Lipoprotein oxidizability and antioxidant activity in type 1 diabetics: relation to duration, glycemic control and hyperketonemia, and the effect of vitamin E supplementation

ABSTRACT

Among many hypotheses, oxidizability of lipoproteins has been implicated in the hyperlipidemia and the development of atherosclerosis and cardiovascular disease in diabetics as well as in the general population. Children with type 1 diabetes are particularly at high risk of early development of atherosclerosis. Studies evaluating LDL oxidizability in type 1 diabetics reported conflicting results and the benefit of antioxidants supplementation is still debatable. The present study included 70 [29 males, 41 females] children and adolescents with type 1 diabetes, attending the diabetic endocrine metabolic pediatric unit at children's hospital of Cairo University, who were investigated and compared to a control group of 36 [18 males, 18 females] healthy children and adolescents regarding lipid profile, susceptibility of LDL to in vitro oxidation as well as antioxidant activity. Special emphasis was done on the relation of increased lipid peroxidation to diabetes duration, glycemic control and hyperketonemia. The benefit of vitamin E supplementation [400 IU/day] was tested in 46/70 type 1 diabetics regarding lipid peroxidation, lipid profile and glycosylation. Results revealed significantly higher mean levels of fasting blood glucose, glycated hemoglobin, acetoacetate, beta-hydroxybuterate, total cholesterol, triglycerides. LDL and phospholipids in diabetics compared to controls. Diabetics also showed significantly increased oxidative stress [LDL oxidizability and serum malondialdehyde] as well as significantly lower antioxidant profile [reduced glutathione, serum vitamin E and vitamin E/cholesterol]. While hyperlipidemia increased significantly with diabetes duration, the increased LDL oxidizability and decreased antioxidant activity did not show significant difference with the diabetes duration, and LDL oxidizability didn't show correlation with diabetes duration or glycated hemoglobin level. On the other hand, diabetics with subclinical hyperketonemia, showed significantly increased oxidative stress [LDL oxidizability and serum malondialdehyde] compared to the normoketonemic, and LDL oxidizability correlated significantly with acetoacetate levels in diabetics. Vitamin E supplementation [400 IU/for 3 months] achieved a significant decrease in glycosylation with improvement of HbA[1], in 30/46 diabetics, a significant improvement of lipid profile, as well as a significant reduction in LDL oxidizability, and serum malondialdehyde, with a significant increase in reduced glutathione and vitamin E levels. There was also a significant increase in vitamin E/cholesterol and HDL/cholesterol indicating cardiovascular protection. Type 1 diabetics are at risk of hyperlipidemia with increased LDL oxidizability and reduced antioxidant activity. LDL oxidizability and antioxidant activity were not related to the duration of diabetes or the level of glycated hemoglobin, but were significantly related to increased serum acetoacetate levels. Hyperketonemic type 1 diabetics appear to be at higher risk of increased LDL oxidizability and reduced antioxidant activity. Vitamin E supplementation in a dose of 400 IU given daily for 3 months was beneficial with improvement of glycated hemoglobin and lipid profile, reduced oxidative stress, and increased antioxidant activity