bluuebunny/crossref_metadata_2025 huggingface dataset:
1098-P: Association of Sleep with ß-Cell Response and Insulin Sensitivity in Youth
Authors: TEMPLE KARLA A. , TJADEN ASHLEY H. , MANCHANDA SHALINI , EHRMANN DAVID , NADEAU KRISTEN J. , EDELSTEIN SHARON , HANNON TAMARA S. , MOKHLESI BABAK , CONSORTIUM RISE
Published: June 2023

Poor sleep may be associated with reduced β-cell response or decreased insulin sensitivity in youth. We explored whether sleep duration, sleep quality or obstructive sleep apnea (OSA) risk factors were associated with measures of β-cell response or insulin sensitivity in youth. At baseline, 88 youth (10-19 yrs of age) with recently diagnosed T2D or prediabetes completed validated questionnaires (Sleep Disturbances Scale and Cleveland Adolescent Sleepiness) in the Restoring Insulin Secretion (RISE) Study. Hyperglycemic clamps measured insulin sensitivity (steady state glucose infusion rate/insulin [M/I]) and β-cell responses: acute (0-10 min) C-peptide response to glucose (ACPRg), steady-state C-peptide at a glucose of 11.1 mmol/L (SSCP), and arginine-stimulated maximum C-peptide responses at glucose >25 mmol/L (ACPRmax). Linear regression models explored the independent association between sleep variables and clamp measures, adjusted for age, race/ethnicity, sex, Tanner stage, metformin use and BMI. Models including β-cell responses were adjusted for M/I to account for the role of insulin sensitivity in β-cell function. The cohort was 70% female, 28% white, 25% black, 36% Hispanic; age 14.3±2.0 yrs and BMI 36.9±6.4 kg/m2 (mean±SD). Using ADA criteria, 60% had prediabetes and 40% had T2D; 27% reported metformin use. Sleep duration <8 h was reported in 59%; 57% reported daytime sleepiness; 28% reported poor sleep quality; 29% had high risk for OSA. Low sleep duration (<8 h) was associated with a trend for lower ACPRg (p=0.069). No sleep variables (sleep duration or quality, OSA risk) were associated with clamp-derived outcomes in unadjusted or adjusted linear regression models. In youth with prediabetes or T2D, subjective measures of sleep quantity, sleep quality and OSA risk were not independently associated with β-cell response or insulin sensitivity. Further research using objective measures of sleep may better delineate the relationship between sleep and β-cell function in youth.

Disclosure

K.A.Temple: None. A.H.Tjaden: None. S.Manchanda: Advisory Panel; Inspire. D.Ehrmann: None. K.J.Nadeau: None. S.Edelstein: None. T.S.Hannon: Advisory Panel; Eli Lilly and Company. B.Mokhlesi: None. Rise consortium: n/a.

Funding

American Diabetes Association (1-20-RISE-01 to S.E.); National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute
1101-P: Glycemia after Pediatric Bariatric Surgery—Outcomes and Predictors
Authors: SISLEY STEPHANIE , SHAH AMY S. , NADEAU KRISTEN J. , KELSEY MEGAN M. , GU TAO , MICHALSKY MARC , JENKINS TODD M. , INGE THOMAS
Published: June 2023

Background: Metabolic and bariatric surgery (MBS) is a safe and efficacious treatment for children and adolescents with severe forms of obesity. However, there are few data on the effects of pre-surgical fasting insulin homeostasis measures on post-surgical weight loss or glycemia.

Methods: We analyzed data from n=216/242 individuals with ≥ Class 2 obesity prospectively enrolled in the multi-center, Teen Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study for up to eight years. Individuals who had type 1 diabetes, a gastric band procedure, or lacked baseline data for insulin homeostasis measurements were excluded, leaving 216 individuals for analysis. Body composition was assessed through bioelectrical impedance measurements. An analysis of fasting markers of insulin homeostasis using homeostatic model of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), or HOMA-β and outcomes following MBS was performed.

Results: Our cohort had a baseline mean age of 16.5 years, BMI of 52.7 kg/m2, and was 75.4% female. At 8-year follow up, participants had a mean BMI of 43.0 kg/m2. Pre-surgical measures of insulin homeostasis did not predict change in BMI or fat mass over eight years. However, larger improvements in HbA1c were positively associated with younger baseline age, higher baseline HOMA-IR and HOMA-β, and lower baseline HbA1c.

Conclusion: Baseline markers of insulin homeostasis were not significantly associated with weight loss outcomes, but did predict glycemia 8 years after MBS.

Disclosure

S.Sisley: Speaker's Bureau; Rhythm Pharmaceuticals, Inc. A.S.Shah: None. K.J.Nadeau: None. M.M.Kelsey: Other Relationship; Boehringer Ingelheim Inc., Janssen Pharmaceuticals, Inc., Rhythm Pharmaceuticals, Inc., Lilly. T.Gu: None. M.Michalsky: Advisory Panel; Lilly, Other Relationship; Intuitive Surgical, Stock/Shareholder; Intuitive Surgical. T.M.Jenkins: None. T.Inge: None.

Funding

National Institutes of Health (U01DK072493); U.S. Department of Agriculture-Agricultural Research Service (3092-5100-065)
1106-P: Feasibility of Continuous Glucose Monitor Use in Publicly Insured Youth with Type 2 Diabetes
Authors: SHAH SEJAL , ARRIZON-RUIZ NORA , LOYOLA ALONDRA , SAGAN PIPER , CONRAD BARRY P. , LEVERENZ JEANNINE , BISHOP FRANZISKA K. , MAAHS DAVID M.
Published: June 2023

T2D disproportionately affects youth of minority and lower SES backgrounds with public insurance. Continuous glucose monitor (CGM) use in youth with T1D and adults with T2D benefits glycemia and quality of life. Use of CGM in youth with T2D has not been sufficiently evaluated.

