Section on Pediatric Diabetes, Obesity, and Metabolism, Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
J Clin Endocrinol Metab. 2022 May 17;107(6):1541-1551. doi: 10.1210/clinem/dgac113.
Youth with obesity and abnormal glucose tolerance have an increased risk for atherosclerosis but the relative contributions of insulin resistance and hyperglycemia to dyslipidemia and the development of subclinical atherosclerosis are unknown.
This work aims to determine the association between insulin resistance, dyslipidemia, and carotid intimal thickness (cIMT) in adolescents with normal and abnormal glucose tolerance.
An observational cohort study in 155 youth: 44 obese insulin sensitive (OIS; fasting insulin ≤ 20 µM/mL, body mass index [BMI] ≥ 95th percentile), 35 obese insulin resistant (OIR; fasting insulin > 20 µM/mL, BMI ≥ 95th percentile), 34 obese abnormal glucose tolerant (AGT; BMI ≥ 95th percentile), and 42 Lean (BMI 5th-85th percentile). Lipids, lipoprotein particle size and concentration (-P), insulin sensitivity (SI an intravenous glucose test), and CMIT were compared using linear models adjusted for age, race/ethnicity, biological sex, and Tanner stage. Lipid/lipoprotein profile and CMIT were reevaluated in a subset after 2 years.
Compared to OIS and Lean, OIR and AGT had elevated triglycerides and low high-density lipoprotein cholesterol (HDL-C) but similar total cholesterol and low-density lipoprotein cholesterol (LDL-C). Among OIS, OIR, AGT, lower SI was associated with atherogenic lipids (higher triglycerides, LDL-C, non-HDL-C, and lower HDL-C) and lipoproteins (higher total LDL-P and small HDL-P, and lower large HDL-P). There was a steeper decline in the association of SI with HDL-C and large HDL-P in AGT compared with OIR and OIS. cIMT was comparable across groups and inversely correlated with SI, with no change after 2 years.
Among youth with obesity, insulin resistance was associated with an atherogenic lipoprotein/lipid profile and cIMT, regardless of glucose tolerance status. Insulin resistance in AGT youth was associated with a shift to smaller HDL-P compared to normoglycemic youth with obesity. Alterations in HDL-P metabolism may be early adverse manifestations of hyperglycemia in youth with obesity.
肥胖和葡萄糖耐量异常的年轻人发生动脉粥样硬化的风险增加，但胰岛素抵抗和高血糖对血脂异常和亚临床动脉粥样硬化发展的相对贡献尚不清楚。
本研究旨在确定在葡萄糖耐量正常和异常的青少年中，胰岛素抵抗、血脂异常与颈动脉内膜中层厚度（cIMT）之间的关系。
对 155 名青少年进行观察性队列研究：44 名肥胖胰岛素敏感（OIS；空腹胰岛素≤20µM/ml，BMI≥第 95 百分位），35 名肥胖胰岛素抵抗（OIR；空腹胰岛素>20µM/ml，BMI≥第 95 百分位），34 名肥胖糖耐量异常（AGT；BMI≥第 95 百分位）和 42 名正常体重（BMI 第 5-85 百分位）。使用线性模型比较血脂、脂蛋白颗粒大小和浓度（-P）、胰岛素敏感性（静脉内葡萄糖试验的 SI）和 cIMT，并根据年龄、种族/民族、生物性别和 Tanner 分期进行调整。在 2 年后对一部分人重新评估了血脂/脂蛋白谱和 cIMT。
与 OIS 和正常体重相比，OIR 和 AGT 的甘油三酯升高，高密度脂蛋白胆固醇（HDL-C）降低，但总胆固醇和低密度脂蛋白胆固醇（LDL-C）相似。在 OIS、OIR、AGT 中，较低的 SI 与致动脉粥样硬化脂质（甘油三酯、LDL-C、非 HDL-C 升高和 HDL-C 降低）和脂蛋白（总 LDL-P 和小 HDL-P 升高，大 HDL-P 降低）相关。与 OIR 和 OIS 相比，在 AGT 中，SI 与 HDL-C 和大 HDL-P 的相关性下降更为陡峭。cIMT 在各组之间无差异，与 SI 呈负相关，且 2 年后无变化。
在肥胖的年轻人中，无论葡萄糖耐量状态如何，胰岛素抵抗都与致动脉粥样硬化的脂蛋白/血脂谱和 cIMT 相关。与葡萄糖耐量正常的肥胖年轻人相比，AGT 年轻人的胰岛素抵抗与更小的 HDL-P 有关。HDL-P 代谢的改变可能是肥胖青少年高血糖的早期不良表现。
