bluuebunny/crossref_metadata_2025 huggingface dataset:
757-P: Cardiometabolic Disease Risk Assessment of HIV Medication Regimens
Authors: ELZARKI ADRIAN , NANDULA SESHAGIRI RAO , AWAL HASSAN , SEN SABYASACHI
Published: June 2021

Objective: To determine the effect of non-nucleoside reverse transcriptase inhibitor (NNRTI) or integrase strand transfer inhibitor (IIh) based regimens on cardiovascular and metabolic disease risk in HIV +ve patients without diabetes, with normal CD4:CD8 count. Our goal was to use hematopoietic progenitor cells (CD34+ve) as the biomarker while examining the traditional serum markers.

Methods: 21 male subjects ages 32-66 years with BMI 21.0- 36.0, were enrolled. This was a single time point analysis study. Subjects were stratified into 2 groups (IIh with 11 and NNRTI with 10 subjects) who were taking stable doses of HAART. The medication regimens were a combination of two NRTI (typically tenofovir-emtricitabine) plus one IIh or NNRTI. We used CD34+ve cells, arterial stiffness measures and serum for the analysis.

Results: The IIh group had a higher average CD34+ve cell count 0.93% vs. 0.75% in NNRTI group. However, colony forming units (CFU) were lower in IIh group, 7.54 vs. 20.62. LDL levels were similar at 103.9 ±40.3 (IIh) vs. 107.8 ±37.5 (NNRTI). Average HDL were also similar. Inflammatory markers such as hs-CRP were lower in IIh at 1.726±1.45 vs. 1.832±1.50 in NNRTI group. Vitals such as average systolic BP in the IIh arm was 126.18±13.53 vs. 141.2±30.0 in NNRTI group. The diastolic BP averages were similar. The average augmentation index-75 (a measure of arterial stiffness) was avg.12.8 in IIh vs. 16.7 in NNRTI group. The average augmentation index (AI) were 15.2 in IIh vs. 20.2 in NNRTI group, with higher values indicating increased arterial stiffness. Average urinary albumin: creatinine ratio was 15.53 in IIh group vs. 76.72 in NNRTI group. No differences were noted in HbA1C, Leptin and adiponectin however average fasting insulin was 11.24 (IIh) vs. 22.96 (NNRTI). No significant differences were noted in CD34+ve cell gene expression assays.

Conclusion: Considering all parameters we conclude that Integrase Inhibitor based regimens may have a better cardiometabolic disease risk profile compared to NNRTI based regimens.

Disclosure

A. Elzarki: None. S. Nandula: None. H. Awal: None. S. Sen: None.

Funding

District of Columbia Center for AIDS Research (to S.S.)
759-P: Effect of Elexacaftor/Tezacaftor/Ivacaftor on Glycemic Control in Cystic Fibrosis-Related Diabetes Mellitus: A Chart Review
Authors: KRAVCHENKO MARIA , WARREN WHITTNEY
Published: June 2021

Introduction: Cystic fibrosis related diabetes mellitus (CFRD) affects up to 50% of adults with cystic fibrosis (CF), causing significant morbidity. CFRD primarily causes insulin deficiency, but exacerbations of CF may result in periods of insulin resistance. Anecdotal reports have suggested improved glycemic control and reduced insulin needs with CFTR modulators. Small pilot studies have shown improved insulin secretion and glycemic control with use of cystic fibrosis transmembrane regulator (CFTR) gene modulators, but the data are conflicting. This is a retrospective observational study investigating the effect of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA), the newest CFTR modulator, on glucose metabolism in CF.

Methods: We identified patients enrolled in the CF clinic at Brooke Army Medical Center who were started on ELX/TEZ/IVA in the last 12 months. Chart review was performed to identify diagnosis of CFRD, glucose and HbA1c values, and insulin dose. Glycemic control was compared for the periods 6 months prior to starting ELX/TEZ/IVA vs. 6 months afterward using paired t-tests.

Results: There were 10 patients with adequate data for analysis; 6 had CFRD and 4 did not. Median duration of CFRD was 10 years. Among patients without CFRD, there was no difference in FPG (p = 0.80), HbA1c (p = 0.20), or 2-hour OGTT (p = 0.09). In patients with CFRD, an improvement was seen in FPG (p=0.006) but not HbA1c (p=0.29) or insulin dose per kilogram (p=0.51). One patient did have a 55% reduction in insulin dose.

Conclusion: ELX/TEZ/IVA may improve FPG in patients with CFRD but does not have a significant effect on glucose metabolism in patients without CFRD. Further research is needed to elucidate metabolic effects of CFTR modulators and patient characteristics associated with improved glycemic control.

Disclosure

M. Kravchenko: None. W. Warren: None.
768-P: MSDC-0602 Is a Direct Mitochondrial Pyruvate Carrier Inhibitor That Modulates Central Carbon Metabolism in Mice and Humans
Authors: RAUCKHORST ADAM J. , PAPE DANIEL J. , COLCA JERRY R. , TAYLOR ERIC B.
Published: June 2021