We aimed to determine feasibility of CGM use, measured by % wear time per 2-week period (>75% wear-time as goal) prior to clinic visit, clinical outcomes including time in range (TIR) and HbA1c. Youth were provided or prescribed Libre 2 CGM and followed using established clinic workflows with data collection at each visit. We present the first 6 months (m) of data.

We enrolled 30 youth with T2D, mean age 15.1 y and mean HbA1c 10.2% (6.5%-15.5%) (Table 1). At baseline, 37% had history of prior intermittent CGM use and 53% did not have glucometer data. At 3 m 47% of youth who attended visits were using CGM, at 6 m 79% were using CGM, with no participant using CGM >75% of the time. Mean HbA1c was lower over 6 months (1.3% decrease in 8 youth with 6m CGM data and HbA1c) and TIR was lower between 3 and 6 m among those who attended clinic visits.

CGM use for 6 m was not sustained in youth with T2D, but CGM was worn by a portion of youth and associated with lower HbA1c in those who used CGM. Strategies for CGM use in youth with T2D may differ from adults with T2D or youth with T1D. Additional studies are needed to evaluate facilitators and barriers of CGM use to optimize CGM use in youth with T2D.

Disclosure

S.Shah: Research Support; Boehringer-Ingelheim, Takeda Pharmaceutical Co., Ltd. N.Arrizon-ruiz: None. A.Loyola: None. P.Sagan: None. B.P.Conrad: Advisory Panel; Edgepark medical supplies, Consultant; Abbott Diabetes. J.Leverenz: None. F.K.Bishop: None. D.M.Maahs: Advisory Panel; Medtronic, LifeScan Diabetes Institute, MannKind Corporation, Consultant; Abbott, Research Support; Dexcom, Inc.

Funding

Stanford Diabetes Research Center (P30DK116074)
1109-P: Barriers and Facilitators to Use of Continuous Glucose Monitors for Type 2 Diabetes in Youth
Authors: PEYYETY VAISHNAVI , ZUPA MARGARET , HEWITT BRIANNA , RODRIGUEZ GONZALEZ ADRIANA , MANI ISWARIYA , PRIOLEAU TEMILOLUWA , MCCURLEY JESSICA L. , KUEI LIN YU , ELLEN VAJRAVELU MARY
Published: June 2023

Objective: Youth-onset type 2 diabetes, most common among racial/ethnic minorities, threatens to widen health disparities due to severe complications in early adulthood and a 15-year reduction in life expectancy. Use of continuous glucose monitors (CGM) improves diabetes management in adults with type 2 diabetes, but socioeconomic and racial/ethnic disparities in diabetes technology use remain. We sought to examine factors impacting the acceptability of CGM use in adolescents and young adults (AYA) with type 2 diabetes.

Methods: In this single center study, we conducted semi-structured interviews with AYA with type 2 diabetes and their parents to determine attitudes about CGM use, including barriers and facilitators. Interviews were audio-recorded, transcribed, and evaluated using thematic analysis.

Results: Twenty AYA and 10 parents participated (n=30 total). AYA were mean age 16.5 years (SD 2.2, range 13.7-20.1) and had median diabetes duration of 1.3 years. Most were female (65%) and minority race/ethnicity (40% non-Hispanic Black; 10% Hispanic; 5% Asian). Seven (35%) used CGM. The primary benefit elicited was convenience over glucometer use. Important barriers included the impact of physically wearing the device and drawing unwanted attention, desire for AYA privacy, and adequate education about the device.

Discussion: In this diverse sample of AYA with type 2 diabetes and their parents, CGMs were generally regarded as convenient, although concerns about worsening stigma and conflict with parents were prevalent. Our findings can guide the development of patient-centered approaches to CGM use for AYA with type 2 diabetes, a critical step toward reducing inequities in diabetes technology uptake.

Disclosure

V.Peyyety: None. M.Zupa: None. B.Hewitt: None. A.Rodriguez gonzalez: None. I.Mani: None. T.Prioleau: None. J.L.Mccurley: None. Y.Lin: None. M.Vajravelu: None.

Funding

Endocrine Fellows Foundation; National Institutes of Health (K23HL157763, K23DK129724, KL2TR001856, K23DK125719, UL1-TR-001857)
111-OR: Effect of Dulaglutide plus Calorie-Restricted Diet vs. Calorie-Restricted Diet on Visceral Fat and Metabolic Profiles in Women with Polycystic Ovary Syndrome—A Randomized Controlled Trial
Authors: ZHANG YUQIN , SHAO XIAOWEN , CAI MEILI , DILIMULATI DILIQINGNA , QU SHEN , ZHANG MANNA
Published: June 2023

This study investigated whether dulaglutide combined with CRD could further reduce VAT and promote clinical benefits compared with the CRD regimen alone in overweight or obese women with PCOS. This single-center, randomized, controlled, open-label clinical trial was conducted between May 2021 and May 2022. Overall, 243 patients were screened, of which 68 overweight or obese women with PCOS were randomly assigned to receive dulaglutide combined with CRD treatment (n=35) or CRD treatment alone (n=33). The duration of intervention was set as the time taken to achieve a 7% weight loss goal from baseline body weight, which was restricted to 6 months. The primary endpoint was the difference in the change in VAT area reduction between the groups. The secondary endpoints contained changes in menstrual frequency, metabolic profiles, hormonal parameters, liver fat, and body composition. The mean time to achieve 7% weight loss was significantly shorter in the dulaglutide+CRD group than in the CRD group. There was no significant between-group difference in the change in VAT reduction (-0.97 cm2, 95% confidence interval, -14.36-12.42; P=0.884). Compared to CRD alone, dulaglutide+CRD had significant advantages in reducing glycated hemoglobin A1c and postprandial plasma glucose levels. Results of analyses of changes in menstrual frequency, other metabolic profiles, hormonal parameters, liver fat, and body composition were not significantly different between the two groups. Nausea, vomiting, constipation, and loss of appetite were the main adverse events of dulaglutide. These findings support the importance of dietary intervention as first-line management in women with PCOS, and glucagon-like peptide 1 receptor agonist (GLP-1 RA) therapy offers an effective and generally tolerable adjunct therapy to aid in achieving weight target based on dietary therapy in overweight/obese women with PCOS.

