bluuebunny/crossref_metadata_2025 huggingface dataset:
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 <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<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<2×10-13) only, but decreased for genetically high HI in both sexes (p<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 > 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<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<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<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<0.05) by adding GLP-1RA, then to -2.7±3.8 ml/min/1.73m2/year (vs baseline: P<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 < 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 < 30 mg/g and eGFR < 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, <70 mg/dL) in 115 T2HD using continuous glucose monitoring (CGM) and evaluated the difference in clinical parameters between well-controlled group (TIR >70% and TBR <4%) and hypoglycemia group (TIR >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 >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 <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<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.
433-P: Syndecan-1, a Marker of Endothelial Glycocalyx Degradation, Is Associated with Albuminuria in Type 2 Diabetes
Authors: KAKUTANI YOSHINORI , MORIOKA TOMOAKI , YAMAZAKI YUKO , OCHI AKINOBU , FUKUMOTO SHINYA , SHOJI TETSUO , EMOTO MASANORI
Published: June 2023

The endothelial glycocalyx (EG) covers the luminal surface of vascular endothelium and is involved in various functions of endothelium including the microvascular permeability. Syndecan (SDC)-1 is a transmembrane heparan sulfate proteoglycan and is a major component of EG. Since the extracellular domain of SDC-1 is shed by inflammatory mediators, increased circulating levels of SDC-1 is considered as a marker of EG degradation. No study has thus far investigated the relationship between EG degradation and albuminuria in type 2 diabetes. This study aimed to investigate the association between EG degradation assessed by serum SDC-1 levels and urinary albumin to creatinine ratio (ACR) in type 2 diabetes. This study enrolled 370 Japanese patients with type 2 diabetes (T2D) and 219 nondiabetic controls (ND). Patients with severe kidney dysfunction whose estimate glomerular filtration rate (eGFR) was less than 30 mL/min/1.73m2 were excluded. T2D patients were divided into normoalbuminuria (A1), microalbuminuria (A2) and macroalbuminuria (A3) by ACR. Median value of serum SDC-1 levels in T2D with A1 stage was 24.5 ng/mL which was higher than that in ND (16.0 ng/mL) (p <0.001). Median values of SDC-1 in T2D with A2 and A3 stages were 29.0 and 38.7 ng/mL, respectively, which were significantly different among albuminuria stages (p <0.001). First, multivariate analysis including T2D patients with A1 stage and ND revealed that the presence of T2D was independently associated with serum SDC-1 level (β = 0.356, p <0.001). Next, multivariate analysis in T2D patients with all albuminuria stages revealed that serum SDC-1 level was independently associated with ACR (β = 0.121, p = 0.012) after adjustment for known other risk factors for albuminuria. In conclusion, serum SDC-1 level is increased in T2D compared to ND and is an independent determinant of ACR in T2D patients. This study suggests a potential involvement of the EG degradation in albuminuria in T2D.

Disclosure

Y. Kakutani: None. T. Morioka: None. Y. Yamazaki: None. A. Ochi: None. S. Fukumoto: None. T. Shoji: Research Support; Ono Pharmaceutical Co., Ltd., Bayer Inc. Other Relationship; Kowa Company, Ltd. M. Emoto: None.
437-P: Establishing a Simple Decision-Making Model for the Differential Diagnosis of Diabetes Kidney Disease and Nondiabetes Kidney Disease in T2D Patients through Machine Learning
Authors: ZHANG LIN
Published: June 2023

Objective: To study the 2-DM patients with renal biopsy, analyze the risk factors of DKD and establish a simple decision model to differentiate DKD and NDKD.

Methods: 99 2-DM patients were admitted to hospital in Beijing from December 1, 2018 to December 31, 2021. All of the patients accepted kidney biopsy and biochemical test, fundus photography and OCTA. According to the pathological reports, 99 cases were divided into DKD group and NDKD group. The difference indicators of the two groups were compared. The risk factors of DKD were analyzed by logistic regression. A simple and convenient method to distinguish DKD and NDKD was established through the decision tree model.

