Insulin-dependent diabetes mellitus (IDDM) is inherited in a multifactorial manner with polygenes and environmental factors contributing to its emergence in a particular individual. The evidence for such a mode of inheritance is reviewed. One of the most important genetic roles is that played by the HLA genes on chromosome 6 and the different alleles which increase or decrease susceptibility in Caucasians, Japanese, Singapore Chinese and Shanghai Chinese are described. It is inferred that these alleles are different in different ethnic groups. The other genes which are important are unknown. The environmental influences are less well known although viral infections may act as triggers. Because the morbidity and mortality are still extremely serious in IDDM patients in spite of insulin therapy, it is proposed that preventive measures should be instituted in families prone to IDDM. The role of prenatal diagnosis is discussed especially in those families with multiple HLA susceptibility genes present. Great care paid to management of hyperglycemia from onset of the disease may reduce future morbidity and mortality.
Matched MeSH terms: Diabetes Mellitus, Type 1/etiology
Type 1 diabetes is an autoimmune disease that results from the destruction of the insulin-producing pancreatic beta islet cells, probably via the influence of cytokines. However, direct correlation between the expression of selected cytokines by various immune cells at different time points during the progression of the disease has not yet been clearly demonstrated. In this study, we showed that the mRNA expression of the pro-inflammatory cytokines, TNF-alpha, IL-1 beta, IL-6, and GM-CSF, were increased while the anti-inflammatory cytokine, TGF-beta, decreased in the peritoneal macrophages of nonobese diabetic (NOD) mice. IL-6 expression however decreased when the mice became diabetic. Surprisingly the expression of IFN-gamma and IL-2 by splenic CD4+ cells were lower in 5-week-old NOD mice as compared to the nonobese diabetic resistant (NOR) control mice, but their expression was higher in older NOD mice. The expression of IL-4 and IL-10 decreased in splenic CD4-positive lymphocytes. Splenic CD8-positive lymphocytes expressed increased levels of IFN-gamma and IL-10 but the latter decreased sharply when diabetes occurred. The relevance of these findings to the pathogenesis of type 1 diabetes is discussed.
Matched MeSH terms: Diabetes Mellitus, Type 1/etiology