Mitochondrial pyruvate carrier (MPC) disruption attenuates type 2 diabetes NAFLD in mice. MSDC-0602, a PPARγ-sparing, TZD-like molecule that inhibits the MPC, was recently tested in a phase 2B trial for treating NASH, which reported beneficial effects on glucose and insulin homeostasis. Yet, the broad, in vivo metabolomic effects of MSDC-0602 treatment have remained undefined. Here, we tested MSDC-062 metabolic mechanisms of action in vitro and in vivo, spanning from mitochondrial pyruvate uptake assays in isolated mouse mitochondria, through cultured mouse liver cells, in vivo in mice, and in humans participating in the EMMINENCE trial. First, we examined MSDC-0602’s effect in isolated mouse liver mitochondria: Pyruvate-oxidation was decreased by MSDC-0602, and 2.5 µM MSDC-0602 was sufficient to decrease mitochondrial pyruvate uptake by >50%. We extended these findings to AML12 mouse liver cells and mouse liver in vivo. In AML12 cells, MSDC-0602 treatment increased pyruvate and lactate and decreased alanine. These results were comparable but not identical to results from parallel testing of the specific MPC inhibitor UK5099. 14-day treatment of NCD and HFD fed mice with MSDC-0602 decreased liver alanine and branched chain amino acids. As we previously observed with MPC liver-specific knockout mice, the HFD-induced liver TCA intermediate pool size expansion was mitigated by MSDC-0602. Accordingly, MSDC-0602-dependent metabolomic changes were more pronounced in HFD- versus NCD-fed mice. Human EMMINENCE trial participants receiving MSDC-0602 showed decreased circulating alanine, ketone bodies, and glucose. Similarly, circulating and liver glucose were decreased in HFD mice treated with MSDC-0602. Together, these data are consistent with MSDC-0602 modulating in vivo metabolism in a partially MPC-dependent manner and by additional mechanisms that remain to be understood.

Disclosure

A. J. Rauckhorst: None. D. J. Pape: None. J. R. Colca: Board Member; Self; Metabolic Solutions Development Company, LLC, Employee; Self; Cirius Therapeutics. E. B. Taylor: None.

Funding

American Diabetes Association (1-18-PDF-060 to A.J.R.); National Institute of Diabetes and Digestive and Kidney Diseases (DK104998); Cirius Therapeutics
778-P: SGLT2 Inhibitors, GLP-1 Receptor Agonists, and DPP-4 Inhibitors and Risk of All-Cause Hospitalization
Authors: LYU BEINI , GRAMS MORGAN , CHANG ALEX R. , INKER LESLEY A. , CORESH JOSEF , SHIN JUNG-IM
Published: June 2021

Introduction: Clinical trials have shown cardiorenal benefits of SGLT2 inhibitors (SGLT2i). However, adoption of SGLT2i in clinical practice has been slow, perhaps in part due to safety concerns. We aimed to assess the association between SGLT2i and risk of all-cause hospitalization as the totality of severe adverse events and benefits, comparing to risks associated with DPP4 inhibitors (DPP4i) and GLP1 receptor agonists (GLP1RA).

Methods: We identified patients with type 2 diabetes who initiated SGLT2i (n=2492), DPP4i (n=4762) or GLP1RA (n=1982) between 2015 and 2018 in Geisinger and performed 1:1 propensity score matching on SGLT2i (n=2171) vs. DPP4i (n=2171) and SGLT2i (n=1605) vs. GLP1RA (n=1605). We examined all-cause hospitalization as the main outcome. We also considered two positive controls (major adverse cardiovascular event [MACE] defined as cardiovascular death, myocardial infarction, and stroke; and heart failure [HF] hospitalization), and a negative control (hospitalization due to major bleeding).

Results: Mean (SD) age was 58 (13) and 56 (13) years and 46% and 53% were women in the SGLT2i-DPP4i and SGLT2i-GLP1RA matched sample, respectively. During a median follow-up of 14 months, SGLT2i had similar risk of all-cause hospitalization compared with DPP4i (HR [95% CI] 0.85 [0.72-1.01]) or GLP1RA (HR 0.93 [0.77-1.13]). SGLT2i was associated with significantly lower risk of MACE and HF hospitalization compared with DPP4i (MACE: HR 0.70 [0.37, 0.98]; HF: HR 0.61 [0.38, 0.97]) but not with GLP1RA (MACE: HR 1.02 [0.50, 2.08]; HF: HR 0.72 [0.42, 1.23]). Risk of hospitalization due to bleeding was similar between SGLT2i vs. DPP4i or SGLT2i vs. GLP1RA.

Conclusions: In this real-world comparison of antidiabetes medications, SGLT2i may be as safe as DPP4i with significant cardiac benefits and have comparable risk-benefit profiles compared with GLP1RA. These results further encourage SGLT2i use in routine diabetes care, particularly among patients at high risk of MACE.

Disclosure

B. Lyu: None. M. Grams: None. A. R. Chang: Advisory Panel; Self; Reata Pharmaceuticals, Inc., Relypsa Inc., Research Support; Self; Novo Nordisk Inc. L. A. Inker: None. J. Coresh: Consultant; Self; Healthy. io, Research Support; Self; National Institutes of Health, National Kidney Foundation. J. Shin: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (K01DK121825)
809-P: The Impact of High-Deductible Health Plans (HDHPS) and Out-of-Pocket (OOP) Costs on Access to Care in Diabetes
Authors: SZABO SHELAGH M. , KUTI EFFIE , FRIESEN MICHAEL , REARDON DEBORAH , JAYKUS ELIZABETH , COREPAL REKESH , DONATO BONNIE M.K.
Published: June 2021

Background: HDHP use and high OOP costs are associated with decreased healthcare resource use (HCRU) and access to care, among those with lower incomes, or racial and ethnic minorities. The potential impact on diabetes care is a public health concern, given that regular access to medications is critical to avoid severe complications. The objective of this study was to characterize the impact of HDHPs and high OOP costs on access to care and HCRU among Americans with diabetes, and the interaction of race/ethnicity and income.

Methods: A systematic review was performed using Medline/EMBASE to identify records from the past 10 years, describing the impact of HDHPs, or high OOP costs or copayments, on access to care (e.g., not pursuing care because of cost) or HCRU (e.g., medication use, physician visits). The focus of the review was on Americans with diabetes; whether the impact of race/ethnicity and income was reported was also captured.