Results: This study was a cross-sectional study. Compared with DKD and NDKD groups, the ratio of male/female in DKD group was higher than that in NDKD group (P=0.033), DR prevalence rate was significantly higher than that in NDKD group (P<0.001), course DM, FBG, HBAIC, SBP, TC and EGFR were also higher than those in NDKD group, and HGB decreased. Binary logistic regression analysis was conducted to determine whether DKD was combined. After adjusting for the above indicators, age, DR, course of DM, HBA1C and HGB were still independently related to DKD. A decision tree model was established with the training set: the course DM, DR, and HBA1C were risk factors of DKD. The accuracy of prediction classification is 75%, the sensitivity was 46.2%, and the specificity was 88.9%.

Conclusion: If the patients with type 2 diabetes kidney injury have poor blood glucose control, no DR but anemia, a renal puncture should be considered for definite diagnosis of NDKD.

Disclosure

L.Zhang: None.

Funding

Beijing Science & Technology Development of Traditional Chinese Medicine (JJ-2020-25)
44-OR: Structural Racism and Prevalence of Diabetes in a Nationally Representative Sample of U.S. Adults
Authors: EGEDE LEONARD E. , WALKER REBEKAH J. , CAMPBELL JENNIFER A. , LINDE SEBASTIAN
Published: June 2023

Background: Prior research has established that historic redlining is a reliable indicator of structural racism. The goal of this study was to investigate the direct and indirect relationships between historic redlining and prevalence of diabetes in a national sample.

Methods: Using a previously validated conceptual model, we hypothesized pathways between structural racism and prevalence of diabetes via discrimination, incarceration, poverty, substance use, housing instability, education, and unemployment. We combined census tract level data including diabetes prevalence from the CDC PLACES 2019 database, redlining using historic Home Owners’ Loan Corporation (HOLC) maps from the Mapping Inequality project, and census tract data from the Opportunity Insights database. HOLC grade (a score between 1=best and 4=redlined) for each census tract was based on overlap with historically HOLC graded areas. The final analytic sample consisted of 9,590 US census tracts. Structural equation modeling was used to investigate direct and indirect relationships adjusting for 2010 population.

Results: Higher prevalence of diabetes was directly associated with increased redlining (B=0.28, p<0.001). Redlining was directly associated with incarceration (B=0.25, p<0.001); poverty (B=-0.28, p<0.001); housing instability (B=-0.09, p<0.001)); education (B=-0.32, p<0.001); and unemployment (B=-0.34, p<0.001). Redlining was indirectly associated with prevalence of diabetes via discrimination, incarceration, poverty, substance use, housing instability, education, and unemployment with strongest associations for discrimination (B=0.32, p<0.001); binge drinking (B=-0.62, p<0.001) and smoking (B=0.39, p<0.001).

Conclusions: Redlining has significant direct and indirect relationships with diabetes prevalence. Discrimination and substance use may be important targets for interventions aiming to mitigate the impact of structural racism on diabetes.

Disclosure

L.E.Egede: None. R.J.Walker: None. J.A.Campbell: None. S.Linde: None.

Funding

National Institutes of Health (R01DK118038, R01DK120861, R01MD013826, K01DK131319)
441-P: Long-Term Effects of Intensive Lifestyle Intervention in Real-World Clinical Practice on Cardiometabolic Outcomes in Patients with Diabetes—A 15-Year Longitudinal Study
Authors: KHATER ABDELRAHMAN , AL-BADRI MARWA , SALAH TAREQ , DHAVER SHILTON E. , KIBAA KARIM , MCCARRAGHER RYAN , HAMDY OSAMA
Published: June 2023

