Diabetes mellitus is the most common metabolic disease with late complications due to chronic hyperglycaemia. Altered carbohydrate and lipid metabolism together with impaired detoxification of carbonyl substrates and impaired trapping of oxygen radicals are responsible for diabetic cell damage. Variable functional capacity of detoxifying systems could contribute to different susceptibility to develop complications. Identification of genetic variants responsible for modulating relevant intermediate phenotype in diabetic milieu could help to define individual risk-profile and to modify therapeutic strategy accordingly.