Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Beijing, 100730, China.
Department of Basic Physiology, The Health School affiliated with Capital Medical University, Beijing, China.
Lipids Health Dis. 2020 Jun 2;19(1):121. doi: 10.1186/s12944-020-01303-w.
Previous studies on the effects of lipotoxicity and oxidative stress on islet beta cell function mainly focused on patients with diabetes, whereas studies on normal glucose tolerance (NGT) are few. The aim of this study was to explore the relationships among triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), oxidative stress indicators, insulin resistance, and beta cell function in populations with different glucose and lipid metabolism states.
A total of 517 individuals were recruited from a rural community in Beijing, China. Glucose metabolism status was defined according to the results of a 75-g oral glucose tolerance test (OGTT). Dyslipidemia was defined as abnormal TG, HDL-c, or LDL-c levels. The population was divided into four groups: individuals with normal glucose and lipid levels (group A, n = 62); those with dyslipidemia alone (group B, n = 82); those with dysglycemia alone (group C, n = 121); and those with dysglycemia and dyslipidemia (group D, n = 247). Oxidative stress indicators, including superoxide dismutase (SOD), glutathione reductase (GR) and 8-hydroxydeoxyguanosine (8-OHdG), were measured. Homeostasis model assessment of insulin resistance (HOMA-IR) and glucose disposition index (DI, DI) were calculated to assess insulin resistance and islet beta cell function, respectively. Stratified multiple linear regression analysis was used to explore relationships between TG, HDL-c, LDL-c, oxidative stress indicators, and insulin resistance (natural log transformation of HOMA-IR, LnHOMA-IR) and beta cell function (natural log transformation of DI, Ln DI).
Compared with the control group, populations with dyslipidemia and/or dysglycemia showed significantly increased insulin resistance. Dyslipidemia aggravated insulin resistance and beta cell dysfunction in individuals with dysglycemia. Stratified regression analysis showed that TG positively correlated with LnHOMA-IR in individuals with normal glucose levels (beta = 0.321, 0.327, P = 0.011, 0.003 in groups A and B, respectively) and negatively correlated with LnDI in participants with dyslipidemia (beta = - 0.225, - 0.122, P = 0.035, 0.048 in groups B and D, respectively). Reduced serum SOD levels in individuals with dysglycemia plus dyslipidemia were observed, and a negative association between TG and SOD levels was found (r = - 0.461, P < 0.001).
TG correlated with both insulin resistance and beta cell function in individuals with dyslipidemia alone. SOD negatively correlated with TG, indicating a close relationship between oxidative stress and glucose-lipid metabolism. Due to the adverse effect of hypertriglyceridemia on insulin sensitivity and islet beta cell function, more attention should be paid to the detection and management of hypertriglyceridemia.
之前关于脂毒性和氧化应激对胰岛β细胞功能影响的研究主要集中在糖尿病患者，而关于正常糖耐量（NGT）的研究较少。本研究旨在探讨不同糖脂代谢状态人群中甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-c）、低密度脂蛋白胆固醇（LDL-c）、氧化应激指标、胰岛素抵抗和β细胞功能之间的关系。
本研究共纳入了来自中国北京一个农村社区的 517 名个体。根据 75g 口服葡萄糖耐量试验（OGTT）结果定义葡萄糖代谢状态。血脂异常定义为 TG、HDL-c 或 LDL-c 水平异常。人群分为四组：血糖和血脂水平正常者（A 组，n=62）；单纯血脂异常者（B 组，n=82）；单纯糖代谢异常者（C 组，n=121）；糖脂代谢异常者（D 组，n=247）。测量超氧化物歧化酶（SOD）、谷胱甘肽还原酶（GR）和 8-羟基脱氧鸟苷（8-OHdG）等氧化应激指标。计算稳态模型评估的胰岛素抵抗（HOMA-IR）和葡萄糖处置指数（DI），以评估胰岛素抵抗和胰岛β细胞功能。采用分层多线性回归分析探讨 TG、HDL-c、LDL-c、氧化应激指标与胰岛素抵抗（HOMA-IR 的自然对数转换，LnHOMA-IR）和β细胞功能（DI 的自然对数转换，LnDI）之间的关系。
与对照组相比，血脂异常和/或糖代谢异常的人群胰岛素抵抗明显增加。血脂异常加重了糖代谢异常者的胰岛素抵抗和β细胞功能障碍。分层回归分析显示，在血糖正常者中，TG 与 LnHOMA-IR 呈正相关（A 组和 B 组的β值分别为 0.321、0.327，P=0.011、0.003），与血脂异常者的 LnDI 呈负相关（B 组和 D 组的β值分别为-0.225、-0.122，P=0.035、0.048）。在糖脂代谢异常者中，血清 SOD 水平降低，且 TG 与 SOD 水平呈负相关（r=-0.461，P<0.001）。
在单纯血脂异常者中，TG 与胰岛素抵抗和β细胞功能均相关。SOD 与 TG 呈负相关，表明氧化应激与糖脂代谢密切相关。由于高甘油三酯血症对胰岛素敏感性和胰岛β细胞功能有不良影响，应更加关注高甘油三酯血症的检测和管理。
