BACKGROUND: There is a highly variable asymptomatic period of beta cell destruction prior to the clinical presentation of type1 diabetes. It is not well known what triggers type 1 diabetes to become a clinically overt disease. This explorative study aimed to identify the association between disease history/medication use and the clinical manifestation of type 1 diabetes. METHODOLOGY/PRINCIPAL FINDINGS: An explorative case control study was conducted in the Dutch PHARMO Record Linkage System. Cases (n = 1,107) were younger than 25 years and had at least 2 insulin prescriptions between 1999 and 2009. For each case, up to 4 controls (without any prescription for the glucose lowering medications (n = 4,424)) were matched by age and sex. Conditional logistic regression analysis was used to evaluate the association between disease history/medication use in the year prior to the diagnosis of type 1 diabetes and clinical manifestation of this disease. Type1 diabetes was significantly associated with a history of mental disorder (odds ratio (OR) 8.0, 95% confidence interval (CI) 1.5-43.7), anemia (OR 5.1, 95% CI 1.1-22.9), and disease of digestive system (OR 2.6, 95% CI 1.2-5.5). The following drug exposures were significantly associated with the clinical manifestation of type 1 diabetes: "systemic hormonal preparations" (OR 1.7, 95% CI 1.1-2.6), medications for "blood and blood forming organs" (OR 1.6, 95% CI 1.1-2.6), "alimentary tract and metabolism" (OR 1.3, 95% CI 1.1-1.6), and "anti-infectives for systemic use" (OR 1.2, 95% CI 1.01-1.4). CONCLUSIONS: Our explorative study demonstrated that in the year prior to the presentation of type 1 diabetes in children and young adults, hospitalization for a diverse group of diseases and drug exposures were significantly more prevalent compared with age- and sex-matched diabetes-free controls.