bluuebunny/crossref_metadata_2025 huggingface dataset:
36-LB: Feasibility and Acceptability of a Family-Based mHealth Intervention in Low-Income Chinese Families with Type 2 Diabetes
Authors: HU LU , CHENG SHEN , ISLAM NADIA , WYLIE-ROSETT JUDITH , WU BEI , FELDMAN NAUMI , SCHOENTHALER ANTOINETTE , OGEDEGBE OLUGBENGA , JIANG NAN , TAMURA KOSUKE , BUBU OMONIGHO , SEVICK MARY ANN
Published: May 2022

Objective: To examine the feasibility and acceptability of implementing a family-based mhealth intervention tailored for low-income Chinese immigrant families with type 2 diabetes (T2D) in New York City (NYC) .

Methods: We recruited 11 patient-family partner adult dyads to receive the intervention. Both the patient and partner were asked to watch 2 brief videos each week for 12 weeks via the social media app WeChat. The culturally and linguistically tailored videos addressed diabetes self-management and provided guidance on how to support the patient’s self-management. Feasibility was evaluated via participant retention and video watch rates. Acceptability was assessed at 12-weeks via a 9-item survey using a 5-point Likert scale (1=strongly agree to 5=strongly disagree) , and a single item on which participants rated satisfaction using an 11-point Likert scale (0=not at all satisfied to 10=totally satisfied) . Participants also were asked about barriers to watching the videos.

Results: The care dyads were mostly middle-aged, married, with less than a high school education, limited English proficiency, and an annual household income <$25,000. Most family members were spouses of the patient. The retention rate was 90.9% at 12 weeks. The mean (SD) video watch rate was 76.7% (7.0%) . Lack of time was the most common barrier to watching videos. Participants reported high satisfaction (mean ± SD: 9.1 ± 1.7 for patients and 10.0 ± 0 for family members) . All strongly agreed or agreed that videos were easy to receive and open on WeChat, and provided helpful information about diet and physical activity. Most strongly agreed or agreed that they would recommend the program to others and preferred video-based diabetes education to in-person programs.

Conclusions: A family-based mHealth intervention is feasible and acceptable among low-income Chinese immigrant families with T2D in NYC.

Disclosure

L. Hu: None. K. Tamura: None. O. Bubu: None. M. Sevick: None. S. Cheng: None. N. Islam: None. J. Wylie-rosett: None. B. Wu: None. N. Feldman: None. A. Schoenthaler: None. O. Ogedegbe: None. N. Jiang: None.

Funding

National Institutes of Health (K99MD012811) ; National Institutes of Health (R00MD012811) ; National Institutes of Health (P30DK111022)
363-OR: Weight Loss, Lifestyle Intervention, and Metformin Effects on the Longitudinal Relationship between Insulin Secretion and Sensitivity in the Diabetes Prevention Program (DPP)
Authors: ARREOLA ELSA VAZQUEZ , KNOWLER WILLIAM C. , HANSON ROBERT L.
Published: May 2022

Insulin secretion and sensitivity regulate glycemia, with inadequately compensated deficiencies in either or both leading to diabetes. Using data from 2931 participants in the DPP repository, we investigate the effects of lifestyle and metformin interventions and of weight loss on the relationship between insulin secretion and sensitivity. Insulin secretion and sensitivity were estimated from insulin concentrations in fasting and 30-minute post-load serum samples at baseline and at 1, 2, and 3 years after randomization during the active intervention phase of the DPP. The relationship of secretion and sensitivity was evaluated by standardized major axis regression and was found to change over time for participants in the lifestyle and metformin interventions. Distances along and away from the regression line were taken to characterize insulin secretory demand and insulin secretion in compensation to the demand, respectively. Both the metformin and lifestyle interventions decreased secretory demand while increasing compensatory insulin secretion, with greater effects of the lifestyle intervention. Improvements were directly related to the amount of weight loss; decreases in weight significantly reduced secretory demand [b=-0.088 SD (-0.102, -0.074) /5 kg loss] and increased compensatory insulin secretion [b=0.169 SD (0.149, 0.189) /5 kg loss]. In time-dependent hazard models, increasing secretory demand associated with increased diabetes risk [hazard ratio (HR) =1.189 per baseline SD (1.004, 1.413) ] while increasing compensatory insulin secretion associated with lower risk [HR=0.1 (0.080, 0.145) ]. These results are consistent with earlier observations in the DPP that diabetes risk reduction was directly related to the amount of weight loss and suggest that this effect is mediated by lowered insulin secretory demand coupled with improved compensatory insulin secretion.

Disclosure

W.C. Knowler: None. R.L. Hanson: None.
364-OR: Apolipoprotein A-I and Clinical Remission in Adults with Type 1 Diabetes-InLipoDiab1 Study
Authors: URUSKA ALEKSANDRA , ROHATGI SR., ANAND , CIELUCH ALEKSANDRA , GRZELKA-WOZNIAK AGATA , FLOTYNSKA JUSTYNA , PYPEC ALEKSANDRA , ZOZULINSKA-ZIOLKIEWICZ DOROTA
Published: May 2022

Introduction: Apolipoprotein A-I (Apo A-I) , the main protein in high-density lipoproteins, improves beta-cell function and insulin sensitivity in experimental models and in people with type 2 diabetes. In those with type 1 diabetes (DM1) , clinical remission (CR) is a key factor for improved prognosis. However, predictors of CR in DM1 are not well described. Whether Apo A-I predicts CR in patients with DM1 remains unknown. Aim To assess the relationship between baseline Apo A-I at the time of diagnosis of DM1 with the presence of CR after 12 months of the disease.

Methods: The participants of Insulin Therapy and Lipoproteins' Profile in Type 1 Diabetes Study (InLipoDiab1; NCT02306005) were prospectively observed from the onset of the disease (the blood collection was performed before exogenous insulin administration) through 12 months. The final observation included 53 adults (62% men, age at onset 27±6 years) . DM1 was confirmed with guideline-based criteria on the presence of specific autoantibodies. The endpoint was the presence of pCR at the end of observation, which was defined as IDAA1C ≤ 9, according to the definition by Mortensen et al.: A1C (%) + [4 × insulin dose (U/kg/day) ]. Apo A-I was measured in serum with an ELISA kit. The group was divided into two according to the presence and absence of pCR.

