2型糖尿病患者血清betatrophin水平变化及其与糖尿病视网膜病变的相关性研究

Changes of serum betatrophin levels in patients with type 2 diabetes mellitus and its relationship with diabetic retinopathy

目的 观察2型糖尿病（T2DM）患者血清中betatrophin水平，初步探讨betatrophin在糖尿病视网膜病变（DR）发病过程中的作用。 方法 临床检查确诊的T2DM患者59例（DM组）和同期健康对照者14名（NC组）纳入研究。均行视力、裂隙灯显微镜、间接检眼镜、荧光素眼底血管造影检查。根据检查结果同时结合国际DR临床分期标准，将患者分为无DR（Non-DR）组、非增生型DR（NPDR）组、增生型DR（PDR）组，分别为30、20、9例。测定受试者空腹血糖（FPG）、胰岛素（FIN）、C肽、糖化血红蛋白（HbA1c）、总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL-C）、低密度脂蛋白（LDL-C）水平。酶联免疫吸附试验测定血清中betatrophin水平。Betatrophin与其他指标之间的相关性采用Spearman相关分析。PDR的影响因素采用logistic回归分析。 结果 与NC组受试者比较，DM组患者空腹FPG（F=-4.316，P＜0.001）、FIN（t=2.142，P=0.001）、HbA1c（F=-5.726，P＜0.001）、TC（t=3.609，P=0.010）、LDL-C（t=0.000，P=0.003）、betatrophin水平（F=-2.263，P=0.024）显著升高，HDL-C水平（F=？3.924，P＜0.001）显著降低，差异均有统计学意义；TG差异无统计学意义（F=-1.422，P=0.155）。与Non-DR组、NPDR组比较，PDR组患者血清C肽（F=7.818，P=0.020）、betatrophin水平（F=12.141，P=0.002）显著升高，差异有统计学意义。Spearman相关性分析结果显示，DM组、Non-DR组、PDR组患者betatrophin水平分别与TC（r=0.304，P=0.019）、体重指数（r=0.513，P=0.004）、舒张压（r=0.685，P=0.042）呈显著正相关。Logistic回归分析结果显示，病程及血清C肽、betatrophin水平是发生PDR的危险因素。在病程和C肽不变的情况下，betatrophin水平≥1.0 ng/ml者PDR发生的风险较betatrophin水平＜1.0 ng/ml者增加了12倍。 结论 T2DM患者血清betatrophin水平明显异常；betatrophin可能参与了PDR的发生、发展。

Objective To observe the serum betatrophin levels in patients with type 2 diabetes mellitus （T2DM） and to explore the role of betatrophin in the pathogenesis of diabetic retinopathy （DR）. Methods A total of 59 patients with T2DM （DM group） and 14 healthy controls （NC group） were enrolled in the study. Vision, slit lamp microscope, indirect ophthalmoscope, fluorescein fundus angiography were performed on all the subjects. According to the results of the examination combined with the international DR clinical staging criteria, the patients were divided into no DR （Non-DR） group, non-proliferative DR （NPDR） group, and proliferative DR （PDR） group, with 30, 20 and 9 patients in each, respectively. The fasting blood glucose （FPG）, insulin （FIN）, C-peptide, glycated hemoglobin （HbA1c）, total cholesterol （TC）, triglyceride （TG）, high-density lipoprotein （HDL-C）, low-density lipid Protein （LDL-C） levels were detected. The level of betatrophin in serum was determined by enzyme-linked immunosorbent assay. The correlation between betatrophin and other indicators was analyzed by Spearman correlation. The influencing factors of PDR were analyzed by logistic regression. Results Compared with subjects in the NC group, the level of FPG （F=-4.316, P〈0.001）, FIN （F=2.142, P=0.001）, HbA1c （F=-5.726, P〈0.001）, TC （t=3.609, P=0.010）, LDL-C （t=0.000, P=0.003）, and betatrophin （F=-2.263, P=0.024） were significantly increased and HDL-C level （F=-3.924, P〈0.001） was decreases in the DM group. The difference of TG level between two groups was not statistically significant （F= -1.422, P=0.155）. Compared with the Non-DR group and the NPDR group, the serum C-peptide （F=7.818, P=0.020） and betatrophin levels （F=12.141, P=0.002） were significantly increased in the PDR group. Spearman correlation analysis showed that the levels of betatrophin in the DM group was positively correlated to TC （r=0.304, P=0.019）. The serum levels of betatrophin was positively correlated to body mass index in the Non-DR group （r=0.513, P=0.004）. Furthermore, in the PDR group, a significant positive correlation was observed between the serum betatrophin levels and diastolic blood pressure （r=0.685, P=0.042）. Logistic regression analysis showed that the duration of diabetes, serum C-peptide and betatrophin levels were risk factors for PDR. After controlling for the duration and serum C-peptide, the PDR risk for betatrophin levels great than or equal to 1.0 ng/ml was 12 times as much as betatrophin levels less than 1.0 ng/ml in T2DM patients. Conclusions The serum betatrophin content of patients with T2DM is abnormal. Betatrophin may be involved in the occurrence and development of PDR.