Røder M E, Knip M, Hartling S G, Karjalainen J, Akerblom H K, Binder C
Steno Diabetes Center, Gentofte, Denmark.
J Clin Endocrinol Metab. 1994 Dec;79(6):1570-5. doi: 10.1210/jcem.79.6.7989457.
The objective of this study was to test whether levels of proinsulin immunoreactivity (PIM) relative to those of insulin immunoreactivity (IRI) or C-peptide are changed and related to subclinical beta-cell dysfunction in siblings of insulin-dependent diabetes mellitus (IDDM) patients. Twenty-three siblings, previously found positive for islet cell antibodies and/or insulin autoantibodies, were divided into 2 groups according to their first phase insulin response (FPIR) to i.v. glucose tolerance tests (IVGTTs) sequentially performed during an observation period of 2 yr. Eleven siblings had diminished FPIR on at least 1 occasion (group 1), whereas 12 siblings had a normal FPIR on all occasions studied (group 2). All underwent a further IVGTT (0.5 g glucose/kg BW), and serum samples were taken at 0, 1, 3, 6, 10, 20, 30, 40, 50, and 60 min. The 2 groups had comparable median age, female/male ratio, weight, height, fasting blood glucose, immunoreactive insulin, C-peptide, and insulin autoantibodies levels, but group 1 had significantly higher islet cell antibodies levels. Fasting median PIM/IRI and PIM/C-peptide ratios were 2- to 3-fold higher in group 1 [10.5% (range, 1.8-93.8%) vs. 5.2% (range, 1.9-14.3%) and 3.3% (range, 0.4-23.1%) vs. 1.3% (range, 0.7-2.6%; P < 0.05]. Fasting PIM/C-peptide ratios correlated inversely with FPIRs (rs = -0.68; P < 0.01). During glucose stimulation, maximal responses of IRI and C-peptide were 4-fold lower in group 1, and the time of maximal responses of IRI and C-peptide occurred later in group 1 than in group 2. In contrast, no difference in maximal responses of PIM was found, but the time of maximal responses of PIM occurred later in group 1. Nine of 11 siblings in group 1 presented with IDDM 1-28 months after the test, compared to none in group 2. In group 1 a paradoxical inhibitory response of PIM was observed during the first 6 min of the IVGTT. These data indicate that fasting PIM/IRI and/or PIM/C-peptide ratio reflects subclinical beta-cell dysfunction in prediabetic subjects with evidence of immunological beta-cell assault and suggests that an elevated ratio may be an additional marker for later development of IDDM.
本研究的目的是检测胰岛素依赖型糖尿病（IDDM）患者的兄弟姐妹中，胰岛素原免疫反应性（PIM）水平相对于胰岛素免疫反应性（IRI）或C肽水平是否发生变化，以及是否与亚临床β细胞功能障碍相关。23名先前检测出胰岛细胞抗体和/或胰岛素自身抗体呈阳性的兄弟姐妹，根据他们在2年观察期内连续进行的静脉葡萄糖耐量试验（IVGTT）中的第一相胰岛素反应（FPIR）分为两组。11名兄弟姐妹至少有1次FPIR降低（第1组），而12名兄弟姐妹在所有研究场合的FPIR均正常（第2组）。所有人都接受了进一步的IVGTT（0.5g葡萄糖/kg体重），并在0、1、3、6、10、20、30、40、50和60分钟采集血清样本。两组的年龄中位数、女性/男性比例、体重、身高、空腹血糖、免疫反应性胰岛素、C肽和胰岛素自身抗体水平相当，但第1组的胰岛细胞抗体水平显著更高。第1组的空腹PIM/IRI和PIM/C肽比值分别比第2组高2至3倍[10.5%（范围1.8 - 93.8%）对5.2%（范围1.9 - 14.3%）和3.3%（范围0.4 - 23.1%）对1.3%（范围0.7 - 2.6%；P < 0.05）]。空腹PIM/C肽比值与FPIR呈负相关（rs = -0.68；P < 0.01）。在葡萄糖刺激期间，第1组IRI和C肽的最大反应降低了4倍，且IRI和C肽最大反应的时间在第1组比第2组出现得更晚。相比之下，PIM的最大反应没有差异，但PIM最大反应的时间在第1组出现得更晚。第1组的11名兄弟姐妹中有9名在试验后1 - 28个月出现IDDM，而第2组无人出现。在第1组中，在IVGTT的前6分钟观察到PIM出现反常的抑制反应。这些数据表明，空腹PIM/IRI和/或PIM/C肽比值反映了有免疫性β细胞攻击证据的糖尿病前期受试者的亚临床β细胞功能障碍，并表明比值升高可能是IDDM后期发展的一个额外标志物。