Results: At 12 months, pCR was present in 43 participants (81%) . Baseline serum Apo A-I was significantly lower in participants without pCR versus those with the presence of pCR [0.79 (0.39-1.58) vs. 4.51 (0.95-5.93) mg/dl, p=0.002, respectively]. In multiple logistic regression, higher baseline Apo A-I was associated with the presence of pCR after 12 months, adjusted for sex, age, weight and the presence of diabetic ketoacidosis at onset (OR 1.74 (CI 95% 1.02-2.96) , p=0.03) .

Conclusion: The higher Apo A-I serum concentration at onset of DM1 the higher chance is for pCR in adults with DM1, after 12 months of observation. Higher serum Apo A-I levels seem to be a good prognostic factor for pCR of DM1.

Disclosure

A.Uruska: Other Relationship; Lilly, Novo Nordisk. A.Rohatgi: Speaker's Bureau; CSL Behring. A.Cieluch: None. A.Grzelka-wozniak: Other Relationship; Novo Nordisk, Roche Diabetes Care. J.Flotynska: None. A.Pypec: None. D.Zozulinska-ziolkiewicz: Advisory Panel; Dexcom, Inc., Medtronic, Speaker's Bureau; Abbott Diabetes, Ascensia Diabetes Care, AstraZeneca, BIOTON S.A., Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi.

Funding

Kosciuszko Foundation and Poznan University of Medical Sciences
365-OR: Interruption of Glucagon Signaling Increases Delta-Cell Proliferation in Mouse and Human Islets
Authors: DAI CHUNHUA , BRADLEY AMBER , SPEARS ERICK , SINGH AJAY K. , OLADIPUPO FAVOUR O. , JENKINS REGINA , COATE KATIE C. , POWERS ALVIN C.
Published: May 2022

The determinants of delta cell mass are not known. As part of studies showing interruption of glucagon signaling (IGS) stimulates alpha cell proliferation in an amino acid (AA) -dependent manner, we noted an increase in delta cells. To investigate, we examined delta cell proliferation and mass in 3 mouse models and a human islet xenograft model. Adult mice with deletion of glucagon (Gcg-/- ) had a 4.7-fold increase in Ki67-positive delta cells (1.50±0.14% vs. 0.32±0.12%, P<0.001, n=8) and a 3.1-fold increase in delta cell mass (0.49±0.vs. 0.16±0.mg, P=0.003, n=10) . Treatment of adult C57BL/6J mice with a Gcg receptor antibody (GCGR Ab) elicited a 6.3-fold increase in delta cell proliferation (2.01±0.4% vs. 0.32±0.07%, P=0.002, n=10) and a 2.6-fold increase in delta cell mass (0.20±0.03 vs. 0.078±0.mg, P=0.001, n=10) , respectively, compared to IgG-treated controls. Since hyperaminoacidemia is necessary for alpha cell proliferation in response to IGS, we investigated the requirement for Slc7a2, a cationic AA transporter, in delta cell growth. Indeed, Slc7a2+/+ mice, but not Slc7a2-/- mice, treated with GCGR Ab had a 3.8-fold increase in delta cell proliferation (3.29±0.14% vs. 0.86±0.05%, P<0.001) and 1.6-fold increase in delta cell mass (0.20±0.02 vs. 0.126±0.mg, P=0.016, n=8) . Given that mTOR is a known intracellular mediator of AA-regulated cellular growth, we evaluated phospho-ribosomal protein S6 (pS6) expression in situ and found a marked increase in pS6 labeling of delta cells in Gcg-/- , but not Gcg+/+ , mice. We also observed a 3.6-fold increase in delta cell proliferation (1.75±0.25% vs. 0.49±0.06%, P=0.004, n=3 adult normal donors) in human islets transplanted into immunodeficient mice treated with GCGR Ab. Taken together, these data indicate that IGS promotes delta cell proliferation and mass through mechanisms involving Slc7a2 and the mTOR signaling pathway and that AAs may be a determinant of delta cell mass.

Disclosure

C.Dai: None. A.Bradley: None. E.Spears: None. A.K.Singh: None. F.O.Oladipupo: None. R.Jenkins: None. K.C.Coate: None. A.C.Powers: None.
37-OR: Childhood Screening and Interception Strategies: An Economic Cohort Simulation Model
Authors: TRUSHEIM MARK , KOSTENSE STEFAN , FERRAT LAURIC A. , MCQUEEN R. BRETT , NEUSNER ROBERT D. , ORAM RICHARD A. , REWERS MARIAN , DUNNE JESSICA L.
Published: May 2022

T1D screening and monitoring studies suggest opportunities for scaling up to public health population-based programs. Genetic Risk Scores (GRS) for T1D are also demonstrating the ability to identify those at higher risk of progressing to T1D as well as an increased opportunity for implementation into public health settings potential as a result of practical considerations, including falling gene sequencing costs.Previous studies have shown that screening and monitoring children for T1D progression significantly decreases DKA events at diagnosis, which has been shown to have both short- and long-term benefits. Furthermore, identification of those at higher risk of T1D provides an opportunity to intervene and delay T1D onset. A non-stochastic, state transition cohort simulation projected 20US births through adolescence. Data from previously collected natural history studies, including TEDDY, DIPP & DAISY were used to model the patient journey. Children seroconverting to islet autoantibodies (IAB) each year and children with lower T1D risk were simulated as separate cohorts with distinct progressions. Interception strategies were layered over this natural history projection. Success of GRS screening followed by annual IAB and glucose monitoring to intercept T1D progression and reduce DKA events was explored. Therapeutic intervention to delay T1D onset was also simulated.Real-world benchmarks for newborn screening (85%) and patient follow-up (80%) as well as rapid T1D progression (<12 months) for some children limited maximum interception at dysglycemia to 52% of children progressing to T1D by age 15 using a GRS screening strategy. Short-term net incremental costs range reach $1.1B at current test costs or $225K per T1D case interception. Breakeven costs could be achieved with $40 IAB test cost and $5 GRS costs with a therapeutic to delay T1D onset by 3 years or possibly by including assessment potential long-term benefits of early intervention and improved glycemic control.

