肥胖和非肥胖糖耐量受损患者胰岛素敏感性和1相胰岛素分泌研究

Study on insulin sensitivity and first-phase insulin secretion in obese and non-obese subjects with impaired glucose tolerance

目的研究肥胖和非肥胖糖耐量受损(IGT)患者的胰岛素敏感性和β细胞1相胰岛素分泌功能,以探讨在IGT患者中肥胖对胰岛素抵抗和1相胰岛素分泌的影响。方法共有99位受试者(包括正常对照者32名,肥胖IGT44例,非肥胖IGT23例)接受了口服75 g葡萄糖耐量试验(OGTT)和胰岛素改良的减少样本数(采血样12次)的Bergman微小模型技术结合静脉葡萄糖耐量试验(FSIGTT)。胰岛素抵抗由FSIGTT中胰岛素敏感性指数(SI)加以评估,而OGTT中糖负荷后30 min胰岛素增值与血糖增值之比值[ΔI30/ΔG30=(I30 min-I0 min) /(G30 min-G0 min)]和FSIGTT中急性胰岛素分泌反应(AIRg)则用以评价胰岛β细胞分泌功能。处理指数(DI =AIRg×SI)用于评价AIRg是否代偿机体的胰岛素抵抗。结果与正常对照组[(7.52±10.89)×10-4]相比,二组IGT患者之SI明显降低,而肥胖IGT组的SI[(1.72±1.11)×10-4]较非肥胖组[(3.15±1.49)×10-4]更低(均P<0.01); AIRg和ΔI30/ΔG30在正常组(412±191,14.45±8.47)和肥胖IGT组(378±235,17.02±11.30)之间差异无统计学意义,但均大于非肥胖组(196±160,8.93±6.69,均P<0.01);与正常组(2 851±1 180)相比,DI指数在二组IGT显著降低(595±485,584±517),但后二组间此值差异无统计学意义。SI与2 h胰岛素、体重指数、尿酸和胆固醇呈显著的负相关性(校正r2=0.603,P<0.01);而AIRg与ΔI30/ΔG30显著正相关,与空腹血糖负相关(校正r2=0.479,P<0.01)。结论IGT患者存在胰岛素抵抗和β细胞功能异常。与非肥胖IGT患者相比,肥胖IGT患者胰岛素抵抗程度更为严重,但胰岛β细胞胰岛素1相分泌相对充分。

Objective To study insulin sensitivity and first-phase insulin secretion of β cells in obese and non-obese subjects with impaired glucose tolerance (IGT) for further exploring the effects of obesity on insulin resistance and first-phase insulin secretion in IGT subjects. Methods A total of 99 subjects (including 32 normal controls, 44 obese patients with IGT and 23 non-obese subjects with IGT) underwent 75 g oral glucose tolerance test (OGTT) and insulin-modified reduced sample number (12 blood samples) of Bergman′s minimal model method with frequently sampled intravenous glucose tolerance test (FSIGTT). Insulin resistance was determined by the insulin sensitivity index (SI) from the FSIGTT. Insulin secretion of β-cells was determined by the insulinogenic index [ΔI 30/ΔG 30=(I 30 min-I 0 min)/(G 30 min-G 0 min)] during the OGTT and by the acute insulin response to glucose (AIRg) during the FSIGTT. The disposition index (DI=AIRg×SI) was used to determine whether AIRg was adequate to compensate for insulin resistance. Results Compared with normal controls [(7.52±10.89)×10 -4], the value of SI was significantly decreased in both IGT groups, and the SI in obese group with IGT [(1.72±1.11)×10 -4] was even much lower than that in non-obese group [(3.15±1.49)×10 -4, all P<0.01]. There was no significant difference in AIRg and ΔI 30/ΔG 30 between normal controls (412±191,14.45±8.47) and obese group with IGT (378±235,17.02±11.30), but the values of AIRg and ΔI 30/ΔG 30 in normal controls and obese group with IGT were all higher than those in non-obese group with IGT (196±160,8.93±6.69, all P<0.01). Compared with the normal control (2851±1180), the disposition index (DI) was lowered in both IGT groups (595±485,584±517) and there was no significant difference between two IGT groups. SI was negatively correlated with 2h insulin,bodymassindex,uricacidandcholesterol(adjustedr 2=0.603, P<0.01). AIRg was positively correlated with ΔI 30/ΔG 30 and negatively correlated with fasting blood glucose (adjusted r 2=0.479, P<0.01). Conclusion Insulin resistance and β cell dysfunction coexist in patients with IGT. Compared with non-obese subjects with IGT, the obese patients with IGT have more severe insulin resistance and higher first phase insulin secretion.