Although the PHARMO RLS covers almost 24% of the Dutch population, still the numbers of several drug exposures and hospital admissions were relatively low leading to statistical power problems. Although cases and controls were matched on age and sex, other potential confounding factors like genetic related risk factors, autoimmune antibodies and family history of type 1 diabetes were not available. We cannot rule out that children in the preamble period of the clinical presentation of type 1 diabetes more often visit doctors with an increased chance of identification of diseases and drug prescriptions. Finally, there is the problem of multiple comparisons that increases the chance for type 1 errors. However, since this is an explorative study and the general picture is that most diseases and drugs are risk factors for type 1 diabetes we do not think it is necessary to control the family wise error rate . In conclusion, it appears that a substantial number of diseases and drugs or the underlying diseases for which these drugs were prescribed were significantly more prevalent among patients who eventually developed type 1 diabetes compared with diabetes-free controls. This knowledge may stimulate further research directed at the prevention of the occurrence and the optimal treatment of these conditions in children and young adults who are susceptible for type 1 diabetes. Few study limitations should be discussed at first. Firstly, our research was undertaken to analyze the role on ventilation behaviour during exercise of a respiratory comorbidity, COPD, in HF patients. We built a COPD model by adding an external dead space. Our model was over-simplistic also as regards lung mechanics because an artificial dead space increase does not generate air trapping which is one of the most characteristic features of COPD during exercise. Secondly, our model was short lasting, so that chronic ventilatory and chemoreceptor adaptations to increased DS were not evaluated as were not evaluated primitive chemoreceptor abnormalities as drivers of the alveolar hypoventilation observed in COPD patients. Thirdly, with the Yintercept we analyze an index of overall DS. However, in the present setting, we were able to change DS only by adding an external DS, so that we do not know if changes in physiological DS similarly Vismodegib influence the VEYint. Fourthly, VE changes during exercise are due to VCO2, VD/ VT and PaCO2 changes, and all may influence the VE vs. VCO2 relationship. In the present study, we added external DS, which at each step of exercise, was associated to an increase of VD/VT and PaCO2 resembling what happens during exercise in COPD patients. Therefore both PaCO2 and VD/VT changes have likely a role in the VE vs. VCO2 relationship changes we observed after adding DS. It is recognized that PaCO2 measurements were done only in HF patients and not in healthy subjects, but a different behaviour in healthy subjects is unlikely.