血清载脂蛋白A5水平变化与妊娠期糖尿病的关系

doi:10.3877/cma.j.issn.1673-5250.2013.02.007

目的

探讨孕中、晚期孕妇血清载脂蛋白A5(ApoA5)浓度变化及其与妊娠期糖尿病(GDM)的关系。

方法

选择2009年7月至2010年5月在本院妇产科门诊就诊及住院的GDM孕妇182例为研究对象，并纳入GDM组，其中，孕中、晚期分别为104例，78例。选择同期于本院就诊孕龄与GDM组相同的正常葡萄糖耐量(NGT)孕妇232例纳入对照组。两组均于孕龄为20～36孕周时抽取空腹肘静脉血5 mL，测定血清总胆固醇(TC)、甘油三酯(TG)，高密度脂蛋白-胆固醇(HDL-C)，低密度脂蛋白-胆固醇(LDL-C)，空腹血糖(FBG)，空腹胰岛素(FINS)，餐后2 h血糖(PBG)，稳态模型的胰岛素抵抗指数(HOMA-IR)等指标，同时检测糖化血红蛋白(HbA1c)及血清ApoA5水平，并对其进行相关统计学分析(本研究遵循的程序符合本院人体试验委员会制定的伦理学标准，得到该委员会批准，分组征得受试对象的知情同意，并与之签署临床研究知情同意书)。两组受试对象年龄、孕龄比较，差异无统计学意义(P>0.05)。

结果

GDM组ApoA5水平高于对照组[(254.56±30.51) ng/mL vs. (219.40±21.35) ng/mL]，HDL-C水平低于对照组，两组比较，差异有统计学意义(P<0.05)。Pearson相关性分析显示，当TG≥1.7 mmol/L时，血清ApoA5水平与TG呈正相关(r＝0.349，P＝0.025)；当TG<1.7 mmol/L时，血清ApoA5水平与TG呈负相关(r＝－0.494，P＝0.003)。非条件logistic多元线性回归分析结果显示，低ApoA5血症、高胆固醇血症和高甘油三酯血症(HTG)是妊娠妇女发生GDM的危险因素。

结论

血清ApoA5变化不仅可反映母体肥胖和胰岛素抵抗(IR)状态，而且低水平的ApoA5可促进孕期糖耐量受损(IGT)发生。

关键词: 妊娠期糖尿病, 载脂蛋白A5, 胰岛素抵抗

Objective

To discuss the relationship between serum apolipoprotein A5 (ApoA5) level changes in pregnant women during second or third trimester and gestational diabetes mellitus (GDM).

Methods

From July 2009 to May 2010, a total of 182 women who were diagnosed as GDM during 20-36 gestational weeks were include into this study. Meanwhile, another 232 pregnant women with normal glucose tolerance (NGT) were recruited into control group. Maternal blood samples of 5 mL were collected to determine serum fasting blood glucose (FBG), total cholesterol (TC), triglyeride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), apolipoprotein (Apo) A5 and ApoB by automatic biochemistry analyzer 7600-020E, Glycosylated hemoglobin (HbA1c) by automatic glycohemoglobin analyzer HLC-723G7, plasma concentrations of ApoA5 by enzyme-linked immunosorbent sandwich assay. The study protocol was approved by the Ethical Review Board of Investigation in Human Being of the Drum Tower Hospital Affiliated to Medical School of Nanjing University. Informed consent was obtained from all participates. There had no significant difference between two groups of age and gestational weeks.

Results

Compared with control group, serum ApoA5 concentration were increased in GDM group[(254.56±30.51) ng/mL vs. (219.40±21.35) ng/mL], there had statistical significance (P<0.05). FBG, TC, TG and HOMA-IR of GDM group were obviously increased, HDL-C was decreased compared with that in control group (P<0.05). Correlation analysis showed, serum ApoA5 concentration was positively correlated with serum TG when the TG≥1.7mmol/L (n=166, r=0.349, P=0.025), negatively correlated with serum TG when TG<1.7 mmol/L (n=16, r=-0.494, P=0.003). Non-conditional logistic regression analysis showed low serum ApoA5, hypercholestrolemia and hypertriglyceridemia (HTC) were risk factors of pregnant women complicating gestational diabetes.

