Twickler T B, Dallinga-Thie G M, Zelissen P M, Koppeschaar H P, Erkelens D W
Department of Internal Medicine, University Medical Center Utrecht (UMCU), 3508 GA Utrecht, The Netherlands.
Clin Endocrinol (Oxf). 2001 Jul;55(1):69-75. doi: 10.1046/j.1365-2265.2001.01326.x.
Premature atherosclerosis is a clinical feature in untreated acromegaly. Increased postprandial lipoprotein remnant levels are associated with premature atherosclerosis. In most studies, remnants have been measured indirectly using retinyl esters (RE) as a chylomicron core label. Remnants can also be directly quantified by immunoseparation using monoclonal antibodies to apolipoprotein (apo) AI and apo B100 to remove nonremnant lipoproteins. Cholesterol is quantified in the remaining apo E-rich remnant fraction (RLP-C).
The aim of the present study was to investigate the role of postprandial lipaemia in patients with acromegaly to further define abnormalities leading to increased susceptibility for atherosclerosis.
In a case-control study, the plasma postprandial lipoprotein remnant fraction (RLP-C and RE) were analysed in six patients with active acromegaly [two females, four males; aged 53 +/- 9 years; body mass index (BMI), 29 +/- 4 kg/m2] and in six normolipidaemic control subjects (matched for age, gender, BMI and apo E genotype). They underwent an oral vitamin A fat loading test.
Baseline plasma triglycerides (TG) were not significantly different in patients (1.75 +/- 0.71 mM) and controls (1.15 +/- 0.46 mM). Lipoprotein lipase activity was significantly lower in patients than in controls (108 +/- 21 vs. 141 +/- 19 U/l, respectively; P < 0.05). Baseline plasma apo E levels were higher in patients (60.8 +/- 7.9 mg/l) than in controls (48.3 +/- 5.9 mg/l; P < 0.05). No differences were found in the area under the postprandial TG curve (AUC-TG), the incremental AUC-TG (DeltaAUC-TG) and AUC-RE in the Sf < 1000 remnant fraction. However, fasting plasma RLP-C concentrations, isolated by immunoseparation, were increased in patients with active acromegaly (0.41 +/- 0.13 mM) compared to control subjects (0.20 +/- 0.07 mM; P < 0.05). Incremental postprandial RLP-C response (corrected for fasting values) was also significantly elevated in patients (2.14 +/- 1.19 mM/h/l) compared to controls (0.86 +/- 0.34 mM/h/l; P < 0.05). In both groups, the maximal RLP-C concentration was reached between 2 and 4 h.
In conclusion, the atherogenic postprandial remnants, represented by RLP-C, were significantly elevated at baseline and in the postprandial period, whereas the larger-sized remnants, represented by retinyl esters (Sf < 1000), were not different from controls. The disturbances in the postprandial RLP-C response increased the susceptibility for premature atherosclerosis as observed in patients with acromegaly.
动脉粥样硬化过早出现是未经治疗的肢端肥大症的临床特征。餐后脂蛋白残粒水平升高与动脉粥样硬化过早发生有关。在大多数研究中,残粒是使用视黄醇酯(RE)作为乳糜微粒核心标记物进行间接测量的。残粒也可以通过免疫分离法直接定量,使用针对载脂蛋白(apo)AI和apo B100的单克隆抗体去除非残粒脂蛋白。在剩余的富含apo E的残粒部分(RLP-C)中对胆固醇进行定量。
本研究的目的是调查餐后血脂异常在肢端肥大症患者中的作用,以进一步明确导致动脉粥样硬化易感性增加的异常情况。
在一项病例对照研究中,对6例活动性肢端肥大症患者[2名女性,4名男性;年龄53±9岁;体重指数(BMI),29±4kg/m²]和6名血脂正常的对照受试者(年龄、性别、BMI和apo E基因型匹配)的血浆餐后脂蛋白残粒部分(RLP-C和RE)进行了分析。他们接受了口服维生素A脂肪负荷试验。
患者组(1.75±0.71mM)和对照组(1.15±0.46mM)的基线血浆甘油三酯(TG)无显著差异。患者组的脂蛋白脂肪酶活性显著低于对照组(分别为108±21和141±19U/l;P<0.05)。患者组的基线血浆apo E水平高于对照组(60.8±7.9mg/l比48.3±5.9mg/l;P<0.05)。在Sf<1000残粒部分,餐后TG曲线下面积(AUC-TG)、增量AUC-TG(ΔAUC-TG)和AUC-RE均未发现差异。然而,通过免疫分离法分离的空腹血浆RLP-C浓度,活动性肢端肥大症患者(0.41±0.13mM)高于对照受试者(0.20±0.07mM;P<0.05)。与对照组(0.86±0.34mM/h/l;P<0.05)相比,患者组餐后RLP-C的增量反应(校正空腹值)也显著升高(2.14±1.19mM/h/l)。两组中,最大RLP-C浓度均在2至4小时达到。
总之,以RLP-C为代表的致动脉粥样硬化餐后残粒在基线和餐后阶段均显著升高,而以视黄醇酯(Sf<1000)为代表的较大尺寸残粒与对照组无差异。如肢端肥大症患者所见,餐后RLP-C反应的紊乱增加了过早发生动脉粥样硬化的易感性。