bluuebunny/crossref_metadata_2025_split huggingface dataset:
405-P: Glycemic Control Impacts Renal Function Decline among People with Type 1 Diabetes after the Onset of Diabetic Kidney Disease
Authors: SHAH HETAL , MCGILL JANET B. , HIRSCH IRL B. , WU CHUN-YI , GALECKI ANDRZEJ , MAUER MICHAEL , DORIA ALESSANDRO , CONSORTIUM PERL 
Published: May 2022

While poor glycemic control increases the risk of diabetic kidney disease (DKD) , its impact on renal function decline among those with established DKD is unclear. To examine this, we tested the relationship between baseline HbA1c and renal outcomes in the 3-year Preventing Early Renal Loss (PERL) trial (n=530) , which included persons with type 1 diabetes (T1D) and early-to-moderate DKD (eGFR 40-100 ml/min/1.73m2 and persistent albuminuria and/or ongoing GFR decline) . In Cox regression models, baseline HbA1c was associated (p&lt;0.0001) with a higher risk of progression to ESKD or serum creatinine doubling (HR 1.87 per HbA1c unit increment, 95% CI 1.42-2.47) , and in mixed-effects linear regression models, with 0.87 and 0.51 ml/min/1.73m2/year higher rates of estimated glomerular filtration rate (eGFR) and iohexol GFR decline (p&lt;0.00for both) . Baseline albumin excretion rate (AER) was a modifier of the HbA1c-GFR slope relationships (p for interaction &lt;0.05) , such that HbA1c was associated with a higher rate of GFR decline among those with AER≥200 μg/min than among those with AER&lt;20 or 20≤AER&lt;200 (Fig.1) . Thus, worse glycemic control in PERL was a major determinant of GFR decline and ESKD risk after DKD onset, especially in persons with overt proteinuria. Efforts to normalize HbA1c should continue among such persons.

Disclosure
H.Shah: None. J.B.Mcgill: Advisory Panel; Gilead Sciences, Inc., Lilly Diabetes, MannKind Corporation, Novo Nordisk A/S, Provention Bio, Inc., Salix Pharmaceuticals, Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; Dexcom, Inc., Novo Nordisk. I.B.Hirsch: Consultant; Abbott Diabetes, Bigfoot Biomedical, Inc., GWave, Roche Diabetes Care, Research Support; Beta Bionics, Inc., Insulet Corporation, Medtronic. C.Wu: None. A.Galecki: None. M.Mauer: None. A.Doria: Research Support; Novo Nordisk Foundation. Perl consortium: n/a.

Funding
National Institutes of Health UC4DK101108Juvenile Diabetes Research Foundation 17-2012-377The Leona M. and Harry B. Helmsley Charitable Trust 2018PG-T1D014
41-LB: A Randomized, Placebo-Controlled Crossover Study to Evaluate the Effect of a Natural Powder Blend (Mulberry Leaf Extract [MLE], Vitamin D, Chromium, and Fiber) on Postprandial (PP) Metabolic Response in Type 2 Diabetes (T2D)
Authors: MOHAMED MAFAUZY , ZAGURY ROBERTO , BHASKARAN KALPANA , NEUTEL JOEL M. , MOHD YUSOF BARAKATUN-NISAK , MOONEY LINDA , PERRIN EMILIE , SMITH ALEX D. , APRIKIAN OLIVIER , VON EYNATTEN MAXIMILIAN , JOHANSEN ODD ERIK 
Published: May 2022

