. Following TE, likelihood of ATMC decreased from 37.2% to 20.2% in those living in rural areas and decreased from 37.3% to 25.7% in those living in urban areas; decreases in ATMC were greater for those living in rural areas versus urban areas (RR of interaction: 0.79; 95% CI: 0.31, 2.01).
Conclusions: Between July 2020 and December 2021, the likelihood of ATMC decreased across the entire pediatric T1D population. Decreases in ATMC were more substantial for those living &lt;100 MFC and/or in rural areas, however, these discrepancies were not statistically significant.

Disclosure
E.S.Mitchell: None. S.B.Andrea: Research Support; Eli Lilly and Company. I.Guttmann-bauman: None.
1175-P: The Alteration of Serum Level and Expression of c-MET in Gestational Diabetes Mellitus (GDM)
Authors: JIN KIM HYUN , LEE JUHEE , WON JUNG YE , LEE MINA , KIM JIMIN , HYE JOUNG KYONG , JEONG KU BON 
Published: June 2023

Objective: The aim of this study was to explore changes in serum levels and tissue expression of HGF and c-MET, and to determine how HGF/c-MET signaling contributes to the pathophysiology of GDM.
Methods: A total of 44 pregnant women with normal glucose tolerance (NGT) and 32 pregnant women with GDM were studied. Blood samples were taken just before delivery, and placenta and visceral adipose tissue were taken immediately after cesarean delivery. Serum levels of HGF, soluble c-MET and insulin were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA expression of HGF and c-MET was measured in the placenta and visceral adipose tissue. In addition, we investigated pregnancy of high fat diet (HFD) mice as an animal model of GDM. The glucose tolerance test (GTT) was performed at GD 10, and measured the serum levels of Hgf and soluble c-Met at GD 16. After scarifying mice, we measured the weight and expression of mRNA of Hgf and c-Met in WAT, placenta, liver and muscle.
Results: Serum soluble c-MET levels were significantly higher in the GDM group (p &lt;0.001). In multiple logistic regression analysis, soluble serum c-MET level was strongly associated with GDM (OR 9.063, p=0.027). There were more patients with increased mRNA expression of HGF and c-MET in placenta. Interestingly, the protein expression of HGF and c-MET in maternal visceral fat tissue was significantly higher in the GDM group. In mouse study, maternal serum levels of soluble c-Met in pregnant HFD (PH) mice were higher than in non-pregnant HFD (NPH) mice and pregnant chow diet (PC) mice. Relative mRNA expression of Hgf was significantly increased in eWAT of PH than PC mice. Relative c-Met mRNA expression was significantly increased in sWAT of PH than PC mice. Conclusion: We observed the differences in serum levels and expression of HGF and c-MET between GDM and control pregnant women in human and mice model. Our results suggest that HGF/c-MET signaling may be altered in GDM, which associated with insulin resistance and pathophysiology in GDM.

Disclosure
H.Kim: None. J.Lee: None. Y.Jung: None. M.Lee: None. J.Kim: None. K.Joung: None. B.Ku: Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company, Sanofi, Novo Nordisk, LG Chem.

Funding
National Research Foundation of Korea (2022R1F1A1074608)
1178-P: Interleukin-17 Signaling in Cerebrum of Offspring from Mother with Diabetes
Authors: SUGAI KEIJI , SASAKI JUNKO , ISHII KEITARO , LI GUOJIAO , ITO MARIKO , AIERKEN MAIERHABA , SUWANAI HIROTSUGU , TORII MASAAKI , HASHIMOTO-TORII KAZUE , ODAWARA MASATO , SUZUKI RYO 
Published: June 2023

A number of human cohort and animal studies suggest that offspring from mother with diabetes (OMD) has an increased risk of both short- and long-term complications, including various neurological issues including learning impairment and autism spectrum disorders. However, the underlying mechanism of the neurobehavioral issues is still not elucidated. The main objective of this study is to examine their mechanisms by examining gene expression in the cerebrum of OMD during the embryonic period. Six-week-old Crl: CD1 (ICR) females were injected intraperitoneally with 150 mg/kg of STZ for generating OMD. This OMD model showed learning impairment using accelerated rotarod as we previously reported at the 81st Scientific Sessions of the American Diabetes Association. Citrate buffer was used to generate the control group. After mating the females with healthy males, both maternal and fetal cerebrums were collected at embryonic day 17.5. RNA was extracted from the collected cerebrums using TRIzol, and RNA sequencing and quantitative PCR were performed. The number of differentially expressed genes common to three types of analysis (EdgeR, Deseq2, and TCC) was 40. Enrichment analysis of these 40 genes using the KEGG pathway identified a group of genes (Lipocalin-2 (Lcn-2), S100a8, and S100a9) related to the Interleukin 17 (IL-17) pathway. Quantitative PCR revealed mRNA expression of these genes was significantly higher in OMD. In order to investigate the distribution of Lcn-2, we next intraperitoneally administered biotinylated Lcn-2 to pregnant dam at gestational day 17.5 and collect maternal and fetal samples 30 minutes after the administration. Immunohistochemical staining showed that biotin expression was observed in the maternal cortex but not in the fetal one, suggesting that maternally derived Lcn-2 does not reach the fetal cortex. Altogether, our results demonstrate that IL-17 signaling in the fetal brain may be involved in learning impairments in OMD.

Disclosure
K.Sugai: None. M.Odawara: Speaker's Bureau; Eli Lilly Japan K.K., Novo Nordisk, Sanofi K.K. R.Suzuki: Consultant; Novo Nordisk A/S, Other Relationship; Sanofi K.K., Eli Lilly Japan K.K. J.Sasaki: None. K.Ishii: None. G.Li: None. M.Ito: None. M.Aierken: None. H.Suwanai: None. M.Torii: None. K.Hashimoto-torii: None.
118-OR: From Learning to Planning for Change—How Continuing Medical Education Drives Clinician Intention to Implement Changes in Diabetes Care
Authors: CHEN PAN , MARDIS CAITLIN , GAWADE SANJAY , WIGGINS ANNETTE , OLIVER YVONNE 
Published: June 2023

Objective: The effectiveness of continuing medical education (CME) in improving clinician knowledge and competence in the management of type 2 diabetes (T2DM) has been widely demonstrated. The current study builds upon existing literature by investigating the pathway by which CME drives clinician intention to implement changes in T2DM management.
Methods: Data from 6 accredited online T2DM CME programs targeting global diabetologists/endocrinologists (diab/endos) and primary care physicians (PCPs) launched in 2021 were analyzed. An objective knowledge/competence assessment was completed by a control group sampled from the target audience prior to the launch of each of the programs (n=301) and by a test group sampled from learners following participation (n=304). Post-education confidence improvement and intention to change were also measured in the test group. Significance of all between-group differences reported was tested using chi-square statistics.
Results: The education had a large effect size in improving clinician knowledge and competence managing T2DM (control vs test group correct response rate: 63% vs 92%, P &lt; .001; Cohen’s d=1.21). Within the test group, 81% increased confidence in managing T2DM, and 73% planned to make clinical practice changes. Knowledge/competence did not directly predict intention to change, but those with improved confidence were more likely to plan for clinical practice change (79% vs 45%; P &lt; .001). While knowledge/competence did not predict confidence improvement for diab/endos, PCPs who answered all questions correctly were more likely to report improved confidence (82% vs 56%; P &lt; .01).
Conclusions: CME may indirectly drive clinician intention to implement practice changes via its impact on confidence for both diab/endos and PCPs. The role that knowledge and competence play in the pathway from CME to intention to change may vary for these two groups of clinicians.

Disclosure
P.Chen: None. C.Mardis: None. S.Gawade: None. A.Wiggins: None. Y.Oliver: None.

Funding
Eli Lilly and Company
1180-P: Impact of Diabetes Exposure In Utero on Mesenchymal Stem Cell Phenotype and Metabolic Function
Authors: HAN LEE WAI , REDLING DAKOTA , BROOKS OLIVIA , TEAGUE APRIL M. , JIANG SHAONING , TRYGGESTAD JEANIE B. 
Published: June 2023

Fetal programming events at the level of the MSC not only direct development of fetal tissues in utero but may also impact these tissues throughout the life span. Exposure to diabetes (DM) in utero appears to affect early programming of MSC; thus, we hypothesized that the phenotype and metabolic characteristics of MSC would be altered by exposure to the diabetic milieu. MSC were isolated from umbilical cord Wharton's Jelly within 24 hours of delivery and confirmed by the presence of CD105 and CD90 and absence of CD34 and CD45. To assess the adipogenic capacity of MSC, they were stained with CD13 or isotype-control antibody. DM-exposed MSC revealed a 14% increase in CD13 abundance (p=0.12) compared to control MSC, indicating a higher propensity for adipocyte differentiation. Changes in energy expenditure were assessed using the Seahorse XF Cell Mito Stress Kit at passage 4-8. Maximal respiration and spare respiratory capacity were reduced by 66% (p=0.08) and 51% (p=0.08), respectively, in the DM MSC (N=3) compared to the control MSC (N=4) (Figure 1). Basal respiration and ATP production did not differ. In this pilot study, reductions in maximal respiration and spare capacity suggest that DM exposure alters the MSC's ability to meet metabolic demands under stress. Further work is needed to understand the exact mechanisms by which exposure to DM in utero alters MSC metabolism and phenotype.