We previously demonstrated that achieving and maintaining ≥7% weight loss at one year in patients with diabetes (DM), through multidisciplinary intensive lifestyle intervention (ILI) in real-world clinical practice, predicts improvement in cardiometabolic outcomes at 5 and 10 years. In this prospective follow-up, we report 15-year results. We evaluated 122 patients with DM and obesity (mean age 53.2±10.0 years, 68% females, 90.2% type 2, mean DM duration 9.1±8.6 years, mean BMI 38.4±5.2 kg/m²) who underwent 12 weeks of ILI. The total cohort lost in average 10.7±4.6 kg (-9.6%, p<0.001) after 12 weeks. At 1 year, they were divided into group A, who maintained <7% weight loss (47.5%), and group B, who maintained ≥7% weight loss (52.5%). At 15 years, average weight loss in the entire cohort was 8.6±11.9 Kg (-7.6%, p<0.001). Group A maintained an average weight loss of 3.9±6.5 kg (-3.6%) at 5 years, 3.8±9.4 kg (-3.9%) at 10 years and 3.8±10.0 kg (-4.0%) at 15 years. Group B maintained an average weight loss of 10.6±9.8 kg (-9.1%) at 5 years, 10.8±9.6 kg (-9.3%) at 10 years and 12.9±12.0 Kg (-11.0%) at 15 years. At 15 years, weight loss in group B remained significantly higher than in group A (p<0.001). In group A, A1C reduced from 7.5±1.4% to 6.7±0.9% at 12 weeks, but rebounded to 8.0±1.9% at 5 years and 10 years and was 7.9±1.8% at 15 years. In group B, A1C decreased from 7.3±1.1% to 6.3±0.8% at 12 weeks, and was 7.4±1.6% at 5 years, 7.2±1.4% at 10 years and 7.3±1.5% at 15 years (p=0.04 between groups). Both groups maintained significant improvements in LDL- and HDL-cholesterol at 15 years, but group A had significant worsening of their serum triglycerides. Both groups had nonsignificant changes in blood pressure at 15 years. In conclusion, ILI in real-world clinical practice that results in ≥7% weight loss at one year in patients with DM and obesity is associated with continued improvement in cardiometabolic outcomes at 15 years.

Disclosure

A.Khater: None. M.Al-badri: None. T.Salah: None. S.E.Dhaver: 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.
444-P: Satisfaction with Information Regarding Pharmaceutic Therapy in Angiographied Coronary Patients with Type 2 Diabetes
Authors: RATZ MAGDALENA , VOGEL JOHANNES , PLATTNER THOMAS , VONBANK ALEXANDER , MADER ARTHUR , SPRENGER LUKAS , MAECHLER MAXIMILIAN , LARCHER BARBARA , LEIHERER ANDREAS , MUENDLEIN AXEL , FRICK MATTHIAS , DREXEL HEINZ , SAELY CHRISTOPH H.
Published: June 2023

Satisfaction with information regarding pharmaceutic therapy is important because it may strongly affect the appropriate use of drug therapy including medication adherence. No data on this parameter are available in the clinically important population of patients with type 2 diabetes (T2DM) undergoing coronary angiography. We therefore consecutively enrolled a cohort of 272 patients who underwent coronary angiography for the evaluation of suspected or established stable coronary artery disease (CAD) from March through December 2022. From our patients, 94 (34.4% of the total study population) had T2DM according to ADA criteria. Satisfaction with information regarding pharmaceutic therapy was measured using the validated Satisfaction with Information about Medicines Scale (SIMS-D) which consists of two sub-scales covering action and usage or potential problems, respectively. Further, health literacy, which includes the ability to understand and follow instructions for treatment was determined using the EU-HLS-Q16 questionnaire. SIMS-D questionnaires were returned by 196 (71.8%) and EU-HLS-Q16 by 229 (83.9%) patients. Median total SIMS-D scores did not differ significantly between T2DM patients and nondiabetic subjects (11, interquartile range (IQR) 9 vs. 9, IQR 8; p=0.383); independent of T2DM status patients scored significantly lower on items targeting satisfaction with information about potential problems of medication than the in sub-scales for action and usage (p<0.001). In analysis of covariance, health literacy independently of age and T2DM predicted SIMS-D (F=18.55; p<0.001). From our findings we conclude that satisfaction with information about medicines in angiographied coronary patients does not depend on the presence of T2DM but is significantly impacted by health literacy.

