Relationship between serum NLRP3 and ANGPTL4 levels and lower extremity arterial disease in type 2 diabetes mellitus

doi:10.3877/cma.j.issn.1674-0785.2022.02.003

Abstract

Abstract:

Objective

To investigate the relationship between serum nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) and angiopoietin-like 4 (ANGPTL4) levels and lower extremity arterial disease (LEAD) in type 2 diabetes mellitus (T2DM).

Methods

From January 2019 to January 2021, 89 T2DM patients with LEAD (LEAD group) treated at the Department of Endocrinology, Suzhou Hospital Affiliated to Anhui Medical University, 55 simple T2DM patients (T2DM group), and 50 healthy volunteers (healthy control group) were selected. Serum NLRP3 and ANGPTL4 levels were detected and clinical data were collected, and the correlation between NLRP3 and ANGPTL4 and resting ankle-brachial index (ABI) was analyzed by Pearson correlation analysis. Logistic regression was used to analyze the relation between NLRP3 and ANGPTL4 and T2DM combined with LEAD. Receiver operating characteristic curve (ROC) was drawn to assess the value of NLRP3 and ANGPTL4 in diagnosing T2DM combined with LEAD.

Results

Serum NLRP3 level in the LEAD group was higher than those in the NLEAD group and healthy control group (P＜0.05), and serum ANGPTL4 level was lower than those in the NLEAD group and healthy control group (P＜0.05). The levels of resting ABI and ANGPTL4 in Fontaine's stage Ⅳ patients were lower than those in stage Ⅲ and stage Ⅱa~Ⅱb patients (P＜0.05), and NLRP3 was higher than that in stage Ⅲ and stage Ⅱa~Ⅱb patients (P＜0.05). NLRP3 was negatively correlated with resting ABI (r=-0.893, P＜0.05), while ANGPTL4 was positively correlated with resting ABI (r=0.805, P＜0.05). T2DM duration ≥5 years, high insulin resistance index, and high NLRP3 were risk factors for T2DM complicated with LEAD (P＜0.05), and high ANGPTL4 was a protective factor for T2DM complicated with LEAD (P＜0.05). The area under the curve of NLRP3 plus ANGPTL4 was 0.902, which was higher than either of them alone (NLRP3: 0.698; ANGPTL4: 0.705; P＜0.05).

Conclusion

Serum NLRP3 level increases and ANGPTL4 level decreases in T2DM patients with LEAD, which is related to the occurrence and severity of T2DM patients with LEAD. The combination of NLRP3 and ANGPTL4 can provide effective information for the diagnosis of LEAD.

Key words: Type 2 diabetes, Arterial disease of lower limb, Nucleotide binding oligomerization domain-like receptor protein 3, Angiopoietin like protein 4

Jing Zhao, Su Wei, Qingfeng Li, Wei Li. Relationship between serum NLRP3 and ANGPTL4 levels and lower extremity arterial disease in type 2 diabetes mellitus[J]. Chinese Journal of Clinicians(Electronic Edition), 2022, 16(02): 124-130.

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Figures/Tables 6

项目	LEAD组（89例）	T2DM组（55例）	健康对照组（50例）	统计值	P值
年龄（岁， $x ¯$ ±s）	65.15±6.03	64.15±5.71	64.03±5.53	F=0.956	0.327
性别［例（%）］				χ²=0.446	0.800
男性	50（56.18）	34（61.82）	29（58.00）
女性	39（43.82）	21（38.18）	21（42.00）
吸烟史［例（%）］	47（52.81）	28（50.91）	20（40.00）	χ²=3.991	0.136
饮酒史［例（%）］	43（48.31）	26（47.27）	18（36.00）	χ²=2.046	0.360
基础疾病［例（%）］
高血压	55（61.80）	23（41.82）	-	χ²=5.467	0.019
高脂血症	48（53.93）	20（36.36）	-	χ²=4.210	0.040
心脑血管疾病	27（30.34）	8（14.55）	-	χ²=4.608	0.032
T2DM病程［例（%）］				χ²=5.574	0.018
≥5年	52（58.43）	21（38.18）	-
＜5年	37（41.57）	34（61.82）	-
TC（mmol/L， $x ¯$ ±s）	5.41±0.72^ab	5.02±0.63^a	4.35±0.69	F=12.349	＜0.001
TG（mmol/L， $x ¯$ ±s）	1.98±0.21^ab	1.62±0.18^a	1.50±0.13	F=19.642	＜0.001
HDL-C（mmol/L， $x ¯$ ±s）	1.02±0.24^a	1.09±0.21^a	1.21±0.29	F=9.154	＜0.001
LDL-C（mmol/L， $x ¯$ ±s）	2.75±0.42^a	2.72±0.39^a	2.51±0.34	F=8.107	＜0.001
FPG（mmol/L， $x ¯$ ±s）	8.65±1.42^ab	7.71±1.03^a	5.01±0.57	F=17.439	＜0.001
FINS（uU/ml， $x ¯$ ±s）	9.15±2.43^ab	8.02±2.17^a	6.11±1.96	F=13.264	＜0.001
HOMA-IR（ $x ¯$ ±s）	3.52±0.61^ab	2.75±0.45^a	1.36±0.20	F=16.669	＜0.001
NLRP3（pg/ml）	263.15±65.09^ab	183.67±41.92^a	87.24±14.42	F=35.165	＜0.001
ANGPTL4（mg/L）	20.33±6.09^ab	35.15±10.18^a	53.26±16.94	F=51.024	＜0.001

