A healthy lifestyle mitigates the risk of heart disease related to type 2 diabetes: a prospective nested case–control study in a nationwide Swedish twin cohort

Aims/hypothesis We aimed to examine the association between type 2 diabetes and major subtypes of heart disease, to assess the role of genetic and early-life familial environmental factors in this association and to explore whether and to what extent a healthy lifestyle mitigates the risk of heart disease related to type 2 diabetes. Methods In this prospective nested case–control study based on the Swedish Twin Registry, 41,463 twin individuals who were aged ≥40 and heart disease-free were followed up for 16 years (from 1998 to 2014) to detect incident heart disease. Type 2 diabetes was ascertained from self-report, the National Patient Registry and glucose-lowering medication use. Heart disease diagnosis (including coronary heart disease, cardiac arrhythmias and heart failure) and onset age were identified from the National Patient Registry. Healthy lifestyle-related factors consisted of being a non-smoker, no/mild alcohol consumption, regular physical activity and being non-overweight. Participants were divided into three groups according to the number of lifestyle-related factors: (1) unfavourable (participants who had no or only one healthy lifestyle factor); (2) intermediate (any two or three); and (3) favourable (four). Generalised estimating equation models for unmatched case–control design and conditional logistic regression for co-twin control design were used in data analyses. Results Of all participants, 2304 (5.5%) had type 2 diabetes at baseline. During the observation period, 9262 (22.3%) had any incident heart disease. In unmatched case–control analyses and co-twin control analyses, the multi-adjusted OR and 95% CI of heart disease related to type 2 diabetes was 4.36 (3.95, 4.81) and 4.89 (3.88, 6.16), respectively. The difference in ORs from unmatched case–control analyses vs co-twin control analyses was statistically significant (OR 1.57; 95% CI 1.42, 1.73; p