Disclosure

M. Ratz: None. J. Vogel: None. T. Plattner: None. A. Vonbank: None. A. Mader: None. L. Sprenger: None. M. Maechler: None. B. Larcher: None. A. Leiherer: None. A. Muendlein: None. M. Frick: None. H. Drexel: None. C.H. Saely: None.
446-P: Antihyperglycemic Medication Initiation after Cardiovascular Hospitalization in Older Adults with Diabetes Increases Hypoglycemia without Improving Survival
Authors: FARAHVASH ARMIN , SIVASWAMY ATUL , ABDEL-QADIR HUSAM , LEGA ILIANA C.
Published: June 2023

Background: The short-term safety and long-term cardiovascular benefits of initiating new antihyperglycemic medications at hospital discharge are unclear, especially for elderly patients with acute cardiovascular disease. This study aimed to determine if initiation of a new diabetes medication is associated with differences in outcomes in this patient population.

Methods: This was a population-based cohort study of individuals ≥65 years with diabetes on antihyperglycemic medication who were discharged from a hospitalization for heart failure, acute myocardial infarction, or stroke in Ontario, Canada from April 2011 to March 2019. We categorized individuals based on initiation of a new diabetes medication (initiators) within 30 days of discharge. Primary outcome was a composite of death or cardiovascular hospitalization. Secondary outcome was rate of hypoglycemia. We performed a Cox-regression on a propensity matched cohort.

Results: A total of 54,117 individuals were included, with 5,129 (9.5%) initiators and 48,988 (90.5%) non-initiators. Median age was 78 years (IQR 71-84) and 56.7% were male. Matched pair analysis included 4,844 pairs of initiators and non-initiators with standardized differences of ≤0.05 for all baseline variables. Median follow-up was near 2.2 years in both groups. There were no significant differences in the hazard of the composite of death/cardiovascular hospitalization (HR 0.97, 95% CI 0.92-1.02, p=0.18) or the hazard of death (HR 0.98, 95% CI 0.93-1.04, p=0.56). There was a higher risk of hypoglycemia among initiators (113 [2.3%] vs 76 [1.6%]) within one year of follow-up (HR: 1.49, 95% CI 1.12-1.98, p=0.007).

Conclusion: Starting a new antihyperglycemic medication in patients with diabetes who are discharged after hospitalization for a cardiovascular event is associated with an increased risk of hypoglycemia but does not reduce mortality or cardiovascular events.

Disclosure

A.Farahvash: None. A.Sivaswamy: None. H.Abdel-qadir: Other Relationship; AstraZeneca, JAZZ Pharmaceuticals. I.C.Lega: None.
45-OR: Newborn Adiposity and Cord Blood DNA Methylation—An Epigenome-Wide Association Study in HAPO with Validation in Gen3G
Authors: JOSEFSON JAMI L. , KUANG ALAN , SCHOLTENS DENISE , ALLARD CATHERINE , LOWE WILLIAM , HIVERT MARIE-FRANCE
Published: June 2023

