bluuebunny/crossref_metadata_2025 huggingface dataset:
189-OR: Food Insecurity and Inability to Obtain Recommended Medications, Diabetes Technology, and Multidisciplinary Services in Youth and Young Adults with Diabetes
Authors: EL KALACH NADINE , JULCEUS EMMANUEL F. , RUDISILL CAROLINE , MALIK FAISAL , FLORY KATE , FRONGILLO EDWARD A. , SAUDER KATHERINE A. , MENDOZA JASON A. , LIESE ANGELA D.
Published: June 2024

Introduction & Objective: Little evidence exists on how household food insecurity (FI) affects youth and young adults (YYA) obtaining medical care related to diabetes. We assessed if FI is cross-sectionally associated with not obtaining recommended diabetes medications, technology, and multidisciplinary services, and explored the most common reasons for not obtaining recommended treatments in YYA with diabetes.

Methods: Using data from 911 YYA with type 1 diabetes (T1D) and 144 YYA with type 2 diabetes (T2D) in the SEARCH Food Security Cohort Study Follow-up 1 (2018-2021) and logistic regression, we evaluated the association of FI and the inability to obtain recommended treatments and tabulated the reasons reported.

Results: Almost 30% of YYA with T1D and FI and 20% of YYA with T2D and FI did not obtain one or more recommended treatment (15.8% and 14.4% in food secure YYA, respectively). YYA with T1D and FI had higher odds of not obtaining insulin (OR 3.2, 95% CI 1.2-8.4), an insulin pump (OR 2.2, 95% CI 1.2-4.4), a continuous glucose monitor (OR 2.5, 95% CI 1.5-4.4), mental health counseling (OR 3.3, 95% CI 1.3-8.2), and diabetes education (OR 3.6, 95% CI 1.4-9.3), adjusted for demographics, household income, food assistance, and diabetes duration. Among YYA with T2D, FI was related to not obtaining dietician services (OR 8.1, 95% CI 1.2-53.8). YYA with T1D mostly reported financial reasons (e.g., unable to afford, insurance issues) for not obtaining diabetes technology and medications, followed by structural reasons (e.g., lack of time, not allowed time off) for not obtaining services such as diabetes education or mental health counseling.

Conclusion: YYA with diabetes and FI face constraints in obtaining medications, diabetes technology, and multidisciplinary services, largely due to financial and structural reasons. New strategies are needed to bridge the gap between medical care required versus obtained by YYA with diabetes.

Disclosure

N. El Kalach: None. E.F. Julceus: None. C. Rudisill: None. F. Malik: None. K. Flory: None. E.A. Frongillo: None. K.A. Sauder: None. J.A. Mendoza: None. A.D. Liese: None.

Funding

1R01DK1174611R01DK12720811UC4DK108173
1891-LB: Glycemic Control in Patients with Type 2 Diabetes Mellitus with A1C ≥9.0% with Oral Hypoglycemic Agents vs. Insulin plus Oral Agents
Authors: VIOLANTE ORTIZ RAFAEL , FERNANDEZ ORDOÑEZ NORMA , NARVAEZ GALLIFA EMANUEL , GUERRA CÁRDENAS JOSÉ E. , TAVERA TAPIA ALEJANDRA , REYNA-BELTRÁN ELIZABETH , PEREZ PEREZ JESSICA , CASTRO CHONG IRENE , VÁZQUEZ GARCIA VIRIDIANA , BADILLO GRIJALVA IZMENE , BAUTISTA SÁNCHEZ JAIDY , WONG DE LEÓN KARLA , OLVERA ESCOBEDO ANA , RAMOS GOMEZ CHRISTIAN , AVILA SILVA ANETTE
Published: June 2024

Introduction & Objective: Insulin therapy in patients with type 2 diabetes mellitus (T2DM) with A1c ≥9% as recommended by some guidelines is not always possible due to different psychological and social factors. Our work compares this strategy with the intensified and combined use of oral hypoglycemic agents (OHAs) in patients with uncontrolled T2DM.

Methods: This was a descriptive and longitudinal study with 426 T2DM patients and A1c ≥9% divided in 2 groups: Group A consisted of OHAs-only therapy (n=188) and Group B of insulin plus OHAs (n=238). We considered the glycemic goal of A1c ≤7%. Cohorts at 3, 6 and 12 months were evaluated using the chi-square test with a significance level of p=≤ 0.05.

Results: Initial Group A vs Group B: age 53.1 ±12.3 vs 56.1 ±12.4 (p= 0.695), weight 77.8 ±15.6 vs 74.3 ±18.1 (p= 0.202), BMI 29.7 ±5.5 vs 29.1±6.0 (p= 0.202); years since T2DM diagnosis 8.6 ±7.6 vs 13.5 ±8.8 (p= 0.000); FPG 223.4 ±69.6 vs 253.6 ±82.8 (p= 0.299); A1c 10.8 ±1.5 vs 11.4 ±1.6 (p= 0.128); At 3 months Group A vs Group B: monotherapy 5 (2.7%) vs 19 (8.0%) p=0.018, dual therapy 53 (28.2%) vs 117 (49.2%) p= 0.000, triple therapy 83 (44.1%) vs 77 (32.4%) p=0.013, quadruple therapy 42 (22.3%) vs 9 (3.8%) p= 0.000; at 6 months: monotherapy 4 (4.3%) vs 13 (11.4%) p=0.064, dual therapy 18 (19.4%) vs 61 (53.5%) p= 0.000, triple therapy 43 (46.2%) vs 37 (32.5%) p= 0.043, quadruple therapy 23 (24.7%) vs 3 (2.6%) p= 0.000; at 12 months: monotherapy 1 (6.8%) vs 8 (10.0%) p= 0.054, dual therapy 16 (27.1%) vs 6 (57.5%) p= 0.000, triple therapy 26 (44.1%) vs 26 (32.5%) p= 0.164. A1c glycemic target achievement at 3 months Group A vs Group B; 46.3% vs 25.2% p=0.000; at 6 months 63.4% vs 37.7% p=0.000; at 12 months 74.6% vs 32.5% p=0.000.

Conclusion: The combined use of OHAs was more effective than insulin therapy plus OHAs in T2DM patients with A1c ≥9.0%, this new approach may be an alternative in patients who do not choose to use insulin or doctors without sufficient knowledge of insulinization.

