糖化血红蛋白与胰岛β细胞功能关系的研究

Relationship between glycosylated hemoglobin and β-cell function

目的 探讨不同糖代谢状态糖化血红蛋白（HbA1c）与胰岛β细胞功能的关系.方法 选取2010年6月至2013年2月为评价糖耐量水平而来南京大学医学院鼓楼医院内分泌科就诊者913例,所有受试者均行75 g口服葡萄糖耐量试验（OGTT）及胰岛素释放试验,测定HbA1c,根据HbA1c水平将受试者分为HbA1c ＜5.7％（277例）、5.7％≤HbA1c≤6.4％（391例）及HbA1c＞6.4％组（245例）;根据OGTT结果分为正常糖耐量组（NGT,205例）,糖调节受损组（IGR,328例）及2型糖尿病组（T2DM,380例）.以1/稳态模型胰岛素抵抗指数（1/HOMA-IR）、Matsuda胰岛素敏感指数（ISIM）评价胰岛素敏感性,以处置指数DI（早时相DI30、总时相DI120）评估校正胰岛素敏感性之后的胰岛β细胞功能.多组计量资料间比较采用方差分析,分类计数资料采用卡方检验,胰岛功能相关指数在校正性别、年龄、BMI之后采用一般线性模型进行比较.结果 与HbA1c ＜5.7％组相比,5.7％≤HbA1c≤6.4％组的DI30、DI120、ISIM、1/HOMA-IR分别下降了39％、33％、13％、14％;HbA1c＞6.4％组的DI30、DI120、ISIM、1/HOMA-IR分别下降了68％、66％、21％、32％（F=12.765 ～ 317.316,均P＜0.05）.在正常糖耐量阶段的人群中,5.7％≤HbA1c≤6.4％组的DI30、DI120明显低于HbA1c＜5.7％组（F=4.516、4.215,P＜0.05）;在HbA1c＜ 5.7％的人群中,DI30及DI120按照NGT→ IGR→T2DM的方向下降（F =87.604、108.369,P＜0.05）.结论 胰岛β细胞功能的进行性衰退及胰岛素抵抗共同促进了HbA1 c的升高;HbA1c与血糖结合能够更好地反映个体胰岛功能情况.

Objective To assess the relations between glycosylated hemoglobin A1c （HbA1c） and β-cell function as measured by indices derived from oral glucose tolerance test （OGTT） in Chinese subjects.Methods A total of 913 subjects,who underwent 75 g OGTT for evaluation of glucose intolerance from June 2010 to February 2013,were included.According to OGTT,the enrolled subjects were divided into the following three groups：normal glucose tolerance （NGT,n =205）,impaired glucose regulation （IGR,n =328）,and type 2 diabetes mellitus （T2DM,n =380）.Meanwhile,the subjects were also divided into three groups according to HbA1c levels：HbA1c 〈 5.7% （n =277）,5.7% ≤ HbA1c ≤ 6.4% （n =391）,and HbA1 c 〉 6.4% （n =245）.Insulin sensitivity was measured by Matsuda insulin sensitivity index （ISIM） and 1/homeostasis model assessment of insulin resistance （1/HOMA-IR）.β-cell function adjusted by insulin sensitivity was assessed from disposition index （DI） at early-phase DI30 and total DI120.ANOVA,Chi-Square test and general linear model were used for data analysis.Results Compared with the HbA1c 〈 5.7% group,the DI30,DI120,ISIM,and 1/HOMA-IR were decreased by-39%,-33%,-13%,and-14%,respectively,in the 5.7% ≤HbA1c≤6.4% group,and-68%,-66%,-21%,and-32%,respectively,in the HbA1c 〉 6.4% group （F =12.765-317.316,all P 〈 0.05）.In NGT group,DI30 and DI120 decreased in subjects with elevated HbA1c; in HbA1c 〈5.7% group,DI30 and DI120 declined as glucose increased.Conclusions Both impairment of β-cell function and insulin sensitivity contributes to the deterioration of HbA1c in Chinese population.A combination of HbA1c and OGTT is effective in screening for subjects with β-cell dysfunction.