Matsui Jun, Tamasawa Naoki, Tanabe Jutaro, Kasai Nobuhiko, Murakami Hiroshi, Yamato Kazumi, Guan JingZhi, Suda Toshihiro
Third Department of Internal Medicine, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, Aomeri-ken 036-8562, Japan.
Diabetes Res Clin Pract. 2004 Dec;66(3):229-36. doi: 10.1016/j.diabres.2004.03.011.
The study was to evaluate the influence of particle size and lipid composition of low-density lipoprotein (LDL) on urinary albumin excretion and oxidative susceptibility of LDL, and to define association between LDL particle size and alpha-tocopherol content in LDL from normotensive and normocholesterolemic patients with type 2 diabetes. Twenty-three patients with type 2 diabetes (13 males, 10 females) were studied, and none of these patients had hypertension, hypercholesterolemia and overt proteinuria. The baseline body mass index of all patients was less than 28 kg/m2. All patients were hospitalized in Hirosaki University Hospital and took dietary therapy whose total intake was restricted to less than 30 kcal/kg of ideal body weight for 3 weeks. Their plasma glucose levels were controlled within fasting plasma glucose <140 mg/dl and 2-h postprandial plasma glucose <200 mg/dl. LDL particle size was evaluated by using high-resolution polyacrylamide gel electrophoresis (Lipoprint LDL System) and expressed by Rf value. LDL was incubated with 0.25 microM CuSO4 for 20 h, and the degree of LDL oxidation was determined by malondialdehide analysis. Twenty-four-hour urinary C-peptide excretion and plasma triglyceride concentration in patients with microalbuminuria were significantly higher than those in normoalbuminuric patients. Rf values in microalbuminuric patients were significantly greater than those in normoalbuminuric patients. There were significantly inverse correlations between Rf value and alpha-tocopherol content in LDL, and between Rf value and LDL-free cholesterol/LDL-total cholesterol. Thiobarbituarte-reactive substance level in LDL had a tendency to correlate with Rf value and significantly inverse correlation to alpha-tocopherol content in LDL. In type 2 diabetics without hypertension, hypercholesterolemia and obvious obesity, smaller LDL particle size, accompanied by mild hyperinsulinemia and mild hypertriglyceridemia seems to be one of the important factors responsible for microalbuminuria. In addition, the present study suggests that the decrease of alpha-tocopherol content in small LDL particle is associated with oxidative susceptibility to Cu2+-induced oxidation.
