Key Points
Question
Is smoking cessation associated with affect the risk of incident diabetic microvascular complications in patients with type 2 diabetes?
Findings
In this cohort study of 209 698 patients with diabetes in Korea, smoking cessation for 8 or more years was associated with significantly lower risk of overall microvascular complications and diabetic nephropathy compared with continuous smokers, and cessation for 6 to 7 years was associated with a significantly lower risk of diabetic neuropathy.
Meaning
This cohort study found that long-term smoking cessation was associated with a progressive reduction in the risk of diabetic microvascular complications.
This cohort study investigates the association between smoking cessation duration and risk of incident diabetic microvascular complications using a nationwide database of patients in Korea with type 2 diabetes.
Abstract
Importance
The risk of diabetic microvascular complications is well established among smokers with type 2 diabetes. However, whether and to what extent this excess risk declines according to smoking cessation duration remains unclear.
Objective
To investigate the association between smoking cessation duration and the risk of incident diabetic microvascular complications in patients with diabetes.
Design, Setting, and Participants
This nationwide, population-based cohort study included participants first diagnosed with type 2 diabetes in Korea between 2003 and 2013 and whose smoking status was assessed at least 4 times across repeated health checkups, with a final checkup during 2009 to 2013. Data were analyzed from November 10, 2025, to April 16, 2026.
Exposure
Smoking status and cessation duration. Quitters were defined as participants who reported current smoking at their initial health checkup and reported smoking cessation at all subsequent checkups without relapse. Continuous smokers were defined as participants who consistently reported current smoking at every health checkup. Among quitters, smoking cessation duration was categorized as less than 2, 2 to 3, 4 to 5, 6 to 7, and 8 or more years.
Main Outcomes and Measures
Outcomes of interest were incident diabetic microvascular complications, including diabetic nephropathy, retinopathy, and neuropathy, identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnostic codes. Cox proportional hazards models were used to estimate unadjusted and adjusted hazard ratios (aHRs) and 95% CIs.
Results
A total of 209 698 adults (mean [SD] age, 57.2 [10.3] years; 127 823 [61.0%] female) were included in the analyses. Compared with continuous smokers, cessation for 8 or more years was associated with a lower risk of all microvascular complications (aHR, 0.81; 95% CI, 0.70-0.95), diabetic nephropathy (aHR, 0.79; 95% CI, 0.64-0.94), diabetic retinopathy (aHR, 0.59; 95% CI, 0.36-0.97), and diabetic neuropathy (aHR, 0.80; 95% CI, 0.66-0.98). Smoking cessation for 6 to 7 years was associated with lower risk of diabetic neuropathy (aHR, 0.76; 95% CI, 0.64-0.89). In subgroup analyses by sex, these associations were significant only among male participants (eg, all microvascular complications: aHR, 0.82; 95% CI, 0.70-0.95).
Conclusions and Relevance
In this retrospective cohort study of patients with diabetes, smoking cessation for 8 or more years was associated with a lower risk of all diabetic microvascular complications, diabetic nephropathy, retinopathy, and neuropathy compared with continuous smoking. These associations were observed mainly among male participants, underscoring the potential importance of sustained long-term smoking cessation for microvascular risk reduction.
Introduction
The global prevalence of diabetes is increasing rapidly, and approximately 852.5 million individuals are projected to have diabetes by 2050, 90% of whom will have type 2 diabetes.1 Diabetic microvascular complications, including diabetic retinopathy, nephropathy, and neuropathy, represent major causes of morbidity, affecting nearly half of patients with diabetes.2 Diabetic retinopathy is one of the major causes of vision loss worldwide,3 diabetic nephropathy is a leading cause of end-stage kidney disease in many populations,4 and diabetic neuropathy is the most common cause of nontraumatic lower-extremity amputation in most high-income countries.5 The development of these complications dramatically worsens patients’ quality of life and imposes a substantial economic burden.6,7 Therefore, lifestyle modifications that prevent or delay these complications are of considerable clinical importance.8
Cigarette smoking has been shown to increase the risk of diabetic nephropathy, retinopathy, and neuropathy through systemic inflammation and endothelial dysfunction.9,10 Previous studies have reported that smoking is associated with an increased risk of diabetic microvascular complications.11,12 Our prior work showed that persistent and heavy cumulative smoking increased overall microvascular complication risk, particularly nephropathy and neuropathy, among men with diabetes.11 However, evidence remains limited as to whether and to what extent the excess risk of diabetic microvascular complications declines in association with smoking cessation duration.