Results: From 2707 abstracts, 2 described the impact of HDHPs among those with diabetes and 9, high OOP/copayment costs. Four studies (36.4%) reported the impact of race/ethnicity: Black and non-Hispanic patients with diabetes tended to be at higher risk of non-adherence than white patients. Three studies (27.2%) reported the impact of income: Lower-income patients with diabetes were at higher risk of non-adherence and decreased HCRU, versus higher-income patients. Only one study reported on both race/ethnicity and income, but not the interaction of these.

Conclusions: These findings suggest that HDHP use and high OOP costs are associated with decreased HCRU and adherence among Americans with diabetes. This effect may be more pronounced among those of non-white race/ethnicity or with low income. Notably, no studies reported the impact of HDHPs and high OOP costs on access to care. Understanding how race/ethnicity and income interact will be important to fully recognize the impact of HDHPs and high OOP costs on outcomes among Americans with diabetes.

Disclosure

S. M. Szabo: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc. E. Kuti: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. M. Friesen: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc. D. Reardon: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. E. Jaykus: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. R. Corepal: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc. B. M. K. Donato: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc.

Funding

Boehringer Ingelheim
815-P: Cost-Effectiveness of Subcutaneous Semaglutide vs. Empagliflozin as Add-On Therapy for Type 2 Diabetes
Authors: ZUPA MARGARET , CODARIO RONALD , SMITH KENNETH J.
Published: June 2021

Background: Efforts to reduce type 2 diabetes morbidity and mortality focus on reducing microvascular and macrovascular complications. Development of GLP-1 receptor agonists and SGLT2 inhibitors has furthered progress toward this goal. As these medication classes have distinct effects on complication risk, the optimal approach is not clear.

Methods: We evaluated the cost-effectiveness of 2 strategies to intensify treatment of patients with type 2 diabetes and cardiovascular disease: addition of 1 mg subcutaneous semaglutide weekly or 25 mg oral empagliflozin daily to usual diabetes treatment. A Markov decision model estimated the impact of each strategy; complications included nonfatal myocardial infarction, hospitalization for congestive heart failure, nonfatal stroke, new or worsening nephropathy, and death. The empagliflozin strategy also included possible genital mycotic infection. Complication rates were based on EMPA-REG and SUSTAIN-6 trials. Modeled cohorts began at age 66 and were followed for 3 years at 1 month intervals. Analyses took a healthcare perspective, discounting 3%/year. For the base case, all patients entered the model with no complications.

Results: Compared to empagliflozin, semaglutide gained 0.053 quality-adjusted life year (QALY) at a cost of $1,006, or $18,897 per QALY gained. In one-way sensitivity analysis, only a semaglutide cost >$38/day (base case $18.04) resulted in empagliflozin being preferred at a willingness-to-pay threshold of $50,000/QALY. In probabilistic sensitivity analysis, semaglutide was preferred in 55% of model iterations at a $50,000/QALY threshold and in 57% at $100,000/QALY. When patients entered the model in complication states based on trial cohorts, semaglutide remained the preferred strategy at $23,518 per QALY gained.

Conclusion: For patients with type 2 diabetes mellitus with cardiovascular disease, semaglutide is likely more cost-effective than empagliflozin as an addition to usual treatment.

Disclosure

M. Zupa: None. R. Codario: None. K. J. Smith: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (5T32DK007052-45)
831-P: The Development of a New Computer Adaptive Test of Medication Adherence for People with Type 2 Diabetes Mellitus: Medication Adherence Item Bank
Authors: MITCHELL SUZANNE , KALLEN MICHAEL A. , BRAGG ALEXA , MOLDOVAN IOANA , HOWARD JESSICA M. , JACK BRIAN W. , MINER JENNIFER A. , GRAVES CHRISTOPHER M. , CARLOZZI NOELLE
Published: June 2021

Over 27 million Americans have type 2 diabetes mellitus (T2DM), accounting for >7.7 million hospital admissions. Social determinants of behavior, including medication adherence, play a critical role in their health outcomes. We developed a new patient-reported outcome (PRO) measure to evaluate medication adherence in people with T2DM, using established measurement development standards. An item pool was created that reflected important content related to medication adherence for people with T2DM. The item pool was then refined, using feedback from experts, a reading-level assessment (ensuring no >5th grade reading-level content was included), a translatability review (e.g., to allow future measure translation into Spanish), and feedback from T2DM patients. Next, 225 people with T2DM completed 58 self-report medication adherence items. Exploratory factor analysis supported the item pool’s essential unidimensionality. Five items were excluded due to low item-rest correlations. Confirmatory factor analysis supported retaining 27 items. All items fit the graded response model, and no items had meaningful differential item functioning for the factors age, sex, education, or socioeconomic status. The final item bank is comprised of 27 items and can be administered as a computer adaptive test or 6-

item short form. Internal consistency reliability was excellent for all administration formats (α’s all ≥ .90). The new Medication Adherence item bank provides a reliable, content-relevant assessment of medication adherence for people with T2DM. It is part of the comprehensive Re-Engineered Discharge for Diabetes Computer Adaptive Test (REDD-CAT) measurement system, which is designed to capture important social determinants of behavior for people with T2DM. Work is underway to establish additional psychometric properties (e.g., test-retest reliability, validity) of this new measure.

