Several observations have linked the great global differences in childhood diabetes incidence to national cow milk consumption [1±3]. Milk is a multi-nutritional food consisting of protein, fat and carbohydrate components. Milk protein can be broadly divided into whey protein and casein protein, and one of the major casein proteins is b-casein. This protein has a number of genetic variants of which the A 1 and A 2 variants are the commonest in most cow breeds [4].As there appeared to be some notable exceptions to the generalisation that the more milk consumed in a country the higher the diabetes incidence, we examined the composition of milk as well as its consumption together with diabetes incidence wherever this was possible. MethodsSources of data. Data for the genetic polymorphism and for breed composition of national dairy herds were from published data [5±18] and personal communications with Gerd Vegurad (Agricultural University of Norway, N-1432 Aas) and O Â lafur Reykdal (University of Iceland, IS-101 Reykjavik). Data for the dairy protein available for consumption were obtained from the FAOSTAT database [19]. Data for the incidence of Type I (insulin-dependent) diabetes mellitus over various eras between 1960 and 1991 were from the WHO/DIAMOND study [20] and included its data sources for the individual countries reported in this study.Selection of countries. Countries were selected that had a complete set of data for breed composition and for milk protein polymorphism that were representative for the country or for the particular region of the country reported in the diabetes study. Countries were not selected if their polymorphism data were for only unique or minor breeds of cow, or their data were for only a small sample population of cows, or they had not phenotyped all b-casein variants. In addition, countries were not selected if they had a high proportion of imported dairy foods since b-casein variants consumption could not be accurately ascertained. The countries and regions selected Diabetologia (1999) Summary Previously published Type I (insulin-dependent) diabetes mellitus incidence in 0 to 14-yearold children from 10 countries or areas was compared with the national annual cow milk protein consumption. Countries which were selected for study had appropriate milk protein polymorphism studies, herd breed composition information and low dairy imports from other countries. Total protein consumption did not correlate with diabetes incidence (r = + 0.402), but consumption of the b-casein A 1 variant did (r = + 0.726). Even more pronounced was the relation between b-casein (A 1 + B) consumption and diabetes (r = + 0.982).These latter two cow caseins yield a bioactive peptide b-casomorphin-7 after in vitro digestion with intestinal enzymes whereas the common A 2 variant or the corresponding human or goat caseins do not.b-casomorphin-7 has opioid properties including immunosuppression, which could account for the specificity of the relation between the consumption of some but not all b-casein varian...

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SUMMARYUsing antisera to insulin, glucagon, pancreatic polypeptide (PP) and somatostatin, the localization and cellular distribution of the four hormones were investigated in the sheep fetal pancreas of day 40-45 gestation by immunofluorescence. All four hormones were immunolocalized at this early gestational period. The endocrine cell types had a characteristic distribution and were present in different numbers. Insulin and glucagon immunoreactive cells were seen in larger numbers compared to fetal PP and somatostatin cells and were located either in the developing islets or as single scattered cells in the epithelium of the embryonic ductules. These cells became more confined to the developing islets at later stages of gestation. In the pancreas of day 40-45 fetuses PP cells were less numerous than glucagon and insulin cells while somatostatin cells were seen rarely. However, PP and somatostatin cells became more numerous at later stages of gestation. Our studies demonstrate the presence of insulin, glucagon, PP and somatostatin within distinct cell types in the early sheep fetal pancreas.

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