新发暴发性1型糖尿病患者胰岛α细胞功能特征研究
Characterization ofα?cell function in patients with newly?onset fulminant type 1 diabetes mellitus
目的 探讨新发暴发性1型糖尿病(FT1DM)患者起病时胰岛α细胞功能的特征.方法 选取2017年10月至2018年7月于南京医科大学第一附属医院符合标准的新诊断FT1DM患者(FT1DM组)4例和经典T1DM患者(经典T1DM组)10例,另招募健康志愿者15名作为健康对照组.收集临床资料,将FT1DM组和经典T1DM组血糖控制在<10 mmol/L后,三组均行100 g标准馒头餐试验(SBMT),检测血糖、C肽及胰高糖素,并以空腹胰高糖素水平为基线,计算SBMT后胰高糖素曲线下增量面积(iAUC glucagon)及C肽曲线下面积(tAUC c-peptide).各组iAUC glucagon及tAUC c-peptide比较前先行方差齐性检验,方差齐者行单因素方差分析(ANOVA),组间多重比较采用LSD检验;方差不齐者行Brown-Forsythe检验,组间多重比较采用Games-Howell检验.结果 (1)各组tAUC c-peptide比较,差异有统计学意义(F=98.343,P<0.001).FT1DM组tAUC c-peptide低于经典T1DM组[(192.62±68.98)比(1535.71±199.73)pmol·L-1·h-1,qcrit=3.830,P<0.001]及健康对照组[(192.62±68.98)比(6798.80±541.40)pmol·L-1·h-1,qcrit=3.688,P<0.001];(2)FT1DM组空腹胰高糖素水平低于健康对照组[(6.19±2.92)比(7.60±0.90)pmol/L],高于经典T1DM组[(4.33±0.69)pmol/L].SBMT后FT1DM组及经典T1DM组各时间点胰高糖素水平均较基线值升高.各组iAUC glucagon比较,差异有统计学意义(F ANOVA=34.344,P<0.001).FT1DM组iAUC glucagon高于经典T1DM组[(21.55±8.88)比(6.72±2.92)pmol·L-1·h-1,t=2.987,P=0.006]及健康对照组[(-13.16±7.68)pmol·L-1·h-1,t=7.348,P<0.001].结论 新发FT1DM患者在起病时不仅存在胰岛β细胞功能的完全衰竭,还伴随着胰岛α细胞功能的障碍,主要表现为餐后高胰高糖素血症.
更多Objective To investigate the islet α-cell function in patients with newly-onset fulminant type 1 diabetes mellitus (FT1DM). Methods Newly-onset type 1 diabetes mellitus (T1DM) patients diagnosed in the First Affiliated Hospital of Nanjing Medical University from October 2017 to July 2018 were recruited and divided into FT1DM group (n=4), typical autoimmune T1DM group (n=10), and 15 healthy volunteers were as controls. When the fasting blood glucose levels were controlled lower than 10 mmol/L, steamed bread meal tests (SBMT) were performed to assess the functions of α-cell and β-cell. Blood glucose, C-peptide and glucagon were tested. The incremental areas under curve of glucagon (iAUC glucagon) and C-peptide (tAUC c-peptide) were calculated based on SBMT. A one-way analysis of variance was used for comparison among multiple groups. The least significant difference test was used to analyze the data with homogeneity of variance, and the Games-Howell test was used to analyze the data with heterogeneity of variance. Results (1) The differences of tAUC c-peptide among three groups were statistically significant (F=98.343, P<0.001). The tAUC c-peptide in FT1DM group was significantly lower than that in typical autoimmune T1DM group [(192.62±68.98) vs (1535.71±199.73) pmol·L-1·h-1, qcrit=3.830, P<0.001] and healthy control group [(192.62 ± 68.98) vs (6798.80 ± 541.40) pmol · L-1 · h-1, qcrit=3.688, P<0.001] respectively;(2) The fasting glucagon concentration in FT1DM group was lower than that in healthy control group [(6.19 ± 2.92) vs (7.60 ± 0.90) pmol/L], but higher than typical autoimmune T1DM group [(4.33 ± 0.69) pmol/L]. Compared with baseline values, the levels of glucagon in both FT1DM group and typical autoimmune T1DM group increased after SBMT. The differences in iAUC glucagon among three groups after SBMT were significant (F=34.344, P<0.001). The iAUC glucagon in FT1DM group was significantly higher than those in typical autoimmune T1DM group [(21.55±8.88) vs (6.72±2.92) pmol·L-1·h-1, t=2.987, P=0.006] and healthy control group [ (-13.16±7.68) pmol·L-1·h-1, t=7.348, P<0.001], respectively. Conclusion Not only complete failure of islet β-cell function, but also dysfunction of islet α-cell can present in patients with FT1DM, which is charicterized by postprandial hyperglucagonemia.
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