Growing prevalence of diabetes (type 2 as well as type 1) and its related morbidity due to vascular complications creates a large burden on medical care worldwide. Understanding the molecular pathogenesis of chronic micro-, macro- and avascular complications mediated by hyperglycemia is of crucial importance since novel therapeutic targets can be identified and tested. Thiamine (vitamin B1) is an essential cofactor of several enzymes involved in carbohydrate metabolism and published data suggest that thiamine metabolism in diabetes is deficient. This review aims to point out the physiological role of thiamine in metabolism of glucose and amino acids, to present overview of thiamine metabolism and to describe the consequences of thiamine deficiency (either clinically manifest or latent). Furthermore, we want to explain why thiamine demands are increased in diabetes and to summarise data indicating thiamine mishandling in diabetics (by review of the studies mapping the prevalence and the degree of thiamine deficiency in diabetics). Finally, we would like to summarise the evidence for the beneficial effect of thiamine supplementation in progression of hyperglycemia-related pathology and, therefore, to justify its importance in determining the harmful impact of hyperglycemia in diabetes. Based on the data presented it could be concluded that although experimental studies mostly resulted in beneficial effects, clinical studies of appropriate size and duration focusing on the effect of thiamine supplementation/therapy on hard endpoints are missing at present. Moreover, it is not currently clear which mechanisms contribute to the deficient action of thiamine in diabetes most. Experimental studies on the molecular mechanisms of thiamine deficiency in diabetes are critically needed before clear answer to diabetes community could be given.

Background. Diabetic nephropathy (DN) represents a devastating complication of diabetes. Family clustering, heterogeneity in the onset and progression and results of segregation studies indicate that susceptibility to DN is a complex trait. Methods. Common single nucleotide polymorphisms in the RAGE (receptor of advanced glycation end-products) gene (−429T/C, −374T/A, G82S, 1704G/T, 2184A/G and 2245G/A) were studied in the association study comprising 605 Caucasian subjects by means of haplotype analysis in order to identify an eventual haplotype marker for DN in type 2 diabetes. Haplotypes were constructed computationally; frequencies were compared among groups of subjects with type 2 diabetes (DM) and DN, diabetics without DN and non-diabetics. Survival analysis was carried out to ascertain whether certain RAGE haplotypes influence onset of DN in type 2 diabetics. Results. Significant differences in haplotype frequencies among DM + DN vs DM non-DN and non-DM groups were found (P = 0.0007 and 0.0013, respectively; permutation test). Frequency of the RAGE₂ haplotype containing minor alleles in positions −429 and 2184 (CTGGGG) in the DN group was significantly higher than in the two control groups (21.7% vs 12.8% and 13.8%, both P_corr<0.003; two-tail Fisher exact test); odds ratios 1.65 [95% confidence interval (CI): 1.08–2.50; P = 0.020] and 1.79 (95% CI: 1.22–2.62; P = 0.003), respectively. In survival analysis, duration of diabetes until the onset of DN (e.g. appearance of persistent proteinuria) was significantly different among RAGE₂ diplotype groups (P<0.05); median DN-free interval was 9.6 years in RAGE₂ +/+ homozygotes, 15.2 years in +/− heterozygotes and 17.0 years in the −/− combination. Conclusions. The RAGE₂ haplotype is associated with DN in type 2 diabetics and with earlier DN onset and, thus, can be regarded a marker for DN.

Objectives: (i) to determine the extent of oxidative stress and DNA damage and repair using a panel of selected markers in patients with type 1 and type 2 diabetes mellitus (T1DM, T2DM), (ii) to find their possible relationships with diabetes compensation and duration, and finally (iii) to test for the effect of functional polymorphisms in the 8-oxoguanin DNA glycosylase (rs1052133), catalase (rs1001179) and superoxide dismutase (rs4880) genes on respective intermediate phenotypes. Methods: A total of 207 subjects (23 children and 44 adults with T1DM, 52 adult patients with T2DM and 88 healthy adult control subjects) were enrolled in the study. The following markers of redox state were determined in participants: erythrocyte superoxide dismutase (Ery-SOD), whole blood glutathione peroxidase (WB-GPx), erythrocyte glutathione (Ery-GSH), plasma total antioxidant capacity (P-tAOC) and plasma malondialdehyde (P-MDA). Furthermore, the extent of DNA damage and repair was ascertained using the following parameters: DNA single strand breaks (DNAssb), DNA repair capacity (DNArc) and DNA repair index (DNRI). Results: Comparison of T1DM vs. T2DM patients revealed significantly higher Ery-GSH content (P < 0.0001) and significantly lower Ery-SOD activity (P = 0.0006) and P-tAOC level (P < 0.0001) in T1DM subjects. T2DM diabetics exhibited a significant increase in DNAssb (P < 0.0001) and significant decrease in both DNArc (P < 0.0001) and DNRI (P < 0.0001) compared with T1DM patients. Patient’s age (irrespective of DM type) significantly correlated with DNAssb (r = 0.48, P < 0.0001), DNArc (r = −0.67, P < 0.0001) and DNRI (r = −0.7, P < 0.0001). Allele frequencies of all studied polymorphisms did not exhibit any significant association with the investigated parameters. Conclusion: We demonstrated significant age- and DM type-related changes of oxidative DNA modification and capacity for its repair in subjects with T1DM and T2DM.