MLE contains iminosugar alkaloids (of which 1-deoxynojirimycin [DNJ] is most abundant) , and phenolic and flavonoid functional ingredients, which can modulate PP metabolism. We tested a 2 g powder blend of 250 mg MLE (containing 12.5 mg DNJ) combined with fibre (1.75 g) , vit D (0.75 μg) , and chromium (75 μg) , versus placebo (PBO) , in a double-blind RCT. In this two-center (US, Singapore) , single-intervention study, in people with T2D (drug-naïve or on metformin) with Asian race, the powder was sprinkled over a 350 kcal breakfast meal (white bread, cheese, apple juice [55.4 g carbs]) , consumed after a 10h fast. PP blood glucose and insulin were assessed over 3h. Thirty individuals (mean age 59 years, HbA1c 7.1%, BMI 26.5 kg/m2) were enrolled. Compared to PBO, the MLE-blend significantly reduced PP incremental area under the glucose curve (iAUC) , at 1h (-20%, p&lt;0.0001) , 2h (-17%, p=0.0001) , and 3h (-15%, p=0.0032) (Figure) . A significant 1h-reduction in insulin iAUC (-24%, p=0.0236) was also observed, but not at 2h, or 3h (Figure) . Compared to PBO, a 2 g natural powder blend of MLE, fibre, Vit D and chromium significantly reduced the overall glycemic burden and early insulin response of a carbohydrate-rich breakfast in T2D, suggesting its use as a convenient dietary adjuvant to improve PP metabolic response.

Disclosure
M. Mohamed: None. M. Von eynatten: Employee; Nestlé Health Science. O. Johansen: Employee; Boehringer Ingelheim International GmbH, Nestlé Health Science. R. Zagury: Consultant; Nestlé Health Science, Speaker’s Bureau; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk, Servier Laboratories. K. Bhaskaran: None. J. M. Neutel: None. B. Mohd yusof: Advisory Panel; Abbott, Merck & Co., Inc., Research Support; Nestlé Health Science, Speaker’s Bureau; Abbott, Boehringer Ingelheim International GmbH, Nestlé Health Science, Novo Nordisk. L. Mooney: None. E. Perrin: Other Relationship; Nestlé. A. D. Smith: Employee; Nestlé Health Science. O. Aprikian: None.

Funding
Nestlé Health Science
423-P: Predictors of Epicardial Adipose Thickness in Overweight and Obese Youth with Type 1 Diabetes
Authors: CIELONKO LUKE , SABATI ARASH A. , CHAMBERS MELISSA , NEWBERN DOROTHEE , CHAKRAVARTHY VARSHINI , SCHMIDT JACLYN , MULLEN JOHN , LUTZ NATALIE , SHAIBI GABRIEL Q. , OLSON MICAH 
Published: May 2022

Objectives: Cardiovascular disease (CVD) is the leading cause of death in adults with type 1 diabetes mellitus (T1D) and risk factors for CVD are present early in the disease course. Epicardial adipose thickness (EAT) , a novel independent marker of CVD, is significantly increased in children with T1D compared to healthy controls. Obesity, a known CVD risk factor, is increasingly prevalent in the pediatric population and may confer additional risk in youth with T1D. The purpose of this study was to examine EAT in overweight/obese pediatric patients with T1D.
Methods: This was a single-center, cross-sectional study of 37 youth with T1D and BMI &gt; 85th percentile (BMI percentile=93.1±4.3, age 13.5y±3.4, 62.1% female) . Waist circumference, blood pressure, HbA1C and a 2D echocardiogram measuring EAT were obtained. Insulin resistance was calculated via estimated glucose disposal rate (eGDR) .
Results: EAT was correlated with age (r=0.45, P=0.006) , BMI (r=0.58, P=0.0001) , waist circumference (r=0.64, P=0.0001) , and diastolic BP (r=0.37, P=0.023) , while inversely correlated with eGDR (r=-0.49, P 0.002) and most recent HDL level (r=-0.43, P=0.027) . There were no significant correlations between EAT and HbA1C (r=-0.01, P=0.9) or duration of diabetes (r=0.16, P=0.4) . After multivariate regression analysis, age and BMI were independent predictors explaining 43.7% of the variance in EAT (P=0.001) .
Conclusions: EAT is associated with measures of adiposity and CVD risk, however, only age and BMI were independent predictors of EAT among overweight and obese youth with T1D. In addition to a focus on tight glycemic control to prevent CVD in overweight and obese youth with T1D, further studies are needed to investigate the impact of BMI lowering interventions on EAT.

