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Background <p>Cognitive impairment in Type 1 diabetes mellitus (T1DM) was linked to abnormal lipid metabolism, and its related metabolic alterations remain unclear. Lipidomics may provide novelty insights into the pathophysiology of cognitive impairment in T1DM.</p> Methods <p>This study aimed to explore lipidomic alterations and identify potential lipidomic signatures associated with cognitive impairment in T1DM patients and mice. In this clinical study, cognitive assessments and serum samples were obtained from T1DM patients without mild cognitive impairment (T1DM-noMCI, <i>n</i> = 36), T1DM patients with mild cognitive impairment (T1DM-MCI, <i>n</i> = 33) and healthy controls (NC, <i>n</i> = 32). Serum lipidomic profiles were analyzed to identify metabolites and metabolic pathways in T1DM patients. Correlation between cognitive scores and levels of differential metabolites were assessed, and the diagnostic performance of biomarkers was evaluated using receiver operator characteristic (ROC) curve. In the animal experiments, Morris water maze (MWM) tests were performed on normal control mice (NC, <i>n</i> = 12) and T1DM mice (<i>n</i> = 24). Hippocampal tissues were harvested for lipidomic analysis to detect lipid metabolic changes in T1DM mice.</p> Results <p>The clinical serum lipidomic patterns in T1DM-noMCI and T1DM-MCI groups were significantly different from those of HCs, and metabolite alterations between T1DM-noMCI and T1DM-MCI groups were also dramatical. Pathway enrichment analysis found that T1DM-noMCI and T1DM-MCI groups had a significant impact on glycerophospholipid metabolism. Cognitive scores were negatively related to serum levels of specific metabolites. We successfully selected 13 lipidomic biomarkers to differentiate T1DM-MCI patients, with good diagnostic efficiency. The hippocampus lipidomic patterns in T1DM mice with cognitive decline were also significantly different from those of NCs, while metabolite alterations in T1DM mice with different levels of cognitive decline were dramatically similar. Notably, the lipid metabolic pathways enriched in the hippocampus of T1DM mice showed remarkable concordance with most of those identified in the clinical serum analysis.</p> Conclusions <p>In this exploratory study, specific signatures in lipid metabolism, particularly glycerophospholipid metabolism, were associated with cognitive impairment in T1DM.</p>

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Lipidomic signatures associated with cognitive impairment in type 1 diabetes mellitus: a pilot study integrating clinical serum and mouse hippocampus

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月19日

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  • Hang Min,
  • Jiayu Li,
  • Jue Wang,
  • Shan Su,
  • Yujie Zhang,
  • Limin Tian

摘要

Background

Cognitive impairment in Type 1 diabetes mellitus (T1DM) was linked to abnormal lipid metabolism, and its related metabolic alterations remain unclear. Lipidomics may provide novelty insights into the pathophysiology of cognitive impairment in T1DM.

Methods

This study aimed to explore lipidomic alterations and identify potential lipidomic signatures associated with cognitive impairment in T1DM patients and mice. In this clinical study, cognitive assessments and serum samples were obtained from T1DM patients without mild cognitive impairment (T1DM-noMCI, n = 36), T1DM patients with mild cognitive impairment (T1DM-MCI, n = 33) and healthy controls (NC, n = 32). Serum lipidomic profiles were analyzed to identify metabolites and metabolic pathways in T1DM patients. Correlation between cognitive scores and levels of differential metabolites were assessed, and the diagnostic performance of biomarkers was evaluated using receiver operator characteristic (ROC) curve. In the animal experiments, Morris water maze (MWM) tests were performed on normal control mice (NC, n = 12) and T1DM mice (n = 24). Hippocampal tissues were harvested for lipidomic analysis to detect lipid metabolic changes in T1DM mice.

Results

The clinical serum lipidomic patterns in T1DM-noMCI and T1DM-MCI groups were significantly different from those of HCs, and metabolite alterations between T1DM-noMCI and T1DM-MCI groups were also dramatical. Pathway enrichment analysis found that T1DM-noMCI and T1DM-MCI groups had a significant impact on glycerophospholipid metabolism. Cognitive scores were negatively related to serum levels of specific metabolites. We successfully selected 13 lipidomic biomarkers to differentiate T1DM-MCI patients, with good diagnostic efficiency. The hippocampus lipidomic patterns in T1DM mice with cognitive decline were also significantly different from those of NCs, while metabolite alterations in T1DM mice with different levels of cognitive decline were dramatically similar. Notably, the lipid metabolic pathways enriched in the hippocampus of T1DM mice showed remarkable concordance with most of those identified in the clinical serum analysis.

Conclusions

In this exploratory study, specific signatures in lipid metabolism, particularly glycerophospholipid metabolism, were associated with cognitive impairment in T1DM.