Dataset Information

Cross-sectional Analysis of AGE-CML, sRAGE, and esRAGE with Diabetes and Cardiometabolic Risk Factors in a Community-Based Cohort.

ABSTRACT:

Background

Advanced glycation end products (AGEs) and their receptors are regarded as central to the development of diabetic complications, but associations with diabetes and cardiometabolic outcomes in previous studies are mixed.

Methods

Using ELISA assays, we measured N(6)-carboxymethyllysine (AGE-CML), soluble receptor for AGEs (sRAGE), and endogenous secreted receptor for AGEs (esRAGE) in 1874 participants from the Atherosclerosis Risk in Communities study. We conducted a cross-sectional analysis to evaluate associations of these biomarkers with demographics, diabetes, hyperglycemia, cardiometabolic measures, and genetic variants in the gene encoding RAGE, AGER (advanced glycosylation end-product specific receptor).

Results

After adjustment for demographics and body mass index (BMI), there were no significant differences in AGE-CML, sRAGE, or esRAGE by diabetes or hemoglobin A_1c. Black race and AGER genetic variants were strongly associated with lower sRAGE and esRAGE even after adjustment [percent difference (95% CI) in black vs whites in sRAGE: -29.17 (-34.86 to -23.48), esRAGE: -26.97 (-33.11 to -20.84); with rs2070600 in sRAGE: -30.13 (-40.98 to -19.29), and esRAGE: -30.32 (-42.42 to -18.21); with rs2071288 in sRAGE: -20.03 (-34.87 to -5.18), and esRAGE: -37.70 (-55.75 to -19.65)]. Estimated glomerular filtration rate and albuminuria significantly correlated with sRAGE and esRAGE. BMI and C-reactive protein significantly negatively correlated with AGE-CML, sRAGE, and esRAGE. AGE-CML was modestly correlated with fructosamine and glycated albumin.

Conclusions

AGE-CML, sRAGE, and esRAGE were more related to genetic, kidney, and inflammatory measures than to diabetes in this community-based population. Our results suggest that, when measured by ELISA, these biomarkers lack specificity and are of limited value in evaluating the role of these compounds in diabetes.

SUBMITTER: Loomis SJ

PROVIDER: S-EPMC5555394 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cross-sectional Analysis of AGE-CML, sRAGE, and esRAGE with Diabetes and Cardiometabolic Risk Factors in a Community-Based Cohort.

Loomis Stephanie J SJ Chen Yuan Y Sacks David B DB Christenson Eric S ES Christenson Robert H RH Rebholz Casey M CM Selvin Elizabeth E

Clinical chemistry 20170309 5

<h4>Background</h4>Advanced glycation end products (AGEs) and their receptors are regarded as central to the development of diabetic complications, but associations with diabetes and cardiometabolic outcomes in previous studies are mixed.<h4>Methods</h4>Using ELISA assays, we measured N(6)-carboxymethyllysine (AGE-CML), soluble receptor for AGEs (sRAGE), and endogenous secreted receptor for AGEs (esRAGE) in 1874 participants from the Atherosclerosis Risk in Communities study. We conducted a cros ...[more]

PMID: 28280052

Similar Datasets

Project description:RationalePlasma soluble Receptor for Advanced Glycation End Product (sRAGE) is considered as a biomarker in COPD. The contribution of endogenous sRAGE (esRAGE) to the pool of plasma sRAGE and the implication of both markers in COPD pathogenesis is however not clear yet. The aim of the current study was therefore to measure plasma levels of esRAGE comparative to total sRAGE in patients with COPD and a control group. Further, we established the relations of esRAGE and total sRAGE with disease specific characteristics such as lung function and DLCO, and with different circulating AGEs.MethodsPlasma levels of esRAGE and sRAGE were measured in an 88 patients with COPD and in 55 healthy controls. FEV1 (%predicted) and FEV1/VC (%) were measured in both groups; DLCO (%predicted) was measured in patients only. In this study population we previously reported that the AGE N?-(carboxymethyl) lysine (CML) was decreased, N?-(carboxyethyl) lysine (CEL) increased and pentosidine was not different in plasma of COPD patients compared to controls.ResultsPlasma esRAGE (COPD: 533.9 ± 412.4, CONTROLS: 848.7 ± 690.3 pg/ml; p = 0.000) was decreased in COPD compared to controls. No significant correlations were observed between plasma esRAGE levels and lung function parameters or plasma AGEs. A positive correlation was present between esRAGE and total sRAGE levels in the circulation. Confirming previous findings, total sRAGE (COPD: 512.6 ± 403.8, CONTROLS: 1834 ± 804.2 pg/ml; p < 0.001) was lower in patients compared to controls and was positively correlated FEV1 (r = 0.235, p = 0.032), FEV1/VC (r = 0.218, p = 0.047), and DLCO (r = 0.308, p = 0.006). sRAGE furthermore did show a significant positive association with CML (r = 0.321, p = 0.003).ConclusionAlthough plasma esRAGE is decreased in COPD patients compared to controls, only total sRAGE showed a significant and independent association with FEV1, FEV1/VC and DLCO, indicating that total sRAGE but not esRAGE may serve as marker of COPD disease state and severity.

Project description:Background and aimThe are sex differences in cardiometabolic risk factors in type 2 diabetes mellitus (T2DM) as well as the age at disease onset. However, the impact of these risk factors on the age at onset of T2DM is less known in the Ghanaian population. An understanding of the differential impact of cardiometabolic risk factors on the age at onset on T2DM may lead to sex-specific interventions in preventive and management strategies for T2DM.MethodsThe study was cross-sectional from January to June 2019 at the Bolgatanga regional hospital. The study involved 163 T2DM patients (Female = 103, Male = 60), aged from 25 to 70 years. The body mass index (BMI) and the waist-to-hip ratio (WHR) were measured following standardized anthropometric techniques. Fasting venous blood samples were collected and analyzed for cardiometabolic risk factors including total cholesterol (TCHOL) and low-density lipoprotein (LDL) cholesterol.ResultsWhile TCHOL was higher in males than females (mean [SD]: F = .78 [1.37], M = 4.27 [1.39]) and LDL higher in females than males (mean [SD]: [F = 4.33 [1.22], M = 3.87 [1.26]), these did not, however, attain conventional statistical significance for TCHOL (t = 1.985, p = 0.05) and LDL (t = 2.001, p = 0.05). There were however, significant interactions between sex and the age at disease onset on TCHOL (t = -2.816, p = 0.006) and LDL (t = -2.874, p = 0.005), which were independent of the BMI, WHR and disease duration. The relationship between the age at disease onset and that of TCHOL and LDL were positive in females but negative in males.ConclusionFasting plasma TCHOL and LDL increases with increasing age at onset of T2DM in females but decreases in males. Strategies for the prevention and management of T2DM should be sex-specific. Females with T2DM should be given more attention regarding their fasting plasma cholesterol (total) and LDL cholesterol as they are more likely than men to have increased levels of these lipids with increasing age at disease onset.

Dataset Information

Cross-sectional Analysis of AGE-CML, sRAGE, and esRAGE with Diabetes and Cardiometabolic Risk Factors in a Community-Based Cohort.

Background

Methods

Results

Conclusions

Publications

Cross-sectional Analysis of AGE-CML, sRAGE, and esRAGE with Diabetes and Cardiometabolic Risk Factors in a Community-Based Cohort.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets