Background Type 2 diabetes mellitus (T2DM) is strongly associated with various complications, including cognitive impairment. Homocysteine (Hcy) may be involved in the pathogenesis of type 2 diabetes (T2DM). Previous studies have focused on the relationship between serum homocysteine and overall cognitive function in patients with type 2 diabetes, but less on attention function. Objective Based on this, we aimed to explore the correlation between serum Hcy levels and cognitive especially attention function in patients with T2DM. Methods Eighty patients with type 2 diabetes were included, and the general information at the time of admission was collected, including gender, age, education level, medical history, personal history, family history, and laboratory test results, among which laboratory results include neutrophil count, lymphocyte count, homocysteine, fasting plasma glucose (FPG), triglycerides (TG), low-density lipoprotein (LDL), folic acid, vitamin B12, and glycated hemoglobin (HbA1c) and calculate neutrophil lymphocyte ratio (NLR). Based on serum Hcy levels, patients were divided into HHcy-T2DM (Hcy ≥ 15 μmmol/L, 40 cases) and T2DM without HHcy (Hcy < 15 μmmol/L, 40 cases) groups. No significant positive signs were observed during neurological examinations. The mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to assess the overall cognitive function of the patients; the trail making tests A and B (TMT-A, TMT-B), digit span test (DST), symbol digit modalities test (SDMT), and Stroop tests (SCWT) were used to assess the patients’ attention function. Results The MoCA and SDMT scores of the HHcy-T2DM group were lower than those of the T2DM without HHcy group, and the test times of TMT-A, TMT-B, and SCWT were significantly longer than those of the T2DM without HHcy group (all p < 0.05), negatively correlated with MoCA scores (r = -0.459, p = 0.003), and positively correlated with TMT-A, TMT-B, SCWT (time), and SCWT (error count) (r = 0.562, p = 0.000; r = 0.491, p = 0.001; r = 0.449, p = 0.004; r = 0.505, p = 0.001). The AUC predicted by Hcy for T2DM patients with cognitive impairment was 0.736, with a cutoff value of 19.65. A linear regression analysis revealed that Hcy levels explained 21.1% of the changes in MoCA, 31.6% of the changes in TMT-A, 24.1% of the changes in TMT-B, 20.2% of the changes in SCWT (time), and 25.5% of the changes in SCWT (error count). Conclusion Higher Hcy levels are associated with more severe cognitive impairment, particularly in attention function. Hcy showed the strongest correlation with attention and executive function indicators (TMT-A/B, SCWT).

Extracellular homocysteine levels and cognitive dysfunction in patients with type 2 diabetes mellitus

期刊论文
发表日期：

2025年11月17日

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Dianlong Hou,
Wenqing Xu,
Hairui Liu,
Yanli Bu,
Yujing Liu,
Baolan Wang

摘要

Background

Type 2 diabetes mellitus (T2DM) is strongly associated with various complications, including cognitive impairment. Homocysteine (Hcy) may be involved in the pathogenesis of type 2 diabetes (T2DM). Previous studies have focused on the relationship between serum homocysteine and overall cognitive function in patients with type 2 diabetes, but less on attention function.

Objective

Based on this, we aimed to explore the correlation between serum Hcy levels and cognitive especially attention function in patients with T2DM.

Methods

Eighty patients with type 2 diabetes were included, and the general information at the time of admission was collected, including gender, age, education level, medical history, personal history, family history, and laboratory test results, among which laboratory results include neutrophil count, lymphocyte count, homocysteine, fasting plasma glucose (FPG), triglycerides (TG), low-density lipoprotein (LDL), folic acid, vitamin B12, and glycated hemoglobin (HbA1c) and calculate neutrophil lymphocyte ratio (NLR). Based on serum Hcy levels, patients were divided into HHcy-T2DM (Hcy ≥ 15 μmmol/L, 40 cases) and T2DM without HHcy (Hcy < 15 μmmol/L, 40 cases) groups. No significant positive signs were observed during neurological examinations. The mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to assess the overall cognitive function of the patients; the trail making tests A and B (TMT-A, TMT-B), digit span test (DST), symbol digit modalities test (SDMT), and Stroop tests (SCWT) were used to assess the patients’ attention function.

Results

The MoCA and SDMT scores of the HHcy-T2DM group were lower than those of the T2DM without HHcy group, and the test times of TMT-A, TMT-B, and SCWT were significantly longer than those of the T2DM without HHcy group (all p < 0.05), negatively correlated with MoCA scores (r = -0.459, p = 0.003), and positively correlated with TMT-A, TMT-B, SCWT (time), and SCWT (error count) (r = 0.562, p = 0.000; r = 0.491, p = 0.001; r = 0.449, p = 0.004; r = 0.505, p = 0.001). The AUC predicted by Hcy for T2DM patients with cognitive impairment was 0.736, with a cutoff value of 19.65. A linear regression analysis revealed that Hcy levels explained 21.1% of the changes in MoCA, 31.6% of the changes in TMT-A, 24.1% of the changes in TMT-B, 20.2% of the changes in SCWT (time), and 25.5% of the changes in SCWT (error count).

Conclusion

Higher Hcy levels are associated with more severe cognitive impairment, particularly in attention function. Hcy showed the strongest correlation with attention and executive function indicators (TMT-A/B, SCWT).