Disclosure
W.Lee: None. D.Redling: None. O.Brooks: None. A.M.Teague: None. S.Jiang: None. J.B.Tryggestad: None.

Funding
National Institutes of Health (1K23DK106533, R03DK125626, P30GM122744)
1182-P: Low Socioeconomic Status and Pregnancy Outcomes in Women with Type 2 Diabetes
Authors: CAMPBELL SARA , TOMLINSON GEORGE , FEIG DENICE 
Published: June 2023

Aims: Pregnant women with pre-existing type 2 diabetes have a high rate of social deprivation. Low socioeconomic status (SES) is associated with adverse pregnancy outcomes. Our objective was to assess the association of low SES with adverse pregnancy outcomes in women with type 2 diabetes. Materials and
Methods: We conducted an observational cohort study of women in the MiTy trial. Maternal and neonatal outcomes were compared in women with and without low SES. Low SES was described as recent immigration within the previous 5 years, low maternal education or single-parent households.
Results: A total of 502 women were included in the MiTy trial. Of the eligible women, 192 (41.60%) met criteria for low SES. Women with low SES had significantly higher HbA1c at 34 weeks gestation (6.18% vs 5.89%, p=&lt;0.01). Low SES was associated with an increase in preterm birth (28.1% vs 19.7%, p=0.05), neonatal hypoglycemia (19% vs 9.8%, p=0.007), and NICU admission &gt;24 hrs (27.2% vs 16.8%, p=0.01). After adjustment for confounders, low SES was associated with an increased risk of an adverse neonatal composite outcome (44.7% vs 31.8%, p=0.007; OR 1.83 (95% CI 1.16-2.92). Of the components of the low SES composite, low maternal education was most strongly associated with the composite neonatal outcome OR 1.71 (95% CI 1.03 - 2.82, p=0.04).
Conclusions: In women with type 2 diabetes, low SES was associated with poorer glycemic control and an increased risk of adverse neonatal outcomes. Special attention should be paid to low maternal education as a predictor of adverse outcomes.

Disclosure
S.Campbell: Speaker's Bureau; Novo Nordisk Canada Inc., HLS Therapeutics Inc. G.Tomlinson: None. D.Feig: Advisory Panel; Novo Nordisk Canada Inc., Speaker's Bureau; Sanofi, Novo Nordisk Canada Inc.

Funding
Canadian Institutes of Health Research
1186-P: Can an Early GCT Value and A1C Eliminate the Need for Repeat GCT Testing during Second-Trimester Pregnancy?
Authors: BEACHAM JORDAN A. , BODYCOT KATHERINE C. , HUANG RACHEL , AL-KOUATLY HUDA B. , MCLAREN RODNEY 
Published: June 2023

Background: While A1c is a widely used marker for IDDM and NIDDM, its clinical use in gestational diabetes mellitus (GDM) is not well elucidated. We aimed to evaluate if an A1c and an early glucose challenge test (GCT) can be used to identify patients who may forgo repeat 2nd trimester GCT testing.
Methods: This was a retrospective cohort study of patients eligible for early GDM screening who had a negative screening at ≤20 weeks gestation and delivered at a single center between 2016-2020. The primary outcome was GDM in the 2nd trimester by Carpenter & Coustan criteria. Receiver operating characteristic (ROC) curve analyses were performed to compare the ability of early GCT value, and in combination with A1c to predict the primary outcome.
Results: Of the 2,025 patients eligible for early GDM screening, 722 met inclusion criteria. Of these, 583 had a 1-hour GCT, 178 had an A1c, and 38 had both. The prediction of GDM diagnosis in the 2nd trimester using an early GCT value, A1c, and both on a ROC plot produced an area under the curve (AUC) of 0.753, 0.659, and 0.672, respectively. The highest A1c where no patients were diagnosed with GDM in 2nd trimester was 4.5%, but of the 43 patients with A1c ≤5.1%, 1 (2.3%) was diagnosed with GDM in the 2nd trimester.
Conclusion: Early GCT value alone was a better predictor of GDM in 2nd trimester than a combination of GCT with A1c. A1c alone was a poor predictor.

