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Canadian Journal of Cardiology

Smoking and diabetes: sex and gender aspects and their impact on vascular diseases

Open AccessPublished:January 22, 2023DOI:https://doi.org/10.1016/j.cjca.2023.01.018

      Abstract

      Smoking and diabetes mellitus (DM) have been identified as two major cardiovascular risk factors for many years. In the field of cardiovascular diseases, considering sex differences, or gender differences, or both has become an essential element in moving toward equitable and quality healthcare. We reviewed the impact of sex or gender on the link between smoking and DM. The risk of type 2 DM (T2DM) due to smoking has been established in both sexes at the same level. As is the case in the general population, the prevalence of smoking in those with DM is higher in men than in women, although the decrease in smoking observed in recent years is more pronounced in men than in women. Regarding chronic DM complications, smoking is an independent risk factor for all-cause mortality, as well as macrovascular and microvascular complications, in both sexes. Nevertheless, in T2DM, the burden of smoking appears to be greater in women than in men for coronary heart disease morbidity, women having a 50% higher risk of fatal coronary event. Women are more dependent to nicotine, cumulate psychosocial barriers to quitting smoking, and are more likely to gain weight, which might make it more difficult for them to quit smoking. Smoking cessation advice and treatments should take into account gender differences to improve the success and long-term maintenance of abstinence in people with and without DM. This might include interventions that address emotions and stress in women or designed to reach specific populations of men.

      Keywords

      Introduction

      Sex and gender dimensions have become a major concern in health and healthcare in recent years, particularly in the field of metabolic and chronic diseases
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      Cigarette smoking is the main avoidable cause of death in high- and middle-income countries. It is responsible for cancers, cardiovascular and respiratory diseases and has been associated with an increasing number of other diseases, including T2DM

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      Figure thumbnail gr1
      Figure 1Sex and gender aspects in smoking and diabetes: a complex interplay. 1a: Sex and gender aspects in smoking. 1b: Sex and gender aspects in diabetes. 1c: Sex and gender aspects in the association between smoking and diabetes
      Taking into account gender and sex dimensions makes it possible to better adapt care for populations in terms of prevention, diagnosis, and the therapeutic approach and thus to move toward socially equitable medicine
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      This article focuses on sex and gender differences in the interplay between smoking and DM; we discuss the impact of smoking on the incidence of T2DM, the prevalence of smoking in people with DM, the impact of smoking on DM complications, smoking cessation interventions and the benefits and risks of smoking cessation in people with T2DM. The consequences of smoking in pregnant women with DM and the association between smoking and gestational DM are not discussed.

      Association between smoking and incident T2DM in men and women

      An association between smoking and the incidence of T2DM has been demonstrated for several decades. Meta-analyses have found an increased risk of around 40% in developing T2DM in smokers

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      . Many studies have evaluated the association between smoking, sex, and the risk of developing T2DM.
      Meta-analyses published in the last two decades support the link between smoking and T2DM in both men and women
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      . A meta-analysis published in 2015, which included 88 studies with more than 5 million participants and more than 220,000 cases of incident DM, found an relative risk (RR) of T2DM in smokers compared with non-smokers of 1.42 (95% Confidence Interval [95% CI]: 1.34-1.50) and 1.33 (95% CI: 1.26-1.41) in men and women, respectively
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      . The authors estimated that, based on the assumption that the association between smoking and T2DM is causal, 11.7% of T2DM cases in men and 2.4% of T2DM cases in women could be attributed to active smoking. This figure is likely an underestimate, since passive smoking was not taken into account
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      . According to some authors, this excess risk appears after age of 35 in men and women
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      . Given the equivalent RR between men and women, it would seem that this risk is equivalent between the two sexes. More recently, Yuan et al. published a meta-analysis assessing the risk of smoking-related T2DM in women compared with that in men. After inclusion of 20 prospective cohort studies with more than 5 million participants and more than 220,000 cases of incident DM, the authors still found a positive association between smoking and T2DM with an increased risk of 35% and 27% in male and female smokers, respectively, compared with that in non-smokers. The relative risk ratio (RRR) between men and women was nonsignificant at 0.98 (95% CI: 0.96-1.01). The authors therefore concluded that there was no sexual dimorphism in the association between active smoking and risk of developing T2DM
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      . Although active smoking is associated with the risk of T2DM, passive smoking has also been shown to be a risk factor for T2DM in both men and women
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      .
      • An association between smoking (active and passive) and the development of T2DM has been established in women and men.
      • The excess risk of T2DM conferred by smoking appears to be comparable between men and women.

      Differences in the prevalence of smoking between men and women with DM

      The prevalence of smoking among people with DM is 20-30%, similar to that observed in the general population
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      . Overall, it seems, that the prevalence of smoking among men is higher than that of women, regardless of the type of DM
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      Smoking and diabetes interplay: A comprehensive review and joint statement.
      . Because of different socio-cultural behaviors and norms, disparities in prevalence are observed by geographic region. In a study conducted by the World Health Organization on vascular complications among people with DM between 1983 and 1990, the prevalence of smoking among men had decreased remarkably, whereas it had remained stable among women (10.7% decrease in men vs 0.5% decrease in women)
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      Prevalence of small vessel and large vessel disease in diabetic patients from 14 centres. The World Health Organisation Multinational Study of Vascular Disease in Diabetics. Diabetes Drafting Group. Diabetologia. 1985;28 Suppl:615-640.

