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Response by Sattar et al to Letters Regarding Article, "Age at Diagnosis of Type 2 Diabetes Mellitus and Associations With Cardiovascular and Mortality Risks".

Circulation. 2019;140:e724–e725. DOI: 10.1161/CIRCULATIONAHA.119.042457 e724 Naveed Sattar, FMedSci Araz Rawshani, PhD Stefan Franzen, PhD In Response: We thank Wang and colleagues for their interest in our article. The main reason for putting a limit on duration at cohort entry is that we were concerned that individuals whose diabetes mellitus was diagnosed a long time ago would not be representative for what will happen to patients diagnosed today or in the near future, especially because treatments and risks have greatly changed. Thus, we were concerned that left censoring would be noninformative if we did not put a limit on duration. This approach also resulted in better overlap (across age at onset groups) in duration of diabetes mellitus, making the analysis more robust. Our duration limit was of course arbitrary, as any other choice would be. In regard to the point about the age at which type 2 diabetes mellitus becomes higher risk, we would respectfully remind others that there is a tension between lifetime risk (often greater in younger-onset disease) and 10-year cardiovascular disease risk (often greater in those who are older). Thus, the point we make in our article1 is that developing type 2 diabetes mellitus when younger leads to greater lifetime risks of adverse cardiovascular outcomes and more life-years lost. It follows, therefore, that earlier preventive treatments in those who develop type 2 diabetes mellitus when younger would lead to more gains in life expectancy, as shown nicely by modeling in the Joint British Societies recommendations for the prevention of cardiovascular disease risk score.2,3 We also thank Wang and Xu for their interest in the effect of age at onset of type 2 diabetes mellitus. We are pleased that they appreciate the complexity of the statistical modeling needed to address this difficult but very interesting topic. There often are several models to choose from, and we agree that both Poisson regression and relative survival are viable options that have distinct advantages. In the model we have selected, the use of control subjects was absolutely critical, and because the control subjects did not have diabetes mellitus and therefore had no duration, they formed the reference group that was captured by the baseline hazard. We agree that the effect of including the second time scale in the model, as we did, is equivalent to adjusting for a linear effect of the second time scale, as pointed out by Iacobelli and Carstensen,4 but this is exactly what we wanted to achieve. The need to use the second time scale did not, however, come from the use of control subjects. The use of duration of diabetes mellitus came from the need to account for type 2 diabetes mellitus being a progressive disease. When we compare individuals in the National Diabetes Registry with diagnosis in different age groups, we need to account for the facts that we cannot follow everyone from disease onset and that the groups may have different distributions of duration of disease. Now, this being noted, the results of our analyses © 2019 American Heart Association, Inc. RESPONSE TO LETTER TO THE EDITOR