糖尿病视网膜病变与患者血清丝氨酸蛋白酶抑制剂、胰岛素抵抗及糖脂代谢相关性的研究

doi:10.3877/cma.j.issn.2095-2007.2017.03.002

目的

研究2型糖尿病视网膜病变(DR)患者血清腹腔脂肪型丝氨酸蛋白酶抑制剂(Vaspin)水平的变化，并分析DR与糖脂代谢、胰岛素敏感性等的相关性，从而进一步探讨Vaspin在2型DR发生发展中所起的作用。

方法

选取山东省临沂市中心医院眼科2014年1月至2016年12月临床检查确诊为DR的150例2型糖尿病患者的临床资料。将患者分为无DR(NDR)组、非增生型DR(NPDR)组及增生型DR(PDR)组，每组均为50例(100只眼)。另选择同期健康体检者50名作为对照组。全部入选的糖尿病患者均行视力、眼压、裂隙灯显微镜、间接检眼镜及荧光素眼底血管造影检查。记录纳入研究者的年龄、2型糖尿病病程、身高、体重及体重指数(BMI)。测定受检者血清空腹血糖(FBG)、空腹胰岛素(FINS)、糖化血红蛋白(HbA1c)、胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDLC)及低密度脂蛋白(LDLC)。Vaspin测定采用酶联免疫吸附试验。对调查者的年龄、身高、体重、BMI及血清指标进行正态分布检验，以均数±标准差(±s)方式表示。组间均数比较采用单因素方差分析，当差异有统计学意义时，进一步两两比较。计算胰岛素分泌指数及胰岛素抵抗指数。血清指标和分期之间的相关性分别进行单因素相关分析，以及校正性别、年龄及BMI等因素后的多因素相关分析。

结果

将NDR组、NPDR组及PDR组受检者的年龄、身高、体重及BMI进行比较，差异均无统计学意义(F＝0.509，0.343，0.348，0.357；P>0.05)；将3组受检者的病程进行比较，差异有统计学意义(F＝2.397，P<0.05)。将NDR组、NPDR组、PDR组及对照组受检者的血清HbA1c、FBG、FINS、TC、HDLC、LDLC、Vaspin、HOMA－IS及HOMA－IR水平经单因素方差分析，差异均有统计学意义(F＝5.66，5.57，7.90，5.06，6.87，9.19，7.27，4.89，8.56；P<0.05)；与对照组相比，NDR组、NPDR组及PDR组的血清中Vaspin含量明显降低。将3组血清TG水平进行比较，差异无统计学意义(F＝2.19，P>0.05)。经单因素相关性分析，DR分期与血清HbA1c、FBG、FINS、LDLC、HOMA－IR、Vaspin、HOMA－IS及HDLC水平显著相关(r＝0.962，0.861，0.862，0.662，0.613，－0.965，－0.678，－0.853；P<0.05)。校正性别、年龄及BMI等因素后，经多因素相关分析，DR分期与HbA1c、FBG、FINS、LDLC及HOMA－IR水平显著相关(r＝0.467，0.598，0.658，0.357，0.377；P<0.05)，并且与血清Vaspin、HOMA－IS及HDLC下降显著相关(r＝－0.612，－0.472，－0.367；P<0.05)。DR各分期组的Vaspin与HDLC、HOMA－IS呈显著相关(r＝0.801，0.715；P<0.05)，与HOMA－IR呈负相关(r＝0.690，P<0.05)。

结论

研究证实糖尿病视网膜病变患者血清中的Vaspin水平明显降低，可以影响胰岛素的敏感性，与血脂代谢异常密切相关。血清中Vaspin水平降低是DR发病过程中的危险因素，Vaspin在DR的发病过程起重要作用。

关键词: 糖尿病视网膜病变, Vaspin, 胰岛素抵抗

Objective

To investigate the changes of serum Vaspin levels in patients with type 2 diabetic retinopathy (DR) and to analyze its correlation with glucose metabolism and insulin sensitivity. To further investigate the role of Vaspin in the development of type 2 DR.

