Wajchenberg Bernardo L, Amâncio Rosângela F, Santomauro Ana T, Maranhão Raul C
Diabetes Section and Lipid Metabolism Laboratory, Heart Institute (InCor), University of São Paulo Medical School, Brazil.
Clin Endocrinol (Oxf). 2004 Sep;61(3):347-52. doi: 10.1111/j.1365-2265.2004.02103.x.
Lipoatrophic diabetes is characterized by the near absence of adipose tissue and the presence of insulin-resistant diabetes. Fasting hypertriglyceridaemia and increased postprandial lipidaemia are also present, but the metabolism of chylomicrons, the triglyceride-rich lipoproteins in the circulation that carry the dietary fats absorbed by the intestine, was not specifically investigated. Because both the activity of insulin-dependent lipoprotein lipase that catalyses the chylomicron lipolysis and the storage of the lipolysis products are affected in the disease, it is important to evaluate how those changes may ultimately affect the chylomicron lipolysis and removal of chylomicron remnants from the circulation.
The aim of the study was to evaluate the chylomicron intravascular metabolism in patients with lipoatrophic diabetes.
Six patients with lipoatrophic diabetes (four females, two males) aged 22.2 +/- 4.4 years, with body mass index (BMI) 21.6 +/- 3.6 kg/m(2), were compared with 12 healthy control subjects (seven females, five males) aged 24.3 +/- 2.1 years with BMI 22.5 +/- 2.7 kg/m(2).
The plasma kinetics of intravenously injected chylomicron-like emulsions labelled with (3)H-triglycerides ((3)H-TG) and with (14)C-cholesteryl esters ((14)C-CE) were determined, the former tracing the chylomicron lipolysis by lipoprotein lipase and the latter the removal of chylomicron remnants from the plasma.
Triglyceride values (8.3 +/- 9.2 mmol/l) in the patients were higher (P < 0.005) and high density lipoprotein (HDL) cholesterol values (0.8 +/- 0.2 mmol/l) lower (P < 0.0005) than in controls (0.7 +/- 0.2 and 1.3 +/- 0.4 mmol/l, respectively) whereas total cholesterol, apoprotein B (apo B) and apo A1 were similar. The fractional clearance rate (FCR, in min(-1)) of (3)H-TG was 0.014 +/- 0.016 and the FCR of (14)C-CE was 0.008 +/- 0.012 in the patients and 0.046 +/- 0.024 and 0.024 +/- 0.012 in the controls, respectively (P < 0.05). Thus FCRs of both emulsion labels were markedly reduced in the patients, indicating that lipolysis and remnant removal were diminished. Diminished remnant removal may be due to either deficient lipolysis or deficient removal mechanisms.
The metabolism of chylomicrons tested by the emulsion method is impaired in lipoatrophic diabetes.
脂肪萎缩性糖尿病的特征是几乎没有脂肪组织且存在胰岛素抵抗性糖尿病。还存在空腹高甘油三酯血症和餐后血脂升高，但未对乳糜微粒（循环中携带肠道吸收的膳食脂肪的富含甘油三酯的脂蛋白）的代谢进行专门研究。由于催化乳糜微粒脂解的胰岛素依赖性脂蛋白脂肪酶的活性以及脂解产物的储存均在该疾病中受到影响，因此评估这些变化最终如何影响乳糜微粒脂解以及从循环中清除乳糜微粒残粒非常重要。
本研究的目的是评估脂肪萎缩性糖尿病患者的乳糜微粒血管内代谢。
6例脂肪萎缩性糖尿病患者（4例女性，2例男性），年龄22.2±4.4岁，体重指数（BMI）为21.6±3.6kg/m²，与12例健康对照者（7例女性，5例男性）进行比较，健康对照者年龄24.3±2.1岁，BMI为22.5±2.7kg/m²。
测定静脉注射用³H-甘油三酯（³H-TG）和¹⁴C-胆固醇酯（¹⁴C-CE）标记的乳糜微粒样乳剂的血浆动力学，前者追踪脂蛋白脂肪酶对乳糜微粒的脂解，后者追踪乳糜微粒残粒从血浆中的清除。
患者的甘油三酯值（8.3±9.2mmol/L）高于对照组（分别为0.7±0.2和1.3±0.4mmol/L，P<0.005），高密度脂蛋白（HDL）胆固醇值（0.8±0.2mmol/L）低于对照组（P<0.0005），而总胆固醇、载脂蛋白B（apo B）和载脂蛋白A1相似。患者中³H-TG的分数清除率（FCR，单位为min⁻¹）为0.014±0.016，¹⁴C-CE的FCR为0.008±0.012，对照组中分别为0.046±0.024和0.024±0.012（P<0.05）。因此，患者中两种乳剂标记物的FCR均显著降低，表明脂解和残粒清除减少。残粒清除减少可能是由于脂解不足或清除机制不足。
通过乳剂法检测的脂肪萎缩性糖尿病患者的乳糜微粒代谢受损。
