bluuebunny/crossref_metadata_2025_split huggingface dataset:
414-P: Multiomic Plasma Markers of Diabetic Kidney Disease in Type 1 Diabetes
Authors: SNELL-BERGEON JANET K. , JOHNSON RANDI K. , PYLE LAURA , CHEN GUAN-YUAN , WELDEMARIAM MEHARI M. , ZHANG QIBIN 
Published: June 2023

Diabetic kidney disease (DKD) is a major complication of type 1 diabetes (T1D). We investigated whether metabolomic, lipidomic and proteomic plasma markers were associated with albuminuria in the Coronary Artery Calcification in Type 1 Diabetes cohort. Two timed overnight urine collections were performed, and albumin excretion rates (AER) were averaged. If overnight samples were unable to be obtained, a spot urine sample was collected and albumin/creatinine ratio (ACR) was used to determine albuminuria status. Albuminuria was defined as an AER ≥ 20 ug/min or an ACR ≥ 30mg/g. Plasma samples from the baseline examination were assayed by LC-MS for multiple omics markers in 225 participants with T1D. Moderated t-tests using false discovery rate (FDR) adjustment for multiple comparisons were used to examine the markers associated with albuminuria presence. An FDR adjusted p-value &lt;0.05 was considered to be statistically significant. Average ± SD for age was 36 ± 9 years and for diabetes duration was 23 ± 9 years, and 58% [n = 120] were female. The prevalence of albuminuria at baseline was 20.4% (n = 46). There were 15 metabolite markers (3 metabolites of symmetric dimethylarginine, 2 of glycyl-glycine, and one each of aspartyl-glycine, glycyl-aspartate and 1-methylhistidine, 7 uncertain) with higher expression in participants with DKD than in those without DKD. There were 7 lipid markers in the acylcarnitine family that were elevated in participants with DKD compared to those without DKD, and 19 glycated peptides (16 in fibrinogen, 1 in kininogen and 1 in hemopexin) showed higher expression in participants with DKD than in those without DKD. None of the unmodified proteins differed by DKD status. Multiple omics markers were higher in T1D participants with albuminuria than in people without any sign of DKD. These findings may suggest changes in lipids, metabolites and glycated proteins early in the course of DKD, and these markers should be explored as potential predictors of worsening DKD.

Disclosure
J.K.Snell-bergeon: None. R.K.Johnson: None. L.Pyle: None. G.Chen: None. M.M.Weldemariam: None. Q.Zhang: None.
416-P: Effect of Intensive Lifestyle Intervention on Renal Function in Patients with Diabetes and Obesity—A 10-Year Longitudinal Study
Authors: SALAH TAREQ , AL-BADRI MARWA , DHAVER SHILTON E. , KHATER ABDELRAHMAN , KIBAA KARIM , MCCARRAGHER RYAN , HAMDY OSAMA 
Published: June 2023

Diabetic nephropathy is a common complication of diabetes mellitus (DM). In this study, we evaluated renal function in patients with DM and obesity 10 years after participating in a multidisciplinary intensive lifestyle intervention (ILI). We evaluated 94 patients with obesity and DM (12.8% type 1 DM and 87.2% type 2 DM) with mean age of 53.9±9.9 years and mean diabetes duration of 10.9±10.3 years who enrolled in a 12-week ILI in real-world clinical practice. At one year, we stratified participants according to their percentage weight loss into: group A, who maintained ≥7% weight loss (48.9%) and group B, who maintained &lt;7% weight loss (51.1%), and followed them for 10 years. At 10 years, group A lost an average of 9.6±11.2 kg (8.5±10%, p&lt;0.0001) and group B lost an average of 4.1±9.7 kg (4.0±9.4%, p=0.004). A1C did not change from baseline in group A, but significantly increased in group B (+0.8±1.9%, p=0.008). Systolic and diastolic blood pressure decreased in both groups but were only statistically significant in group A from (from 132±15.9/ 76.9±9.1 mmHg at baseline to 125.6±14.4/ 73.4±9.3 mmHg at 10 years, p=0.02, p=0.047 respectively). Serum creatinine significantly decreased in group A from 0.92±0.2 mg/dL to 0.86±0.2 mg/dL (p=0.013) but did not change in group B (0.93±0.2 mg/dL to 0.89±0.3 mg/dL). eGFR significantly increased in group A from 83.3±27 to 90.3±34 mL/min/1.73 m2 (p=0.03) and in group B from 80.2±24 to 89.5±44 mL/min/1.73 m2 (p=0.046). There was no significant change in urinary albumin/creatinine ratio in both groups. LDL-cholesterol and HDL-cholesterol significantly improved in both groups. We conclude that 12 weeks of ILI improves renal function for up to 10 years after intervention. This improvement is particularly evident in those who maintained ≥7% weight loss at one year.

