Association of body mass index and its long-term changes with cardiometabolic diseases: A nationwide twin study

The association between higher body mass index (BMI) and cardiometabolic diseases (CMDs, including type 2 diabetes and cardiovascular diseases) is not well understood. We aimed to examine the association of BMI and its long-term changes with cardiometabolic diseases (CMDs) and explore the role of familial background and healthy lifestyle in this association.

Within the Swedish Twin Registry, 36 622 CMD-free individuals aged ≥40 were followed for up to 16 years. BMI data was collected at baseline and 25-35 years prior to baseline. Healthy lifestyle (non-smoking, no/mild alcohol consumption, and regular physical activity) was assessed as unfavourable (none or only one of these factors) vs. favourable (two or three). Incident CMDs were identified by linkage with the Swedish National Patient Registry. Two strategies were followed: 1) Cox models in all twin individuals; 2) stratified Cox models in CMD-discordant twin pairs.

At baseline, 16 195 (44.2%) study participants had overweight/obesity (BMI ≥ 25 kg/m²) and 11 202 (30.6%) developed CMDs over follow-up. Among all participants, the hazard ratio (HR) and 95% confidence interval (CI) of developing any CMD was 1.52 (1.45-1.58) for people with overweight/obesity compared to normal BMI (20-25 kg/m²). Compared to stable normal BMI, HRs (95% CIs) of CMDs were 1.28 (1.02-1.59) and 1.33 (1.24-1.43) for only earlier life or only later life overweight/obesity, respectively, and 1.69 (1.55-1.85) for overweight/obesity both in earlier and later life. In stratified Cox analyses conducted among all CMD-discordant twin pairs, overweight/obesity was associated with greater risk of CMDs (1.37, 95% CI 1.18-1.61). In joint effect analysis, the risk of CMDs related to overweight/obesity was diminished 32% among people with a favourable lifestyle (1.51, 95% CI 1.44-1.58) compared to those with overweight/obesity and an unfavourable lifestyle (2.20, 95% CI 2.03-2.38).

Overweight/obesity is associated with an increased risk of CMDs, and shared genetic and early-life environmental factors might not account for this association. However, a favourable lifestyle could attenuate the risk of high BMI-related CMDs.