Disclosure

Y.Zhang: None. X.Shao: None. M.Cai: None. D.Dilimulati: None. S.Qu: None. M.Zhang: None.

Funding

National Natural Science Foundation of China (81601269)
1112-P: Soluble Suppression of Tumorigenicity 2 Is Directly Correlated with Body Fat, Metabolic Dysfunction, and Inflammation in Children and Adolescents
Authors: HASAN AMAL , KOCHUMON SHIHAB P. , ALBASIRI IMAN D. , ALMULLA FAHD , AHMAD RASHEED
Published: June 2023

Purpose: Childhood obesity is a major risk factor for chronic diseases such as type 2 diabetes (T2D) and cardiovascular disease. Elevated soluble suppression of tumorigenicity 2 (sST2) is associated with obesity, diabetes, and cardiovascular disease in adults, and is used as a biomarker of cardiometabolic disease. Such biomarkers play an important role in the management of obesity and cardiometabolic disease. In this cross-sectional study, we examined the levels of circulating sST2 in children and adolescents, as well as its association with inflammatory and metabolic markers.

Methods: A total of 85 children and adolescents (aged 5-16 years) were included. Participants' characteristics included being of normal weight (body mass index, BMI <85th percentile; n=13), overweight (BMI 85-94th percentile; n=2), or obese (BMI ≥95th percentile; n=70; a total of 8 with confirmed T2D). Clinical and biochemical markers (including plasma glucose, glycated hemoglobin (HbA1c), insulin, vitamin D, and lipid, liver, and renal profiles) were assessed using established procedures on peripheral blood samples. The levels of sST2, interleukin (IL)-33, IL-6, C-reactive protein (CRP), leptin, and adiponectin, were quantified using commercially available ELISA kits.

Results: sST2 level was directly correlated with body fat % (r=0.3, P=0.016, n=64) and fat to muscle ratio (r=0.37, P=0.01, n=45), but inversely correlated with muscle mass % (r=-0.34, P=0.02, n=45). sST2 level was directly correlated with insulin (r=0.29, P=0.04, n=50), HbA1c (r=0.29, P=0.04, n=51), and urea (r=-0.34, P=0.01, n=54). sST2 level was directly correlated with the inflammatory markers CRP (r=0.34, P=0.008, n=59) and IL-6 (r=0.32, P=0.0045, n=77). The data were consistent after adjustment for age and sex.

Conclusion: Increased circulating levels of sST2 is associated with increased body fat, metabolic dysfunction, and inflammation in children and adolescents.

Disclosure

A.Hasan: None. S.P.Kochumon: None. I.D.Albasiri: None. F.Almulla: None. R.Ahmad: None.

Funding

The Kuwait Foundation for the Advancement of Sciences (RA2011-018)
1113-P: Alanine Aminotransferase Elevation in Youth-Onset Type 2 Diabetes—Prevalence and Risk Factors
Authors: DELACEY SEAN E. , FENG SIYUAN , RANGANNA ADESH , FISHBEIN MARK , BIANCO MONICA E.
Published: June 2023

Purpose: Fatty liver and Type 2 Diabetes (T2D) are components of insulin resistance, but the prevalence of fatty liver disease at diagnosis of youth onset T2D is unknown. Fatty liver disease is typically identified initially by elevated alanine aminotransferase (ALT). We aim to describe the prevalence of ALT elevation in youth onset T2D at diagnosis and associated risk factors.

Methods: We conducted a single center retrospective review of patients (age≤21) diagnosed with T2D (5/1/2015-12/31/21). Chi-squared and two sample t-tests were used to compare those with ALT values in the highest and lowest quartiles at diagnosis for categorical and linear variables.

Results: Analysis included 455 patients. ALT was elevated at diagnosis and varied widely (mean=70.4 IU/L, standard deviation=76.0 IU/L). At diagnosis 48% of patients had ALT ≥45 IU/L and 14% had ALT ≥135 IU/L. Compared to those with ALT values in the lowest quartile, those in the highest quartile were more likely to be male (p=0.0001), Hispanic (p<0.00001), have a lower HgbA1C (8.9% vs 9.8%, p=0.001), and not identify as Black (p<0.00001). There was no difference in BMI Z-score. A follow-up ALT (6-18 months later) was available in 49% of patients: 37% had ALT≥45 IU/L and 7% had ALT≥135 IU/L (Figure 1).

Conclusions: Elevation of ALT is common at diagnosis of youth onset T2D, but often improves. Those with elevated ALT tend to have a lower HgbA1C and a similar BMI.

Disclosure

S.E.Delacey: None. S.Feng: None. A.Ranganna: None. M.Fishbein: None. M.E.Bianco: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007169)
112-LB: Proof-of-Concept Testing of an Artificial Intelligence–Based Fully Closed-Loop System in Hospitalized Patients with Diabetes
Authors: ZAHEDI TAJRISHI FARBOD , DAVIS GEORGIA M. , PEREZ-GUZMAN MIREYA , GUERRERO ARROYO LIZDA I. , BLANCO GERARDO , SAM VARGHESE JITHIN , HIRA ZAHID SYEDA , DEJOURNETT JEREMY , DEJOURNETT LEON , PASQUEL FRANCISCO J.
Published: June 2023

Objective: Achieving tight glucose control safely and effectively is challenging in the Intensive Care Unit (ICU). We conducted the first-in-human test of an artificial intelligence (AI)-based fully autonomous glucose control system in a simulated ICU setting.