Disclosure

S. Mitchell: Other Relationship; Self; See Yourself Health LLC, Speaker’s Bureau; Self; Merck Sharp & Dohme Corp. M. A. Kallen: None. A. Bragg: None. I. Moldovan: None. J. M. Howard: None. B. W. Jack: None. J. A. Miner: None. C. M. Graves: None. N. Carlozzi: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R21DK121092)
832-P: Implementation of Depression Screening in a Pediatric Diabetes Clinic with Limited Mental Health Services
Authors: GURNURKAR SHILPA , VYAS NEHA V. , PATEL UNNATI , PIERCE JESSICA
Published: June 2021

Objective: Depression is up to 3 times more common in adolescents with diabetes than in their healthy peers and is associated with higher A1c values, and increased rates of diabetes-related hospitalizations. The ADA standards of care recommend integration of psychosocial screening into comprehensive medical care, but this is challenging in settings with limited mental health services. Here, we describe our quality improvement (QI) process for implementing depression screening in a pediatric diabetes center with limited mental health services.

Methods: This QI project took place in a pediatric children’s hospital that includes 3 satellite clinics. Routine diabetes care does not include integrated social work or psychology providers. Our goal is to increase PHQ-9 screening from 0% to 80% over 2 years in patients with diabetes (T1 or T2D) >11 yrs old across all 4 sites and to provide appropriate follow-up services for 100% of positive screens. We began our QI project in Dec. 2019 and present data through Oct. 2020. This includes 4 Plan-Do-Study-Act (PDSA) cycles ranging from trialing PHQ-9 screening with a single provider (Cycle 1) to implementing PHQ-9 screening across all providers and sites utilizing more efficient EMR processes (Cycle 4).

Results: Cycle 1 demonstrated a baseline screening average of 35.7%, of which 11.4% had a positive PHQ-9 screen. Screening rates improved by the end of Cycle 4 to 46-88% across the 4 sites. 100% of patients with positive screens were referred to Behavioral Health for further evaluation and treatment. Of note, screening rates decreased in April/May 2020 (Cycle 2), due to COVID and subsequent clinic closure.

Conclusions: Our QI methodology was effective in implementing depression screening in adolescent patients with rates of screening increasing over time and at all of our sites as more efficient methods were utilized. Continued efforts to screen and follow-up will focus on addressing barriers to evaluating and obtaining treatment for depression.

Disclosure

S. Gurnurkar: None. N. V. Vyas: None. U. Patel: None. J. Pierce: None.
865-P: Care Management Processes That Improve Diabetes Outcomes
Authors: PETERSON KEVIN A. , CARLIN CAROLINE , SOLBERG LEIF , EDER MILTON
Published: June 2021

Although previous work suggests that high performing practices focus on proactive patient outreach, the specific care management processes (CMP) that improve diabetes outcomes remain unclear. We evaluated 60 CMP from a state-wide practice survey in 2017 and 2019. Previously validated, the survey included 586 practices in 2017 (71% response, N=415) and 627 practices in 2019 (71% response, N= 445). Electronic health record data for A1c, blood pressure (BP), and lipid management were extracted for all patients with type 1 or type 2 diabetes in the practices. The longitudinal data set included 395 practices providing care to 204,745 patients. We used a longitudinal Bayesian model to correlate CMPs with A1c, systolic/diastolic BP, and probability of taking a statin. Patient outcomes were controlled for age, sex, diabetes type, insurance, comorbidity, community-level race-ethnicity, wealth, education, and income. Practices were controlled for rurality, size, FQHC status, system size, and practice-level random effects. Significance was reduced to <.01 for multiple comparisons. Although 7 CMPs significantly improved the overall diabetes performance measures for an average practice, CMPs affected individual outcomes differently. A1c improved by: 1) implementing a systematic approach to identifying and reminding patients when they were due for testing, and 2) having a nurse or care manager provide after visit follow up. BP was reduced by: 1, 2, and 3) tracking lab tests, 4) using checklists in the practice for required testing, and 5) guideline based reminders for preventive services. Statin use increased by: 5, and 6) screening for substance-abuse, and 7) a formal process for measuring performance. Together, CMPs with a statistically significant impact on performance measures accounted for a drop in average A1c in a practice from 7.39 to 7.25 (P<.01) BP from 127/75 to 121/71 (P<.01) and a 3.9% (P<.01) statin use increase. CMP 1 and 2 exemplify specific proactive patient outreach processes proven to improve diabetes care delivery.

Disclosure

K. A. Peterson: Board Member; Self; Treatment.com International Inc. C. Carlin: None. L. Solberg: None. M. Eder: None.

Funding

National Institutes of Health (R18DK110732)
883-P: Evaluating Impact of the Physician-Pharmacist Collaborative Management (PPCM) Team Providing Diabetes Preventative Care Services
Authors: VASCIMINI ANGELINA , SULLIVAN TARA , SAKDIPANICHKUL SUTHIDA S. , DEREMER CHRISTINA E.
Published: June 2021

Type 2 diabetes more than doubled in the last 20 years, putting an increase demand on the limited number of physicians practicing in rural areas. Implementing a physician-pharmacist collaborative management (PPCM) team, pharmacists can help increase access to care. The goal of this study is to determine if active PPCM patients have improved preventative care measures and associated drug therapy management. A single center retrospective chart review was conducted for patients seen by the PPCM team between March 2019 and December 2020. The comparator groups consisted of active PPCM patients (seen twice by the team in the last 12 months) versus inactive PPCM patients. The primary outcomes included annual foot exam, annual/biennial eye exam, blood pressure control, timely preventative care lab monitoring and appropriate therapy based on labs and atherosclerotic cardiovascular disease (ASCVD) risk. This project was approved by the institutional quality improvement performance registry process. Descriptive statistics, T test and Chi-square test were used for data analysis. Data was collected for 172 patients (92 active PPCM patients and 80 inactive PPCM patients). Baseline demographics were similar, however there were statistically more males in the inactive PPCM group. The primary outcome for annual foot exam (p value 0.0012), annual/biennial eye exam (p value <.001) and annual UACR (p value <.001) and lipid monitoring (p value 0.003) were statistically significant when comparing active PPCM patients to inactive PPCM patients. The other primary outcomes, appropriate drug therapy based on albuminuria and ASCVD risk and blood pressure control, were not statistically significant. Sample population data shows the PPCM team models improve preventative care measures, lab monitoring and may improve related drug therapy. When access to care is limited in rural areas, an effective PPCM team can extend the reach of the physician improving care for patients.

