bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic offset and vulnerability modelling: misinterpretations of results and violations of evolutionary principles
Authors: Ahrens Collin W , Rymer Paul D , Miller Adam D
Published: June 2023

Genetic offset models have become a popular component of the landscape
genetics toolbox, with over 150 peer-reviewed publications applying
these models to plant and animal systems. Genetic offset models are most
frequently performed following the identification of putatively adaptive
alleles from genotype-environment association analyses in natural
populations of non-model organisms. These models allow the researcher to
make predictions about the likely vulnerability of species populations
to climate change, by estimating the extent of genetic change needed
(i.e., genetic offset) to maintain ‘optimal’ allele frequencies and
population fitness under future climate change scenarios. However, a
number of critical assumptions and knowledge gaps are often overlooked
when undertaking these analyses, undermining their reliability and
usefulness for making genetically informed management decisions. In this
commentary, we describe seven assumptions in detail and discuss a range
of common violations that can lead to misleading outcomes. While genetic
offset models may have a place for predicting the vulnerability of
natural populations of non-model organisms in the future, we argue that
current applications are likely to be problematic and risk both wasting
resources and misleading conservation management.
processo de formação da Aliança Renovadora Nacional (ARENA) e do Movimento Democrático Brasileiro (MDB) no Rio Grande do Sul (1965-1966)
Authors: Batistella Alessandro
Published: June 2023

O presente artigo visa a analisar o processo de formação da ARENA e do MDB no Rio Grande do Sul. Para tais propósitos, primeiramente, pretende-se analisar a crise político-militar de 1965, que resultou na decretação do Ato Institucional nº 2 (AI-2), e o processo de implantação do bipartidarismo. Em um segundo momento, o foco de análise será o processo de organização da ARENA e do MDB no Rio Grande do Sul.
10-LB: Activation of Sigma-1 Receptor as a Novel Therapeutic Target in Diabetic Kidney Disease
Authors: BALOGH DORA B. , LENART LILLA , HOSSZU ADAM , SAEED ADAR , HODREA JUDIT , TOTH AKOS R. , SZABO ATTILA J. , FEKETE ANDREA
Published: June 2023

Introduction and aims: Diabetic kidney disease (DKD) is a major health concern among diabetic patients. Current therapies cannot halt the progression of renal failure; thus, the development of additional novel therapies is of paramount importance. We previously showed that the Sigma-1 receptor (S1R) agonism is protective in acute kidney injury (AKI). Inflammation and tubular hypoxia are key processes in the pathogenesis of DKD. S1R agonist treatment inhibits these pathologic pathways in AKI, therefore we assume that a similar protective effect can be shown in DKD as well.

Methods: Diabetes mellitus (DM) was induced by streptozotocin (65 mg/bwkg, ip.) in adult, male Wistar rats and they were treated for seven weeks with fluvoxamine (D+FLU, 20 mg/bwkg/day, po.). Metabolic parameters, renal function, and histology were evaluated. Inflammation was tested in lipopolysaccharide-stimulated (LPS, 1 µg/mL) human proximal tubular epithelial cells (HK-2). To test hypoxia cells were placed in a hypoxic chamber (1% O2, 2h). Cells were treated with 10 µM FLU. Proinflammatory and hypoxia markers were measured.

Results: Renal function (BUN: DM: 26.6±2.42 vs. DM+FLU: 17.3±2.30 mmol/L; Serum creatinine: DM: 42.0±2.39 vs.DM+FLU: 34.5±2.74 µmol/L; Proteinuria: DM: 42.5±6.38 vs. DM+FLU: 21.5±4.99 mg/mL; p<0.05), structural damage (PAS staining), and fibrotic tissue accumulation (Masson’s trichrome staining) were reduced by FLU. FLU decreased LPS-induced IL6, TLR4, and NFKB1 expressions in HK-2 cells. Hypoxia-induced HIF1A and HIF2A elevation were suspended by FLU treatment. Moreover, VEGFA and SLC2A1 expressions were also increased in hypoxia and FLU prevented their elevation.

Conclusions: Activation of S1R slows the progression of chronic renal impairment in DKD. Moreover, S1R agonist FLU prevents hypoxic and inflammatory damage in HK-2 cells, which may explain the molecular mechanisms behind its renoprotective effect. We propose S1R as a novel target for the prevention of DKD.

Disclosure

D. B. Balogh: None. L. Lenart: None. A. Hosszu: None. A. Saeed: None. J. Hodrea: None. A. R. Toth: None. A. J. Szabo: None. A. Fekete: None.

Funding

National Research, Development and Innovation Fund (UNKP-22-4-II-SE-2, TKP2021-EGA-24); Hungarian Academy of Sciences (LP2021-3/2021)
100-OR: A Novel Macrophage-Regulation Drug for Treating Diabetic Foot Ulcer—A Phase III MRCT Study and Taiwan Experience
Authors: CHEN SHYI-GEN , CHU SHUN-TIEN , PU CHI-MING , CHEN JUI-CHING , WU YI-HSIN
Published: June 2023

Macrophage regulation plays an essential role in Diabetic foot ulcer (DFU) healing. By recognizing the therapeutic potential in M1/M2-macrophage-regulation for DFUs, we aim to investigate the efficacy and safety of ON101, a topical new drug with a M1/M2-macrophage-regulating mechanism in phase 3 MRCT across the US, China, and Taiwan (NCT01898923). There are 236 eligible subjects with Wagner Grade 1 or 2 DFU(s), randomized 1:1 to receive ON101 or comparator for up to 16 weeks, followed by a 12-week follow-up. The incidence of complete healing was 60.7% by ON101 and 35.1% by the comparator (P=0.0001). The time to complete ulcer healing was faster in the ON101 group (P=0.002). Since the high levels of HbA1C, ulcer persistence, ulcer location, and amputation history as the risk factors leading to poor DFU outcomes, ON101 also showed demonstrated robust efficacy and safety in hard-to-heal ulcers. ON101, approved by Taiwan FDA in 2021, was shown with excellent therapeutic efficacy and safety in the treatment of DFUs. In a real-world scenario, case collation from 133 patients, ulcer severity with Wagner grade 1 to 4, after applying ON101, the average ulcer complete healing rate is 71%, no adverse events were related to ON101, which validates the drug safety of ON101. ON101 further supports its excellent ability to promote wound healing in DFU patients with various severities (Wagner grade 1 to 4). All those patients who applied ON101 alone or with other therapies reached ulcer healing under infection control and with necessary debridement. Macrophage-regulating drug achieved superior therapeutic efficacy in a large Phase 3 MRCT and has demonstrated excellent therapeutic efficacy in the real-world scenario where Wagner grade 3 and 4 DFUs reached ulcer healing when ON101 was combined with other therapies. This enlightens the future treatment in Wagner grade 1 to 4 DFUs by macrophage immunomodulation new drug as a promising solution.