Methods: We admitted seven participants with type1 and type 2 (n=6) diabetes mellitus for 24-hour closed-loop glucose control sessions that included three unannounced meals. The AI-based system uses glucose control software that controls intravenous insulin and glucose infusions based on real-time continuous glucose monitoring derived data from two real-time CGM devices. The primary efficacy endpoint was the percentage of glucose values within the range of 70-180 mg/dL. The primary safety endpoint was the percentage of glucose values < 70 mg/dL.

Results: Participants were on average 48±9.7 years-old, 71% female, and BMI 36±7.8 m/kg2. Mean time in the target range (70-180 mg/dl) was 87.8%. Mean time in the hypoglycemic range (< 70 mg/dL) was 0.2%, Figure. No adverse events occurred.

Conclusion: This first in-human results show this novel fully autonomous closed-loop glucose control system designed for the ICU setting has the potential to achieve unparalleled glycemic control with minimal risk of hypoglycemia and paves the way for further research in the actual ICU setting.

Disclosure

F. Zahedi tajrishi: None. F. J. Pasquel: Consultant; Dexcom, Inc., Medscape, Research Support; Dexcom, Inc., Ideal Medical Technologies. G. Davis: Consultant; Medscape, Research Support; Insulet Corporation. M. Perez-guzman: None. L. I. Guerrero arroyo: None. G. Blanco: None. J. Varghese: None. S. Zahid: None. J. Dejournett: Stock/Shareholder; Ideal Medical Technologies. L. Dejournett: Employee; Ideal Medical Technologies.

Funding

Ideal Medical Technologies; Dexcom, Inc.
1121-P: Association between Self-Monitored Blood Glucose and Continuous Glucose Monitor in Youth with Type 1 Diabetes and Medicaid
Authors: CHAN JANICE , YEE JENNIFER K. , MOIN TANNAZ , EVERETT ESTELLE M.
Published: June 2023

Background: In many states, patients with type 1 diabetes (T1D) and public insurance must demonstrate self-monitored blood glucose (SMBG) 3 times per day for continuous glucose monitor (CGM) approval. On January 2022, a policy change in California led to less stringent criteria for CGM approval, allowing for the evaluation of whether lower baseline SMBG leads to poor compliance and outcomes with CGM use.

Method: We used electronical health record data of pediatric patients with T1D, Medicaid at UCLA who started CGM after January 2019. Patients were stratified by SMBG frequency (< 3 times per day vs ≥ 3 times per day). We used descriptive statistics to report baseline demographics, and chi-squared test, t-test and logistic regression to evaluate differences in compliance and change in A1c.

Results: We found 52 patients who met the criteria - 52% with SMBG < 3 vs. 48% with SMBG ≥ 3. The patients were mostly male in both groups (63% vs. 60%). Patients with SMBG < 3 were older at time of T1D diagnosis (10 vs 6.2 years old), started CGM at older age (16.1 vs 11.7 years old), more likely to start CGM after January 2022 (82% vs 40%), and had higher baseline A1c (10.9% vs 9.0%). At 3 and 6 months after starting CGM, there was significantly greater reduction in A1c in those with SMBG <3 (1.6% vs 0.3%, p = 0.021, and 1.5% vs 0.23%, p = 0.01). There was no significant difference in CGM compliance (60% vs 72%, p = 0.21, and 69% vs 80%, p = 0.24, respectively) between the two groups. In adjusted models for 3 and 6 months, there were no significant association between CGM compliance (OR 1.04, 95%CI 0.68-1.60, and OR 1.06, 95%CI 0.76-1.28, respectively) and change in A1c.

Conclusion: Patients with lower baseline SMBG had similar CGM compliance and greater improvement in A1c than patients with higher baseline SMBG. This suggests that restricting CGM approval to those who are adherent to SMBG ≥3 may exclude use in patients who would benefit the most from CGM technology. Larger studies are needed to confirm these findings.

Disclosure

J.Chan: None. J.K.Yee: None. T.Moin: None. E.M.Everett: None.

Funding

University of California, Los Angeles Children's Discovery and Innovation Institute (CDI-FRSA-07012022); National Center for Advancing Translational Sciences (UL1TR001881)
1124-P: Outcomes of Health-Related Social Needs Screening in a Midwest Pediatric Diabetes Clinic Network
Authors: HALPIN KELSEE , RELAN SHILPI , ROGHAIR JASMINE , POMERANTZ RHIANNON , EVANS KATELYN , BARNES MITCHELL S. , FEINGOLD HEATHER , JACOB SAMANTHA N. , WINTERER COURTNEY , COLVIN JEFFREY D. , CLEMENTS MARK A. , DEWIT EMILY L.
Published: June 2023

Background: Screening for health-related social needs (HRSNs) is recommended as part of standard diabetes care given the strong impact of social factors on health outcomes. We implemented a HRSN screen at routine diabetes clinic visits and assessed differences between youth with positive and negative screens.

Methods: A 6-item questionnaire was adapted from the Accountable Health Communities Health-related Social Needs Screening Tool to screen for HRSNs in 4 domains: 1) housing, 2) utilities 3) transportation, 4) food. A positive screen was defined as any positive response to a HRSN. Cross-sectional data was analyzed using chi-square or independent t-test.

Results: There were 4,119 screens completed over 14 months with 10% (n=438) being positive. The majority of positive screens were positive for a single HRSN (73%), most commonly food insecurity (66%). Table 1 compares youth with positive vs. negative screens. A higher percentage of positive screens was found in minority youth (p<0.001), while a lower percentage was seen in youth with commercial insurance (p<0.001) and diabetes technology use (p<0.001). Most indicators of diabetes control were less optimal in the positive screen group.

Summary: Youth with HRSNs are at risk for adverse health outcomes. Screening for HRSNs can be incorporated into routine pediatric diabetes care and may help enhance health equity in delivery of care.

