bluuebunny/crossref_metadata_2025 huggingface dataset:
1044-P: A Best Practice Advisory (BPA) Alert within the EHR Reduces Hypoglycemia Related to Insulin Administration in a Real-World Hospital Setting
Authors: PATHAM BHARGAVI , SALDIVAR VIDYA , YARLAGADDA SRI LAKSHMI L. , SADHU ARCHANA R.
Published: June 2024

Basal bolus insulin regimen (BB) is standard practice for managing hyperglycemia. For optimal outcomes with BB, the nursing workflow of timing the point of care glucose (POC-G) measurement with insulin pharmacokinetics is essential. In real-world hospital settings, this is a challenge and can result in iatrogenic hypoglycemia and hyperglycemia. We aimed to improve hypoglycemia by changing nursing practice to reduce the time interval between POC-G measurement and insulin administration. A best practice advisory (BPA) was created to fire within the EHR at the time of insulin administration to alert the nurse to repeat a POC-G if the prior measurement was over 30 minutes for fast acting (FA) or intermediate acting (IA) or over 60 minutes for long acting (LA) insulin. Retrospective data was collected from our hospital system in all hospitalized patients receiving subcutaneous insulin for four months before and after implementation of the BPA. Of total insulin administrations (n=300,462), BPA was fired on 90% (n=270,370) with 94% (n=253,551) acknowledgment rate. The median length of time (LoT) between POC-G and insulin administration pre-BPA to post-BPA decreased from 42 min to 23 min for FA and IA, and from 52 min to 29 min for LA insulin. Concurrently, the median patient days with hypoglycemia defined as POC-G <70 mg/dL reduced from 4.8% to 4.3%, a relative reduction of 10.4%. A real-time EHR based BPA for nurses improved timing of POC-G with insulin administration and resulted in reduction of hypoglycemia in a real-world hospital setting.

Disclosure

B. Patham: None. V. Saldivar: None. S.L. Yarlagadda: None. A.R. Sadhu: Advisory Panel; Abbott Diagnostics.
1046-P: Cost-Effectiveness of Insulin Icodec for the Treatment of Type 2 Diabetes (T2D) in Canada
Authors: GARCIA DAVID A. , MAU GODFREY , VUONG VIVIAN , SINGH SUMEET , JENSEN MORTEN S. , GOLDENBERG RONALD
Published: June 2024

Objective: To assess the cost-effectiveness of insulin icodec (IIco), the first once-weekly basal insulin, for the treatment of T2D from the Canadian public payer perspective using the Institute for Health Economics - Diabetes Cohort Model.

Three T2D patient groups were analyzed: insulin naïve (IN), basal insulin experienced (BExp), and basal-bolus insulin experienced (BBExp). Comparators included basal insulin analogs currently reimbursed in Canada: insulin glargine (IGlar) U100 & U300, insulin degludec (IDeg) U100 & U200, and insulin detemir (IDet). Comparative data were derived from IIco phase 3 ONWARDS trials and network meta-analyses. Three price points for IIco were considered: equal to originator IGlar U100, equal to IDeg, and 10% higher than IDeg. Outcomes were expressed as quality-adjusted life-years (QALYs), and cost-effectiveness as incremental cost utility ratios (ICUR [cost/QALY]).

Results: For the IN and BExp populations, IIco is either dominant or associated with an ICUR ≤ $28,824 in all analyses. For the BBExp population, IIco is either dominant or associated with an ICUR ≤ $45,433 in all analyses, except for the comparison versus IGlar U100 when IIco price is ≥ IDeg, and versus IGlar U300 when IIco price is = IDeg +10%.

At a willingness-to-pay threshold of $50,000/QALY gained, IIco is a cost-effective treatment option for T2D versus once daily basal insulin analogues currently reimbursed in Canada.

Disclosure

D.A. Garcia: Other Relationship; Novo Nordisk Canada Inc. G. Mau: Employee; Novo Nordisk Canada Inc. V. Vuong: Other Relationship; Novo Nordisk Canada Inc. S. Singh: Other Relationship; EVERSANA. M.S. Jensen: Employee; Novo Nordisk A/S. R. Goldenberg: Speaker's Bureau; Bayer Inc., Boehringer-Ingelheim. Advisory Panel; Eli Lilly and Company, HLS Therapeutics Inc., Novo Nordisk, Sanofi.
1061-P: Interdisciplinary Approach to Outpatient Diabetes Management with Pharmacist-Led Interventions
Authors: HAJOU CHRISTOPHER , ZHOU APRIL , WOODLEY JOHN , POLICEPATIL SEEMA M.
Published: June 2024

Introduction and Objective: Diabetes mellitus impacts 37.3 million individuals in the U.S., and Fresno, California, has a higher prevalence of 11.4% among adults compared to the state average of 10.5%. With 45 primary care physicians per 100,000 patients, ensuring consistent follow-up and monitoring is challenging. This study assesses the impact of pharmacist-led interventions on glycemic control in diabetes patients at a Federally Qualified Health Center (FQHC) in California's Central Valley.

Methods: This single-center cohort study assesses type I and type II diabetic patients in Primary Care and Endocrinology Clinics. Participants were grouped into standard care or standard care with pharmacist-led interventions. The primary endpoint measured average HbA1c change from baseline, and secondary endpoints included adjustments in anti-diabetic agents, attendance and referrals to multidisciplinary professionals. Average A1c change between groups was assessed using an unpaired t-test, and A1c change was analyzed with a generalized linear model.

Results: The intervention group showed a significant average HbA1c reduction of 1.96% in 12 weeks, exceeding the standard group's 0.88% reduction. Additionally, the intervention group received 77 more referrals to various guideline recommended specialties regarding diabetes care. Appointments typically occurred every 2-3 weeks for 12 weeks with significant improvements in HbA1c for those who attended at least 3 visits.

Conclusion: This study highlights how a collaborative approach to treating diabetes in an underserved patient population may lead to meaningful outcomes and allow physicians to spend more time treating acute issues necessitating less time spent on chronic disease. Implementing a proactive interprofessional model involving ambulatory care pharmacists may also enable precise identification and intervention for high-risk populations in need of meticulous diabetes monitoring and management.

