bluuebunny/crossref_metadata_2025 huggingface dataset:
668-P: Exploring Attitudes toward Autoantibody Screening in People Living with T1D, Caregivers, and First-Degree Relatives
Authors: PETER MEGAN , CHAPMAN KATHERINE S.M. , DUNNE JESSICA L. , KELLY CAITLIN S. , WOLF WENDY
Published: June 2023

Background: T1D autoantibodies can be detected months to years before disease onset, but few people undergo screening. We explored attitudes toward autoantibody screening in people with T1D and caregivers and relatives of people with T1D.

Methods: Participants were recruited from the T1D Exchange Registry or referred by an Online Registry participant. Guided by the Health Belief Model, we conducted 4 focus groups with 26 participants (11 adults with T1D with a child without T1D; 8 caregivers to a child with T1D and a child without T1D; 7 biological siblings to a person with T1D). Transcripts were analyzed using NVivo.

Results: Responses are summarized in Table 1. Most participants held positive attitudes toward screening. The most common perceived benefit was to obtain knowledge; the anticipated emotional burden of a positive screen was the most frequently reported barrier. Anxiety and relief were emotions associated with a positive and negative screen, respectively. Participants desired information about antibody screening and its interpretation and accuracy. A healthcare providers’ recommendation might prompt the decision to screen.

Conclusions: Participants expressed positive attitudes and perceived benefits of autoantibody screening but also reported barriers to screening, particularly the emotional burden of a positive result.

Disclosure

M.Peter: None. K.S.M.Chapman: None. J.L.Dunne: Employee; Janssen Research & Development, LLC. C.S.Kelly: None. W.Wolf: None.
669-P: Factor Analysis of the Diabetes-Specific Risk-Taking Inventory
Authors: MONZON ALEXANDRA , PIERCE JESSICA , WASSERMAN RACHEL M.
Published: June 2023

Introduction: Adolescence is marked by increased risk-taking behaviors and challenges engaging in optimal type 1 diabetes (T1D) treatment. We developed the Diabetes-Specific Risk-Taking Inventory (DSRI) to assess risky adolescent T1D self-management behaviors. In the current study, we conducted confirmatory factor analyses (CFAs) for the DSRI and examined model fit.

Methods: We surveyed a national sample of 224 adolescents (age 15-18 years; M age 16.9 ± 1.1 years; 49% female, 11% identified as Black, Indigenous, or Persons of Color; 76.8% used insulin pumps; M HbA1c= 8.5% ± 1.3); from the T1D Exchange registry in a cross-sectional design. Participants completed the DSRI, and we collected the most recent HbA1c value from registry data. We performed CFAs in R using the Lavaan package to evaluate three models: 1) a one-factor structure, 2) a two-factor structure reflecting items higher and lower in risk (item level of risk assessed by surveying diabetes health care providers), and 3) another two-factor structure reflecting items that associate with higher HbA1c (>9%) and lower HbA1c (<9%).

Results: The DSRI measure contains 31 items; however, one item was removed from CFA analyses due to a nonsignificant factor loading value. The one-factor CFA model demonstrated poor fit χ2(399, n=224) =1714.94, p<0.001, RMSEA=0.12, CFI=0.52, TLI=0.49, as did the two-factor structure differentiating between higher and lower HbA1c χ2(399, n=224) =1121.02, p<0.001, RMSEA=0.090, CFI=0.72, TLI=0.69. The two-factor CFA reflecting higher and lower risk items model demonstrated improved fit χ2(399, n=224) =896.19, p<0.001, RMSEA=0.085, CFI=0.77, TLI=0.75.

Conclusions: The DSRI is a valuable self-report measure that providers may use to screen for high-risk behaviors not routinely assessed in T1D clinical care. The results suggest that the high-risk vs. low-risk two-factor model is slightly better fitting than the one-factor model; however, additional factor structures should be assessed to identify a more robust structural model.

Disclosure

A.Monzon: None. J.Pierce: None. R.M.Wasserman: None.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust (2016PG-T1D053); National Institutes of Diabetes and Digestive and Kidney Diseases (1K12DK097696)
670-P: Improving Diabetes Distress in Emerging Adults with Type 1 Diabetes—The AHEAD Program
Authors: MALIK FAISAL , HIRSCH IRL B. , PIHOKER CATHERINE , ROBERTS ALISSA J. , TAPLIN CRAIG , LOWRY SARAH J. , YI-FRAZIER JOYCE P. , MOSS ASHLEY , HUANG ALYSSA , EHRHARDT NICOLE M. , HOCH KATRINA , WEAVER KATHRYN
Published: June 2023

Background: The Achieving Health in Emerging Adults with Diabetes (AHEAD) Program is designed to meet the health care transition and psychosocial needs of emerging adults (EA) with type 1 diabetes (T1D).

Objective: To evaluate the impact of the AHEAD Program on diabetes distress (DD) in EA with T1D.

Methods: DD was evaluated using the Problem Areas in Diabetes-Teen survey (PAID-T). Mixed-effects linear regression with a random effect for individual to account for repeated measures was used to evaluate change in DD over time. Models were adjusted for age, race, ethnicity, technology use, and insurance. We assessed whether improvement varied by age, technology use, insurance, or baseline (BL) elevated DD (PAID-T≥44).

Results: Sample included 489 EA with T1D (BL visit: mean age 20.3 years, 52% male, 75% Non-Hispanic White, 26% public insurance, 59% continuous glucose monitor use, 58% insulin pump use, 19% elevated DD). Overall mean PAID-T scores decreased from 31.4 at BL (95% CI: 30.1, 32.8) by 4.6 points (95% CI: -7.4, -1.7; p=0.001) at 2 years (Figure). By 2 years, mean PAID-T scores for patients with elevated DD at BL decreased by 16.2 points (95% CI: -22.9, -9.5; p<0.001) compared to a 3.3 point (95% CI: -6.2, -0.5; p=0.02) decrease in those without elevated DD at BL. PAID-T improvement did not vary by age, technology use, or insurance (all p>0.05).