Disclosure

K.Halpin: None. J.D.Colvin: None. M.A.Clements: Consultant; Glooko, Inc., Research Support; Dexcom, Inc., Abbott Diabetes. E.L.Dewit: None. S.Relan: None. J.Roghair: None. R.Pomerantz: None. K.Evans: None. M.S.Barnes: None. H.Feingold: None. S.N.Jacob: None. C.Winterer: None.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust
1125-P: Real-World Pediatric Outcomes of Hybrid Closed-Loop Systems at a Large Urban Center
Authors: TILLOTSON CARA V. , NICHOLS PRESLEY H. , MOFFORD KAISHA , LEIBEL NATASHA , GANDICA RACHELLE
Published: June 2023

Objectives: To study the real-world effect of hybrid closed loop systems (HCLS) on glycemic control and quality of life (QoL) in pediatric patients with T1D.

Methods: Patients 2-20 years old with T1D for ≥ 1 year were recruited when starting t:slim x2 with CIQ (TS) or Omnipod 5 (O5). We collected time in range (TIR), time low (BG <70 mg/dl), A1c, and QoL survey responses at baseline and 3 months. Kruskal-Wallis rank sum test and chi-squared test were used for data analysis.

Results: Baseline data is in Figure 1. TIR improved by 7% after 3 months of HCLS use (p=0.004). Time low was unchanged after 3 months (p=0.3). Figure 2 shows results by subject.

Discussion: In this real-world study, HCLS improved TIR at 3 months without change in hypoglycemia. Data collection, enrollment, and analysis are ongoing with more results (A1c, QoL surveys) expected shortly.

Disclosure

C.V. Tillotson: None. P.H. Nichols: None. K. Mofford: None. N. Leibel: None. R. Gandica: None.

Funding

National Institutes of Health (5T32DK065522-18)
1126-P: Smart Insulin Pens—A Randomized, Crossover Pilot Trial Assessing Glycemic Control and Diabetes-Related Burdens in Adolescents and Emerging Adults with Diabetes
Authors: JACKSON SARAH , KUMAR SEEMA , AL NOFAL ALAA , HENTZ ROLAND , PITTOCK SIOBHAN , CREO ANA
Published: June 2023

Introduction: Despite advancements in diabetes technology, some adolescents, and emerging adults with type 1 diabetes (T1D) remain on insulin injections. There is a need to reduce the burden of managing T1D in adolescents who use insulin injections.

Objective: To determine whether a smart insulin pen (InPen™) alters the glycemic control, glucose variability, burden of diabetes care, and parental experience in adolescents and emerging adults with T1D.

Methods: We performed a randomized, cross-over prospective pilot trial in participants 13-21 years with T1D. Participants were randomized to either 90 days of standard multiple daily injection management with continuous glucose monitor (CGM) use or 90 days of InPen™ and CGM use with a cross-over design, switching to the other arm for 90 days. We assessed diabetes control, diabetes distress, transition readiness, and parental experience of illness scales.

Results: Fourteen participants were enrolled in the trial, 1 withdrew. At baseline, median HbA1C was 8.1%, (IQR 7.7, 9.1). There was no statistically significant change in HbA1C, average glucose, glucose SD, total insulin dose, or time in range using the InPen™ relative to standard of care. Participants using the InPen™ had declining engagement with time, calculator use was 41.5% (IQR 5.0, 84.0) and 7% (IQR 0.0, 59.0) at 30 and 90 days, respectively. Questionnaire outcomes did not demonstrate statistically significant differences between treatments; diabetes distress did improve but not statistically significant.

Conclusion: InPen ™ use was not associated with improved diabetes control but did trend to decreasing diabetes distress. Low InPen™ calculator use could be a potential factor for the lack of improvement in glycemic control. Larger studies are warranted to study the effect of smart insulin pen technology on glycemic metrics and diabetes-related burdens in adolescents and emerging adults with T1D.

Disclosure

S.Jackson: Research Support; Medtronic. S.Kumar: None. A.Al nofal: None. R.Hentz: None. S.Pittock: None. A.Creo: None.
113-OR: The OPTIFAST (OP) Total and Partial Meal Replacement Program Improves Cardiometabolic Risk in Adults With Obesity—Secondary and Exploratory Analysis of the OPTIWIN Study
Authors: ARD JAMY D. , NEELAND IAN , ROTHBERG AMY E. , CHILTON ROBERT , DE LUIS DANIEL , HAWKINSON ANDREA H. , COHEN SARAH S. , ERIK JOHANSEN ODD
Published: June 2023

The effects of weight loss on atherosclerotic cardiovascular disease (ASCVD) risk factors using a partial or total meal replacement program (MRP) are not fully understood. We performed secondary and exploratory analyses of changes in blood pressure (BP), lipids, and global ASCVD risk in a randomized, controlled MRP trial using OP (n=135) compared with a low-calorie food-based (FB) dietary plan (n=138) that resulted in significant weight loss at week (W) 26 (reduction phase) and W52 (maintenance). Baseline characteristics were well balanced (mean [standard deviation] age OP/FB 47 [11]/47 [11] years, BMI 38.4 [5.5]/39.2 [6.2] kg/m2, females 86/79%, 10-year ASCVD risk <5% 87/74%, dysglycemia 52/50%). Changes in risk factors were estimated by a linear mixed model. At W26, systolic/diastolic BP were significantly reduced with OP vs FB (table), and a greater proportion achieved ≤ 130/80 mmHg (66.7% vs 53.6%, OR 2.11 [95% CI 1.10, 4.03], p=0.024). All lipid parameters significantly improved, as did the global ASCVD risk. A similar, but slightly attenuated pattern was observed at W52. In subgroup analysis by age (<40, 40-59, ≥ 60 years), SBP (</≥ 130 mmHg) and sex, greater treatment effects were generally seen with higher SBP and age, and in men. In people with obesity at low ASCVD risk, OP significantly improved CV risk factors and global ASCVD risk.