Disclosure

R. Violante Ortiz: None. N. Fernandez Ordoñez: None. A. Tavera Tapia: None. E. Reyna-Beltrán: None. J. Perez Perez: None. I. Castro Chong: None. V. Vázquez Garcia: None. I. Badillo Grijalva: None. J. Bautista Sánchez: None. K. Wong De León: None. A. Olvera Escobedo: None. C. Ramos Gomez: None. A. Avila Silva: None.
1909-LB: Patient Preferences for Continuous Glucose Monitoring Devices—A Discrete Choice Experiment Study of People Living with Type 2 Diabetes
Authors: LAI TIM C. , WHITLEY HEATHER P. , NGORSURACHES SURACHAT
Published: June 2024

Introduction & Objective: While continuous glucose monitoring (CGM) devices have received approval for use in eligible patients, there remains limited evidence regarding patient preferences for these devices. This study aims to determine the important attributes of CGM devices for patients with type 2 diabetes (T2D).

Methods: A cross-sectional, web-based, discrete choice experiment (DCE) survey was conducted. Seven attributes of CGM devices, including the approach to access data, alarm function, information on receiver screen (including measurement frequency and prediction arrow), accuracy, calibration frequency, sensor lifespan, and out-of-pocket cost, were identified through a literature review and consultation with five clinical experts. A D-efficient design was used to generate DCE choice sets. Data were collected from 242 American adults living with T2D who were proficient in English. A mixed logit model was used to determine the preference weights of all attributes. Conditional relative importance was calculated by differentiating each attribute’s highest and lowest level of its preference weights.

Results: A total of 182 patients were included in the analysis. The preference weights of all attributes, except the information on receiver screen, were statistically significant and in the expected direction (e.g., patients prefer lower out-of-pock cost). The conditional relative importance of out-of-pocket cost was the greatest (3.19, SE=0.75), followed by accuracy (1.40, SE=0.37), calibration frequency (1.01, SE=0.27), alarm function (0.94, SE=0.27), sensor lifespan (0.60, SE=0.22), and approach to access data (0.26, SE=0.13).

Conclusion: While patients with T2D considered various attributes when selecting CGM devices, out-of-pocket cost was their primary concern. Notably, information on receiver screen was not a significant attribute, underscoring the need for further investigation into its implications.

Disclosure

T.C. Lai: None. H.P. Whitley: None. S. Ngorsuraches: Research Support; Bristol-Myers Squibb Company.
1934-LB: Evaluating the Efficacy of Decentralized Trials and Digital Marketing Tactics in Diabetes Management in Habitual’s DIGEST Study
Authors: GOROBZOV MELANIE
Published: June 2024

Introduction/Rationale: Advances in diabetes remission programs have markedly improved type 2 diabetes (T2D) management, addressing glycemia, blood pressure, and microvascular health. However, the high demand for in-person medical consultations increases costs and decreases patient engagement. Recognizing these challenges, the DIGEST study by Habitual explores the efficiency of a remote-delivered diet replacement and digital therapy for T2D remission and weight loss, circumventing the traditional clinical visit model. The study employed Lindus Health for a fully virtual trial, navigating strict recruitment criteria through digital outreach and a primary care network.

Methods: Lindus Health executed a fully virtual design, enabling remote monitoring for six months. The approach utilized digital marketing and referrals from ten GP sites to attract participants, directing them to a study website for initial screening. Eligible individuals underwent a virtual assessment by Lindus Health nurses for deeper engagement and informed consent.

Results: Lindus Health's strategies enabled Habitual to reach its recruitment goal of 100 patients in five months, significantly ahead of the initial 12-month prediction. The trial's decentralization allowed for UK-wide participant inclusion, reaching over 16,000 people through online advertising. Remote monitoring facilitated home-based study participation, allowing real-time tracking of patient progress and enhancing the trial's patient-centric approach.

Conclusion: The DIGEST study demonstrates the potential of fully decentralized trials in T2D management, showcasing the Habitual Remission Program's efficacy. The model's success, driven by virtual designs and strategic recruitment, highlights a shift towards more accessible, efficient clinical research, suggesting a scalable and patient-friendly future for digital health solutions in disease management.

Disclosure

M. Gorobzov: None.
1943-LB: The Fresh Start Program—Refreshing Management of Type 2 Diabetes Mellitus
Authors: GRDINOVAC KRISTINE , DAVIES GAGE , STEGER FELICIA
Published: June 2024

Objective: Intensive type 2 diabetes mellitus (T2DM) intervention programs can improve clinical outcomes for patients and reduce costs to patients, insurance providers, and health care systems. We piloted an intensive T2DM intervention program consisting of a multidisciplinary team of diabetes providers. We tested feasibility of our program and examined its impact on hemoglobin A1c (HbA1c) and glycemic time in range (TIR).

Methods: The program was piloted at a large, urban, academic hospital. Adults with T2DM and HbA1c >9% were enrolled in a 24-week program consisting of regular visits with a Nurse Practitioner, Certified Diabetes Care and Education Specialist, pharmacist, and social worker (if needed). There were a total of 12 individual provider visits and nine group T2DM lifestyle education classes. All participants were given continuous glucose monitors (CGMs).

Results: Ten participants were enrolled. Eight patients completed 12 weeks and seven patients completed the 24 week program (70% retention). Participants were 50% female and 80% Caucasian, with mean HbA1c 11.4 ± 1.4%. Mean HbA1c after 12 weeks was significantly reduced by 3.3 ± 2.5% (n=7; p=0.02). Change in HbA1c at 24 weeks approached statistical significance (-2.5 ± 3.4%, n=8, p=0.06). CGM TIR increased by 24 ± 26% after 24 weeks (n=6, p=0.03) and average glucose decreased by 23 ± 20 mg/dL (n=6, p=0.03).

Conclusion: We demonstrated the feasibility of a 24-week multidisciplinary diabetes intervention program for patients with uncontrolled T2DM. Overall time in range and average glucose via CGM improved. Future studies should evaluate sustained improvements in glycemic measure with intensive behavior change programs as well as their impact on health system utilization.