Conclusion: The AHEAD Program offers a promising approach to reduce DD in EA with T1D.

Disclosure

F.Malik: None. N.M.Ehrhardt: Advisory Panel; Novo Nordisk, Dexcom, Inc., Consultant; Nestlé Health Science. K.Hoch: None. K.Weaver: None. I.B.Hirsch: Consultant; Abbott Diabetes, Lifecare, Inc., Hagar, Research Support; Beta Bionics, Inc., Insulet Corporation, Dexcom, Inc. C.Pihoker: None. A.J.Roberts: None. C.Taplin: Stock/Shareholder; Quest Diagnostics. S.J.Lowry: None. J.P.Yi-frazier: None. A.Moss: Other Relationship; American Diabetes Association. A.Huang: None.

Funding

Forest Foundation; Sequoia Foundation
673-P: Youth with Type 1 Diabetes and Elevated A1C during the Coronavirus Disease-2019 (COVID-19) Pandemic—Examination of Family, Caregiver, and Medical Team Factors
Authors: WAGNER DAVID V. , PERRY MEGAN , CLEMENTS MARK A. , WONG JENISE C. , NARANJO DIANA , REED ALISON , JENISCH CELESTE , CRUZ CRISTIAN , MITCHELL SUSANNE , YGLECIAS LOREN , FLORES GARCIA JAQUELIN , TORRES SANCHEZ ALEJANDRA , BONILLA OSPINA ANDREA , RAYMOND JENNIFER , HARRIS MICHAEL A.
Published: June 2023

Introduction: A subset of youth with T1D experience avoidable health problems, but it is unclear how specific social factors relate to these problems, particularly during the COVID-19 pandemic. We examined how systemic factors (caregiver, family, medical team) were related to medical outcomes in youth with elevated A1c from five academic medical centers during the pandemic.

Methods: Youth 12-17 yrs with 1) T1D for ≥1 yr and 2) A1c≥10% in the past year were enrolled. Caregivers and youth completed measures of family conflict (Diabetes Family Conflict Scale-R); parent practices, stress, and health literacy (Alabama Parenting Questionnaire, Stress Index for Parents of Adolescents, BRIEF Health Literacy Scale); youth strengths and social support (Diabetes Strengths and Resilience, PROMIS); and family-medical team relationship (Quality of Healthcare Relationship) with EHR review including baseline A1c and acute complications (e.g., ED visits).

Results: Participants were 157 youth with mean age 14.6 ± 1.6 years and mean A1c 11.0% ± 1.9%. 51% self-identified as Non-Hispanic White. Caregiver, family, and relational factors were significantly (p<.05) related to frequency of complications and A1c, with higher family conflict associated with higher A1c (r=.23) and more ED visits (r=.18). For caregivers, low health literacy (r=.17), inconsistent discipline practices (r=.20), and high parental stress related to low adolescent achievement (r=.26), were significantly (p<.05) associated with acute complications, as was youth report of low social support (r=-.20, p<.01). Positive family-medical team relationship was strongly related to lower A1c (r=-.30, p<.01).

Discussion: Given these findings, screening and intervention efforts should emphasize targeting multiple systems and relationships with this population of youth, potentially with increased focus on the family-medical team relationship.

Disclosure

D.V.Wagner: None. L.Yglecias: None. J.Flores garcia: None. A.Torres sanchez: None. A.Bonilla ospina: None. J.Raymond: None. M.A.Harris: None. M.Perry: None. M.A.Clements: Consultant; Glooko, Inc., Research Support; Dexcom, Inc., Abbott Diabetes. J.C.Wong: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc. D.Naranjo: None. A.Reed: None. C.Jenisch: None. C.Cruz: None. S.Mitchell: None.

Funding

JDRF
675-P: Coparenting Cooperation and Conflict Predict Parent Depressive Symptoms 1.5 Years after Young Child T1D Diagnosis
Authors: KANG LEYI , WANG CHRISTINE H. , HILLIARD MARISA E. , TULLY CARRIE , MONAGHAN MAUREEN , STREISAND RANDI
Published: June 2023

Background: Managing T1D in a newly diagnosed young child significantly impacts family dynamics and is linked with elevated parental depressive symptoms. We examined the relationship among diabetes-related co-parenting cooperation and conflict soon after diagnosis with parent depressive symptoms 1 and 1.5 years later.

Method: Participants were 157 primary caregivers (91.7% female, 76.4% married, 62.2% non-Hispanic White) of young children age 1-6 years (Mage=4.41.7 years; 54.8% female, 61.5% non-Hispanic White) in a behavioral intervention trial after child T1D diagnosis (M=29 days). Parents self-reported on Cooperation and Conflict subscales of the Diabetes-Specific Co-parenting Questionnaire (DCQ) and the Center for Epidemiological Studies Depression Scale (CES-D; ≥16=clinical elevation). Multiple logistic regressions were used with elevated depression score as outcome. Subjective socioeconomic status (SSES) and treatment condition were included as covariates.

Results: Higher co-parenting conflict at baseline was associated with a 3.70 (OR=3.70, 95% CI=(1.68, 8.18) and 2.36 (OR=2.36, 95% CI=(1.13, 4.91)) higher odds of clinically elevated CES-D score risk at 1 and 1.5 years post-diagnosis, respectively. Higher co-parenting cooperation at baseline marginally reduced elevated CES-D odds by 0.58 (OR=0.58, 95% CI=(0.31, 1.10)) at 1.5 (but not 1) years post-diagnosis; higher SSES at baseline reduced depression odds by 0.97 (OR=0.97, 95% CI=(0.96, 1.00) at 1.5 (but not 1) years post-diagnosis.

Discussion: Increased parental disagreements following T1D diagnosis may predict higher burden of managing T1D in a young child over time and possibly contribute to later depressive symptoms. Parental care strategies and interventions at T1D diagnosis that enhance supportive cooperation and communication among caregivers may help support parent psychosocial functioning over time.