Disclosure

M.Trusheim: Other Relationship; CO BIO CONSULTING LLC. S.Kostense: Employee; Janssen Research & Development, LLC. L.A.Ferrat: None. R.Mcqueen: Consultant; Merck & Co., Inc., Monument Analytics, Research Support; Eli Lilly and Company. R.D.Neusner: Employee; Janssen Pharmaceuticals, Inc. R.A.Oram: Consultant; Janssen Research & Development, LLC, Research Support; Randox R & D. M.Rewers: Consultant; Janssen Research & Development, LLC, Medscape, Provention Bio, Inc., Research Support; Dexcom, Inc., JDRF, Roche Diagnostics USA. J.L.Dunne: Employee; Janssen Research & Development, LLC, JDRF.
38-OR: Glycemic Control with Ultrarapid Lispro (URLi) vs. Lispro in Children and Adolescents with T1D: PRONTO-Peds
Authors: WADWA R. PAUL , LAFFEL LORI M. , FRANCO DENISE R. , DELLVA MARY A. , POLLOM ROBYN K.
Published: May 2022

This phase 3, treat-to-target study evaluated efficacy and safety of URLi vs. lispro in 716 pediatric patients (pts) with type 1 diabetes (T1D) . After 4-week lead-in to optimize basal insulin, pts were randomized to double-blind URLi (n=280) or lispro (n=298) injected 0-2 min prior to meals, or open-label URLi (n=138) injected up to 20 min after meals (URLi+20) . Pts remained on prestudy basal insulin (degludec, detemir, or glargine) . Primary endpoint was HbA1c change from baseline after 26 weeks.

Noninferiority was shown in HbA1c change with URLi vs. lispro: estimated treatment difference (ETD) -0.02% (95% CI -0.17, 0.13) and with URLi+20 vs. lispro: ETD -0.02% (95% CI -0.20, 0.17) . Postprandial glucose (PPG) measured by self-monitored blood glucose (SMBG) was lower with URLi vs. lispro 1 h after breakfast (p<0.001) and dinner (p=0.006) . URLi significantly reduced 1 h postmeal glucose daily mean vs. lispro (p=0.001) . Total daily insulin dose was similar between treatments.

There were no significant differences among treatments in rate or incidence of severe, nocturnal or documented hypoglycemia (<54 mg/dL) . With URLi vs. lispro, rate of postdose hypoglycemia (<54 mg/dL) was higher at ≤2 h (p=0.034) . Incidence of treatment-emergent adverse events was similar between groups. More pts reported an injection site reaction related event with URLi (7.9%) and URLi+20 (2.9%) vs. lispro (2.7%) . All injection site reactions were mild or moderate in severity. Two URLi patients discontinued the study due to injection site reactions.

In children and adolescents with T1D, URLi demonstrated similar overall glycemic control and greater PPG lowering with an acceptable safety and tolerability profile compared with lispro. URLi dosed at the start of meals or up to 20 min after the start of meals showed noninferiority for HbA1c change from baseline vs. lispro. URLi dosed at the beginning of meals showed lower PPG at 1 h after breakfast and dinner and lower 1 h postmeal glucose daily mean vs. lispro.

Disclosure

R. Wadwa: Advisory Panel; Dompé. Consultant; Beta Bionics, Inc. Research Support; Dexcom, Inc., Eli Lilly and Company, Tandem Diabetes Care, Inc. Other Relationship; Tandem Diabetes Care, Inc. L.M. Laffel: Advisory Panel; Medtronic, Roche Diabetes Care. Consultant; Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompé, Insulet Corporation, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk, Provention Bio, Inc. D.R. Franco: Advisory Panel; Abbott Diabetes, Medtronic, Novo Nordisk, Sanofi. Research Support; Eli Lilly and Company. Speaker's Bureau; Abbott Diabetes, AstraZeneca, Medtronic, Roche Diabetes Care, Sanofi. M.A. Dellva: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. R.K. Pollom: Employee; Eli Lilly and Company.

Funding

Eli Lilly and Company
393-P: SGLT2 Inhibitors Reduce Cardiovascular and Renal Risks Compared with GLP-1 Receptor Agonists and DPP4 Inhibitors in Patients with Diabetic Kidney Disease: A Systematic Review and Network Meta-analysis
Authors: CAO HONGWEI , LIU TAO , WANG LI , JI QIUHE
Published: May 2022

Background: This systematic review and network meta-analysis compared the effectiveness of sodium-glucose co-transporter 2 inhibitors (SGLT2Is) , glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 inhibitors (DPP4Is) on cardiovascular (CV) and renal outcomes in patients with diabetic kidney disease (DKD) (INPLASY2021120070) .

Methods: The MEDLINE database was searched systematically to identify articles that reported CV and renal outcomes from Phase III or IV randomised, placebo-controlled trials after intervention with SGLT2Is, GLP-1 RAs or DPP4Is in patients with DKD. HRs and 95% CIs were calculated using a network meta-analysis.

Results: 16 trials representing a total of 46,292 patients were analysed. SGLT2Is significantly reduced the risks of kidney-specific composite outcome by 26% (HR=0.74, 95% CI 0.62-0.88) and 36% (HR=0.64, 95% CI 0.52-0.79) ; and the risks of hospitalisation for heart failure (HHF) by 28% (HR=0.72, 95% CI 0.56-0.92) and 41% (HR=0.59, 95% CI 0.49-0.71) , compared to GLP-1 RAs and DPP4Is respectively. SGLT2Is also reduced the risk of major adverse cardiovascular events (MACE) by 18% (HR=0.82, 95% CI 0.69-0.96) compared to DPP4Is. The risk of MACE was comparable between SGLT2Is and GLP-1 RAs (HR=0.95, 95% CI 0.82-1.10) . The risk of CV death was not significantly different between the three treatments.

