sFlt-1、Lp-PLA2、MHR、ICAM-1联合预测糖尿病足溃疡严重程度与预后的临床价值

doi:10.3969/j.issn.1006-5725.2026.10.003

Abstract

Abstract:

Objective To explore the clinical value of the combined measurement of soluble vascular endothelial growth factor receptor-1 （sFlt-1）， lipoprotein-associated phospholipase A2 （Lp-PLA2）， monocyte/high-density lipoprotein cholesterol ratio （MHR）， and intercellular adhesion molecule-1 （ICAM-1） in predicting the severity and prognosis of patients with diabetic foot ulcers （DFU）. Methods A total of 415 patients with DFU who were admitted to Qingdao Central Hospital， University of Health and Rehabilitation Sciences （Qingdao Central Hospital） between January 2022 and January 2025 were selected for this study （DFU group）. Meanwhile， 108 patients with type 2 diabetes mellitus but without DFU （T2DM group） and 108 healthy individuals undergoing physical examinations were recruited from the same hospital （control group）. According to the Wagner classification， the patients with DFU were classified into the grade 1 group （155 cases）， the grade 2 group （127 cases）， the grade 3 group （72 cases）， and the grade 4 group （61 cases）. After a 6-month follow-up during which the prognosis was recorded， the patients were further categorized into 303 cases （good prognosis group） and 112 cases （poor prognosis group） based on their prognosis. The levels of sFlt-1， Lp-PLA2， MHR， and ICAM-1 were compared among the DFU group， the T2DM group， and the control group， as well as among different severity groups. The correlations between the levels of these markers （sFlt-1， Lp-PLA2， MHR， and ICAM-1） and the severity of the disease were analyzed. Additionally， multivariate logistic regression analysis was used to identify the risk factors for poor prognosis in patients with DFU. The predictive value of the combined detection of sFlt-1， Lp-PLA2， MHR， and ICAM-1 for poor prognosis in DFU was analyzed using the receiver operating characteristic curve （ROC）. Results The levels of sFlt-1， Lp-PLA2， MHR， and ICAM-1 in both the DFU group and the T2DM group were higher than those in the control group， and the levels in the DFU group were significantly higher than those in the T2DM group （P < 0.05）. The levels of sFlt-1， Lp-PLA2， MHR， and ICAM-1 increased progressively as the Wagner grades increased （P < 0.05）. The results of the correlation analysis indicated that the levels of sFlt-1， Lp-PLA2， MHR， and ICAM-1 were positively correlated with the severity of the disease （r = 0.531， 0.568， 0.624， 0.615， P < 0.05）. In comparison with the group with a good prognosis， the group with a poor prognosis was older， had higher levels of glycosylated hemoglobin， fasting blood glucose， sFlt-1， Lp-PLA2， monocyte count， MHR， and ICAM - 1， and lower HDL-C （P < 0.05）. The results of the multivariate Logistic regression analysis demonstrated that older age （OR = 1.855， 95%CI： 1.261 - 2.730）， higher glycosylated hemoglobin （OR = 1.719， 95%CI： 1.247 - 2.371）， higher fasting blood glucose （OR = 1.747， 95%CI： 1.237 - 2.467）， higher sFlt - 1 （OR = 1.719， 95%CI： 1.227 - 2.409）， higher Lp-PLA2 （OR = 1.921， 95%CI： 1.321 - 2.794）， higher monocyte count （OR = 1.889， 95% CI 1.249 - 2.856）， higher MHR （OR = 1.624， 95%CI： 1.192 - 2.214）， and higher ICAM-1 （OR = 1.948， 95% CI： 1.203 - 3.156） were all risk factors for a poor prognosis in patients with DFU. High HDL-C （OR = 0.652， 95%CI： 0.490 - 0.869） is a protective factor for a poor prognosis in patients with DFU （all P < 0.05）. The area under the curve （AUC） values for diagnosing the poor prognosis of DFU through the combined detection of soluble fms-like tyrosine kinase-1 （sFlt-1）， lipoprotein-associated phospholipase A2 （Lp-PLA2）， monocyte-to-high-density lipoprotein cholesterol ratio （MHR）， intercellular adhesion molecule-1 （ICAM-1）， and Logistic combined detection were 0.742， 0.815， 0.800， 0.811， 0.827， and 0.899， respectively. Among these， the AUC values of the combined detection of the four indicators and Logistic combined detection were relatively higher. Conclusions The levels of sFlt-1， Lp-PLA2， MHR， and ICAM-1 are closely associated with the severity of DFU. Older age， high glycated hemoglobin， high fasting blood glucose， high sFlt-1， high Lp-PLA2， high monocyte count， high MHR， and high ICAM-1 are all independent risk factors for poor prognosis in DFU patients， while HDL-C is a protective factor for poor prognosis in patients with DFU. The combined detection of sFlt-1， Lp-PLA2， MHR， and ICAM-1 has a higher predictive value than individual indicators and may provide a novel perspective for the prognostic assessment of DFU.