      .
      The intersectionality between sex or gender, ethnicity, and socio-economic level is of interest. For example, in a population of 1,899 patients with DM (16% smokers, 31% ex-smokers, and 51% non-smokers) in London, Gulliford et al. observed
      • Gulliford M.C.
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      • Pearce A.J.
      Cigarette smoking, health status, socio-economic status and access to health care in diabetes mellitus: a cross-sectional survey.
      that smoking was more prevalent among people of Caucasian origin than it was among people of African or Afro-Caribbean origin. Few differences were observed between men and women among people of Caucasian origin (22% vs 20%, respectively), whereas a greater difference existed among men and women of Afro-Caribbean (15% vs 10%, respectively) or African (8 vs 2%, respectively) origin
      • Gulliford M.C.
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      Cigarette smoking, health status, socio-economic status and access to health care in diabetes mellitus: a cross-sectional survey.
      . A Centers for Disease Control and Prevention study conducted between 2001 and 2010 found a decrease in smoking prevalence in all ethnic subgroups
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      . However, the decrease was less pronounced in people with DM, especially women with DM compared with men with DM (-2.2% in men and -0.8% in women). In contrast to many studies showing a male preponderance in the prevalence of smoking in people with DM, a Canadian study found that female sex was more frequently associated with the risk of being a smoker, regardless of type of DM
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      Demographic, health, and behavioral factors associated with smoking in adults with type 1 or type 2 diabetes.
      . One of the explanations put forward by the authors was the greater decline in smoking prevalence among men than among women. Similarly, studies in young populations with or without DM have shown that young girls were more exposed to tobacco than were young boys
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      . In a recent Austrian study, an increase in smoking prevalence was observed among women between 2007 and 2014, whereas it remained stable among men
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      Sex-specific trends in smoking prevalence over seven years in different Austrian populations: results of a time-series cross-sectional analysis.
      . Furthermore, in this study, analyses of people with DM revealed that the most notable increase was observed in populations of women with DM, more specifically in women between 30 and 64 years old and in those over 65 years old, with the prevalence increasing from 9.9% to 16.9%.
      Thus, although the prevalence of smoking is globally higher among men than it is among women with DM, some data tend to show that women with DM have increased their smoking prevalence in recent years, particularly the younger generations, or at least that the decrease in smoking prevalence is less pronounced in women than in men. This phenomenon can be explained by the tobacco industry's advertising campaigns targeting women
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      Sy D, Mackay J. Women and the Tobacco Industry https://exposetobacco.org/wp-content/uploads/Women-and-the-Tobacco-Industry-3.5.21.pdf: J for Global Center for Good Governance in Tobacco Control (GGTC); 2021.

      . Moreover, countries with higher gender empowerment have a higher proportion of women who smoke, in keeping with the industry’s use of female empowerment to promote smoking behavior
      • Hitchman S.C.
      • Fong G.T.
      Gender empowerment and female-to-male smoking prevalence ratios.
      . Women entering the workforce have not only assumed more traditional male roles, but they have also combined family care and paid work, resulting in stressful life experiences that women try to cope with by using cigarettes

      Graham H. When Life’s a Drag: Women, Smoking and Disadvantage. University of Warwick, UK: Great Britain Department of Health; 1993.

      . In high-income countries, it has been reported that smoking affects more people of low socioeconomic classes and women with stress, mental health disorders or with histories of violence, resulting in increasing health inequalities
      • Greaves L.
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      . It is therefore important that health and prevention policies target particularly women.
      • As observed in the general population, the prevalence of smoking varies between men and women with DM, it being overall higher in men than in women.
      • The trend toward a decrease in smoking observed in men in recent years seems to be less pronounced in women.

      Influence of sex and gender in interaction with smoking on complications of chronic DM

      The role of smoking in all-cause mortality, developing macrovascular and microvascular complications in the population with DM has been demonstrated by numerous studies, smoking being the strongest predictor of death among all risk factors
      • Rawshani A.
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      Risk Factors, Mortality, and Cardiovascular Outcomes in Patients with Type 2 Diabetes.
      . Studies in the general population have shown a greater negative health impact of smoking in women than in men for cardiovascular diseases
      • Huxley R.R.
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      Cigarette smoking as a risk factor for coronary heart disease in women compared with men: a systematic review and meta-analysis of prospective cohort studies.
      . In people with DM, studies show sex differences in the occurrence of several chronic diabetic complications, especially a higher burden of DM on cardiovascular risk in women
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      • Mishra G.D.
      • Woodward M.
      Risk of all-cause mortality and vascular events in women versus men with type 1 diabetes: a systematic review and meta-analysis.
      • de Ritter R.
      • de Jong M.
      • Vos R.C.
      • et al.
      Sex differences in the risk of vascular disease associated with diabetes.
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      Excess risk of mortality and cardiovascular events associated with smoking among patients with diabetes: meta-analysis of observational prospective studies.
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      Sex differences in cardiovascular and total mortality among diabetic and non-diabetic individuals with or without history of myocardial infarction.
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      • Fonseca V.
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      Sex and Gender and Allostatic Mechanisms of Cardiovascular Risk and Disease.
      (Table 1). In a meta-analysis of 37 prospective studies that included people with and without T2DM, Huxley et al. found a higher RR of fatal coronary events in women than in men with DM compared to women and men without DM
      • Huxley R.
      • Barzi F.
      • Woodward M.
      Excess risk of fatal coronary heart disease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies.
      . The RRR between women and men with DM was 1.46 (95% CI: 1.14-1.88), indicating that women with DM had about a 50% higher risk of a fatal coronary event than did men with DM. For T1DM, the same authors found an excess risk of all-cause mortality of about 40% in women compared with men. The risk of fatal and nonfatal vascular events was twice as high in women as in men
      • Huxley R.R.
      • Peters S.A.
      • Mishra G.D.
      • Woodward M.
      Risk of all-cause mortality and vascular events in women versus men with type 1 diabetes: a systematic review and meta-analysis.
      . Similar results were found for the risk of stroke in another study
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      Diabetes as a risk factor for stroke in women compared with men: a systematic review and meta-analysis of 64 cohorts, including 775,385 individuals and 12,539 strokes.
      .
      Table 1Sex-stratified impact of diabetes on chronic macro- and microvascular complications
      StudyType of diabetesOutcomeWomen RR* (95% CI)Men RR* (95% CI)Men HR** (95% CI)Women:Men Ratio of RR (95% CI)
      Macrovascular complications
      Huxley et al.

      2006
      • Qin R.
      • Chen T.
      • Lou Q.
      • Yu D.
      Excess risk of mortality and cardiovascular events associated with smoking among patients with diabetes: meta-analysis of observational prospective studies.
      T2DMCHD mortality (37 studies)3.50 (2.70-4.53)2.06 (1.81-2.34)1.70 (1.27-2.27)
      CHD mortality (Multiple adjusted;

      29 studies;)
      2.95 (2.39-3.65)2.02 (1.76-2.31)1.46 (1.14-1.88)
      Peters et al.

      2014
      • Hu G.
      • Jousilahti P.
      • Qiao Q.
      • Katoh S.
      • Tuomilehto J.
      Sex differences in cardiovascular and total mortality among diabetic and non-diabetic individuals with or without history of myocardial infarction.
      T2DMStroke (64 studies)2·28 (1.93-2.69)1·83 (1.60-2.08)1.27 (1.10-1.46)
      Microvascular complications
      Singh et al.