Differential cord blood DNA methylation (cb DNAm) in response to hyperglycemia in pregnancy may be associated with neonatal adiposity, a risk factor for childhood obesity. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study enrolled a multiethnic cohort to evaluate glycemia in pregnancy and newborn adiposity measured by skinfold thicknesses. We conducted an epigenome-wide association study using HAPO as a discovery sample and performed a replication study in an independent cohort, Gen3G. We analyzed cb DNAm with Illumina EPIC arrays (791,359 CpG sites after QC) on 2712 HAPO samples. We assessed the association between sum of 3 skinfolds and cb DNAm using linear regression models adjusted for maternal and offspring covariates and cell counts. We identified 90 CpG sites after accounting for multiple testing (Bonferroni-adjusted p<0.05). Using these sites identified in HAPO, we conducted similar regression analyses in 139 Gen3G cb DNAm samples to replicate findings. Similar associations at 7 CpG sites were identified including loci near KLF7, which encodes a regulator of cell proliferation and inhibitor of adipogenesis, and IGF1R, which encodes a transmembrane receptor involved in cell growth and survival that binds IGF1 and insulin, the latter especially during fetal life. These findings support epigenetic mechanisms in the developmental origins of neonatal adiposity.

Disclosure

J.L.Josefson: None. A.Kuang: None. D.Scholtens: None. C.Allard: None. W.Lowe: None. M.Hivert: None.

Funding

National Institutes of Health (R01HD034243, R01DK118403)
453-P: Serum Lipocalcin-2 Levels, Fat Distribution, and the Risk of Cardiovascular Events—A Chinese Community-Based Longitudinal Cohort
Authors: HU TINGTING , XU YITING , SHEN YUN , WANG YUFEI , MA XIAOJING , BAO YUQIAN
Published: June 2023

Aims: We aimed to explore whether there was a joint effect of serum lipocalcin-2 (LCN2) levels and fat distribution or interaction on the development of cardiovascular disease (CVD) in a middle-aged and elderly, community-based cohort.

Methods: This prospective study included 1,349 participants (583 men and 766 postmenopausal women) aged 50-80 years, without evident CVD from Shanghai communities in 2013-2014. All participants underwent complete risk factor survey and body composition measurement at baseline. The follow-up assessment was conducted in 2021-2022 for cardiovascular events via phone calls and electronic medical records. Magnetic resonance imaging was used to assess fat distribution including subcutaneous fat area (SFA) and visceral fat area (VFA). SFA ≥ 75th percentile was classified as high, and VFA ≥ 80 cm2 was defined as high.

Results: During a mean follow-up of 7.6 years, 140 (10.4%) cases of cardiovascular events occurred, with 56 cases of ischemic heart diseases and 84 cases of cerebrovascular events. In fully adjusted Cox proportional hazards models, increasing baseline serum LCN2 levels were associated with a higher risk of cardiovascular events in women (HR for per 10 ng/mL increase: 1.11, 95%CI 1.02-1.20), but disappeared in men (HR for per 10 ng/mL increase: 1.00, 95%CI 0.93-1.08). Fat distribution modified the association between serum LCN2 levels and cardiovascular events in women, strengthening the association at low VFA levels (P interaction = 0.024), regardless of SFA levels (P interaction = 0.190).

Conclusions: Increasing LCN2 levels were independently and positively associated with the risk of cardiovascular events in women, which could be interacted by fat distribution at baseline.

Disclosure

T.Hu: None. Y.Xu: None. Y.Shen: None. Y.Wang: None. X.Ma: None. Y.Bao: None.
458-P: Proinflammatory Macrophage Phenotype Modulates Vascular Smooth Muscle Cell Differentiation via the Histone Demethylase JMJD3
Authors: MANGUM KEVIN D. , JOSHI AMRITA , MAZUMDER PURBA , WOLF-FORTUNE SONYA , BARRETT EMILY , MOORE BETHANY , DAVIS FRANK M. , GALLAGHER KATHERINE
Published: June 2023

