For a number of these drugs the mechanism by which this influence occurs has been disclosed. For instance, hypokalemia which induced by thiazides lowers the GSI-IX Gamma-secretase inhibitor insulin secretion and corticosteroids enhance the gluconeogenesis, impair glucose uptake by cells and stimulate alpha cells in the pancreas . It can be questioned whether these mechanisms are relevant for type 1 diabetes, since type 1 diabetes is an end-stage insulitis which clinically manifests itself when less than 10–20% of the insulin-producing beta cells are still functioning. The way drugs influence glucose tolerance can probably be neglected compared with the critical role of the proportion of functioning beta cells. We hypothesize that a general mechanism by which the diseases and drugs identified in our study may trigger the clinical presentation of type 1 diabetes is that these conditions can change the state of metabolism and thereby increase insulin requirement in the body. Diabetogenic hormones like glucocorticoids and growth hormone may play a role in such a scenario. This increased insulin requirement can induce an earlier presentation of type 1 diabetes and/or an increasing incidence by enlarging the proportion of susceptible children progressing to overt disease. However, we cannot rule out that the increased prevalence of diseases and drug exposures in the year prior to the clinical manifestation of type 1 diabetes can be explained by a clustering of the diseases or can be caused by the prodromal type 1 diabetes. The main strength of this study includes its population-based case control design without too many exclusion criteria. Routinely collected detailed data on medication use and hospital admissions reduced the probability of information bias. Also, the use of insulin as a proxy for type 1 diabetes is strong since the treatment of hyperglycemia is the only indication. We assumed that most of the insulin users in our study had type 1 diabetes, because we excluded patients who ever used oral blood glucose lowering medicines, had cystic fibrosis or malignancies in the year prior to the index date, and other types of diabetes needing insulin and mitochondrial diabetes, etc.) have low prevalences compared with type 1 diabetes. Therefore misclassification of type of diabetes is probably a minor problem. Similar to other studies based solely on administrative databases, there are several limitations that must be recognized. It is possible that our results underestimated the prevalence of a number of comorbidities which did not result in hospitalization. While there may be misclassification of drugs and diseases, several studies have validated the exposure of drugs retrieved from the prescription records in the Netherlands and some of the hospital diagnoses have been validated. Furthermore, information on drugs used in hospitals and over the counter drugs was not available in the current.