Conclusions: This meta-analysis integrated data from recent high-quality CV and renal outcome trials, providing high statistical power. SGLT2Is significantly lowered risks of kidney-specific outcome, MACE and HHF compared to DPP4Is and placebo, and reduced risks of kidney-specific outcome and HHF compared to GLP-1 RAs. GLP-1 RAs also showed CV and renal outcome benefits compared to placebo, but not compared to SGLT2Is or DPP4Is for most outcomes. DPP4Is did not improve either CV or renal outcomes compared to placebo.

Disclosure

H.Cao: None. T.Liu: None. L.Wang: None. Q.Ji: None.
395-P: BeAM Value and Glycemia Assessed by Continuous Glucose Monitoring among Participants with Type 2 Diabetes and Chronic Kidney Disease
Authors: MAYEDA LAURA , ZELNICK LEILA , TRIKUDANATHAN SUBBULAXMI , HIRSCH IRL B. , DE BOER IAN
Published: May 2022

Introduction: The difference between bedtime and morning glucose levels (BeAM value) is a clinically relevant measure that can guide clinicians regarding insulin titrations. As chronic kidney disease (CKD) develops, changes in insulin sensitivity and kinetics and limitations to available medications may contribute to over-basalization, insufficient prandial control, and large BeAM. We hypothesized that CKD and less time in range (TIR) derived from continuous glucose monitoring (CGM) are associated with large BeAM in T2DM.

Methods: This was a prospective observational cohort study of 1people with T2DM treated with insulin or sulfonylurea, 81 participants with CKD (eGFR <60 mL/min/1.73 m2) , and 24 controls with eGFR ≥60 frequency matched on age, duration of diabetes, HbA1c, and glucose-lowering medications. Each participant wore a CGM for two 6-day periods. BeAM was calculated as the difference between mean bedtime sensor glucose values and mean morning sensor values, with large BeAM defined as ≥30 mg/dL glucose drop from bedtime to morning.

Results: Participants had a mean age of 68 years, diabetes duration years and HbA1c 7.7%. CKD and controls had a mean eGFR 38 and 83 mL/min/1.73 m2 respectively. Median (IQR) BeAM was 29 (9-52) mg/dL for participants with CKD and (-4-31) mg/dL for controls (p = 0.11) . Forty participants with CKD (49%) and 7 controls (29%) had a large BeAM. Those with a large BeAM had less TIR (58 v 68%) , higher HbA1c (8.0 vs. 7.5%) , and higher glucose management indicator (GMI, 7.5 vs. 7.2%) compared to those with BeAM <30 mg/dL (each p<0.05, adjusting for age, sex, and race) . Coefficient of variation, diabetes duration, and insulin dose (total or basal) did not correlate with BeAM.

Conclusions: Large BeAM was common among participants with long-standing T2DM and CKD and was associated with less TIR and higher GMI. These data suggest that there is opportunity for improvement in daytime and prandial diabetes management among patients with CKD.

Disclosure

L.Mayeda: None. L.Zelnick: None. S.Trikudanathan: Research Support; Bionic pancreas, Bionic pancreas , Insulet Corporation, Insulet Corporation. I.B.Hirsch: Consultant; Abbott Diabetes, Bigfoot Biomedical, Inc., GWave, Roche Diabetes Care, Research Support; Beta Bionics, Inc., Insulet Corporation, Medtronic. I.De boer: Advisory Panel; AstraZeneca, Bayer AG, Cyclerion Therapeutics, Inc., George Clinical, Goldfinch Bio, Inc., Other Relationship; American Society of Nephrology, Research Support; Dexcom, Inc.

Funding

American Diabetes Association (4-15-CKD-20) ; National Institute of Diabetes and Digestive and Kidney Diseases (R01DK088762, R01087726)
4-LB: Remission of Type 2 Diabetes and Improvement in Metabolic Markers with the Twin Precision Treatment Technology (TPT) —A Multicenter, Randomized, Controlled Trial
Authors: SHAMANNA PARAMESH , SHAH LISA , MOHAMMED JAHANGIR , MOHAMED MALUK , POON TERRENCE , DHARMALINGAM MALA , SABOO BANSHI , DAMODHARAN SURESH , VADAVI ARUN , THAJUDEEN MOHAMED , KESHAVAMURTHY ASHOK , KAUFMAN FRANCINE R. , JOSHI SHASHANK R.
Published: May 2022

The study was designed to determine the effect of TPT vs. standard care (SC) on change in A1C and T2DM remission at 90 day intervals, in addition to multiple secondary endpoints. The TPT intervention uses the Whole-Body Digital Twin Platform, with AI and Internet of Things, to integrate multi-dimensional data to give precision nutrition and health recommendations via the TPT app and by coaches. Baseline mean age, diabetes duration and A1C obtained in 319 pts were 45y (±9.7y) , 3.9y (±2.9y) and 9.0% (±1.9%) , respectively. Interim analysis of 262 pts (TPT n=199; SC n=63) who reached 180d showed 94.9% (189/199) of TPT pts had A1C < 6.5%, on no medications or metformin only; 83.9% (167/199) achieved diabetes remission based on ADA criteria. All 9 insulin-using pts stopped insulin before 90d. The Table shows significant improvement in secondary endpoints in TPT pts at baseline and 180d, including A1C (9.0% to 5.7%, P<0.001) . TPT pts had -3.3% change in A1C (95% CI -3.6 to -3%, P=<0.001) compared to SC with -0.39% (95% CI -0.73 to -0.043%, P=0.028) , with a significant between-group difference (P=<0.0001) . The TPT intervention in pts with T2DM allowed for significant reduction in A1C, diabetes remission (∼84%) and improvement in multiple metabolic parameters at 6 months. Future long-term studies are needed to support these initial findings.