Disclosure

S.Chen: Employee; Oneness Biotech Co., Ltd. S.Chu: None. C.Pu: None. J.Chen: Employee; Oneness Biotech Company. Y.Wu: Employee; Oneness Biotech Co., Ltd.
1068-P: Correleations of HbA1c, Continuous Glucose Monitor (CGM) Use, Insurance Type, and Language in a Large Pediatric Diabetes Practice in Phoenix, Arizona
Authors: ANN HOLZMEISTER LEA , CHMELNIK SANDRA
Published: June 2023

Background: Inequities among technology use in pediatric type 1 diabetes (T1D) patients remains prevalent. These disparities contribute to poor glycemic control.

Method: This study was a retrospective chart review of HbA1C and CGM use by type of insurance, ethnicity and language spoken at home in 2022.

Results: In a cohort of nearly 2000 T1D pediatric patients, differences were found in HbA1c levels between ethnicities (mean of 8.6% Hispanics and 8.1% non-Hispanics). However, when stratified by insurance type (Private vs Medicaid), the relationship of ethnicity to HbA1C levels was no longer present, suggesting insurance drives differences in HbA1C levels rather than ethnicity. The effects of insurance may in part be related to technology use. An average of 45% of patients with private insurance use CGMs, in comparison with 32% of those with Medicaid. The use of CGMs compared with non-use of CGMs had a positive effect on HbA1C (8.3% vs 9.0%).

Conclusions: CGM use is associated with lower HbA1C levels in our practice. Patients on Medicaid had higher HbA1C levels and less use of CGM. Hispanic and non-English speaking patients were more likely to be on Medicaid, and to have higher HbA1C levels and lower use of CGMs. These findings highlight the need to reduce health inequities among these populations. Our clinic will aim to develop interventions to improve technology use and access in Medicaid, Hispanic, and non-English speaking populations.

Disclosure

L.Holzmeister: None. S.Chmelnik: None.
1083-P: Interventions to Improve Equity of CGM Use for Pediatric Patients with Type 1 Diabetes
Authors: TURNER JOEL , NELSON GRACE , ADAMS BLAKE V.
Published: June 2023

Background: Continuous Glucose Monitors (CGMs) have been shown to improve outcomes for patients with T1D. However, various obstacles prevent some patient groups from utilizing these technologies. This was evident by the discrepancy in non-Hispanic black patients using CGMs (25%) vs non-Hispanic white patients (60%) in our clinic. Our goal is to identify and overcome these obstacles in order to increase the number of patients using CGMs and create equity in CGM use between groups.

Methods: An initial barrier for many patients is getting CGM approved by insurance. In response we created a “CGM champion”, a member of the team who created a streamlined process for initiating CGMs. She was able to build relationships with DME companies and provide appropriate information to insurance companies to make the process more efficient. We also created patient education folders with up-to-date information for our families. We worked with staff to increase CGM knowledge, and utilized EMR functionality to make sure all orders were entered, trackable, and documented in a standardized fashion. Finally, we used surveys to gauge the interest of each patient in trying CGMs and other technology.

Results: As of December 2022, we have helped 54% of our interested patients navigate the process of obtaining a CGM. Equity was also improved, with ~65% of our non-Hispanic black patients now using CGM vs ~80% of non-Hispanic white patients.

Conclusions: We have seen improvement in both the total number of patients which are utilizing CGMs as well as equity between patient groups. We are continuing to adjust our processes in an effort to make CGMs more accessible and equitable.

Disclosure

J.Turner: None. G.Nelson: None. B.V.Adams: None.
11-LB: The Efficacy and Safety of Abelmoschus manihot for Reduction of Microalbuminuria in Patients with Type 2 Diabetes and Diabetic Nephropathy—A Multicenter, Randomized, Open-Label, Parallel-Controlled Clinical Trial
Authors: YIN JUN , CHEN SI , WEI LI , JIA WEIPING
Published: June 2023

Objective: Huangkui capsule, an extract from the flowers of Abelmoschus Manihot, has been proved clinically effective in improving chronic kidney disease. This study aimed to evaluate the efficacy and safety of Huangkui capsule in patients with stage 3 diabetic nephropathy.

Methods: This multicenter, randomized, open-label, parallel-controlled trial was conducted in six hospitals. The inclusion criteria were 30 mg/g ≤ albumin creatinine ratio (ACR) <300 mg/g, eGFR ≥ 60 mL/min/1.73 m2, and type 2 diabetes with glycosylated hemoglobin ≤ 9%. We enrolled 239 patients who were randomly assigned to the two groups in a 1:1 ratio. They were treated with Huangkui capsule 2.15 g three times a day, or losartan potassium tablets 100 mg/day for 24 weeks. The primary outcome was the change in ACR from baseline and the secondary outcome was the change in eGFR.

Results: The ACR in the losartan group was 119.47±78.16 mg/g at baseline and 90.51±136.12 mg/g after 24 weeks of treatment, with a decrease of 30.46±134.16 mg/g (P=0.049). In the Huangkui group, the ACR decreased from 121.98±84.31 mg/g to 88.13±76.66 mg/g, with a drop of 31.94±91.66 mg/g (P=0.002). The change in eGFR was -3.58±10.35 mL/min/1.73 m2 and -3.82±13.05 mL/min/1.73 m2 in the losatan and Huangkui groups, respectively. In subgroup analysis of patients with baseline ACR ≥ 100 mg/g, losatan and Huangkui lowered ACR by 56.83 mg/g (P=0.044) and 78.72 mg/g (P<0.001), respectively. There were no significant differences between the two groups (P>0.05).