Disclosure
L.Cielonko: None. M.Olson: None. A.A.Sabati: None. M.Chambers: None. D.Newbern: None. V.Chakravarthy: None. J.Schmidt: None. J.Mullen: None. N.Lutz: None. G.Q.Shaibi: None.
424-P: Body-Weight Variability and Risk of Cardiovascular Outcomes in Type 1 Diabetes: Results from the DCCT/EDIC Studies
Authors: PETRIA IULIA , ALBUQUERQUE SAMUEL , VAROQUAUX GAEL , VIE JILL-JÊNN , VELHO GILBERTO , PERSEGHIN GIANLUCA , ROUSSEL RONAN , POTIER LOUIS 
Published: May 2022

Cardiovascular (CV) complications are a major cause of morbimortality in long-standing type 1 diabetes (T1D) . Excessive weight gain has been associated with higher rates of CV events in the DCCT/EDIC studies. Moreover, fluctuation of body weight has emerged as an independent predictor of increased mortality and risk of CV outcomes, with evidence from the general population, from patients with coronary artery disease, and from patients with type 2 diabetes. We evaluated the association between weight fluctuation and CV events in patients with T1D from the DCCT/EDIC population.
Body-weight fluctuation was measured by the average successive variability (ASV: average absolute difference between successive values) over the 9-year period of the DCCT. The primary outcome was a composite of major adverse CV events (MACE: nonfatal myocardial infarctions or cerebrovascular events, CV deaths) occurring during the first 15 years of EDIC follow-up. The risk of outcomes during follow-up was analyzed using adjusted Cox models according to tertiles of ASV.
For the primary outcome, 1371 out of 1441 patients fulfilled the inclusion criteria for analysis [males: 52.41%, age: (37.53±6.82) years, mean HbA1c: (8.08±1.35) %, conventional/intensive treatment: 690/681 patients]. The cumulative incidence of MACE was 4.81%, 5.02%, and 6.58% for tertiles 1, 2, and 3, respectively (T1, T2, T3) (p=0.44) during (15.40±6.24) years of follow-up. Cox analysis adjusted for baseline EDIC characteristics (age, sex, treatment group) and time-dependent variables during DCCT (average BMI, CV risk factors, nephropathy) showed a hazard ratio (HR) for MACE of 1. (95% CI 0.58-1.92; p=0.85) for T2 and 1.34 (0.74-2.41; p=0.34) for T3, both compared to T1. For every increase of 1 standard deviation of ASV, the HR for MACE was 1. (0.86-1.42; p=0.44) .
Despite a trend for a positive association, body-weight fluctuation was not significantly associated with an increased risk of MACE in patients with T1D.

Disclosure
I.Petria: None. S.Albuquerque: None. G.Varoquaux: None. J.Vie: None. G.Velho: None. G.Perseghin: Advisory Panel; AstraZeneca, Lilly, Merck Sharp & Dohme Corp., Novo Nordisk, PIKDARE S.p.A., Sanofi. R.Roussel: None. L.Potier: Board Member; Boehringer Ingelheim International GmbH, Lilly, Novo Nordisk, Consultant; AstraZeneca, Sanofi.
432-P: Single and Joint Impact of Type 2 Diabetes and of Coronary Artery Disease on Albuminuria
Authors: MAECHLER MAXIMILIAN , SPRENGER LUKAS , MADER ARTHUR , LARCHER BARBARA , VONBANK ALEXANDER , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H. 
Published: May 2022

