血清血管生成素样蛋白2与2型糖尿病性视网膜病变的关系

doi:10.3969/j.issn.1004-583X.2024.06.003

摘要/Abstract

摘要：

目的探讨血清血管生成素样蛋白2(angiopoietin-like protein 2,ANGPTL2)与2型糖尿病性视网膜病变(diabetic retinopathy,DR)的关系。方法选取2019年1-12月在宁波大学附属第一医院内分泌科就诊的2型糖尿病(type 2 diabetes mellitus,T2DM)患者168例,其中合并DR患者84例(DR组),无DR患者84例(NDR组)。收集并比较两组一般资料和血清学指标。通过二分类logistic回归分析探究DR的危险因素,并绘制受试者工作特征(receiver operating characteristic, ROC)曲线评估血清ANGPTL2、糖化血红蛋白(glycosylated hemoglobin,HbA₁c)对DR的预测价值。结果一般资料比较:与NDR组比较,DR组病程更长,臀围较小,差异均有统计学意义(P<0.05);血清学指标比较:与NDR组比较,DR组患者血清ANGPTL2、空腹血糖、HbA₁c较高,2 hC肽水平较低,差异均有统计学意义(P<0.05)。二分类logistic回归分析提示,高水平血清ANGPTL2(OR=1.766,95%CI:1.115~2.797)、HbA₁c(OR=2.423, 95%CI:1.258~4.669)是DR的危险因素。血清ANGPTL2预测DR的ROC曲线下面积为0.728(95%CI:0.653~0.803),预测效能中等。HbA₁c预测DR的ROC曲线下面积为0.682(95%CI:0.580~0.784),预测效能较低。结论高水平血清ANGPTL2、HbA₁c是DR的危险因素,血清ANGPTL2对预测该疾病的发生具有一定的参考意义。

关键词: 血管生成素样蛋白2, 2型糖尿病性视网膜病变, 糖化血红蛋白

Abstract:

Objective To explore the correlation between serum angiopoietin-like protein 2 (ANGPTL2) and diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM). Methods A total of 168 T2DM patients aged 18-80 years who attended the Department of Endocrinology of the First Affiliated Hospital of Ningbo University from January 2019 to December 2019 were selected, including 84 patients with DR (DR group) and 84 patients without non-DR (NDR group). The baseline information and serological indicators were collected and compared between the two groups. The risk factors of DR were explored by binary logistic regression analysis, and the predictive value of serum ANGPTL2 and glycosylated hemoglobin (HbA₁c) for DR was assessed by plotting receiver operating characteristic (ROC) curves. Results In the comparison of baseline information, DR group had significantly longer disease duration and smaller hip circumference relative to the NDR group (all P<0.05). In the comparison of serological indicators, DR group had significantly higher serum ANGPTL2, fasting blood glucose (FBG) and HbA₁c, and lower 2-hour postprandial C-peptide compared to the NDR group (all P<0.05). Binary logistic regression analysis suggested that high serum ANGPTL2 (OR=1.766, 95%CI: 1.115-2.797) and HbA₁c (OR=2.423, 95%CI: 1.258-4.669) levels were risk factors for DR (all P<0.05). The area under the ROC curve (AUC) for serum ANGPTL2 predicting DR was 0.728(95%CI: 0.653-0.803), with a moderate predictive efficacy. The AUC for HbA₁c predicting DR was 0.682(95%CI: 0.580-0.784), with a low predictive efficacy. Conclusion High serum levels of ANGPTL2 and HbA₁c levels are risk factors for DR, and serum ANGPTL2 levels are informative in predicting the disease.

Key words: angiopoietin-like protein 2, type 2 diabetic retinopathy, glycosylated hemoglobin

中图分类号:

R587

王翔, 林仿, 励丽, 孙杰辉. 血清血管生成素样蛋白2与2型糖尿病性视网膜病变的关系[J]. 临床荟萃, 2024, 39(6): 501-505.

Wang Xiang, Lin Fang, Li Li, Sun Jiehui. Correlation between serum angiopoietin-like protein 2 and diabetic retinopathy in type 2 diabetes mellitus[J]. Clinical Focus, 2024, 39(6): 501-505.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2024.06.003

https://huicui.hebmu.edu.cn/CN/Y2024/V39/I6/501

图/表 3

参考文献 26

[1]	Magliano DJ, Boyko EJ, IDF Diabetes Atlas 10th edition scientific committee. IDF DIABETES ATLAS[M]. 10th edition. Brussels: International Diabetes Federation, 2021.
[2]	Saeedi P, Petersohn I, Salpea P, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition[J]. Diabetes Res Clin Pract, 2019, 157: 107843.
[3]	Willis JR, Doan QV, Gleeson M, et al. Vision-related functional burden of diabetic retinopathy across severity levels in the United States[J]. JAMA Ophthalmol, 2017, 135(9): 926-932. doi: 10.1001/jamaophthalmol.2017.2553 pmid: 28750122
[4]	Lin K, Hsih W, Lin Y, et al. Update in the epidemiology, risk factors, screening, and treatment of diabetic retinopathy[J]. J Diabetes Investig, 2021, 12(8): 1322-1325.
[5]	Wong TY, Cheung CMG, Larsen M, et al. Diabetic retinopathy[J]. Nat Rev Dis Primers, 2016, 2(1): 16012.
[6]	Sasaki Y, Ohta M, Desai D, et al. Angiopoietin-like protein 2 (ANGPTL2) promotes adipose tissue macrophage and T lymphocyte accumulation and leads to insulin resistance[J]. PLoS One, 2015, 10(7): e0131176.
[7]	Kadomatsu T, Endo M, Miyata K, et al. Diverse roles of ANGPTL2 in physiology and pathophysiology[J]. Trends Endocrinol Metab, 2014, 25(5): 245-254.
[8]	Hirasawa M, Takubo K, Osada H, et al. Angiopoietin-like protein 2 is a multistep regulator of inflammatory neovascularization in a murine model of age-related macular degeneration[J]. J Biol Chem, 2016, 291(14): 7373-7385. doi: 10.1074/jbc.M115.710186 pmid: 26839315
[9]	Teo ZL, Tham YC, Yu M, et al. Global prevalence of diabetic retinopathy and projection of burden through 2045: Systematic review and meta-analysis[J]. Ophthalmology, 2021, 128(11): 1580-1591. doi: 10.1016/j.ophtha.2021.04.027 pmid: 33940045
[10]	Morinaga J, Kadomatsu T, Miyata K, et al. Angiopoietin-like protein 2 increases renal fibrosis by accelerating transforming growth factor-β signaling in chronic kidney disease[J]. Kidney Int, 2016, 89(2): 327-341. doi: 10.1016/j.kint.2015.12.021 pmid: 26806834
[11]	Yang S, Zhang J, Wang S, et al. Knockdown of angiopoietin-like protein 2 ameliorates diabetic nephropathy by inhibiting TLR4[J]. Cell Physiol Biochem, 2017, 43(2): 685-696. doi: 10.1159/000480654 pmid: 28946139
[12]	Goldfine AB, Shoelson SE. Therapeutic approaches targeting inflammation for diabetes and associated cardiovascular risk[J]. J Clin Invest, 2017, 127(1): 83-93. doi: 88884 pmid: 28045401
[13]	Mussa BM, Srivastava A, Al-Habshi A, et al. Inflammatory biomarkers levels in T2DM emirati patients with diabetic neuropathy[J]. Diabetes Metab Syndr Obes, 2021, 14: 3389-3397.
[14]	Soto I, Krebs MP, Reagan AM, et al. Vascular inflammation risk factors in retinal disease[J]. Annu Rev Vis Sci, 2019, 5(1): 99-122.
[15]	Doi Y, Ninomiya T, Hirakawa Y, et al. Angiopoietin-like protein 2 and risk of type 2 diabetes in a general Japanese population[J]. Diabetes Care, 2013, 36(1): 98-100.
[16]	Gellen B, Thorin-Trescases N, Sosner P, et al. ANGPTL2 is associated with an increased risk of cardiovascular events and death in diabetic patients[J]. Diabetologia, 2016, 59(11): 2321-2330. doi: 10.1007/s00125-016-4066-5 pmid: 27491833
[17]	Wang Y, Zheng Z, Yang Y, et al. Angiopoietin-like 2 is a potential biomarker for diabetic foot patients[J]. BMC Endocr Disord, 2020, 20(1): 178.
[18]	Sun H, Zheng J, Chen S, et al. Enhanced expression of ANGPTL2 in the microvascular lesions of diabetic glomerulopathy[J]. Nephron Exp Nephrol, 2007, 105(4): e117-e123.
[19]	Ishii T, Furuya F, Takahashi K, et al. Angiopoietin-like protein 2 promotes the progression of diabetic kidney disease[J]. J Clin Endocrinol Metab, 2019, 104(1): 172-180. doi: 10.1210/jc.2017-02705 pmid: 30137449
[20]	Toyono T, Usui T, Yokoo S, et al. Angiopoietin-like protein 2 is a potent hemangiogenic and lymphangiogenic factor in corneal inflammation[J]. Invest Ophthalmol Vis Sci, 2013, 54(6): 4278-4285.
[21]	Tabata M, Kadomatsu T, Fukuhara S, et al. Angiopoietin-like protein 2 promotes chronic adipose tissue inflammation and obesity-related systemic insulin resistance[J]. Cell Metab, 2009, 10(3): 178-188. doi: 10.1016/j.cmet.2009.08.003 pmid: 19723494
[22]	Jang HN, Moon MK, Koo BK. Prevalence of diabetic retinopathy in undiagnosed diabetic patients: A nationwide population-based study[J]. Diabetes Metab J, 2022, 46(4): 620-629. doi: 10.4093/dmj.2021.0099 pmid: 35193173
[23]	Bethel MA, Diaz R, Castellana N, et al. HbA1c change and diabetic retinopathy during GLP-1 receptor agonist cardiovascular outcome trials: A meta-analysis and meta-regression[J]. Diabetes Care, 2021, 44(1): 290-296.
[24]	Yao L, Zhong Y, Wu J, et al. Multivariable logistic regression and back propagation artificial neural network to predict diabetic retinopathy[J]. Diabetes Metab Syndr Obes, 2019, 12: 1943-1951.
[25]	Keles A, Sonmez K, Erol YO, et al. Vitreous levels of vascular endothelial growth factor, stromal cell-derived factor-1α, and angiopoietin-like protein 2 in patients with active proliferative diabetic retinopathy[J]. Graefes Arch Clin Exp Ophthalmol, 2021, 259(1): 53-60.
[26]	Yin R, Zhang N, Zhang D, et al. Higher levels of circulating ANGPTL2 are associated with macular edema in patients with type 2 diabetes[J]. Medicine (Baltimore), 2021, 100(6): e24638.