Methods

Seclected the clinical data of 150 patients with type 2 diabetes mellitus diagnosed in the Department of Ophthalmology of Linyi Central Hospital of Shandong from January 2014 to December 2016. The patients were divided into non DR (NDR) group, non proliferative group DR (NPDR) group and proliferative type DR (PDR) group, with 50 cases in each group. Another 50 healthy subjects were chosen as control group at the same time. All patients underwent routine ophthalmologic examination. Age, type 2 diabetes, height, weight, and body mass index (BMI) were recorded. Determination of subjects serum fasting blood glucose (FBG), fasting insulin (FINS), glycosylated hemoglobin (HbA1c), cholesterol (TC), triglyceride (TG), high density lipoprotein (HDLC) and low density lipoprotein (LDLC). Enzyme linked immunosorbent assay (ELISA) was used for the determination of Vaspin. The age, height, weight, BMI and serum indexes of the subjects were tested by normal distribution, and expressed by mean±standard(±s)deviation. The mean between groups were compared by single factor analysis of variance. When the difference was statistically significant, they were further compared with each other. The correlation between serum markers and stages was analyzed by univariate correlation analysis, and the multivariate correlation analysis was performed after adjusting for gender, age, and BMI.

Results

Three DR groups subject age height, weight and BMI were compared, there were no significant differences (F=0.509, 0.343, 0.348, 0.357; P>0.05); the 3 groups of subjects was compared, the difference was statistically significant (F=2.397, P<0.05). Three DR groups and control group by comparing the subjects of each serum level, using single factor variance analysis, the differences were statistically significant (F=5.66, 5.57, 7.90, 5.06, 6.87, 9.19, 7.27, 4.89, 8.56; P<0.05); compared with the control group, significantly decreased the serum levels of Vaspin in three DR groups. The difference of serum TG levels between the 3 groups was not statistically significant (F=2.19, P>0.05). By single factor analysis correlation, DR stage were significantly correlated with each serum level (r=0.962, 0.861, 0.862, 0.662, 0.613, -0.965, -0.678, -0.853; P<0.05). Adjusted for gender, age and BMI factors, multivariate analysis, DR stage were significantly correlated with HbA1c, FBG, FINS, LDLC and HOMA-IR levels (r=0.467, 0.598, 0.658, 0.357, 0.377; P<0.05), and the decline was significantly correlated with serum Vaspin, HOMA-IS and HDLC (r=-0.612, -0.472, -0.367; P<0.05). Was significantly related to DR stage group Vaspin and HDLC, HOMA-IS (r=0.801, 0.715; P<0.05), and negatively correlated with HOMA-IR (r=0.690, P<0.05).

Conclusions

tudies have shown that the serum levels of Vaspin in diabetic retinopathy patients are significantly lower, which can affect the sensitivity of insulin, and is closely related to abnormal lipid metabolism. The decrease of serum Vaspin level is a risk factor in the pathogenesis of DR, and Vaspin plays an important role in the pathogenesis of DR.

Key words: Diabetic retinopathy, Vaspin, Insulin resistance

表1 NDR、NPDR及PDR组受检者的年龄、病程、身高、体重及BMI资料的比较

组别	例数	平均年龄(岁)	平均病程(年)	平均身高(cm)	平均体重(kg)	平均BMI(kg/m²)
NDR组	50	42.4±7.4	6.1±0.9	160.5±9.3	65.8±15.7	22.9±4.2
NPDR组	50	48.3±5.1	8.5±1.6	163.7±11.2	70.1±12.6	23.1±7.7
PDR组	50	53.0±8.7	15.1±3.3	165.4±8.6	65.9±10.2	23.6±3.9
F值	?	0.509	2.397	0.343	0.348	0.357
P值	?	>0.05	<0.05	>0.05	>0.05	>0.05

表1 NDR、NPDR及PDR组受检者的年龄、病程、身高、体重及BMI资料的比较

组别	例数	平均年龄(岁)	平均病程(年)	平均身高(cm)	平均体重(kg)	平均BMI(kg/m²)
NDR组	50	42.4±7.4	6.1±0.9	160.5±9.3	65.8±15.7	22.9±4.2
NPDR组	50	48.3±5.1	8.5±1.6	163.7±11.2	70.1±12.6	23.1±7.7
PDR组	50	53.0±8.7	15.1±3.3	165.4±8.6	65.9±10.2	23.6±3.9
F值	?	0.509	2.397	0.343	0.348	0.357
P值	?	>0.05	<0.05	>0.05	>0.05	>0.05