Disclosure

C. Hajou: None. A. Zhou: None. J. Woodley: None. S.M. Policepatil: None.
1063-P: A Carbohydrate-Restricted Intervention and Continuous Remote Care Improves Health Outcomes across All Socioeconomic Groups at Two Years
Authors: VOLK BRITTANIE M. , ATHINARAYANAN SHAMINIE J. , ADAMS REBECCA N. , ROBERTS CAROLINE G.P. , ZOLLER ALISON R. , MCKENZIE AMY L.
Published: June 2024

Socioeconomic conditions of one’s community have been attributed to disparities in type 2 diabetes (T2D). Prior research has shown no difference between levels of socioeconomic disadvantage in glycemic outcomes after one year of a carbohydrate-restricted nutrition therapy delivered via continuous remote care (CRNT-CRC). This retrospective analysis explored the likelihood of meeting glycemic targets and changes in cardiometabolic markers over 2 years among people with T2D (n= 10859; 49% female; enrollment mean age 55, BMI 35.7, weight 231.8 lbs, HbA1c 7.7%) utilizing a CRNT-CRC by area deprivation index quintiles. Upon enrollment, patients in more disadvantaged areas had lower odds of meeting glycemic targets than those in the least disadvantaged areas. HbA1c significantly improved at 2 years in all groups, and the disparity was eliminated, where at least 80% in each achieved A1c<8% and at least 60% achieved A1c<7%. Weight, triglycerides, HDL-C, and liver enzymes also significantly improved across groups with no changes in total and LDL-C. This demonstrates that a CRNT-CRC can reduce health disparities of people living with T2D.

Disclosure

B.M. Volk: Employee; Virta Health Corp. Stock/Shareholder; Virta Health Corp. S.J. Athinarayanan: Employee; Virta Health Corp. R.N. Adams: Employee; Virta Health Corp. Stock/Shareholder; Virta Health Corp. C.G.P. Roberts: Other Relationship; Virta Health Corp. A.R. Zoller: Employee; Virta Health Corp. Stock/Shareholder; Virta Health Corp. A.L. McKenzie: Employee; Virta Health Corp. Stock/Shareholder; Virta Health Corp. Employee; Abbott.
1064-P: Order Set Design and "Nudges" to Change Care in Diabetes—Towards a Novel Pragmatic Clinical Trial Design
Authors: FLORY JAMES , ANCKER JESSICA , KIM SCOTT Y. , VICKERS ANDREW , AUSTRIA MIA , MARTIROSOVA HELEN , DIAZ RUBEN , HIESTAND AMY , KUPERMAN GILAD
Published: June 2024

Introduction and Objective: When there are multiple reasonable treatment approaches, electronic health record (EHR) design can ‘nudge’ providers to choose one: for example, a default drug selected on an order set may be more likely to be used. Our group has proposed use of such nudges in a pragmatic trial design called a Decision Architecture Randomization Trial (DART).

Methods: Retrospective analysis of how 3 modifications to an inpatient electronic health record ‘nudged’ prescribing practices: 1) introduction of an order set to facilitate use of nutritional + correction insulin (as opposed to sliding scale); 2) phased rollout of an order set change to encourage long-acting insulin use by adding a radio button to facilitate ordering; and 3) introduction of default diabetes orders pre-checked in order sets for patients undergoing colorectal surgery.

Results: The first nudge increased use of nutrition-correction insulin; the second nudge actually decreased rates of long-acting insulin use; and the third nudge increased glucose monitoring and insulin use for surgery patients (Figure).

Conclusion: EHR design offers opportunities to improve care and power innovative randomized trials. These findings support the feasibility of the DART clinical trial design, but research plans should take into account the potential for unpredictable nudge effects.

Disclosure

J. Flory: None. J. Ancker: Other Relationship; Ambry Genetics. S.Y. Kim: None. A. Vickers: None. M. Austria: None. H. Martirosova: None. R. Diaz: None. A. Hiestand: None. G. Kuperman: None.

Funding

Patient Centered Outcomes Research Institute (ME-2022C1-26378)
1069-P: Regular Insulin vs. NPH Insulin for Controlling Hyperglycemia in Hospitalized Patients on Continuous Enteral Tube Feeding
Authors: KALANGI SREEVASTAV T. , KENT DEVON , GARG RAJESH K.
Published: June 2024

Hyperglycemia in the hospital setting is associated with adverse clinical outcomes. Enteral tube feed (TF), required for many acutely ill patients, often worsens glycemic control. Different insulin regimens have been proposed to manage hyperglycemia during TF. However, no data are comparing one insulin regimen Vs another. This study was conducted to evaluate the differences in glycemic control between NPH insulin Vs regular insulin, two regimens frequently used for continuous TF at our hospital. Patients who received continuous TF between June 2022 and May 2023 were identified retrospectively. Baseline demographic and POC blood glucose (BG) data were obtained from the electronic databases while all other data were collected using manual chart review. All BG values and insulin data (scheduled and correctional injections) were collected for 7 days after the start of TF. Glucometerics were derived as per the Society of Hospital Medicine. The results of the study are shown in the adjoining Table 1. Mean daily BG levels were similar in the two groups but the number of days with hyperglycemia (>180mg/dl) was fewer in the regular insulin group. Average number of insulin injections were also fewer in the regular insulin group. The study shows that in hospitalized patients on continuous TF, regular insulin achieves better glycemic control with fewer injections as compared to NPH insulin.

Disclosure

S.T. Kalangi: None. D. Kent: None. R.K. Garg: None.
1074-P: Exploring Real-World Outcomes of Virtual Obesity Programs Integrated into Primary Care and Community Practices, With and Without AOM, in Patients with Type 2 Diabetes
Authors: RAMI BAILONY M.
Published: June 2024

Background: This study evaluates the effectiveness of virtual obesity programs in Type II Diabetes patients, with a focus on those treated with and without Anti-Obesity Medications (AOM) over 12 months. The integration of telehealth and remote patient monitoring in community clinics is examined as a method to enhance obesity management.