Conclusions: Huangkui capsule significantly reduced ACR of patients with type 2 diabetes and microalbuminuria and is a promising medicine for diabetic nephropathy.

Disclosure

J. Yin: None. S. Chen: None. L. Wei: None. W. Jia: None.

Funding

National Natural Science Foundation of China (82070885); Shanghai Municipal Education Commission (20172025); Xuhui Joint Research Projects on Important Diseases (XHLHGG202110)
1100-P: Real-World Use of GLP-1 Agonists in Youth with Type 2 Diabetes Is Associated with Improvements in Hemoglobin A1c—A Multicenter Analysis
Authors: SAMUELS STEPHANIE , CHAJECKI ANASTASIA , HU PAMELA , KAYSER MICHELLE , WEYMAN KATE , PAN BERNARD , BROWN ELIZABETH A. , VAN NAME MICHELLE A. , WOLF RISA M.
Published: June 2023

Background: Despite the high risk of diabetes complications at an early age in youth with type 2 diabetes (T2D), there are limited pharmacologic options to manage T2D in youth. The first Glucagon-like-peptide-1 agonist (GLP-1a) was approved for pediatric T2D treatment in 2019. However, little is known on the real-world use and effectiveness of GLP-1a for management of T2D in the pediatric population.

Objectives: To assess the real-world use and effectiveness of GLP-1a (exenatide, dulaglutide, liraglutide, semaglutide) in managing T2D in a diverse cohort of youth. Methods: This multicenter retrospective analysis included adolescents and young adults (ages 11-25y) from two academic pediatric diabetes centers who were prescribed a GLP-1a for management of T2D. Patient HbA1c, weight, and BMI within 12 months of follow-up after GLP-1a prescription were compared to baseline using Signed Rank tests. Secondary outcomes included insulin and metformin use after GLP-1a initiation and were compared using McNemar's test.

Results: A total of 153 patients (median age 16.1 years (IQR 13.9-17.8), 57% female, 59% non-Hispanic Black, 23% Hispanic or Latino, 76% with public insurance) were prescribed GLP-1a and 36 patients discontinued the GLP-1a. At a median follow-up of 8.2 months, 117 patients were taking GLP-1a and were included in pre-post analyses. From baseline to follow-up, HbA1c decreased from 8.3% to 7.5% (p<0.007), while weight and BMI remained stable. At baseline, 48% of patients were taking prandial insulin, compared to 36% at follow-up (p=0.001), 71% were taking basal insulin compared to 62% at follow-up (p = 0.025), and 85% were prescribed metformin at baseline compared to 74% at follow-up (p=0.005).

Conclusion: Real-world use of GLP-1a in youth with T2D is associated with decreased HbA1c levels. GLP-1a treatment may reduce doses of insulin and other medications for diabetes in youth, which can mitigate the burden of daily diabetes management.

Disclosure

S.Samuels: None. A.Chajecki: None. P.Hu: None. M.Kayser: None. K.Weyman: None. B.Pan: None. E.A.Brown: None. M.A.Van name: Research Support; Provention Bio, Inc. R.M.Wolf: Research Support; Dexcom, Inc., Boehringer Ingelheim Inc.

Funding

American Diabetes Association (7-22-JDFN-03 to S.S.); National Institutes of Health (R01DK134955)
112-OR: Low Carbohydrate vs. Mediterranean Diets in Adolescents with Type 1 Diabetes—A Randomized Control Trial
Authors: LEVRAN NERIYA , LEVEK NOAH , MAZOR-ARONOVITCH KINERET , MONSONEGO-ORNAN EFRAT , PINHAS-HAMIEL ORIT
Published: June 2023

Objective: To compare glycemic parameters and metabolic health of a low carbohydrate diet (LCD) versus a Mediterranean diet (MED) in adolescents with type 1 diabetes.

Research Design and Methods: In an open-label, randomized, non-inferiority trial, 40 individuals with type 1 diabetes, aged 12 to 22 years, were randomly assigned (1:1) to LCD (50-80g of carbohydrates per day) or MED for 24 weeks. Glycemic outcomes included time in range (TIR), time below range (TBR) time above range (TAR), and glycosylated hemoglobin (HbA1c).

Results: Baseline characteristics were similar between the two groups. After 6 months intervention, the median (IQR) TIR70-180 mg/dL increased from 47% (35;55) to 58% (51;72) in the LCD and from 52% (38;60) to 67% (50;73) in the MED group (p=0.21, p=0.86, respectively). There was no difference in %TBR<54 mg/dL. The delta %TAR>250 mg/dL was significantly greater in the LCD (-11.0 (-5.0; -16) than the MED group (-3.1 (0.0; -9.4)) (p=0.008). HbA1c level improved in both groups, after correcting for gender, age, diabetes duration, and, maternal education; the delta HbA1c was significantly greater in LCD than MED after 6 months -0.8 (-1.3; -0.3) and -0.1 (-0.8;0.2) respectively (p=0.02). Median daily carbohydrate intake was 60gr (45;88) for the LCD and 128gr (IQR 104;155) for the MED group. Delta BMI Z-score was greater in the LCD -0.1 (-0.3-0.1) than the MED group 0.0 (-0.1-0.1) (p=0.08). Lipid levels did not differ between the groups.

Conclusions: Non-inferiority (13% relative margin) of LCD versus MED was demonstrated on %TIR70-(primary endpoint) among adolescents with type 1 diabetes, with no increased risk for hypoglycemia and no effect on cardiovascular risk factors.

Disclosure

N.Levran: None. N.Levek: None. K.Mazor-aronovitch: None. E.Monsonego-ornan: None. O.Pinhas-hamiel: None.
1122-P: Disparities in Glycemic Outcomes in High Technology–Using Youth with Type 1 Diabetes
Authors: NATH MERYL C. , ATCHISON JOYCELYN , SCHMITT JESSICA
Published: June 2023

Introduction: Socioeconomic status (SES) is associated with health disparities in youth with T1D. We aimed to evaluate SES and glycemic metrics in youth with T1D using continuous glucose monitors (CGM).