      2020
      • Blomster J.I.
      • Woodward M.
      • Zoungas S.
      • et al.
      The harms of smoking and benefits of smoking cessation in women compared with men with type 2 diabetes: an observational analysis of the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron modified release Controlled Evaluation) trial.
      T2DMMicroalbuminuria1.64 (1.21–2.24)
      Retinopathy1.27 (0.93–1.74)$
      Neuropathy1.35 (0.99–1.83)$
      RR: Relative Risk; HR: Hazard Ratio; 95% CI: 95% Confidence Interval; CHD: coronary heart disease; T2DM: Type 2 Diabetes Mellitus.
      *People without diabetes are the reference group
      **Women are the reference group
      $ Not significant
      Regarding the sex-specific impact of smoking on cardiovascular and some microvascular complications in populations with DM, the deleterious impact of smoking is higher among women than men (summarized in Table 2 and Figure 2). As early as 1990, Moy et al. described the deleterious role of tobacco in women with DM in a US cohort of 723 participants with T1DM
      • Moy C.S.
      • LaPorte R.E.
      • Dorman J.S.
      • et al.
      Insulin-dependent diabetes mellitus mortality. The risk of cigarette smoking.
      . In this cohort, smoking was an independent risk factor of mortality in women but not in men. The excess mortality in women with DM could be explained by the higher occurrence of coronary heart disease (CHD) and mediated by higher contribution of cardiovascular risk factors such as high blood pressure and higher plasma lipids in women with DM than in men with DM
      • Huxley R.
      • Barzi F.
      • Woodward M.
      Excess risk of fatal coronary heart disease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies.
      . Several mechanisms may explain the higher toxicity of smoking in women, but they are not fully understood. First, women have on average a smaller body surface than men do and so they may extract more carcinogens and toxic substances from tobacco smoke than men do
      • Woodward M.
      • Tunstall-Pedoe H.
      • Smith W.C.
      • Tavendale R.
      Smoking characteristics and inhalation biochemistry in the Scottish population.
      . Second, hormones such as estrogens have an influence on the metabolism of nicotine, increasing its clearance
      • Hukkanen J.
      • Jacob 3rd, P.
      • Benowitz N.L.
      Metabolism and disposition kinetics of nicotine.
      . As a consequence women might smoke more intensely to compensate, leading to an increase in toxicity
      • Berlin I.
      Incidence of Lung Cancer among Young Women.
      . Third, women are more exposed to second hand smoke than men
      • Oberg M.
      • Jaakkola M.S.
      • Woodward A.
      • Peruga A.
      • Pruss-Ustun A.
      Worldwide burden of disease from exposure to second-hand smoke: a retrospective analysis of data from 192 countries.
      . Thus, women who smoke are more likely to be doubly exposed to second hand smoke and to their own consumption, leading to higher total exposure than occurs for men. Nevertheless, this excess risk is not found in all studies; for example, in several studies that report an increased risk of cardiovascular disease in women with T1DM compared with that in men, smoking was not considered to be an explanation for the sex difference
      • Colhoun H.M.
      • Rubens M.B.
      • Underwood S.R.
      • Fuller J.H.
      The effect of type 1 diabetes mellitus on the gender difference in coronary artery calcification.
      • Livingstone S.J.
      • Looker H.C.
      • Hothersall E.J.
      • et al.
      Risk of cardiovascular disease and total mortality in adults with type 1 diabetes: Scottish registry linkage study.
      • Dabelea D.
      • Kinney G.
      • Snell-Bergeon J.K.
      • et al.
      Effect of type 1 diabetes on the gender difference in coronary artery calcification: a role for insulin resistance? The Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study.
      . Furthermore, in the EURODIAB Prospective Complications Study, current smoking was identified as a risk factor for CHD only in men, although the difference between men and women was not statistically significant after multivariate adjustment
      • Soedamah-Muthu S.S.
      • Chaturvedi N.
      • Toeller M.
      • et al.
      Risk factors for coronary heart disease in type 1 diabetic patients in Europe: the EURODIAB Prospective Complications Study.
      . In the Finnish Diabetic Nephropathy (FinnDiane) study, which included 4,506 individuals with T1DM, no interaction was found between smoking and sex in cardiovascular disease risk with the exception of stroke
      • Feodoroff M.
      • Harjutsalo V.
      • Forsblom C.
      • Groop P.H.
      • FinnDiane Study G.
      Dose-dependent effect of smoking on risk of coronary heart disease, heart failure and stroke in individuals with type 1 diabetes.
      . This risk was higher in both current and former smokers than in never smokers in men only.
      Table 2Sex-stratified impact of smoking on chronic macro- and microvascular complications in people with diabetes
      StudyType of diabetesOutcomeWomen RR or HR (95% CI)Men RR or HR (95% CI)Women:Men Ratio of HR (95% CI)
      Macrovacular complications
      Moy et al. 1990
      • de Ferranti S.D.
      • de Boer I.H.
      • Fonseca V.
      • et al.
      Type 1 diabetes mellitus and cardiovascular disease: a scientific statement from the American Heart Association and American Diabetes Association.
      T1DMMortalityRR 2.57 (1.04–6.36)*RR 1.21 (0.57–2.55)$,*
      CHD mortalityRR 5.16 (1.29–20.57)*RR 0.78 (0.21–2.86)$,*
      Nilsson et al.

      2009
      • Dabelea D.
      • Kinney G.
      • Snell-Bergeon J.K.
      • et al.
      Effect of type 1 diabetes on the gender difference in coronary artery calcification: a role for insulin resistance? The Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study.
      T2DMFatal/non-fatal myocardial infarctionHR 2.17 (1.69–2.79)*HR 1.45 (1.19–1.77)*
      Barengo et al.

      2017
      • Soedamah-Muthu S.S.
      • Chaturvedi N.
      • Toeller M.
      • et al.
      Risk factors for coronary heart disease in type 1 diabetic patients in Europe: the EURODIAB Prospective Complications Study.
      T2DMAll-cause mortalityHR 4.51 (2.91-7.00)**HR 3.76 (2.95-4.78)**
      CHD mortalityHR 6.92 (2.79-17.19)**HR 2.62 (1.60-4.29)**
      CHD incidenceHR 4.55 (2.48-8.33)**HR 3.27 (2.45-4.36) **
      Blomster et al.

      2016
      • Feodoroff M.
      • Harjutsalo V.
      • Forsblom C.
      • Groop P.H.
      • FinnDiane Study G.
      Dose-dependent effect of smoking on risk of coronary heart disease, heart failure and stroke in individuals with type 1 diabetes.
      T2DMMajor coronary events1.64 (0.83-3.26)$,∗∗∗
      Microvascular complications
      Blomster et al.