Disclosure
T.Salah: None. M.Al-badri: None. S.E.Dhaver: None. A.Khater: None. K.Kibaa: None. R.Mccarragher: None. O.Hamdy: Advisory Panel; Abbott Nutrition, Nemaura Medical, L-Nutra Inc., Twin Health, Consultant; Sanofi, Research Support; Novo Nordisk, Eli Lilly and Company, Gilead Sciences, Inc., Stock/Shareholder; Healthimation.
418-P: Allometric Body Shape Indices, T2D, and Kidney Function—A Two-Sample Mendelian Randomization Study
Authors: KJAERGAARD ALISA D. , KRAKAUER JESSE , KRAKAUER NIR , TEUMER ALEXANDER , WINKLER THOMAS W. , ELLERVIK CHRISTINA 
Published: June 2023

In a two-sample Mendelian randomization (MR) analysis, using summary statistics from UK Biobank, CKDGen and DIAGRAM, we examined the association between BMI independent allometric body shape indices (a body shape index [ABSI], waist-hip index [WHI] and hip index [HI]) and kidney function (urinary albumin-to-creatinine ratio [UACR], estimated glomerular filtration rate and blood urea nitrogen). Furthermore, we investigated T2D as a potential mediator on the pathway to albuminuria. One standard deviation (SD) increase in genetically predicted ABSI and WHI levels was associated with higher UACR (β=0.039 [0.016, 0.063] log [UACR], p=0.001 for ABSI, and β=0.028 [0.012, 0.063] log [UACR], p=6×10-4 for WHI) in women, but not in men. Meanwhile, one SD increase in genetically predicted HI was associated with lower UACR in women (β=-0.021 [-0.041, 0.000] log [UACR], p=0.05) and in men (β=-0.026 [-0.058, 0.005] log [UACR], p=0.10). Corresponding estimates in individuals with diabetes were substantially augmented. Risk of T2D increased for genetically high ABSI and WHI in women (p&lt;2×10-13) only, but decreased for genetically high HI in both sexes (p&lt;2×10-4). No other associations were observed. Genetically high HI was associated with decreased risk of albuminuria, mediated through decreased T2D risk in both sexes. Opposite associations applied to genetically high ABSI and WHI in women only.

Disclosure
A.D.Kjaergaard: None. J.Krakauer: None. N.Krakauer: None. A.Teumer: None. T.W.Winkler: None. C.Ellervik: None.

Funding
Novo Nordisk Foundation (22OC0076023)
421-P: Methylglyoxal-Derived Advanced Glycation End Products Are Prognostic Biomarkers for Diabetic Complications and Drivers of Endothelial Dysfunction
Authors: LAI SEIGMUND , LOPEZ GONZALEZ EDWIN D.J. , SHUCK SARAH 
Published: June 2023

