Hughes T A, Gaber A O, Amiri H S, Wang X, Elmer D S, Winsett R P, Hathaway D K, Hughes S M, Ghawji M
Department of Medicine, University of Tennessee, Memphis 38163.
Metabolism. 1994 Mar;43(3):333-47. doi: 10.1016/0026-0495(94)90102-3.
Chronic renal failure (CRF) in nondiabetics is associated with a number of lipoprotein abnormalities that place these patients at high risk for atherosclerosis. This study compared the lipoprotein composition of nondiabetic controls (n = 68) with that of patients with insulin-dependent diabetes mellitus ([IDDM] n = 13) and of patients with IDDM and CRF ([IDDM + CRF] n = 74). Six lipoprotein subfractions (very-low-density lipoprotein [VLDL], intermediate-density lipoprotein [IDL], low-density lipoprotein [LDL], high-density lipoprotein-light [HDL-L], HDL-medium [HDL-M], and HDL-dense [HDL-D]) were isolated by rapid gradient ultracentrifugation using a fixed-angle rotor. The apolipoprotein (by reverse-phase high-performance liquid chromatography [HPLC]) and lipid (by enzymatic assays) composition of each subfraction was determined. The only abnormalities found in IDDM patients were increases in IDL and HDL-L triglyceride (TG) levels and an increase in the HDL-L free cholesterol (FC) level. The IDDM + CRF group had multiple abnormalities including (1) elevated TG, apolipoprotein (apo) C-II, and apo C-III levels in all lipid subfractions; (2) elevated VLDL and IDL apo B, TG, FC, cholesterol ester (CE), and phospholipid (PL) levels (with an increased CE/TG ratio in VLDL only); (3) decreased HDL-M apo A-I, apo A-II, CE, and PL levels, but an increased HDL-D apo A-I level; and (4) decreased lecithin:cholesterol acyltransferase (LCAT) activity. Twenty-five of the IDDM + CRF patients underwent combined pancreas and kidney (P + K) transplantation, and 12 patients received only a kidney transplant. Lipoprotein composition was determined at 3, 6, and 12 months posttransplant. Both types of transplantation resulted in similar alterations in lipoprotein composition, even though there was essential normalization of blood glucose levels in most of the patients who received a pancreas transplant (hemoglobin A1C [HbA1C], 9.1% +/- 1.1% v 5.7% +/- 0.3% at 12 months, P < .01). These posttransplant changes included (1) no improvement in the elevated TG level in any lipid subfraction even though there was some reduction in apo C-III levels in VLDL; (2) reductions in levels of VLDL and IDL apo B but increases in LDL apo B; (3) increases in HDL apo C-III and FC concentrations despite an increase in LCAT activity; and (4) increases in apo A-I levels in HDL-L and HDL-M. The addition of a pancreas to a kidney transplant had no obvious impact on the lipoproteins.(ABSTRACT TRUNCATED AT 400 WORDS)
非糖尿病患者的慢性肾衰竭（CRF）与多种脂蛋白异常有关，这些异常使这些患者处于动脉粥样硬化的高风险中。本研究比较了非糖尿病对照组（n = 68）、胰岛素依赖型糖尿病患者（[IDDM]，n = 13）以及IDDM合并CRF患者（[IDDM + CRF]，n = 74）的脂蛋白组成。通过使用固定角度转头的快速梯度超速离心法分离出六种脂蛋白亚组分（极低密度脂蛋白[VLDL]、中间密度脂蛋白[IDL]、低密度脂蛋白[LDL]、高密度脂蛋白-轻组分[HDL-L]、高密度脂蛋白-中组分[HDL-M]和高密度脂蛋白-重组分[HDL-D]）。测定了每个亚组分的载脂蛋白（通过反相高效液相色谱法[HPLC]）和脂质（通过酶法测定）组成。在IDDM患者中发现的唯一异常是IDL和HDL-L甘油三酯（TG）水平升高以及HDL-L游离胆固醇（FC）水平升高。IDDM + CRF组有多种异常，包括：（1）所有脂质亚组分中的TG、载脂蛋白（apo）C-II和apo C-III水平升高；（2）VLDL和IDL的apo B、TG、FC、胆固醇酯（CE）和磷脂（PL）水平升高（仅VLDL中的CE/TG比值增加）；（3）HDL-M的apo A-I、apo A-II、CE和PL水平降低，但HDL-D的apo A-I水平升高；（4）卵磷脂：胆固醇酰基转移酶（LCAT）活性降低。25例IDDM + CRF患者接受了胰肾联合移植（P + K），12例患者仅接受了肾移植。在移植后3、6和12个月测定脂蛋白组成。两种类型的移植导致脂蛋白组成发生相似的改变，尽管接受胰腺移植的大多数患者血糖水平基本恢复正常（糖化血红蛋白[HbA1C]，12个月时为9.1%±1.1%对5.7%±0.3%，P <.01）。这些移植后的变化包括：（1）任何脂质亚组分中升高的TG水平均未改善，尽管VLDL中的apo C-III水平有所降低；（2）VLDL和IDL的apo B水平降低，但LDL的apo B水平升高；（3）尽管LCAT活性增加，但HDL的apo C-III和FC浓度增加；（4）HDL-L和HDL-M中的apo A-I水平增加。在肾移植基础上加做胰腺移植对脂蛋白没有明显影响。（摘要截断于400字）