Methods: This IRB approved study included demographics, insulin administration type (pump/injections), and glycemic data from HbA1c and corresponding 14 day (d) and 90 d CGM metrics. Analysis was performed in MiniTab®.

Results: A total of 205 patients, 161 Non-Hispanic White (NHW) and 44 Non-Hispanic Black (NHB), were included. A minority (n=45, 22.0%) were publicly insured. Half (49.7%) used an insulin pump. There was no significant difference between sex, age, age at diagnosis, diabetes duration, or pump use between NHB and NHW patients. A higher proportion of NHB patients were on public insurance (45.5 vs 15.5%, p<0.0001). No difference in pump use was seen based upon insurance. Glycemic metrics for NHW and NHB patients differed including: HbA1c (median (med) 7.6 vs 9.2, p<0.001), 14 d mean glucose (mg/dL) (189.6 vs 207.4, p=0.038), 14 d standard deviation (SD) (67.2 vs 77.7, p=0.006), 14 d time in range (TIR) (51.8 vs 42.0%, p=0.016), 14 d time < 250 (med 52.9 vs 37.3%, p=0.005), 90 d mean glucose (181.0 vs 220.0, p<0.001), 90 d SD (69.5 vs 79.4, p=0.006), 90 d TIR (50.7 vs 37.9%, p=0.001) and 90 d time < 250 (med 16.4 vs 34.7%, p<0.001). Similar differences were seen between public and privately insured patients including: HbA1c (med 8.7 vs 7.6%, p=0.003), 14 d mean glucose (214.0 vs 183.5, p=0.019), 14 d TIR (43.2 vs 51.7%, p=0.034), 14 d time < 250 (med 30.6 vs 17.9%, p=0.031), 90 d mean glucose (219.5 vs 181.0, p<0.0001), 90 d SD (77.6 vs 70.0, p=0.023), 90 d TIR (39.1 vs 50.4%, p=0.004) and 90 d time < 250 (med 35.4 vs 16.3%, p<0.0001).

Discussion: Disparities in glycemic control were seen in NHB and publicly insured patients despite CGM use and a high and equitable use of insulin pumps. While access to technology for diabetes is important, in this cohort it was not adequate to reduce disparities in glycemic outcomes based on SES.

Disclosure

M.C.Nath: None. J.Atchison: None. J.Schmitt: None.
1127-P: 4T Study—Early CGM Initiation and Tighter Glucose Targets Improves A1C in Youth with T1D
Authors: PRAHALAD PRIYA , DING VICTORIA , ZAHARIEVA DESSI P. , ADDALA ANANTA , BISHOP FRANZISKA K. , SCHEINKER DAVID , JOHARI RAMESH , DESAI MANISHA , HOOD KOREY K. , MAAHS DAVID M. , STUDY GROUP 4T
Published: June 2023

Methods to optimize care after T1D diagnosis are needed. We hypothesized lowering A1c targets to <7% would further lower A1c in the 4T Study in which CGM with asynchronous remote patient monitoring (RPM) is initiated after T1D diagnosis. All youth with newly diagnosed T1D (June 2020-March 2022) were offered CGM and RPM after diagnosis (Study 1, n=133). We compared A1c at 1-year in Study 1 with the 4T Pilot (2018-20) and Historical cohorts (2014-16). We visualized population-based A1c trajectories using locally estimated scatter plot smoothing (Fig) and % meeting A1c targets. Mean A1c at diagnosis was similar in Pilot (12.2%±2.1%) and Study 1 (12.2±2.4%) and higher than the Historical cohort (10.7±2.5%). In Study 1, the median age of diagnosis was 10.8 years, 55% male, 40% non-Hispanic White, and 38% with public insurance. CGM initiation occurred within 30 days of diagnosis in 98.5%. At 3, 6, 9, and 12 months post-diagnosis, the Study 1 cohort had LOESS-based mean A1c differences of 0.16%, 0.24%, 0.31%, and 0.58% lower than the Pilot and 0.04%, 0.60%, 0.83%, and 1.06% lower than the Historical cohort. A1c target <7% was met by 61% of youth in Study 1, 51% in the Pilot and 28% in the Historical cohort. Time <70mg/dl was ≤2.3%. The 4T program which emphasizes early CGM initiation, RPM, tighter glucose targets, and consistent team messaging was associated with lower A1c. These data support implementation of the 4T program in youth with T1D.

Disclosure

P.Prahalad: None. D.M.Maahs: Advisory Panel; Medtronic, LifeScan Diabetes Institute, MannKind Corporation, Consultant; Abbott, Research Support; Dexcom, Inc. 4t study group: n/a. V.Ding: None. D.P.Zaharieva: Advisory Panel; Dexcom, Inc., Research Support; Hemsley Charitable Trust, International Society for Pediatric and Adolescent Diabetes, Insulet Corporation, Speaker's Bureau; American Diabetes Association, Ascensia Diabetes Care, Medtronic. A.Addala: None. F.K.Bishop: None. D.Scheinker: None. R.Johari: None. M.Desai: None. K.K.Hood: Consultant; Cecelia Health.

Funding

National Institutes of Health (P30DK116074), (R18DK122422 to D.M.M.); Dexcom, Inc.; Lucile Packard Children’s Hospital Auxiliaries Endowment; Stanford Maternal and Child Health Research Institute
1129-P: Continuous Glucose Monitoring (CGM) Initiation Shortly after Diagnosis Does Not Worsen Psychosocial States
Authors: ADDALA ANANTA , RITTER VICTOR , SHAW BLAKE , PANG ERICA , CORTES-NAVARRO ANA L. , BALISTRERI ILENIA , LOYOLA ALONDRA , ALAMARIE SELMA A. , SCHNEIDER-UTAKA AIKA , BISHOP FRANZISKA K. , ZAHARIEVA DESSI P. , PRAHALAD PRIYA , DESAI MANISHA , MAAHS DAVID M. , HOOD KOREY K.
Published: June 2023

Psychosocial impacts of early CGM initiation in youth soon after T1D diagnosis are underexplored. We report parent/guardian (PG) and youth trends in Patient Reported Outcomes (PROs) for families in the 4T Study 1.