      2016
      • Feodoroff M.
      • Harjutsalo V.
      • Forsblom C.
      • Groop P.H.
      • FinnDiane Study G.
      Dose-dependent effect of smoking on risk of coronary heart disease, heart failure and stroke in individuals with type 1 diabetes.
      T2DMNephropathy1.04 (0.57-1.89)$,∗∗∗
      RR: Relative Risk; HR: Hazard Ratio; 95% CI: 95% Confidence Interval; CHD: coronary heart disease; T1DM: Type 1 Diabetes Mellitus ; T2DM: Type 2 Diabetes Mellitus.
      * Cox regression analysis
      ** People without diabetes and without smoking are the reference group (HR=1). In the table, results are for women or men with T2DM and smokers. In women with T2DM and non-smokers, HRs (95%CI) were 2.11 (1.71-2.59), 4.06 (2.83-5.82), 2.60 (2.02-3.35) for all-cause mortality, CHD mortality and CHD incidence, respectively. In men with T2DM and non-smokers, HRs (95%CI) were 2.03 (1.51-2.74), 2.62 (1.60-4.29), 1.56 (1.08-2.24) for all-cause mortality, CHD mortality and CHD incidence, respectively.
      ***Ratio of the HRs (women:men) for daily smoking versus never smoking
      $ Not significant
      Figure thumbnail gr2
      Figure 2Impact of smoking on chronic complications of type 2 diabetes mellitus according to sex
      In T1DM, data are scarce and conflicting concerning the role of smoking in the sex-specific cardiovascular morbi-mortality. In a British prospective study of women, with a mean follow-up of 6.1 years, smoking was the strongest modifiable cardiovascular risk factor in middle-aged women with DM, particularly in those treated with insulin, compared to women of the same age without DM
      • Spencer E.A.
      • Pirie K.L.
      • Stevens R.J.
      • et al.
      Diabetes and modifiable risk factors for cardiovascular disease: the prospective Million Women Study.
      . The 5-year incidence rate of cardiovascular disease was 4.6 per 100 non-smoking women with DM, 5.9 in non-insulin-treated smoking women with DM, and 11.0 in insulin-treated smoking women with DM all aged 50-69 years
      • Spencer E.A.
      • Pirie K.L.
      • Stevens R.J.
      • et al.
      Diabetes and modifiable risk factors for cardiovascular disease: the prospective Million Women Study.
      . In a Swedish cohort of T2DM, the hazard ratio (HR) for the risk of heart attack (fatal or not) attributable to smoking was higher in women than in men (HR=2.17 [95% CI:1.69-2.79] vs 1.45 [95% CI:1.19-1.77], respectively)
      • Nilsson P.M.
      • Cederholm J.
      • Eeg-Olofsson K.
      • et al.
      Smoking as an independent risk factor for myocardial infarction or stroke in type 2 diabetes: a report from the Swedish National Diabetes Register.
      . In a Finnish cohort of people with and without T2DM that included 28,712 men and 30,700 women aged 25-64 years, smokers with DM had higher all-cause and CHD mortality than non-smokers with DM did, regardless of sex. In addition, the HRs for coronary mortality or incidence of CHD were higher in female smokers with DM than in male smokers with DM, suggesting a more deleterious role of smoking in women with DM
      • Barengo N.C.
      • Teuschl Y.
      • Moltchanov V.
      • Laatikainen T.
      • Jousilahti P.
      • Tuomilehto J.
      Coronary heart disease incidence and mortality, and all-cause mortality among diabetic and non-diabetic people according to their smoking behavior in Finland.
      .
      In the ADVANCE study (Action in Diabetes and Vascular Disease: Preterax and Diamicron modified release Controlled Evaluation), which included 11,140 people with T2DM, 17% of men and 9% of women were smokers, whereas 38% of men and 14% of women had stopped smoking
      • Blomster J.I.
      • Woodward M.
      • Zoungas S.
      • et al.
      The harms of smoking and benefits of smoking cessation in women compared with men with type 2 diabetes: an observational analysis of the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron modified release Controlled Evaluation) trial.
      . Smoking was a risk factor for all cardiovascular events (except major cerebrovascular events), as well as for all-cause mortality, nephropathy, and cancer. The female-to-male HR for smokers vs non-smokers did not reach significance for any of the events, but tended to be higher in women for major coronary events (HR =1.64 [95% CI: 0.83-3.26], p=0.08). Although this result did not reach significance, the authors concluded that there was a signal in favor of an increased risk of smoking in women with T2DM compared with that in men with T2DM who were smokers.
      Results are contradictory as to the incidence of microvascular complications. Some authors report a greater incidence in men than in women, whereas others find no difference
      • Yang J.Y.
      • Kim N.K.
      • Lee Y.J.
      • et al.
      Prevalence and factors associated with diabetic retinopathy in a Korean adult population: the 2008-2009 Korea National Health and Nutrition Examination Survey.
      • Liu Z.
      • Fu C.
      • Wang W.
      • Xu B.
      Prevalence of chronic complications of type 2 diabetes mellitus in outpatients - a cross-sectional hospital based survey in urban China.
      • Pop-Busui R.
      • Lu J.
      • Lopes N.
      • Jones T.L.
      • Investigators B.D.
      Prevalence of diabetic peripheral neuropathy and relation to glycemic control therapies at baseline in the BARI 2D cohort.
      . These studies mainly concern patients with T2DM. Nevertheless, only a few studies evaluated the role of smoking in order to explain such differences. In the previously mentioned ADVANCE study, a similar impact was observed for active smoking on the risk of diabetic nephropathy between men and women (HR between women and men: 1.04 [95% CI: 0.57-1.89])
      • Blomster J.I.
      • Woodward M.
      • Zoungas S.
      • et al.
      The harms of smoking and benefits of smoking cessation in women compared with men with type 2 diabetes: an observational analysis of the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron modified release Controlled Evaluation) trial.
      . The authors acknowledged the lack of statistical power to detect a sex-differentiated impact of smoking. Indeed, the number of women smokers or ex-smokers was 434 and 658, respectively, compared with 1,116 and 2,466 male smokers or ex-smokers, respectively
      • Blomster J.I.
      • Woodward M.
      • Zoungas S.
      • et al.
      The harms of smoking and benefits of smoking cessation in women compared with men with type 2 diabetes: an observational analysis of the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron modified release Controlled Evaluation) trial.
      . In a Dutch prospective cohort of 1,886 patients with T2DM with a mean follow-up of about 7 years, the incidence of microalbuminuria was significantly higher in men than in women (HR = 1.64 [95% CI: 1.21-2.24])
      • Singh S.S.
      • Roeters-van Lennep J.E.
      • Lemmers R.F.H.
      • et al.
      Sex difference in the incidence of microvascular complications in patients with type 2 diabetes mellitus: a prospective cohort study.
      . No sex difference was found in the incidence of diabetic retinopathy or diabetic neuropathy. When assessing the effect of smoking on microvascular complications, the interaction analyses indicated a more deleterious effect of smoking on microalbuminuria in women than in men. No interaction was found in the assessment of the role of smoking on the occurrence of other microvascular complications.
      Few data of this type are available in populations with T1DM making it difficult to conclude that smoking has a differentially deleterious effect on microvascular complications according to sex.
      • In people with DM, smoking is an independent risk factor for all-cause mortality and macrovascular and microvascular complications in both women and men.
      • In T2DM, the burden of smoking appears to be greater in women than in men in terms of coronary morbidity.
      • In T1DM, it is difficult to conclude whether smoking has a different impact on men or women due to scarce and conflicting data.