Disclosure

L.Kang: None. C.H.Wang: None. M.E.Hilliard: None. C.Tully: None. M.Monaghan: Employee; National Institute of Diabetes and Digestive and Kidney Diseases, Research Support; American Diabetes Association. R.Streisand: None.

Funding

National Institutes of Health (1R01DK102561-01A1)
677-P: Exploring the Impact of CGM on Perceived Control of Non-Intensive Insulin Treated Type 2 Diabetes—“I liked keeping my line with as few spikes as possible”
Authors: CRAWFORD MARGARET A. , HICKS CHRISTIAN , GENGE PAUL , GREENAWALD KENNETH , TRESSLER MICHELLE , CHERÑAVVSKY DANIEL R. , SINGH HARSIMRAN
Published: June 2023

Background and Aims: Progression of type 2 diabetes (T2D) demands complex treatment modalities, which may impair patients’ confidence and psychological health. Technologies allowing improved understanding of the dynamic disease process may improve engagement with therapy.

Methods: As part of a larger observational study, we previously reported findings highlighting the impact of using Dexcom G6 real-time CGM (rtCGM) with T2D adults (diverse therapies) and prediabetes over a 12-week period. We now explored qualitative data generated from a subsample of T2D participants (N=38) on non-intensive insulin therapy (Basal only=24%, No insulin=76%). Participants answered open-ended questions about their experiences using CGM including self-reported learnings and changes in behavior. Primary themes from qualitative data were derived using content analysis and confirmed with inter-coder reliability.

Results: Overall, most participants (>90%) ended the study with high levels of perceived control (PC) of their diabetes. For further analysis, participants’ change in PC at study end were plotted based on low, medium, or high PC before CGM use. Interesting group differences emerged wherein fewer participants reporting medium PC at baseline reported high PC at study end (vs. others with low and high baseline PC). Qualitative themes around perceived illness severity, depressive symptoms, and self-efficacy along with differences in demographics and glycemic metrics helped translate these meaningful findings.

Conclusions: rtCGM use provided valuable improvements in participants’ engagement and understanding of their diabetes with potential for long-term clinical benefits. Future studies exploring relationships between perceived control of diabetes and progression of T2D may indicate potential areas for improved engagement with diabetes technology.

Disclosure

M.A.Crawford: Employee; Dexcom, Inc. C.Hicks: Employee; Dexcom, Inc. P.Genge: Employee; Dexcom, Inc. K.Greenawald: Employee; Dexcom, Inc. M.Tressler: Employee; Dexcom, Inc. D.R.Cherñavvsky: None. H.Singh: Employee; Tandem Diabetes Care, Inc., Dexcom, Inc.

Funding

Dexcom, Inc.
678-P: Impact of COVID-19 on Black Youth with T1D and Their Parents
Authors: HOWARD KELSEY R. , FELDMAN MARISSA , CARCONE APRIL I. , GARZA KIMBERLY P. , EVANS MEREDYTH A. , WEISSBERG-BENCHELL JILL , ELLIS DEBORAH A.
Published: June 2023

Purpose: The COVID-19 pandemic has contributed to financial and psychosocial stressors, particularly among individuals from minoritized groups. The goal of the current study was to provide a description of the financial and emotional burdens experienced by Black youth with T1D and their parents during the pandemic.

Method: Data for the present study were obtained from a subset of families participating in a clinical trial providing an eHealth intervention to parents of Black adolescents with T1D. Adolescents (n = 63), young adults (n = 9), and their parents (n = 65) completed questionnaires on their experiences with emotional, social, and financial stressors during the pandemic.

Results: Parents reported changes in occupational and financial stress during the pandemic. Nearly half (45.2%) reported reduced work hours, involuntary job loss, or voluntary job loss to care for a family member. A third (31.2%) reported significant changes in household income, with 10.9% of parents indicating that they were unable to meet their basic needs, such as paying bills. Many (50%) parents reported that their child missed a diabetes-related appointment; of these, 59.4% reported missing an appointment for a pandemic-related reason (e.g. clinic was closed due to COVID; family canceled appointment to avoid being around other people). Adolescents and young adults reported a variety of emotional responses to the pandemic, including moderate to extreme stress (46%), anger (28%), and anxiety (36%).

Discussion: Families of Black youth with T1D experienced financial and emotional burden during the pandemic. Many also experienced disruptions in their diabetes care, as evidenced by missed appointments. Future studies should explore the relationship between these burdens and subsequent diabetes management.

Disclosure

K.R.Howard: Stock/Shareholder; Abbott, AbbVie Inc. M.Feldman: None. A.I.Carcone: None. K.P.Garza: None. M.A.Evans: None. J.Weissberg-benchell: Advisory Panel; Beta Bionics, Inc., Research Support; Beta Bionics, Inc. D.A.Ellis: None.

Funding

National Institutes of Health (3RO1DK110075-04S1)
679-P: Impact of Diabetes Distress on Glycemic Control, Diet Behaviors, and Diabetic Complications in Type 2 Diabetes Mellitus
Authors: CHO YONGIN , KIM YOUNGJOON , HEA SEO DA , HEE AHN SEONG , HONG SEONGBIN , HUN KIM SO
Published: June 2023

Background: We investigated the clinical features of patients with high diabetes distress, focusing on changes in glycemic control, dietary behaviors, and risk of diabetic complications.

Methods: From the Korean National Diabetes Program data, we investigated 1,862 individuals with type 2 diabetes mellitus (T2DM) who completed the Korean version of the Problem Areas in Diabetes Survey (PAID-K). A total score ≥40 was considered indicative of high distress.

Results: Individuals with high distress (n=589) had significantly higher levels of glycated hemoglobin (HbA1c) than those without distress, and this trend persisted for three years. In a subgroup of individuals with HbA1c <6.5% at baseline, patients with high distress were less likely to maintain HbA1c <6.5% after three years of follow-up (41.2% vs. 60.6%, p=0.007). Higher PAID-K scores were associated with younger age, longer duration of diabetes, higher HbA1c level, higher carbohydrate intake, and lower fiber intake (all p<0.05). There was a significant association between high distress and diabetic neuropathy (adjusted odds ratio, 1.63; p=0.002), but no significant association was found with other complications, including retinopathy, albuminuria, and carotid artery plaque.