Disclosure

A. Vascimini: None. T. Sullivan: None. S. S. Sakdipanichkul: None. C. E. Deremer: Research Support; Self; Pfizer Inc., Speaker’s Bureau; Spouse/Partner; Pharmacy Times, Stock/Shareholder; Self; Portola Pharmaceuticals, Inc.
894-P: Monophasic Glucose Response Curve Is Associated with Increased C-Reactive Protein in Obese Adolescents
Authors: HOFFMAN ROBERT P. , CAZEAU RACHEL-MARIE , RAUCH LINDSEY , BAUER JOHN A.
Published: June 2021

Three distinct glucose response curves, biphasic, monophasic and incessant increase, have been demonstrated in adults and adolescents during OGTT. Individuals with incessant increase and monophasic curves have increased risk of type 2 diabetes and decreased insulin sensitivity and secretion and thus are likely at increased risk for other cardiometabolic diseases. We, therefore, examined differences in traditional, and nontraditional cardiometabolic risk factors between obese adolescents with biphasic (n=9; age=12.6±0.9 yr, BMI=31.8±5.9 kg/m2; mean±SD) and monophasic (n=6; age=13.1±0.9; BMI=35.3±6.9) glucose response curves. Traditional risk factors were blood pressure and lipids while non-traditional risk factors included reactive hyperemia (RH), inflammatory markers [c-reactive protein (CRP), interleukin-6 (IL-6)], adiponectin, soluble intracellular adhesion molecule 1 (SICAM1), and insulin sensitivity and secretion (OGTT, Matsuda and insulinogenic indices). Systolic and diastolic blood pressure, triglycerides, HDL and LDL did not differ between groups. RH, Il-6 and Matsuda index also did not differ. Subjects with monophasic curves tended to have increased SICAM1 (260±33 vs. 184±21; mean±SE; p=0.087) and had significantly increased CRP levels (4.40±1.03 vs. 1.66±0.28 ng/ml; p=0.009) compared to subjects with biphasic curves. Adiponection (3570±450 vs. 2350±440 ng/ml; p=0.089) and insulin secretion (4.31±0.52 vs. 2.89±0.53 µU dl/mg ml; p=0.089) tended to be lower in subjects with monophasic curves. The difference in CRP remained significant when BMI was included as a covariate (p=0.02). Obese adolescents with monophasic glucose response curves to OGTT have increased inflammation compared to subjects with biphasic curves. Longitudinal studies are needed to determine whether this early phase of glucose intolerance causes increased inflammation or whether early inflammation reduces insulin secretion and causes early glucose intolerance.

Disclosure

R. P. Hoffman: Consultant; Self; Provention Bio, Inc., Other Relationship; Self; Medscape, Research Support; Self; Provention Bio, Inc. R. Cazeau: None. L. Rauch: None. J. A. Bauer: None.

Funding

National Center for Research Resources (UL1RR05755)
899-P: Body Composition and Cardiometabolic Risk in South Asian Adolescents Compared with African American and White Peers
Authors: MANFREDO JACQUELYN A. , ANAND NEHA S. , ZEMEL BABETTE S. , KELLY ANDREA , MAGGE SHEELA N.
Published: June 2021

Background: South Asian (SA) adults have greater cardiometabolic risk (CMR) at lower BMI compared to White (W) and African American (AA) ancestry groups, thought to be due to increased visceral fat (VFAT). Few studies have examined adolescents for early ancestry differences.

Objective: Examine ancestry-related differences in body composition and CMR factors in SA, AA, and W youth.

Methods: SA, AA and W youth, 12-21 y, BMI ≥ 80%ile (or ≥23kg/m2 if ≥18y) had pubertal staging (PUB), whole body DXA, and measurement of CMR factors, including fasting metabolic labs. Insulin and glucose were used to calculate HOMA-IR. ANOVA or Kruskal Wallis compared groups, and linear regression adjusted for covariates (age, sex, PUB, BMI-Z) and analyzed interaction by group.

Results: Participants (34 SA, 23 AA, 44 W) were similar in sex and PUB, but SA were older [median (IQR) 20.2y (18.9, 21.2)] and AA had higher BMI [37.0 kg/m2 (32.7, 39.8)] compared to SA [28.6 (25.7, 30.6)] and W [27.7 (15.2, 32.5)]. Lipid panel, glucose, BP, and VFAT were similar among groups. Insulin [SA 15.0 µIU/mL (10.2, 25.1); AA 19.3 (15.4, 33.9); W 10.9 (7.1, 16.4), p=0.0005] and HOMA-IR [SA 3.5 (2.2, 5.6); AA 4.2 (3.4, 7.2); W 2.5 (1.5, 3.4), p=0.0005] were higher in SA and AA compared to W. In adjusted models: SA and W had greater increases in VFAT with increasing BMI-Z (SA*BMI-Z p=0.006; W*BMI-Z p<0.0005) and with increasing total body fat (BF) (SA*BF p=0.007; W*BF p<0.0005) compared to AA. SA had higher fasting insulin [β 6.45, p=0.01] and HOMA-IR [β 1.56, p=0.009] compared to W, even after adjusting for BF (p=0.004) or VFAT (p=0.009).

Conclusion: SA and W adolescents had greater increases in VFAT with increasing BMI-Z and with increasing BF, compared to AA. For a given BMI-Z, SA youth had higher HOMA-IR than W, even after adjustment for BF or VFAT. Further mechanistic studies are needed to understand the etiology of this higher insulin resistance in SA youth.