      Smoking cessation in people with DM: sex and gender specificities

      Benefits of smoking cessation in people with DM

      Smoking cessation in the population with DM is associated with a reduced risk of mortality and chronic diabetic complications, both macrovascular and microvascular
      • Pan A.
      • Wang Y.
      • Talaei M.
      • Hu F.B.
      • Wu T.
      Relation of active, passive, and quitting smoking with incident type 2 diabetes: a systematic review and meta-analysis.
      ,
      • Qin R.
      • Chen T.
      • Lou Q.
      • Yu D.
      Excess risk of mortality and cardiovascular events associated with smoking among patients with diabetes: meta-analysis of observational prospective studies.
      ,
      • Liu G.
      • Hu Y.
      • Zong G.
      • et al.
      Smoking cessation and weight change in relation to cardiovascular disease incidence and mortality in people with type 2 diabetes: a population-based cohort study.
      • Chuahirun T.
      • Simoni J.
      • Hudson C.
      • et al.
      Cigarette smoking exacerbates and its cessation ameliorates renal injury in type 2 diabetes.
      • Al-Delaimy W.K.
      • Willett W.C.
      • Manson J.E.
      • Speizer F.E.
      • Hu F.B.
      Smoking and mortality among women with type 2 diabetes: The Nurses' Health Study cohort.
      • Al-Delaimy W.K.
      • Manson J.E.
      • Solomon C.G.
      • et al.
      Smoking and risk of coronary heart disease among women with type 2 diabetes mellitus.
      . Some studies have focused exclusively on populations of women with DM, showing a clear benefit of smoking cessation in this population, particularly in terms of cardiovascular disease
      • Al-Delaimy W.K.
      • Willett W.C.
      • Manson J.E.
      • Speizer F.E.
      • Hu F.B.
      Smoking and mortality among women with type 2 diabetes: The Nurses' Health Study cohort.
      • Al-Delaimy W.K.
      • Manson J.E.
      • Solomon C.G.
      • et al.
      Smoking and risk of coronary heart disease among women with type 2 diabetes mellitus.
      • Luo J.
      • Rossouw J.
      • Margolis K.L.
      Smoking cessation, weight change, and coronary heart disease among postmenopausal women with and without diabetes.
      . Few studies have reported sex-stratified data that compared the benefits of smoking cessation in men and women. In the previously mentioned ADVANCE study, no difference in the benefit of smoking cessation in terms of all-cause mortality, cardiovascular morbidity, nephropathy, or cancer was found between men and women with T2DM
      • Blomster J.I.
      • Woodward M.
      • Zoungas S.
      • et al.
      The harms of smoking and benefits of smoking cessation in women compared with men with type 2 diabetes: an observational analysis of the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron modified release Controlled Evaluation) trial.
      . Notably, however, in that study, only the benefit for all-cause mortality after smoking cessation was found to be significant (30% risk reduction) in both sexes
      • Blomster J.I.
      • Woodward M.
      • Zoungas S.
      • et al.
      The harms of smoking and benefits of smoking cessation in women compared with men with type 2 diabetes: an observational analysis of the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron modified release Controlled Evaluation) trial.
      . Similarly, in the Finnish study by Barengo et al., ex-smokers with DM showed a reduction in the risk of all-cause and coronary mortality compared with that for smokers with DM, and this was comparable between men and women
      • Barengo N.C.
      • Teuschl Y.
      • Moltchanov V.
      • Laatikainen T.
      • Jousilahti P.
      • Tuomilehto J.
      Coronary heart disease incidence and mortality, and all-cause mortality among diabetic and non-diabetic people according to their smoking behavior in Finland.
      . However, in both sexes, an excess risk persisted in comparison with non-smoking people with DM. On the other hand, in terms of the incidence of CHD, the benefit of quitting smoking compared with continuing to smoke was greater in women than in men
      • Barengo N.C.
      • Teuschl Y.
      • Moltchanov V.
      • Laatikainen T.
      • Jousilahti P.
      • Tuomilehto J.
      Coronary heart disease incidence and mortality, and all-cause mortality among diabetic and non-diabetic people according to their smoking behavior in Finland.
      . At the microvascular level, the data are even more scarce. In T2DM, sex was not found to be an independent predictor of the absence of microalbuminuria at 1 year after smoking cessation
      • Voulgari C.
      • Katsilambros N.
      • Tentolouris N.
      Smoking cessation predicts amelioration of microalbuminuria in newly diagnosed type 2 diabetes mellitus: a 1-year prospective study.
      . Thus, even if the data are tenuous, it seems that smoking cessation is beneficial in the population with DM in a comparable manner between men and women. Moreover, this benefit of smoking cessation persists beyond the associated weight gain secondary to cessation in both sexes, even if an attenuation is sometimes described
      • Liu G.
      • Hu Y.
      • Zong G.
      • et al.
      Smoking cessation and weight change in relation to cardiovascular disease incidence and mortality in people with type 2 diabetes: a population-based cohort study.
      ,
      • Luo J.
      • Rossouw J.
      • Margolis K.L.
      Smoking cessation, weight change, and coronary heart disease among postmenopausal women with and without diabetes.
      ,
      • Clair C.
      • Rigotti N.A.
      • Porneala B.
      • et al.
      Association of smoking cessation and weight change with cardiovascular disease among adults with and without diabetes.
      .

