脂联素和白细胞介素-1 受体拮抗剂的血液水平可区分 3c 型和 2 型糖尿病：对新诊断糖尿病中早期胰腺癌检测的影响。

Blood levels of adiponectin and IL-1Ra distinguish type 3c from type 2 diabetes: Implications for earlier pancreatic cancer detection in new-onset diabetes.

机构信息

Department of Molecular and Clinical Cancer Medicine, University of Liverpool, UK.

Department of Diabetes and Endocrinology, Royal Liverpool University Hospital, UK.

出版信息

EBioMedicine. 2022 Jan;75:103802. doi: 10.1016/j.ebiom.2021.103802. Epub 2022 Jan 3.

DOI:10.1016/j.ebiom.2021.103802

PMID:34990893

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8741427/

Abstract

BACKGROUND

Screening for pancreatic ductal adenocarcinoma (PDAC) in populations at high risk is recommended. Individuals with new-onset type 2 diabetes mellitus (NOD) are the largest high-risk group for PDAC. To facilitate screening, we sought biomarkers capable of stratifying NOD subjects into those with type 2 diabetes mellitus (T2DM) and those with the less prevalent PDAC-related diabetes (PDAC-DM), a form of type 3c DM commonly misdiagnosed as T2DM.

METHODS

Using mass spectrometry- and immunoassay-based methodologies in a multi-stage analysis of independent sample sets (n=443 samples), blood levels of 264 proteins were considered using Ingenuity Pathway Analysis, literature review and targeted training and validation.

FINDINGS

Of 30 candidate biomarkers evaluated in up to four independent patient sets, 12 showed statistically significant differences in levels between PDAC-DM and T2DM. The combination of adiponectin and interleukin-1 receptor antagonist (IL-1Ra) showed strong diagnostic potential, (AUC of 0.91; 95% CI: 0.84-0.99) for the distinction of T3cDM from T2DM.

INTERPRETATION

Adiponectin and IL-1Ra warrant further consideration for use in screening for PDAC in individuals newly-diagnosed with T2DM.

FUNDING

North West Cancer Research, UK, Cancer Research UK, Pancreatic Cancer Action, UK.

摘要

背景

建议对高危人群进行胰腺导管腺癌 (PDAC) 的筛查。新发 2 型糖尿病 (NOD) 患者是 PDAC 的最大高危人群。为了便于筛查，我们寻求能够将 NOD 患者分为 2 型糖尿病 (T2DM) 和 PDAC 相关糖尿病 (PDAC-DM) 的生物标志物，PDAC-DM 是一种常见误诊为 T2DM 的 3c 型糖尿病。

方法

在独立样本集的多阶段分析中使用基于质谱和免疫测定的方法（n=443 个样本），使用Ingenuity Pathway Analysis、文献综述和靶向培训和验证考虑了 264 种蛋白质的血液水平。

发现

在多达四个独立患者组中评估的 30 个候选生物标志物中，有 12 个在 PDAC-DM 和 T2DM 之间的水平上显示出统计学显著差异。脂联素和白细胞介素-1 受体拮抗剂 (IL-1Ra) 的组合具有很强的诊断潜力（AUC 为 0.91；95%CI：0.84-0.99），可用于区分 T3cDM 与 T2DM。