Prediabetes in obese youth: a syndrome of impaired glucose tolerance, severe insulin resistance, and altered myocellular and abdominal fat partitioning
Prediabetes in obese youth: a syndrome of impaired glucose tolerance, severe insulin resistance, and altered myocellular and abdominal fat partitioning
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DOI：
10.1016/s0140-6736(03)14364-4
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发表时间：
2003-09-20
期刊：
影响因子：
168.9
通讯作者：
Caprio, S
中科院分区：
文献类型：
--
作者：
Weiss, R;Dufour, S;Caprio, S
背景：糖耐量受损在肥胖青少年中很常见，但胰岛素敏感性和分泌的变化导致这种糖尿病前期状态尚不清楚。我们研究了糖尿病前期肥胖青少年中心肌细胞和腹部脂肪分配的改变是否与葡萄糖稳态异常有关。方法选取年龄、性别分布、肥胖程度相近的14例糖耐量受损肥胖儿童和14例糖耐量正常肥胖儿童为研究对象。采用血糖-高胰岛素钳和高血糖钳评估胰岛素敏感性和胰岛素分泌。用质子核磁共振波谱法测定细胞内脂质，用磁共振成像法测定腹部脂肪分布。结果：糖耐量受损个体的外周葡萄糖处理明显低于糖耐量正常的个体（平均35.4 [SE 4.0] vs 60.6[7.2]摩尔/公斤瘦体重/分钟，p=0.023），这是由于非氧化性葡萄糖处理代谢（储存）减少。糖耐量受损的个体细胞内脂肪含量较高（3.04 [0.43]vs 1.99 [0.19]%, p=0.03），下腹部皮下脂肪含量较高（460 [471]vs 626 [39] cm(2), p=0.04），内脏脂肪含量略高于对照组（70 [111]vs 47 [6] cm(2), p=0.065），导致内脏脂肪与皮下脂肪的比例较高（0.15 [0.02]vs 0.07 [0.01], p=0.002）。细胞内和内脏脂质含量与葡萄糖处理和非氧化糖代谢呈负相关，与2 h血浆葡萄糖浓度呈正相关。在患有前驱糖尿病的肥胖儿童和青少年中，淀粉细胞内和腹腔内脂质积累与严重外周胰岛素抵抗的发展密切相关。
Background Impaired glucose tolerance is common among obese adolescents, but the changes in insulin sensitivity and secretion that lead to this prediabetic state are unknown. We investigated whether altered partitioning of myocellular and abdominal fat relates to abnormalities in glucose homoeostasis in obese adolescents with prediabetes.Methods We studied 14 obese children with impaired glucose tolerance and 14 with normal glucose tolerance, of similar ages, sex distribution, and degree of obesity. Insulin sensitivity and secretion were assessed by the euglycaemic-hyperinsulinaemic clamp and the hyperglycaemic clamp. Intramyocellular lipid was assessed by proton nuclear magnetic resonance spectroscopy and abdominal fat distribution by magnetic resonance imaging.Findings Peripheral glucose disposal was significantly lower in individuals with impaired than in those with normal glucose tolerance (mean 35.4 [SE 4.0] vs 60.6 [7.2] mumoles per kg lean body mass per min; p=0.023) owing to a reduction in non-oxidative glucose disposal metabolism (storage). individuals with impaired glucose tolerance had higher intramyocellular lipid content (3.04 [0.43] vs 1.99 [0.19]%, p=0.03), lower abdominal subcutaneous fat (460 [471 vs 626 [39] cm(2), p=0.04), and slightly higher visceral fat than the controls (70 [111 vs 47 [6] cm(2), p=0.065), resulting in a higher ratio of visceral to subcutaneous fat (0.15 [0.02] vs 0.07 [0.01], p=0.002). Intramyocellular and visceral lipid contents were inversely related to the glucose disposal and non-oxidative glucose metabolism and positively related to the 2 h plasma glucose concentration.Interpretation In obese children and adolescents with prediabetes, intramyocellular and intra-abdominal lipid accumulation is closely linked to the development of severe peripheral insulin resistance.