Disclosure

P. Shamanna: None. M. Thajudeen: None. A. Keshavamurthy: None. F. R. Kaufman: Consultant; Twin Health, Employee; Senseonics. S. R. Joshi: Advisory Panel; AstraZeneca, Consultant; Biocon, Franco India, Glenmark Pharmaceuticals, Marico, Sanofi, Twinhealth, Zydus Cadila, Speaker’s Bureau; Abbott, Serdia Pharmaceuticals (India) Pvt. Ltd. L. Shah: None. J. Mohammed: None. M. Mohamed: None. T. Poon: None. M. Dharmalingam: None. B. Saboo: None. S. Damodharan: None. A. Vadavi: None.
40-LB: Mobile Health App Can Be Effective in a Real-World Environment for Those with Diabetes Needing Weight Loss
Authors: HORVAT SHERRI L. , NOVAK LUCIA M. , VALENTINE VIRGINIA , CHILDS BELINDA P. , BARRY ROMIYA , WARNER JAY
Published: May 2022

BEATdiabetes is based on Joslin Diabetes Center’s Why WAIT program, a 12-week program designed to help improve weight and diabetes glycemia, incorporating structured diet, learning sessions and individualized exercises. The Why WAIT program has demonstrated effectiveness virtually. Endpoints included weight, BMI, and A1c. The program employed a version of BEATdiabetes app (developed by Healthimation Inc®, licensed by Nemaura Medical) and utilized gamification to engage users. In addition, participants shared 2-hour, weekly virtual visits to review food logs, exercise sessions, and CGM data with diabetes medications adjusted accordingly. This initial pilot study uses the BEATdiabetes app and seeks to identify if results can be replicated in a real-world environment (RWE) without virtual visits, CGM data and program medication adjustment. The APRN, CDCES live coach had phone calls with users weekly for the first 4 weeks, then 4-week intervals for the next 8 weeks with more touchpoints available (emails, in-app chat, phone calls) . Self-reported endpoints showed users remained engaged utilizing the app 70/84 days, completed 74% of 7 daily tasks, and positively received education, resulting in weight loss, reduction in BMI and waist circumference, and improvement/maintenance in glycemia all during the holiday season. Based upon pilot study learnings changes were identified for next steps in RWE.

Disclosure

S. L. Horvat: Consultant; Nemaura Medical, Employee; W5 Insights, LLC. L. M. Novak: Advisory Panel; Novo Nordisk, Provention Bio, Inc., Xeris Pharmaceuticals, Inc., Consultant; Abbott Diabetes, Novo Nordisk, Xeris Pharmaceuticals, Inc., Speaker’s Bureau; Abbott Diabetes, Eli Lilly and Company, Novo Nordisk, Xeris Pharmaceuticals, Inc. V. Valentine: Advisory Panel; Abbott Diabetes, Xeris Pharmaceuticals, Inc., Consultant; Nemaura, Pendulum, Zealand Pharma A/S, Speaker’s Bureau; Lilly Diabetes. B. P. Childs: Consultant; W5 Insight LLC, Other Relationship; Sanofi-Aventis U. S., Research Support; Abbott Diabetes. R. Barry: Consultant; W5 Insights, LLC. J. Warner: Consultant; Nemaura Medical, Tandem Diabetes Care, Inc.
406-P: Effects of Butyrate Supplementation on Inflammation and Kidney Parameters in Type 1 Diabetes—A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: TOUGAARD NINNA H. , FRIMODT-MOELLER MARIE , SALMENKARI HANNE , STOUGAARD ELISABETH BUUR , MATTILA ISMO , HANSEN TINE W. , LEGIDO-QUIGLEY CRISTINA , HÖRKKÖ SOHVI , FORSBLOM CAROL , GROOP PER-HENRIK , LEHTO MARKKU , ROSSING PETER
Published: May 2022

Background: Fecal calprotectin, a marker of inflammation, is increased in persons with type 1 diabetes (T1D) and kidney disease. This may be explained by a reduction of butyrate-producing bacterial species in the gut. Butyrate supplementation has beneficial effects on intestinal inflammation in inflammatory bowel disease but has never been tested in persons with T1D.

Objective: To assess the effect of sodium butyrate on fecal calprotectin and other inflammatory markers, kidney parameters, hba1c and gastrointestinal symptoms in persons with T1D and intestinal inflammation.

Methods: Randomized placebo-controlled, double-blind, parallel clinical study including 53 participants with T1D, albuminuria and intestinal inflammation (elevated fecal calprotectin) . Participants were assigned to receive 3.6 g sodium butyrate daily (n=28) or placebo (n=25) for 12 weeks. Primary endpoint was fecal calprotectin changes, and additional outcomes were fecal short chain fatty acids, intestinal alkaline phosphatase activity and immunoglobulins; serum lipopolysaccharide, serum C-reactive protein, albuminuria, kidney function, hba1c and gastrointestinal symptoms.

Results: Mean age of the participants was 54±13 years, 43% were women, diabetes duration was 30±15 years and median [Q1:Q3] urinary albumin excretion was 46 [14:121] mg/g. Median fecal calprotectin in the butyrate group was 48 [26:100] μg/g at baseline and change was -1.0 [-20:10] μg/g, the median in the placebo group was 61 [25:139] μg/g at baseline and change was -12 [-95:1] μg/g. Difference in change between groups was not significant (p=0.24) . Neither did we find an effect of butyrate compared to placebo on the other fecal and circulating inflammatory markers, kidney parameters, hba1c or gastrointestinal symptoms.

Conclusion: Oral butyrate supplementation for 12 weeks did not reduce fecal calprotectin in persons with T1D and intestinal inflammation.