Of the 133 participants in the 4T Study 1, 125 PG and 60 youth (≥11 years) were eligible for PROs. PROs included Diabetes Distress Scale - Parent (mean DDS-P) for PG and for youth, Diabetes Distress Scale (DDS sum), PROMIS Pediatric Global Health (PGH sum), Diabetes Technology Attitudes (DTA sum), and CGM Benefits/Burden (BenCGM and BurCGM sum). Kruskal Wallis rank sum test evaluated temporal trends and sociodemographics were evaluated (Numerical: Wilcoxon rank; Categorical: Fisher's if n<5, Chi-squared if n≥5).

PROs completion rates were higher for PG than youth at baseline (74% v 59%), 3 months (70% v 53%), and 6 months (66% v 50%). PG DDS-P remained low throughout the study (Table). Youth had favorable psychosocial trends (low DDS and high PGH), and perceived technology positively (high DTA and BenCGM with low BurCGM). Age, DKA at diagnosis, gender, ethnicity, insurance status, and language spoken were not associated with PROs scores in PG or youth.

CGM initiation shortly after T1D diagnosis is not associated with poor or worsening PROs for PG and youth. These data suggest that early CGM initiation does not adversely impact psychosocial states for families and youth with T1D.

Disclosure

A.Addala: None. F.K.Bishop: None. D.P.Zaharieva: Advisory Panel; Dexcom, Inc., Research Support; Hemsley Charitable Trust, International Society for Pediatric and Adolescent Diabetes, Insulet Corporation, Speaker's Bureau; American Diabetes Association, Ascensia Diabetes Care, Medtronic. P.Prahalad: None. M.Desai: None. D.M.Maahs: Advisory Panel; Medtronic, LifeScan Diabetes Institute, MannKind Corporation, Consultant; Abbott, Research Support; Dexcom, Inc. K.K.Hood: Consultant; Cecelia Health. V.Ritter: None. B.Shaw: None. E.Pang: None. A.L.Cortes-navarro: None. I.Balistreri: None. A.Loyola: None. S.A.Alamarie: None. A.Schneider-utaka: None.

Funding

National Institutes of Health (K23DK13134201, R18DK122422)
113-LB: Daytime Time in Range Is Associated with Weight Loss Success in Patients with Prediabetes or Moderately Controlled Type 2 Diabetes
Authors: BARUA SOUPTIK , UPADHYAY DHAIRYA A. , POPP COLLIN , HU LU , CURRAN MARGARET , BERUBE LAUREN , LI HUILIN , WANG CHAN , LOU POMPEII MARY , MOTTERN MEREDITH , ST-JULES DAVID , SEGAL ERAN , BERGMAN MICHAEL , ALEMAN JOSE O. , MARIE SCHMIDT ANN , ANN SEVICK MARY
Published: June 2023

Objective: We quantified the association of overall and daytime time in range (TIR, 70-140 mg/dL) with weight change in a behavioral weight loss intervention.

Methods: Data for this study came from the Personal Diet Study, a 6-month weight loss trial in adults with prediabetes or moderately controlled T2D (HbA1c<8%) involving remote behavioral counseling and dietary self-monitoring via a smartphone app. Participants wore blinded Abbott Freestyle Libre Pro CGMs for ≤2 weeks at baseline and 6 months. Based on clinically meaningful changes in two TIR metrics: “All-TIR” (all CGM readings) and “Day-TIR” (6am-midnight CGM readings), participants were categorized as “Improved” (>5%), “No Change” (-5 to 5%), or “Declined” (<-5%). Associations between TIR change categories and %weight change were determined using one-way ANOVAs.

Results: We analyzed baseline and 6-month CGM data from 66 participants (age 63±8 years, 62% female, 64% White, 20% African American, BMI 31.5±5.0 kg/m2, HbA1c 5.8±0.5%). When stratified by Day-TIR change, Improved had greater weight loss compared to No Change and Declined (p=0.006) (Figure 1). When stratifying using All-TIR, no significant weight change differences were observed across groups (p=0.15).

Conclusion: Improved daytime TIR, but not overall TIR, was associated with greater weight loss in a behavioral weight loss intervention.

Disclosure

S. Barua: None. M. Mottern: None. D. St-jules: Consultant; Ardelyx, Inc. E. Segal: None. M. Bergman: None. J. O. Aleman: Advisory Panel; Intellihealth, Consultant; Novo Nordisk, Employee; Veterans Administration, Research Support; NIH - National Institutes of Health, Veterans Administration. A. Schmidt: None. M. Sevick: None. D. A. Upadhyay: None. C. Popp: None. L. Hu: None. M. Curran: None. L. Berube: None. H. Li: None. C. Wang: None. M. Pompeii: None.

Funding

American Heart Association (17SFRM33590133)
117-OR: Provider Perspectives on Diabetes Education for Emerging Adults (EAs)
Authors: MEHROTRA NEHA , KRALL JODI S. , NG JASON , SIMINERIO LINDA M.
Published: June 2023

Emerging adulthood, the developmental stage between 18 to 25 years, is a critical time when individuals with type 1 diabetes mellitus (T1DM) assume self-care responsibility and transfer to adult care. Current diabetes self-management education and support (DSMES) has been cited for not meeting the needs of EAs. Models addressing this problem need to be explored. This study was designed to gain perspectives on current DSMES delivery from DM providers.

Methods: Health care professionals (HCPs, n=52, 40% endocrinologists, 34% diabetes care and education specialists) who provide adult care to EAs with T1DM completed an online survey designed to gain insights on the provision of DSMES to EAs.

Results: Most HCPs (60%) were unsure or disagreed that EAs with T1DM received sufficient DSMES while in pediatric care. 74% felt strongly that their patients had not received adequate education to successfully transfer to adult care. In terms of frequency of DSMES, when asked 52% HCPs answered at every visit, 35% said annually, and 13% when a change in care was identified. Most HCPs (80%) agreed that one-to-one, in person visits are the best format for DSMES, but also agreed that telehealth (73%) could be used to augment DSMES delivery. Interestingly, 93% HCPS agreed that there was a role for a peer support. In considering use of CGM data and self-management, uniformly HCPs (99%) felt confident in their ability to interpret CGM data and reported reviewing downloads with EA at every visit (98%), however HCPs (92%) were not confident that EAs can self-manage diabetes in response to their CGM data.

