Smoking, all-cause, and cause-specific mortality in individuals with diabetes in Mexico: an analysis of the Mexico City Prospective Study

BACKGROUND Evidence from low– and middle-income countries regarding the effect of smoking in people with diabetes is lacking. Here, we report the association of smoking with mortality in a large cohort of Mexican adults with diabetes. METHODS Participants with diabetes mellitus (self-reported medical diagnosis, use of antidiabetic medications or HbA1c ≥6.5%) aged 35-74 years when recruited into the Mexico City Prospective Study were included. Cox regression confounder-adjusted mortality rate ratios (RRs) associated with baseline smoking status were estimated. FINDINGS Among 15,975 women and 8225 men aged 35-74 years with diabetes but no other comorbidities at recruitment, 2498 (16%) women and 2875 (35%) men reported former smoking and 2753 (17%) women, and 3796 (46%) men reported current smoking. Smoking less than daily was common: 39.4% of female current smokers and 30.7% of male current smokers. During a median of 17 years of follow-up there were 5087 deaths at ages 35-74 years. Compared with never smoking, the all-cause mortality RR was 1.08 (95%CI 1.01–1.17) for former smoking, 1.09 (95%CI 0.99–1.20) for non-daily smoking, 1.06 (95%CI 0.96–1.16) for smoking <10 cigarettes per day (median during follow-up 4 cigarettes/day) and 1.28 (95% CI 1.14–1.43) for smoking ≥10 cigarettes/day (median during follow-up 15 cigarettes/day). Excess mortality among current daily smokers was greatest for COPD, lung cancer, cardiovascular diseases, and acute diabetic complications. INTERPRETATION In this cohort of Mexican adults with diabetes, low-intensity daily smoking was associated with increased mortality, despite observing smoking patterns which are different from other populations. Of those smoking ≥10 cigarettes per day, over one fifth were killed by their habit. Quitting substantially reduced these risks. Evidence before this study We conducted a search in PubMed to identify studies on smoking-related mortality in individuals with diabetes before September 1st, 2023, using the terms ((diabetes mellitus) OR (type 2 diabetes mellitus)) AND ((smoking) OR (tobacco)) AND ((mortality) OR (survival analysis) OR (death)). We identified a meta-analysis published in 2015 which analysed data from 1,132,700 participants with diabetes from 89 cohort studies. Among current and former smokers, the pooled adjusted relative risk for all-cause mortality was 1.55 (95% CI 1.46–1.64) and 1.19 (95% CI 1.11–1.28), respectively. Among current smokers, there was considerably higher risk of death due to cardiovascular disease, coronary heart disease, stroke, peripheral arterial disease, and heart failure. Most included studies were conducted in high income countries and only one was done in Latin America (Argentina, 1,730 participants). In Mexico, epidemiological studies related to smoking have been primarily descriptive in nature. A previous study of the MCPS that analysed all-cause smoking-related mortality among disease-free individuals found adjusted rate ratios among daily smokers of 1.17 (95% CI 1.10–1.25) for those using <10 cigarettes/day and 1.54 (95% CI 1.42–1.67) for those using ≥10 cigarettes/day. In this study, mortality risk in people with diabetes was not assessed separately. Instead, mortality risk estimates were obtained for several chronic diseases as a group. No other studies have analysed changes in smoking habits and smoking-related mortality in Mexican individuals with diabetes. Added value of this study To our knowledge, this is the first analysis of longitudinal data of Mexican adults with diabetes (n=24,200) followed over 17 years, to examine the association between smoking and all-cause and cause-specific mortality. Compared with never smokers with diabetes, former and daily smokers with diabetes had elevated mortality. Among daily smokers there was higher risk of death due to cardiovascular disease, acute diabetes complications, lung cancer and COPD. Our results are generally consistent with previous analyses that have found smoking as a significant risk factor for higher mortality in individuals with diabetes. Our estimates, however, are comparably lower for all-cause mortality, possibly related to distinct smoking habits specific to the Mexican population with diabetes. Implications of all available evidence Our results confirm that smoking is a significant risk factor for all-cause and cause-specific mortality among Mexican adults with diabetes. Strategies to promote smoking cessation among individuals with diabetes should be encouraged, particularly given that tobacco use is a modifiable risk factor. This is especially meaningful in middle-to lower-income countries like Mexico, where diabetes prevalence is increasing and achieving glycaemic targets remains a challenge. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was supported by Instituto Nacional de Geriatria in Mexico. The funding sources had no role in the design, conduct or analysis of the study or the decision to submit the manuscript for publication. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study protocol was approved by the corresponding ethics committees at the Mexican Ministry of Health, the Mexican National Council for Science and Technology, and the University of Oxford. All study participants provided written informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes