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Beta-cell autoimmunity associated with human T lymphotropic virus type 1 infection. Type 1 diabetes is one of the autoimmune diseases most frequently associated with human T lymphotropic virus type 1 (HTLV-1). A significant association between HTLV-1 and type 1 diabetes has been reported in some European studies, whereas it was not observed in the US. Most of the studies conducted in the Americas have been carried out in asymptomatic HTLV-1 carriers or HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients and no case of diabetes was reported in these patients. To investigate whether HTLV-1 infection is associated with diabetes in an HTLV-1 endemic area in the South of Brazil, we evaluated two groups of HTLV-1 carriers, one composed of asymptomatic carriers and the other of HAM/TSP patients. Diabetes was diagnosed using World Health Organization criteria and autoantibodies were investigated using the glutamic acid decarboxylase (GADA) test, islet cell antigen-2 (ICA-2A), and the protein tyrosine phosphatase like protein (IA-2A). Among the asymptomatic carriers, GADA was positive in 17.7% (6/34). The prevalence of diabetes was lower in the HTLV-1 carriers when compared with non-HTLV-1 carriers (3.6%, 3/84; p < 0.01, Fisher's exact test), even when adjusted for age and sex (OR 0.13, p = 0.0082, logistic regression). For HAM/TSP patients, GADA was positive in 50% of the patients. Thus, the results indicate that HTLV-1 infection may be a protective factor for diabetes in HTLV-1 endemic areas. However, the higher prevalence of diabetes observed in the HAM/TSP patients suggests that host genetic factors also play a role. The impact of HTLV-1 infection on the development of autoimmune diseases in HTLV-1 endemic areas is discussed.