Disclosure

J. A. Manfredo: None. N. S. Anand: None. B. S. Zemel: None. A. Kelly: Consultant; Self; Vertex Pharmaceuticals Incorporated, vTv Therapeutics. S. N. Magge: None.
90-OR: Vision-Threatening Diabetic Retinopathy (DR) Is Associated with Modifiable Risk Factors in Children with Type 1 Diabetes (T1D)
Authors: JACOBA CRIS MARTIN , SAMPANI KONSTANTINA , GILBERT CATHERINE , SILVA PAOLO S. , KEADY JOYCE , LAFFEL LORI M. , AIELLO LLOYD P. , SUN JENNIFER
Published: June 2021

Vision-threatening DR (vtDR) is commonly defined as moderate nonproliferative or more severe DR, or the presence of diabetic macular edema (DME). Modifiable risk factors of DR and vtDR are well-established in adults. This study identified risk factors associated with DR and vtDR in a large pediatric cohort with T1D. Medical chart review was performed of baseline visits of pediatric (≤21 yrs old) patients at an academic eye center from 2005-2020 to collect demographic characteristics, medical history and DR severity. Analyses were adjusted for correlation between eyes of the same person. In total, 1735 subjects (3454 eyes) were included with mean±SD age 15.4±4.6 years, T1D duration 7.1±5.3 years, T1D onset 8.3±5.4 years, and A1c 8.4±1.3; 50.7% were female, 30.7% were overweight/obese and 4.1% had elevated/high BP. Any DR was present in 8.5% and vtDR in 2.4% of eyes. Unadjusted analyses found DR presence associated with higher A1c (p<.0001), longer T1D duration (p<.0001), younger age of T1D onset (p=0.0002), older age (p<.0001), female sex (p=0.001), higher BMI (p<.0001) and elevated/high BP (p<.0001). After backwards elimination modeling, older age (p<.0001), longer T1D duration (p=0.002) and higher A1c (p=0.01) were significantly associated with DR. In unadjusted analyses, vtDR was associated with higher A1c (p<.0001), longer T1D duration (p<.0001), younger age of T1D onset (p=0.001), older age (p<.0001), female sex (p=0.009), higher BMI (p=0.009) and elevated/high BP (p<.0001). Using backwards elimination modeling, older age (p<.0001), younger age of T1D onset (p<.0001) and elevated/high BP (p=0.0007) were significantly related to vtDR. In this pediatric cohort, DR or vtDR were present in 8.5% of eyes and were associated with modifiable risk factors of hyperglycemia and elevated BP. Future longitudinal studies can assess if early intervention to improve glycemic control and BP can reduce vtDR in youth with T1D.

Disclosure

C. Jacoba: None. K. Sampani: None. C. Gilbert: None. P. S. Silva: Research Support; Self; Hillrom, Optomed, Optos plc. J. Keady: None. L. M. Laffel: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompe, Insulogic LLC, Janssen Pharmaceuticals, Inc., Laxmi Therapeutic Devices, LifeScan, Lilly Diabetes, Medtronic, Provention Bio, Inc. L. P. Aiello: Consultant; Self; KalVista Pharmaceuticals, Novo Nordisk, Regeneron Pharmaceuticals Inc., Stock/Shareholder; Self; KalVista Pharmaceuticals. J. Sun: Other Relationship; Self; Novo Nordisk, Roche Pharma, Research Support; Self; Adaptive Sensory Technology, Boehringer Ingelheim Pharmaceuticals, Inc., KalVista Pharmaceuticals, Optovue, Roche Pharma.
902-P: Screening for Gastric Motor Abnormalities in Pediatric Patients with Type 1 Diabetes: A Cross-Sectional Study
Authors: MASHALI GAMAL , KAUL AJAY A. , DOLAN LAWRENCE M. , KHOURY JANE C. , SHAH AMY S.
Published: June 2021

Diabetes is the 2nd most common cause of delayed gastric emptying in adults. As a result, patients with type 1 diabetes are at increased risk of gastric motor abnormalities that can include delayed gastric emptying (gastroparesis) and the related symptoms. Limited information exists regarding presence of gastric motility disorders in youth with type 1 diabetes. An improved understanding of whether these gastric motility symptoms are present may influence screening, diagnosis, treatment, and quality of life.

A cross sectional study was conducted to assess symptoms suggestive of gastroparesis in pediatric patients with type 1 diabetes using the standardized Gastroparesis Cardinal Symptom Index (GCSI) questionnaire. The GCSI consists of 9 questions to assess the presence and severity of gastric motility symptoms. Severity is rated from none (0) to very severe (5) using a likert scale and three symptom subscale (presence of nausea/vomiting, fullness/early satiety, and bloating). The total GCSI score is calculated as the mean of the three subscales. A GCSI score ≥ 1.9 has been associated with delayed gastric emptying.

Initial data from 247 patients with type 1 diabetes; mean±SD age 18.1±3.4 years (range 15-20 years old), 61% female, 90% Caucasian, duration of the disease 8.4 ±5.3 years, A1c 8.1±1.8% who answered the GCSI questionnaire found 190 (77%) had at least one symptom associated with gastric motility disorder. Nausea was the most common symptom (75%) followed by stomach fullness (63%). Of those with at least one positive symptom, 37 (20%) had a score ≥ 1.9. Those with a GCSI score ≥ 1.9 were older (19.5 vs. 17.8, p=0.008), but there was no association with race, sex, body mass index, duration of the disease, or glycemic control, as measured by HbA1c.

Gastrointestinal symptoms suggestive of gastric motor abnormalities, as measured by the GCSI questionnaire are present in youth with type 1 diabetes. Older patients may be at higher risk.