Disclosure

K. Grdinovac: Consultant; AmalgamRx. G. Davies: None. F. Steger: None.
1946-LB: Patterns of Insulin Discontinuation in Youth with New-Onset Type 2 Diabetes
Authors: HAO SHUAI , WESTBROOK ADRIANNA , SINHA CYNTHIA B. , HSIA DANIEL S. , VELLANKI PRIYATHAMA
Published: June 2024

Heterogeneity in the clinical course of T2D in youth presenting with and without diabetic ketoacidosis (DKA) at diagnosis is not well described. In this study, we aimed to characterize if presentation with DKA affects rates of insulin discontinuation compared to T2D without ketosis (non-DKA). This single-center retrospective cohort study included patients (BMI 33.7 IQR 29.1,38.6) with mean age 15 years (IQR 13,16), admitted for new-onset DKA (n= 77) or non-DKA (n=361) from 2019-2021 with 1-year follow-up. All patients were initiated on insulin and titrated per their care team. Type 1 diabetes was excluded by presence of autoimmune antibodies. Primary outcomes were discontinuation of insulin therapy and maintenance of discontinuation 1 year after diagnosis. There were no differences in the proportion of (p=0.63) or time to insulin discontinuation (p=0.20) between DKA and non-DKA. Trajectory analyses identified 3 insulin discontinuation groups: early (within 2 months), late (within 6 months), and never (Figure 1). Multinomial regression shows that DKA at presentation is not associated with early (p=0.60) or late insulin discontinuation (p=0.59) compared to never discontinuation. We identified heterogeneity in duration of insulin treatment in youth with new-onset T2D with and without DKA at presentation. Prospective studies are needed to characterize differences in β-cell function that may predict insulin dependence.

Disclosure

S. Hao: None. A. Westbrook: None. C.B. Sinha: None. D.S. Hsia: None. P. Vellanki: Consultant; Eli Lilly and Company.
195-OR: Efficacy and Feasibility of a Telemedicine Program for Institutionalized Elderly People with Insulin-Treated Diabetes Using Continuous Glucose Monitoring and a Connected Insulin Pen Cap—The Trescasas Study
Authors: GOMEZ-PERALTA FERNANDO , ABREU CRISTINA , MAZO ESTEFANIA S.
Published: June 2024

Introduction & Objective: Investigate the feasibility and efficacy of a telemedicine program in institutionalized elderly people with insulin-treated diabetes.

Methods: This multicenter, prospective study comprised of three two-week phases: Phase 1 (baseline): blind CGM (Freestyle Libre Pro®); Phase 2a: CGM (Freestyle Libre2®) without alarms; Phase 2b: CGM with alarms for hypo and hyperglycemia. Two telemedicine visits from the reference diabetes units to adjust the treatment before phases 2a and 2b. The insulin treatment was tracked using the Insulclock® connected insulin pen cap. The caregivers’ opinion about the program was measured. Feasibility criteria included the number of eligible patients, recruitment, attrition and the capture of glucose readings. The insulin or antidiabetic drugs changes were recorded.

Results: From 82 eligible residents (87.7 +7.1, 68-102 y, 56% women, baseline HbA1c 6.9 +1.6) at 7 nursing homes, 54 completed all the procedures. The caregivers expressed an overall positive view of the program (3.8 out of 4 points); greater convenience (4.5 out of 5 points) and potential to reduce hypoglycemia (3.7 out of 5 points) by using Freestyle Libre2® over glucometer. The rate of glucose events <70 mg/dl in every phase (mean +SD) decreased: 4.9 +6.2, 3 +3.8, and 2.1 +3.1 (p 0.036). GMI and TIR 70-180 increased: 7.1 +1.2, 7.2 +1.4, 7.5 +1.7 (p 0.01); 65.6 +24.8, 65.1 +25.2, 60.4 +26.4 (p 0.02), respectively. The number of insulin injections (mean +SD): (1.2 +0.9 to 0.9 +0.8; p 0.02), and basal insulin dose (median) (16 to 14 IU; p 0.0003) decreased. The number of rapid insulin doses increased: 1.6 +3.8 to 2.9 +4.3 (p 0.02).

Conclusion: A telemedicine program using CGM is well-perceived by caregivers and achieves a safer and more adequate glycemic profile in the challenging population of institutionalized older people with diabetes treated with insulin.

Disclosure

F. Gomez-Peralta: Advisory Panel; Abbott. Speaker's Bureau; Abbott. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Advisory Panel; Insulcloud S.L. Speaker's Bureau; Medtronic. Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Advisory Panel; Sanofi. C. Abreu: None. E.S. Mazo: None.

Funding

Abbott Diabetes Care Investigator Initiated Study (ADC-OUS-IIS-20-55)
1954-LB: Health Care Resource Utilization in Newly Diagnosed Children with Type 1 Diabetes in U.S. Clinical Practice
Authors: STOKES MICHAEL E. , LI QIAN , CAGLE ANDREW , WILSON LAURA
Published: June 2024

Introduction & Objective: There are limited contemporary data available on healthcare resource utilization (HCRU) in children newly diagnosed with type 1 diabetes (T1D). This study estimated HCRU in newly diagnosed pediatric patients with T1D in US clinical practice.

Methods: Merative MarketScan® data were retrospectively analyzed for newly diagnosed pediatric patients with T1D enrolled in Commercial or Medicaid health plans (January 1, 2014-June 30, 2019). Included patients had ≥2 T1D claims ≥30 days apart (first claim was index date), ≥12 months of pre-index enrollment, ≥1 month of follow-up, and were aged <18 years at index. Outcomes included T1D-related inpatient care, TD1-related outpatient visits, and emergency room (ER) visits and hospitalizations for hypoglycemia.

Results: We identified 4092 patients in Commercial and 1153 patients on Medicaid plans (mean [SD] age: 10.5 [4.3] vs 11.1 [4.1] years; 44.5% vs 51.4% female); median (range) follow-up was 27.9 (1.2-54.0) versus 24.7 (1.2-54.0) months. Almost all patients experienced T1D-related outpatient care (Commercial 99.3%; Medicaid 97.3%). T1D-related inpatient care (42.3% vs 36.0%) and use of insulin pumps (45.8% vs 30.5%) and continuous glucose monitoring (66.1% vs 51.9%) appeared higher for patients on Commercial versus Medicaid plans. ER visits for hypoglycemia occurred in 4.4% of patients on Commercial plans and 7.3% of patients on Medicaid plans. Few patients were hospitalized for hypoglycemia (Commercial 0.7%; Medicaid 1.0%).