Methods: Participants were adults (≥18 years) with BMI ≥30 kg/m² and starting A1c >6.5, enrolled in an Enara affiliated digital obesity program before March 1st, 2022. Exclusions were made for pregnancy during the study. Patients were categorized based on AOM use, assessing weight change and cardiometabolic markers at 12 months.

Findings: The cohort of 134 patients (92 non-AOM, 42 AOM users) showed no significant difference in weight loss between groups (AOM: -11.15%; non-AOM: -11.19%). Key improvements included A1C (mean reduction: -0.93, p < 0.001), fasting glucose (-30.13, p < 0.001), HDL (+4.3, p < 0.001), and Triglycerides (-48.55, p < 0.001). Notably, AOM users had greater changes in A1C (-1.34 vs -0.61), glucose (-38.77 vs -23.01), HDL (+5.15 vs +3.58), and triglycerides (-54.63 vs -43.59).

Conclusion: Virtual obesity programs in community practices are effective, producing significant weight loss and improved cardiometabolic markers in patients, regardless of AOM use. The addition of AOM showed marginal extra weight loss benefit but notably better cardiometabolic improvements. This underscores the potential of digital health interventions in diabetes and obesity management in primary care and community settings.

Disclosure

M. Bailony: None.
109-OR: GIP Acutely Blunts Insulin- and GLP-1–Induced Muscle Microvascular Perfusion
Authors: LIU JIA , AYLOR KEVIN W. , LIU ZHENQI
Published: June 2024

Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone with extrapancreatic effects beyond glycemic control. Though vascular endothelium expresses GIP receptors, GIP’s vascular action has not been well defined. To assess the effect of GIP on muscle microvascular perfusion, adult male rats were fed either a chow or high-fat diet (HFD) for 2 weeks, fasted overnight, and randomly assigned to one of the following subgroups: 1) saline or GIP (4 pmol/kg/min) infusion for 120 min; 2) euglycemic hyperinsulinemic clamp (3 mU/kg/min) plus saline or GIP infusion for 120 min; 3) glucagon-like peptide 1 (GLP-1, 30 pmol/kg/min) plus saline or GIP infusion for 120 min. Compared to chow rats, HFD-fed rats exhibited increased visceral adiposity and higher fasting levels of serum insulin, GIP, and GLP-1. Hindlimb muscle microvascular perfusion was measured using contrast-enhanced ultrasound. Neither saline nor GIP infusion altered muscle microvascular perfusion in chow or HFD-fed rats. Insulin and GLP-1 infusion each significantly enhanced muscle microvascular perfusion in chow rats within 30 min and this effect lasted during the entire infusion period. GLP-1, but not insulin, also enhanced muscle microvascular perfusion in HFD-fed rats. Superimposing GIP infusion to either insulin or GLP-1 infusion completely abolished insulin-mediated microvascular perfusion in chow rats or GLP-1-induced microvascular perfusion in either chow- or HFD-fed rats, without altering serum levels of insulin or GLP-1. In cultured primary microvascular endothelial cells isolated from rat hindlimb muscle, GIP incubation for 24 h does-dependently increased ET-1 and inhibited GLP-1 (1 ng/mL)-induced nitric oxide (NO) production. We conclude that microvascular endothelium is a direct target of GIP action, and GIP modulates insulin’s and GLP-1’s vascular actions partly through the ET-1 and NO signaling pathways.

Disclosure

J. Liu: None. K.W. Aylor: None. Z. Liu: None.

Funding

National Institutes of Health (R01DK125330)
110-OR: Paternal Metabolism Modulates the Metabolome of Offspring during the Early Embryonic Period
Authors: FERRAZ-BANNITZ RAFAEL , OZTURK BERKCAN , EFTHYMIOU VISSARION , PATTI MARY-ELIZABETH
Published: June 2024

Introduction & Objective: Obesity in females and males of reproductive age may impact health of offspring. Data indicate that paternal metabolism can contribute to intergenerational disease risk, likely via epigenetic modification. This study investigated the impact of paternal obesity and hyperglycemia on metabolomes of pre-implantation embryos.

Methods: C57BL/6J male mice (6 weeks) were fed low fat diet (LFD; 10% calories from fat) or high fat diet (HFD; 60% from fat) ad lib to induce obesity. After 4 weeks, HFD-fed mice were separated, creating 4 groups: (1) continued LFD, (2) continued HFD, (3) HFD with SGLT2i canagliflozin (CANA, 25 mg/kg/day), or (4) HFD with 15-30% caloric restriction (CR) to achieve weight matched to HFD-CANA (n=16/group). HFD-CANA and HFD-CR had lower weight and glucose vs. HFD (P<0.05). At 16 weeks, males were bred with chow-fed females. After pregnancy confirmation, day 3.5 blastocysts were isolated, and pools from each of the 4 groups were analyzed using mass spectrometry; metabolomic data were analyzed using Metaboanalyst.

Results: Blastocysts derived from HFD males had reductions in acetyl-CoA, α-ketoglutarate (α-KG), and S-adenosyl-L-methionine (SAM) (P<0.05), while decarboxylated-SAM (dc-SAM) (P<0.05) was increased vs. LFD. This pattern was largely reversed in blastocysts derived from HFD-CANA males, with increased acetyl-CoA, α-KG and SAM and decreased dc-SAM (P<0.05) vs. HFD. Changes in HFD-CR shared some features with HFD-CANA, including reduced dc-SAM (P<0.05) and increased spermidine and spermine (P<0.05).

Conclusion: Paternal HFD and interventions to improve paternal metabolism can modulate the blastocyst metabolome. Top-ranking regulated metabolites are key constituents of one-carbon metabolism and cofactors for epigenetic regulation including DNA methylation and histone modification; thus, changes in the early-embryo metabolome could contribute to sustained differences in epigenetic control and offspring phenotypes.