      Weight gain after smoking cessation in people with DM

      Weight gain after cessation is a major concern and often constitutes an obstacle to smoking cessation
      • Siahpush M.
      • Singh G.K.
      • Tibbits M.
      • Pinard C.A.
      • Shaikh R.A.
      • Yaroch A.
      It is better to be a fat ex-smoker than a thin smoker: findings from the 1997-2004 National Health Interview Survey-National Death Index linkage study.
      . In this context, the question of a difference in weight gain between men and women may be raised. This question is all the more important in the context of metabolic disease such as DM. Patients with DM do not seem to have a greater weight gain after smoking cessation than that observed in the general population
      • Clair C.
      • Rigotti N.A.
      • Porneala B.
      • et al.
      Association of smoking cessation and weight change with cardiovascular disease among adults with and without diabetes.
      ,
      • Driva S.
      • Korkontzelou A.
      • Tonstad S.
      • Tentolouris N.
      • Katsaounou P.
      The Effect of Smoking Cessation on Body Weight and Other Metabolic Parameters with Focus on People with Type 2 Diabetes Mellitus.
      . The observations concerning the gender difference in weight gain secondary to cessation may sometimes be contradictory
      • Aubin H.J.
      • Farley A.
      • Lycett D.
      • Lahmek P.
      • Aveyard P.
      Weight gain in smokers after quitting cigarettes: meta-analysis.
      ,
      • Harris K.K.
      • Zopey M.
      • Friedman T.C.
      Metabolic effects of smoking cessation.
      . Some authors observe a greater average weight gain in women than in men. Thus, Williamson et al. found a mean weight gain attributable to smoking cessation at 1 year after cessation of 2.8 kg in men and 3.8 kg in women after adjustment for confounding factors
      • Williamson D.F.
      • Madans J.
      • Anda R.F.
      • Kleinman J.C.
      • Giovino G.A.
      • Byers T.
      Smoking cessation and severity of weight gain in a national cohort.
      . Significant weight gain (>13 kg) was observed in 9.8% of men and in 13.4% of women
      • Williamson D.F.
      • Madans J.
      • Anda R.F.
      • Kleinman J.C.
      • Giovino G.A.
      • Byers T.
      Smoking cessation and severity of weight gain in a national cohort.
      . In another study evaluating weight change in the 5 years following smoking cessation, women observed an average weight gain of 5.2 kg in the first year and 3.4 kg between 1 and 5 years, whereas for men these figures were 4.9 and 2.6 kg, respectively
      • O'Hara P.
      • Connett J.E.
      • Lee W.W.
      • Nides M.
      • Murray R.
      • Wise R.
      Early and late weight gain following smoking cessation in the Lung Health Study.
      . Conversely, some authors have found a higher weight gain in men than in women. In one study, the average weight gain at 1 year after quitting was 3.3 kg for women vs 3.9 kg for men. In addition, in this study, male sex was associated with greater weight gain after smoking cessation
      • Prod'hom S.
      • Locatelli I.
      • Giraudon K.
      • et al.
      Predictors of weight change in sedentary smokers receiving a standard smoking cessation intervention.
      . Another study found an interaction between weight gain after quitting, sex, and pre-quitting smoking status. Specifically, men with a low level of smoking (about 10 cigarettes/day) gained more weight at 1 year after quitting than women did, whereas with a higher level of smoking (25 cigarettes/day), the opposite was observed
      • Locatelli I.
      • Collet T.H.
      • Clair C.
      • Rodondi N.
      • Cornuz J.
      The joint influence of gender and amount of smoking on weight gain one year after smoking cessation.
      . However, no study to date has specifically evaluated the difference in weight between men and women with DM. Beyond the actual weight gain, fear of weight gain constitutes a barrier to the quitting process, particularly among women in the general population. Indeed, one study compared the weight gain tolerated after smoking cessation by male and female smokers
      • Pomerleau C.S.
      • Kurth C.L.
      Willingness of female smokers to tolerate postcessation weight gain.
      . Men reported a weight gain of 4.9 kg (±3.5 kg), whereas women reported a weight gain of 2.3 kg (±2.6 kg).

      Motivations and barriers to quitting in people with DM

      In addition to weight gain, there are other sex- or gender-related barriers to quitting. In a Dutch qualitative study of 11 female and 9 male smokers, the main barriers to smoking cessation were psycho-social (emotion and stress) among women, but more related to environmental factors among men
      • Dieleman L.A.
      • van Peet P.G.
      • Vos H.M.M.
      Gender differences within the barriers to smoking cessation and the preferences for interventions in primary care a qualitative study using focus groups in The Hague, The Netherlands.
      . Thus, the authors emphasized the need to adapt cessation strategies according to gender, notably by targeting internal problems in women vs external problems in men
      • Dieleman L.A.
      • van Peet P.G.
      • Vos H.M.M.
      Gender differences within the barriers to smoking cessation and the preferences for interventions in primary care a qualitative study using focus groups in The Hague, The Netherlands.
      . Nevertheless, such findings are not necessarily transposable to people with DM. In this specific population, barriers to quitting smoking between men and women might differ, and specificities inherent to diabetic status are observed
      • Georges A.
      • Galbiati L.
      • Clair C.
      Smoking in men and women with type 2 diabetes: A qualitative gender-sensitive exploration of barriers to smoking cessation among people with type 2 diabetes.
      . In people with DM, apprehension about weight gain could be exacerbated because of its possible impact on glycemic control. Furthermore, health professionals may also be more likely to focus on the weight objective after smoking cessation
      • Haire-Joshu D.
      • Heady S.
      • Thomas L.
      • Schechtman K.
      • Fisher Jr., E.B.
      Beliefs about smoking and diabetes care.
      . In patients with T1DM, weight concern was more prevalent in women than in men, as well as in patients with poor glycemic control
      • Haire-Joshu D.
      • Heady S.
      • Thomas L.
      • Schechtman K.
      • Fisher Jr., E.B.
      Beliefs about smoking and diabetes care.
      . However, on the question of the link between smoking cessation and DM management or control, there was no difference between men and women. Furthermore, in another study of barriers to smoking cessation in T2DM by gender, weight gain did not emerge as a major concern
      • Georges A.
      • Galbiati L.
      • Clair C.
      Smoking in men and women with type 2 diabetes: A qualitative gender-sensitive exploration of barriers to smoking cessation among people with type 2 diabetes.
      . Moreover, in this study, DM significantly modulated the barriers to smoking cessation compared with that in the general population, making it difficult to generalize to people with DM
      • Georges A.
      • Galbiati L.
      • Clair C.
      Smoking in men and women with type 2 diabetes: A qualitative gender-sensitive exploration of barriers to smoking cessation among people with type 2 diabetes.
      . Studies specifically targeting people with DM are needed. Furthermore, in T2DM, several studies report a lack of knowledge concerning the links between smoking and T2DM
      • Georges A.
      • Galbiati L.
      • Clair C.
      Smoking in men and women with type 2 diabetes: A qualitative gender-sensitive exploration of barriers to smoking cessation among people with type 2 diabetes.
      ,
      • Chau T.K.
      • Fong D.Y.
      • Chan S.S.
      • et al.
      Misconceptions about smoking in patients with type 2 diabetes mellitus: a qualitative analysis.
      . Thus, smoking cessation strategies must take into account gender differences to improve the success and long-term maintenance of abstinence.

      Smoking cessation interventions in people with DM

      Regarding non-pharmacological smoking cessation strategies, some authors found sex and gender differences in their effectiveness. However, no data are available to date for people with DM. This is the objective of the DISCGO-RCT study, which evaluates the effectiveness of smoking cessation interventions in the T2DM population by also integrating gender specificities
      • Clair C.
      • Augsburger A.
      • Birrer P.
      • et al.
      Assessing the efficacy and impact of a personalised smoking cessation intervention among type 2 diabetic smokers: study protocol for an open-label randomised controlled trial (DISCGO-RCT).
      . Concerning pharmacological strategies, in the general population, the literature shows differences according to sex or gender. Nicotine replacement therapies or bupropion are more effective in men, whereas varenicline is more efficient in women
      • Perkins K.A.
      • Scott J.
      Sex differences in long-term smoking cessation rates due to nicotine patch.
      • McKee S.A.
      • Smith P.H.
      • Kaufman M.
      • Mazure C.M.
      • Weinberger A.H.
      Sex Differences in Varenicline Efficacy for Smoking Cessation: A Meta-Analysis.
      • Smith P.H.
      • Kasza K.A.
      • Hyland A.
      • et al.
      Gender differences in medication use and cigarette smoking cessation: results from the International Tobacco Control Four Country Survey.
      • Smith P.H.
      • Zhang J.
      • Weinberger A.H.
      • Mazure C.M.
      • McKee S.A.
      Gender differences in the real-world effectiveness of smoking cessation medications: Findings from the 2010-2011 Tobacco Use Supplement to the Current Population Survey.
      • Smith P.H.
      • Weinberger A.H.
      • Zhang J.
      • Emme E.
      • Mazure C.M.
      • McKee S.A.
      Sex Differences in Smoking Cessation Pharmacotherapy Comparative Efficacy: A Network Meta-analysis.
      . These differences are linked to pharmacogenetic factors
      • Schnoll R.A.
      • Patterson F.
      Sex heterogeneity in pharmacogenetic smoking cessation clinical trials.
      . As reviewed in this paper, sex affects enzymes that metabolize drugs such as CYP2B6, or genes that influence dopamine concentrations such as DRD2 or COMT
      • Smith P.H.
      • Bessette A.J.
      • Weinberger A.H.
      • Sheffer C.E.
      • McKee S.A.
      Sex/gender differences in smoking cessation: A review.
      ,
      • Schnoll R.A.
      • Patterson F.
      Sex heterogeneity in pharmacogenetic smoking cessation clinical trials.
      . Such observations have not been tested specifically in people with DM. Differences between men and women in barriers or responses to smoking cessation strategies have an impact on the success of smoking cessation. In the general population, data are divergent between studies, but it seems that there is no difference in the proportion of women initiating cessation compared with men, nor in the success of cessation. On the other hand, a difference in the ability to maintain abstinence over the long term has been observed
      • Smith P.H.
      • Bessette A.J.
      • Weinberger A.H.
      • Sheffer C.E.
      • McKee S.A.
      Sex/gender differences in smoking cessation: A review.
      . Another study has found a higher rate of cessation at 1 year among women than among men, particularly among young people, whereas this rate is higher among men as they get older
      • Jarvis M.J.
      • Cohen J.E.
      • Delnevo C.D.
      • Giovino G.A.
      Dispelling myths about gender differences in smoking cessation: population data from the USA, Canada and Britain.
      . To date, such observations have not been published for people with DM. Finally, the management of smoking cessation by health professionals might vary according to the sex or gender of patients. Indeed, the management of cardiovascular risk factors was more aggressive in men than in women, whether in T2DM or T1DM
      • Wexler D.J.
      • Grant R.W.
      • Meigs J.B.
      • Nathan D.M.
      • Cagliero E.
      Sex disparities in treatment of cardiac risk factors in patients with type 2 diabetes.
      ,
      • Larkin M.E.
      • Backlund J.Y.
      • Cleary P.
      • et al.
      Disparity in management of diabetes and coronary heart disease risk factors by sex in DCCT/EDIC.
      . However, these data mainly concern the management of dyslipidemia or hypertension on the basis of prescription data for lipid-lowering and anti-hypertensive medications. In these studies, the occurrence of smoking cessation advice by sex or gender was not reported. In a study published in 1995 in the United States, the percentage of people with DM who received advice to stop or reduce smoking from their doctor was approximately the same between men and women
      • Malarcher A.M.
      • Ford E.S.
      • Nelson D.E.
      • et al.
      Trends in cigarette smoking and physicians' advice to quit smoking among people with diabetes in the U.S.
      . Thus, it is important to draw the attention of health professionals to the management of cardiovascular risk factors, especially smoking cessation, in both sexes.
      Smoking cessation advice and treatments should be systematically proposed to every smoker with DM regardless of sex or gender. Interventions that have been proven effective in people without DM, such as behavioral interventions, nicotine replacement therapy, and the administration of bupropion or varenicline, are also effective in smokers with DM
      • Zhang L.
      • Curhan G.C.
      • Hu F.B.
      • Rimm E.B.
      • Forman J.P.
      Association between passive and active smoking and incident type 2 diabetes in women.
      . Few data exist on sex or gender specificities in people with DM regarding smoking cessation. Interventions might be tailored to better reach patients on the basis of their sex or gender specificities, as well as their DM specificities
      • Bottorff J.L.
      • Haines-Saah R.
      • Kelly M.T.
      • et al.
      Gender, smoking and tobacco reduction and cessation: a scoping review.
      . This includes interventions that address emotions and stress in women
      • Torchalla I.
      • Okoli C.T.
      • Bottorff J.L.
      • Qu A.
      • Poole N.
      • Greaves L.
      Smoking cessation programs targeted to women: a systematic review.
      or an implementation design to reach specific populations of men
      • Bottorff J.L.
      • Haines-Saah R.
      • Kelly M.T.
      • et al.
      Gender, smoking and tobacco reduction and cessation: a scoping review.
      .
      • The benefit of smoking cessation appears to be similar between men and women with DM.
      • As in the general population, weight change following smoking cessation in people with DM appears to be greater in women than in men.
      • No data are available to date regarding a sex or gender difference in the effectiveness of smoking cessation interventions specifically in people with DM.
      • Smoking cessation advice and treatments should be systematically proposed to every smoker with DM regardless of sex or gender.

