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机器学习结合血清神经调节蛋白4水平对2型糖尿病合并甲状腺功能亢进症的预测研究

Predictive study of machine learning combined with serum Neuregulin 4 levels for hyperthyroidism in type II diabetes mellitus.

作者信息

Gu Huilan, Lu Ye

机构信息

Department of Endocrinology, Suzhou Ninth People's Hospital, Suzhou, China.

出版信息

Front Oncol. 2025 Jul 16;15:1595553. doi: 10.3389/fonc.2025.1595553. eCollection 2025.

Abstract

BACKGROUND

Neuregulin 4 (NRG4) is a novel metabolic regulator closely associated with insulin resistance and thyroid dysfunction. However, its role in the pathogenesis of comorbid type 2 diabetes mellitus and hyperthyroidism (T2DM-FT) remains to be systematically elucidated. Given the complex clinical characteristics of T2DM-FT patients, traditional statistical methods are often insufficient to effectively analyze nonlinear relationships among multiple variables. Machine learning techniques have garnered widespread attention due to their advantages in modeling high-dimensional, heterogeneous data.

OBJECTIVE

This study was to evaluate the predictive capability of a support vector machine (SVM) model based on serum NRG4 combined with a convolutional neural network (CNN) and long short-term memory network (LSTM)-based ultrasound feature classification (SVM-CNN+LSTM) model for predicting the occurrence of FT in patients with T2DM.

METHODS

Studied 500 T2DM patients (60 with FT, 440 without), and 200 healthy controls. Collected data on demographics, disease characteristics, NRG4, and thyroid indices. Pearson correlation was used to identify features correlated with NRG4. A parameter-optimized SVM model (C=1, linear kernel) was constructed for structured data modeling. Additionally, a CNN+LSTM network was employed to extract spatial (thyroid morphology) and temporal (hemodynamics) features from ultrasound sequences. These features were then fused with biochemical indicators, such as NRG4, to develop the final SVM-CNN+LSTM multimodal predictive model.

RESULTS

Serum NRG4 levels in T2DM+FT patients were significantly higher than those in the healthy Ctrl group (4.44 ± 1.25 2.17 ± 0.48 μg/L, < 0.05). NRG4 levels were positively correlated with HOMA-IR ( = 0.593), FT3 ( = 0.773), FT4 ( = 0.683), thyroid volume ( = 0.652), and the resistance index (RI) ( = 0.473) (< 0.05). The optimized SVM model demonstrated a sensitivity of 86.23%, specificity of 90.33%, and an area under the curve (AUC) of 0.887. In contrast, the fusion model SVM-CNN+LSTM outperformed the SVM model across all metrics, achieving a sensitivity of 91.32%, specificity of 94.18%, and an AUC of 0.943 (< 0.05).

CONCLUSION

The SVM-CNN+LSTM multimodal model, which integrates serum NRG4 levels with ultrasound features, significantly enhances the predictive accuracy of hyperthyroidism in T2DM patients. This approach effectively reveals the multifactorial mechanisms underlying T2DM-FT comorbidity, providing a powerful tool for early clinical intervention.

摘要

背景

神经调节蛋白4(NRG4)是一种新型代谢调节因子,与胰岛素抵抗和甲状腺功能障碍密切相关。然而,其在2型糖尿病合并甲状腺功能亢进症(T2DM-FT)发病机制中的作用仍有待系统阐明。鉴于T2DM-FT患者复杂的临床特征,传统统计方法往往不足以有效分析多个变量之间的非线性关系。机器学习技术因其在高维、异质数据建模方面的优势而受到广泛关注。

目的

本研究旨在评估基于血清NRG4的支持向量机(SVM)模型结合基于卷积神经网络(CNN)和长短期记忆网络(LSTM)的超声特征分类(SVM-CNN+LSTM)模型对T2DM患者甲状腺功能亢进症发生的预测能力。

方法

研究了500例T2DM患者(60例患有FT,440例未患)和200例健康对照者。收集了人口统计学、疾病特征、NRG4和甲状腺指标数据。采用Pearson相关性分析确定与NRG4相关的特征。构建了参数优化的SVM模型(C=1,线性核)用于结构化数据建模。此外,采用CNN+LSTM网络从超声序列中提取空间(甲状腺形态)和时间(血流动力学)特征。然后将这些特征与NRG4等生化指标融合,建立最终的SVM-CNN+LSTM多模态预测模型。

结果

T2DM+FT患者血清NRG4水平显著高于健康对照组(4.44±1.25 2.17±0.48μg/L,<0.05)。NRG4水平与HOMA-IR(=0.593)、FT3(=0.773)、FT4(=0.683)、甲状腺体积(=0.652)和阻力指数(RI)(=0.473)呈正相关(<0.05)。优化后的SVM模型敏感性为86.23%,特异性为90.33%,曲线下面积(AUC)为0.887。相比之下,融合模型SVM-CNN+LSTM在所有指标上均优于SVM模型,敏感性为91.32%,特异性为94.18%,AUC为0.943(<0.05)。

结论

将血清NRG4水平与超声特征相结合的SVM-CNN+LSTM多模态模型显著提高了T2DM患者甲状腺功能亢进症的预测准确性。该方法有效揭示了T2DM-FT合并症的多因素机制,为早期临床干预提供了有力工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9561/12307509/1487c1bfeb39/fonc-15-1595553-g001.jpg

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