Disclosure

J.D.Ard: Advisory Panel; Novo Nordisk, Consultant; Eli Lilly and Company, Intuitive Surgical, Regeneron, Other Relationship; Optum Labs, Weight Watchers International, Research Support; Nestlé Health Science, Boehringer Ingelheim Inc., Epitomee, KVK Tech. I.Neeland: Consultant; Nestlé Health Science, Speaker's Bureau; Boehringer Ingelheim and Eli Lilly Alliance, Bayer Inc. A.E.Rothberg: None. R.Chilton: None. D.De luis: None. A.H.Hawkinson: Employee; Nestlé Health Science. S.S.Cohen: Consultant; Nestlé Health Science. O.Johansen: Employee; Nestlé Health Science.

Funding

Nestlé Health Science
1136-P: Type A Insulin Resistance Masquerading as Type 1 Diabetes Mellitus
Authors: LOS EVAN A. , WIRTHWEIN KACI
Published: June 2023

More than 150 mutations in the INSR gene encoding the insulin receptor have been identified causing a spectrum of insulin resistance syndromes from mild (type A insulin resistance) to more severe (Rabson-Mendenhall syndrome, Donahue syndrome). Type A insulin resistance typically presents in childhood or early adulthood. We describe a 19-year-old male with type A insulin resistance due to heterozygous INSR gene mutation, c.3470A>G (His1157Arg). This mutation has previously been identified in female patients with hyperglycemia, insulin resistance. The patient presented at age 14 with polyuria, polydipsia, hyperglycemia (glucose 200s) without acidosis, and normal BMI (50th%) and was presumed to have type 1 diabetes. He was treated with insulin though required escalating doses to 2-2.5 units/kg/day and was started on metformin to improve insulin sensitivity which had a minor effect on total daily insulin requirements. HbA1c was typically 7-9% for several years with this treatment plan and BMI remained near 50th%. The patient was subsequently lost to follow-up and after self-discontinuing insulin for approximately 1 year, re-presented with hyperglycemia, the absence of ketonuria or acidosis, elevated insulin level (92.2 μIU/ml), negative islet cell antibodies, HbA1c 10.9%. Notably, he did not have acanthosis nigricans. Subsequent genetic testing revealed a mutation in the INSR gene consistent with type A insulin resistance. This case highlights the importance of considering monogenic forms of diabetes and insulin resistance syndromes in lean patients who require higher-than-expected insulin doses with presumed type 1 diabetes.

Disclosure

E.A.Los: Other Relationship; Medtronic. K.Wirthwein: None.
1138-P: INNOVATIONS—Improving Care of Patients with Type 1 Diabetes Mellitus through Utilization of Telemedicine and Outreach—Twelve-Month Outcomes
Authors: RASBACH LISA E. , PURRINGTON VIRGINIA C. , ADKINS DEANNA , BENJAMIN ROBERT
Published: June 2023

Despite advances in diabetes treatment options, many youth fail to meet glucose targets and remain at risk of developing complications. Additional diabetes support in the form of telehealth may help youth meet diabetes related goals. Eligible youth had insulin dependent diabetes, Medicaid insurance, were ages 8-18, and willing to use a continuous glucose monitor (CGM). The quality improvement project provided weekly check-ins with a diabetes educator and monthly video visits with a nurse practitioner. Participants also received visit reminder calls. We measured A1c at quarterly clinic visits and tracked ED/hospitalization rates. 12-month data presented. Youth (N=26, 65% female, 88% NHB), aged 8-18 yr, diabetes duration 6.3±4.3 years, 23% were on insulin pumps. There was a significant difference between baseline A1c (mean 12.3%) at 6 months (mean A1c 11.2%) (p=0.02) and at 9 months (mean A1c 11.2%) (p=0.02). There was no significant difference in hospitalization rates during the 12-month intervention. There was no difference in visit adherence at 3, 6, 9, or 12 months during the intervention compared to those times prior. Participants were wearing CGM significantly more 3 months into the intervention compared to 3 months prior (p=0.008). Although not statistically significant, more participants were using CGM consistently at 6, 9 and 12-month time points compared to prior. 27% of participants started insulin pumps during the intervention. An intensive telehealth intervention provided interim improvement in glycemic control. Although not statistically significant, more participants used CGM consistently during the intervention, which could have clinical significance over time. Efforts to improve the durability of technology use and glycemic control warrant exploration.

Disclosure

L.E.Rasbach: None. V.C.Purrington: None. D.Adkins: None. R.Benjamin: None.

Funding

Innovation Health Grant (2933476)
1142-P: Use of a Relational Agent Smart Phone App Aims to Improve Time in Range (TIR) for Youth with Type 1 Diabetes (T1D)
Authors: MACCOLL SOPHIE , SPARTZ BRITANEY , DEWIT EMILY L. , LOCKEE BRENT , WILLIAMS DAVID D. , BARNES MITCHELL S. , CLEMENTS MARK A.
Published: June 2023

Background: Youth with T1D struggle to achieve blood glucose (BG) TIR targets. However, their inclination for technology makes a glucose self-management app an ideal intervention. We aimed to improve TIR using a relational agent smart phone app. The Happy Bob (HB) app uses Dexcom Continuous Glucose Monitor (CGM) data with personified nudges to gamify engagement for users in BG monitoring.

Method: We collaborated with HB developers to customize an app for youth ≥12 years old with T1D, who use Dexcom and a smartphone. We analyzed participants’ CGM data 28-days pre- and post-enrollment and required at least 7-days of wear time in both 28-day periods.

Results: For a cohort of N=31, average %TIR was (Mean±SD) 54.35±23.61 vs 56.32±22.54 pre- to post-intervention (p=0.3560), with % low and very low showing modest changes (Table 1). We further divided the cohort into 2 groups: those with a change in TIR <5.0% (n=22) vs those with a change ≥5.0% (n=9). Notably, the ≥5.0% group had lower %TIR values pre-intervention compared to the <5.0% group (33.56±11.63 to 62.86±22.00; p=0.0008) and showed an average increase in TIR of 15.1%.