Albuminuria is a characteristic feature of diabetic nephropathy, and increased urine albumin excretion is associated with an increased risk of coronary artery disease (CAD) . However, type 2 diabetes (T2DM) and CAD frequently coincide, and the single and joint effects of T2DM and angiographically determined CAD with albuminuria are unclear. This issue therefore was addressed in the present study. We investigated 831 patients with angiographically proven CAD, of whom 261 had T2DM (CAD+/T2DM+) and 570 did not have diabetes (CAD+/T2DM-) and 263 controls without CAD, of whom 63 had T2DM (CAD-/T2DM+) and 200 did not have diabetes (CAD-/T2DM-) . The albumin / creatinine ratio (ACR) was 37±1in CAD-/T2DM- patients. Compared to this group it was higher in CAD-/T2DM+ patients (193±642; p&lt;0,001) , but not in CAD+/T2DM- patients (52±184; p=0,421) , in whom it was significantly lower than in CAD-/T2DM+ patients (p&lt;0.001) . In CAD+/T2DM+ patients the ACR (162±466) was higher than in CAD-/T2DM- (p&lt;0,001) and in CAD+/T2DM- patients (p&lt;0,001) , but did not differ significantly to that in CAD-/T2DM+ patients (p=0,225) . In multivariate analysis of covariance, T2DM but not CAD proved to be an independent predictor of ACR after adjustment for age, sex, body mass index, LDL-C, smoking, hypertension and the use of ACE inhibitors /AT2-antagonists and statins (F=22.06; p&lt;0.0 and F=0.520; p=0.471, respectively) . We conclude that T2DM but not CAD is an independent determinant of albuminuria.

Disclosure
M.Maechler: None. L.Sprenger: None. A.Mader: None. B.Larcher: None. A.Vonbank: None. A.Leiherer: None. A.Muendlein: None. H.Drexel: None. C.H.Saely: None.
448-P: Clinical Conversations Exchange: A Cardiologist-PCP Collaboration Discussing GLP-1 Receptor Agonists for Reducing Cardiovascular Risk in Patients with Diabetes
Authors: ALLEN RUSSIE , WELCH LAUREN K. 
Published: May 2022

MLG is conducting a large-scale, Clinical Conversations Exchange series on type 2 diabetes (T2DM) inclusive of 25 case-based, collaborative workshops for cardiologists and primary care physicians (PCPs) . The education seeks to enhance HCPs ability to ability to determine the clinical implications of results from cardiovascular outcomes trials of GLP-1 receptor agonists; identify patients with T2DM who are most likely to benefit from the use of GLP-1 receptor agonists; personalize the selection of GLP-1 receptor agonists based on indications, guidelines recommendations and clinical data; and develop strategies for increasing collaboration between cardiologists and PCPs in managing cardiovascular risk in patients with T2DM. Despite being virtual, the meetings are conversational in nature, led by both a cardiologist and a PCP as faculty, and include discussions with active Q&A on specific patient scenarios. We have worked with our faculty to also develop a Clinical Conversations Exchange Treatment Simulator tool (available here) , an application that is accessible on desktop or mobile device through an internet browser, where users can quickly decide the best course of action for their T2DM patients. Learners can also download whiteboard animations on the MoA of treatments and patient-specific factors to reinforce learning gains and also share with patients. Finally, learners can also access an online Personalized Poster Portal where they can choose a variety of images and design a poster that was shipped to their practice setting. There have been with half of the programs complete reaching 712 learners so far, there have already been 315 Posters ordered, 221 Simulator Views, and 190 Animation Downloads. The outcomes that MLG has collected regarding this unique program and its point-of-care tools indicate how CME can lead to not only improved knowledge but can also translate to practice behavior and care coordination. MLG is looking forward to sharing the outcome of the program via a poster at the ADA Scientific Session.

