Effects of insulin resistance and type 2 diabetes on lipoprotein subclass particle size and concentration determined by nuclear magnetic resonance
Effects of insulin resistance and type 2 diabetes on lipoprotein subclass particle size and concentration determined by nuclear magnetic resonance
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DOI：
10.2337/diabetes.52.2.453
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发表时间：
2003-02-01
期刊：
影响因子：
7.7
通讯作者：
Liao, YL
中科院分区：
文献类型：
--
作者：
Garvey, WT;Kwon, S;Liao, YL
胰岛素抵抗综合征（IRS）与血脂异常和心血管疾病风险增加有关。一种利用全血清核磁共振（NMR）详细分析脂蛋白亚类大小和颗粒浓度的新方法已经成为可能。为了确定胰岛素抵抗的影响，我们使用核磁共振脂蛋白亚类分析和常规脂质面板测量了血脂异常，并将胰岛素敏感性作为56例胰岛素敏感（IS）患者在高胰岛素钳夹期间的最大葡萄糖处置率（GDR），平均值+/- SD: GDR 15.8 +/- 2.0 mg. kg（-1）。min(-1)，空腹血糖[FBG] 4.7 +/- 0.3 mmol/l, BMI 26 +/- 5)， 46例胰岛素抵抗（IR; GDR 10.2 +/- 1.9, FBG 4.9 +/- 0.5, BMI 29 +/- 5）， 46例未治疗的2型糖尿病患者（GDR 7.4 +/- 2.8, FBG 10.8 +/- 3.7, BMI 30 +/- 5）。在整个组中，GDR的回归分析显示，进进性胰岛素抵抗与VLDL大小的增加（r = -0.40）和大VLDL颗粒浓度的增加（r = -0.42）有关，由于小LDL颗粒的显著增加（r = -0.34）和大LDL颗粒的减少（r = 0.34）， LDL大小的减少（r = 0.42）， LDL颗粒数量的总体增加（r = -0.44）。由于大HDL颗粒的消耗（r = 0.38）， HDL尺寸减小（r = 0.41），而小HDL尺寸适度增加（r = -0.21，均P < 0.01）。当分析中只包括血糖正常的个体（即IS + IR但不包括糖尿病）时，这些相关性也很明显，并且在调整年龄、BMI、性别和种族的多重回归分析中仍然存在。也进行了不连续分析。与IS相比，IR和糖尿病亚组表现出大VLDL颗粒浓度增加两到三倍（中等或小VLDL没有变化），这导致血清甘油三酯增加；由于小LDL亚类的增加和大LDL亚类的减少而导致LDL大小的减少，加上总体LDL颗粒浓度的增加，这些共同导致LDL胆固醇无差异（IS与IR）或微小差异（IS与糖尿病）；大的保护心脏的高密度脂蛋白减少，同时小的高密度脂蛋白亚类增加，因此高密度脂蛋白胆固醇没有显著的净差异。我们得出结论：1)胰岛素抵抗对VLDL、LDL和HDL的脂蛋白大小和亚类颗粒浓度有深远的影响；2)在2型糖尿病中，脂蛋白亚类改变中度加重，但主要归因于潜在的胰岛素抵抗；3)这些胰岛素抵抗引起的核磁共振脂蛋白亚类谱的变化可预测地增加心血管疾病的风险，但在常规脂质组中并不完全明显。研究NAIR脂蛋白亚类参数是否可以更有效地用于IRS患者的风险管理和预防心血管疾病将具有重要意义。
The insulin resistance syndrome (IRS) is associated with dyslipidemia and increased cardiovascular disease risk. A novel method for detailed analyses of lipoprotein subclass sizes and particle concentrations that uses nuclear magnetic resonance (NMR) of whole sera has become available. To define the effects of insulin resistance, we measured dyslipidemia using both NMR lipoprotein subclass analysis and conventional lipid panel, and insulin sensitivity as the maximal glucose disposal rate (GDR) during hyperinsulinemic clamps in 56 insulin sensitive (IS; mean +/- SD: GDR 15.8 +/- 2.0 mg. kg(-1). min(-1), fasting blood glucose [FBG] 4.7 +/- 0.3 mmol/l, BMI 26 +/- 5), 46 insulin resistant (IR; GDR 10.2 +/- 1.9, FBG 4.9 +/- 0.5, BMI 29 +/- 5), and 46 untreated subjects with type 2 diabetes (GDR 7.4 +/- 2.8, FBG 10.8 +/- 3.7, BMI 30 +/- 5). In the group as a whole, regression analyses with GDR showed that progressive insulin resistance was associated with an increase in VLDL size (r = -0.40) and an increase in large VLDL particle concentrations (r = -0.42), a decrease in LDL size (r = 0.42) as a result of a marked increase in small LDL particles (r = -0.34) and reduced large LDL (r = 0.34), an overall increase in the number of LDL particles (r = -0.44), and a decrease in HDL size (r = 0.41) as a result of depletion of large HDL particles (r = 0.38) and a modest increase in small HDL (r = -0.21; all P < 0.01). These correlations were also evident when only normoglycemic individuals were included in the analyses (i.e., IS + IR but no diabetes), and persisted in multiple regression analyses adjusting for age, BMI, sex, and race. Discontinuous analyses were also performed. When compared with IS, the IR and diabetes subgroups exhibited a two- to threefold increase in large VLDL particle concentrations (no change in medium or small VLDL), which produced an increase in serum triglycerides; a decrease in LDL size as a result of an increase in small and a reduction in large LDL subclasses, plus an increase in overall LDL particle concentration, which together led to no difference (IS versus IR) or a minimal difference (IS-versus diabetes) in LDL cholesterol; and a decrease in large cardioprotective HDL combined with an increase in the small HDL subclass such that there was no net significant difference in HDL cholesterol. We conclude that 1) insulin resistance had profound effects on lipoprotein size and subclass particle concentrations for VLDL, LDL, and HDL when measured by NMR; 2) in type 2 diabetes, the lipoprotein subclass alterations are moderately exacerbated but can be attributed primarily to the underlying insulin resistance; and 3) these insulin resistance-induced changes in the NMR lipoprotein subclass profile predictably increase risk of cardiovascular disease but were not fully apparent in the conventional lipid panel. It will be important to study whether NAIR lipoprotein subclass parameters can be used to manage risk more effectively and prevent cardiovascular disease in patients with the IRS.