Introduction

Type 1 diabetes (T1D) is caused by the destruction of pancreatic islet beta cells resulting in total loss of insulin production. Recent studies have suggested that the destruction may be interrelated to plasma lipids.

Objectives

Specific lipids have previously been shown to be decreased in children who develop T1D before four years of age. Disturbances of plasma lipids prior to clinical diagnosis of diabetes, if true, may provide a novel way to improve prediction, and monitor disease progression.

Methods

A lipidomic approach was utilized to analyze plasma from 67 healthy adolescent subjects (10–15 years of age) with or without islet autoantibodies but all with increased genetic risk for T1D. The study subjects were enrolled at birth in the Diabetes Prediction in Skåne (DiPiS) study and after 10–15 years of follow-up we performed the present cross-sectional analysis. HLA-DRB345, -DRB1, -DQA1, -DQB1, -DPA1 and -DPB1 genotypes were determined using next generation sequencing. Lipidomic profiles were determined using ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry. Lipidomics data were analyzed according to genotype.

Results

Variation in levels of several specific phospholipid species were related to level of autoimmunity but not development of T1D. Five glycosylated ceramides were increased in insulin autoantibody (IAA) positive adolescent subjects compared to adolescent subjects without this autoantibody. Additionally, HLA genotypes seemed to influence levels of long chain triacylglycerol (TG).

Conclusion

Lipidomic profiling of adolescent subjects in high risk of T1D may improve sub-phenotyping in this high risk population.

中文翻译：

---

DiPiS 队列中 1 型糖尿病风险增加的青少年受试者的血浆脂质组学特征

介绍

1 型糖尿病 (T1D) 是由胰岛 β 细胞破坏导致胰岛素生产完全丧失引起的。最近的研究表明，这种破坏可能与血浆脂质有关。

目标

先前已证明特定脂质在四岁前发展为 T1D 的儿童中会降低。糖尿病临床诊断前的血脂紊乱，如果属实，可能会提供一种新的方法来改善预测和监测疾病进展。

方法

脂质组学方法用于分析来自 67 名健康青少年受试者（10-15 岁）的血浆，这些受试者有或没有胰岛自身抗体，但都具有增加的 T1D 遗传风险。研究对象在出生时就参加了斯科讷糖尿病预测 (DiPiS) 研究，经过 10-15 年的随访，我们进行了当前的横断面分析。HLA-DRB345、-DRB1、-DQA1、-DQB1、-DPA1 和-DPB1 基因型使用下一代测序确定。使用超高效液相色谱四极杆飞行时间质谱法测定脂质组谱。根据基因型分析脂质组学数据。

结果

几种特定磷脂种类的水平变化与自身免疫水平有关，但与 T1D 的发展无关。与没有这种自身抗体的青少年受试者相比，胰岛素自身抗体 (IAA) 阳性青少年受试者的五种糖基化神经酰胺增加。此外，HLA 基因型似乎影响长链甘油三酯 (TG) 的水平。

结论

对 T1D 高危青少年受试者进行脂质组学分析可能会改善这一高危人群的亚表型。