Disclosure

G. Mashali: None. A. A. Kaul: None. L. M. Dolan: None. J. C. Khoury: None. A. S. Shah: None.
904-P: Discordance between Youth and Parent Report of Diabetes Distress in Type 1 Diabetes (T1D): The Importance of Youth Perceptions
Authors: WENTZELL KATHERINE , FU MEI R. , VOLKENING LISA K. , LAFFEL LORI M.
Published: June 2021

Diabetes Distress (DD) can be experienced differently by family members living with T1D. We examined concordance and discordance between youth and parent report of DD and the relationship with youth glycemic control, diabetes-specific family conflict and parent involvement in diabetes tasks in a sample of youth starting real-time continuous glucose monitoring (CGM).

Youth (N=120, 51% male) with T1D ages 8-17 years and their parents (84% mothers) completed surveys assessing DD, family conflict and parent involvement. Previously validated cut-points of >41 (PAID-Peds, youth) and >56 (PAID-PR, parents) identified clinically significant DD. Youth/parent dyads were classified as concordant when both youth and parents scored below (Youth Low/Parent Low) or above (Youth High/Parent High) the cut-points. Youth/parent dyads were classified as discordant when youth scored below and parent scored above (Youth Low/Parent High) or youth scored above and parent scored below (Youth High/Parent Low) the cut-points.

Youth had a mean±SD age of 12.7±2.7 years, T1D duration 6.1±3.6 years and A1c 8.0±0.8%; 84% were pump treated. About ¼ of youth (26%) and parents (23%) reported clinically significant DD with 62% of dyads concordant for low DD, 10% concordant for high DD and 28% discordant for DD. Concordant groups did not differ significantly from discordant groups. In the 2 discordant groups, A1c and youth-reported family conflict differed significantly; A1c: 7.5±0.9% vs. 8.3±0.7% (p=.043) and family conflict: 5.6±5.1 vs. 22.9±22.0 (p=.036) in the Youth Low/Parent High and Youth High/Parent Low groups, respectively. Parent involvement did not differ across the groups.

DD can be perceived differently by youth with T1D and their parents. When youth perceive high DD and parents do not, youth appear at risk for adverse outcomes, highlighting the importance of youth perceptions.

Disclosure

K. Wentzell: None. M. R. Fu: None. L. K. Volkening: None. L. M. Laffel: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompe, Insulogic LLC, Janssen Pharmaceuticals, Inc., Laxmi Therapeutic Devices, LifeScan, Lilly Diabetes, Medtronic, Provention Bio, Inc.

Funding

National Institutes of Health (R01DK089349, K12DK094721, P30DK036836)
928-P: Psychosocial Factors in Diabetes-Specific Risk Taking among Adolescents with Type 1 Diabetes
Authors: THOMAS COURTNEY , ENLOW PAUL , WASSERMAN RACHEL M. , MILKES AMY , PIERCE JESSICA , GURNURKAR SHILPA , CARAKUSHANSKY MAURI , DOYLE DANIEL A. , PENDLEY JENNIFER S. , WYSOCKI TIM , ALDERFER MELISSA A.
Published: June 2021

Background: Diabetes-specific risk taking (DSRT) refers to unhealthy, risky behaviors that put someone with diabetes at increased risk for suboptimal health outcomes (e.g., drinking alcohol with others who are unaware you have T1D). DSRT is associated with less engagement in T1D management and higher HbA1c. This study set out to determine if lower levels of parental involvement in T1D care and higher levels of diabetes distress, also associated with less optimal T1D outcomes, were associated with DSRT among adolescents with T1D.

Methods: Participants were 104 adolescents with T1D (Mage = 13.50 years, SDage = 1.69 years, 53.8% female, MHbA1c = 8.74%, SDHbA1c = 1.24%) who enrolled with their caregivers in a randomized controlled trial integrating psychologists and dietitians into T1D care visits (35% enrollment). Adolescents completed baseline measures of parental involvement, diabetes distress, and DSRT; caregivers reported demographics; and HbA1c was collected from the electronic medical record. Hierarchical linear regression was used to examine whether parental involvement and diabetes distress predicted DSRT after controlling for participants’ sex, race, ethnicity and HbA1c.

Results: The full model was statistically significant and accounted for 29.7% of the variance in diabetes-specific risk taking (F(2, 91)= 19.1, p < .001). Neither HbA1c, sex, race nor ethnicity were statistically significant predictors of DSRT. Higher levels of diabetes distress (β = .23, p = .01) and lower parental involvement (β = -.44, p < .001) predicted more frequent DSRT.

Conclusions: Adolescents with more diabetes distress and less collaborative parental involvement in T1D management reported more diabetes-specific risk taking. While causality cannot be asserted, these results can inform targeted behavioral interventions to help youth who are more likely to take risks in their T1D care. Future research should consider other factors contributing to diabetes-specific risk taking.

Disclosure

C. Thomas: None. T. Wysocki: None. M. A. Alderfer: None. P. Enlow: None. R. M. Wasserman: None. A. Milkes: None. J. Pierce: None. S. Gurnurkar: None. M. Carakushansky: None. D. A. Doyle: None. J. S. Pendley: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (DP3DK113235)
929-P: A Population-Based Study of Long-Term HbA1c Associated with Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes in Western Australian Children
Authors: CLAPIN HELEN , SMITH GRANT J. , VIJAYANAND SATHYAKALA , JONES TIM , DAVIS ELIZABETH A. , HAYNES AVENI
Published: June 2021

Background: In addition to the acute illness associated with DKA at diagnosis of T1D in children, there is some evidence of its association with poor long-term glycaemic outcomes, increasing risk of complications. With growing global interest in screening for pre-diabetes in children, long-term outcomes are an important consideration in terms of economic viability but there is limited high quality data. This population-based study helps to address this gap.