Conclusion: Newly diagnosed T1D in children was associated with generally high rates of T1D-related HCRU. Distinct disparities in HCRU were identified between Commercial and Medicaid plan participants. Patients in Medicaid plans had higher ER visits for hypoglycemia compared to those with Commercial plans. Medicaid plan participants had lower use of continuous glucose monitoring and insulin pumps.

Disclosure

Q. Li: None. A. Cagle: Employee; Sanofi-Aventis U.S. L. Wilson: Employee; Sanofi. Stock/Shareholder; Sanofi.

Funding

Sanofi
1957-LB: Transition between Pediatric and Adult Diabetes Services—The Experiences and Perceptions of Health Care Professionals Worldwide
Authors: JAMES STEVEN , CUDIZIO LAURA , NG SZE M. , LYONS SARAH , ARASZKIEWICZ ALEKSANDRA , GOMBER APOORVA , MARUTHUR NISA M. , SNOEK FRANK J. , TOFT EVA H. , WEISSBERG-BENCHELL JILL , DE BEAUFORT CARINE
Published: June 2024

Introduction: Youth with diabetes should transition from paediatric to adult diabetes services in a deliberate, organized and cooperative way. International diabetes specific consensus guidelines are currently lacking. We sought to identify the experiences of healthcare professionals (HCPs) providing transition care, around readiness planning, policies, and the actual transfer to adult services, plus their perceptions around barriers in offering a good transition experience.

Methods: Data were collected via an online global survey (seven language options), broadly advertised by ISPAD, EASD, team members and research partners, via newsletters, websites, e-mails and social media.

Results: Respondents (n=372) were mainly physicians (74.5%), practicing in government funded (59.4%), pediatric (54.0%), metropolitan settings (85.8%) in Europe (44.9%); 37.1% in low or middle-income countries (LMICs). Youth were typically introduced to transition between 15-17 years (49.2%) and adult diabetes teams at ≥18 years (62.4%). Few centers used a transition readiness checklist (31.7%), written transition information (29.6%), or had a dedicated staff member (23.7%). Similarly, few involved a psychologist (25.8%), had combined (35.2%) or transition/young person only clinics (34.9%), or a structured transition education program (22.6%); 49.8% advised youth to use technology to assist the transfer. Most (91.9%) respondents reported barriers in offering a good transition experience; additional staffing (72.0%) and a structured protocol (71.5%) were perceived to improve the transition process. A greater proportion of respondents from LMICs sought more funding (p=0.01), a structured protocol (p<0.001) and education (p<0.001).

Conclusion: HCPs’ experiences and perceptions related to transition between pediatric and adult diabetes services vary widely. There is a pressing need for international consensus transition guidelines.

Disclosure

S. James: None. L. Cudizio: Other Relationship; Novo Nordisk. S. Lyons: None. A. Araszkiewicz: Other Relationship; Sanofi, Novo Nordisk, Eli Lilly and Company, Ascensia Diabetes Care, Boehringer-Ingelheim. A. Gomber: None. N.M. Maruthur: Other Relationship; Johns Hopkins Health Care Solutions. F.J. Snoek: Advisory Panel; Abbott, Sanofi, Eli Lilly and Company, Roche Diabetes Care. J. Weissberg-Benchell: Consultant; Beta Bionics, Inc. Advisory Panel; American Diabetes Association. Research Support; Juvenile Diabetes Research Foundation (JDRF), National Institute of Diabetes and Digestive and Kidney Diseases. C. de Beaufort: None.
1973-LB: Postpartum Dysglycemia Screening with Continuous Glucose Monitoring
Authors: CABRERA CAMILA , OGYAADU SELASSIE J. , KAPLAN LEAH , IPEK ASLIHAN , LEVY CAROL J. , O'MALLEY GRENYE
Published: June 2024

Introduction & Objective: Up to one third of birthing persons with gestational diabetes (GDM) will have persistent dysglycemia, and more than half do not complete the recommended postpartum oral glucose tolerance test (OGTT). This study assessed the feasibility of postpartum continuous glucose monitoring (CGM) to detect dysglycemia by assessing sensor return rates and participant experience and calculated the predictive power of CGM to predict OGTT results.

Methods: CGM was placed on postpartum day 1-3 after pregnancy complicated by GDM and worn at home for up to 10 days. Participants were encouraged to undergo standard of care 6-week OGTT. CGM data was analyzed according to time-above cutoffs. Analysis with removal of data within 4 half-lives of steroid administration was also performed.

Results: Fifty women (36±6 years; 40% non-Hispanic White, 24% non-Hispanic Black, 22% Asian, 14% Hispanic; 34% Medicaid insured) were consented; 86% returned CGM and 66% completed OGTT. All CGM downloads included at least 72 hours of data, and 19% provided data after recent steroid administration. Fasting data was available on 88% of CGM and 42% of OGTT. Mean CGM glucose was 122±14 mg/dL. Median time >140, >180, and >200 mg/dL was 17%, 1.9%, and 0.6%, respectively; and 91%, 21%, and 33% had time >140 mg/dL of >5%, >180 mg/dL of >5%, and >200 mg/dL of >1%. Mean fasting CGM glucose was 113±15 mg/dL and was 100-125 mg/dL in 51% and >125 mg/dL in 23%. Dysglycemia on OGTT (7 impaired glucose tolerance, 1 diabetes) was well predicted by percent time >180 of >4% (sensitivity 86%, specificity 85%, positive predictive value 60%, negative predictive value 96%). Removal of steroid affected data did not improve performance. CGM and OGTT were considered burdensome by 7% and 52%, respectively.

Conclusion: Completion rates and acceptability scores were better for CGM than OGTT. Percent time >180 mg/dL had strong predictive power for OGTT. Time above range for this population was also found to be higher than reported for people without diabetes.

Disclosure

C. Cabrera: None. S.J. Ogyaadu: None. L. Kaplan: None. A. Ipek: None. C.J. Levy: Research Support; Dexcom, Inc. Consultant; Dexcom, Inc. Research Support; MannKind Corporation, T1D Exchange, Tandem Diabetes Care, Inc., Abbott, Insulet Corporation. G. O'Malley: Research Support; Dexcom, Inc., Insulet Corporation, Abbott, Tandem Diabetes Care, Inc., MannKind Corporation.

