Nephrology Division, Massachusetts General Hospital, Boston, Massachusetts 02129, USA.
J Clin Invest. 2011 Apr;121(4):1402-11. doi: 10.1172/JCI44442. Epub 2011 Mar 14.
Dyslipidemia is an independent risk factor for type 2 diabetes, although exactly which of the many plasma lipids contribute to this remains unclear. We therefore investigated whether lipid profiling can inform diabetes prediction by performing liquid chromatography/mass spectrometry-based lipid profiling in 189 individuals who developed type 2 diabetes and 189 matched disease-free individuals, with over 12 years of follow up in the Framingham Heart Study. We found that lipids of lower carbon number and double bond content were associated with an increased risk of diabetes, whereas lipids of higher carbon number and double bond content were associated with decreased risk. This pattern was strongest for triacylglycerols (TAGs) and persisted after multivariable adjustment for age, sex, BMI, fasting glucose, fasting insulin, total triglycerides, and HDL cholesterol. A combination of 2 TAGs further improved diabetes prediction. To explore potential mechanisms that modulate the distribution of plasma lipids, we performed lipid profiling during oral glucose tolerance testing, pharmacologic interventions, and acute exercise testing. Levels of TAGs associated with increased risk for diabetes decreased in response to insulin action and were elevated in the setting of insulin resistance. Conversely, levels of TAGs associated with decreased diabetes risk rose in response to insulin and were poorly correlated with insulin resistance. These studies identify a relationship between lipid acyl chain content and diabetes risk and demonstrate how lipid profiling could aid in clinical risk assessment.
血脂异常是 2 型糖尿病的一个独立危险因素，尽管许多血浆脂质中哪些与这种疾病有关尚不清楚。因此，我们通过对 189 名发生 2 型糖尿病的患者和 189 名匹配的无疾病个体进行基于液相色谱/质谱的脂质谱分析，在弗雷明汉心脏研究中进行了超过 12 年的随访，研究了脂质谱分析是否可以通过提供糖尿病预测信息。我们发现，碳数和双键含量较低的脂质与糖尿病风险增加有关，而碳数和双键含量较高的脂质与风险降低有关。这种模式在三酰甘油（TAG）中最强，并且在多变量校正年龄、性别、BMI、空腹血糖、空腹胰岛素、总甘油三酯和高密度脂蛋白胆固醇后仍然存在。两种 TAG 的组合进一步提高了糖尿病的预测效果。为了探索调节血浆脂质分布的潜在机制，我们在口服葡萄糖耐量试验、药物干预和急性运动试验期间进行了脂质谱分析。与糖尿病风险增加相关的 TAG 水平随着胰岛素作用而降低，并在胰岛素抵抗的情况下升高。相反，与降低糖尿病风险相关的 TAG 水平随着胰岛素而升高，与胰岛素抵抗相关性差。这些研究确定了脂质酰链含量与糖尿病风险之间的关系，并证明了脂质谱分析如何有助于临床风险评估。