Conclusion: High diabetes distress was associated with uncontrolled hyperglycemia, a high-carbohydrate and low-fiber diet, and higher odds of diabetic neuropathy.

Disclosure

Y.Cho: None. Y.Kim: None. D.Seo: None. S.Ahn: None. S.Hong: None. S.Kim: None.
681-P: Insulin Pump Use in Teens with Executive Function (EF) Problems and Type 1 Diabetes Is Associated with Lower A1C
Authors: VITALE REBECCA J. , VOLKENING LISA K. , TINSLEY LIANE J. , LAFFEL LORI M.
Published: June 2023

Aim: Providers may avoid offering pump therapy to teens with EF challenges (planning, organization). We assessed whether the association of pump use and A1c is modified by EF status, adjusting for relevant factors.

Methods: EF was assessed by parent proxy-report using Behavior Rating Inventory of Executive Function (BRIEF). T-score ≥60 defined risk of EF problems for Global Executive Composite (GEC), Behavioral Regulation Index (BRI), and Metacognition Index (MI). Parents also completed the Diabetes Family Conflict Scale (DFCS). T-tests stratified by EF status compared A1c by pump use and non-use. Generalized linear models were adjusted (Tukey) for variables with p<.1 in univariate analysis.

Results: Teens (N=169, 54% male) had mean age 14.9±1.3 yrs, diagnosis age 7.5±3.6 yrs, A1c 8.5±1%, 69% pump use, 9% CGM use, and 31% with GEC ≥60. With GEC <60, A1c was similar in pump users and non-users (8.3 vs 8.6%, p=.25); with GEC ≥60, A1c was lower in pump users vs non-users (8.5 vs 9.2%, p=.009). Similar A1c patterns were seen when stratified by EF problems in BRI or MI. In multivariate analysis, with GEC <60, A1c did not differ in pump users vs non-users (8.4 vs 8.6%, p=.36), adjusting for DFCS; a similar pattern was seen with BRI <60 (p=.26) and MI <60 (p=.25). With GEC ≥60, there was a trend towards lower A1c in pump users vs non-users (8.1% vs 8.7%, p=.07), adjusting for income and CGM use. With BRI ≥60, A1c was lower in pump users vs non-users (7.8 vs 8.4%, p=.03), adjusting for CGM use and DFCS score. With MI ≥60, A1c was not significantly different in pump users vs non-users (8.0% vs 8.4%, p=.25), adjusting for income, CGM use, and DFCS score. With elevated GEC, BRI, or MI scores in above multivariate analyses, A1c was lower in CGM users vs non-users (all p<.05).

Conclusion: The association of diabetes technology use with lower A1c in those with elevated BRIEF scores suggests a need to re-evaluate provider reluctance to recommend use of diabetes technologies in teens presenting with potential EF problems.

Disclosure

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

Funding

National Institutes of Health (P30DK036836, R01DK095273); JDRF (2-SRA-2014-253-M-B); Iacocca Family Foundation
69-LB: Sex-Specific Dynamics of GLP-1R and GIPR Expression in the Hypothalamus and the Amygdala of Mice
Authors: HOFMANN SUSANNA M. , ZHANG SHIQI , TOM ROBBY , MÜLLER TIMO D. , TSCHÖP MATTHIAS H.
Published: June 2023

GIPR:GLP-1R co-agonism improves obesity and cardio-metabolic disease with superior efficacy in both male and female mice compared to mono-agonism. We detected sex-specific differences in metabolic phenotypes, which may point to differing sensitivity for GLP-1R and/or GIPR in areas of the hypothalamus regulating energy balance (ARC, VMH, DMH) and in areas of the amygdala regulating cardiovascular functions. To optimize future therapeutic benefits and minimize side effects from a perspective of sex differences, we investigated whether GLP1R and GIPR expression levels in specific cell populations of the hypothalamus and the amygdala regions are co-determined by sex and diet. Female and male C57Bl6 mice were fed normal chow or 58% high fat diet (HFD) for 21 days (n = 4, total mouse number 16). Spatial transcriptomics by in-situ hybridization method RNAscope™ was combined with immunofluorescence staining for neurons (NeuN), astrocytes (GFAP) and microglia (iba1) to identify cell type specific gene expression patterns of GLP1R and GIPR in female and male brains. In the hypothalamus, both sexes, gene expression of GLP-1R was higher compared to GIPR (ARC, VMH and DMH). In our studies GLP-1R and GIPR were mostly expressed in neurons, marginally in microglia and not observed in astrocytes in both sexes. HFD exposure reduced GLP-1R and GIPR gene expression in males only. In the Amygdala, neuronal GIPR gene expression levels were higher compared to GLP-1R in both sexes. HFD reduced GIPR and GLP-1R gene expression in males only. In females, HFD induced a slight increase of GIPR gene expression specifically in the central and basolateral amygdala. Our results reveal sex-specific dynamics in GLP-1R and GIPR expression patterns in metabolically relevant areas of the hypothalamus and the amygdala induced by HFD exposure. This may imply sex-specific dosing regimens of GIP:GLP-1R co-agonists for future treatments of cardio-metabolic disease

