Overnight lowering of free fatty acids with acipimox improves insulin resistance and glucose tolerance in obese diabetic and nondiabetic subjects
Overnight lowering of free fatty acids with acipimox improves insulin resistance and glucose tolerance in obese diabetic and nondiabetic subjects
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DOI：
10.2337/diabetes.48.9.1836
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发表时间：
1999-09-01
期刊：
影响因子：
7.7
通讯作者：
Wajchenberg, BL
中科院分区：
文献类型：
--
作者：
Santomauro, ATMG;Boden, G;Wajchenberg, BL
肥胖通常与血浆游离脂肪酸(FFA)水平升高有关，也与胰岛素抵抗和高胰岛素血症有关，这两个重要的心血管危险因素。导致肥胖的胰岛素抵抗和高胰岛素血症的原因尚不清楚。在这里，我们验证了FFA是肥胖和胰岛素抵抗/高胰岛素血症之间的联系的假设，因此，降低长期升高的血浆FFA水平将改善肥胖、非糖尿病和糖尿病受试者的胰岛素抵抗/高胰岛素血症和糖耐量。长效降脂药物Acipimox(250毫克)或安慰剂连夜服用(晚上7：00，凌晨1：00，上午7：00)。至9名瘦身对照受试者、13名肥胖的非糖尿病受试者、10名肥胖并糖耐量受损的受试者和11名2型糖尿病患者。在Acipimox或安慰剂治疗过夜后，分别在不同的早晨进行正常血糖-高胰岛素钳夹试验和口服葡萄糖耐量试验(75g)。在三个肥胖研究组中，Acipimox降低了空腹血浆FFAs水平(下降了60%-70%)和血浆胰岛素水平(下降了类似50%)。在正常血糖-高胰岛素钳制期间，Acipimox组胰岛素刺激的葡萄糖摄取量是安慰剂组的两倍多。口服葡萄糖耐量试验中血糖和胰岛素曲线下的面积在服用Acipimox后都比服用安慰剂后低30%。我们的结论是，降低升高的血浆FFA水平可以降低瘦身和肥胖的非糖尿病受试者以及肥胖的2型糖尿病患者的胰岛素抵抗/高胰岛素血症，并改善口服葡萄糖耐量。
Obesity is commonly associated with elevated plasma free fatty acid (FFA) levels, as well as with insulin resistance and hyperinsulinemia, two important cardiovascular risk factors. What causes insulin resistance and hyperinsulinemia in obesity remains uncertain. Here, we have tested the hypothesis that FFAs are the link between obesity and insulin resistance/hyperinsulinemia and that;, therefore, lowering of chronically elevated plasma FFA levels would improve insulin resistance/hyperinsulinemia and glucose tolerance in obese nondiabetic and diabetic subjects. Acipimox (250 mg), a long-acting antilipolytic drug, or placebo was given overnight (at 7:00 P.M., 1:00 A.M., 7:00 A.M.) to 9 lean control subjects, 13 obese nondiabetic subjects, 10 obese subjects with impaired glucose tolerance, and 11 patients with type 2 diabetes. Euglycemic-hyperinsulinemic clamps and oral glucose tolerance tests (75 g) were performed on separate mornings after overnight Acipimox or placebo treatment. In the three obese study groups, Acipimox lowered fasting levels of plasma FFAs (by 60-70%) and plasma insulin (by similar to 50%). Insulin-stimulated glucose uptake during euglycemic-hyperinsulinemic clamping was more than twofold higher after Acipimox than after placebo. Areas under the glucose and insulin curves during oral glucose tolerance testing were both similar to 30% lower after Acipimox administration than after placebo. We conclude that lowering of elevated plasma FFA levels can reduce insulin resistance/hyperinsulinemia and improve oral glucose tolerance in lean and obese nondiabetic subjects and in obese patients with type 2 diabetes.