Conclusion: Efforts to engage EAs for improved participation in DSMES need to be explored for effective self-management.

Disclosure

N. Mehrotra: None. J.S. Krall: Research Support; Sanofi, Becton, Dickinson and Company. J. Ng: Research Support; Sanofi-Aventis U.S. L.M. Siminerio: Advisory Panel; Abbott. Research Support; Becton, Dickinson and Company, Sanofi.
1195-P: Is Gestational Diabetes by IADPSG Criteria Associated with Risk of Autism in Offspring?
Authors: XIANG ANNY , CARTER SARAH A. , LIN JANE C. , CHOW TING , MARTINEZ MAYRA P. , PAGE KATHLEEN A. , KLARA FELDMAN R.
Published: June 2023

We assessed whether only one abnormal value from the OGTT screening during pregnancy, which qualify as GDM by the IADPSG criteria (GDM_IADPSG), was associated with risk of offspring autism spectrum disorders (ASD). The cohort included 590,001 singletons from a large integrated healthcare system with electronic medical records. GDM was largely screened by two-steps and Carpenter-Coustan criteria (GDM_CC). We excluded those exposed to pre-existing diabetes or 1-hr 50g glucose challenge test ≥ 200mg/dl. OGTT glucose levels were used to define GDM_IADPSG. Cox models with hazard ratio (HR) were used to assess associations. Among the cohort, 7.6% were exposed to maternal GDM_CC, an additional 5.9% to GDM_IADPSG with only one abnormal OGTT value. Within GDM_CC, 41.3% had abnormal fasting, 30.5% were diagnosed at ≤ 26 wks and 30.7% prescribed medications. Within GDM_IADPSG, 28.4% had abnormal fasting alone, 27.0% at ≤ 26 wks and none received medications. Table 1 shows the HRs (95% CI). GDM_IADPSG was associated with increased risk of ASD, with risk slightly lower compared to GDM_CC. However, the risk appeared greater if abnormal fasting presented at diagnosis. The risk of ASD associated with GDM_IADPSG by abnormal fasting alone was comparable to GDM_CC treated with medications. Studies are needed to assess whether diabetes management for pregnancies with only elevated fasting will reduce adverse effect on offspring.

Disclosure

A.Xiang: None. S.A.Carter: None. J.C.Lin: None. T.Chow: None. M.P.Martinez: None. K.A.Page: None. R.Feldman: None.
120-OR: Muscle Lipid Turnover Predicts Aerobic Training Effects on Body Composition
Authors: CHOW LISA S. , BANTLE ANNE , ALVEAR ALISON C. , MASHEK DOUGLAS G. , JENSEN MICHAEL D.
Published: June 2023

Aerobic exercise utilizes muscle lipid. We hypothesize that high pre-training muscle lipid turnover, suggesting high muscle lipid utilization, predicts the effects of aerobic training. Obese, insulin-resistant subjects [mean(SD), BMI:37.7 kg/m2(6.2), VO2max 25 ml/kg/min (6.3)] underwent a 16 week of supervised, weight-stable, aerobic training (n=16). Body composition (DXA), fitness level (VO2max) and insulin sensitivity (hyperinsulinemic-euglycemic clamp) were performed at baseline and end-training. Two muscle biopsies (Bx) were acquired during a pulse-chase experiment using [U-13C]palmitate and [9-2H]palmitate infusions (6 h each), overlapping by 1 hour. Bx#1 captured muscle lipid incorporation and was performed during the infusion overlap [last hour of 6 h [U-13C]palmitate infusion, 1 hour after starting [9-2H]palmitate. Bx#2 captured muscle lipid breakdown and was performed at study conclusion [last hour of [9-2H]palmitate infusion, 6 hours after stopping [U-13C]palmitate]. As expected, aerobic training increased VO2max, fat-free mass, insulin sensitivity and hepatic insulin sensitivity while decreasing fat mass and visceral fat (Table 1). Baseline measures, especially muscle palmitate incorporation and breakdown, best predicted training effects on body composition. Muscle lipid turnover, along with other baseline measures, predicts aerobic training effects on body composition.

Disclosure

L.S.Chow: Research Support; Dexcom, Inc. A.Bantle: None. A.C.Alvear: None. D.G.Mashek: None. M.D.Jensen: Other Relationship; Novo Nordisk, Elsevier.

Funding

National Institutes of Health (R01DK098203)
1294-P: Prevalence of Islet Autoantibodies in Adults from the General Population
Authors: PAULEY MEGHAN E. , GENO RASMUSSEN CRISTY , DONG FRAN , SIMMONS KIMBER M. , REWERS MARIAN
Published: June 2023

Objective: Over half of cases of type 1 diabetes are diagnosed in adults, yet the prevalence of islet autoantibodies (IA) in general population adults is unknown.

Methods: The Autoimmunity Screening for Kids (ASK) Study screened 1,087 adults (age 41±7 years, 78% female, 63% non-Hispanic white, 10% first-degree relatives) and 29,441 youth (age 1-17 years, 52%, 36%, and 5%, respectively) for IA to GAD, IA-2, insulin, and ZnT8 using electrochemiluminescence (ECL) or radiobinding assays (RBA).

Results: In adults, 3.9% screened positive; 0.6% were positive for multiple IA, 1.7% were positive for a single high-affinity IA, and 1.6% were positive for a single low-affinity IA. GADA was most prevalent, found in 2.7%. Unexpectedly, the prevalence of IA in adults and youth screened by ASK was not statistically different (Figure).

Conclusion: IA positivity is similar in youth and adults in the general population. Expanded access to type 1 diabetes screening and monitoring will aid in determining if early detection is similarly beneficial in adults as seen in youth, such as reducing rates of diabetic ketoacidosis at diagnosis of clinical type 1 diabetes.