项目	LEAD组（89例）	T2DM组（55例）	健康对照组（50例）	统计值	P值
年龄（岁， $x ¯$ ±s）	65.15±6.03	64.15±5.71	64.03±5.53	F=0.956	0.327
性别［例（%）］				χ²=0.446	0.800
男性	50（56.18）	34（61.82）	29（58.00）
女性	39（43.82）	21（38.18）	21（42.00）
吸烟史［例（%）］	47（52.81）	28（50.91）	20（40.00）	χ²=3.991	0.136
饮酒史［例（%）］	43（48.31）	26（47.27）	18（36.00）	χ²=2.046	0.360
基础疾病［例（%）］
高血压	55（61.80）	23（41.82）	-	χ²=5.467	0.019
高脂血症	48（53.93）	20（36.36）	-	χ²=4.210	0.040
心脑血管疾病	27（30.34）	8（14.55）	-	χ²=4.608	0.032
T2DM病程［例（%）］				χ²=5.574	0.018
≥5年	52（58.43）	21（38.18）	-
＜5年	37（41.57）	34（61.82）	-
TC（mmol/L， $x ¯$ ±s）	5.41±0.72^ab	5.02±0.63^a	4.35±0.69	F=12.349	＜0.001
TG（mmol/L， $x ¯$ ±s）	1.98±0.21^ab	1.62±0.18^a	1.50±0.13	F=19.642	＜0.001
HDL-C（mmol/L， $x ¯$ ±s）	1.02±0.24^a	1.09±0.21^a	1.21±0.29	F=9.154	＜0.001
LDL-C（mmol/L， $x ¯$ ±s）	2.75±0.42^a	2.72±0.39^a	2.51±0.34	F=8.107	＜0.001
FPG（mmol/L， $x ¯$ ±s）	8.65±1.42^ab	7.71±1.03^a	5.01±0.57	F=17.439	＜0.001
FINS（uU/ml， $x ¯$ ±s）	9.15±2.43^ab	8.02±2.17^a	6.11±1.96	F=13.264	＜0.001
HOMA-IR（ $x ¯$ ±s）	3.52±0.61^ab	2.75±0.45^a	1.36±0.20	F=16.669	＜0.001
NLRP3（pg/ml）	263.15±65.09^ab	183.67±41.92^a	87.24±14.42	F=35.165	＜0.001
ANGPTL4（mg/L）	20.33±6.09^ab	35.15±10.18^a	53.26±16.94	F=51.024	＜0.001

Fontaine's分期	例数	静息ABI指数	NLRP3（pg/ml）	ANGPTL4（mg/L）
Ⅱa~Ⅱb期	35	0.81±0.07	229.35±12.44	24.51±1.36
Ⅲ期	30	0.74±0.10^a	260.30±23.81^a	20.16±5.19^a
Ⅳ期	24	0.68±0.07^ab	316.00±11.38^ab	14.45±0.21^ab
F值		13.094	23.061	26.412
P值		＜0.001	＜0.001	＜0.001

因素	β值	SE	Wald χ²值	OR值	95%CI	P值
高血压	0.063	0.057	1.222	1.065	0.952~1.191	0.356
高脂血症	0.101	0.093	1.179	1.106	0.922~1.327	0.437
心脑血管疾病	0.213	0.192	1.231	1.237	0.849~1.803	0.349
T2DM病程	0.359	0.101	12.634	1.432	1.175~1.745	＜0.001
TC	0.042	0.039	1.160	1.043	0.966~1.126	0.504
TG	0.071	0.068	1.090	1.074	0.940~1.227	0.624
FPG	0.163	0.157	1.078	1.177	0.865~1.601	0.719
FINS	0.143	0.131	1.192	1.154	0.892~1.491	0.401
HOMA-IR	0.477	0.119	16.067	1.611	1.276~2.034	＜0.001
NLRP3	0.609	0.195	9.754	1.839	1.255~2.694	0.002
ANGPTL4	-0.413	0.176	5.506	0.662	0.469~0.934	0.009

因素	AUC（95%CI）	P值	敏感度（%）	特异度（%）	约登指数
NLRP3	0.698（0.616~0.772）	＜0.001	71.10	69.09	0.425
ANGPTL4	0.705（0.623~0.778）	＜0.001	74.16	65.45	0.337
联合	0.902（0.841~0.945）	＜0.001	91.01	90.09	0.799

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