Funding

Product and research support for this investigator initiated study provided by Dexcom, Inc.
1975-LB: A Randomized Trial of Real-Time Continuous Glucose Monitoring in Gestational Diabetes
Authors: EHRHARDT NICOLE M. , FAY EMILY , ABDALLA GHADA , MANDAVA PATALI , FONDA STEPHANIE J.
Published: June 2024

Background: Gestational diabetes is common. Real-time continuous glucose monitoring (RT-CGM) may improve glycemia during pregnancy, but data is lacking.

Methods: We conducted a randomized controlled study in which patients with GDM performed SMBG with RT or blinded CGM. This analysis compares CGM metrics at EGA 32 and 36 weeks (+/-10 days). Outcomes included CGM metrics (see table), A1c and diabetes medication use.

Results: 107 participants with GDM enrolled (RT-CGM: N=53; SMBG: N=54). 35 SMBG participants withdrew, reporting desire for RT-CGM. Average EGA at CGM start was 30.2 (+/-1.7) weeks, age was 33.8 (+/-4.8) years, and 31% (RT-CGM) and 14% (SMBG) groups were on diabetes medication at screening. The 32-week CGM metrics for the groups were similar except mean glucose (RT-CGM=106.7 +/- 9 and SMBG=97.7 +/- 13, P=.01) and TBR54 (0.1 +/- 0.2) and 0.6 (+/- 1.2), P=0.08). 36-week mean glucose decreased for the RT-CGM group but increased for the SMBG group, and TBR54 was lower for the RT-CGM group (P=.03). A1c was similar between groups. Diabetes medication use at study end was 69% for RT-CGM and 32% for SMBG.

Conclusions: RT-CGM and SMBG group indices were similar despite higher initial mean glucose and diabetes medication use. Glucose changes were slight when CGM was started at EGA of 30 weeks but desire for CGM was high. More studies are needed to evaluate if earlier RT-CGM use will significantly affect glycemic indices.

Disclosure

N.M. Ehrhardt: Advisory Panel; Bayer Inc., Dexcom, Inc. Research Support; Dexcom, Inc., Novo Nordisk. Advisory Panel; Novo Nordisk. Research Support; Merck & Co., Inc. E. Fay: None. G. Abdalla: None. P. Mandava: None. S.J. Fonda: None.

Funding

Investigator initiated grant DexcomIIS-2019-101
1984-LB: Secretagogin—A Potential Circulating Biomarker of Acute Pancreatic ß-Cell Injury
Authors: QI XIAO-YAN , ZHANG MEILIN , WANG XIN , YANG JING
Published: June 2024

Introduction & Objective: Beta cell dysfunction is the fundamental pathogenesis of type 1 diabetes mellitus (T1DM), but there are few clinical biomarkers available to assess β-cell injury. Secretagogin, a protein enriched in pancreatic islets, demonstrates protective effects on β-cell function in animals. However, its potential as a circulating biomarker released from injured islet β-cell has not been studied.

Methods: Streptozotocin (STZ) induced diabetes mouse model and 21 T1DM patient were recruited to explore secretion and expression of secretagogin in relation to the T1DM pathology. Secretagogin expression was detected by western blotting and immunofluorescence staining while circulating secretagogin levels was measured by ELISA kit.

Results: Secretagogin was abundantly expressed in mouse and human islets, specifically co-localized with insulin positive β-cell. STZ administration induced loss of β-cell and progressive depletion of pancreatic secretagogin. There’s a sharp peak in mouse plasma secretagogin level 24 h after STZ injection and declined gradually. Western blot analysis also revealed a notable reduction in secretagogin levels within the pancreas 1 week following the STZ treatment. Furthermore, T1DM patients exhibited a significant decrease in plasma secretagogin levels compared to matched healthy controls. Interestingly, 4 subjects with fulminant type 1 diabetes (FT1DM) displayed considerably higher plasma secretagogin concentrations during the early stage of disease onset, in comparison to the average levels observed within the cohort. However, a clinical follow-up study revealed a significant reduction in plasma secretagogin levels among all FT1DM subjects during the observation period.

Conclusion: Our findings indicate that secretagogin is a potential novel biomarker reflecting acute pancreatic β-cell injury.

Disclosure

X. Qi: None. J. Yang: None.

Funding

National Natural Science Foundation of China (82170852); The Major Project of Science and Technology in the Health System of Nanshan District, Shenzhen (NSZD2023044).
1990-LB: Associations of SARS-CoV-2 Infection with Incident Diabetes among U.S. Veterans in a Longitudinal Observational Cohort
Authors: HUANG LIUYE , SUGIMOTO JONATHAN D. , SHAH JAVEED A. , LEE JENNIFER , WANDER PANDORA
Published: June 2024

Existing estimates of diabetes incidence after SARS-CoV-2 infection are derived from retrospective electronic health records (EHR) studies, which may lead to surveillance and misclassification bias given differences in receiving clinical care between the exposed and unexposed groups. We used data from the Veterans Health Administration (VHA)-based, longitudinal observational cohort study Epidemiology, Immunology and Clinical Characteristics of COVID-19 (EPIC3) and the VHA Corporate Data Warehouse to compare diabetes hazard rates over 12 months of follow-up (n=1245) in participants with and without a positive test for SARS-CoV-2. We fit Cox proportional hazard models, adjusted for age, sex, race/ethnicity, Charlson comorbidity index (CCI), and annual number of laboratory tests of any type except for SARS-CoV-2 related types.

Results: Compared to participants with a positive test for SARS-CoV-2, participants without a positive test were older and had a higher number of laboratory tests. They were more likely to have taken at least one dose of COVID19 vaccine, live in an urban area, being current smoker, and have a hospital stay within 30 days post enrollment. After adjustment, SARS-CoV-2 was not significantly associated with risk of incident diabetes overall (HR 0.71, 95%CI 0.33-1.51), in inpatients (HR 1.22, 95%CI 0.08-18.78), or in outpatients (HR 0.50, 95%CI 0.19-1.34).

