Young, low-birth-weight men are not more susceptible to the diabetogenic effects of a prolonged free fatty acid exposure than matched controls.
Young, low-birth-weight men are not more susceptible to the diabetogenic effects of a prolonged free fatty acid exposure than matched controls.
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DOI：
10.1016/j.metabol.2005.05.005
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发表时间：
2005-10
期刊：
影响因子：
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通讯作者：
C. Jensen;H. Storgaard;J. Holst;F. Dela;S. Madsbad;A. Vaag
中科院分区：
文献类型：
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作者：
C. Jensen;H. Storgaard;J. Holst;F. Dela;S. Madsbad;A. Vaag
低出生体重（LBW）与以后患2型糖尿病的风险增加有关。从正常到糖耐量受损和显性糖尿病的进展可能在一定程度上取决于血浆游离脂肪酸（FFA）的升高。我们进行了这项研究，以阐明是否长期的生理脂质负荷可以揭露或增加现有的代谢缺陷，否则健康的年轻LBW受试者。40名无糖尿病家族史的19岁男性（LBW [n = 20]，对照组[正常出生体重，NBW] [n = 20]）接受静脉葡萄糖耐量试验（0.3 g kg−1），随后进行2步高胰岛素-正常血糖钳夹（2 × 120分钟：10和40 mU m− 2 min −1）联合[3- 3 H]-葡萄糖和间接热量测定。在试验之前，以随机顺序，连续24小时输注胰岛素（20%，0.4 mg mL−1h−1）或生理盐水。获得细胞葡萄糖代谢的估计值并计算处置指数。在脂质输注期间，钳夹FFA浓度高4至10倍。两组在胰岛素刺激的葡萄糖处置方面对脂质输注的反应相似（15%; P <0.05），这主要是由于葡萄糖氧化减少（15%; P <0.001）。糖酵解、葡萄糖储存和葡萄糖产生没有被脂质输注显著改变。然而，LBW组在脂质输注过程中胰岛素刺激的糖酵解显著低于NBW组（1.27%; P < .05）。两组胰岛素分泌的适当增加与胰岛素敏感性的下降相匹配。24小时低浓度胰岛素输注对19岁、健康、消瘦、糖耐量正常的LBW男性和NBW对照者的全身葡萄糖代谢和第一时相胰岛素分泌具有相似的作用。我们重复了我们以前在这一人群中胰岛素刺激糖酵解较低的发现。
Low birth weight (LBW) is associated with increased risk of developing type 2 diabetes later in life. Progression from normal to impaired glucose tolerance and overt diabetes may depend, to some extent, on elevation of plasma free fatty acids (FFAs). We undertook this study to elucidate whether a prolonged physiological lipid load could unmask or augment existing metabolic defects in otherwise healthy young LBW subjects. Forty 19-year-old men (LBW [n = 20], controls [normal birth weight, NBW] [n = 20]) without a family history of diabetes underwent an intravenous glucose tolerance test (0.3 g kg−1), followed by 2-step hyperinsulinemic-euglycemic clamps (2 × 120 minutes: 10 and 40 mU m−2min−1) in combination with [3-3H]-glucose and indirect calorimetry. The tests were preceded, in randomized order, by a 24-hour continuous intralipid (20%, 0.4 mg mL−1h−1) or saline infusion. Estimates of cellular glucose metabolism were obtained and a disposition index calculated. Clamp FFA concentrations were 4- to ten-fold higher during lipid infusion. Both groups experienced a similar decrease in insulin-stimulated glucose disposal in response to lipid infusion (∼15%; P < .05), which was mainly accounted for by reduced glucose oxidation (∼30%; P < .001). Glycolysis, glucose storage, and glucose production were not significantly altered by lipid infusion. Nevertheless, the LBW group had significantly lower insulin-stimulated glycolysis during lipid infusion (∼27%; P < .05) than the NBW group. An appropriate increase in insulin secretion matched the decline in insulin sensitivity in both groups. A 24-hour low-grade intralipid infusion has similar effects on whole-body glucose metabolism and first-phase insulin secretion in 19-year-old, healthy, lean, LBW men with normal glucose tolerance and in NBW controls. We reproduced our previous finding of lower insulin-stimulated glycolysis in this population.