Disclosure

R. Ferraz-Bannitz: None. B. Ozturk: None. V. Efthymiou: None. M. Patti: Research Support; Dexcom, Inc. Consultant; Hanmi Pharm. Co., Ltd., MBX Biosciences. Other Relationship; Fractyl Health, Inc. Consultant; AstraZeneca, Spruce Biosciences.
1110-P: Endocrinologists' Perceptions and Implementation of Hemoglobin A1c Targets for Adults with Type 1 Diabetes
Authors: KAUSHAL SANCHIT , HALPERIN ILANA , HAWKER GILLIAN A. , WEISMAN ALANNA
Published: June 2024

Introduction & Objective: ​​Most adults with T1D do not meet the HbA1c target of ≤7.0%. Endocrinologists’ perceptions may influence target attainment among patients, but have not been previously evaluated. We evaluated endocrinologists’ acceptability of the HbA1c target of ≤7.0%.

Methods: An online REDCap survey was sent to all 309 adult endocrinologists in Ontario. Acceptability of the HbA1c target of ≤7.0% was assessed using the Theoretical Framework of Acceptability (TFA), which evaluates interventions according to seven domains: affective attitude (feelings), burden (required effort), perceived effectiveness (likelihood of achieving purpose), ethicality (fit with personal values), intervention coherence (understanding), opportunity costs (potential negative effects), and self-efficacy (confidence). Agreement with statements representing each domain was rated by 5-point Likert scale. Acceptability was considered high if the proportion agreeing or strongly agreeing (A/SA) was >70% (or proportion disagreeing or strongly disagreeing was <30% for opportunity costs domain).

Results: 120 eligible endocrinologists (39%) completed the survey [69 (58%) female, 95 (82%) urban practice, and 53 (46%) aged 30-40 years]. TFA domains with high acceptability were intervention coherence (91% A/SA), ethicality (87% A/SA) and affective attitude (75% A/SA). Domains with low acceptability were self-efficacy (46% A/SA), perceived effectiveness (67% A/SA), burden (35.8% A/SA) and opportunity costs (33% disagree/strongly disagree). Responses suggest a disconnect whereby endocrinologists highly value the HbA1c target of ≤7.0% but perceive challenges in implementation.

Conclusion: Endocrinologists’ endorsement of the HbA1c target despite acknowledged barriers to implementation could negatively influence the physician-patient relationship. The potential benefits and risks of alternative patient-centered HbA1c targets requires further exploration.

Disclosure

S. Kaushal: None. I. Halperin: Advisory Panel; Dexcom, Inc. Speaker's Bureau; Dexcom, Inc., Novo Nordisk, Sanofi. Advisory Panel; Sanofi, Abbott. Speaker's Bureau; Tandem Diabetes Care, Inc. G.A. Hawker: None. A. Weisman: None.

Funding

Banting & Best Diabetes Centre Sunlife Financial New Investigator Award
1114-P: Management Outcomes by Provider Type in People with Diabetes Receiving Care at a Federally Qualified Health Center
Authors: SAN DIEGO EMILY ROSE N. , VINCENT LAUREN , ORENDAIN NATALIA , SPIERLING BAGSIC SAMANTHA R. , GORDON CHRIS , PHILIS-TSIMIKAS ATHENA
Published: June 2024

Introduction: Federally Qualified Health Centers (FQHCs) provide crucial health services to medically underserved populations. While primary care has been shown to improve outcomes in people with diabetes, comprehensive care from a multidisciplinary team of endocrinologists and other diabetes care specialists can optimize management outcomes.

Objectives: Examine differences in management outcomes by provider type using data from an FQHC offering a recently established Diabetes Specialty Care service to people with diabetes in San Diego, CA.

Methods: t-tests and linear regressions models.

Results: Of N = 35,092 adults with diabetes seen between 2017-2022, 7% were seen by an endocrinologist. Compared to patients only seen by a primary care provider (PCP), patients receiving diabetes care from an endocrinologist had higher A1C (M=8.9% vs. M=7.8%; p < 0.001) and lower systolic blood pressure (M=108 mmHg vs. M=114 mmHg; p < 0.001), and higher prescription rates of metformin (55% vs 52%, p < 0.01), insulin (25% vs 22%, p < 0.01), sulfonylureas and meglitinides (24% vs 22%, p = .005), and continuous glucose monitors (CGM) (54% vs 10%, p < .0001). After controlling for age, sex, race, education, and provider type, patients seen by an endocrinologist had 17% increased odds of metformin (p = .0005) and insulin (p = .0009) prescriptions, 14% increased odds of sulfonylurea and meglitinide prescriptions (p = .010), and 1699% increased odds of CGM (p = <.0001) compared to patients seen by a PCP. While not significant (p’s > .05), there were more patients seen by an endocrinologist who were prescribed SGLT2i (9% vs 8%), GLP-1 RA (11% vs 10%), and DPP-4i (15% vs 13%).

Conclusion: Higher prescription rates of diabetes medications and technology were observed in patients seen by an endocrinologist at an FQHC. These findings emphasize the importance of integrating endocrinologists and other diabetes specialty care services into FQHCs, where many vulnerable people with diabetes receive care.

Disclosure

E.N. San Diego: None. L. Vincent: None. N. Orendain: None. S.R. Spierling Bagsic: None. C. Gordon: None. A. Philis-Tsimikas: Advisory Panel; Dexcom, Inc., Lilly Diabetes, Novo Nordisk, Sanofi, Medtronic, Bayer Inc.

Funding

National Institutes of Health (K12 TR004410)National Institutes of Health (KL2 TR001112)
1119-P: Patient Directives to Improve Care for Gestational Diabetes Informed by Lived Experience—A Systematic Review of Qualitative Studies
Authors: JULIANNE FENG YUYANG , DENG ZHIDI , YEUNG ROSEANNE O. , NAGPAL TANIYA
Published: June 2024

Introduction & Objective: Gestational diabetes (GDM) can negatively impact the long-term metabolic health of patients and their infants, and mixed experiences with GDM care have been reported. The objective of this study was to identify themes and directives for improving quality of prenatal care from patients with lived experiences of GDM or their partners.

Methods: This study is a systematic review of qualitative studies and was registered on PROSPERO (CRD42023394014). A comprehensive search strategy was developed to identify qualitative studies including pregnant or postpartum patients with GDM, or their partners. A thematic synthesis approach, following meta-aggregation was applied to identify patient-directives for GDM care. The Critical Appraisal Skills Programme qualitative checklist was used to assess quality and risk of bias.

