Karjalainen J, Vähasalo P, Knip M, Tuomilehto-Wolf E, Virtala E, Akerblom H K
Department of Paediatrics, University of Oulu, Finland.
Eur J Clin Invest. 1996 Aug;26(8):640-9. doi: 10.1111/j.1365-2362.1996.tb02147.x.
Insulin-dependent diabetes mellitus (IDDM) risk was evaluated in 765 siblings based on prospective observation of islet cell antibodies (ICAs) and insulin autoantibodies (IAAs) as a function of the degree of HLA identity to the proband and HLA-DR alleles. Twenty-eight (3.7%) siblings progressed to IDDM over a median observation period of 5.8 years. ICAs had higher sensitivity than IAAS (100% vs. 33% , P < 0.001), whereas persistent ICA positivity and double ICA/IAA positivity defined the highest actuarial risk (47% and 70%). Diabetes manifested after a mean of 3.2 years from the detection of ICAs in those siblings who were initially ICA negative and, importantly, the risk was equal to that of the siblings constantly positive from the first sample obtained. Although the combination of HLA identity and ICAs at or above 80 Juvenile Diabetes Foundation units carried the highest positive predictive value (77%), the high-risk HLA markers were insufficient to predispose siblings with low ICA levels to IDDM and low-risk HLA markers did not provide complete protection against high ICA levels and from subsequent IDDM. These results emphasize ICAs as the primary tool for risk evaluation in siblings followed by restricted HLA subtyping to reduce the population to be subjected to clinical intervention trials.
基于对胰岛细胞抗体（ICA）和胰岛素自身抗体（IAA）的前瞻性观察，并将其作为与先证者的HLA一致性程度以及HLA - DR等位基因的函数，对765名兄弟姐妹的胰岛素依赖型糖尿病（IDDM）风险进行了评估。在5.8年的中位观察期内，28名（3.7%）兄弟姐妹发展为IDDM。ICA的敏感性高于IAA（100%对33%，P<0.001），而持续性ICA阳性和ICA/IAA双重阳性定义了最高的精算风险（47%和70%）。在最初ICA阴性的那些兄弟姐妹中，从检测到ICA起平均3.2年后出现糖尿病，重要的是，这种风险与从首次采集样本就持续呈阳性的兄弟姐妹的风险相当。尽管HLA一致性与80个或以上青少年糖尿病基金会单位的ICA组合具有最高的阳性预测值（77%），但高风险的HLA标记不足以使ICA水平低的兄弟姐妹易患IDDM，而低风险的HLA标记也不能完全保护其免受高ICA水平及后续IDDM的影响。这些结果强调ICA是评估兄弟姐妹风险的主要工具，其次是进行受限的HLA亚型分型，以减少需要进行临床干预试验的人群。