Funding
Eli Lilly
455-P: Artificial Intelligence Approach to Treatment Classification in Painful Diabetic Neuropathy
Authors: TEH KEVIN , WILKINSON IAIN D. , SLOAN GORDON P. , TESFAYE SOLOMON , SELVARAJAH DINESH 
Published: May 2022

Aim: Our study predicted treatment responses in patients with painful DPN (diabetic peripheral neuropathy) by developing a deep learning model using resting state functional magnetic resonance imaging (fMRI) neuroimaging datasets.
Methods: Forty-three consecutive patients who received intravenous lidocaine treatment for painful DPN were assessed. All subjects (responders n=29 and non-responders n=14) underwent detailed clinical and neurophysiological assessments to phenotype their pain sensory profile. Subjects also underwent brain resting-state fMRI. After pre-processing we performed a group concatenated independent component analysis (ICA) set to 30 components and automatically chose 7 highly correlated (p&lt;0.05) ICA components. A 3D convolutional neural network (CNN) classification framework was trained using a VoxNet based architecture. This deep learning architecture compared models using (1) 7 correlated ICA networks 2) all 30 ICA networks generated 3) pre-processed resting state images.
Results: The deep learning treatment response classification in a ten-fold cross validation experiment using 7 ICA spatial maps has a mean AUC of 0.85 and an F1-Score of 0.90. However, with the extra information of all 30 ICA maps the mean AUROC increased to 0.97 with an F1-Score of 0.95. Using only pre-processed resting-state fMRI data achieved suboptimal F1-Score of 69% and AUC score of 44%.
Conclusion: Through the use of our deep learning model, we have demonstrated high classification performance. Our method improves painful DPN treatment efficiency by stratifying patients to receive the correct treatment from the outset. We believe to our knowledge this is the first study utilising deep learning methods to classify treatment response in painful DPN.

Disclosure
K.Teh: None. I.D.Wilkinson: None. G.P.Sloan: None. S.Tesfaye: Advisory Panel; Astellas Pharma Inc., Bayer AG, Grünenthal Group, Nevro Corp., Wörwag Pharma GmbH & Co. KG, Speaker's Bureau; Eva Pharma, Pfizer Inc., Viatris Inc. D.Selvarajah: None.

Funding
National Instituteof Health Research Efficacy and Mechanism Evaluation Programme (NIHR 129921) European Foundation for the Study of Diabetes (Microvascular Complications Project Grant) University of Sheffield, Health Education England, Knowledge Exchange
47-LB: Higher Weight Loss Is Associated with Improved Quality of Life in Patients with Type 2 Diabetes—SURPASS Program
Authors: BOYE KRISTINA , THIEU VIVIAN , YU MARIA , SAPIN HELENE 
Published: May 2022

In addition to glycemic control, the ADA recommends weight management for patients with type 2 diabetes (T2D) with overweight or obesity. This analysis explored the association between weight loss and patients’ quality of life using pooled data from the SURPASS clinical trials, regardless of treatment and dosing. SURPASS 1 to 5 participants achieving ≥5%, ≥10%, or ≥15% weight loss were assessed for patient-reported outcomes (PRO) at baseline and endpoint. Weight related PROs investigated were Ability to Perform Physical Activities of Daily Living (APPADL) , Impact of Weight on Quality of Life-Lite Clinical Trials (IWQOL-Lite-CT) , Impact of Weight on Self-Perceptions (IW-SP) , and other measures were the EQ-5D-5L and Diabetes Treatment Satisfaction Questionnaire change (DTSQc) . Higher PRO scores indicate better outcomes. At endpoint, improvements were observed from baseline in all assessed PRO measures across weight loss categories (Table) . As we narrow the groups to those with higher weight loss percentages, we observed greater improvements in APPADL, IWQOL-Lite-CT, IW-SP, and EQ VAS scores. EQ-5D-5L index score changes and the DTSQc scores also increased but to a lesser extent. Weight loss was associated with improved quality of life with greater improvement seen in higher percentages of weight loss in patients with T2D, regardless of therapy.

Disclosure
K. Boye: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. V. Thieu: None. M. Yu: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. H. Sapin: Employee; Eli Lilly and Company.

