The Belgrade Childhood Diabetes Study: Association of Infections and Vaccinations on Diabetes in Childhood SANDRA S ˇ IPETIC ´ , PHD, HRISTINA VLAJINAC, PHD, NIKOLA KOCEV, MSC, AND SLOBODAN RADMANOVIC ´ , PHD PURPOSE: The aim of this study was to investigate whether individual infections or combination of infections or vaccination affect the risk of developing diabetes in childhood. METHODS: A case-control study was conducted in Belgrade during the period between 1994 and 1997. A total of 105 recent onset diabetics were compared with 210 controls chosen among children with skin disease (the first control group). Cases and controls were individually matched by age (1 year), sex, and place of residence. Eighty-six diabetic children were also compared with their brothers/sisters (the second control group). RESULTS: After adjustment for confounding variables, independent association with diabetes was found for infections during the 6 months preceding the onset of the disease, when cases were compared with both the first control group (OR = 4.23, 95% CI, 1.95–9.17, p  0.001) and the second control group (OR = 4.68, 95% CI, 2.09–10.47, p  0.001), and for regular vaccination when cases were compared with the first control group (OR = 0.08, 95% CI, 0.01–0.50, p = 0.03). CONCLUSION: The results obtained support the hypotheses that infections play a role in the develop- ment of type 1 diabetes and that regular vaccination has a preventive effect. Ann Epidemiol 2003;13:645–651.  2003 Elsevier Inc. All rights reserved. KEY WORDS: Type 1 Diabetes, Infections, Vaccinations. INTRODUCTION Involvement of viruses in the etiology of type 1 diabetes has been suggested a century ago (1). The first support for virus-induced diabetes in men is derived from an Australian study (2) showing that 20% of individuals with congenital rubella syndrome had developed type 1 diabetes at the 10-year follow-up. Later, coxsackie and other enteroviruses (3–7), cytomegalovirus (8), mumps virus (9–11) and some others were related to type 1 diabetes. The aim of this study was to investigate whether individ- ual infections or combination of infections affect the risk of developing diabetes in childhood, and whether there is any relationship between vaccination and development of type 1 diabetes in children. From the Institute of Epidemiology, School of Medicine, Belgrade Univer- sity, Belgrade, Yugoslavia (S.S, H.V.); Institute of Social Medicine, Statistics and Health Research, School of Medicine, Belgrade University, Belgrade, Yugoslavia (N.K.); and University Children’s Hospital, Belgrade, Yugoslavia (S.R.). Address correspondence to: Dr. Hristina Vlajinac, Institute for Epidemiology, School of Medicine, Belgrade University, Vis ˇegradska 26, Belgrade 11000, Yugoslavia. Tel.: +381-11-361-57-71; Fax: +381-11-361-57-68. E-mail: sandragru@ptt.yu Received September 25, 2002; accepted February 17, 2003.  2003 Elsevier Inc. All rights reserved. 1047-2797/03/$–see front matter 360 Park Avenue South, New York, NY 10010 doi:10.1016/S1047-2797(03)00065-6 MATERIAL AND METHODS A case-control study was conducted in Belgrade (about 320,000 inhabitants, 0 to16 years old) during the period between 1994 and 1997. The population of Belgrade is multiethnic but the majority of Belgrade citizens, almost 90%, are Serbs. The case group comprised 105 children 16 years old who were hospitalized for the first time because of type 1 diabetes at the two hospitals in Belgrade to which all chil- dren up to 16 years of age with suspected diabetes are re- ferred. Diagnosis of type 1 diabetes was made according to WHO criteria (12). Out of 116 children and adolescents diagnosed as type 1 diabetes cases during the mentioned period, 105 (90.5%) were included in the study. Five cases subsequently changed their place of residence and could not be traced, and parents of six cases refused participation in the study. Children with diabetes were compared with two control groups. The first control group (for each case two outpatient controls) were chosen among children treated for skin dis- eases (erytema solarae, 18 subjects; urticaria, 17; verrucae vulgares, 15; verrucae plantaris, 18; herpes simplex, 20; im- petigo contagiosa streptococcica, 5; impetigo staphylococ- cica, 3; impetigo vulgaris, 1; ecthyma, 2; strophulus infantum, 3; eczema, 10; acne vulgaris, 20; angulus infekciosus, 28; onychomycosis, 20; pediculosis capitis, 17; and scabies, 13).