Endocrine Abstracts

Introduction: Type 2 diabetes mellitus have been associated with excessive production of reactive oxygen species. Glutathione S-transferase (GST) polymorphisms result in decreased or absent enzyme activity and altered oxidative stress. Meta-analyses have indicated that deletion of either GSTM1 or GSTT1 is associated with a significant increased risk of coronary heart disease. The aim of this study was to evaluated if ascorbic acid (AA) plasma levels differ by GST genotype in diabetic patients with and without angiopathy.

Methods: An observational analytical case-control study in 123 Caucasians type 2 diabetic patients was performed. GI - 65 diabetics with angiopathy, GII - 58 diabetics without angiopathy. Plasma levels of AA were measured by a validated HPLC method. The genotyping of GSTT1 and GSTM1 it was determined simultaneously by PCR-Multiplex technique.

Results: The frequency of GSTM1 and GSTT1 single-null genotypes was 42.9% and 30.8% in group I and 43.9% and 31.0% among in group II. The percentage of diabetics patients who had both GSTM1 and GSTT1 functional genotypes was GI:46.0% and GII:42.9%, who had one of the present genotypes was GI:33.4% and GII:37.5% and who had both null genotypes was GI:20.6% and GII:19.6%. Plasma AA concentrations were lower in those with the GSTT1 null genotype than in those with the GSTT1 functional genotype. GSTM1 null genotypes had higher plasma AA levels than those with functional GSTM1 allele. Suboptimal AA plasma concentrations (<4.93 μmol/L) were more frequent in GSTT1 deletion genotype (76.3%) compared to GSTT1-1 (69.4%). Inversely, the percentage of patients with functional GSTM1 allele (72.1%) was higher than null genotype (67.3%).

Conclusion: Plasmatic levels of AA differ by GSTM1 and GSTT1 polymorphisms in Caucasians diabetic patients with or without angiopathy. The upper and lower regulation of AA plasma levels in subjects with nonfunctional GSTT1 or GSTM1 could be partially understood to compensate the lack of functionality.