2型糖尿病先证者腰臀比对遗传表型的影响

目的 探讨2型糖尿病先证者腰臀比对糖耐量正常一级亲属的胰岛素抵抗及胰岛β细胞功能的影响.方法 选择186个2型糖尿病核心家系中的先证者和489名糖耐量正常的一级亲属.根据先证者腰臀比的四分位数,分别选取最低四分位数腰臀比的先证者(男性<0.86,女性<0.84)的一级亲属115名(为FDRl组)和最高四分位数腰臀比的先证者(男性>0.92,女性>0.89)的一级亲属106名(为FDR2组)进行研究.应用稳态模型评估胰岛素抵抗指数(HOMA-IR)、△I30/△G30(△I30:30 min胰岛素增值,△G30:30 min血糖增值)、△I30·△G-1<30·HOMA-IR-1来分别评估胰岛素敏感性和胰岛β细胞功能.结果 FDR2组的体重指数、女性一级亲属的腰围以及腰围/身高比值(WHtR)、收缩压、甘油三酯、HOMA-IR均高于FDRl组,高密度脂蛋白胆固醇、△I30/△G,,30>、△I30·△G-130·HOMA-IR-1均低于FDRl组,差异有统计学意义(P<0.05或P<0.01).相关分析显示两组中腰围、WHtR均与HOMA-IR呈正相关.最小平方回归分析显示,FDR2组中HOMA-IR与腰围、WHiR间回归直线斜率显著高于FDRI组(均P<0.01).结论 较高腰臀比的2型糖尿病先证者的糖耐量正常一级亲属可能具有更明显的胰岛素抵抗表型特点和β细胞功能降低,同时腹型肥胖轻度增加可能会带来更加明显的胰岛素抵抗.

Impact of waist-to-hip ratio on the genetic phenotype in probands of type 2 diabetes

Objective To explore the impact of waist-to-hip ratio (WHR) in type 2 diabetic probands on the phenotype of insulin resistance and β-cell function in normoglycemic first-degree relatives. Methods One hundred and eighty-six type 2 diabetic probands and 489 normoglycemic first-degree relatives were selected from 186 type 2 diabetes core families. 115 first-degree relatives (FDR1 group) of probands with low WHR (1st quartile: <0.86 for males and <0.84 for females) and 106 first-degree relatives (FDR2 group) of probands with high WHR (4th quartile: >0.92 for males and >0.89 for females) were identified to intensively study from 489 normoglycemic first-degree relatives. The homeostasis model assessment of insulin resistance (HOMA-IR) was used to estimate insulin sensitivity, and β-cell function was quantified as the ratio of the incremental insulin to glucose responses over the first 30 min (△I30/△G30) during the oral glucose tolerance test. The latter measure was also adjusted for the assay of insulin sensitivity as it modulated β-cell function (△I,,30>·△G-1,30·HOMA-IR-1). Results The body mass index, the waist circumference and waist-to-height ratio in female first-degree relatives, systolic blood pressure, triglyceride and HOMA-1R were significantly higher in FDR2 group than those in FDR1 group and high density lipoprotein cholesterol,△I30/△G30, △I-130·HOMA-IR-1were significantly lower in FDR2 group than those in FDRI group (P < 0.05 or P < 0.O1). The waist circumference and waist-to-height ratio in relatives of probands with low and high WHR were positively correlated with the HOMA-IR. However, the least square regression analysis showed that the slope from regression in FDR2 group were significantly steeper than that in FDR1 group(both P <0.01). Conclusion The normoglycemic first-degree relatives of the type 2 diabetic probands with high WHR had much more evident phenotype of insulin resistance and decreased β-cell function, and a slight increase in abdominal obesity had a greater impact on insulin resistance.