Читать книгу Clinical Dilemmas in Diabetes - Группа авторов - Страница 39

There is evidence that cow's milk proteins can act as triggers for the autoimmune process of β‐cell destruction based on studies indicating bottle feeding as a triggering factor for an autoimmune response to β‐cell [15].

There are several arguments for the milk hypothesis in T1D, including the following:

 Epidemiological studies show increased risk for T1D if the breast‐feeding period is short and cow's milk is introduced before 3–4 months of age.

 Skim milk powder can be "diabetogenic" in diabetes‐prone BB rats.

 Patients with T1D have increased levels of antibodies against cow's milk constituents.

 Milk albumin and β‐casein have some structural similarity to the islet autoantigen ICA69 and GLUT‐2, respectively.

A number of hypotheses have been postulated to explain the pathogenic role of cow's milk. One of the most convincing ones is that immature gut mucosa allows the passage of high molecular weight, potentially antigenic proteins which share some molecular mimicry with pancreatic β‐cells. Among diabetogenic proteins in cow's milk, β‐casein, β‐lactoglobulin, and albumin have been implicated as sources of potential antigens.

Casein represents the major protein in cow's milk. Human and bovine β‐casein are approximately 70% homologous and 30% identical. There are several reasons why it is thought that β‐casein is a good candidate to explain the observed association between cow's milk consumption and T1D: (1) it has several structural differences from the homologous human protein; (2) casein is probably the milk fraction promoting diabetes in the NOD mouse, since a protein‐free diet prevents the disease while a diet containing casein as the sole source of protein produces diabetes in the same animals; (3) several sequence homologies exist between bovine β‐casein and β‐cell autoantigens; (4) specific cellular and humoral immune responses toward bovine β‐casein are detectable in most T1D patients at the time of diagnosis, highly suggestive that this protein may participate in the immune events triggering the disease; (5) casein hydrolysate was shown to be non‐diabetogenic in the BB rat and NOD mouse models, therefore it was thought that this dietary intervention might be beneficial in humans as well for disease prevention.

The rationale behind the use of cow's milk hydrolysate for primary prevention of T1D is based on several epidemiological and in vitro studies, indicating that intact cow's milk, if given before three months of age, may induce an immune response towards β‐cells. The TRIGR trial (see section on primary prevention of T1D) investigated whether the administration of a cow's milk hydrolysate could prevent or delay the onset of T1D.