Objectives To examine the association between low birth weight (LBW) and cardiometabolic diseases (CMDs, including heart disease, stroke and type 2 diabetes mellitus) in adulthood, and to explore whether genetic, early-life environmental and healthy lifestyle factors play a role in this association.

Design A population-based twin study.

Setting Twins from the Swedish Twin Registry who were born in 1958 or earlier participated in the Screening Across the Lifespan Twin (SALT) study for a full-scale screening during 1998-2002 and were followed up until 2014.

Participants 19 779 twin individuals in Sweden with birthweight data available (mean age: 55.45 years). Primary and secondary outcome measures CMDs were assessed based on self-reported medical records, medication use and records from the National Patient Registry. A lifestyle index encompassing smoking status, alcohol consumption, exercise levels and Body Mass Index was derived from the SALT survey and categorised as unfavourable, intermediate or favourable. Data were analysed using generalised estimating equation (GEE) models and conditional logistic regression models.

Results Of all participants, 3998 (20.2%) had LBW and 5335 (27.0%) had incident CMDs (mean age at onset: 63.64 +/- 13.26 years). In GEE models, the OR of any CMD was 1.39 (95% CI 1.27 to 1.52) for LBW. In conditional logistic regression models, the LBW-CMD association became non-significant (OR=1.21, 95% CI 0.94 to 1.56). The difference in ORs from the two models was statistically significant (p<0.001). In the joint effect analysis, the multiadjusted OR of CMDs was 3.47 (95% CI 2.72 to 4.43) for participants with LBW plus an unfavourable lifestyle and 1.25 (95% CI 0.96 to 1.62) for those with LBW plus a favourable lifestyle.

Conclusion LBW is associated with an increased risk of adult CMDs, and genetic and early-life environmental factors may account for this association. However, a favourable lifestyle profile may modify this risk.