Results: Our search strategy was executed in six databases and a total of 80 studies were included. Patient-reported directives for improving care included: education on GDM and its management, personalized or tailored care, patient-centered care, digital or online adjuncts to care, and peer support. Additional directives for care arising from interpretation of patient-reported barriers and enablers of GDM management included providing support from healthcare professionals and facilitating support from partners and family, and acknowledging the stigma around GDM and patients’ motivations and concerns.

Conclusion: Many patient and environmental factors affect the experience of GDM. Our systematic review findings identify several patient-reported directives for care, and our interpretation of additional directions through barriers and enablers experienced by patients. These findings provide rich direction for improving antenatal GDM care from the patient perspective.

Disclosure

Y. Feng: None. Z. Deng: None. R.O. Yeung: Research Support; Abbott. Advisory Panel; Dexcom, Inc. T. Nagpal: None.
1121-P: Nurse-Led Diabetes Screening Protocol
Authors: LI CARRIE
Published: June 2024

Introduction and Objective: Approximately 8.7 million Americans live with undiagnosed diabetes, with one in five of them being unaware they have Type 2 diabetes, and an additional 97.6 million American adults have prediabetes, with disproportionate impacts on minority communities. Screening for prediabetes is essential for early identification and intervention in this population. The study objective was to determine if implementing a standardized diabetes risk screening protocol in an urban New York primary care facility increases screening and early intervention for Type 2 diabetes.

Methods: A quantitative descriptive design was implemented using a pre-and post-design and the Plan, Do, Study, Act Model. Participants were new adult clinic patients aged 35 to 70, exclusion criteria were: comprising pregnancy, screening declination, having Type 2 diabetes, cognitive impairment, or materials not available in the preferred language. The American Diabetes Association (ADA)/Centers for Disease Control and Prevention (CDC) Prediabetes Risk Test (PRT) was used for screening diabetes risk (independent variable). Dependent variables included nurse-led diabetes prevention education, nutritionist referrals, and ordering hemoglobin A1c (HbA1c). A three-month retrospective chart review included individuals identified using the ADA/CDC PRT for comparison. Data were analyzed using descriptive statistics and Pearson correlation.

Results: There were 31 eligible participants; the ADA/CDC Risk Test correctly identified 74% (n =31) with HbA1c levels indicating prediabetes or diabetes. Pearson correlation analysis showed moderate positive associations between the ADA/CDC PRT score and HbA1c levels (0.359, p<0.05), age (0.623, p<0.05), and BMI (0.350, p<0.05). Performance improved in patient diabetes prevention education, nutritionist referrals, and HbA1c screening.

Conclusion: Study results highlight the importance of improving screening strategies and early identification in diabetes prevention and management.

Disclosure

C. Li: None.
1136-P: Post–Metabolic Bariatric Surgery Protein Profiles—Navigating the Proteomic Landscape of Glycemic Regulation
Authors: JI CHOI YE , NGUYEN NHUNG , NARONGKIATIKHUN PHOOM , NASH KELLY , TOMMERDAHL KALIE L. , INGE THOMAS , RYDER JUSTIN R. , BJORNSTAD PETTER , PYLE LAURA
Published: June 2024

This study aims to investigate the effects of metabolic bariatric surgery (MBS) on plasma proteins linked to loss of glycemic control, insulin resistance and impaired insulin secretion in youth with type 2 diabetes (T2D).We measured 7604 Aptamers in 326 plasma samples from youth with obesity, both with and without T2D, in Teen-LABS cohort, examining pre- and post-MBS changes. This analysis focused on proteins previously identified in the TODAY cohort as predictors of glycemic control loss, defined by sustained HbA1c ≥8% or insulin dependence, in youth with T2D. A mixed model evaluated proteomic changes post-MBS, maintaining a 5% false discovery rate with reported q-values. In Teen-LABS, several proteins associated with a higher glycemic control loss risk in TODAY showed notable post-surgical downregulation. Key proteins such as Fructose-bisphosphate aldolase B, Liver carboxylesterase 1, Semaphorin-6A, Interleukin-18 receptor 1, Neurofascin, and Plexin-D1 were among those most affected (Figure). These proteins participate in metabolic and immunomodulatory pathways, potentially influencing glucose homeostasis. The study identified specific proteomic changes following MBS that potentially impact metabolic and immune function relevant to glycemic regulation. Recognizing these proteins as biomarkers could tailor post-MBS care, achieving long-term glycemic control.

Disclosure

Y. Choi: None. N. Nguyen: None. P. Narongkiatikhun: None. K. Nash: None. K.L. Tommerdahl: None. T. Inge: Consultant; Medtronic, Eli Lilly and Company, Brainstorm Therapeutics. Stock/Shareholder; Standard Bariatrics. Consultant; Teleflex. J.R. Ryder: None. P. Bjornstad: Consultant; AstraZeneca, Boehringer-Ingelheim. Advisory Panel; Lilly Diabetes, Novo Nordisk, Bayer Inc., Horizon Therapeutics plc. L. Pyle: None.

Funding

American Diabetes Association (7-23-ICTSTDY-08); NIH/NIDDK (U01 DK61242)
1138-P: Continuous Glucose Monitor (CGM)–Based Glycemic Variability Is Associated with Beta-Cell Function in Youth at Risk for Type 2 Diabetes
Authors: HARRISON CALEB , RODRIGUEZ GONZALEZ ADRIANA , HEWITT BRIANNA , ARSLANIAN SILVA A. , ELLEN VAJRAVELU MARY
Published: June 2024

Introduction & Objective: Screening for type 2 diabetes (T2D) is recommended for youth with risk factors, but current tests do not assess β-cell function, a predictor of disease progression. We evaluated whether CGM-based glycemic variability (GV) is associated with β-cell function in youth at risk for T2D.