Disclosure

L. Huang: None. J. Lee: None.

Funding

GR014814
1999-LB: GenomicKB—A Knowledge Graph for Human Genomic Data to Advance Understanding of Diabetes
Authors: FENG FAN , TANG FEITONG , GAO YIJIA , ZHU DONGYU , LI TIANJUN , YANG SHUYUAN , YAO YUAN , HUANG YUANHAO , SAUNDERS DIANE C. , PARKER STEPHEN C. , CARTAILLER JP , BRISSOVA MARCELA , LIU JIE
Published: June 2024

With rapid advancements in technologies involving genetic testing, epigenomic and transcriptomic profiling, many landmark consortia have generated rich multimodal data for the human genome. Among those, the consortia focused on human pancreas and islet research have greatly enhanced our understanding of different forms of diabetes. Despite new insights provided at an unprecedented scale and depth, current islet and pancreas data are fragmented across different portals with lack of common metadata/ontology standards, varying maturity of quality control pipelines, and disconnected from clinical research communities. To overcome these challenges, we developed Genomic Knowledgebase (GenomicKB), a graph database that integrates human genomic data, allowing researchers to explore and investigate human genome, epigenome, transcriptome, and 4D nucleome. The database uses a knowledge graph to consolidate genomic datasets and annotations from over 30 consortia and portals, resulting in 347 million entities, 1.36 billion relations, and 3.9 billion properties, which covers extensive pancreas and diabetes-related data including GWAS, disease ontology, and eQTL. Compared with traditional tabular data stored in separate data portals, GenomicKB emphasizes the relations among genomic entities and intuitively connects isolated data entries. With GenomicKB, complicated analysis among multiple modalities is transformed into coding-free queries and facilitates data-driven discoveries. Our knowledge graph structure is machine learning-ready and can be coupled with evolving artificial intelligence algorithms. In the future, GenomicKB will include pancreas and islet imaging and physiology datasets to build a comprehensive resource, PanKGraph, that will accelerate progress towards understanding diabetes etiology and pathophysiology, contribute to new diagnostic tool development, and inform transformative changes in diabetes prevention and care.

Disclosure

F. Feng: None. F. Tang: None. Y. Gao: None. D. Zhu: None. T. Li: None. S. Yang: None. Y. Yao: None. Y. Huang: None. D.C. Saunders: None. S.C. Parker: Research Support; Pfizer Inc. J. Cartailler: None. M. Brissova: None. J. Liu: None.
2004-LB: Elucidating Causal Genes of Severe Insulin Resistance Diabetes through Polygenic Exploration of Type 2 Diabetes Heterogeneity
Authors: YOSHIJI SATOSHI , RUEBENACKER OLIVER A. , SMADBECK PATRICK , SAYICI AHMET , LLAMAS EDGAR A. , FLANNICK JASON
Published: June 2024

Background: Severe insulin resistance diabetes (SIRD) is a subgroup of type 2 diabetes (T2D) with particularly high risk of cardiovascular complications. A subset of T2D genome-wide association study (GWAS) associations are suggested to act through pathways underlying SIRD, but the number of known loci are limited (<50), and the unavailability of large SIRD patient cohorts hampers directly conducting SIRD GWAS. We developed a novel model to computationally infer a full GWAS for SIRD, aiming to expand our understanding of its causal genes and relevant biological pathways.

Methods and Results: We developed a Bayesian model of latent SIRD association statistics conditional upon observed association statistics for 6 insulin resistance (IR)-related traits in up to 1 million individuals. We trained this model using 43 genetic variants within T2D GWAS loci suggested to be associated with SIRD, observing the expected “lipodystrophy” pattern such as positive effect sizes for insulin, TG, waist-hip-ratio, and negative for HDL and adiponectin. We then used the trained model to infer SIRD associations for over 2 million additional variants that were present in 6 IR-related GWAS. The resulting SIRD GWAS identified 429 independent variants at P < 5×10-8, which were mapped to 316 putatively causal genes, including known genes IRS1, COBLL1, PPARG, as well as novel ones such as TGFB2. Notably, TGFB2 encodes TGF-β2, an adipokine linked to IR in mice, and our data suggest its potential as a therapeutic target for SIRD in humans. Pathway-enrichment analysis showed enrichment in multiple lipid-related pathways. Furthermore, a polygenic risk score built with the GWAS was strongly associated with coronary artery disease risk (P < 1 × 10-10).

Conclusions: Using a novel Bayesian method, we inferred the first GWAS of SIRD, providing insights into molecular mechanisms of SIRD. The method is also applicable to other diabetes subtypes for which a training set of variants is available.

Disclosure

S. Yoshiji: None. P. Smadbeck: None. A. Sayici: Employee; Evotec International GmbH. J. Flannick: None.
2009-LB: Deep Learning Enhances Chromatin Accessibility Signals and Discovers Links with Genetic Variations in Skeletal Muscle Rare Cells
Authors: VU HA T.H. , VARSHNEY ARUSHI , ORCHARD PETER , LAAKSO MARKKU , TUOMILEHTO JAAKKO , LAKKA TIMO A. , MOHLKE KAREN L. , BOEHNKE MICHAEL , SCOTT LAURA , KOISTINEN HEIKKI A. , COLLINS FRANCIS S. , PARKER STEPHEN C.
Published: June 2024

Chromatin accessibility quantitative trait loci (caQTL) discovery is vital for linking epigenomic features with genetic variations in Type 2 diabetes (T2D). However, caQTL scans require clear epigenomic signals, posing challenges in rare cell types from single nucleus (sn) studies. To address this, we proposed using deep learning (DL) to upscale chromatin accessibility signals e.g. snATAC-seq data in skeletal muscle (SM) to uncover new caQTLs in rare cells.

We used snATAC-seq data from a recent study representing ~260K nuclei across 287 human SM biopsies and a DL model to upscale profiles. The study identified 13 cell populations and performed caQTL scans in the five most prevalent types: muscle fibers (Type 1, 2a, 2x), endothelial cells (ECs) and fibro-adipogenic progenitors (FAPs). Their abundance ranged from 29% (Type 1) to 12% (ECs) and 5% (FAPs) of ATAC nuclei. We trained a model with two Type 1 fiber read sets: a sparse set with read count matching the median count across per-sample EC nuclei, and an abundant set 50x larger than the sparse set. The model was used to upscale ECs and FAPs’ snATAC signals for caQTL scans. CaQTLs identified with upscaled profiles were compared against those identified without upscaling (“base”).