Funding
Eli Lilly and Company
476-P: Role of TGR5 Signalling in Hepatic Lipid and Lipoprotein Metabolism in Normal and Insulin-Resistant States
Authors: ALVARES DANIELLE C.L. , HOFFMAN SIMON S. , ADELI KHOSROW 
Published: May 2022

Fasting dyslipidemia is characterized by a lipid profile with elevated triglycerides, increased small dense LDL and low HDL-cholesterol, and is a commonly comorbid with insulin resistance. Bile acid (BA) signalling has been suggested to improve hepatic insulin sensitivity and lipid accumulation through activation of the Takeda G protein-coupled receptor 5 (TGR5) . As the role of TGR5 in regulating hepatic lipid and lipoprotein metabolism has not been explored, the present study was performed to characterize the role of bile acid signaling via TGR5 in hepatic lipid and lipoprotein metabolism. We have recently developed novel Tgr5-/- and GLP1R-/- hamster models. Tgr5+/+ and Tgr5-/ - hamsters were fed a high fat, high fructose, and low cholesterol (FFLC) diet for 6 weeks. Glucose tolerance, insulin tolerance, and fasting plasma lipids were examined at baseline, and following 6-weeks on diet. Loss of TGR5 signalling appeared to be initially protective against diet induced hypertriglyceridemia, however this effect was lost with prolonged feeding. Following 6 weeks of diet, Tgr5-/ - hamsters were less glucose tolerant, with similar insulin sensitivity. Fasting plasma deoxycholic acid (DCA) and taurocholic acid (TCA) compositions differed under chow fed conditions, with additional changes in postprandial DCA, TCA and cholic acid (CA) . Finally, chow fed Tgr5+/+ and Tgr5-/ - hamsters received intraduodenal injections (IDI) of DCA or TCA. Both DCA and TCA administration were associated with reduced VLDL-triglyceride secretion in Tgr5+/+ hamsters, an effect that was blunted in Tgr5-/ -hamsters. The lipid lowering effects of DCA were similarly blunted in GLP1R-/- hamsters, suggesting this effect is dependent on GLP-1R signalling. The present research will set a framework to expand our knowledge of the role of BA signaling through TGR5 in hepatic lipogenesis.

Disclosure
D.C.L.Alvares: None. S.S.Hoffman: None. K.Adeli: None.
48-LB: Retention in the National Diabetes Prevention Program Lifestyle Change Program by Participant-Level Factors
Authors: ZHANG XUANPING , CANNON MICHAEL , ELY ELIZABETH , SMITH BRYCE 
Published: May 2022

Retention is closely linked to clinical outcomes in the National Diabetes Prevention Program (National DPP) lifestyle change program (LCP) . We examined retention, defined as the number of sessions attended, using data collected by the CDC Diabetes Prevention Recognition Program, the quality assurance component of the National DPP. We evaluated participants who enrolled in in-person lifestyle change programs from March 2018 to November 2020 and had the opportunity to complete at least 9 months of the 12-month program. To control for programmatic changes due to COVID-19, we divided enrollment into 3 cohorts: 1) 3/1/2018 - 5/31/2019 (before) , 2) 6/1/2019-2/29/2020 (mixed) , and 3) 3/1/2020-11/30/2020 (during COVID-19 pandemic) . Mean sessions attended was lower in cohort 3 (10.8, p&lt;0.05) than in cohorts 1 (12.9) and 2 (12.6) . As shown in Table 1, across the 3 cohorts the following factors were associated with lower mean number of sessions attended: younger age, Hispanic ethnicity and non-White race, lower educational attainment, and Medicaid as a payer source. Our findings highlight that new strategies could be useful to improve retention among some demographic and socioeconomic groups (e.g., younger adults, Hispanic individuals, individuals with lower educational attainment, and Medicaid recipients) in the National DPP.

Disclosure
X. Zhang: None. M. Cannon: None. E. Ely: None. B. Smith: None.

Funding
CDC