Endocrinology Clinic, Antalya Research and Education Hospital, Antalya, Turkey.
Lipids Health Dis. 2013 Apr 24;12:54. doi: 10.1186/1476-511X-12-54.
Insulin treatment can lead to good glycemic control and result in improvement of lipid parameters in type 2 diabetic patients. This study was designed to evaluate the effect of insulin analog initiation therapy on low-density lipoprotein (LDL)/ high-density lipoprotein (HDL) sub-fractions and HDL associated enzymes in type 2 diabetic patients during early phase.
Twenty four type 2 diabetic patients with glycosylated hemoglobin (HbA1c) levels above 10% despite ongoing combination therapy with sulphonylurea and metformin were selected. Former treatment regimen was continued for the first day followed by substitution of sulphonylurea therapy with different insulin analogs (0.4 U/kg/day) plus metformin. Glycemic profiles were determined over 72 hours by continuous glucose monitoring system (CGMS) and blood samples were obtained from all patients at 24 and 72 hours. Plasma levels of cholesteryl ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT), apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-I) were determined by enzyme-linked immunosorbent assay (ELISA). Measurement of CETP and LCAT activity was performed via fluorometric analysis. Paraoxonase (PON1) enzyme activity was assessed from the rate of enzymatic hydrolysis of phenyl acetate to phenol formation. LDL and HDL subfraction analysis was done by continuous disc polyacrylamide gel electrophoresis.
Mean blood glucose, total cholesterol (TC), triglyceride (TG) and very low-density lipoprotein cholesterol (VLDL-C) levels were significantly decreased while HDL-C levels were significantly increased after insulin treatment. Although LDL-C levels were not significantly different before and after insulin initiation therapy a significant increase in LDL-1 subgroup and a significant reduction in atherogenic LDL-3 and LDL-4 subgroups were observed. Insulin analog initiation therapy caused a significant increase in HDL-large, HDL- intermediate and a significant reduction in HDL-small subfractions. CETP protein level and activity was significantly increased while apoB levels were significantly decreased following insulin analog initiation therapy. No significant difference was found in LCAT mass, LCAT activity, apoA-I and PON-1 arylesterase levels following insulin initiation therapy.
These findings indicate that insulin analog initiation therapy activates lipid metabolism via up-regulating CETP and shows anti-atherogenic effects by increasing HDL-large and decreasing LDL-3 and LDL-4 subfractions in a short time period.
胰岛素治疗可有效控制血糖，改善 2 型糖尿病患者的血脂参数。本研究旨在评估在早期阶段，2 型糖尿病患者起始胰岛素类似物治疗对 LDL/HDL 亚组分和 HDL 相关酶的影响。
选择 24 例糖化血红蛋白（HbA1c）水平高于 10%的 2 型糖尿病患者，这些患者正在接受磺脲类药物和二甲双胍的联合治疗。起始治疗的第一天继续使用之前的治疗方案，随后用不同的胰岛素类似物（0.4 U/kg/天）替代磺脲类药物，并联合二甲双胍治疗。通过连续血糖监测系统（CGMS）在 72 小时内监测血糖谱，并在第 24 小时和第 72 小时采集所有患者的血样。采用酶联免疫吸附试验（ELISA）法测定胆固醇酯转移蛋白（CETP）、卵磷脂胆固醇酰基转移酶（LCAT）、载脂蛋白 B（apoB）和载脂蛋白 A-1（apoA-I）的血浆水平。通过荧光分析测定 CETP 和 LCAT 的活性。通过苯乙酸酯酶促水解生成苯酚的速率评估对氧磷酶（PON1）的酶活性。采用连续圆盘聚丙烯酰胺凝胶电泳法分析 LDL 和 HDL 亚组分。
胰岛素治疗后，患者的平均血糖、总胆固醇（TC）、甘油三酯（TG）和极低密度脂蛋白胆固醇（VLDL-C）水平显著降低，而高密度脂蛋白胆固醇（HDL-C）水平显著升高。虽然 LDL-C 水平在起始胰岛素治疗前后无显著差异，但 LDL-1 亚组显著增加，致动脉粥样硬化 LDL-3 和 LDL-4 亚组显著减少。胰岛素类似物起始治疗后，HDL-大、HDL-中显著增加，HDL-小显著减少。起始胰岛素类似物治疗后，CETP 蛋白水平和活性显著增加，apoB 水平显著降低。起始胰岛素治疗后，LCAT 质量、LCAT 活性、apoA-I 和 PON-1 芳基酯酶水平无显著差异。
这些发现表明，胰岛素类似物起始治疗通过上调 CETP 激活脂代谢，并在短时间内通过增加 HDL-大、减少 LDL-3 和 LDL-4 亚组分发挥抗动脉粥样硬化作用。
