Laakso M, Sarlund H, Salonen R, Suhonen M, Pyörälä K, Salonen J T, Karhapää P
Department of Medicine, Kuopio University Central Hospital, Finland.
Arterioscler Thromb. 1991 Jul-Aug;11(4):1068-76. doi: 10.1161/01.atv.11.4.1068.
High plasma insulin has been shown to be associated with the risk of coronary heart disease in nondiabetic subjects in prospective population studies. Furthermore, insulin resistance measured by the euglycemic glucose clamp technique has been shown to be related to lipid and lipoprotein changes favoring atherosclerosis and to high blood pressure. No study, however, has demonstrated that insulin resistance per se is directly associated with atherosclerosis. With this aim, we studied 30 middle-aged nonobese subjects with asymptomatic atherosclerosis in the femoral or carotid arteries and 13 corresponding control subjects. Fasting blood glucose, insulin, and C-peptide levels were only slightly and nonsignificantly higher in subjects with atherosclerosis than in controls, and during the oral glucose tolerance test 1- and 2-hour glucose, insulin, and C-peptide levels were similar in both groups. During the euglycemic hyperinsulinemic (1,200 pmol/l) clamp studies, subjects with atherosclerosis had a 20% reduced whole-body glucose uptake (58 +/- 2 versus 71 +/- 4 mumol/kg/min, p = 0.004). Glucose oxidation, lipid oxidation, suppression of free fatty acid levels, and potassium disposal were similar in both groups. In contrast, nonoxidative glucose disposal was significantly reduced in patients compared with that in controls (37 +/- 2 versus 50 +/- 4 mumol/kg/min, p = 0.004). When glucose uptakes were matched during the hyperglycemic clamp studies, the rate of nonoxidative glucose uptake was normalized in the patients. These results provide the first direct evidence that asymptomatic atherosclerosis is associated with insulin resistance. This insulin resistance is characterized by reduced whole-body and nonoxidative glucose uptake. In contrast, glucose and lipid oxidation, potassium disposal, and suppression of free fatty acid levels during hyperinsulinemia did not differ between the subjects with and without atherosclerosis.
前瞻性人群研究表明，高血浆胰岛素水平与非糖尿病受试者患冠心病的风险相关。此外，通过正常血糖胰岛素钳夹技术测得的胰岛素抵抗与有利于动脉粥样硬化的脂质和脂蛋白变化以及高血压有关。然而，尚无研究表明胰岛素抵抗本身与动脉粥样硬化直接相关。为此，我们研究了30名患有股动脉或颈动脉无症状动脉粥样硬化的中年非肥胖受试者以及13名相应的对照受试者。动脉粥样硬化患者的空腹血糖、胰岛素和C肽水平仅略高于对照组，且无显著差异，在口服葡萄糖耐量试验期间，两组的1小时和2小时血糖、胰岛素和C肽水平相似。在正常血糖高胰岛素血症（1200 pmol/l）钳夹研究中，动脉粥样硬化患者的全身葡萄糖摄取降低了20%（58±2对71±4 μmol/kg/min，p = 0.004）。两组的葡萄糖氧化、脂质氧化、游离脂肪酸水平抑制和钾处置情况相似。相比之下，与对照组相比，患者的非氧化葡萄糖处置显著降低（37±2对50±4 μmol/kg/min，p = 0.004）。在高血糖钳夹研究中，当葡萄糖摄取相匹配时，患者的非氧化葡萄糖摄取率恢复正常。这些结果提供了首个直接证据，表明无症状动脉粥样硬化与胰岛素抵抗相关。这种胰岛素抵抗的特征是全身和非氧化葡萄糖摄取减少。相比之下，有和没有动脉粥样硬化的受试者在高胰岛素血症期间的葡萄糖和脂质氧化、钾处置以及游离脂肪酸水平抑制没有差异。
