Disturbances of micronutrient and antioxidant status in diabetes.

Oxidants or reactive oxygen species (ROS) have been implicated in the pathology of a number of human diseases including insulin-dependent diabetes mellitus (IDDM) and non-isulin-dependent diabetes mellitus (NIDDM). Sato et al. (1979) were the first to report increased levels of plasma thiobarbituric acid-reactive substances (TBARS), a putative measure of ROS-induced lipid peroxidative damage, in IDDM and NIDDM patients. Subsequent studies have confirmed this observation of increased lipid peroxides in blood from NIDDM (Kaji et af. 1985; Uzel et 01. 1987) and IDDM (Jongkind et al. 1989) patients and in various tissues from rats with streptozotocin (STZ)or alloxaninduced diabetes (Higuichi, 1982; Karpen et al. 1982; Matkovics et ul. 1982). The possibility that the long-term complications of diabetes are associated with increased ROS-mediated damage is also supported by the work of Sat0 et a f . (1979) who found higher plasma TBARS in diabetic patients with angiopathy compared with those without angiopathy. Moreover, increased lipid peroxide levels were also found in lenses of both diabetic patients (Costagliola et al. 1988) and STZ-induced diabetic rats (Yeh & Ashton, 1990). The elevated levels of lipid peroxides in diabetes could result from the hyperglycaemic state as there is a significant relationship between erythrocyte membrane lipid peroxidation and hyperglycaemia in diabetic patients (Jain et al. 1989) and plasma lipid peroxides are higher in poorly-controlled compared with well-controlled diabetic patients (Sato et al. 1979). Jain et al. (1990) found that the increase in TBARS in erythrocytes from STZ-induced diabetic rats could be prevented in those rats in which hyperglycaemia was controlled by insulin treatment. Further indications that complications of diabetes associated with elevated levels of apparently oxidative changes to proteins and lipids are reviewed by Baynes (1991). It has been suggested that increased generation of ROS may arise from transition-metal catalysed autoxidation of glucose and other small autoxidizable molecules (Hunt & Wolff, 1990) or oxidation of glycated proteins (Gillery et al. 1989; Mullarkey et al. 1990). These mechanisms may explain the increased lipid peroxidation associated with hyperglycaemia. Alternatively, increased ROS-mediated lipid peroxidation in diabetes may result from disturbances in antioxidant defence. There is now ample evidence of substantial and complex antioxidant enzyme alterations in experimental and clinical diabetes (Godin et al. 1988), although results from different laboratories are not consistent (Oberley, 1988; Asayama et al. 1989). Some of the inconsistent observations of antioxidant enzymes in diabetes could arise from inter alia effects of starvation (Wohaieb & Godin, 1987) or ageing (Cand & Verdetti, 1989) on these enzymes.