Smoking Cessation and Weight Change in Relation to Cardiovascular Disease Incidence and Mortality in People with Type 2 Diabetes: a Population-based Cohort Study

Background: To reduce their overall substantially increased risk of cardiovascular disease and premature mortality, smoking cessation is especially important for people with diabetes. However, the effect of weight change after quitting smoking on the long-term health consequences of smoking cessation is unclear. We aimed to examine smoking cessation and subsequent weight change in relation to incident cardiovascular disease events and mortality among adults with type 2 diabetes.

Methods: In this population-based cohort study, we analysed data from people with type 2 diabetes from two prospective cohorts in the USA: the Nurses' Health Study (1976-2014) and the Health Professionals Follow-Up Study (1986-2014). We included participants from both cohorts who either had prevalent type 2 diabetes or were diagnosed during the study, and who were either current smokers or never smokers without cardiovascular disease or cancer at diagnosis of diabetes. Information on demographics, newly diagnosed diseases, medical history, and lifestyle factors, including smoking status and weight change, was updated every 2 years through validated questionnaires. We assessed the incidence of cardiovascular disease and all-cause and cause-specific mortality among recent quitters (within 6 years of stopping) and long-term quitters (>6 years) associated with weight change within 6 years of smoking cessation among people with type 2 diabetes. We did a multivariable-adjusted Cox proportional hazard models to estimate hazard ratios (HRs) for the associations of smoking cessation and weight change on the outcomes.

Findings: Of 173 229 total cohort participants (121 700 from the Nurses' Health Study and 51 529 from the Health Professionals Follow-Up Study), 10 809 people with type 2 diabetes were included in the incident cardiovascular disease analysis and 9688 were included in the mortality analysis. 2580 incident cases of cardiovascular disease occurred during 153 166 person-years of follow-up, and 3827 deaths occurred during 152 811 person-years of follow-up. Recent quitters (2-6 consecutive years since smoking cessation) without weight gain within the first 6 years of quitting had a significantly lower risk of cardiovascular disease than people who continued to smoke (multivariable-adjusted HR 0·83 [95% CI 0·70-0·99] among all recent quitters, 0·77 [0·62-0·95] among recent quitters without weight gain, 0·99 [0·70-1·41] among recent quitters with weight gain of 0·1-5·0 kg, 0·89 [0·65-1·23] among recent quitters with weight gain of >5·0 kg, and 0·72 [0·61-0·84] among longer-term quitters [>6 consecutive years since smoking cessation]). Weight gain within 6 years after smoking cessation did not attenuate the inverse relation between long-term cessation and all-cause mortality (multivariable-adjusted HR 0·69 [95% CI 0·58-0·82] among long-term quitters without weight gain, 0·57 [0·45-0·71] among long-term quitters with weight gain of 0·1-5·0 kg, and 0·51 [0·42-0·62] among long-term quitters with weight gain of >5·0 kg), with similar results observed for cardiovascular disease and cancer mortality.

Interpretation: Smoking cessation without subsequent weight gain is associated with a reduced risk of cardiovascular disease and mortality among smokers with type 2 diabetes. Weight gain after smoking cessation attenuates the reduction in risk of developing cardiovascular disease, but does not attenuate the beneficial effect of smoking cessation with respect to mortality. These findings confirm the overall health benefits of quitting smoking among people with type 2 diabetes, but also emphasise the importance of weight management after smoking cessation to maximise its health benefits.

Funding: US National Institutes of Health.