Conclusions

Serum ApoA5 concentration not only reflects maternal obesity and insulin resistance (IR), but also low levels of ApoA5 could accelerate the occurrence of impaired glucose tolerance (IGT) during pregnancy.

Key words: gestational diabetes mellitus, apolipoprotein A5, insulin resistance

表1 两组孕妇一般资料比较(±s)

Table 1 Comparison of the general information between GDM group and control group(±s)

组别	n	年龄(岁)	孕龄(孕周)	孕前BMI(kg/m²)	TG(mmol/L)	TC(mmol/L)
GDM组	182	27.63±3.27	28.02±1.51	24.13±1.90	3.82±1.64	6.30±1.23
对照组	232	28.04±3.34	27.79±1.24	23.81±1.75	2.71±1.08	5.13±0.55
t		1.25	1.70	1.78	8.27	13.00
P		>0.05	>0.05	>0.05	0.000	0.000
组别	HDL-C(mmol/L)	LDL-C(mmol/L)	ApoAⅠ(mmol/L)	ApoB(mmol/L)	FBG(mmol/L)
GDM组	1.74±0.43	2.76±0.88	1.74±0.31	1.33±0.52	8.09±1.60
对照组	1.86±0.46	2.64±0.80	1.84±0.71	1.26±0.33	4.60±0.52
t	－2.4	1.41	0.46	1.43	41.50
P	0.014	0.160	0.014	0.080	0.000
组别	2 h PBG(mmol/L)	FINS(mU/L)	2 h INS(mU/L)	HbA1c(%)	CRP(mg/L)
GDM组	10.77±1.42	15.82±4.44	53.20±8.36	7.79±1.32	5.12±0.70
对照组	6.32±1.28	11.38±4.12	30.54±9.21	4.39±1.21	0.36±0.11
t	10.51	9.79	25.84	35.20	102.01
P	0.000	0.001	0.000	0.000	0.000
组别	ApoA5(ng/mL)	HOMA-IR
GDM组	254.56±30.51	4.70±0.58
对照组	219.40±21.35	2.09±0.32
t	13.76	20.53
P	0.001	0.000

表1 两组孕妇一般资料比较(±s)

Table 1 Comparison of the general information between GDM group and control group(±s)

组别	n	年龄(岁)	孕龄(孕周)	孕前BMI(kg/m²)	TG(mmol/L)	TC(mmol/L)
GDM组	182	27.63±3.27	28.02±1.51	24.13±1.90	3.82±1.64	6.30±1.23
对照组	232	28.04±3.34	27.79±1.24	23.81±1.75	2.71±1.08	5.13±0.55
t		1.25	1.70	1.78	8.27	13.00
P		>0.05	>0.05	>0.05	0.000	0.000
组别	HDL-C(mmol/L)	LDL-C(mmol/L)	ApoAⅠ(mmol/L)	ApoB(mmol/L)	FBG(mmol/L)
GDM组	1.74±0.43	2.76±0.88	1.74±0.31	1.33±0.52	8.09±1.60
对照组	1.86±0.46	2.64±0.80	1.84±0.71	1.26±0.33	4.60±0.52
t	－2.4	1.41	0.46	1.43	41.50
P	0.014	0.160	0.014	0.080	0.000
组别	2 h PBG(mmol/L)	FINS(mU/L)	2 h INS(mU/L)	HbA1c(%)	CRP(mg/L)
GDM组	10.77±1.42	15.82±4.44	53.20±8.36	7.79±1.32	5.12±0.70
对照组	6.32±1.28	11.38±4.12	30.54±9.21	4.39±1.21	0.36±0.11
t	10.51	9.79	25.84	35.20	102.01
P	0.000	0.001	0.000	0.000	0.000
组别	ApoA5(ng/mL)	HOMA-IR
GDM组	254.56±30.51	4.70±0.58
对照组	219.40±21.35	2.09±0.32
t	13.76	20.53
P	0.001	0.000

表2 两组在不同TG浓度时ApoA5与血脂指标及胰岛素的相关性

Table 2 Correlation among ApoA5, serum lipids and insulin when TG at different concentrations in two groups

