Elucidating causal effects of type 2 diabetes on ischemic heart disease from observational data on middle‑aged Swedish women: a triangular analytical approach Sundquist, Kristina Jiménez Mejías, Eladio Open access funding provided by Lund University. The study was supported by ALF medel from Region Skane to Susanna Calling and Kristina Sundquist and by the Swedish Heart-Lung Foundation to Kristina Sundquist. The funders had no role in study design, analysis, interpretation of data or preparation of the manuscript. The association between type 2 diabetes (T2D) and ischemic heart disease (IHD) is well established but the potential causal association needs further studying. In an attempt to elucidate the causal effect of T2D on IHD, we used three different analytical approaches in two different datasets. A well-defined cohort of 6047 women aged 50–59 years were included at baseline (1995 to 2000) and followed until 2015 for IHD. The median follow-up was 16.3 years. We used a Marginal Structural Cox model (MSM Cox) to account for time-varying exposure (time at onset of T2D) and for ten confounders (using inverse probability weighting, IPW). We also compared the MSM-Cox models with traditional Cox regression modelling in the cohort. Finally, we analyzed information on individuals from Swedish population-based registers with national coverage in a comprehensive co-relative design and extrapolated the results to MZ twins. The Hazard Ratio (HR) for IHD in relation to T2D at baseline and T2D occurring during the follow-up in the MSM Cox model weighted by IPW (based on the ten included confounders) was 1.43 (95% confidence interval [CI] 1.07–1.92). The corresponding HR from the traditional Cox regression model was of similar effect size. The average extrapolated MZ twin estimate from our co-relative model was 1.61 (95% CI 1.48–1.86). Our findings, based on a triangular approach, support the existence of a causal association between T2D and IHD and that preventive long-term measures in order to avoid or postpone IHD should include monitoring and treatment of both the T2D itself as well as other cardiovascular risk factors. 2021-09-16T08:22:03Z 2021-09-16T08:22:03Z 2021-06-15 info:eu-repo/semantics/article Sundquist, K... [et al.]. Elucidating causal effects of type 2 diabetes on ischemic heart disease from observational data on middle-aged Swedish women: a triangular analytical approach. Sci Rep 11, 12579 (2021). [https://doi.org/10.1038/s41598-021-92071-9] http://hdl.handle.net/10481/70221 10.1038/s41598-021-92071-9 eng http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Atribución 3.0 España Nature