Disclosure

S. M. Hofmann: None. S. Zhang: None. R. Tom: None. T. D. Müller: Research Support; Novo Nordisk A/S, Speaker's Bureau; Eli Lilly and Company, AstraZeneca, Mercodia AB, Stock/Shareholder; Novo Nordisk A/S, Eli Lilly and Company. M. H. Tschöp: Consultant; Boehringer Ingelheim Pharma GmbH&Co. KG.
69-OR: Multiancestry Genome-Wide Association Study Reveals Distinct Biological Pathways and Cell Types Driving Type 2 Diabetes Risk with Heterogeneous Effects across Diverse Populations
Authors: SUZUKI KEN , HATZIKOTOULAS KONSTANTINOS , SOUTHAM LORRAINE , YIN XIANYONG , LORENZ KIMBERLY , MANDLA RAVI , TAYLOR HENRY J. , HUERTA ALICIA , RAYNER NIGEL W. , CONSORTIUM DIAMANTE , MILLION VETERAN PROGRAM VA , MEIGS JAMES B. , MCCARTHY MARK I. , MAHAJAN ANUBHA , MERCADER JOSEP M. , SPRACKLEN CASSANDRA , BOEHNKE MICHAEL , VUJKOVIC MARIJANA , ROTTER JEROME I. , VOIGHT BENJAMIN F. , ZEGGINI ELEFTHERIA , MORRIS ANDREW , 2 DIABETES GLOBAL GENOMICS INITIATIVE TYPE
Published: June 2023

The Type 2 Diabetes Global Genomics Initiative aggregated genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 428,452 affected individuals and 2,107,149 controls from five major ancestries (39.7% non-European ancestry) to enhance power for locus discovery and improve understanding of the pathophysiological basis of the disease. We identified 1,289 independent association signals (P < 5 x 10-8) at 611 loci, of which 145 were previously unreported. We applied K-means clustering to the signals based on their associations with 37 cardiometabolic traits and identified eight clusters with distinct profiles. Three clusters were related to insulin secretion and had a positive, negative, or no effect on proinsulin levels. These clusters were significantly enriched (P < 0.05/222, Bonferroni correction for the number of cell types) for epigenomic annotations from single-cell ATAC-seq data in pancreatic islets but had different enrichment in pancreatic ductal cells and intestinal endocrine cells. The remaining five clusters related to insulin resistance (IR) physiology: increased body fat; unfavourable fat distribution (decreased gluteofemoral fat and increased visceral fat); obesity (increased body mass index); lipodystrophy (increased fasting insulin and decreased body fat); and liver lipid metabolism (increased liver fat and liver enzymes). IR clusters showed more diverse patterns of enrichment: obesity in adrenal cells; fat distribution in endothelial cells and pericytes in blood vessels; and lipodystrophy in adipocytes. T2D signals were more strongly enriched for ancestry-correlated heterogeneity in effect sizes in insulin secretion clusters than IR clusters. These data demonstrate distinct clusters of T2D association signals representing different trajectories to disease with observable differences in effect sizes across ancestry groups.

Disclosure

K.Suzuki: None. Diamante consortium: n/a. Va million veteran program: n/a. J.B.Meigs: Consultant; Quest Diagnostics. M.I.Mccarthy: Employee; Genentech, Inc., Stock/Shareholder; Roche Pharmaceuticals. A.Mahajan: Employee; Genentech, Inc. J.M.Mercader: None. C.Spracklen: None. M.Boehnke: None. M.Vujkovic: None. J.I.Rotter: None. K.Hatzikotoulas: None. B.F.Voight: None. E.Zeggini: None. A.Morris: None. Type 2 diabetes global genomics initiative: n/a. L.Southam: None. X.Yin: None. K.Lorenz: None. R.Mandla: None. H.J.Taylor: None. A.Huerta: None. N.W.Rayner: None.
693-P: Diabetes Distress Is Common in Newly Diagnosed Families in the 4T Study and Families Are Receptive to Psychological Services
Authors: SCHNEIDER-UTAKA AIKA , PANG ERICA , CORTES-NAVARRO ANA L. , BALISTRERI ILENIA , LOYOLA ALONDRA , ARRIZON-RUIZ NORA , ALAMARIE SELMA A. , RITTER VICTOR , SHAW BLAKE , BISHOP FRANZISKA K. , ZAHARIEVA DESSI P. , PRAHALAD PRIYA , DESAI MANISHA , MAAHS DAVID M. , HOOD KOREY K. , ADDALA ANANTA
Published: June 2023

Psychosocial states significantly impact T1D care and management for youth and their families. As part of a clinical pragmatic study, we report the number of elevated Patient Reported Outcomes (PROs) in newly diagnosed families and track their progress to psychological care. Parents/guardians (PG, n=125/133 4T Study 1 participants) and youth ≥11 years (n=60) were eligible to complete baseline, 3-, and 6-month PROs. PG completed Diabetes Distress Scale - Parent (DDS-P) and youth completed Diabetes Distress Scale (DDS-2) and PROMIS Pediatric Global Health Scale (PGH). Elevated PROs were based on published guidelines and were referred to the clinic's psychological services. Survey completeness was verified by staff to identify false flags. Staff reapproached the participant's psychologist for re-flagged PROs >3 months after the last visit.

Over the three study time periods, a total of 99 PROs flags were evaluated (Table). At baseline, there were 32% flagged PROs, which decreased to 27% and 23% at 3 and 6 months, respectively. Elevated DDS-P was the most common reason for referral (75%). Early psychological intervention may explain the reduction in elevated PROs over the study period.

With the implementation of systematic PROs in this new onset population, we observed it was common to have diabetes distress and families were receptive to psychological services.

Disclosure

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

Funding

National Institutes of Health (R18DK122422)
695-P: Emotional Burden of Diabetes Varies by Demographic Factors, Management Strategies, and Duration of Diabetes
Authors: COX EVELYN , ZENG ALISON , LIN EMILY , XU EMILY , BELL TREVOR , BRISTOW TRACY L.
Published: June 2023

The impact of diabetes on emotional well-being is well founded in the literature, though research on who experiences the brunt of this burden is lacking. The present study aims to quantify the emotional burden of diabetes and investigate the relationship between demographic factors, diabetes management, and severity of diabetes burden.

From October-December 2022, 10,338 adults living with diabetes in the U.S., Canada, France, Germany, Italy, Netherlands, Sweden, and U.K. took an online survey in which they reported their diabetes technology and therapy usage and demographic information. Respondents also answered four 7-point questions about the effort and motivation behind their diabetes management and the degree to which they feel overwhelmed or burnt out by their diabetes. These items were averaged to create a composite variable on emotional burden (α = 0.85, M= 3.43, SD = 1.51). Subsequent responses were analyzed using SPSS; all significant findings are reported at p<0.05.