Disclosure

N.H.Tougaard: None. P.Groop: Advisory Panel; Novo Nordisk, Sanofi, Other Relationship; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Mundipharma, Speaker's Bureau; Medscape. M.Lehto: None. P.Rossing: Consultant; Astellas Pharma Inc., AstraZeneca, Bayer AG, Gilead Sciences, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Speaker's Bureau; Eli Lilly and Company. M.Frimodt-moeller: None. H.Salmenkari: None. E.Buur stougaard: Other Relationship; Novo Nordisk. I.Mattila: None. T.W.Hansen: Stock/Shareholder; Novo Nordisk A/S. C.Legido-quigley: None. S.Hörkkö: None. C.Forsblom: None.
410-P: Preoperative Diabetes Optimization and Clinical Outcomes
Authors: MENDEZ CARLOS E. , WALKER REBEKAH J. , GARACCI EMMA , PFEIFER KURT
Published: May 2022

A diabetes optimization pathway for elective surgical patients with uncontrolled diabetes (A1c> 8%) has been in place at our institution for the last 5 years. Although we reported on improvement in glucose control before surgery in patients undergoing the intervention, impact on longer-term clinical outcomes was not known. We extracted EPIC medical record data for adult surgical patients in the diabetes optimization program between January 2016 and October 2021 (n=85) . The control group had uncontrolled diabetes and underwent surgery but had no intervention (n=1,111) . Logistic regression, GLM and Cox proportional hazard models were used to investigate relationship with 30 day complications, glucose at surgery, and overall mortality. Table 1 shows bivariate comparisons for the study cohort. The rates of perioperative complications were numerically lower in the intervention group, however, were not statistically significant. Unadjusted regression analyses found significantly lower glucose at surgery (β =-14.19, 95% CI=-27.94,-0.43) , and significantly lower hazard ratio for overall mortality (HR=0.34, 95% CI=0.13,0.93) for the intervention. After adjusting for demographics, clinical risk, and comorbidities, only glucose at surgery maintained significance (β =-16.89, 95% CI=-30.83,-2.95) . Prospective studies or a larger sample may be needed to confirm findings.

Disclosure

C.E.Mendez: Advisory Panel; Monarch Medical Technologies . R.J.Walker: None. E.Garacci: None. K.Pfeifer: None.
411-P: Potential to Utilize DNA Methylation as a Biomarker to Predict Major Coronary Artery Disease (CAD) Risk in Type 1 Diabetes (T1D)
Authors: MILLER RACHEL G. , MYCHALECKYJ JOSYF , ONENGUT-GUMUSCU SUNA , ORCHARD TREVOR J. , COSTACOU TINA
Published: May 2022

DNA methylation (DNAme) has been associated with risk of future CAD in the general population and is a potential target for pharmacological intervention. In T1D, DNAme has been associated with microvascular complications but its association with CAD has not been examined in this high risk population. Thus, we performed an epigenome-wide association study (EWAS) of DNAme and 28-year major CAD (CAD death, nonfatal myocardial infarction) incidence in an observational T1D cohort. Whole blood DNAme was assayed via Illumina EPIC beadchip in the Pittsburgh Epidemiology of Diabetes Complications (EDC) study of childhood onset (<17 years) T1D (n=400; mean age 29, T1D duration 21 yrs) . After quality control DNAme at 683,597 CpGs was analyzed in Cox models for time-to-CAD, adjusting for T1D duration, sex, smoking pack-years, estimated blood cell composition, and technical/batch covariates. Over 28 years 102 (25%) developed major CAD. DNAme at two CpGs was associated with lower CAD risk: cg06125996 (Chr 5, NLN; log HR per 5% DNAme= -1.10, p=6.0e-11) and cg051638 (Chr 9, CARD9; log HR= -0.97, p=1.2e-08) . Other associations with FDR<5% included CpGs in MRPS21, ZNF428, PCMTD1, and LYRM4. KEGG pathway analysis of all CpGs with FDR<10% (n=44) suggested enrichment for renin-angiotensin-aldosterone system, lipid metabolism, and immune system pathways. In GWAS we identified methylation quantitative trait loci (QTL) associated with DNAme at cg06125996 and cg05163804, three of which were annotated as expression QTLs in GTEx including SNPs in genes involved in insulin receptor signaling (SIK2) and cytokine activity (CMTM2, CMTM4) , and calcium ion binding (EFHB) . DNAme was not correlated with cross-sectional HbA1c at either CpG and adjusting for baseline HbA1c did not alter CpG-CAD associations. Our results demonstrate that DNAme may be an early marker of CAD risk in T1D, but the potential role of glycemic exposure in this association is unclear and warrants further study.

Disclosure

R.G.Miller: Stock/Shareholder; Becton, Dickinson and Company. J.Mychaleckyj: None. S.Onengut-gumuscu: None. T.J.Orchard: None. T.Costacou: None.

Funding

American Diabetes Association (1-19-JDF-109) ; NIH/NIDDK R01-DK034818, Rossi Memorial Fund
417-P: Prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) in Children with Type 1 Diabetes (T1D) and Its Association with Arterial Stiffness
Authors: ZEIAD RAWAH , CRESPO MARICRUZ , WOOD JAMIE R. , FARRELL RYAN M.
Published: May 2022

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children. NAFLD has become increasingly recognized in pediatric populations with type 1 diabetes (T1D) . Also, NAFLD is emerging as an independent risk factor for cardiovascular disease (CVD) . Arterial stiffness is an index of subclinical atherosclerosis and can predict cardiovascular events and mortality.

Objectives: The aim of this pilot study was to estimate the prevalence of NAFLD in children with T1D and to examine the relationship between NAFLD and arterial stiffness.

Subjects and Methods: A cross-sectional pilot study of 18 children (age 7-20 years) with a diagnosis of T1D for at least 5 years without secondary causes of chronic liver disease. The main study measures included: 1. Detection of fatty liver in children with T1D measured by controlled attenuation parameter (CAP) using FibroScan and 2. Measurement of arterial stiffness by pulse wave velocity (PWV) using SphygmoCor. We also aimed to measure hepatic fibrosis by FibroScan and insulin sensitivity (IS) by using a validated surrogate marker.

Results: The prevalence of NAFLD was approximately 19% of study participants. We found positive correlations between CAP and PWV values, which suggests higher arterial stiffness with higher degree of fatty liver. Median PWV was higher in participants with steatosis compared to those without steatosis, 6.vs. 6.5 m/s. We also found negative correlations between IS and both arterial stiffness and steatosis (R=-0.56, p=0.038) , (R=-0.56, p=0.063) , respectively.

Conclusions: Our findings suggest that NAFLD is common in participants with T1D and in this study was associated with higher arterial stiffness. Our study is consistent with previously reported associations between decreased IS and presence of microvascular complications. Larger randomized controlled trials are required to evaluate whether NAFLD predicts the incidence of CVD events in T1D.