Methods: Prospective observational study of pubertal youth ages 8-18y not on glucose-altering medications, with overweight/obesity (BMI ≥ 85th percentile) and at least one ADA-defined T2D risk factor or HbA1c 5.7-6.4%, fasting glucose (FG) ≥100 mg/dL, or 2-hour plasma glucose (2hG) on oral glucose tolerance test (OGTT) ≥140 mg/dL. Participants completed a 75g 2-hour OGTT, with every-30-minute glucose (G), insulin (I), and c-peptide (C). Blinded Dexcom G6 CGM was placed after OGTT and worn for 10 days. GV measures were calculated using the R package iglu, including coefficient of variation (CV), standard deviation (SD), mean amplitude of glycemic excursions (MAGE), and mean of daily difference (MODD). β-cell function was calculated using 2 versions of the OGTT-based oral disposition index (oDI): 1) I-oDI = 1/IF x ΔI30/ΔG30 and 2) C-oDI = 1/CF x ΔC30/ΔG30; Δ30 is the difference from 0 to 30 minutes. Log-transformation was performed for skewed distributions. Linear regression was used to evaluate the association between oDI outcomes and GV measures, adjusted for BMI Z-score.

Results: Of 39 youth enrolled, 33 (55% F; 30% Black, 58% White, 12% multiracial; mean ± SD 14.9±1.8y; BMI 36.8±6.6 kg/m2; HbA1c 5.6±3.2%; FG 84.8±8.2 mg/dL; 2hG 116.2±28.9 mg/dL) had evaluable CGM data. MAGE and MODD were inversely associated with I-oDI (p=0.04, p=0.02) and C-oDI (p=0.009, p=0.016). CV (p=0.047) and SD (p=0.03) were inversely associated with C-oDI but not associated with I-oDI.

Conclusion: Based on its demonstrated association with β-cell function, CGM-based GV offers a novel approach to evaluating T2D risk in youth with overweight/obesity and other risk factors.

Disclosure

C. Harrison: None. A. Rodriguez Gonzalez: None. B. Hewitt: None. S.A. Arslanian: Consultant; AstraZeneca, Eli Lilly and Company, Nestlé Health Science, Avoro Capital Advisor LLC. Research Support; Eli Lilly and Company, Novo Nordisk. Advisory Panel; Novo Nordisk. M. Vajravelu: None.

Funding

Endocrine Fellows Foundation; Tanner Scholar Advancing Equity Award
1139-P: Discovery of a Potent, Orally Efficacious Small Molecule Agonist of Glucagon-Like Peptide-1 (GLP-1) Receptor
Authors: BEARSS DAVID J. , LIN CHENYU , MEDLEY KYLE , VANKAYALAPATI HARIPRASAD
Published: June 2024

Introduction: Given its physiological roles, GLP-1 agonists are considered a class of drugs used in the treatment of type 2 diabetes and obesity. These agents mimic 7-36 amide Semaglutide, increase insulin release, decrease glucagon secretion, and a slowing of gastric emptying but are injectables, week half-life, and cold chain storage limit their utility. Several small molecule agonists of the GLP-1 receptor have been investigated as potential alternatives to peptide-based GLP-1 agonists like Danuglipron, and Orforglipron. Here we present the discovery of the MLX-7005 series exhibited on target-specific GLP-1 agonist activity in its binding and cellular studies.

Methods: Tag-Lite GLP-1 receptor binding assay. Ca2+ mobilization in Min6-c4 cells. cAMP in PSC-HEK293 Cell Line Expressing GLP-1R. cAMP β-Cell Line 1.2B4. The cAMP Gs dynamic and a LANCE Ultra cAMP kit. GLP-1 agonist in db/db and DIO models of T2D and obesity.

Results: Small molecule GLP-1 agonists we discovered are orally available, stable, lower manufacturing costs than peptide-based drugs. We disclose MLX-7005 and its analogs, exhibiting potent activity in vitro MIN6 Ca2+ assay dose-dependently with an EC50 of 241 nM and reference Danuglipron, GLP-1 peptide are 219 nM and 70 nM. MLX-7005 additional in vitro and in vivo pharmacology profile results consistent with its on-target potency. MLX-7005 has a high binding affinity to human GLP-1R. MLX-7005 strongly activated the GLP-1R cAMP pathway without inducing measurable β-arrestin recruitment signaling. The insulin secretion effect of MLX-7005 was evaluated in a functional human pancreatic beta cell line, in which MLX-7005 showed dose-dependent induction of insulin secretion.

Conclusion: In conclusion, MLX-7005 is a highly potent, orally available, GLP-1 agonist. pre-clinical in vivo DIO, db/db rodent models studies are underway along with safety, and tolerability to further evaluation as a potential therapy for T2DM and obesity will be presented.

Disclosure

D.J. Bearss: Employee; BioLexis Therapeutics, Halia Therapeutics. C. Lin: None. K. Medley: None. H. Vankayalapati: Board Member; Biolexis Therapeutics, Inc. Stock/Shareholder; Arrien Pharmaceuticals. Board Member; Oncolexis Therapeutics, Inc.

Funding

Biolexis Therapeutics, Inc.
1143-P: Early Aged Mice Stay Metabolically Stable with High-Fat Diet
Authors: BAHMAN FATEMAH , KOCHUMON SHIHAB P. , ALRASHED FATEMA , ABUKHALAF NERMEEN A. , THOMAS REEBY S. , ALMULLA FAHD , AHMAD RASHEED
Published: June 2024

The relationship between obesity, aging, and the risk of metabolic diseases is a crucial area of study. This research focuses on understanding how aging influences the body's response to high-fat diet (HFD) consumption and its subsequent impact on metabolic health. Our hypothesis posits that aging significantly affects how the body adapts to HFD intake, potentially improving metabolic outcomes. To explore this, we conducted a study using mice of varying ages (4, 6, 8, and 10 weeks old, with 6-8 mice per age group). Over a period of 16 weeks, these mice were fed either a standard chow diet or an HFD. Our findings indicate that older mice (aged) demonstrate a more rapid weight gain in response to HFD compared to younger (early-aged) mice. Interestingly, younger mice appeared to be protected against HFD-induced obesity. Additionally, adipose tissues from younger mice showed fewer inflammatory markers. We also investigated the characteristics of non-alcoholic fatty liver disease (NAFLD), including fatty deposition, lesions, atypical yellowish coloration, and enlargement. These were notably absent in younger mice consuming HFD. Further analysis involved staining liver sections with hematoxylin and eosin (H&E) and Oil Red O to assess lipid accumulation. Results revealed a higher presence of lipid vacuoles in the livers of older mice compared to their younger counterparts on an HFD. Consistent with increased adiposity, fat accumulation in the liver, and inflammation, older mice exhibited impaired glucose tolerance and reduced insulin sensitivity compared to younger mice fed the same diet.

