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Background <p>Early vascular aging (EVA) is highly prevalent among individuals with type 2 diabetes mellitus (T2DM), yet the metabolic and calcific determinants underlying this accelerated vascular decline remain insufficiently understood. Small dense LDL cholesterol (sdLDL-C) reflects lipid-driven vascular injury, whereas alkaline phosphatase (ALP) is a key mediator of medial calcification. However, their combined role—and potential age-dependent interactions—in EVA has not been systematically investigated.</p> Methods <p>This retrospective cross-sectional study included 480 consecutive T2DM patients. Vascular aging was assessed using brachial–ankle pulse wave velocity (baPWV), with EVA defined as baPWV &gt; mean + 2 SD of an age-stratified healthy reference population. sdLDL-C, ALP, and the sdLDL-C/ALP ratio were evaluated as primary exposures through multivariable linear and logistic regression, forward stepwise modeling, age-stratified analyses, interaction testing, and ROC curve assessment.</p> Results <p>sdLDL-C, ALP, and particularly the sdLDL-C/ALP ratio were significantly associated with EVA. The sdLDL-C/ALP ratio demonstrated the strongest independent association (per 0.001 increase: OR = 1.32, 95% CI 1.15–1.51), with a clear dose–response trend across tertiles (<i>P</i> for trend &lt; 0.001). Age-stratified analyses revealed a pronounced age-dependent gradient: the ratio showed a 2.32-fold increased risk of EVA in adults ≤ 55&#xa0;years, attenuated associations in the 56–65 group, and no significant association beyond 65&#xa0;years. The interaction term (ratio × age) was significant (<i>P</i> = 0.009), confirming age as a major effect modifier. In ROC analysis, the sdLDL-C/ALP ratio outperformed sdLDL-C and ALP alone (AUC = 0.742), whereas the combined model achieved the highest discrimination (AUC = 0.811).</p> Conclusions <p>sdLDL-C, ALP, and especially their composite ratio are robustly associated with EVA in T2DM patients. The sdLDL-C/ALP ratio captures integrated metabolic and calcific vascular stress and exhibits clear age-dependent effect attenuation. These findings highlight the sdLDL-C/ALP ratio as a potentially valuable biomarker for EVA screening and early vascular risk stratification, particularly in younger and middle-aged diabetic populations.</p>

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sdLDL-C, alkaline phosphatase, and their composite ratio are associated with early vascular aging in type 2 diabetes mellitus: a retrospective cross-sectional study

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  • 发表日期：

    2026年4月11日

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  • Yunxia Ji,
  • Chunling Mu,
  • Yingjuan Han

摘要

Background

Early vascular aging (EVA) is highly prevalent among individuals with type 2 diabetes mellitus (T2DM), yet the metabolic and calcific determinants underlying this accelerated vascular decline remain insufficiently understood. Small dense LDL cholesterol (sdLDL-C) reflects lipid-driven vascular injury, whereas alkaline phosphatase (ALP) is a key mediator of medial calcification. However, their combined role—and potential age-dependent interactions—in EVA has not been systematically investigated.

Methods

This retrospective cross-sectional study included 480 consecutive T2DM patients. Vascular aging was assessed using brachial–ankle pulse wave velocity (baPWV), with EVA defined as baPWV > mean + 2 SD of an age-stratified healthy reference population. sdLDL-C, ALP, and the sdLDL-C/ALP ratio were evaluated as primary exposures through multivariable linear and logistic regression, forward stepwise modeling, age-stratified analyses, interaction testing, and ROC curve assessment.

Results

sdLDL-C, ALP, and particularly the sdLDL-C/ALP ratio were significantly associated with EVA. The sdLDL-C/ALP ratio demonstrated the strongest independent association (per 0.001 increase: OR = 1.32, 95% CI 1.15–1.51), with a clear dose–response trend across tertiles (P for trend < 0.001). Age-stratified analyses revealed a pronounced age-dependent gradient: the ratio showed a 2.32-fold increased risk of EVA in adults ≤ 55 years, attenuated associations in the 56–65 group, and no significant association beyond 65 years. The interaction term (ratio × age) was significant (P = 0.009), confirming age as a major effect modifier. In ROC analysis, the sdLDL-C/ALP ratio outperformed sdLDL-C and ALP alone (AUC = 0.742), whereas the combined model achieved the highest discrimination (AUC = 0.811).

Conclusions

sdLDL-C, ALP, and especially their composite ratio are robustly associated with EVA in T2DM patients. The sdLDL-C/ALP ratio captures integrated metabolic and calcific vascular stress and exhibits clear age-dependent effect attenuation. These findings highlight the sdLDL-C/ALP ratio as a potentially valuable biomarker for EVA screening and early vascular risk stratification, particularly in younger and middle-aged diabetic populations.