      Electronic nicotine delivery systems

      Few data exist on the use and health impact of electronic nicotine delivery systems (ENDS or e-cigarettes) and the potential differences between men and women with DM. In populations without DM, a higher prevalence of ENDS use has been shown in men, especially in younger populations
      • Cooper M.
      • Day H.R.
      • Ren C.
      • et al.
      Correlates of tobacco product initiation among youth and young adults between waves 1-4 of the population assessment of tobacco and Health (PATH) study (2013-2018).
      ,
      • Mattingly D.T.
      • Zavala-Arciniega L.
      • Hirschtick J.L.
      • Meza R.
      • Levy D.T.
      • Fleischer N.L.
      Trends in Exclusive, Dual and Polytobacco Use among U.S. Adults, 2014-2019: Results from Two Nationally Representative Surveys.
      . The trends might change, but limited data suggest that men are early adopters, similar to what has been observed with cigarette smoking. Regarding the association between ENDS use and the incidence of T2DM or prediabetes in never cigarette smokers, studies suggest that, similar to smokers, ENDS users are at increased risk of impaired glucose tolerance compared with non-users
      • Zhang Z.
      • Jiao Z.
      • Blaha M.J.
      • et al.
      The Association Between E-Cigarette Use and Prediabetes: Results From the Behavioral Risk Factor Surveillance System, 2016-2018.
      • Gorna I.
      • Napierala M.
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      Electronic Cigarette Use and Metabolic Syndrome Development: A Critical Review.
      • Atuegwu N.C.
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      E-cigarette use is associated with a self-reported diagnosis of prediabetes in never cigarette smokers: Results from the behavioral risk factor surveillance system survey.
      . It is important to note that most of the available studies have short follow-ups and consist mainly of dual cigarette smokers and ENDS users, making it difficult to isolate the health effect associated with ENDS use. In a study that used data from the Behavioral Risk Factor Surveillance System (BRFSS) survey, the odds ratio (OR) of self-reported prediabetes for non-smoking ENDS users compared with never ENDS users was higher in men than in women (OR 2.36 [95% CI 1.26–4.40] vs OR 1.88 [95% CI 1.00–3.53], respectively)
      • Atuegwu N.C.
      • Perez M.F.
      • Oncken C.
      • Mead E.L.
      • Maheshwari N.
      • Mortensen E.M.
      E-cigarette use is associated with a self-reported diagnosis of prediabetes in never cigarette smokers: Results from the behavioral risk factor surveillance system survey.
      . Animal studies suggest that glycerol contained in ENDS liquids can affect glucose homeostasis in both males and females
      • Lechasseur A.
      • Mouchiroud M.
      • Tremblay F.
      • et al.
      Glycerol contained in vaping liquids affects the liver and aspects of energy homeostasis in a sex-dependent manner.
      . Finally, regarding the effects of ENDS use on diabetic complications few studies exists and none with sex or gender specific data. One Chinese study found that ENDS use was associated with impaired angiogenesis and wound healing in people with DM because of increased endothelial oxidative stress and reduced nitric oxide bioavailability, but sex specificities were not assessed

      Liu Z, Zhang Y, Youn JY, et al. Flavored and Nicotine-Containing E-Cigarettes Induce Impaired Angiogenesis and Diabetic Wound Healing via Increased Endothelial Oxidative Stress and Reduced NO Bioavailability. Antioxidants (Basel). 2022;11.

      .
      • Few data exist on the use and health impact of ENDS in men and women with DM.
      • ENDS use aiming at smoking cessation should be of limited duration, once abstinence is achieved and the urge to smoke is suppressed, regardless of sex and gender.

      Conclusion

      In this article, we reviewed available data on sex or gender differences in the interplay between smoking and DM. Smoking is a risk factor for the development of T2DM in both men and women and the risk conferred by smoking appears to be comparable between them. As observed in the general population, the prevalence of smoking varies between men and women with DM, being overall higher in men than in women. However, the trend toward a decrease in smoking observed in men in recent years seems to be less pronounced in women. Tobacco prevention policies should target people with DM with a specific attention on women who might be especially exposed to tobacco industry’s marketing strategies.
      Smoking is an independent risk factor for all-cause mortality, macrovascular and microvascular complications in both women and men with DM. However in T2DM, the burden of smoking appears to be greater in women than in men in terms of coronary morbidity. Even if mechanisms are not all understood, the higher susceptibility of women to smoking toxicity argues for special attention from health professionals in the management of cardiovascular risk factors and diabetes complications in women with DM.
      Regarding smoking cessation, women with DM tend to be more dependent to nicotine and to have more stress and psychosocial barriers to quitting smoking. Weight change following smoking cessation also appears to be greater in women than in men. These factors may hinder smoking cessation and should be addressed when managing smokers with DM. People with DM should be offered the same first-line therapies smoking cessation treatment as the general population, including behavioral interventions and pharmacological treatments (such as nicotine replacement therapies, varenicline, and bupropion). There is to date limited evidence regarding the efficacy and safety of pharmacotherapies in patients with DM and sex or gender specific data are even more scarce or lacking, particularly in T1DM.
      Smoking cessation should be proposed to all patients with diabetes, regardless of their sex or gender. Further research that takes into account sex or gender dimensions are required. This could help tailor smoking prevention and smoking cessation interventions in order to better reach people with DM on the basis of their sex or gender specificities.

      Acknowledgments

      We thank the Société Francophone du Diabète (SFD), Société Francophone de Tabacologie (SFT), the Fédération Française des Diabétiques (FFD), and all members of the study group “Tabac et Diabète.”

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