Ceramide stearic to palmitic acid ratio predicts incident diabetes
Ceramide stearic to palmitic acid ratio predicts incident diabetes
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DOI：
10.1007/s00125-018-4590-6
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发表时间：
2018-06-01
期刊：
影响因子：
8.2
通讯作者：
Laaksonen, Reijo
中科院分区：
文献类型：
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作者：
Hilvo, Mika;Salonurmi, Tuire;Laaksonen, Reijo
目的/假设神经酰胺脂质在胰岛素抵抗、糖尿病和心血管疾病风险的发生中发挥作用。在这里，我们研究了四种神经酰胺及其比例，以找到糖尿病发生的最佳预测因子。 方法 采用经过验证的质谱方法测量血清或血浆样本中的 Cer(d18:1/16:0)、Cer(d18:1/18:0)、Cer(d18:1/24:0) 和 Cer(d18:1/24:1)。这些神经酰胺在一项基于人群的危险因素研究（FINRISK 2002，n = 8045）、一组因疑似稳定型心绞痛而接受选择性冠状动脉造影的参与者队列（挪威西部冠状动脉造影队列 [WECAC]，n = 3344）和一项干预试验中进行了分析，该试验调查了代谢综合征高危个体改善生活方式的方法（预防代谢综合征） [PrevMetSyn]，n = 371）。开发了糖尿病风险评分模型来估计 10 年发生糖尿病的风险。FINRISK 2002 中的结果分析表明，Cer(d18:1/18:0)/Cer (d18:1/16:0) 神经酰胺比率可预测糖尿病发生风险（HR per SD 2.23, 95% CI 2.05, 2.42），并且在调整包括 BMI、BMI、空腹血糖和 HbA(1c)（HR 1.34，95% CI 1.14，1.57）。这一发现在 WECAC 研究中得到了验证（未经调整的 HR 1.81，95% CI 1.53，2.14；调整后的 HR 1.39，95% CI 1.16，1.66）。在干预试验中，体重减轻 5% 或以上的个体的神经酰胺比率和糖尿病风险评分显着下降。结论/解释 Cer(d18:1/18:0)/Cer(d18:1/16:0) 比率是糖尿病发生的独立预测生物标志物，可以通过生活方式干预进行调节。
Aims/hypothesis Ceramide lipids have a role in the development of insulin resistance, diabetes and risk of cardiovascular disease. Here we investigated four ceramides and their ratios to find the best predictors of incident diabetes.Methods A validated mass-spectrometric method was applied to measure Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0) and Cer(d18:1/24:1) from serum or plasma samples. These ceramides were analysed in a population-based risk factor study (FINRISK 2002, n = 8045), in a cohort of participants undergoing elective coronary angiography for suspected stable angina pectoris (Western Norway Coronary Angiography Cohort [WECAC], n = 3344) and in an intervention trial investigating improved methods of lifestyle modification for individuals at high risk of the metabolic syndrome (Prevent Metabolic Syndrome [PrevMetSyn], n = 371). Diabetes risk score models were developed to estimate the 10 year risk of incident diabetes.Results Analysis in FINRISK 2002 showed that the Cer(d18:1/18:0)/Cer (d18:1/16:0) ceramide ratio was predictive of incident diabetes (HR per SD 2.23, 95% CI 2.05, 2.42), and remained significant after adjustment for several risk factors, including BMI, fasting glucose and HbA(1c) (HR 1.34, 95% CI 1.14, 1.57). The finding was validated in the WECAC study (unadjusted HR 1.81, 95% CI 1.53, 2.14; adjusted HR 1.39, 95% CI 1.16, 1.66). In the intervention trial, the ceramide ratio and diabetes risk scores significantly decreased in individuals who had 5% or more weight loss.Conclusions/interpretation The Cer(d18:1/18:0)/Cer(d18:1/16:0) ratio is an independent predictive biomarker for incident diabetes, and may be modulated by lifestyle intervention.