INSULIN RESISTANCE IN OBESITY IS ASSOCIATED WITH ELEVATED BASAL LACTATE LEVELS AND DIMINISHED LACTATE APPEARANCE FOLLOWING INTRAVENOUS GLUCOSE AND INSULIN
INSULIN RESISTANCE IN OBESITY IS ASSOCIATED WITH ELEVATED BASAL LACTATE LEVELS AND DIMINISHED LACTATE APPEARANCE FOLLOWING INTRAVENOUS GLUCOSE AND INSULIN
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DOI：
10.1016/0026-0495(92)90185-d
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发表时间：
1992-01-01
影响因子：
9.8
通讯作者：
DIGIROLAMO, M
中科院分区：
文献类型：
--
作者：
LOVEJOY, J;NEWBY, FD;DIGIROLAMO, M
肥胖会改变乳酸代谢。一夜禁食后，增加的肥胖与血乳酸水平升高有关。相反，我们最近发现肥胖受试者口服葡萄糖负荷后急性乳酸生成能力显著下降，我们假设这可能与胰岛素敏感性改变有关。在本研究中，我们系统地分析了瘦肉和肥胖受试者在基础状态和静脉注射葡萄糖和胰岛素后胰岛素敏感性（敏感性指数[S1]使用最小模型推导）、体重指数（BMI）、葡萄糖、胰岛素和乳酸水平之间的关系。结果显示s1和BMI呈负相关，正如预期的那样。与肥胖本身相比，胰岛素敏感性与葡萄糖、胰岛素和乳酸水平（基础和综合）的关系更为密切。s1与基础乳酸水平呈显著负相关（r= - 0.56）。此外，s1与曲线下乳酸增量面积（反映急性乳酸生成）呈显著正相关（r= 0.41）。在分离肥胖（BMI）和胰岛素敏感性的独立影响的多元回归分析中，在调整年龄、性别和种族后，s1占基础乳酸盐方差的34%，占增量乳酸盐面积方差的24%。肥胖单独占基础乳酸变异量的10%和增量乳酸面积变异量的11%，两者均无统计学意义。我们得出结论，基础乳酸水平的升高与胰岛素抵抗的发展有关。此外，随着胰岛素抵抗的逐渐增加，在葡萄糖和胰岛素刺激下急性产生乳酸的能力也会降低。胰岛素敏感性的降低似乎对葡萄糖、胰岛素和乳酸盐的改变有比肥胖程度本身更大的影响。
Lactate metabolism is altered in obesity. Increasing obesity is associated with increased blood lactate levels after an overnight fast. In contrast, we have recently shown a marked decrease in the capacity for acute lactate generation in obese subjects following an oral glucose load, which we postulated might be linked to altered insulin sensitivity. In the present study, we systematically analyzed the relationship between insulin sensitivity (the Sensitivity Index [S1] derived using the minimal model), body mass index (BMI), and glucose, insulin, and lactate levels in the basal state and following intravenous (IV) glucose and insulin administration in lean and obese subjects. The results showed that S1and BMI were inversely related, as expected. Insulin sensitivity was more tightly associated with glucose, insulin, and lactate levels (both basal and integrated) than obesity per se. A significant inverse relationship was found between S1and basal lactate levels (r= −.56). Moreover, a significant and positive relationship was found between S1and incremental lactate area under the curve (reflecting acute lactate production) (r= .41). In a multiple regression analysis to separate the independent effects of obesity (BMI) and insulin sensitivity, after adjusting for age, sex, and race, S1accounted for 34% of the variance in basal lactate and 24% of the variance in incremental lactate area. Obesity independently accounted for 10% of the variance in basal lactate and 11% of the variance in incremental lactate area, neither of which were statistically significant. We conclude that elevations in basal lactate are associated with the development of insulin resistance. Furthermore, the ability to produce lactate acutely in response to a glucose and insulin challenge is reduced with progressively increased insulin resistance. Diminished insulin sensitivity appears to have a greater influence on alterations in glucose, insulin, and lactate that the degree of obesity per se.