2型糖尿病家系正常糖耐量一级亲属血清瘦素、肿瘤坏死因子-α、神经肽Y水平及与胰岛素抵抗、β细胞分泌功能相关性的临床研究

Changes of Leptin,Tumor Necrosis Factor-α,Neuropeptide Y Levels and Their Association with Insulin Resistance and Insulin Secretion Function in Normal Glucose Tolerant First-degree Relatives of Familial Type 2 Diabetic Pedigrees

研究2型糖尿病家系中正常糖耐量的一级亲属血清脂肪细胞因子瘦素(Leptin)、肿瘤坏死因子-α(TNF-α)及神经肽Y(NPY)的水平及与胰岛素抵抗、胰岛β细胞分泌功能的相关性。纳入2型糖尿病家系中糖尿病患者(DM)86例、糖耐量正常的一级亲属(NGT)73例及无糖尿病家族史的正常对照(NC)65例,测定空腹Leptin、TNF-α、NPY及血脂水平。所有研究对象行75 g葡萄糖耐量试验(OGTT),并测定0和2 h血糖、免疫原性胰岛素(IRI)、真胰岛素(TI)水平。以空腹血糖(FPG)和空腹真胰岛素(FTI)计算HOMA-IR及HOMA-B,分别评价胰岛素抵抗和胰岛β细胞分泌功能。结果表明:在校正年龄、体重指数(BMI)后,DM组和NGT组的Leptin水平均高于NC组(P<0.05)。DM组TNF-α水平高于NC组,HOMA-IR高于NGT组和NC组,HOMA-B低于NGT组及NC组(P值均<0.05)。NPY在各组间无显著性差异。NGT组甘油三酯(TG)、空腹IRI、2hIRI、HOMA-IR明显高于NC组(P<0.05)。Leptin与年龄、BMI、A1C、腰围、空腹及OGTT-2h血糖、TG、2hIRI、TNF-α呈正相关,女性中与HOMA-B呈负相关。2型糖尿病家系糖耐量正常的一级亲属Leptin水平显著升高,提示Leptin的异常可能由于原发的遗传缺陷,并可能通过影响胰岛素抵抗和胰岛β细胞分泌功能而促进2型糖尿病发生。

This investigation was made in regard to the changes of plasma Leptin,Tumor Necrosis Factor-α（TNF-α） and Neuropeptide Y（NPY） levels and their association with insulin resistance and β-cell secretion function in normal glucose tolerant first-degree relatives of familial type 2 diabetic pedigrees in Chengdu area.Levels of Leptin,TNF-α,NPY and lipids（TG,TC,HDL-C） were determined in 86 type 2 diabetic mellitus（DM） patients,73 normal glucose tolerant（NGT） first-degree relatives in familial type 2 diabetic pedigrees and 65 normal controls（NC） from non-diabetic families.All of the subjects underwent 75g oral glucose tolerance test（OGTT）.Plasma glucose,immumoreactive insulin（IRI） and true insulin（TI） levels were also determined.Fasting glucose and TI levels were used to calculate homeostasis model assessment-insulin resistance（HOMA-IR） and HOMA-β cell indexes.After being adjusted for age and body mass index（BMI）,the levels of Leptin in DM and NGT first-degree relatives were all significantly higher than that in normal controls（P0.05）.Type 2 diabetic patients showed significantly elevated TNF-α levels than did the normal controls（P0.05）.Furthermore,diabetic subjects showed significantly higher HOMA-IR and lower HOMA-B levels,compared with those in NGT and NC groups（P0.05）.No statistically significant difference was found in regard to NPY among three groups.NGT first-degree relatives showed significantly higher levels of TG,fasting IRI,OGTT-2h IRI and HOMA-IR than did the normal controls（P0.05）.Leptin was positively correlated with age,BMI,waist,A1c,fasting and OGTT2h glucose,OGTT-2h TI and TNF-α in all subjects,and was negatively correlated with HOMA-B in females.Leptin levels were significantly elevated in NGT first-degree relatives,which implied that genetic defects of Leptin may play a role in the development of familial type 2 diabetic pedigrees.