Severity of emotional burden varies across several health-related and demographic factors. Respondents with T1D experience higher levels of emotional burden relative to those with T2D. Emotional burden is lowest among those who have had diabetes for 20 years or more and among those with an A1c ≤ 7%. People with diabetes in Canada report the highest severity, while those in Germany report the lowest. Emotional burden also varies by therapy and technology usage.

CGM users experience greater emotional burden than non-users; however, there were no differences among pump users. Additionally, T2s on insulin experienced a greater degree of emotional burden than T2s not on insulin therapy.

This research reveals several disparities in the mental burden of diabetes and suggests a link between intensity and duration of diabetes management and burden severity. Additional research is needed to identify avenues for support and burden reduction, targeted towards at-risk groups.

Disclosure

E.Cox: Employee; dQ&A. A.Zeng: Employee; dQ&A. E.Lin: Employee; dQ&A. E.Xu: Employee; dQ&A. T.Bell: Employee; dQ&A. T.L.Bristow: Employee; dQ&A.
697-P: How Does Daily Experience of Social Determinants of Health (SDOH) Impact Diabetes Self-Management and Glycemic Control in Underserved Young Adults (YA) with Type 1 Diabetes (T1D)?
Authors: CRESPO-RAMOS GLADYS , SCHECHTER CLYDE , FINNAN MOLLY , HOOGENDOORN CLAIRE J. , GONZALEZ JEFFREY S. , AGARWAL SHIVANI
Published: June 2023

Background: While it is recognized that SDOH can impact diabetes self-management and glycemic control in underserved YA with T1D, the real-time dynamic interplay among these variables within a given individual is poorly understood, which limits intervention potential.

Methods: We recruited 61 underserved YA with T1D (ages 18-30 yo) from the Bronx, New York. We administered 14 days of 3 times daily Ecological Momentary Assessment (EMA) surveys via smartphone, paired with blinded continuous glucose monitoring (CGM). Young adults reported twice daily on their experience of SDOH and once daily on their diabetes self-management. Using dynamic structural equation modeling, we evaluated within-person direct and indirect effects of SDOH on glycemic control, mediated through self-management.

Results: We included 51 YA with complete data (mean age 23 yo, 36% Black, 54% Hispanic, 73% Medicaid-insured, mean A1c 8.6%). Within an individual, on days when reported, presence of SDOH predicted lower time in range (TIR, 70-180 mg/dl) by 0.8% and increased mean blood glucose by 1.7 mg/dl that same day, but only when diabetes self-management was affected (indirect pathway). Separately, on days when daily self-management rating was higher, regardless of whether SDOH were experienced, TIR (+6.3%) and mean blood glucose (-14 mg/dl) improved that same day.

Conclusions: We examined the daily dynamic interplay of changes in SDOH, self-management, and glycemia in a novel way in underserved YA with T1D. While experiencing daily SDOH negatively affected glycemic control, it was only when self-management was also impacted. Just-in-time self-management support delivered in the context of daily SDOH experiences offers a new approach to timely targeted intervention. Interrupting the chronic cycle of cumulative effects of daily SDOH on glycemia could affect long-term outcomes.

Disclosure

G.Crespo-ramos: None. C.Schechter: None. M.Finnan: None. C.J.Hoogendoorn: None. J.S.Gonzalez: Consultant; Virta Health Corp. S.Agarwal: Advisory Panel; Medtronic, Consultant; Beta Bionics, Inc., Research Support; Abbott Diabetes, Dexcom, Inc.

Funding

NY-Regional Center for Diabetes Translational Research (5P30DK111022-08); National Institute for Diabetes and Digestive and Kidney Diseases (K23DK115896-05)
70-LB: Tirzepatide Reduces the Predicted Risk of Developing Type 2 Diabetes—Post Hoc Analysis of the SURMOUNT-1 Trial
Authors: HANKOSKY EMILY R. , WANG HUI , NEFF LISA M. , KAN HONGJUN , WANG FANGYU , AHMAD NADIA , STEFANSKI ADAM , TIMOTHY GARVEY W.
Published: June 2023

Background: The effect of tirzepatide (TZP) on the risk of developing type 2 diabetes (T2D) in people with obesity or overweight is unknown. We aimed to assess the impact of TZP treatment on T2D risk in the Phase 3 SURMOUNT-1 trial through predictive modelling.

Methods: Cardiometabolic Disease Staging, a validated robust tool providing 10-year risk estimates of T2D, was applied to the SURMOUNT-1 trial to derive risk scores at baseline, 24, and 72 weeks. Mean risk scores and change from baseline to week 72 were calculated from a mixed model.

Results: A total of 2539 participants were randomized 1:1:1:1 to TZP 5/10/15 mg and placebo (PBO) (mean age=45 years; female=68%; White=71%). Mean risk scores at baseline ranged from 23-24% and did not differ between groups. Mean risk scores for TZP 5, 10, 15 mg, and PBO groups were 13%, 11%, 11%, and 21% at week 24 and 11%, 9%, 9%, and 23% at week 72, respectively. At week 72, the absolute mean risk reductions from baseline were 12%, 14%, 15%, and 1% for TZP 5 mg, 10 mg, 15 mg, and PBO groups, corresponding to median relative risk reductions of -60.3%, -68.3%, -69%, and -10.8%, respectively. This resulted in significantly greater risk reduction between TZP groups vs. PBO (5 mg: 12%, 10 mg: 14%, 15 mg: 14%; p<0.001).

Conclusion: Treatment with TZP significantly reduced the 10-year predicted risk of developing T2D compared to PBO; most of the reduction in predicted risk was achieved by week 24.

Disclosure

E. R. Hankosky: Employee; Eli Lilly and Company, Other Relationship; Eli Lilly and Company. H. Wang: None. L. M. Neff: Employee; Eli Lilly and Company, Research Support; Aegerion Pharmaceuticals, Stock/Shareholder; Eli Lilly and Company. H. Kan: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. F. Wang: None. N. Ahmad: Employee; Eli Lilly and Company. A. Stefanski: Employee; Eli Lilly and Company. W. Garvey: Advisory Panel; Boehringer-Ingelheim, Novo Nordisk, Eli Lilly and Company, Merck & Co., Inc., Alnylam Pharmaceuticals, Inc., Fractyl Health, Inc., Inogen, Research Support; Novo Nordisk, Eli Lilly and Company, Epitomee, Pfizer Inc., Neurovalens.

Funding

Eli Lilly and Company
702-P: Similarities and Differences in Type 1 and Type 2 Diabetes Diagnosis Stories
Authors: PUGH ANDREW M. , BEVERLY ELIZABETH A.
Published: June 2023

Background: Research on the diagnosis of diabetes portrays it as a functional process of adapting to the condition. People experience variations in physical and psychosocial responses to their diagnosis. No known research has compared diagnosis experiences between people with type 1 diabetes (T1D) and type 2 diabetes (T2D). The purpose of this study was to identify similarities and differences in T1D and T2D diagnosis stories.

Methods: We conducted in-depth interviews with adults with T1D and T2D. Two researchers coded the interviews, met to resolve discrepancies, and agreed on themes using NVivo software.

Results: A purposive sample of 48 adults participated (mean A1C=7.7±1.8%; mean duration=13.4±12.9 years, mean age=45.8±21.7 years). Nineteen (39.6%) reported a diagnosis of T1D and 29 (60.4%) reported a diagnosis of T2D. Qualitative analysis revealed three themes: 1) Similar Emotional Reactions to Diagnosis: Both participants with T1D and T2D expressed feelings of frustration, depression, fear, and denial in their diagnosis experiences. Interestingly, only T2D participants expressed worry for long-term complications, with some individuals equating their diagnosis to a “death sentence.” 2) Similar Experiences with Diagnosis as a Major Life Event: Both T1D and T2D participants described their diagnosis as a significant life event, with several noting that their life will never be the same. 3) Different Perceptions of Diagnosis as a Surprise: Participants with T1D described their diagnosis as a surprise, whereas participants with T2D did not. Those with T1D expressed initial feelings of denial, while those with T2D referred to their diabetes as inevitable.

Conclusion: T1D and T2D participants shared similar emotional reactions, and both described their diagnosis as a major life event. Differently, T1D participants perceived their diagnosis as a surprise, while T2D participants expected their diagnosis. This information may assist clinicians in supporting people with diabetes at diagnosis.

Disclosure

A.M.Pugh: None. E.A.Beverly: None.
704-P: Effects of Comorbidity Burden among Adult Medicaid Beneficiaries with Type 2 Diabetes
Authors: MCQUEEN AMY , VERDECIAS NIKO , CABURNAY CHARLENE A. , SMITH RACHEL E. , BROUSSARD DARRELL J. , VON NORDHEIM DAVID A.
Published: June 2023

Diabetes self-management and health outcomes are complicated by comorbid conditions. Obesity, arthritis, pain conditions and others can create barriers to exercise and blood sugar goals. The burden patients experience managing chronic conditions may affect subsequent behaviors and outlook, creating a negative cycle. Understanding the impact of patients’ perceptions of comorbidity burden may inform future patient-centered healthcare services and community supports. We conducted a secondary data analysis using baseline and 3 month follow up survey data from an ongoing social needs intervention trial involving adult Medicaid beneficiaries with Type 2 diabetes. The sample (N=350) was 24-68 years old (M=52, SD=9), mostly female (n = 274; 78%), African American (n = 232; 66%) or White (n = 98; 28%), and had a mean of 7.6 (SD=3.0) of the 21 conditions, including diabetes, assessed at baseline. Each condition was rated by participants for impact on their daily activities (1=not at all; 5=a lot). Sum scores reflect ratings for diabetes burden only (M=2.9, SD=1.6) and all other conditions combined (M=21.0, SD=12.7). Bivariate correlations showed significant (p<.05) positive associations between diabetes burden and three month outcomes: sum social needs (r= .17), stress (r= .11), depression (r= .14), diabetes distress (r= .35), frequency of checking blood sugar (r= .16), but inverse associations with difficulty sleeping (r= -.17) and diabetes self-efficacy (r= -.15). The associations with other comorbidity burden ratings were similar except stronger with depression (r= .33) and receipt of government assistance programs (r= .17). Although people with diabetes have substantial self-management responsibilities, the effect was not different from other comorbidity burden on social needs and psychosocial outcomes, suggesting that similar or holistic interventions to reduce the negative effects of disease burden may be more efficient and effective to implement than disease-focused interventions.

Disclosure

A.Mcqueen: None. N.Verdecias: None. C.A.Caburnay: None. R.E.Smith: None. D.J.Broussard, jr.: None. D.A.Von nordheim: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK115916-01)
705-P: Examining Psychosocial Correlates of HbA1c Testing Frequency
Authors: MCQUEEN AMY , HERRICK CYNTHIA J. , LI LINDA , SMITH RACHEL E. , VERDECIAS NIKO , BROUSSARD DARRELL J. , VON NORDHEIM DAVID A.
Published: June 2023