Diabetic kidney disease (DKD) affects over 30% of individuals with T1D, significantly increasing mortality risk in this population. Canonical tools to predict DKD such as glomerular filtration rate (GFR) or albumin excretion rate (AER) alone may not be sufficient to predict disease risk, as they often do not become apparent until significant kidney damage has already occurred. Therefore, there is an unmet need to identify additional clinically useful biomarkers to predict DKD risk. Methylglyoxal (MG) is an abundant, reactive electrophile produced during metabolic flux from glycolysis and protein and lipid metabolism. MG covalently modifies macromolecules such as DNA, RNA, and protein forming MG-advanced glycation end products (MG-AGEs). Both MG and MG-AGEs have been correlated with diabetes and cancer, but the ability of nucleoside MG-AGEs to predict DKD risk has not been examined. Using a novel mass spectrometry method, we measured levels of MG-AGEs in patient urinary samples collected from the DCCT/EDIC study and found MG-AGEs independently predicted DKD risk up to 16 years pre-diagnosis. This association was more significant than the association of AER, GFR, or HbA1c with DKD. In DKD, endothelial cells (ECs) become dysfunctional, which contributes to the development of the disease. To understand the extent to which MG-AGEs impact EC dysfunction, we synthesized pure MG-AGEs and exposed human umbilical vein endothelial cells (HUVECS) to these compounds. We found MG-AGEs activated pathways associated with the receptor for AGEs (RAGE) and EC dysfunction as evidenced by increased leukocyte adhesion, oxidative stress, pro-inflammatory gene expression, and NFkB activation. This suggests that MG-AGEs are not only predictive of DKD, but may also contribute to EC dysfunction preceding disease.

Disclosure
S.Lai: None. E.D.J.Lopez gonzalez: None. S.Shuck: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (X01DK118575); National Institutes of Health (1R21DK127285); Wanek Family Project to Cure T1D; Diabetes Complications Consortium
422-P: GLP-1 RA Should Be Used with SGLT2 Inhibitor in People with Rapidly Progressive CKD
Authors: KASHIMA KOJI , SHIMIZU HIROYUKI , YAMADA MASANOBU 
Published: June 2023

Objective: Either GLP-1RA or SGLT2i is recommended to use in people with type 2 diabetes (T2D) with CKD. Whether these drugs jointly work for reno-protection are not well known. We evaluated add-on effects of GLP-1RA (liraglutide 95%) in Japanese people with T2D treated by SGLT2i by assessing individual eGFR trajectory.
Methods: A total of 75 persons with T2D (CKD stage 3-4), treated by SGLT2i (empagliflozin 65%) were analyzed. At the time of recruitment, average age was 70.3±12.2 yr-old, the duration of diabetes was 15.4±10.1 yrs, and macroalbuminuria (Macro-Alb) existed in 49% (37/75). To trace the eGFR trajectory in each person, most rapid eGFR slope was calculated individually from the data for 46±20 months before using SGLT2i and 46±16 months after adding it. GLP-1RA was initially or additionally used in 53%.
Results: 1) Proportion of responders (defined as their ratios of slopes are reduced &gt; 1.0 after addition of SGLT2i) in each stage were as follows: stage 3a; (21/29), stage 3b; (21/28), stage 4; (16/18). Slopes in responders (58/75) were improved as follows, -7.8±9.9 to -0.8±3.0ml/min/1.73m2/year (P&lt;0.001) with GLP-1RA use in 52%. Slopes in non-responders (17/75) were worsened as follows, -1.8±1.9 to -3.6±3.1ml/min/1.73m2/year (P&lt;0.001), despite GLP-1RA use in 59%. Macro-Alb was observed in 53% and 35%, respectively. 2) Slopes in rapid decliners (defined as most rapid individual eGFR slope greater than -10.0ml/min/1.73m2/y) (13/75) were improved from -18.9±16.4 to -1.3±3.3ml/min/1.73m2/year (P&lt;0.01) by combined use of GLP-1RA in 85% (11/13). Macro-Alb existed in 69% (9/13) and nephrosis in 54% (7/13). 3) Sub-analysis (one of different GLP-1RA initiation regimes): Baseline slopes -16.7±19.8 were improved to -5.0±5.8 (P&lt;0.05) by adding GLP-1RA, then to -2.7±3.8 ml/min/1.73m2/year (vs baseline: P&lt;0.03) by adding SGLT2i. (n=11) Macro-Alb highly existed in 82% (9/11) and nephrosis in 46% (5/11).
Conclusion: GLP-1RA should be used with SGLT2i in rapid eGFR decliners or persons with Macro-Alb.

Disclosure
K.Kashima: None. H.Shimizu: None. M.Yamada: None.
427-P: Comparison of Diabetic Kidney Disease Risk Factors between Normoalbuminuric Reduced and Albuminuric Preserved Kidney Function Groups
Authors: MOSSLEMI MITRA , COSTACOU TINA 
Published: June 2023

The prevalence of normoalbuminuric diabetic kidney disease (NA-DKD) in the U.S. has increased over the past 20 years, and it is higher among patients with good glycemic control. However, the factors associated with NA-DKD remained to be elucidated. Studies have compared NA-DKD with albuminuric DKD (ALB-DKD: ACR ≥ 30 mg/g and eGFR &lt; 60 mL/min/1.73m2); however, ALB-DKD may include cases who have progressed from NA-DKD. Therefore, we aimed to compare DKD risk factors between patients with NA-DKD and those with only albuminuria (only-ALB) status. Among NHANES (1999-2016) adult participants with diagnosed diabetes, we compared DKD risk factors (including demographics) between patients with NA-DKD (ACR &lt; 30 mg/g and eGFR &lt; 60 mL/min/1.73m2) and only-ALB (ACR ≥ 30 mg/g and eGFR ≥ 60 mL/min/1.73m2) using univariate and multivariable analyses. In our diabetes cohort, there were 827 (17.9%) NA-DKD and 923 (16.6%) only-ALB cases. In the multivariable model, diabetes diagnosis age, total cholesterol, HOMA-IR, CRP, and serum uric acid were not significantly associated with albuminuric status, while blood pressure control was the strongest predictor followed by gender [Table]. Future studies should characterize pathways separate from hyperglycemia and elevated BP which contribute to NA-DKD.

Disclosure
M.Mosslemi: None. T.Costacou: None.
429-P: Evaluation of Hypoglycemic Risk in Patients with Type 2 Diabetes on Hemodialysis under Tight Glycemic Control
Authors: HAYASHI AKINORI , SHIMIZU NAOYA , SUZUKI AGENA , FUJISHIMA REI , MATOBA KENTA , MASAKI TSUGUTO , MIYATSUKA TAKESHI 
Published: June 2023

Patients with type 2 diabetes on hemodialysis (T2HD) have unique glycemic profile resulting from hemodialysis, especially hemodialysis-related hypoglycemia, which is present in approximately 20% of them. We analyzed 48-hour sensor glucose level (SGL) on dialysis and non-dialysis days, and time in range (TIR, 70-180 mg/dL), time below range (TBR, &lt;70 mg/dL) in 115 T2HD using continuous glucose monitoring (CGM) and evaluated the difference in clinical parameters between well-controlled group (TIR &gt;70% and TBR &lt;4%) and hypoglycemia group (TIR &gt;70% and TBR ≥4%). Sixty-six patients of well-controlled group (46 males, age 62±12 years, HbA1c 6.0±0.9%, glycated albumin (GA) 18.5±4.1%) and 11 cases of hypoglycemia group (8 males, age 65±13 years, HbA1c 5.9±0.7%, GA 17.4±3.6%) were selected for retrospective analysis. There were no differences in sex, age, dry weight, body mass index, duration of diabetes, or duration of dialysis between two groups. Likewise, HbA1c and GA were not significantly different (P=0.7044, P=0.4151). Glucose levels at both the beginning and the end of dialysis were significantly lower in the hypoglycemia group (164.1±42.8 mg/dL vs. 131.0±49.2 mg/dL (P=0.0227) and 118.8±40.2 mg/dL vs. 86.8±26.1 mg/dL (P=0.0130), respectively). On the other hand, CGM data showed significantly lower mean SGL (P=0.0005) and significantly higher coefficient of variation of SGL (P=0.0014) in the hypoglycemia group. Thus, both HbA1c and GA are not sufficient to predict the presence of hypoglycemia in strict glycemic control in T2HD. Therefore, for good glycemic control without hypoglycemia in T2HD, it is important to measure glucose levels at the beginning and end of dialysis and to evaluate glucose profiles by CGM.

