No abstract

The aim of this study was to investigate the relationship between advanced glycation end products (AGEs) and arterial stiffness (AS) in subjects with type 1 diabetes without clinical cardiovascular events. A set of 68 patients with type 1 diabetes and 68 age-and sex-matched healthy subjects were evaluated. AGEs were assessed using serum concentrations of N-carboxymethyl-lysine (CML) and using skin autofluorescence. AS was assessed by aortic pulse wave velocity (aPWV), using applanation tonometry. Patients with type 1 diabetes had higher serum concentrations of CML (1.18 vs 0.96 mg/ml; PZ0.008) and higher levels of skin autofluorescence (2.10 vs 1.70; P!0.001) compared with controls. These differences remained significant after adjustment for classical cardiovascular risk factors. Skin autofluorescence was positively associated with aPWV in type 1 diabetes (rZ0.370; PZ0.003). No association was found between CML and aPWV. Skin autofluorescence was independently and significantly associated with aPWV in subjects with type 1 diabetes (bZ0.380; P!0.001) after adjustment for classical cardiovascular risk factors. Additional adjustments for HbA1c, disease duration, and low-grade inflammation did not change these results. In conclusion, skin accumulation of autofluorescent AGEs is associated with AS in subjects with type 1 diabetes and no previous cardiovascular events. These findings indicate that determination of tissue AGE accumulation may be a useful marker for AS in type 1 diabetes.

The oxidized nucleoside 8-hydroxy-2'-deoxyguanosine has been widely studied as a marker of DNA oxidation; however, data on the occurrence of other metabolites in plasma that are related to DNA damage are scarce. We have applied an improved, sensitive, robust, and reliable method, involving solid phase extraction and ultrahigh-performance liquid chromatography (UHPLC)-tandem mass spectrometry (MS/MS), to the precise quantitation of seven metabolites in the plasma of 15 elite triathletes after a 2-week training program. All compounds were eluted in the first 1.6 min, with limits of detection and quantification ranging between 0.001 and 0.3 ng.mL(-1) and 0.009 and 0.6 ng.mL(-1), respectively. Four compounds were detected in plasma: guanosine-3'-5'-cyclic monophosphate, 8-hydroxyguanine, 8-hydroxy-2'-deoxyguanosine, and 8-nitroguanosine. After two weeks of training, 8-hydroxyguanine exhibited the highest increase (from 0.031 ± 0.008 nM to 0.036 ± 0.012 nM) (p < 0.05), which could be related to the enhanced activity of DNA-repairing enzymes that excise this oxidized base. Increased levels of guanosine-3'-5'-cyclic monophosphate and 8-hydroxy-2'-deoxyguanosine were also observed. In contrast, levels of 8-nitroguanosine (p < 0.05) were significantly reduced, which might be a protective measure as this compound strongly stimulates the generation of superoxide radicals, and its excess is related to pathologies such as microbial (viral) infections and other inflammatory and degenerative disorders. The results obtained indicate an induced adaptive response to the increased oxidative stress related to elite training, and point to the benefits associated with regular exercise.

sTWEAK concentrations are lower in patients with GDM compared with healthy pregnant women, and low concentrations of sTWEAK are associated with insulin resistance. These findings suggest that insulin resistance during pregnancy is closely linked to inflammatory imbalance and sTWEAK may represent a new candidate associated with GDM.