scholarly journals Monitoring of early and advanced glycation in relation to the occurrence of microvascular complications in children and adolescents with type 1 diabetes mellitus

2009 ◽  
pp. 553-561
Author(s):  
J Kostolanská ◽  
V Jakuš ◽  
Ľ Barák

The authors aimed to evaluate if the monitoring of serum advanced glycation end-products (s-AGEs) could help to predict a development of diabetic complications. Clinical and biochemical parameters including fructosamine (FAM), glycated hemoglobin (HbA1c) and serum AGEs were investigated in children and adolescents with 1 type diabetes with (+DC) and without (–DC) complications. FAM levels (in mmol/l) were significantly elevated in +DC diabetic group compared to –DC one (3.043±0.459 vs. 2.614±0.430; p<0.001) or to controls (3.043±0.459 vs. 1.620±0.340; p<0.001) as well as in –DC compared to controls (2.614±0.430 vs. 1.620±0.340; p<0.001). HbA1c (in %) were significantly elevated in +DC diabetic group compared to –DC one (10.48±1.83 vs. 8.41±1.19; p<<0.001) or to controls (10.48±1.83 vs. 5.0±0.38, p<<0.001) and also in –DC compared to controls (8.41±1.19 vs. 5.0±0.38; p<0.001). Serum AGEs levels (in A. U.) were significantly higher in +DC group than in – DC (73.0±14.09 vs. 65.8±9.05; p<0.05) and in group +DC than in controls (73.0±14.09 vs. 60.17±13.78; p<0.05), whereas there was no difference between –DC and controls. FAM correlated with HbA1c in both diabetic groups (+DC: r=0.374; p<0.05; –DC: r=0.719; p<0.001), but not in controls. Serum AGEs were correlated with HbA1c (r=0.478; p=0.003) in +DC, but not in –DC or controls. Enhanced serum AGEs levels show that they could be not only an attendant phenomenon of microangiopathies, but also a predictor of their development.

2008 ◽  
Vol 3 (3) ◽  
pp. 243-249 ◽  
Author(s):  
Constantina Heltianu ◽  
Simona-Adriana Manea ◽  
Cristian Guja ◽  
Carina Mihai ◽  
Constantin Ionescu-Tirgoviste

AbstractAdvanced glycation end products (AGEs) are involved in the occurrence of vascular complications in diabetes. The present study was undertaken to investigate the level of low-molecular weight products of AGEs (LMW-AGEs) in relation to microvascular complications in type 1 diabetes, and the possible relationship with nitric oxide (NO) as a marker of endothelial function. Patients with normal renal function (NRF) were classified into two groups: (1) without, and (2) with diabetic neuropathy; and patients with renal impairment also into two groups: (3) diabetic renal disease, and (4) end-stage renal disease. The fluorescence of LMW-AGEs and measurement of NO metabolites was assessed in 277 serum samples. In addition, multiple regression analysis was performed. In group 1, LMW-AGEs level (9.3±1.1 AF%) was higher than in the control group (2.4±0.3 AF%). A trend in the increase of LMW-AGEs with neuropathy (29.7±5.5 AF%, group 2), and further with renal impairment (47.0±8.0, group 3 and 137.8±25.5 AF%, group 4), was observed. In multivariate regression analysis LMW-AGEs were associated with NO metabolites in group 2. In NRF patients, diabetic neuropathy was significantly correlated with LMW-AGEs and NO metabolites, independently of serum creatinine and duration of diabetes. This relationship suggests that the NO and LMW-AGEs’ actions (possibly synergistic) in endothelial activation possess a role in the initiation and development of diabetic microvascular complications.


2015 ◽  
Vol 29 (6) ◽  
pp. 503-506
Author(s):  
Letícia Carneiro Gomes ◽  
Marciane Welter ◽  
Luiza Cristina Gobor ◽  
Izabella Castilhos Ribeiro Santos-Weiss ◽  
Suzana Nesi França ◽  
...  

2016 ◽  
Vol 64 (3) ◽  
pp. 800.3-800
Author(s):  
JM Corletto ◽  
S Accacha ◽  
I Voloshyna ◽  
N Siegart ◽  
L Kasselman ◽  
...  

Purpose of StudyAdvanced glycation end products (AGE), proteins formed by nonenzymatic glycation, are prevalent in patients with diabetes mellitus (DM) and contribute to the development of atherosclerosis. We have demonstrated that plasma from patients with type 1 DM (T1DM) decreases expression of cholesterol efflux proteins in cultured THP-1 macrophages compared to healthy control (HC) plasma. Here we explore a mechanism that restores cholesterol efflux in T1DM plasma through blockade of the receptor for AGE (RAGE).Methods UsedCarboxy-methyl-lysine-modified proteins (CML-MP), the most prevalent AGE in vivo, were measured in the plasma of 20 pediatric T1DM patients and 20 sex and age-matched HC by ELISA. THP-1 macrophages (106/ml) were incubated for 18 h in RPMI media in the presence of 10% plasma from each enrolled patient in triplicate±anti-RAGE antibody. Cholesterol efflux proteins: ATP binding cassette transporter (ABC)A1 and 27-hydroxylase were quantified by real-time RT-PCR using specific primers for each gene.Summary of ResultsThe level of CML-MP was significantly elevated in T1DM plasma (1.65±1.3 ng/ml) versus HC plasma (1.05±0.4 ng/ml) (P<0.05, n=20). ABCA1 expression was significantly lower in macrophages exposed to T1DM plasma (1.108±0.8 U) versus HC plasma (1.624±0.6) (P<0.05, n=20). Exposure of THP-1 macrophages to T1DM plasma downregulated 27-hydroxylase mRNA to 1.94±0.9 U in T1DM versus 3.4±2.9 U in HC (P<0.01, n=20). Inactivation of RAGE before exposure to T1DM plasma increased ABCA1 expression by 20%. However, we observed no effect on the level of 27-hydroxylase.ConclusionsWe demonstrate that elevated AGE in plasma of T1DM patients inhibits cholesterol efflux and suppresses intracellular cholesterol processing via 27-hydroxylase and ABCA1 in naïve macrophages. RAGE inactivation restores mRNA level of the ABCA1 transporter, but not the 27-hydroxylase enzyme. These findings impart new targets for prevention of cardiovascular disease in DM and suggest that factors other than AGE may impact cholesterol transport.


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