Patients with diabetes are at increased risk of a multitude of vascular diseases, including atherosclerosis, which is driven by macrophage-mediated inflammation. While it is known that atherosclerosis is characterized by a proliferative, synthetic smooth muscle phenotype that underlies disease, the exact role of other cell types, namely myeloid cells and their interaction with smooth muscle cells is less understood. Furthermore, how diabetes modifies atherosclerotic severity is another important question. To address this, we performed an epigenetic superarray to identify key chromatin modifying enzymes in vascular smooth muscle cells (vSMC) from normal diet (ND) and diabetic-induced obese (DIO) aortas. We identified the histone demethylase, JMJD3, which was significantly decreased in DIO compared to ND vSMC (p<0.05). Furthermore, in our single cell RNA-seq data set from human atherosclerotic lesions, JMJD3 was expressed in smooth muscle cells. It is known that macrophages in atherosclerotic lesions exhibit a pro-inflammatory phenotype. To model this pro-inflammatory process, we stimulated bone marrow derived macrophages with LPS and found that supernatant from LPS-stimulated BMDMs significantly inhibited smooth muscle specific gene expression (SMA, SM22, CNN1, SM-MHC) as well as expression of JMJD3 compared to control media (p<0.05). Additionally, siRNA-mediated knockdown of JMJD3 in vSMC reduced SMC-specific gene expression, and treatment of mouse aortic vSMC with the JMJD3 selective inhibitor, GSK4J, decreased smooth muscle gene expression (p<0.05). Our data shows that pro-inflammatory macrophages drive reduced vascular smooth muscle gene expression and that JMJD3 in SMC is a regulator of this process. These results implicate JMJD3 in macrophage-smooth muscle cell crosstalk in the pro-inflammatory state and identify it as a potential therapeutic target in the management of atherosclerosis.

Disclosure

K.D.Mangum: None. A.Joshi: None. P.Mazumder: None. S.Wolf-fortune: None. E.Barrett: None. B.Moore: None. F.M.Davis: None. K.Gallagher: None.

Funding

National Institutes of Health (1F32DK131799-01); American College of Surgeons; Vascular & Endovascular Surgery Society
46-OR: Amelioration of Insulin Resistance after Delivery Lowers the Risk of Postpartum Type 2 Diabetes in Women with Gestational Diabetes Mellitus
Authors: SON HEEJUN , HO MOON JOON , CHO NAM H. , CHUL JANG HAK
Published: June 2023

Background: Detecting the risk of postpartum diabetes in women with gestational diabetes mellitus (GDM) is essential for proper intervention. We investigated whether changes in insulin sensitivity after delivery affect the risk of diabetes in Korean women with GDM.

Method: In a prospective cohort including women with GDM, we included those who attended the postpartum visit at 2 months and yearly thereafter. The change in insulin sensitivity was defined as ∆Matsuda index, the difference between the initial postpartum visit and during pregnancy. We analyzed the risk of diabetes according to tertiles of ∆Matsuda index.

Results: During 3.4 years of follow-up, 60 out of 347 subjects (17.3%) developed diabetes. The incidence of diabetes decreased as the tertile of ∆Matsuda index increased (26.7%, 17.2%, and 7.8%, P = 0.001). Subjects in the second and third tertile of ∆Matsuda index showed lower risk of diabetes compared to the subjects in the first tertile (HR, 0.45; 95% CI, 0.24-0.82; HR, 0.18; 95% CI, 0.07-0.48) after adjusting for age, family history of diabetes, gravida, lactation, fasting glucose, and postpartum BMI.

Conclusion: Amelioration of insulin resistance lowers the risk of diabetes in Korean women with GDM. Although the assessment of insulin sensitivity is not standardized, changes in insulin sensitivity may be a useful predictor for diabetes in women with GDM.

Disclosure

H.Son: None. J.Moon: None. N.H.Cho: None. H.Jang: None.
460-P: Pulse Pressure Predicts Future Cardiovascular Events in Cardiovascular Disease Patients with Type 2 Diabetes
Authors: PLATTNER THOMAS , VONBANK ALEXANDER , MADER ARTHUR , SPRENGER LUKAS , MAECHLER MAXIMILIAN , LARCHER BARBARA , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H.
Published: June 2023

