不同糖耐量个体胰岛β细胞功能观察及评价

Evaluation of islet beta cell function in subjects with normal glucose tolerance, impaired glucose regulation, and type 2 diabetes mellitus

目的评价正常糖耐量(NGT)、糖调节受损(IGR)、新诊断2型糖尿病(T2DM)个体胰岛β细胞功能及其相关指标的适用性。方法 178例入选者行口服和静脉葡萄糖耐量试验。检测胰岛素生成指数(ΔI_(30)/ΔG_(30))、胰岛素急性分泌时相(AIR)、β细胞功能指数(HOMA β)、空腹胰岛素原(FPI)及胰岛素原/胰岛素(PI/I)比值反映胰岛素分泌功能。结果 IGR 组的ΔI_(30)/ΔG_(30)、AIR 较 NGT组分别下降了38%、39%,HOMA β轻度下降(19%);T2DM 组的胰岛β细胞功能降低更明显,其中AIR 下降84%,ΔI_(30)/ΔG_(30)下降70%、HOMA β下降62%。T2DM 组 FPI 和 PI/I 比值也比 NGT 组明显升高(24.4 pmo/L±18.0 pmol/L or 10.9 pmol/L±6.7 pmol/L;14.7%±10.5%or10.0%±6.5%,P<0.05)。ΔI_(30)/ΔG_(30)和 AIR 相关性好(r=0.75,P<0.001)。结论 IGR 患者主要表现胰岛素分泌时相缺陷和 HOMA β降低,至糖尿病阶段则伴有胰岛素分泌质量下降。ΔI_(30)/ΔG_(30)和AIR 均可准确反映 IGR 患者胰岛β细胞功能,而在新诊断2型糖尿病患者中 AIR 更适用,若应用ΔI_(30)/ΔG_(30)须校正胰岛素抵抗。

Objective To investigate the function of islet beta cells in subjects with normal glucose tolerance （NGT）, impaired glucose regulation （IGR）, and type 2 diabetes mellitus （T2DM）. Different indexes of insulin secretion, includingΔI30/ΔG30, AIR or HOMAβ, were compared. Methods 178 subjects without overt diabetes were classified into three groups according to the results of 75g oral glucose tolerance test （OGTT） ： NGT group （n =68）, IGR group （n =75）, and T2DM group （n =35）. Intravenous glucose tolerance test （IVGTT） was carried out 1 ～ 3 days later in all participants, with measurement of plasma insulin. The ratio of insulin-to-glucose levels increment during the first 30 min of OGTT （ ΔI30/ΔG30 ） and the acute insulin response （AIR） in IVGTT were used as indexes of early insulin secretion. Homeostasis model assessment of insulin secretion （HOMAβ） was another indicator of insulin secretion. The fasting plasma proinsulin level （FPI） was measured and the ratio fasting proinsulin to fasting insulin （PI/I） was calculated. HOMA insulin resistance index （HOMA IR） was used to assess the insulin resistance. Results The ΔI30/ΔG30 and AIR of the IGR group, adjusted by age, sex, and BMI, were both significantly lower than those of the NGT group. But the HOMAβ of the IGR group was only slightly lower than that of the NGT group. Compared with the NGT subjects, the T2DM patients had a very severe islet beta cell dysfunction （84% decrease in AIR, 70% decrease in ΔI30/ΔG30 and 62% decrease in HOMA β）. When the ΔI30/ΔG30 was adjusted by HOMR IR, the extent of impairment in early insulin response was similar to that of AIR （87% versus 84% lower than that of the NGT group）. The FPI and ratio of proinsulin to insulin were higher in the T2DM subjects compared with the NGT subjects （24.4 pmol/L ± 18.0 pmol/L vs 10. 9 pmol/ L ±6.7 pmol/L; and 14. 7% ± 10. 5% vs. 10. 0% ± 6. 5%, both P 〈 0. 05 ）. There was a significantly positive correlation between ΔI30/ΔG30 and AIR （ r = 0. 75, P 〈 0. 001 ）. Conclusion In the stage of IGR, an evident deficit in phasic insulin secretion after glucose load and a decreasing HOMAβ are exhibited. In addition to this, qualitative decrease of insulin secretion appears in the DM stage. AIR is a reliable index of isletβcell function.ΔI30/ΔG30 is an ahemative one in the subjects with NGT and IGR. But it should be adjusted by IR in diabetic patients.