参数	GDM group						Control group
	All cases(n＝182)		TG<1.7 mmol/L(n＝16)		TG≥1.7 mmol/L(n＝166)		All cases(n＝232)		TG<1.7 mmol/L(n＝41)		TG≥1.7 mmol/L(n＝191)
	r	P	r	P	r	P	r	P	r	P	r	P
TG	0.188	0.177	－0.494	0.003	0.349	0.025	－0.533	0.042	－0.695	0.003	0.094	0.036
TC	0.321	0.312	0.580	0.557	－0.060	0.062	0.074	0.462	0.083	0.395	0.045	0.309
HDL-C	0.311	0.035	0.290	0.046	0.305	0.030	0.381	0.019	0.355	0.016	0.375	0.024
LDL-C	0.206	0.513	0.500	0.207	0.231	0.223	0.379	0.179	0.107	0.110	0.500	0.207
CRP	0.221	0.211	0.442	0.217	0.276	0.265	0.069	0.038	0.019	0.104	0.042	0.267
FBG	－0.182	0.044	－0.132	0.062	－0.213	0.010	0.104	0.670	0.060	0.615	－0.121	0.006
FINS	－0.225	0.031	－0.086	0.093	－0.291	0.027	0.048	0.109	0.125	0.185	0.074	0.030
HOMA-IR	－0.312	0.008	－0.220	0.021	－0.365	0.002	0.016	0.074	0.090	0.146	0.103	0.064

表2 两组在不同TG浓度时ApoA5与血脂指标及胰岛素的相关性

Table 2 Correlation among ApoA5, serum lipids and insulin when TG at different concentrations in two groups

参数	GDM group						Control group
	All cases(n＝182)		TG<1.7 mmol/L(n＝16)		TG≥1.7 mmol/L(n＝166)		All cases(n＝232)		TG<1.7 mmol/L(n＝41)		TG≥1.7 mmol/L(n＝191)
	r	P	r	P	r	P	r	P	r	P	r	P
TG	0.188	0.177	－0.494	0.003	0.349	0.025	－0.533	0.042	－0.695	0.003	0.094	0.036
TC	0.321	0.312	0.580	0.557	－0.060	0.062	0.074	0.462	0.083	0.395	0.045	0.309
HDL-C	0.311	0.035	0.290	0.046	0.305	0.030	0.381	0.019	0.355	0.016	0.375	0.024
LDL-C	0.206	0.513	0.500	0.207	0.231	0.223	0.379	0.179	0.107	0.110	0.500	0.207
CRP	0.221	0.211	0.442	0.217	0.276	0.265	0.069	0.038	0.019	0.104	0.042	0.267
FBG	－0.182	0.044	－0.132	0.062	－0.213	0.010	0.104	0.670	0.060	0.615	－0.121	0.006
FINS	－0.225	0.031	－0.086	0.093	－0.291	0.027	0.048	0.109	0.125	0.185	0.074	0.030
HOMA-IR	－0.312	0.008	－0.220	0.021	－0.365	0.002	0.016	0.074	0.090	0.146	0.103	0.064

表3 妊娠期糖尿病相关危险因素的非条件logistic多元回归分析

Table 3 Non-conditional Logistic multiple regression analysis of risk factors of gestational diabetes mellitus

项目	回归系数	标准误	P	OR	95%CI
TC	1.150	0.400	0.019	2.905	1.303～5.908
TG	1.362	0.428	0.021	3.211	1.802～7.537
ApoA5	－0.355	0.132	0.012	1.102	0.845～1.950

表3 妊娠期糖尿病相关危险因素的非条件logistic多元回归分析

Table 3 Non-conditional Logistic multiple regression analysis of risk factors of gestational diabetes mellitus

项目	回归系数	标准误	P	OR	95%CI
TC	1.150	0.400	0.019	2.905	1.303～5.908
TG	1.362	0.428	0.021	3.211	1.802～7.537
ApoA5	－0.355	0.132	0.012	1.102	0.845～1.950

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Association of Serum Apolipoprotein A5 Level With Gestational Diabetes Mellitus

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Association of Serum Apolipoprotein A5 Level With Gestational Diabetes Mellitus