Tuomilehto-Wolf E, Tuomilehto J, Hitman G A, Nissinen A, Stengård J, Pekkanen J, Kivinen P, Kaarsalo E, Karvonen M J
Department of Epidemiology, National Public Health Institute, Helsinki, Finland.
BMJ. 1993 Jul 17;307(6897):155-9. doi: 10.1136/bmj.307.6897.155.
To test the hypothesis that the genetic susceptibility to non-insulin dependent diabetes mellitus is the same as that to insulin dependent disease and to see whether glucose intolerance is associated with specific HLA haplotypes.
Population based study of men in 1989 first tested for glucose tolerance in 1984. HLA haplotypes, including HLA-A, C, B, DR, and DQ, were defined serologically. HLA haplotype data from a population based Finnish study of childhood diabetes were used for predicting non-insulin dependent diabetes and impaired glucose tolerance.
Two communities in Finland.
Representative cohort of Finnish men aged 70-89, comprising 98 men with non-insulin dependent diabetes mellitus and a randomly selected group of 74 men, who served as controls, who were tested for glucose tolerance twice within five years.
Non-insulin dependent diabetes, impaired glucose tolerance, blood glucose concentration.
Diabetes associated HLA haplotypes were present in 94% (85/90) of diabetic subjects, 79% (27/34) of subjects with impaired glucose tolerance, and only 13% (3/23) of non-diabetic subjects. In this group of elderly men sensitivity of the diabetes associated HLA haplotypes for non-insulin dependent diabetes and impaired glucose tolerance was 90%, specificity 87%, and predictive power 97%. Mean fasting blood glucose concentration was only just significantly higher in men with diabetes associated haplotypes than in men with no such haplotypes, but there was a substantial difference in blood glucose values two hours after glucose loading (10.4 and 6.4 mmol/l in men with diabetes associated HLA haplotypes and men with no such haplotypes, respectively (p < 0.0001)).
These findings support the hypothesis that specific HLA haplotypes exhibit a common genetic determinant for insulin dependent and non-insulin dependent diabetes. Furthermore, HLA is a major genetic determinant of glucose intolerance in elderly Finnish men. The belief that the HLA predisposition to diabetes is specific for insulin dependent diabetes mellitus is largely incorrect.
检验非胰岛素依赖型糖尿病的遗传易感性与胰岛素依赖型糖尿病相同这一假设，并观察葡萄糖耐量异常是否与特定的HLA单倍型相关。
基于人群的研究，研究对象为1989年的男性，他们于1984年首次接受葡萄糖耐量检测。HLA单倍型，包括HLA - A、C、B、DR和DQ，通过血清学方法确定。来自芬兰一项基于人群的儿童糖尿病研究的HLA单倍型数据用于预测非胰岛素依赖型糖尿病和葡萄糖耐量受损情况。
芬兰的两个社区。
70 - 89岁芬兰男性的代表性队列，包括98名非胰岛素依赖型糖尿病男性以及随机选取的74名男性作为对照，这些男性在五年内接受了两次葡萄糖耐量检测。
非胰岛素依赖型糖尿病、葡萄糖耐量受损、血糖浓度。
糖尿病相关的HLA单倍型在94%（85/90）的糖尿病患者、79%（27/34）的葡萄糖耐量受损患者以及仅13%（3/23）的非糖尿病患者中出现。在这群老年男性中，糖尿病相关HLA单倍型对非胰岛素依赖型糖尿病和葡萄糖耐量受损的敏感性为90%，特异性为87%，预测能力为97%。糖尿病相关单倍型男性的空腹血糖平均浓度仅略高于无此类单倍型的男性，但葡萄糖负荷后两小时的血糖值存在显著差异（糖尿病相关HLA单倍型男性和无此类单倍型男性分别为10.4和6.4 mmol/L（p < 0.0001））。
这些发现支持了特定HLA单倍型对胰岛素依赖型和非胰岛素依赖型糖尿病具有共同遗传决定因素这一假设。此外，HLA是芬兰老年男性葡萄糖耐量异常的主要遗传决定因素。认为HLA对糖尿病的易感性仅特定于胰岛素依赖型糖尿病的观点在很大程度上是不正确的。
