Increased Insulin following an Oral Glucose Load, Genetic Variation near the Melatonin Receptor MTNR1B, but No Biochemical Evidence of Endothelial Dysfunction in Young Asian Men and Women.
Increased Insulin following an Oral Glucose Load, Genetic Variation near the Melatonin Receptor MTNR1B, but No Biochemical Evidence of Endothelial Dysfunction in Young Asian Men and Women.
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DOI：
10.1371/journal.pone.0133611
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Armstrong NJ
中科院分区：
文献类型：
--
作者：
Matuszek MA;Anton A;Thillainathan S;Armstrong NJ
确定与不同种族的年轻瘦男性和女性患 2 型糖尿病和心血管疾病风险增加相关的生化和遗传变异。对 90 名白种人、南亚人和东南亚/东亚人的空腹血液和尿液以及口服葡萄糖摄入后的非空腹血液进行了分析。年龄、出生体重、血压、体重指数、体脂百分比、总能量、宏量营养素摄入百分比、微量白蛋白、瘦素、皮质醇、促肾上腺皮质激素、一氧化氮代谢物、C反应蛋白、同型半胱氨酸、肿瘤坏死因子-α、白细胞介素-6、血管性血友病因子、血管细胞粘附分子-1、纤溶酶原激活剂抑制剂-1和组织纤溶酶原没有差异激活剂。与白人相比，南亚人的空腹总胆固醇 (P = .000)、甘油三酯 (P = .050)、低密度脂蛋白 (P = .009) 和非空腹血糖 (15 分钟) (P = .024) 升高，但葡萄糖曲线下面积 (AUC) 没有显着差异。与白种人相比，南亚人（15-120 分钟）、东南亚/东亚人（60-120 分钟）的非空腹胰岛素以及南亚人和东南亚/东亚人的胰岛素 AUC 升高（P≤0.006）。与白种人相比，南亚人的 C 肽 AUC/胰岛素 AUC (P = .045) 和脂联素 (P = .037) 摩尔比较低。在白种人和南亚人中，rs2166706 (P = 0.022) 和 rs10830963 (P = 0.009) 的等位基因频率分布存在显着差异，它们都靠近褪黑激素受体 MTNR1B。空腹血糖和胰岛素正常的年轻南亚人中存在非空腹胰岛素升高的情况。南亚人的肝脏胰岛素清除率可能会降低。目前尚无生化证据表明在此发育阶段存在内皮功能障碍。 MTNR1B 信号传导可能是亚洲人群预防 2 型糖尿病的有用治疗靶点。
To identify biochemical and genetic variation relating to increased risk of developing type 2 diabetes mellitus and cardiovascular disease in young, lean male and female adults of different ethnicities. Fasting blood and urine and non-fasting blood following oral glucose intake were analysed in 90 Caucasians, South Asians and South East/East Asians. There were no differences in age, birthweight, blood pressure, body mass index, percent body fat, total energy, percentage of macronutrient intake, microalbumin, leptin, cortisol, adrenocorticotropic hormone, nitric oxide metabolites, C-reactive protein, homocysteine, tumor necrosis factor-α, interleukin-6, von Willebrand factor, vascular cell adhesion molecule-1, plasminogen activator inhibitor-1, and tissue plasminogen activator. Fasting total cholesterol (P = .000), triglycerides (P = .050), low density lipoprotein (P = .009) and non-fasting blood glucose (15 min) (P = .024) were elevated in South Asians compared with Caucasians, but there was no significant difference in glucose area under curve (AUC). Non-fasting insulin in South Asians (15–120 min), in South East/East Asians (60–120 min), and insulin AUC in South Asians and South East/East Asians, were elevated compared with Caucasians (P≤0.006). The molar ratio of C-peptide AUC/Insulin AUC (P = .045) and adiponectin (P = .037) were lower in South Asians compared with Caucasians. A significant difference in allele frequency distributions in Caucasians and South Asians was found for rs2166706 (P = 0.022) and rs10830963 (P = 0.009), which are both near the melatonin receptor MTNR1B. Elevated non-fasting insulin exists in young South Asians of normal fasting glucose and insulin. Hepatic clearance of insulin may be reduced in South Asians. No current biochemical evidence exists of endothelial dysfunction at this stage of development. MTNR1B signalling may be a useful therapeutic target in Asian populations in the prevention of type 2 diabetes mellitus.