Disclosure
A.Hayashi: Research Support; Abbott Japan Co., Ltd., Roche Diabetes Care, Speaker's Bureau; Abbott Japan Co., Ltd., Medtronic, Terumo Corporation. N.Shimizu: None. A.Suzuki: None. R.Fujishima: None. K.Matoba: None. T.Masaki: None. T.Miyatsuka: Speaker's Bureau; Eli Lilly Japan K.K., Novo Nordisk, Sanofi K.K., Mitsubishi Tanabe Pharma Corporation, Sumitomo Dainippon Pharma Co., Ltd., Teijin Pharma Limited, Sanwa Kagaku Kenkyusho, Daiichi Sankyo.

Funding
TERUMO Life Science Foundation (21-III-5030); Japan Association for Diabetes Education and Care (2021-YNG-028); Japan Society for the Promotion of Science (22K15674)
43-LB: Preliminary Evidence of the Validity of a Measure to Assess Diet Acceptability—the Advancing Care for Type 1 Diabetes and Obesity Network (ACT1ON) Study
Authors: CRISTELLO SARTEAU ANGELICA , IGUDESMAN DARIA , MAAHS DAVID M. , PRATLEY RICHARD E. , MAYER-DAVIS ELIZABETH J. 
Published: June 2023

Diet acceptability is widely considered to be an important driver of behavioral adherence and health benefits in dietary interventions, yet there is an absence of measures with evidence of validity to assess this construct and guide decision-making. Informed by existing literature and content validity appraisal of subject matter experts, we developed and evaluated the validity of a five-item measure of diet acceptability (total score range: 5-20, total score &gt;10 = “unacceptable”) with Likert response options (1- Strongly Agree, 2- Agree, 3- Disagree, 4- Strongly Disagree), which we administered six times during a 10.5 month Sequential, Multiple Assignment, Randomized Trial pilot that tested effects of three diets on weight and glycemic management in adults 19-30 years with type 1 diabetes ≥1 year (n=68, HbA1c &lt;13%, BMI: 27-39). To maximize sample size (n=51), preliminary validity analyses relied predominantly on data from the first diet period (0-3 months). Greater diet acceptability according to continuous and dichotomous total and individual item scores at 3 months was associated with greater weight loss 0-3 months (e.g., total score ≤10 was associated with 2.4kg more weight loss [95% CI: 0.6, 4.2; p=0.01; n=48]). Cronbach’s α was 0.93. Exploratory factor analysis supported a 1-factor structure, explaining 99.7% of common variance. High item-total correlations (0.72 - 0.87), average inter-item correlation (0.88), and item - factor correlations (0.75 - 0.93), together with criterion validity analyses suggest item redundancy and indicate item 1 (i.e., “I am satisfied with the diet that I am currently on”) shares the strongest association with the underlying construct. Our analyses indicate robust preliminary evidence of reliability and validity of the five-item measure, while also suggesting potential adequacy of item 1 to assess the construct and minimize participant response burden in future studies that employ the measure.

Disclosure
A. Cristello sarteau: None. D. Igudesman: None. D. M. Maahs: Advisory Panel; Medtronic, LifeScan Diabetes Institute, MannKind Corporation, Consultant; Abbott, Research Support; Dexcom, Inc. R. E. Pratley: Other Relationship; Bayer Inc., Corcept Therapeutics, Dexcom, Inc., Gasherbrum Bio, Inc., Hanmi Pharm. Co., Ltd., Hengrui (USA) Ltd., Merck Sharp & Dohme Corp., Novo Nordisk, Pfizer Inc., Rivus Pharmaceuticals Inc., Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. E. J. Mayer-davis: None.