Pulse pressure, i.e. the difference between systolic and diastolic blood pressure is a measure of arterial stiffness, which is a strong predictor of cardiovascular risk. Its impact on the risk of cardiovascular events in patients with type 2 diabetes (T2DM) is unclear and is addressed in the present study. We enrolled a large high risk cohort of 1327 patients with established cardiovascular disease (1009 patients with angiographically proven stable CAD and 318 patients with sonographically proven peripheral artery disease). T2DM was diagnosed according to ADA criteria. Prospectively, cardiovascular events were recorded over a mean follow-up period of 9.3±4.6 years. At baseline, pulse pressure was 60±17 mmHg in patients with T2DM (n=481) and 57±17 mmHg in subjects who did not have T2DM (p=0.002). During follow-up, 614 patients suffered cardiovascular events. The event rate was higher in patients with T2DM than in those who did not have diabetes (54.8% vs. 42.2% p<0.001). Pulse pressure significantly predicted cardiovascular events after multivariate adjustment including diabetes status in the total study cohort, with a standardized adjusted hazard ratio (HR) of 1.14 [1.05-1.24]; p=0.003. Importantly, pulse pressure also predicted cardiovascular events in the very high risk subgroup of cardiovascular disease patients with T2DM (HR 1.20 [1.06-1.37]; p=0.006). We conclude that pulse pressure predicts cardiovascular events in cardiovascular disease patients with T2DM.

Disclosure

T.Plattner: None. C.H.Saely: None. A.Vonbank: None. A.Mader: None. L.Sprenger: None. M.Maechler: None. B.Larcher: None. A.Leiherer: None. A.Muendlein: None. H.Drexel: None.
461-P: Treatment with Mild Electrical Stimulation + Heat Shock (MET) Suppresses the Progression of Atherosclerosis in ApoE-Deficient Mice
Authors: YOSHIZUMI RINTARO , KONDO TATSUYA , WATANABE TAKURO , MIYAKAWA NOBUKAZU
Published: June 2023

[Purpose] We have previously reported that mild electrical stimulation + heat shock (MET) treatment promotes the expression of heat shock protein 72 (HSP72), which works as molecular chaperone to suppresses oxidative stress, JNK activity and mitochondrial dysfunction, and thus ameliorates insulin resistance and hyperglycemia. Macrophage polarity and atherogensis with MET were investigated.[Methods] RAW264.7 and mouse bone marrow-derived macrophages (BMM) were treated with MET (42°C, 55 pulses/sec, 0.1 ms duration) and LPS 1 ng/mL. Six-week-old HSP+/+/ApoE-/- and HSP-/-/ApoE-/- mice were given a high-fat diet (HFD) for 14 weeks, and Sham/MET treatment was started from 10 weeks of age onwards. Glucose tolerance, biochemical parameters were examined, and the degree of arteriosclerosis (AS) formation and oxidative stress were evaluated histologically in aorta. [Results] After MET treatment in RAW264.7, HSP72 mRNA was increased, and LPS-stimulated MCP-1 and iNOS expression and JNK phosphorylation were all decreased. Experiment using BMM showed similar results with RAW264.7. There were no significant differences in physiologocal and metabolic parameters between Sham and MET groups after HFD. Compared with the MET group of HSP-/-/ApoE-/- mice, the degree of AS formation, necrotic core and fibrous capsule thickness were all significantly decreased in the MET group of HSP+/+/ApoE-/- mice. However, no beneficial effects were observed either in Sham or MET in HSP-/-/ApoE-/- mice. Immunostaining of the plaque showed significant suppression of 4-HNE and F4/80 in the HSP+/+/ApoE-/- mice treated with MET compared to those with Sham. Neither Sham nor MET had an inhibitory effect of 4-HNE and F4/80 in HSP-/-/ApoE-/- mice.[Conclusion] The enhancement of HSP72 expression by MET showed anti-inflammatory effect by polarity changes in macrophages and suppression of oxidative stress, which may lead to the suppression of atherosclerosis.

Disclosure

R.Yoshizumi: None. T.Kondo: None. T.Watanabe: None. N.Miyakawa: None.