观察指标	NDR组(n=84)	DR组(n=84)	t/Z/χ²值	P值
性别[例(%)]
男女	53(63.1) 31(36.9)	53(63.1) 31(36.9)	0.000	1.000
年龄(岁)	55.30±10.29	56.25±10.40	-0.597	0.552
身高(m)	1.64(1.58, 1.70)	1.65(1.60, 1.69)	-0.587	0.557
体重(kg)	65.75(59.23, 77.00)	66.60(58.00, 76.60)	-0.271	0.787
BMI(kg/m²)	24.22(23.07, 27.26)	24.05(21.79, 27.14)	-1.204	0.229
收缩压(mmHg)	135.50(127.00, 147.00)	134.00(124.00, 147.00)	-0.205	0.838
舒张压(mmHg)	80.50(74.50, 88.00)	77.00(71.00, 86.00)	-1.383	0.167
腰围(cm)	86.50(81.25, 95.00)	90.00(81.50, 94.00)	-0.223	0.824
臀围(cm)	95.00(90.25, 100.75)	93.00(89.00, 97.00)	-2.258	0.024
吸烟[例(%)]
无有	22(26.2) 62(73.8)	29(34.5) 55(65.5)	1.380	0.240
饮酒[例(%)]
无有	21(25.0) 63(75.0)	29(34.5) 55(65.5)	1.822	0.177
病程(年)	5.00(2.00, 10.00)	8.00(4.25, 10.00)	-2.786	0.005
TC(mmol/L)	4.89±1.15	4.84±1.10	0.254	0.800
LDL-C(mmol/L)	3.05±0.96	3.02±0.88	0.145	0.885
TG(mmol/L)	1.53(0.96, 2.37)	1.45(1.15, 2.20)	-0.620	0.536
HDL-C(mmol/L)	1.10(0.99, 1.25)	1.10(0.97, 1.33)	-0.187	0.852
FPG(mmol/L)	8.40±2.67	10.29±3.21	-3.048	0.003
2 hPBG(mmol/L)	14.05±5.43	15.24±5.16	-1.064	0.290
FINS(mIU/L)	7.41(4.58, 15.35)	5.21(2.92, 11.92)	-1.068	0.285
2 hINS(mIU/L)	24.29(13.28, 46.10)	19.37(8.38, 30.91)	-1.395	0.163
FC-P(nmol/L)	2.05±0.95	1.81±0.93	1.229	0.222
2 hC-P(nmol/L)	4.61(2.02, 6.40)	2.74(2.01, 4.61)	-2.235	0.025
HbA₁c(mmol/L)	7.40(6.60, 8.50)	8.95(7.55, 11.03)	-3.199	0.001
HOMA-IR	2.28(1.65, 4.54)	2.80(0.95, 4.66)	-0.487	0.626
HOMA-β	32.54(16.41, 47.97)	19.19(10.43, 32.52)	-1.786	0.074
ANGPTL2(ng/ml)	7.59(6.66, 8.64)	8.85(7.75, 10.42)	-5.103	0.000