Disclosure

M.Pauley: None. C.Geno rasmussen: None. F.Dong: None. K.M.Simmons: Advisory Panel; Provention Bio, Inc., Consultant; Dexcom, Inc., Provention Bio, Inc., Research Support; Novartis. M.Rewers: Research Support; Provention Bio, Juvenile Diabetes Research Foundation (JDRF), Hemsley Charitable Trust, Dexcom, Inc., Janssen Research & Development, LLC.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (T325T32DK063687); JDRF (2-SRA-2022-1270-S-B)
1319-P: Vascular Multimorbidity in Danish Persons with Type 2 Diabetes Is Decreasing, Contributing to Mortality Decline
Authors: CARSTENSEN BENDIX , CLEMMENSEN KIM K.B. , KOSJERINA VANJA , PERSSON FREDERIK
Published: June 2023

Background: Multimorbidity in persons with type 2 diabetes (T2D) has not been studied in population wide settings. We used a Danish nation-wide diabetes register to assess trends in incidence and prevalence of vascular multimorbidity.

Methods: All Danish persons with T2D since 1996 were followed from diagnosis to death or 2020-12-31. Follow-up was classified by the number of vascular morbidities from: atrial fibrillation, heart failure, myocardial infarction, ischemic stroke, hemorragic stroke, transient cerebral ischemia, amputation, retinopathy and nephropathy. Persons could enter with any number of vascular morbidities. We analyzed mortality rates and rates of each additional morbidity, using age, calendar time and number of attained morbidities as predictors. Prevalence of morbidities at diagnosis and at calendar times was modeled by binomial regression.

Results: 505,124 persons entered the study. Occurrence of first morbidity increased mortality by a factor 2. Further morbidities increased mortality by a factor of 1.5. Mortality decreased 4%/year regardless of morbidity status. Incidence of additional morbidities increased only for the first 2 acquired morbidities by factors 1.8 and 1.2 and decreased by 3%/year regardless of morbidity status. The prevalence of morbidities at date of T2D increased until 2015. The prevalence of 1+ morbidity in all persons with T2D increased till 2008 and remained stable at 40% for men and 25% for women at age 65, and for 2+ at 10 and 5%.

Conclusion: The decrease in morbidity and mortality rates is an indication of successful treatment of Danish persons with diabetes with respect to adverse vascular outcomes. This could be the result of earlier diagnosis of T2D; including persons earlier in the course of T2D would result in a “healthier” population. The increase in prevalence of morbidities at T2D diagnosis and the constant prevalence over time among all T2D persons may be an indication that management of morbidities is improving.

Disclosure

B.Carstensen: Stock/Shareholder; Novo Nordisk. K.K.B.Clemmensen: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. V.Kosjerina: Research Support; Sanofi-Aventis Deutschland GmbH. F.Persson: Advisory Panel; AstraZeneca, Bayer Consumer Care AG, Boehringer-Ingelheim, Novo Nordisk A/S, Consultant; AstraZeneca, Boehringer-Ingelheim, Novo Nordisk A/S, Research Support; Boehringer-Ingelheim, Novo Nordisk A/S, Speaker's Bureau; AstraZeneca, Bayer Consumer Care AG, Boehringer-Ingelheim, Novo Nordisk A/S, Sanofi.
1358-P: Disparities in Acute and Chronic Complications of Diabetes in Rural U.S.
Authors: STEIGER KYLE , HERRIN JEPH , SWARNA KAVYA , MCCOY ROZALINA G.
Published: June 2023

Rural Americans are more likely than urban Americans to be diagnosed with diabetes, to have poorly controlled diabetes, and to die from diabetes-related complications; however, there is little published data about the rates of acute and chronic diabetes complications in rural as compared to urban areas. We examined the rates of acute and chronic diabetes complications across the spectrum of rurality among U.S. adults with diabetes using OptumLabs Data Warehouse, a de-identified dataset of commercially insured and Medicare Advantage beneficiaries: remote (population <2,500; N=75,077), town (population 2,500-50,000; N=409,152), and city (population >50,000; N=2,417,334). As compared to cities, small towns had greater incidence of severe hyperglycemia (HR=1.1; 95% CI: 1.06, 1.14), severe hypoglycemia (HR= 1.15; 95% CI: 1.12, 1.18), end-stage kidney disease (HR=1.06; 95% CI: 1.04, 1.08), heart failure (HR=1.08; 95% CI: 1.07, 1.1), myocardial infarction (HR=1.14; 95% CI: 1.12, 1.16), osteomyelitis (HR=1.06; 95% CI: 1.04, 1.08), and revascularization (HR=1.06; 1.05, 1.08). Compared to cities, remote areas had higher incidence of myocardial infarction (HR=1.09; 95% CI: 1.05, 1.13), osteomyelitis (HR=1.09; 95% CI: 1.04, 1.14), and revascularization (HR=1.05; 95% CI: 1.03, 1.07). Urban areas had lower incidence of stroke: (Remote: HR=0.93; 95% CI: 0.89, 0.96); (Town: HR=0.98; 95% CI: 0.96, 0.99). There were no significant differences between the groups in the development of atrial fibrillation, Charcot joint, retinopathy, or lower extremity ulcer. Overall, rural areas had greater incidence of diabetes complications (remote areas in 3 out of 12 complications and towns in 7 out of 12 complications); however, cities had decreased incidence of stroke. An important limitation of this study is that it measures treatment/diagnosis rates, necessitating health care utilization. We therefore likely underestimate the rate of complications in rural areas, where gaps in access to health care is widely recognized.

Disclosure

K.Steiger: None. J.Herrin: Consultant; Johnson & Johnson Medical Devices Companies. K.Swarna: None. R.G.Mccoy: Consultant; Emmi.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (K23DK114497)
1371-P: Factors Influencing the Development of Polycystic Ovary Syndrome in Premenopausal Women with Type 1 Diabetes
Authors: BAYONA ANE , NATTERO-CHÁVEZ LÍA , ESTHER DE LA CALLE DE LA VILLA MARÍA , DURÁN ELENA F. , DORADO AVENDAÑO BEATRIZ , LUQUE-RAMÍREZ MANUEL , ESCOBAR-MORREALE HÉCTOR F.
Published: June 2023

Objective: Polycystic ovary syndrome (PCOS) is common in women with type 1 diabetes (T1D). Reported prevalence rates vary according to diagnostic criteria used for PCOS. However, not all women with T1D develop hyperandrogenic traits and factors that influence the occurrence of PCOS have not been well stablished yet. We aim to assess the factors associated to the occurrence of PCOS in premenopausal women with T1D.