Methods: All children <16 years presenting to Perth Children’s Hospital with new onset T1D 2000-2019 were included and followed up for ≤ 14 years. Moderate-severe DKA at diagnosis was defined as serum pH <7.2 or bicarb <15mmol/l in the presence of hyperglycaemia and ketosis. HbA1c was recorded at each clinic visit, ~3 monthly from diagnosis. A linear mixed model, adjusted for sex, diagnosis age, socioeconomic status and metro/regional area of residence, was used to examine long-term HbA1c associated with DKA at diagnosis at each year of duration.

Results: The population-based cohort included 2063 patients and median [IQR] follow-up time was 5.4 [3.0-8.4] years. The incidence of DKA at diagnosis was 25%. Patients presenting with DKA had a higher mean HbA1c at diagnosis as expected but from 2 to 7 years post-diagnosis there was no difference between the two groups. Mean HbA1c of patients presenting with DKA increased relative to the remainder from 7 years. The only comparable study, conducted in Colorado in 2017, reported an immediate and sustained relationship between DKA severity at onset and HbA1c over 15 years.

Conclusion: The difference in findings for similar cohorts in Australia and the US raises questions regarding the variables that influence long-term glycaemic outcomes in children diagnosed with T1D. Further studies are required to explore the association between DKA at diagnosis and HbA1c over time and to understand the importance of sociodemographic, physiological and other factors.

Disclosure

H. Clapin: None. G. J. Smith: None. S. Vijayanand: None. T. Jones: None. E. A. Davis: None. A. Haynes: None.
931-P: Supporting Physical Activity in Children with Type 1 Diabetes: A Survey of Health Care Professionals
Authors: COCKCROFT EMMA , NARENDRAN PARTH , WOODING EVA , ANDREWS ROBERT C.
Published: June 2021

Background: The risk of some of the co-morbidities associated with type 1 diabetes (T1D) can be mitigated through physical activity. Despite benefits, research shows that children and adolescents with T1D are not meeting recommended levels of physical activity. Health Care Professionals (HCPs) have an important role in supporting and encouraging children and adolescents to be physically active. Therefore it is important to understand the perspectives of HCPs in relation to understanding physical activity behaviours in children and adolescents, prior to designing interventions to support physical activity.

Methods: An online mixed methods survey of HCPs in England and Wales. Respondents were asked questions about how they support physical activity in the clinic and their perceptions of barriers/enablers of physical activity. Quantitative data were analysed descriptively, qualitative data were analysed using a combined deductive framework and inductive thematic analysis using the Capability, Opportunity, Motivation model of behaviour (COM-B).

Results: Responses were received from 114 individual HCPs, representing 45% of paediatric diabetes units in England and Wales. Results show that HCPs felt that the promotion of physical activity is important in their clinic (90%) and advise children and adolescents to increase levels of physical activity (88%). Many respondents (43%) felt there was lack of education opportunities for HCPs on this topic. Qualitative responses highlighted three key areas of behaviour that might be a barrier to physical activity in their patients: (1) psychological capacity (i.e., fear of hypoglycaemia and lack of understanding of how to manage insulin and glucose levels), (2) physical opportunity (i.e., time, cost, and access to resources), and (3) social opportunity (i.e., family, school, and peer support).

Conclusion: This understanding will help develop future interventions to support physical activity in children and adolescents with T1D.

Disclosure

E. Cockcroft: None. P. Narendran: Speaker’s Bureau; Self; Novo Nordisk Inc., Sanofi. E. Wooding: None. R. C. Andrews: None.

Funding

National Institute for Health Research Applied Research Collaboration South West Peninsula (to E.C.)
932-P: Impact of Insurance Source on Health Care Transition Progress in College Youth with Type 1 Diabetes
Authors: TSEVAT REBECCA K. , WEITZMAN ELISSA R. , WISK LAUREN E.
Published: June 2021

Background: The transition from pediatric to adult models of care can be challenging for adolescents with chronic diseases, like type 1 diabetes (T1D). Among the challenges they often face is the issue of health insurance, which can be difficult to navigate, and which may affect access to effective transitional care. In this study, we examined the impact of insurance source on healthcare transition (HCT) progress in college youth with T1D.

Methods: Data are from 138 respondents to a multi-national, web-based study of college youth with T1D recruited via social media platforms and direct outreach. Participants were asked to report their health insurance source and answer questions about the HCT process and their diabetes care team. Descriptive statistics and multivariable regression were used to evaluate HCT measures as a function of sociodemographic variables, adjusting for confounders.

Results: Participants were from 85 universities across 30 states and Canada, and 87.0% were covered on a parent’s insurance plan. Those not covered on a parent’s insurance plan were more likely to list a general adult practitioner as their main diabetes care provider (22.2% vs. 8.3%, p=0.067) but were less likely to have received help with finding an adult provider than their counterparts (44.4% vs. 76.3%, p=0.042). Participants not covered on a parent’s insurance plan (vs. those who were) also were more likely to have discussed obtaining health insurance with their provider (61.1% vs. 25.0%, p=0.002). These differences persisted after adjustment.

Conclusion: College youth with T1D demonstrate differences in indicators of HCT progress according to insurance source. Lack of parental insurance may instigate independent - though not necessarily smooth - transitions, potentially leaving an increasing number of adolescents with dependent coverage vulnerable to a prolonged HCT. Efforts to improve the HCT process should consider insurance source to advance HCT preparation for all college youth with T1D.

Disclosure

R. K. Tsevat: None. E. R. Weitzman: None. L. E. Wisk: None.

Funding

Boston Children’s Hospital (FP01017994)