Disclosure
J.A.Beacham: None. K.C.Bodycot: None. R.Huang: None. H.B.Al-kouatly: None. R.Mclaren: None.
119-OR: Sex and Diabetes Status Interact to Affect Human Skeletal Muscle Mitochondrial Function
Authors: ABUSHAMAT LAYLA , SCALZO REBECCA L. , SCHAUER IRENE E. , KNAUB LESLIE , RAFFERTY DEIRDRE , CLARK ETHAN , WHIPPLE MARY O. , HUEBSCHMANN AMY G. , REUSCH JANE E.B. , REGENSTEINER JUDITH G. 
Published: June 2023

People with type 2 diabetes (T2D) have lower cardiorespiratory fitness (CRF)–a predictor of cardiovascular disease, morbidity, and mortality–than those without T2D. The impact of diabetes on CRF is greater in females than males. T2D confers worse CRF, in part, due to impairments in mitochondrial function, but it is unclear to what extent sex and T2D attenuate the expected improvements in mitochondrial function due to exercise training (ExTr). We hypothesized that female sex and T2D decrease mitochondrial response to ExTr. Mitochondrial respiration measures in vastus lateralis of physically inactive overweight adults aged 30-55 years with and without T2D were analyzed pre- and post- ExTr. We found increases in state 3 respiration (p=0.01), state 4 respiration (p=0.0002), and uncoupled respiration (p=0.02) after ExTr in all groups, suggesting a consistent effect of ExTr. Sex and T2D status interact to affect state 3 respiration (p=0.0003), State 4 respiration (p=0.003) and oxidative phosphorylation (P/E) ratio (p=0.0002) (Figure); females with T2D have lower mitochondrial respiration than males with T2D, unlike overweight control participants. Sex and T2D did not statistically interact with ExTr. These findings suggest that differences in muscle mitochondrial function due to T2D and sex persist despite improvements in mitochondrial respiration with ExTr.

Disclosure
L.Abushamat: None. J.G.Regensteiner: None. R.L.Scalzo: None. I.E.Schauer: None. L.Knaub: None. D.Rafferty: None. E.Clark: None. M.O.Whipple: None. A.G.Huebschmann: None. J.E.B.Reusch: Advisory Panel; Medtronic.

Funding
American Diabetes Association (1-21-CMF-003 to L.A.); U.S. Department of Veterans Affairs (CX001532)
1193-P: GDM Treatment, Diagnosis Timing, and Glycemic Control—Associations with Newborn Outcomes in the SWIFT Study
Authors: JOSEFSON JAMI L. , SUN BAIYANG , XIANG ANNY , GREENBERG MARA , GREENSPAN LOUISE , LO JOAN C. , DAVIS JAIMIE N. , GUNDERSON ERICA P. 
Published: June 2023

Suboptimal glycemic control in GDM increases risk of adverse perinatal outcomes. We evaluated GDM treatment type (glyburide vs diet), timing of diagnosis (&lt;20w gestation: early (E) vs. &gt;20w: standard (S), glycemic control (optimal vs suboptimal), and perinatal outcomes. In a diverse cohort of 902 GDM mother-infant dyads (77% Hispanic, Asian, or Black; 23% White), prenatal glycemic control was measured by self-home glucose monitoring and categorized as optimal (≥80% of tests met target, fasting glucose ≤95 mg/dL and 1h post-prandial ≤140 or 2h ≤120) or suboptimal (&lt;80% of tests met target). Compared to the S diagnosis and diet treatment group, the E diagnosis and glyburide treatment group was older, more likely to have prior GDM, and higher prepregnancy BMI and glucose levels on the 3h 100 g prenatal OGTT. Glyburide treatment was associated with suboptimal control (P&lt;0.001). Multivariable logistic regression estimated odds ratios (OR, 95%CI) of perinatal outcomes associated with GDM treatment type, timing of diagnosis, and glycemic control vs. the referent group with S diagnosis and optimal control on diet treatment alone, adjusted for pre-pregnancy BMI, infant sex and gestational age. Among E and S diagnosis groups with suboptimal control both before and after glyburide treatment, ORs, 95%CI were higher for neonatal length of stay ≥3 days: (E 3.6, 1.6-8.1; S 2.0, 1.1-3.6), neonatal hypoglycemia (E 2.4, 1.0-5.9; S 1.9, 1.0-3.6) and large-for-gestational age (LGA) birthweight (E 4.1, 1.8-9.1; S 2.8, 1.6-4.9). For E diagnosis with suboptimal control before, and optimal control after glyburide, the odds of LGA were elevated (2.8, 1.2-6.6) similar to the S diagnosis with suboptimal control after glyburide. Associations did not affect Cesarean delivery or NICU admission. These findings show that even with post-glyburide optimal glycemic control, odds of LGA development associated with exposure to GDM from early gestation may be only partially ameliorated by glyburide treatment.

Disclosure
J.L.Josefson: None. B.Sun: None. A.Xiang: None. M.Greenberg: None. L.Greenspan: None. J.C.Lo: None. J.N.Davis: None. E.P.Gunderson: None.

Funding
National Institutes of Health (R01DK122700)