观察指标	NDR组(n=84)	DR组(n=84)	t/Z/χ²值	P值
性别[例(%)]
男女	53(63.1) 31(36.9)	53(63.1) 31(36.9)	0.000	1.000
年龄(岁)	55.30±10.29	56.25±10.40	-0.597	0.552
身高(m)	1.64(1.58, 1.70)	1.65(1.60, 1.69)	-0.587	0.557
体重(kg)	65.75(59.23, 77.00)	66.60(58.00, 76.60)	-0.271	0.787
BMI(kg/m²)	24.22(23.07, 27.26)	24.05(21.79, 27.14)	-1.204	0.229
收缩压(mmHg)	135.50(127.00, 147.00)	134.00(124.00, 147.00)	-0.205	0.838
舒张压(mmHg)	80.50(74.50, 88.00)	77.00(71.00, 86.00)	-1.383	0.167
腰围(cm)	86.50(81.25, 95.00)	90.00(81.50, 94.00)	-0.223	0.824
臀围(cm)	95.00(90.25, 100.75)	93.00(89.00, 97.00)	-2.258	0.024
吸烟[例(%)]
无有	22(26.2) 62(73.8)	29(34.5) 55(65.5)	1.380	0.240
饮酒[例(%)]
无有	21(25.0) 63(75.0)	29(34.5) 55(65.5)	1.822	0.177
病程(年)	5.00(2.00, 10.00)	8.00(4.25, 10.00)	-2.786	0.005
TC(mmol/L)	4.89±1.15	4.84±1.10	0.254	0.800
LDL-C(mmol/L)	3.05±0.96	3.02±0.88	0.145	0.885
TG(mmol/L)	1.53(0.96, 2.37)	1.45(1.15, 2.20)	-0.620	0.536
HDL-C(mmol/L)	1.10(0.99, 1.25)	1.10(0.97, 1.33)	-0.187	0.852
FPG(mmol/L)	8.40±2.67	10.29±3.21	-3.048	0.003
2 hPBG(mmol/L)	14.05±5.43	15.24±5.16	-1.064	0.290
FINS(mIU/L)	7.41(4.58, 15.35)	5.21(2.92, 11.92)	-1.068	0.285
2 hINS(mIU/L)	24.29(13.28, 46.10)	19.37(8.38, 30.91)	-1.395	0.163
FC-P(nmol/L)	2.05±0.95	1.81±0.93	1.229	0.222
2 hC-P(nmol/L)	4.61(2.02, 6.40)	2.74(2.01, 4.61)	-2.235	0.025
HbA₁c(mmol/L)	7.40(6.60, 8.50)	8.95(7.55, 11.03)	-3.199	0.001
HOMA-IR	2.28(1.65, 4.54)	2.80(0.95, 4.66)	-0.487	0.626
HOMA-β	32.54(16.41, 47.97)	19.19(10.43, 32.52)	-1.786	0.074
ANGPTL2(ng/ml)	7.59(6.66, 8.64)	8.85(7.75, 10.42)	-5.103	0.000

变量	回归系数	标准误	Waldχ²值	P值	OR值	95%CI
变量	回归系数	标准误	Waldχ²值	P值	OR值	下限	上限
ANGPTL2	0.569	0.235	5.878	0.015	1.766	1.115	2.797
FPG	-0.178	0.196	0.827	0.363	0.837	0.570	1.228
2 hC-P	-0.181	0.206	0.775	0.379	0.834	0.557	1.249
病程	0.053	0.074	0.499	0.480	1.054	0.911	1.219
臀围	-0.087	0.053	2.661	0.103	0.917	0.826	1.018
HbA₁c	0.885	0.335	6.994	0.008	2.423	1.258	4.669
常量	-2.442	5.689	0.184	0.668	0.087

变量	回归系数	标准误	Waldχ²值	P值	OR值	95%CI
变量	回归系数	标准误	Waldχ²值	P值	OR值	下限	上限
ANGPTL2	0.569	0.235	5.878	0.015	1.766	1.115	2.797
FPG	-0.178	0.196	0.827	0.363	0.837	0.570	1.228
2 hC-P	-0.181	0.206	0.775	0.379	0.834	0.557	1.249
病程	0.053	0.074	0.499	0.480	1.054	0.911	1.219
臀围	-0.087	0.053	2.661	0.103	0.917	0.826	1.018
HbA₁c	0.885	0.335	6.994	0.008	2.423	1.258	4.669
常量	-2.442	5.689	0.184	0.668	0.087