Methods: Cross-sectional study. For this analysis, we included 110 patients with T1D, 24 diagnosed with PCOS by ESHRE/ASRM-Rotterdam criteria (prevalence: 22%, 95%CI: 15-30%). Women aged 18 to 45 years were consecutively recruited from a Diabetes Clinic at a tertiary hospital in Madrid, Spain. All participants were under intensive insulin treatment, had been diagnosed with T1D at least 1 year ago, and had a gynecological age of at least 2 years. A comparison between both groups T1D-PCOS and T1D-without PCOS was performed. We used Stata software v23 (StataCorp LLC) for statistical analysis.

Results: Mean age was 30.3 ± 8.7 yrs and mean HbA1c was 7.31 ± 1.4%. Three-quarters (75%) of these patients were on multiple insulin doses. Women with T1D and PCOS were younger than those without PCOS (26.3 ± 7.4 in DM1-PCOS vs 31.2 ± 8.7, P < 0.05). Total daily insulin dose (TDI) was higher in T1D-PCOS group compared to T1D-without PCOS (0.71 ± 0.35 vs 0.58 ± 0.19, P = 0.025). There was a trend towards a more common premenarcheal diagnosis of T1D in T1D-PCOS (62.5% vs 46.5%, P = 0.116). Age (OR: 0.93, P = 0.016) and TDI (OR: 7.84; P = 0.043) were significant predictors of PCOS in the univariate logistic regression analysis. After introducing these variables in a multivariate regression analysis, only age was retained as a significant predictor factor of PCOS in women with T1D (OR: 0.93; P = 0.040).

Conclusions: In this study, premenopausal women with T1D and PCOS were younger, used higher daily insulin doses and tend to have a more common premenarcheal diagnosis of T1D as compared to T1D women without PCOS.

Disclosure

A.Bayona: None. L.Nattero-chávez: None. M.De la calle de la villa: None. E.F.Durán: None. B.Dorado avendaño: None. M.Luque-ramírez: None. H.F.Escobar-morreale: None.
138-OR: Characterization and Prediction of Genetic Risk of T1D in Individuals without HLA-DR3 or HLA-DR4
Authors: MCGRAIL CAROLYN , GAULTON KYLE J.
Published: June 2023

The Major Histocompatibility (MHC) class II haplotypes HLA-DR3 and HLA-DR4 confer substantial genetic risk for type 1 diabetes (T1D), where 90% of individuals with T1D carry at least one copy of DR3 and/or DR4. We sought to understand whether the remaining 10% of T1D individuals without DR3 or DR4 haplotypes (non-DR3/DR4) have differences in genetic risk and whether current risk scores are effective for these individuals. We tested for T1D association using 12,716 non-DR3/DR4 samples from five European ancestry cohorts using genotypes imputed into the Michigan HLA and TOPMed v2 reference panels and identified independent signals using stepwise conditional analyses. There were 21 signals with significant effects on T1D, including 13 at the MHC locus and 8 genome-wide, of which 5 were novel. Across all T1D signals, 14 lead variants exhibited significant heterogeneity in effects on T1D in the non-DR3/DR4 subset compared to the full T1D population, including HLA-B*39 and the PTPN22 locus. Nearly 50% of non-DR3/DR4 T1D would be misclassified by a current T1D genetic risk score (T1D GRS1), which is weighted heavily by DR3/DR4 tag variants. We developed a new GRS using the 21 independent signals and determined whether this GRS could better discriminate T1D in individuals with non-DR3/DR4 haplotypes. The non-DR3/DR4 T1D GRS effectively differentiated T1D case and control samples (AUC=0.87) including in samples not in the initial discovery set (AUC=0.86), and improved prediction compared to GRS1 (AUC=0.52 using all controls, AUC=0.79 using only non-DR3/DR4 controls). These findings reveal a subset of T1D cases with heterogeneity in genetic risk and which are not as well represented by current risk scores, and argue that risk scores developed within heterogeneous subsets may enable even more accurate prediction of T1D.

Disclosure

C.Mcgrail: None. K.J.Gaulton: Consultant; Genentech, Inc., Stock/Shareholder; Neurocrine Biosciences, Inc., Vertex Pharmaceuticals Incorporated.

Funding

National Institutes of Health (DK120429, DK122607)
1394-P: Risk for Newly Diagnosed Type 2 Diabetes Mellitus after SARS-CoV-2 Infection among Korean Adults—A Nationwide Matched Cohort Study
Authors: HAN CHOI JONG , SONG KEE-HO
Published: June 2023

Background: There is growing evidence that coronavirus disease 2019 (COVID-19) can cause various extrapulmonary sequelae, including diabetes. However, it is unclear whether these effects persist even after 30 days from the date of diagnosis. We investigated the incidence of newly diagnosed type 2 diabetes mellitus (T2DM) during the post-acute phase of COVID-19.

Methods: This cohort study used data from the Health Insurance Review and Assessment Service, a representative national healthcare database in Korea. We initially established a cohort of 348,180 people among those diagnosed with COVID-19 without a history of any diabetes between January 2020, and September 2021. Among people with neither a history of any diabetes nor a diagnosis of COVID-19, the control group consisted of sex- and age-matched people with the cohort. We assessed the hazard ratio (HR) of newly diagnosed T2DM in patients with COVID-19 compared to the control adjusted for age, sex, and presence of hypertension and dyslipidemia.

Results: In the post-acute phase of COVID-19, patients with COVID-19 had an increased risk of newly diagnosed T2DM than those without COVID-19 (adjusted HR 1.30, 95% CI 1.27-1.33). The adjusted HRs of non-hospitalized, hospitalized, and intensive care unit-admitted patients were 1.14 (95% CI 1.08-1.19), 1.34 (95% CI 1.30-1.38), and 1.78 (95% CI 1.59-1.99), respectively.

Conclusion: COVID-19 may increase the risk of developing T2DM beyond the acute period. The higher the severity of COVID-19 in the acute phase, the higher the risk of newly diagnosed T2DM. Therefore, T2DM should be included as a component for managing long COVID.

Disclosure

J.Choi: None. K.Song: None.