Summary: In this pilot cohort, TIR values did not improve from pre- to post-intervention Future work should examine whether HB has a positive impact when bundled with additional interventions like remote patient monitoring.

Disclosure

S.Maccoll: None. B.Spartz: None. E.L.Dewit: None. B.Lockee: None. D.D.Williams: None. M.S.Barnes: None. M.A.Clements: Consultant; Glooko, Inc., Research Support; Dexcom, Inc., Abbott Diabetes.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust
115-LB: Human Feasibility of a Semiconductor-Based Continuous Glucose Monitoring System
Authors: MUJEEB-U-RAHMAN MUHAMMAD , HONARVAR NAZARI MEISAM , SENCAN MEHMET , NADIR ABDULLAH , HEITHAUS JOHN H. , MARCUS ALAN O.
Published: June 2023

CGMs have advanced significantly in recent years. However, accuracy, response speed, size, and cost improvements are still required for better adoption and outcomes. We combine semiconductor and nano technologies to create an extremely miniaturized (5x smaller than a rice grain) electrochemical sensing platform, IMSense. It is user-insertable under the skin using a custom injector and is also user-removable. It has a multi-sensor array and sends multiplexed data to an external transmitter which processes and relays it to a reader via BLE. It also has a reference sensor to monitor the system status. We previously validated the system in the lab and in animals. Recently, a study in a cohort of 10 persons (with and without diabetes) was approved. In the study, fingerprick readings from each subject were taken every 15 minutes for one day (6 hours) using a Contour SMBG meter (reference) and compared against readings from IMSense, Dexcom, and Abbott CGMs. The results show that the IMSense tracks the reference precisely. A response curve in a person with diabetes and the Clarke error grid for the study are shown (the correlation coefficient between IMS and reference is 93%). The three glucose sensors and the reference sensor on an IMSense device are used to formulate an accurate combined signal. These results demonstrate the human feasibility of monitoring glucose using an integrated sensor array on a single semiconductor device.

Disclosure

M. Mujeeb-u-rahman: None. M. Honarvar nazari: None. M. Sencan: None. A. Nadir: None. J. H. Heithaus: None. A. O. Marcus: Other Relationship; Integrtated Medical Sensors.

Funding

National Institutes of Health (DK111001)
1150-P: Improving Early Diagnosis of Presymptomatic Stage 2 Type 1 Diabetes with a Sample-Sparing Assay
Authors: TSAI JASON
Published: June 2023

Teplizumab was approved by the FDA in Nov 2022 as the first therapeutic to delay progression of type 1 diabetes from pre-symptomatic stage 2 to clinical onset stage 3. Nevertheless, individuals with stage 2 type 1 diabetes do not exist in hospital systems, and more than 85% of them do not have family history. Large scale population testing remains the only effective way of identifying eligible patients for disease interventional drugs. Thus, accurate, accessible and low cost tests are urgently needed to implement such screening programs. To that end, we have conducted a pilot retrospective screening efficacy study with blinded serum specimens from the Diabetes Prevention Trial of Type 1 Diabetes (DPT-1) study from the NIDDK central repository. A total of 97 serum specimen from subjects that either developed T1D within 5 years (i.e. 50 progressors) or had at least 5 years of follow-up (i.e. 47 progressors) were included in the study. A subject was considered high-risk for T1D progression if positive for two or more islet autoantibodies, and vice versa. Under this scheme, the multiplex ADAP assay achieved PPV and NPV of 49% and 92% for 5 years progression risks. The matching radiobinding assay (RBA) had PPV and NPV of 50% and 77% in this cohort. The improved NPV stemmed from 12 progressors tested positive for multiple islet autoantibodies by multiplex ADAP but not by RBA. Notably, 6 out of these 12 subjects tested positive for multiple islet autoantibodies by RBA in subsequent sampling events with a median delay of 2.8 years compared to multiplex ADAP.

In summary, the multiplex ADAP assay could be an ideal tool for large scale identification of individuals with stage 2 type 1 diabetes due to its sample-sparing nature (i.e. 4µL serum input), non-radioactiveness, compatibility with widely-available real-time qPCR instruments and favorable risk prediction capability.

Disclosure

J. Tsai: Stock/Shareholder; Enable Biosciences.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R44DK124009-01)
1162-P: Promoting Career Development of Physicians Engaged in Type 1 Diabetes (T1D) Research—The New DiabDocs Multicenter National K12 Program
Authors: DASANI KOMAL D. , BISHOP FRANZISKA K. , GOLDEN SHERITA , LAFFEL LORI M. , MIRMIRA RAGHAVENDRA G. , STECK ANDREA , TAMBORLANE WILLIAM V. , WILLI STEVEN M. , MAAHS DAVID M. , DIMEGLIO LINDA
Published: June 2023

Background: Given low rates of physicians entering diabetes research, NIH recently funded a multi-center National K12 “DiabDocs” Program to train and support physician-scientists for productive academic careers in T1D. Specific aims for the program include: 1) Expand the geographical access to diabetes K12 programs in the US, 2) Create a diverse nationwide cohort of promising physician-scientists through shared programmatic training experiences, 3) Develop a national mentor community, 4) Ensure consistency and effectiveness of mentoring, including focused attention on diversity, equity and inclusion.

Methods: DiabDocs program administration is comprised of 2 Program Directors, an Executive Leadership Committee, a National Advisory Committee and Scientific Review Committee. Recruitment for the first cohort of program Scholars began in August 2022. Candidates self-nominated with a Letter of Intent (LOI). Eligible Scholars were then invited to submit a full application and attend a program retreat. Of the 12 LOIs received from 12 different institutions, 10 candidates were invited to submit a full application and attend the program retreat. At the retreat, 19 reviewers from 16 different institutions participated in diversity training, conducted interviews, and gathered as a study section to discuss applications.