表2 NDR组、NPDR组、PDR组及对照组受检者相关指标检测结果的比较

组别	例数	TC(mmol/L)	TG(mmol/L)	HDLC(mmol/L)	LDLC(mmol/L)	HbA1c(%)
NDR组	50	5.64±0.47^*	2.69±0.68	1.96±0.34^*	2.79±0.45	7.96±1.32^*
NPDR组	50	6.54±0.81^*	2.86±0.65	1.86±0.45^*	3.78±0.65^*	10.13±0.76^*
PDR组	50	7.15±1.32^*	3.04±0.50	1.34±0.02^*	4.41±0.57^*	12.25±0.74^*
对照组	50	4.38±0.66	1.96±0.32	2.88±0.41	2.72±0.41	4.67±0.84
F值	?	5.66	2.19	5.57	7.90	5.06
P值	?	<0.05	>0.05	<0.05	<0.05	<0.05
组别	FBG(mmol/L)	FINS(mu/l)	Vaspin(ng/ml)	HOMA－IS	HOMA－IR
NDR组	6.67±0.56^*	9.67±0.83^*	0.55±0.12^*	92.91±0.92^*	3.64±0.97^*
NPDR组	8.59±0.78^*	12.87±0.91^*	0.50±0.63^*	83.32±0.54^*	8.21±1.79^*
PDR组	11.05±1.14^*	23.33±0.60^*	0.37±0.15^*	74.91±0.75^*	11.44±1.90^*
对照组	5.81±0.56	8.87±0.62	1.01±0.31	105.60±0.98	2.57±0.37
F值	6.87	9.19	7.27	4.89	8.56
P值	<0.05	<0.05	<0.05	<0.05	<0.05

表2 NDR组、NPDR组、PDR组及对照组受检者相关指标检测结果的比较

组别	例数	TC(mmol/L)	TG(mmol/L)	HDLC(mmol/L)	LDLC(mmol/L)	HbA1c(%)
NDR组	50	5.64±0.47^*	2.69±0.68	1.96±0.34^*	2.79±0.45	7.96±1.32^*
NPDR组	50	6.54±0.81^*	2.86±0.65	1.86±0.45^*	3.78±0.65^*	10.13±0.76^*
PDR组	50	7.15±1.32^*	3.04±0.50	1.34±0.02^*	4.41±0.57^*	12.25±0.74^*
对照组	50	4.38±0.66	1.96±0.32	2.88±0.41	2.72±0.41	4.67±0.84
F值	?	5.66	2.19	5.57	7.90	5.06
P值	?	<0.05	>0.05	<0.05	<0.05	<0.05
组别	FBG(mmol/L)	FINS(mu/l)	Vaspin(ng/ml)	HOMA－IS	HOMA－IR
NDR组	6.67±0.56^*	9.67±0.83^*	0.55±0.12^*	92.91±0.92^*	3.64±0.97^*
NPDR组	8.59±0.78^*	12.87±0.91^*	0.50±0.63^*	83.32±0.54^*	8.21±1.79^*
PDR组	11.05±1.14^*	23.33±0.60^*	0.37±0.15^*	74.91±0.75^*	11.44±1.90^*
对照组	5.81±0.56	8.87±0.62	1.01±0.31	105.60±0.98	2.57±0.37
F值	6.87	9.19	7.27	4.89	8.56
P值	<0.05	<0.05	<0.05	<0.05	<0.05

表3 DR分期与检测指标的多因素相关性分析结果

检测指标	简单相关系数(r)	P值	协相关系数(r)	P值
Vaspin	－0.965	<0.05	－0.612	<0.05
FINS	0.862	<0.05	0.658	<0.05
FBG	0.861	<0.05	0.598	<0.05
HbA1c	0.962	<0.05	0.467	<0.05
TC	0.020	<0.05	0.065	>0.05
TG	0.378	>0.05	0.076	>0.05
HDLC	－0.853	<0.05	－0.367	<0.05
LDLC	0.662	<0.05	0.357	<0.05
HOMA－IS	－0.678	<0.05	－0.472	<0.05
HOMA－IR	0.613	<0.05	0.377	<0.05

表3 DR分期与检测指标的多因素相关性分析结果

检测指标	简单相关系数(r)	P值	协相关系数(r)	P值
Vaspin	－0.965	<0.05	－0.612	<0.05
FINS	0.862	<0.05	0.658	<0.05
FBG	0.861	<0.05	0.598	<0.05
HbA1c	0.962	<0.05	0.467	<0.05
TC	0.020	<0.05	0.065	>0.05
TG	0.378	>0.05	0.076	>0.05
HDLC	－0.853	<0.05	－0.367	<0.05
LDLC	0.662	<0.05	0.357	<0.05
HOMA－IS	－0.678	<0.05	－0.472	<0.05
HOMA－IR	0.613	<0.05	0.377	<0.05

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Association of diabetic retinopathy with serum serine protease inhibitors, insulin resistance and glycolipid metabolism

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Association of diabetic retinopathy with serum serine protease inhibitors, insulin resistance and glycolipid metabolism