With upscaled profiles, we found 4,753 and 8,722 significant caQTL peaks in ECs and FAPs, respectively, surpassing the base’s 3,412 EC and 4,762 FAP significant caQTL peaks (5% FDR). The upscaled and base scans showed high correlation (Spearman ρ = 0.96 and 0.95 for signed -log10(p-value); Spearman ρ = 1 and 0.99 for effect sizes in ECs and FAPs). Notably, DL upscaling additionally discovered 1,847 EC and 4,652 FAP caQTL peaks not detected in base scans.

DL is expected to help characterize rare cells’ genetic regulatory landscapes. We are working on colocalization between caQTLs from upscaling analysis and T2D and related trait GWAS signals to determine novel ones that may share common causal variants and nominate rare effector cell types in SM.

Disclosure

H.T.H. Vu: None. A. Varshney: None. P. Orchard: None. M. Laakso: None. J. Tuomilehto: Stock/Shareholder; Orion Pharma, Aktivolabs, Digostics. T.A. Lakka: None. K.L. Mohlke: None. M. Boehnke: None. L. Scott: None. H.A. Koistinen: Other Relationship; AstraZeneca, Novo Nordisk. F.S. Collins: None. S.C. Parker: Research Support; Pfizer Inc.

Funding

NIH NIDDK (U24DK138515)
201-OR: Fasting and Postprandial Triglycerides in Early Pregnancy Correlate with Mean Glucose and Time-in-Range by CGM at 28 Weeks of Gestation
Authors: BARBOUR LINDA A. , FOSDICK BAILEY K. , DUNN EMILY Z. , PIERCE STEPHANIE , ROLLOFF KRISTY P. , PHILLIPS ELIZABETH , MOSS LAURA K. , PHIPERS JOCELYN , EDWARDS RODNEY K. , FRIEDMAN JACOB E. , HERNANDEZ TERI L.
Published: June 2024

Recent studies of obesity in pregnancy have demonstrated a link between higher maternal fasting and postprandial triglycerides (FTG, PPTG) and neonatal subcutaneous and liver fat. Maternal TG can be hydrolyzed by placental lipases to free fatty acids (FFA) for fetal fat accretion, which may be further stimulated by fetal hyperinsulinemia from maternal glucose exposure. We hypothesized that higher FTG and PPTG in early pregnancy are predictive of abnormal glucose metabolism later in pregnancy at 28 weeks gestation using a point-of-care (POC) TG meter and continuous glucose monitor (CGM) metrics that have been associated with fetal overgrowth. At 15.4±0.9 weeks gestation (Mean±SD; early pregnancy), 31 healthy pregnant participants who were overweight or obese (32±5 years; pre-pregnancy BMI 30.6±3.0 kg/m2; 81% White, 19% Hispanic/Latino) were provided an FDA-approved POC TG meter to measure FTG and 2-hr PPTG after each meal for 4 days on an ad libitum diet. At 22, 28, and 34 weeks, 4 days of FTG and PPTG measures were repeated; a CGM was worn at 15 and 28 weeks. In early pregnancy across 119 fasting samples, the average median FTG was 126 mg/dL (68 - 191) and across 329 postprandial samples, the 2-hr PPTG was 153 mg/dL (92 - 247) at 15.4 weeks. At 28 weeks, the mean 24-hr glucose was 100±9 mg/dL and % time-in-range (%TIR 63-140 mg/dl) was 94±6% by CGM. Early FTG were positively correlated with mean 24-hr glucose at 28 weeks (r=0.41; p=0.02) and negatively correlated with %TIR (r=-0.44; p=0.01) by CGM. Moreover, early PPTG correlated with mean 24-hr glucose at 28 weeks (r=0.38; p=0.03). By associating ~450 TG measures with CGM metrics, these data suggest that TG concentrations during early pregnancy in obesity may identify women at risk for higher glycemic measures later in pregnancy. Because both TG and glucose contribute to excess infant adiposity, the timing, interaction, and contribution of both exposures to excess fetal fat deposition warrant further investigation.

Disclosure

L.A. Barbour: None. B.K. Fosdick: None. E.Z. Dunn: None. S. Pierce: None. K.P. Rolloff: None. E. Phillips: None. L.K. Moss: None. J. Phipers: Research Support; Pfizer Inc., Aerogen, Cepheid, Natera, Myriad Genetics. R.K. Edwards: None. J.E. Friedman: None. T.L. Hernandez: None.

Funding

NIH (R01 HD102726); Harold Hamm Diabetes Center/Presbyterian Health Foundation Team Science Grant Pilot
2023-LB: Type 2 or Type 3c Diabetes Not an Exclusion Criteria for Total Pancreatectomy with Islet Auto Transplantation (TPIAT)
Authors: KANAK MAZHAR A. , BALAJI SARAVANAN PRATHAB , KALIVARATHAN JAGAN , MOHAMMED SHUJAUDDIN , KHAN AAMIR , LEVY MARLON F.
Published: June 2024

Purpose: Total pancreatectomy with islet auto-transplantation (TPIAT) is now a standard of care for patients with severe chronic pancreatitis. However, evaluation and patient selection is necessary to benefit from this difficult procedure. Several patients with CP also have underlying diabetes, Type 2 or type 3c. In this study, we performed a comparative analysis of the outcomes of the TPIAT procedure between our pre-transplant diabetic and non-diabetic patient cohorts.

Methods: A total of 100 Patients who underwent TPIAT at Virginia Commonwealth University from June 2016 to March 2024 have been included in this study. 26 out of 100 patients were diabetic before undergoing TPIAT and were either insulin-dependent or under other diabetic medications and with an HbA1c of more than 6.0%. Islet isolation outcomes were compared along with metabolic outcomes and pain management data at clinical time points post-transplantation. Maintenance of hypoglycemic awareness was also assessed in these patients.

Results: Islet yields in diabetic and non-diabetic patients undergoing transplantation were significantly different (Diabetic vs. Non-Diabetic; 158362±185600 vs. 345126±219809; P<0.05). All Patients that were diabetic before TPIAT procedure continued to be insulin-dependent, whereas 40% of non-diabetic patients became insulin-independent at 1-year post-transplantation. Most interestingly, narcotic dependence was reduced in more than 50% at 1 year in patients with diabetes which was similar to patients who were non-diabetic. Similarly, pain scores were also reduced in patients equally regardless of their diabetic status prior to transplantation.

Conclusion: Pre-transplant diabetes should not be considered as a contra-indication for TPIAT, as these patients can maintain hypoglycemic awareness after transplantation of islets which is a major benefit along with relief from narcotic dependence.