In conclusion, our study unveils a significant link between the body's adaptations during early aging and its metabolic responses to HFD. These findings suggest potential avenues for preventing obesity and its associated complications, particularly those exacerbated by overnutrition. This research contributes valuable insights to the field, highlighting the importance of age as a factor in dietary and metabolic health.

Disclosure

F. Bahman: None. S.P. Kochumon: None. F. Alrashed: None. N.A. Abukhalaf: None. R.S. Thomas: None. F. Almulla: None. R. Ahmad: None.

Funding

Kuwait Foundation for the Advancement of Sciences (KFAS)
1148-P: Trajectories of Abnormalities in Metabolic Parameters in Japanese Adolescents and Young Adults
Authors: IKEDA IZUMI , FUJIHARA KAZUYA , SHIOZAKI HARUKA , MORIKAWA SAKIKO Y. , HORIKAWA CHIKA , TAKEDA YASUNAGA , ISHIGURO HAJIME , YAMADA TAKAHO , KODAMA SATORU , OGAWA YOHEI , SONE HIROHITO
Published: June 2024

Childhood obesity mostly transitions into adulthood and leads to non-communicable diseases such as type 2 diabetes and metabolic syndrome. We aimed to examine individual-level transitions in metabolic parameters during adolescence and young adulthood. We analyzed metabolic parameters in 523 participants (311 males) who underwent health examinations at the ages of 14 y (8th grade) and 20 y. Weight status was assessed by the International Obesity Task Force at 14 y and by BMI (thinness: <18.5; normal: 18.5-24.9; obesity: ≥25.0) at 20 y. HbA1c ≥5.7% was defined as high. Clustered metabolic risk score (CMR) was calculated by summing the sex-age specific Z-scores of each metabolic factor (mean arterial pressure, non-HDLC, and HbA1c) with ≥1 SD defined as high. Among participants who were obese at 14 y, 56% of males and 29% of females remained obese at 20 y. In both sexes, 30-50% had high HbA1c and 30-50% had high CMR as tracked from adolescence to adulthood (table). Furthermore, the high CMR of obese females increased markedly from about 20% at 14 y to 50% at 20 y. In addition, 60% of females who were obese at both 14 y and 20 y had high HbA1c at 20 y. Results suggested the importance of lifestyle interventions from childhood, as about half of the high metabolic parameters observed in adolescents were tracked into adulthood, and obesity complications, which were rarely shown at 14 y, appeared in many at age 20 y.

Disclosure

I. Ikeda: None. K. Fujihara: None. H. Shiozaki: None. S.Y. Morikawa: None. C. Horikawa: None. Y. Takeda: None. H. Ishiguro: None. T. Yamada: None. S. Kodama: None. Y. Ogawa: None. H. Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Eisai Inc., Sumitomo Dainippon Pharma Co., Ltd.
1154-P: Diabetes-Specific Distress Persists over Time in Adolescents with Type 2 Diabetes—A Longitudinal Study
Authors: LUU YASMIN , SHAH MARK , OXLAD MELISSA , CURRAN JACQUELINE A. , SPAJIC DANA , PENA ALEXIA S.
Published: June 2024

Introduction: Diabetes-specific distress (DD) is the least evaluated psychological comorbidity among adolescents with type 2 diabetes (T2D). We aimed to assess longitudinally DD levels in adolescents with T2D.

Methods: Adolescents with T2D completed the Diabetes Distress Scale (DDS), World Health Organisation-5 Wellbeing Index (WHO-5), and Patient Health Questionnaire-2 (PHQ-2) at baseline, 3 and 6 months to measure DD levels, general emotional wellbeing, and depressive symptoms, respectively. A linear regression model was used to estimate differences in means and 95% confidence intervals with Generalised Estimating Equations.

Results: Thirty-seven adolescents with T2D participated (24 females, 34 from non-Indigenous background, mean+SD age 15.9±2.2 years, mean diabetes duration of 2.2±1.6 years, median [IQR] HbA1c 6.7[5.9-8.9]%. Adolescents with T2D have persistent DD (highest levels in the emotional burden and regimen-related domains), high depressive symptoms and deterioration of emotional wellbeing over six months (See Table 1).

Conclusion: DD and depressive symptoms persisted over time, whilst emotional wellbeing deteriorated, approaching suboptimal levels in adolescents with T2D. Regular screening and management of DD (especially emotional burden and regimen-related distress) and emotional wellbeing should occur during follow-up of adolescents with T2D.

Disclosure

Y. Luu: None. M. Shah: None. M. Oxlad: Research Support; Ferring Pharmaceuticals Australia. J.A. Curran: Other Relationship; Novo Nordisk, Eli Lilly and Company. D. Spajic: None. A.S. Pena: None.
1165-P: Untangling the Interactions of Glycemic Control and Obesity on Hypothalamic Gliosis in Youth with Type 1 Diabetes
Authors: HUANG ALYSSA , MELHORN SUSAN J. , EITEL KELSEY B. , PIHOKER CATHERINE , SCHUR ELLEN
Published: June 2024

Introduction and Objective: Adolescents and young adults (AYA) with T1D experience high rates of disordered eating behavior (DEB), and obesity, which are linked to worse health outcomes including glycemic control. Inflammatory changes in the brain such as gliosis specifically in the mediobasal hypothalamus (MBH) -a critical area for weight regulation- may contribute. Adults with T2D have greater MBH gliosis compared to those with impaired glucose tolerance or normoglycemia, independent of adiposity. We investigated the presence of MBH gliosis in AYA with T1D and assessed its association with adiposity and glycemic control.