Evidence supports guidelines for quarterly HbA1c testing for optimum diabetes control. Understanding patient-level factors associated with testing frequency may inform future interventions. Previous research with insured patients found greater testing frequency was associated with older age, uncontrolled baseline HbA1c, and comorbidities. This secondary analysis used baseline survey data from an ongoing intervention trial with the first 383 adult Medicaid beneficiaries with type 2 diabetes to have 12 months of follow up and medical claims data. Participants had an HbA1c test date <4mo prior to enrollment and reported the value >7.0 or “don’t know”. Associations with ≤2 vs. 3+ test dates over 12 months and demographic, health, and psychosocial correlates were examined. Participants were female (77%), White (30%), Black (70%), age M=51.66 (SD=9.32), had M=2.90 social needs (SD=1.70), and including diabetes, had M=7.62 (SD=3.05) chronic conditions. Of 1,710 HbA1c claims; 119 were excluded for <30 days of a previous claim. Participants with 1-2 claims (N=110, 29%) were compared to those with 3+ claims (N=273, 71%). Greater testing frequency was associated (p<.05) with: less likelihood of having children at home, more likely to be on insulin, more likely to report an HbA1c >9.0 or “don’t know”, more compliant with diabetes medicine and glucose testing at home, poorer physical functioning and general health, less future time orientation, and more diabetes distress. Testing frequency was not associated with age, race, employment, disability, sum social needs, sum comorbidities, stress, depression, diabetes self-efficacy or social functioning. Only having children at home (OR=0.53; 95%CI 0.53-0.88) and future time orientation (OR=.50; 0.30-0.82) were significant in a multivariable model. Some participants with 3+ tests may be more engaged in better diabetes care due to fewer family demands. Others in better health with less diabetes distress may need messaging to increase the perceived need for quarterly testing.

Disclosure

A.Mcqueen: None. C.J.Herrick: Consultant; Teladoc Health, Other Relationship; Merck & Co., Inc., Eli Lilly and Company. L.Li: None. R.E.Smith: None. N.Verdecias: None. D.J.Broussard, jr.: None. D.A.Von nordheim: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK115916-01)
708-P: Within-Person Relationships of Sleep Duration with Next-Day Stress and Affect in the Daily Life of Adults with Type 1 Diabetes
Authors: JIN HAOMIAO , GONZALEZ JEFFREY S. , PYATAK ELIZABETH , SCHNEIDER STEFAN , HOOGENDOORN CLAIRE J. , HERNANDEZ RAYMOND , LEE PEY-JIUAN , SPRUIJT-METZ DONNA
Published: June 2023

Introduction: Daily short sleep duration may negatively impact individuals with type 1 diabetes’ (T1D) ability to manage emotional well-being and to cope with daily stressors. Nevertheless, existing research is limited and mostly focused on between-person differences rather than impact of fluctuations in sleep duration on individuals.

Methods: Participants in the Function and Emotion in Everyday Life with Type 1 Diabetes (FEEL-T1D) study completed 14 days of intensive longitudinal data collection. Sleep duration was derived by synthesizing objective (actigraphy) and self-report measures. General and diabetes-specific stress, positive affect (PA), and negative affect (NA) were measured via ecological momentary assessment (5-6 times per day at 3-hr intervals). Multilevel regression was used to examine within-person relationships between sleep duration and next-day stress and affect. Cross-level interactions were used to explore whether gender and baseline depression and anxiety moderated these relationships.

Results: Adults with T1D (N=166) with at least 7 days of complete data were analyzed. Participants were 41.0 years, and 54.8% female. Average sleep duration was 7.3 hours (SD=1.2). Longer sleep was significantly associated with lower general stress (p<0.001) but not diabetes-specific stress (p=0.18) on the next day. Longer sleep was related to lower levels on all next-day NA (overall, p=0.002; disappointed, p=0.05; sad, p=0.05; tense, p<0.001; upset, p=0.008; anxious, p=0.04). There were no significant associations with PA (all p>0.05). Examination of interaction effects did not reveal significant differential relationships by gender, depression or anxiety.

Conclusion: Findings from this study suggest optimizing sleep duration as an important intervention target for better managing stress and improving daily emotional wellbeing of individuals with T1D.

Disclosure

H.Jin: None. J.S.Gonzalez: Consultant; Virta Health Corp. E.Pyatak: Research Support; Abbott Diabetes. S.Schneider: None. C.J.Hoogendoorn: None. R.Hernandez: None. P.Lee: None. D.Spruijt-metz: None.

Funding

National Institutes of Health (1R01DK121298)
71-OR: The Landscape of Pharmacogenetic Variants Associated with Noninsulin Antidiabetic Drugs in the Indian Population
Authors: SIVADAS AMBILY , SAHANA S. , JOLLY BANI , BHOYAR RAHUL C. , JAIN ABHINAV , SHARMA DISHA , IMRAN MOHAMED , SENTHIVEL VIGNESHWAR , DIVAKAR MOHIT K. , MISHRA ANUSHREE , MUKHOPADHYAY ARPITA , VENKAT NARAYAN K.M. , SIVASUBBU SRIDHAR , SCARIA VINOD , KURPAD ANURA
Published: June 2023

Genetic variants contribute to differential responses to non-insulin antidiabetic drugs (NIADs), and consequently to variable plasma glucose control. India’s distinct genetic architecture and its exploding burden of Type 2 Diabetes (T2D) warrants a population-specific survey of NIAD-associated pharmacogenetic (PGx) variants. We mined 1029 Indian whole genomes for PGx variants, drug-drug (DDI) and drug-drug-gene interactions (DDGI) associated with 44 NIADs. Overall, we found 76 known and 52 predicted deleterious common PGx variants associated with response to T2D therapy among Indians. We report remarkable inter-ethnic differences in the relative cumulative counts of decreased and increased response-associated alleles across NIAD classes. Indians and South Asians showed a significant excess of decreased metformin response-associated alleles compared to other global populations. Network analysis of shared PGx genes predicts high DDI risk during co-administration of NIADs with other metabolic disease drugs. We also predict an increased CYP2C19-mediated DDGI risk for CYP3A4/3A5-metabolized NIADs, saxagliptin, linagliptin and glyburide when co-administered with PPIs. Our findings provide an actionable resource for accelerating future diabetes PGx studies in Indians and reconsidering NIAD dosing guidelines to ensure maximum efficacy and safety in the population.

Disclosure

A.Sivadas: None. A.Mishra: None. A.Mukhopadhyay: None. K.Narayan: None. S.Sivasubbu: None. V.Scaria: None. A.Kurpad: None. S.Sahana: None. B.Jolly: None. R.C.Bhoyar: None. A.Jain: None. D.Sharma: None. M.Imran: None. V.Senthivel: None. M.K.Divakar: None.

Funding

DBT/Wellcome Trust India Alliance (IA/E/19/1/504945)