Disclosure

R.Zeiad: None. M.Crespo: None. J.R.Wood: Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Insulet Corporation, MannKind Corporation. R.M.Farrell: Stock/Shareholder; Dexcom, Inc., Tandem Diabetes Care, Inc.

Funding

18117-FRAP 2020-21
419-P: Chronic Kidney Disease, Type 2 Diabetes, and the Risk of Major Cardiovascular Events in Coronary Artery Disease vs. Peripheral Artery Disease Patients
Authors: SPRENGER LUKAS , MAECHLER MAXIMILIAN , VONBANK ALEXANDER , LARCHER BARBARA , MADER ARTHUR , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H.
Published: May 2022

Chronic kidney disease (CKD) is a paramount indicator of cardiovascular risk and is highly prevalent in patients with established cardiovascular disease, especially among those with type 2 diabetes (T2DM) . Peripheral artery disease (PAD) confers an even higher risk than coronary artery disease (CAD) . How cardiovascular risk compares between PAD and CAD patients when analyses are stratified by the presence of CKD is unclear and is addressed in the present study.

We prospectively recorded major cardiovascular events (MACE) over 10.0±4.7 years in 1356 patients who had stable CAD, of whom 18.4% had CKD, and in 382 patients with PAD, of whom 20.9% had CKD. Four groups were analyzed: CAD patients without CKD (CAD/CKD-; n=1106) , CAD patients with CKD (CAD/CKD+; n=250) , PAD patients without CKD (PAD/CKD-; n=316) and PAD patients with CKD (PAD/CKD+; n=66) .

The incidence of MACE was lowest in CAD/CKD- patients (27.2%) and significantly higher in CAD/CKD+ patients (49.6%; p<0.001) , in PAD/CKD- patients (40.9%; p<0.001) , and in PAD/CKD+ patients (56.9%; p<0.001) , who in turn were at a higher risk than CAD/CKD+ or PAD/CKD- patients (p=0.015 and p<0.001, respectively) . The risk of MACE did not differ significantly between CAD/CKD+ and PAD/CKD- patients (p=0.063) . In Cox regression analysis after multivariate adjustment including gender, age, BMI, hypertension, history of smoking, LDL-C, and HDL-C the presence of PAD versus CAD (HR=1.51 [1.25-1.84]; p<0.001) , CKD (HR=1.85 [1.51- 2.26]; p<0.001) and T2DM (HR=1.53 [1.29-1.83; p<0.001) were mutually independent predictors of MACE.

We conclude that CKD, T2DM and the presence of PAD versus CAD are mutually independent predictors of MACE.

Disclosure

L.Sprenger: None. M.Maechler: None. A.Vonbank: None. B.Larcher: None. A.Mader: None. A.Leiherer: None. A.Muendlein: None. H.Drexel: None. C.H.Saely: None.
422-P: Predictive Role of Triglyceride-Glucose Index on All-Cause Mortality and Incidence of Vascular Events in Type 2 Diabetes (T2D) : A 13-Year Follow-Up Observational Study
Authors: GAROFOLO MONIA , LUCCHESI DANIELA , GUALDANI ELISA , FALCETTA PIERPAOLO , GIAMBALVO MASSIMO , FRANCESCONI PAOLO , DEL PRATO STEFANO , PENNO GIUSEPPE
Published: May 2022

Triglyceride glucose index (TyG-i) is an alternative marker of insulin resistance and an independent predictor of CV events; yet its prognostic value in T2D remains poorly assessed.A cohort of 961 T2D was followed-up for 13.1±2.8 years. Vital status was retrieved on December 31, 2017 and data for CV events were available for 947 of them. TyG-i [ln (fasting triglycerides (mg/dL) x fasting glucose (mg/dL) / 2) ] was calculated at baseline and divided in tertiles (thresholds: 8.97 and 9.51) . Events were assessed by Kaplan-Meier (K-M) curves and HRs (95% CI) by unadjusted and adjusted Cox regressions (Cox-r) in TyG-i tertiles.At follow-up, 229 (23.8%) subjects died (18.25 x 1000 PYs) ; CV events occurred in 273 (28.8%; 25.68 x 1000 PYs) , coronary events (CHD) in 181 (19.1%; 16.20 x 1000 PYs) , hospitalization for heart failure (hHF) in 82 (8.7%; 6.79 x 1000 PYs) , cerebrovascular events (CVE) in 1 (10.7%) , peripheral vascular events (PVE) in 39 (4.1%) , ESRD in 71 subjects (7.5%; 5.87 x 1000 PYs) . On K-M, CVD (24.2%, 25.6% and 36.7%; p=0.001) and CHD (14.5%, 17.1% and 25.9%; p=0.001) increased with TyG-i. All other outcomes increased across tertiles in a not significant manner. On unadjusted Cox-r, cumulative incidence of CV events and CHD increased significantly across TyG-i tertiles (T3 vs. T1) for major CVD (HR 1.65, 95% CI 1.24-2.20, p=0.001) and CHD (1.91, 1.33-2.74, p<0.00for) , or marginally for PVD (1.99, 0.93-4.29, p=0.078) . After adjusting for age, diabetes duration, age at diagnosis, sex, BMI, active smoking, HbA1c, uric acid, fibrinogen, hypertension, dyslipidemia, prior CVD, CKD, retinopathy and neuropathy, HRs still increased with TyG-i for CV events (T3 vs. T1, 1.96, 95% CI 1.44-2.67, p<0.0001) , and CHD (T3 vs. T1, 2.03, 1.40-2.93, p<0.0001) .

In conclusion, TyG-i was significantly and independently associated with CVD and CHD, suggesting that it may be a simple yet valid marker for risk stratification in T2D.