Disclosure

M.A. Kanak: None. P. Saravanan: None. J. Kalivarathan: None. S. Mohammed: None. A. Khan: None. M.F. Levy: None.
2026-LB: Investigating the Role of NKX6.1 in Pancreatic Endocrine Cell Differentiation
Authors: LADD ANDREW D. , KRATZ AUSTIN T. , BARRA JESSIE , RUSS HOLGER A.
Published: June 2024

Protocols to generate stem cell-derived beta cells have allowed novel investigations into the differentiation, specification and function of human beta cells. The transcription factor Nkx6.1 is critical to the specification of insulin-producing pancreatic β cells in mice. Knockout of Nkx6.1 in an inducible mouse model has been shown to demonstrated lack of β cell specification when Nkx6.1 is absent and instead a preferred differentiation to α cells. While Nkx6.1 is a highly conserved transcription factor between mice and humans, the role of NKX6.1 in human endocrine specification has not been studied in detail. Using CRISPR/CAS9 genome engineering, we generated an NKX6.1 knockout (KO) embryonic stem cell line to allow us to investigate NKX6.1 in the human context. Utilizing a directed differentiation protocol to produce stem-cell derived pancreatic β cells (sBCs), we hypothesize that the lack of NKX6.1 will induce a preference for α cell specification and eliminate β cell fate in NKX6.1 KO cells but not control wild-type (WT) cells, similar to what is observed in rodents. In addition, we will use an α-like cell differentiation protocol to test if α cell differentiation is altered between NKX6.1 KO and WT cells. Our experiments will provide genetic evidence that NKX6.1 is necessary for the specification of pancreatic β cells in humans and more fully elucidate the role of NKX6.1 in pancreatic endocrine cell fate.

Disclosure

A.D. Ladd: None. A.T. Kratz: None. J. Barra: None. H.A. Russ: Advisory Panel; Sigilon Therapeutics, Inc. Consultant; Minutia. Advisory Panel; Prellis Biologics. Consultant; Eli Lilly and Company.
2035-LB: Value of TyG Combined with Albumin in Predicting MAFLD in Mulam Type 2 Diabetes Mellitus Patients
Authors: QIU YAWEI , ZHU HENGLIANG , XU YANCHUN , SU GUOQIANG , JIANG SHU , YANG ZHIJUN
Published: June 2024

Objective: There is no report on the study of T2DM combined with metabolic associated fatty liver disease(MAFLD)in Mulam nationality in China. This paper reports the value of triglyceride-glucose (TyG) combined with albumin in predicting MAFLD in Mulam T2DM patients.

Methods: A total of 105 Mulam T2DM inpatients in the Department of Endocrinology, Luocheng Mulam Autonomous County People's Hospital from July 2022 to August 2023 were enrolled and grouped according to whether they had MAFLD. 45 cases in the group with MAFLD and 60 cases in the control group without MAFLD.

Results: The proportion of newly diagnosed T2DM, waist circumference, hip circumference, weight, BMI, total protein, albumin, ALT, cholinesterase, TC, TG, LDL-C, non-HDL-C and TyG in MAFLD group were significantly higher than those in control group (P < 0.05) (Table 1). Logistic regression analysis showed that TyG (OR=1.887, 95%CI: 1.124-3.357, P=0.021) was a risk factor for MAFLD in Mulam patients with T2DM. ROC curve analysis showed that the AUC of TyG in predicting MAFLD was 0.704 (95%CI: 0.597-0.812), the sensitivity and specificity were 0.865 and 0.481. The AUC of the diagnostic model established by TyG combined with albumin was 0.787 (95%CI: 0.692-0.882), the sensitivity and specificity was 0.730 and 0.788.

Conclusion: TyG is a risk factor for MAFLD in Mulam T2DM patients. TyG combined with albumin has a high predictive value for MAFLD in Mulam T2DM patients.

Disclosure

Y. Qiu: None. H. Zhu: None. Y. Xu: None. G. Su: None. S. Jiang: None. Z. Yang: None.
2039-LB: Insulin Sensitivity Is Impaired Independent of Changes in Body Weight in Liver-Specific GDF15 Knockout Mice
Authors: KASTROLL JAKE , JURCZAK MICHAEL J. , ALDER JONATHAN , VANDEVENDER AMBER , DEDOUSIS NIKOLAOS , SIPULA IAN J.
Published: June 2024

Introduction & Objective: Growth differentiation factor 15 (GDF15), a stress-induced protein, constrains body weight gain in models of obesity by reducing feeding and potentially increasing energy expenditure, leading to improved insulin sensitivity. Whether GDF15 affects insulin sensitivity independent of changes in body weight remains an open question.

Methods: To address this question directly, we generated liver-specific GDF15 knockout mice (Gdf15fl/fl x Albcre-/+ to yield Gdf15fl/fl/Albcre-/+ LKO or Gdf15fl/fl/Albcre-/- WT mice). GDF15 LKO mice were fed either standard chow or high-fat diet (HFD) for 4 and 12 weeks. After the dietary challenge, we performed comprehensive metabolic phenotyping.

Results: Chow-fed GDF15 LKO mice were similar to WT mice and there were no differences in body weight, feeding, circulating GDF15 levels or glucose homeostasis. After 12 weeks HFD, circulating GDF15 was 50% less in LKO mice, which was associated with a modest increase in body weight and significantly increased plasma insulin levels during glucose tolerance tests, indicative of insulin resistance. To avoid the confounding influence of body weight on comparisons of insulin resistance, we fed LKO mice HFD for 4 weeks. Circulating GDF15 was 20% less in LKO mice and there were no differences in body weight or feeding compared to WT. Hyperinsulinemic euglycemic clamps demonstrated impaired whole-body insulin sensitivity in LKO mice that was due primarily to impaired suppression of hepatic glucose output by insulin, indicative of liver insulin resistance.

Conclusion: These data demonstrate body weight-independent effects of hepatocyte GDF15 on insulin sensitivity and suggest the potential for local, GFRAL-independent effects of hepatocyte-derived GDF15 on liver insulin signaling.

Disclosure

J. Kastroll: None. M.J. Jurczak: None. J. Alder: None. A. Vandevender: None. N. Dedousis: None. I.J. Sipula: None.