Diabetes mellitus is a disease characterized by hyperglycemia and its complications have been attributed to long duration of this condition due to the abnormality of glucose metabolism 1,2) On the other hand, hyperlipidemia has been frequently observed in insulin-dependent 3,4) and non-insulindependent diabetic patients, 5) it was also observed in experimental insulin-dependent 6,7) and non-insulin-dependent diabetic animal models. 8) Therefore, hyperlipidemia in addition to hyperglycemia has also been thought to be a major risk factor for the development and progression of diabetic complications such as vasospastic angina, 9) nephropathy, 10,11) cataract 12) and peripheral neuropathy.13)

Diabetic nephropathy is characterized by persistent proteinuria, hypertension and declining renal function. Microalbuminuria is detected at the early stage of diabetic nephropathy. Approximately 30-40% of type 1 diabetic patients have renal complications, which are a major cause of mortality.1-3) Diabetes mellitus is a disease characterized by hyperglycemia. On the other hand, hyperlipidemia in addition to hyperglycemia has been frequently observed in insulin-dependent 4,5) and non-insulin-dependent diabetic patients. 6)Likewise, hyperlipidemia was also observed in experimental insulin-dependent 7,8) and non-insulin-dependent diabetic animal models.9) Hyperlipidemia in addition to hyperglycemia has been thought to be a major risk factor for the development and progression of diabetic complications such as nephropathy. 10,11) Recently, oxidative stress has been indicated to play an important role in the development and progression of diabetic nephropathy.12) Under hyperglycemic conditions, oxygen-derived free radicals are produced mainly through a glycation reaction. 13,14) Scheuer et al. 15) have shown that hyperlipidemia can aggravate glomerulosclerosis and chronic tubulointerstitial damage in kidneys and oxidative stress contributes to the deleterious effects of hyperlipidemia on renal damage. Chen et al. 16) have demonstrated that oxidized low density lipoprotein (LDL) enhances superoxide production by diabetic rat glomeruli. Their findings strongly suggest that oxidized LDL may play important roles in the pathogenesis of diabetic nephropathy through increased generation of oxygen-derived free radicals.It is well known that vitamin E, a lipid-soluble and antioxidant vitamin, protects unsaturated fatty acid, a main component of cell membranes, from attack by oxygen-derived free radicals. There have been a few reports concerning the effect of vitamin E on experimental diabetes. Je et al. 17) reported that vitamin E inhibited the oxidation of proteins in organs such as liver and kidney in streptozotocin (STZ)-induced diabetic rats. Baydas et al. 18) have shown that vitamin E as well as melatonin protects organisms from oxidative damages. On the other hand, insulin has been widely used for the treatment of type 1 (insulin-dependent) diabetes mellitus as hormone supplement therapy. These findings suggest that insulin in combination with vitamin E may exert a more beneficial effect than insulin alone on diabetic nephropathy. Recently, we reported that a long-term high cholesterol diet for STZ-induced diabetic rats not only precipitated the onset of cataracts but also increased the incidence of this complication with an increased death rate.19) Furthermore, in this report, we demonstrated that long-term combined treatment with vitamin E and insulin synergistically prevents the development and progression of cataracts of STZ-induced diabetic rats fed a high cholesterol diet.In a pilot experiment, we observed that a long-term high cholesterol diet aggravated STZ-induced renal damage in rats with increased urinary ...

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