Islet cell antibody-positive relatives with human leukocyte antigen DQA1*0102, DQB1*0602: identification by the Diabetes Prevention Trial-type 1.

The presence of human leukocyte antigen (HLA) haplotype DQA1*0102, DQB1*0602 is associated with protection from type 1 diabetes. The Diabetes Prevention Trial-type 1 has identified 100 islet cell antibody (ICA)-positive relatives with this protective haplotype, far exceeding the number of such subjects reported in other studies worldwide. Comparisons between ICA+ relatives with and without DQB1*0602 demonstrated no differences in gender or age; however, among racial groups, African-American ICA+ relatives were more likely to carry this haplotype than others. The ICA+ DQB1*0602 individuals were less likely to have additional risk factors for diabetes [insulin autoantibody (IAA) positive or low first phase insulin release (FPIR)] than ICA+ relatives without DQB1*0602. However, 29% of the ICA+ DQB1*0602 relatives did have IAA or low FPIR. Although half of the ICA+ DQB1*0602 relatives had a high risk second haplotype, this was not associated with the additional risk factors for diabetes. Hispanic ICA+ individuals with DQB1*0602 were more likely to be IAA positive or to have low FPIR than other racial groups. In conclusion, the presence of ICA in the relatives described here suggests that whatever the mechanism that protects DQB1*0602 individuals from diabetes, it is likely to occur after the diabetes disease process has begun. In addition, there may be different effects of DQB1*0602 between ethnic groups.

Assessment of pancreatic islet-cell population in the hyperglycemic athymic nude mouse: immunohistochemical, ultrastructural, and hormonal studies.

Previous studies in diabetic animal models have demonstrated altered pancreatic islet-cell populations. To further characterize the diabetic syndrome in our athymic nude mouse colony, we studied the population of endocrine cells in pancreatic islets of 4-week-old normoglycemic and 8-week-old hyperglycemic athymic nude (nu/nu) mice using immunohistochemistry, morphometry, and electron microscopy. In normoglycemic 4-week athymic nu/nu mice, the proportions of B (insulin-secreting) cells and A (glucagon-secreting) cells were similar to those in control Balb/c mice; however, the D (somatostatin-secreting) cells were significantly decreased in nu/nu mice. The populations of B and A cells appeared to be normal in hyperglycemic 8-week-old nu/nu mice while there was a significant increase in the proportion of D cells when compared with the proportion in Balb/c mice. Electron microscopic studies indicated that the appearance of B and A cells was similar in the 8-week-old hyperglycemic nu/nu and in controls; however, the D cells appeared to be enlarged and were finely packed with electron-dense secretory granules. Radioimmunoassays of the pancreatic content (micrograms/g fresh pancreas) of insulin, glucagon, and somatostatin in pancreata in 8-week-old normal Balb/c and hyperglycemic athymic nude mice were similar; however, the somatostatin content was significantly increased in the 8-week-old hyperglycemic nu/nu mice compared with age and sex-matched controls. These results demonstrate an altered D cell population and an increase in somatostatin levels in the pancreatic islets of the hyperglycemic athymic nude mouse animal model.(ABSTRACT TRUNCATED AT 250 WORDS)