Methods: We recruited females aged 15-25 years; 24 with T1D and 5 healthy controls. AYA with T1D had stable insulin regimens and had diabetes duration for at least 1 year. Those with history of serious chronic conditions, eating disorder, extreme fluctuations in weight or glycemic control were excluded. Participants completed fasting labs, DEB surveys, DEXA scan and multi-echo brain MRI. T2 relaxation time (a measure for gliosis) was quantified in the MBH and control regions: amygdala (AMY) and putamen (PUT). Linear regression tested if T2 relaxation time in brain regions of interest were associated with body mass index (BMI) and HbA1c.

Results: For those with T1D, diabetes duration was 8.9±2.8 y and mean HbA1c was 7.9 ±1.7% (range 5.7 to 11.8%). 10 were lean and 14 had overweight or obesity based on BMI. There was a positive trend between MBH T2 relaxation time and BMI but not for other brain regions (MBH p=0.12; R = 0.28; AMY p=0.26, R=0.22; PUT p=0.30, R=0.2). There was no association between HbA1c and T2 relaxation in all brain regions (MBH p=0.88, R=0.3; AMY p=0.79, R= 0.05; PUT p=0.93, R=0.01).

Conclusion: We observed a trend that suggests that BMI but not HbA1c may be associated with MBH gliosis in AYA with T1D. Although glycemic control is associated with MBH gliosis in adults with T2D or insulin resistance, this relationship may not be present in AYA with T1D.

Disclosure

A. Huang: None. S.J. Melhorn: None. K.B. Eitel: None. C. Pihoker: None. E. Schur: Consultant; Amgen Inc.

Funding

UW Diabetes Research Center Pilot and Feasibility Award (P30DK017047-45S2)
1170-P: Comparative Measurement Utility of Diabetes Distress (DD) Surveys in Adolescents and Young Adults (AYA) with Type 1 Diabetes (T1D)
Authors: WENTZELL KATHERINE , ALAMARIE SELMA A. , HERNDON CHRISTOPHER , TINSLEY LIANE J. , LAFFEL LORI M. , HOOD KOREY K.
Published: June 2024

Introduction: The AYA developmental period is marked by higher A1c values and higher levels of DD. To better understand how to best measure DD in AYAs, we compared 3 diabetes-related emotional distress scales.

Methods: In a multi-site project, we collected sociodemographic, clinical, and DD measures in a cross-sectional sample of 14-25 year olds with T1D ≥1 year and eligibility A1c 7-13%. DD measures included the 2 most widely used, PAID-Peds and DDS, and our new measure, PAID-EA (Table). We assessed internal consistency, reliability, and construct validity. Pearson correlations, t-tests, and ANOVAs determined the strength and direction of relationships.

Results: In 191 participants, mean (±SD) age was 19.8±3.4, T1D duration 11.4±5.4, and A1c 8.0±1.2%; 98% used CGM, 86% used an insulin pump. In this sample, Cronbach alpha was acceptable for all measures, showing internal consistency. Evidence of construct validity was observed as measures were all correlated. Females reported more DD than males on all measures. DD did not differ by health insurance status. Young adults (19-25) reported more DD compared with teens (14-18) on all measures, but the PAID-EA and DDS were the only scales positively correlated with A1c in 19-25 age group.

Conclusion: PAID-Peds, PAID-EA, and DDS performed well in AYAs. The PAID-EA and DDS were more closely tied to A1c in young adults, and thus may be preferable.

Disclosure

K. Wentzell: None. S.A. Alamarie: None. C. Herndon: None. L.J. Tinsley: None. L.M. Laffel: Consultant; Dexcom, Inc. Advisory Panel; Medscape, Medtronic, Vertex Pharmaceuticals Incorporated. Consultant; Novo Nordisk. Advisory Panel; Lilly Diabetes, Provention Bio, Inc., Sanofi-Aventis U.S., Janssen Pharmaceuticals, Inc., MannKind Corporation. K.K. Hood: Consultant; Cecelia Health, Sanofi.

Funding

NIH (R01DK129479); Mary K. Iacocca Foundation
1172-P: Evaluating Factors that Predict Time Spent in Automated Mode (AM) among Youth with Type 1 Diabetes Using AID
Authors: GRUNDMAN JODY , LONGENDYKE RACHEL L. , PERKINS AMANDA G. , MONAGHAN MAUREEN , STREISAND RANDI , MAJIDI SHIDEH
Published: June 2024

Introduction: Demographic and medical factors influencing AID AM use were evaluated to better understand inequities in glycemic outcomes among youth with T1D.

Methods: Retrospective chart review was conducted for 74 youth with T1D who started AID between 12/1/2022 to 5/31/2023 to examine time spent in AM 0-3 and 3-6 months after AID initiation. Mixed effects models assessed age, T1D duration, sex, race/ethnicity, insurance, AID system and input, and CGM metrics’ impact on time spent in AM. X2 and Mann Whitney U tests assessed for differences between youth with optimal (>90%) and suboptimal (<90%) time spent in AM.

Results: Demographic and glycemic characteristics are described in Table 1. Race/ethnicity differed significantly among optimal and suboptimal AID use with NHB youth more likely to have suboptimal use (3mo p<.05, 6mo<0.001). Youth with optimal AID use had better glycemic outcomes at 3 and 6 months versus suboptimal use. Mixed effects models demonstrated that AID system type (p<.05) was predictive of optimal AM use at 3 months. Younger age at pump start, longer duration of T1D, more boluses/day, and higher % CGM wear time (all p’s <.05) were associated with higher AID use at 6 months.

Conclusions: Youth with optimal AID use had significantly better glycemic outcomes. Efforts to address individual level AID use and barriers can help to promote optimal AM use and improve health outcomes for all youth living with T1D.

Disclosure

J. Grundman: Research Support; Dexcom, Inc. R.L. Longendyke: None. A.G. Perkins: Research Support; Tandem Diabetes Care, Inc., Dexcom, Inc. M. Monaghan: Employee; National Institute of Diabetes and Digestive and Kidney Diseases. R. Streisand: None. S. Majidi: Other Relationship; Sanofi.