Kissebah A H, Alfarsi S, Evans D J, Adams P W
J Clin Invest. 1983 Mar;71(3):655-67. doi: 10.1172/jci110812.
Plasma low density lipoprotein (LDL) transport kinetics were determined from the disappearance of 125I-LDL injected into age- and weight-matched groups of 13 normal subjects, 20 mild diabetics, and 8 moderately severe diabetic patients (fasting plasma glucose less than 150 and greater than 150 mg/100 ml, respectively). In mild diabetics, LDL apo-lipoprotein-B (apo-B) synthetic rate (SR) was significantly greater than normal. The fractional catabolic rate (FCR), however, was also increased so that plasma LDL concentration remained normal. In moderately severe diabetics, LDL SR was normal but FCR was reduced resulting in increased plasma LDL cholesterol and apo-B concentrations. In normal subjects, moderate obesity was associated with increased LDL secretion. In diabetic subjects, however, changes in LDL turnover were of equal magnitude in obese and nonobese patients. In normolipemic and hyperlipemic mild diabetic subjects with equal degrees of glucose intolerance, both LDL apo-B SR and FCR were greater than normal. The magnitude of these increases, however, was lower in the hyperlipemic individuals. Stepwise regression analysis revealed that both LDL SR and FCR correlated positively and linearly with insulin response to glucose loading, but negatively and curvilinearly with fasting plasma glucose and glucose response. We propose that in noninsulin-dependent diabetes, mild hyperglycemia is accompanied by increased LDL turnover, despite normal plasma LDL levels, whereas moderately severe hyperglycemia is associated with decreased LDL catabolism, resulting in increased plasma LDL levels. These changes cannot be attributed to the presence of obesity or hypertriglyceridemia, and may relate to varying degrees of insulin resistance and decreased insulin secretion affecting plasma very low density lipoprotein (VLDL) secretion, VLDL conversion to LDL, and LDL catabolism. Both increased LDL turnover in mild diabetes and delayed removal of LDL in moderately severe diabetes could increase cholesterol ester availability to peripheral tissues, and may result in an increased risk of atherosclerosis.
通过向年龄和体重匹配的13名正常受试者、20名轻度糖尿病患者和8名中度严重糖尿病患者（空腹血糖分别低于150和高于150mg/100ml）注射125I -低密度脂蛋白（LDL），并观察其消失情况来测定血浆低密度脂蛋白（LDL）转运动力学。在轻度糖尿病患者中，LDL载脂蛋白B（apo - B）合成率（SR）显著高于正常水平。然而，分解代谢率（FCR）也升高，因此血浆LDL浓度保持正常。在中度严重糖尿病患者中，LDL SR正常但FCR降低，导致血浆LDL胆固醇和apo - B浓度升高。在正常受试者中，中度肥胖与LDL分泌增加有关。然而，在糖尿病患者中，肥胖和非肥胖患者LDL周转率的变化幅度相同。在葡萄糖耐量相同的血脂正常和高脂血症轻度糖尿病患者中，LDL apo - B SR和FCR均高于正常水平。然而，高脂血症个体的这些升高幅度较低。逐步回归分析显示，LDL SR和FCR均与葡萄糖负荷后的胰岛素反应呈正线性相关，但与空腹血糖和葡萄糖反应呈负曲线相关。我们提出，在非胰岛素依赖型糖尿病中，尽管血浆LDL水平正常，但轻度高血糖伴有LDL周转率增加，而中度严重高血糖与LDL分解代谢降低有关，导致血浆LDL水平升高。这些变化不能归因于肥胖或高甘油三酯血症的存在，可能与不同程度的胰岛素抵抗和胰岛素分泌减少影响血浆极低密度脂蛋白（VLDL）分泌、VLDL转化为LDL以及LDL分解代谢有关。轻度糖尿病中LDL周转率增加和中度严重糖尿病中LDL清除延迟均可增加外周组织的胆固醇酯可用性，并可能导致动脉粥样硬化风险增加。
