Wasmuth H E, Kolb H
German Diabetes Research Institute at the University of Düsseldorf, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany.
Proc Nutr Soc. 2000 Nov;59(4):573-9. doi: 10.1017/s0029665100000811.
Cow's milk-based infant formulas and cow's milk consumption in childhood have been suggested to promote the development of type 1 diabetes mellitus and other immune-mediated or neurological diseases. Epidemiological studies in man have led to the hypothesis that introduction of cow's milk-based infant formula within the first 3 months of life is associated with increased risk of type 1 diabetes mellitus. Furthermore, in animal models of type 1 diabetes mellitus, cow's milk proteins have been proven to be 'diabetogenic'. However, the issue seems far from being resolved. Several epidemiological studies and, more importantly, the first prospective trials did not show an association between early exposure to cow's milk and type 1 diabetes mellitus. In animal models, cow's milk proteins are modestly and variably diabetogenic, wheat or soybean proteins in the diet cause higher rates of autoimmune diabetes. In both man and rodents there is increasing evidence that the gut-associated immune system plays a major role in disease development, probably because of disturbed oral tolerance mechanisms. Oral tolerance depends on immunological homeostasis and normal maturation of the gut. These factors are influenced by growth factors and cytokines from breast milk, normal bacterial colonization, infections and diet. All these factors have been proposed as risk factors for type 1 diabetes mellitus. Hence, cow's milk proteins may provide mimicry epitopes relevant in autoimmunity, as well as destabilizing oral tolerance mechanisms by biologically active peptides. The concept of dietary regulation of autoimmunity does not apply only to cow's milk protein, but also to other dietary proteins.
有人认为，以牛奶为基础的婴儿配方奶粉以及儿童时期饮用牛奶会促进1型糖尿病和其他免疫介导性疾病或神经疾病的发展。对人类的流行病学研究提出了这样一种假说，即在生命的前3个月内引入以牛奶为基础的婴儿配方奶粉与1型糖尿病风险增加有关。此外，在1型糖尿病的动物模型中，牛奶蛋白已被证明具有“致糖尿病性”。然而，这个问题似乎远未得到解决。多项流行病学研究，更重要的是，首批前瞻性试验并未显示早期接触牛奶与1型糖尿病之间存在关联。在动物模型中，牛奶蛋白的致糖尿病作用程度适中且存在差异，饮食中的小麦或大豆蛋白导致自身免疫性糖尿病的发生率更高。在人类和啮齿动物中，越来越多的证据表明，肠道相关免疫系统在疾病发展中起主要作用，这可能是由于口服耐受机制受到干扰。口服耐受取决于免疫稳态和肠道的正常成熟。这些因素会受到母乳中的生长因子和细胞因子、正常的细菌定植、感染和饮食的影响。所有这些因素都被认为是1型糖尿病的风险因素。因此，牛奶蛋白可能提供与自身免疫相关的模拟表位，以及通过生物活性肽破坏口服耐受机制。自身免疫的饮食调节概念不仅适用于牛奶蛋白，也适用于其他饮食蛋白。