Disclosure

M.Garofolo: Employee; Eli Lilly and Company. D.Lucchesi: None. E.Gualdani: None. P.Falcetta: Speaker's Bureau; Abbott Diabetes. M.Giambalvo: None. P.Francesconi: None. S.Del prato: Advisory Panel; Applied Therapeutics, Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Sanofi, Consultant; Menarini Group, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Sanofi, Stock/Shareholder; Novo Nordisk A/S. G.Penno: Advisory Panel; Eli Lilly and Company.
439-P: Disparate Effects of Menopause on Cardiovascular Risk in Women with Type 1 Diabetes
Authors: WISE HALEY K. , MALECHA EMILY , CHARTIER-LOGAN CATHERINE J. , PYLE LAURA , KESHAWARZ AMENA , SNELL-BERGEON JANET K.
Published: May 2022

Introduction: Women with type 1 diabetes (T1D) are at increased risk for cardiovascular disease (CVD) , and menopause increases CVD risk. However, little is known about menopause and CVD risk in T1D.

Methods: Women with (N=64) and without T1D (n=63) ages 47-55 years were examined for CVD risk factors and surrogate CVD markers: pulse wave velocity (PWV) , augmentation pressure (AP) and pulse height (PH) , brachial artery distensibility (BrachD) , and subendocardial viability index (SVI) . Body composition was measured by Dual Xray Absorptiometry. Menopausal status was determined by self-report. CVD markers were examined by diabetes and menopausal status using linear regression models adjusted for age.

Results: Mean ± SD age was 51±2.5 years in women with T1D and 51 ± 2.4 years in women without diabetes (p=0.32) . The percentage postmenopausal did not differ (30% vs. 32%, p=0.8) between T1D and nondiabetes women. As shown in the table, women with T1D had higher systolic blood pressure and measures of arterial stiffness (PWV, AP, PH, and BrachD) and lower SVI than women without diabetes. Menopause was associated with a greater loss in fat free mass and a greater increase in PWV and AP among women with T1D compared to women without diabetes.

Conclusions: Women with T1D have worse CVD markers, and menopause is associated with greater increases in arterial stiffness and loss in lean body mass than in nondiabetes women, independent of age.

Disclosure

H.K.Wise: None. E.Malecha: None. C.J.Chartier-logan: None. L.Pyle: None. A.Keshawarz: None. J.K.Snell-bergeon: Stock/Shareholder; GlaxoSmithKline plc.

Funding

American Diabetes Association (7-13-CD-10)
443-P: Structural Echocardiographic Abnormalities in T2D: Mexico Cohort of Take Care of Me Program
Authors: SAHAGÚN-SÁNCHEZ GUILLERMO , BHOGRAJ CHARIT , GUTIÉRREZ-FAJARDO PEDRO , RODRIGUEZ-VALADEZ FLORISA , LAVALLE-GONZALEZ FERNANDO J. , VAZQUEZ-MENDEZ ESTEFANIA , MEZA-LEDEZMA OMAR
Published: May 2022

Rationale: Due to gaps in detecting subclinical cardiac abnormalities in T2D, we evaluated prevalence and clinical manifestations of early echocardiographic (echo) abnormalities in primary care in Mexico.

Methods: Mexico cohort of the ongoing ‘Take CaRe of Me program’ enrolled 2760 people with T2D (between 7 Dec 2020 - Dec 2021) and no cardiorenal disease per index visit history. We present descriptive data of documented echo performed by cardiologists as routine clinical care (499) in high-risk T2D identified by Systematic Coronary Risk Evaluation (ESC 2019) .

Results: With mean age of 54.2±11.4 years, 55.4% were females and 189 patients (37.9%) had echo abnormalities — left ventricular hypertrophy (21%, 105) , left atrial enlargement (24.2%, 121) , diastolic dysfunction (6.8%, 34) , pulmonary hypertension (5.4%, 27) and valvular disease (4.8%, 24) . Substantial proportion of people with echo abnormalities had high or very high CV risk (Table) . Overall, 23 people had presumptive diagnosis of pre-HF based on symptoms and echo. Per documented data, 18 people had HF with preserved ejection fraction (EF) , 4 had mid-range EF and 1 had reduced EF.

Conclusion: Structural abnormalities are prevalent in 37.9% of people with T2D referred for an echo, even in absence of symptoms. Timely diagnosis of silent structural heart abnormalities in T2D is an opportunity for using novel cardiorenal pharmacotherapy for preventing HF.

Disclosure

G.Sahagún-sánchez: None. C.Bhograj: None. P.Gutiérrez-fajardo: None. F.Rodriguez-valadez: None. F.J.Lavalle-gonzalez: Speaker's Bureau; Abbott Diagnostics, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi, Servier Laboratories. E.Vazquez-mendez: None. O.Meza-ledezma: None.

Funding

The preparation of the abstract was funded by AstraZeneca Pharma Limited.
444-P: Associations of LDL-C with New-Onset Coronary Artery Disease (CAD) According to HDL-C Levels and Glucose Status
Authors: YAMADA MAYUKO H.
Published: May 2022

Whereas elevated LDL-C is a major risk factor for CAD, the inverse association between HDL-C levels and risk of CAD is well-known. Although insulin resistance and glucose intolerance are associated with low HDL-C levels, it is not clear whether the association of LDL-C with CAD differs depending on glucose status and HDL-C values. We examined associations of LDL-C with new-onset CAD according to HDL-C and glucose status using a nationwide claims database on 600,6individuals during 2008-20with no history of CAD. Cox proportional hazards model identified risks of CAD events among combinations of tertiles of HDL-C and sextiles of LDL-C according to glucose status. During a mean follow-up period of 5.6 years, 2,391 CAD events occurred. CAD risk increased from lower LDL-C levels accompanied by lower HDL-C levels regardless of glucose status (Table) . Compared with the highest tertile of HDL-C and lowest sextile of LDL-C, groups with the highest tertile of HDL-C and highest sextile of LDL-C and the lowest tertile of HDL-C and highest sextile of LDL-C had approximately 4-fold and 9-fold, respectively, increased risks of CAD regardless of glucose status. Despite the necessity of a lower LDL-C target for people with than without diabetes, our results demonstrated that the necessity of modulating the LDL-C target according to HDL-C levels is not affected by concomitant diabetes.

Disclosure

M.H.Yamada: None.