Funding
Clinical Trial Registration (NCT03651622)
43-OR: Beliefs about Medicines, Self-Efficacy, and Health Care Coverage Predict Glycemic Control in Young Adults with Youth-Onset Type 2 Diabetes—The TODAY2 iCount Study
Authors: TRIEF PAULA M. , USCHNER DIANE , ANDERSON BARBARA , WEN HUI , BULGER JANE D. , WEINSTOCK RUTH S. 
Published: June 2023

Background: Little is known about psychosocial factors that predict glycemic control (A1c) in young adults with youth-onset type 2 diabetes.
Aim: To identify psychosocial predictors of A1c in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY2) cohort.
Design: Longitudinal, measured at T1 (baseline) and T2 (1 year later). Logistic and linear regressions, adjusted for covariates (including T1 A1c), identified T1 predictors of A1c at T2. Participants: N= 348 participants in TODAY2. Mean age=26.0 years, 65.8% female, 37.6% non-Hispanic Black, 36.5% Hispanic, 20.4% non-Hispanic white, mean A1c=9.4%.
Measures: Reliable, valid measures of beliefs about medicines, depressive and anxiety symptoms, diabetes distress, diabetes self-efficacy, diabetes attitudes, self-management support and material need insecurities. A1c was examined categorically (high vs. low: high ≥8%) and continuously (percent).
Key Results: The high A1c group had more belief in the necessity of (p=0.023), but concerns about (p=0.029), medicines, higher diabetes distress (p&lt;0.001), and lower diabetes self-efficacy (p=0.017). In adjusted analyses, every 5-point higher score measuring beliefs that medicines are overused predicted 3.6 times higher odds of high A1c at T2 (p=0.010). Every 5-point higher self-efficacy score predicted 16.7% lower odds of high A1c at T2 (p=0.033). Surprisingly, those who lacked healthcare coverage were less likely to have high A1c at T2 vs. those with coverage (p=0.10). Every 5-point higher medicines are overused score predicted 48.5% higher % A1c at T2 (p=0.017). No other psychosocial measures predicted A1c.
Conclusions: High A1c is common in young adults with youth-onset type 2 diabetes and is predicted over time by beliefs about medicines, diabetes self-efficacy and healthcare coverage status. We must address these factors to help this vulnerable group establish optimal glycemic control.

Disclosure
P.M.Trief: None. D.Uschner: None. B.Anderson: None. H.Wen: None. J.D.Bulger: None. R.S.Weinstock: Consultant; Jaeb Center for Health Research, Other Relationship; Wolters Kluwer Health, Research Support; Insulet Corporation, Medtronic, Eli Lilly and Company, Novo Nordisk, Boehringer Ingelheim Inc., Hemsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases, Tandem Diabetes Care, Inc., Kowa Pharmaceuticals America, Inc.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK110456)
431-P: Effects of CB1 Antagonist INV-202 in Patients with Metabolic Syndrome—A Randomized, Placebo-Controlled, Double-Blind Phase 1B Study
Authors: CRATER GLENN D. , RAVENELLE FRANCOIS , LALONDE KARINE , DESPRÉS JEAN-PIERRE 
Published: June 2023

Cannabinoid blockers have been successful for the treatment of obesity. However, due to CNS side effects drug development programs were halted. We present data from INV-202, a peripherally acting next generation CB1 blocker with very low CNS penetration. This randomized, DB, PC, PG, 28day study (NCT05282446) enrolled subjects with metabolic syndrome. Subjects received INV-202 25 mg or placebo and assessed weekly by lipid profile, weight, waist, and biomarkers. Oral glucose tolerance test (OGTT) was performed at baseline and at the end of study. All statistical comparisons are post-hoc.37 subjects were enrolled (46% Fem, Age 55 years, HgbA1c 5.7%, TG 2.22 mmol/L, BMI 38.1) INV-202 exhibited a mean weight loss of 3.5 kg (3.3%) compared with placebo subjects who gained a mean of 0.6 kg (0.5%). All other biomarkers showed improvements. There were no discontinuations, no SAEs and all AEs were mild to moderate. (nausea, decreased appetite, and diarrhea) INV-202 was well tolerated over 28 days of treatment. Significant improvements were noted. Further studies on the long-term cardiometabolic effect of this novel CB1 blocker are warranted.

Disclosure
G.D.Crater: Employee; Inversago Pharma. F.Ravenelle: Employee; Inversago. K.Lalonde: Employee; Inversago. J.Després: Advisory Panel; Inversago Pharma Inc., Other Relationship; Rockpointe Corporation – Steering Committee.