Key words: diabetic foot ulcer, soluble vascular endothelial growth factor receptor-1, lipoprotein-associated phospholipase A2, monocyte/high-density lipoprotein cholesterol ratio, intercellular adhesion molecule-1, severity of disease, prognosis

CLC Number:

R587.2

Xuan SUN,Lu XU,Yan GAO,Yingying MA,Jidong ZHAO. The combined predictive value of sFlt-1， Lp-PLA2， MHR and ICAM-1 for the severity and prognosis of diabetic foot ulcers[J]. The Journal of Practical Medicine, 2026, 42(10): 1703-1711.

Figures/Tables 9

Tab.1

Comparison of baseline data among the three groups of research subjects"

基线资料	DFU组（n = 415）	T2DM组（n = 108）	对照组（n = 108）	χ² /F值	P值
年龄（ $x ˉ$ ± s）/岁	60.34 ± 6.87	59.41 ± 6.42	58.99 ± 6.36	2.156	0.117
病程（ $x ˉ$ ± s）/年	10.12 ± 1.21	9.82 ± 1.06	-	1.608	0.109
BMI（ $x ˉ$ ± s）/（kg/m²）	23.05 ± 1.34	22.92 ± 1.23	22.79 ± 1.19	1.876	0.154
糖化血红蛋白（ $x ˉ$ ± s）/%	8.71 ± 0.89^*#	7.94 ± 0.81^*	4.96 ± 0.51	888.365	< 0.001
空腹血糖（ $x ˉ$ ± s）/（mmol/L）	8.57 ± 0.86^*#	7.82 ± 0.83^*	5.67 ± 0.74	517.555	< 0.001
性别				0.577	0.749
男	221（53.25）	52（48.16）	55（50.93）
女	194（46.75）	56（51.85）	53（49.07）
冠心病	132（31.81）	31（28.70）	30（27.78）	0.528	0.768
高血压	153（36.87）	39（36.11）	36（33.33）	0.281	0.869
吸烟史	191（46.02）	48（44.44）	46（42.59）	0.263	0.877
饮酒史	283（68.19）	72（66.67）	69（63.89）	0.446	0.800

Tab.1

Tab.2

Tab.3

Tab.4

Tab.5

Univariate analysis of the prognosis of DFU patients"

因素	预后不良组（n = 112）	预后良好组（n = 303）	χ² /t值	P值
年龄/岁	64.67 ± 6.52	58.74 ± 6.02	8.708	< 0.001
病程/年	10.29 ± 1.22	10.06 ± 1.16	1.768	0.078
BMI/（kg/m²）	23.10 ± 2.35	22.92 ± 2.31	0.701	0.483
糖化血红蛋白（ $x ˉ$ ± s）/%	9.51 ± 0.97	8.42 ± 0.85	11.152	< 0.001
空腹血糖/（mmol/L）	9.17 ± 0.93	8.35 ± 0.84	8.571	< 0.001
性别/[例（%）]			0.553	0.457
男	63（56.25）	158（52.15）
女	49（43.75）	145（47.85）
冠心病/[例（%）]	39（34.82）	93（30.69）	0.643	0.423
高血压/[例（%）]	44（39.29）	109（35.97）	0.385	0.535
吸烟史/[例（%）]	55（49.11）	136（44.88）	0.587	0.444
饮酒史/[例（%）]	80（71.43）	203（67.00）	0.740	0.390
sFlt-1/（ng/mL）	0.96 ± 0.17	0.78 ± 0.14	10.949	< 0.001
Lp-PLA₂/（μg/L）	284.19 ± 45.02	238.82 ± 31.28	11.557	< 0.001
单核细胞计数/（×10⁹·L^-1）	0.51 ± 0.10	0.40 ± 0.07	12.561	< 0.001
HDL-C/（mmol/L）	0.88 ± 0.15	0.99 ± 0.24	4.532	< 0.001
MHR	0.58 ± 0.17	0.40 ± 0.09	13.911	< 0.001
ICAM-1/（μg/L）	436.37 ± 103.65	322.96 ± 78.36	11.671	< 0.001