Results: Ultimately 4 scholars were selected: 2 with pediatric endocrinology and 2 with adult endocrinology backgrounds. Three scholars are women, and 1 scholar self-identifies as from a group underrepresented in medicine (25%). The next application cycle is planned for Jan-March 2023.

Conclusions: The DiabDocs program will address the critical shortage of trained physician-scientists focused on T1D. We anticipate that the planned program training combined with existing research infrastructures will engage a talented and diverse pool of scholars and accelerate their career trajectories.

Disclosure

K.D.Dasani: None. L.Dimeglio: Advisory Panel; Merck & Co., Inc., Consultant; Abata Therapeutics, Vertex Pharmaceuticals Incorporated. F.K.Bishop: None. S.Golden: Advisory Panel; Abbott Diabetes, Medtronic. 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. R.G.Mirmira: None. A.Steck: None. W.V.Tamborlane: None. S.M.Willi: Advisory Panel; Boehringer Ingelheim International GmbH, Medtronic. D.M.Maahs: Advisory Panel; Medtronic, LifeScan Diabetes Institute, MannKind Corporation, Consultant; Abbott, Research Support; Dexcom, Inc.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (K12DK133995)
1166-P: Identifying Knowledge Strengths and Deficits of Young Adults with Type 1 Diabetes (T1D)
Authors: KUBOTA-MISHRA ELIZABETH A. , MIRANDA NELLY , HILLIARD MARISA E. , MCKAY SIRIPOOM
Published: June 2023

Among challenges that young adults with T1D face in their care are expectations for independence with healthcare system navigation and diabetes knowledge competency. This is a particular concern given increased hemoglobin A1c (HbA1c) and complications among young adults. A 50-item diabetes-specific knowledge assessment (KA) was developed and utilized in a young adult diabetes program to identify the areas of strength and deficits to guide education and care. To identify the competency of diabetes knowledge, KA items were categorized to describe strengths, deficits, and variable responses. A retrospective chart review was performed in patients with T1D transferring from Texas Children's Hospital to a single adult endocrinology program. Inclusion criteria included T1D for >1 year and completion of KA by diabetes educator or provider. Each KA item was scored on a 1-4 scale (4 = high). Scores were grouped into 3 categories: strengths as >80% of the young adults scoring ≥3, deficits as >50% score <3, and Variable (V) not meeting criteria for strength nor deficit. Over 4.5 years, 142 patients had KAs (M age 20.5 ± 1.4 yrs, HbA1c = 8.8 ± 1.9%, T1D duration = 10.4 ± 4.7 yrs, 54% pump, 52% CGM). KA strengths (18) included questions addressing insurance card, safe sex practices, teaching treatment of mild hypoglycemia, and insulin pump management. KA deficits (11) included diabetes specific knowledge, alcohol use, tobacco, pregnancy, and acute and chronic complications of diabetes. Variable questions (21) included diabetes pathophysiology, identifying an adult PCP and hospital, and counting carbohydrates. Complications of diabetes, the effect of alcohol on blood glucose, glucagon administration, and pregnancy and diabetes should be re-educated upon transfer to adult healthcare. Questions related to insurance cards, safe sex, and insulin pump management may not need to be immediately prioritized at transfer. Further research with this KA will validate it for implementation in clinics and research.

Disclosure

E.A.Kubota-mishra: None. N.Miranda: None. M.E.Hilliard: None. S.Mckay: None.
1168-P: Time-Limited Eating in Youth with Newly Diagnosed Type 1 Diabetes—Feasibility and Impact on Beta-Cell Function
Authors: BERMAN CASEY , VIDMAR ALAINA , FLORES GARCIA JAQUELIN J. , RAYMOND JENNIFER
Published: June 2023

Introduction: Time limited eating (TLE) improves β-cell function, increases insulin sensitivity, lowers fasting glucose, and increases time in range in adults with T2D. Objectives: This study aims to evaluate TLE in pediatric new-onset T1D, at which time residual β-cell function may be preserved.

Aim 1) Evaluate feasibility, acceptability, and safety of TLE. Aim 2) Test impact of TLE on β-cell function and insulin sensitivity. Aim 3) Assess effectiveness of TLE on glycemic control.

Methods: A randomized controlled trial of youth aged 12-25 years diagnosed with T1D within 12 months; randomization to intervention (8-hour feed/16-hour fast) or control group (≥12-hour feed) for an 8-week period. Feasibility is evaluated using questionnaires and adherence. Safety is indicated by hypoglycemia frequency. β-cell function is evaluated by mixed meal tolerance test (MMTT) with area under C-peptide curve (AUC). Glycemic control is evaluated by time in range (TIR 70-180 mg/dL) on CGM and HbA1c.

Results: Six youths have entered, three have completed (2 intervention, 1 control). Participants in intervention group adhered to TLE ~94% of time. Both reported TLE felt safe, noted improved stability of glucose, chose to continue TLE after study ended, and would recommend to others with T1D. No increased hypoglycemia frequency noted on CGM. Participant 2 (intervention) had increase in AUC from baseline (87.45 to 152.4) and decrease in HbA1c (-1.3 percentage points), although participant 1 (intervention) had decrease in AUC and no change in HbA1c. Participant 3 (control) had increase in AUC and decrease in HbA1c, both changes less than participant 2. No improvement in TIR on CGM was demonstrated in either group.

Conclusion: This is the only known study evaluating TLE in youth with T1D and has the potential to advance management of T1D by introducing meal-timing early in diagnosis. Thus far the intervention appears feasible and safe, however more data is needed. Recruitment continues to be underway.

Disclosure

C.Berman: None. A.Vidmar: Advisory Panel; Rhythm Pharmaceuticals, Inc., Research Support; Dexcom, Inc. J.J.Flores garcia: None. J.Raymond: None.