Tab.5

Tab.6

Tab.7

Tab.8

Fig.1

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组别	例数	sFlt-1/（ng/mL）	Lp-PLA₂/（μg/L）	单核细胞计数/ （×10⁹·L^-1）	HDL-C/（mmol/L）	MHR	ICAM-1/（μg/L）
DFU组	415	0.83 ± 0.26^*#	251.06 ± 38.13^*#	0.43 ± 0.13^*#	0.96 ± 0.24^*#	0.45 ± 0.09^*#	353.57 ± 78.62^*#
T2DM组	108	0.61 ± 0.18^*	191.51 ± 29.02^*	0.32 ± 0.08^*	1.32 ± 0.30^*	0.24 ± 0.06^*	146.48 ± 26.16^*
对照组	108	0.23 ± 0.06	128.74 ± 18.53	0.22 ± 0.05	1.41 ± 0.33	0.16 ± 0.03	102.95 ± 18.24
F值		312.417	597.821	164.991	165.172	755.287	877.772
P值		< 0.001	< 0.001	< 0.001	< 0.001	< 0.001	< 0.001

组别	例数	sFlt-1/（ng/mL）	Lp-PLA₂/（μg/L）	单核细胞计数/ （×10⁹·L^-1）	HDL-C/（mmol/L）	MHR	ICAM-1/（μg/L）
1级组	155	0.66 ± 0.11	219.884 ± 24.76	0.34 ± 0.07	1.17 ± 0.20	0.29 ± 0.09	309.89 ± 28.42
2级组	127	0.79 ± 0.18^*	252.59 ± 27.64^*	0.42 ± 0.08^*	0.94 ± 0.18^*	0.45 ± 0.13^*	342.86 ± 35.07^*
3级组	72	0.97 ± 0.28^*#	274.98 ± 32.03^*#	0.51 ± 0.10^*#	0.80 ± 0.15^*#	0.64 ± 0.21^*#	385.71 ± 42.14^*#
4级组	61	1.19 ± 0.34^*#&	298.87 ± 42.86^*#&	0.60 ± 0.12^*#&	0.67 ± 0.13^*#&	0.90 ± 0.28^*#&	448.93 ± 81.22^*#&
F值		103.956	121.562	152.509	147.703	223.331	160.621
P值		< 0.001	< 0.001	< 0.001	< 0.001	< 0.001	< 0.001

变量	变量性质	赋值方法
DFU	Y	0=预后良好，1=预后不良
年龄	X₁	原值输入
糖化血红蛋白/%	X₂	原值输入
空腹血糖/（mmol/L）	X₃	原值输入
sFlt-1/（ng/mL）	X₄	原值输入
Lp-PLA₂/（μg/L）	X₅	原值输入
单核细胞计数/（×10⁹·L^-1）	X₆	原值输入
HDL-C/（mmol/L）	X₇	原值输入
MHR	X₈	原值输入
ICAM-1/（μg/L）	X₉	原值输入

变量	β	SE	Wald χ²	P值	OR	95%CI
年龄	0.618	0.197	9.841	0.002	1.855	1.261 ~ 2.730
糖化血红蛋白	0.542	0.164	10.922	0.001	1.719	1.247 ~ 2.371
空腹血糖	0.558	0.176	10.052	0.002	1.747	1.237 ~ 2.467
sFlt-1	0.542	0.172	9.930	0.002	1.719	1.227 ~ 2.409
Lp-PLA₂	0.653	0.191	11.689	0.001	1.921	1.321 ~ 2.794
单核细胞计数	0.636	0.211	9.086	0.003	1.889	1.249 ~ 2.856
HDL-C	-0.427	0.146	8.554	0.003	0.652	0.490 ~ 0.869
MHR	0.485	0.158	9.423	0.002	1.624	1.192 ~ 2.214
ICAM-1	0.667	0.246	7.352	0.007	1.948	1.203 ~ 3.156

指标	截断值	AUC值	95%CI	P值	敏感度/%	特异度/%
sFlt-1/（ng/mL）	0.86	0.742^*	0.697 ~ 0.783	< 0.001	67.86	70.96
Lp-PLA₂/（μg/L）	275.42	0.815^*	0.774 ~ 0.851	< 0.001	65.18	86.80
MHR	0.49	0.800^*	0.758 ~ 0.837	< 0.001	67.86	86.47
ICAM-1/（μg/L）	373.12	0.811^*	0.770 ~ 0.848	< 0.001	76.79	72.28
4项指标联合检测	-	0.827	0.787 ~ 0.862	< 0.001	82.14	71.29
logistic联合	-	0.899	0.866 ~ 0.926	< 0.001	92.86	81.85

The combined predictive value of sFlt-1， Lp-PLA2， MHR and ICAM-1 for the severity and prognosis of diabetic foot ulcers

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