Therefore, we aimed to investigate the association between smoking cessation duration and the risk of incident diabetic microvascular complications among patients with type 2 diabetes. This approach may provide clinically relevant evidence on how long smoking cessation should be sustained before meaningful benefits in microvascular complication risk become apparent.
Methods
This cohort study was approved by the institutional review board of Kyung Hee University Hospital. The requirement for informed consent was waived because the study used an anonymized retrospective dataset. This study is reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cohort studies.
Database and Study Design
We conducted a retrospective cohort study using the National Health Insurance Service database, a single-payer system covering nearly the entire Korean population that includes claims for medical visits, diagnoses, procedures, and prescriptions, as well as biennial national health checkup records for adults aged 40 years and older, available for research since 2002. As illustrated in the cohort timeline (eFigure 1 in Supplement 1), this study included individuals who were first diagnosed with type 2 diabetes between 2003 and 2013. Accordingly, individuals with a diagnosis of diabetes before 2003 were not eligible for inclusion. Repeated health checkup records from 2002 onward were used to assess longitudinal smoking status, and only participants with at least 4 health checkups and intervals shorter than 37 months between examinations were retained. The index date was defined as each participant’s last health checkup conducted during 2009 to 2013, and participants were followed up from the index date until the first occurrence of diabetic microvascular complications, loss to follow-up, death, or December 31, 2023, whichever came first.
Smoking Status and Cessation Duration
Smoking status was assessed using self-reported questionnaires administered during the national health checkups program and categorized as never smokers, quitters, or continuous smokers. At each checkup, participants were asked whether they had ever smoked at least 5 packs (100 cigarettes) in their lifetime (yes or no) and, if currently smoking, whether they were a current smoker (yes or no). Smoking information was repeatedly collected across health checkups from 2002 to 2013.
To ensure reliable exposure classification, only participants with consistent smoking status across repeated assessments were included (eFigure 3 in Supplement 1). Participants were classified into 3 mutually exclusive categories based on their longitudinal smoking behavior. Never smokers were defined as those who consistently reported never smoking at all health checkups. Quitters were defined as individuals who reported current smoking at an initial health checkup but subsequently reported smoking cessation at all following health checkups without relapse. Continuous smokers were those who consistently reported active smoking at each health checkup. Participants who reported nonsmoking at an initial checkup but subsequently initiated smoking were classified as starters and excluded, and those whose reported smoking status changed more than once were classified as inconsistent and excluded (eFigure 2 and eFigure 3 in Supplement 1).
Among sustained quitters, smoking cessation duration was defined as the time since quitting smoking. The date of smoking cessation was approximated as the midpoint between the health checkup at which cessation was first reported and the preceding checkup. The duration of smoking cessation was then calculated as the time from this estimated quit date to the index date and categorized into less than 2, 2 to 3, 4 to 5, 6 to 7, and 8 or more years.
Diabetic Microvascular Complications
The primary outcome was incident diabetic microvascular complications, including diabetic nephropathy (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] codes E11.2, E12.2, E13.2, and E14.2), diabetic retinopathy (E11.3, E12.3, E13.3, and E14.3), and diabetic neuropathy (E11.4, E12.4, E13.4, and E14.4), identified using diagnostic codes recorded in the National Health Insurance Service database. For the all diabetic microvascular complications, incident events were defined as the first occurrence of any of these 3 complications after the index health checkup. For each individual complication, incident events were defined independently of the other 2; therefore, a participant could contribute an event to more than 1 complication-specific analysis if multiple complications developed during follow-up.
Covariates
Covariates were assessed using data obtained from the index date health checkup. The following variables were included as covariates: age, sex, body mass index (BMI), systolic blood pressure, γ-glutamyl transpeptidase (γ-GTP), total cholesterol, alcohol consumption, physical activity, hypertension, pack-years, and duration of diabetes. Detailed measurement protocols are provided in the eMethods in Supplement 1.
Statistical Analysis
Characteristics are presented as means (SDs) for continuous variables and frequencies (percentages) for categorical variables. Differences between groups across smoking status categories were assessed using analysis of variance for continuous variables and the χ2 test for categorical variables. The incidence rates of diabetic microvascular complications were calculated as the number of events divided by person-years (PYs) of follow-up.
Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs for the association between smoking cessation and diabetic microvascular complications. Time since the index date was used as the underlying time scale. In the main Cox analyses, deaths occurring before the development of diabetic microvascular complications were treated as censoring events. Kaplan-Meier curves were generated to illustrate the cumulative incidence of all diabetic microvascular complications according to smoking cessation duration, and differences between groups were assessed using the log-rank test (eFigure 4 in Supplement 1). The proportional hazards assumption was assessed by inspecting log-minus-log survival plots, with no clear evidence of violation. Covariates were selected a priori based on the literature. Multivariable models were adjusted for age,13 sex,14 BMI,15 systolic blood pressure,16 γ-GTP,17,18 total cholesterol,19 alcohol consumption,20 physical activity,21 hypertension,13 pack-years,11 and duration of diabetes.13,19 Multivariable regression analyses were performed using complete-case analysis, excluding participants with missing covariate data.
To examine the association between smoking cessation and risk of diabetic microvascular complications, smoking cessation duration among sustained quitters was categorized (<2, 2-3, 4-5, 6-7, and ≥8 years), and continuous smokers were used as the reference group. As secondary analyses, never smokers were used as the reference group, and subgroup analyses were conducted with stratification by sex. In addition, smoking cessation duration among quitters was modeled as a continuous variable to estimate the risk of diabetic microvascular complications associated with each 1-year increase in cessation duration.
Several additional sensitivity analyses were performed, including comparison of characteristics between included and excluded participants, analyses using a less restrictive inclusion criterion of at least 3 health checkups, propensity score matching (PSM) to account for confounding, and estimation of subdistribution HRs using the Fine-Gray competing-risk model to account for the competing risk of death (eMethods in Supplement 1).22
All statistical analyses were performed using SAS software version 9.4 (SAS Institute). Data analysis was conducted from November 10, 2025, to April 16, 2026. A 2-sided P < .05 was considered statistically significant.
Results
From an initial cohort of 1 599 870 patients with type 2 diabetes who underwent health checkups in 2009 to 2013, we excluded participants with preexisting type 1 diabetes or diabetic microvascular complications, fewer than 4 health checkups or intervals longer than 37 months between examinations, and missing smoking status data, yielding 315 090 eligible participants (eFigure 2 and eMethods in Supplement 1). Among these, participants with unstable smoking status across repeated checkups were further excluded (eMethods in Supplement 1), resulting in a final analytic cohort of 209 698 patients with type 2 diabetes (mean [SD] age, 57.2 [10.3] years; 127 823 [61.0%] female), including 162 861 never smokers, 11 848 quitters, and 34 989 continuous smokers (Table 1). Never smokers (mean [SD] age, 58.8 [9.7] years) were older than quitters (mean [SD] age, 53.0 [10.0] years) and continuous smokers (mean [SD] age, 51.1 [10.3] years) (P < .001).
Table 1. Characteristics of Study Participants According to Smoking Status.
| Characteristic | Participants, No. (%) | P value | |||
|---|---|---|---|---|---|
| Total (N = 209 698) | Never smokers (n = 162 861) | Quitters (n = 11 848) | Continuous smokers (n = 34 989) | ||
| Follow-up years, mean (SD), y | 9.0 (3.4) | 9.1 (3.4) | 8.8 (3.4) | 8.8 (3.4) | |
| Age, mean (SD), y | 57.2 (10.3) | 58.8 (9.7) | 53.0 (10.0) | 51.1 (10.3) | <.001 |
| Sex | |||||
| Male | 81 875 (39.0) | 36 163 (22.2) | 11 643 (98.3) | 34 069 (97.4) | <.001 |
| Female | 127 823 (61.0) | 126 698 (77.8) | 205 (1.7) | 920 (2.6) | |
| BMI, mean (SD) | 25.1 (3.3) | 25.1 (3.3) | 25.4 (3.1) | 25.0 (3.2) | <.001 |
| Blood pressure, mean (SD), mm Hg | |||||
| Systolic | 127.2 (14.8) | 127.4 (15.0) | 127.4 (13.9) | 126.4 (14.0) | <.001 |
| Diastolic | 77.8 (9.6) | 77.5 (9.6) | 79.0 (9.4) | 78.6 (9.5) | <.001 |
| Laboratory measures, mean (SD) | |||||
| Fasting blood glucose, mg/dL | 127.2 (40.0) | 123.7 (36.2) | 134.9 (43.3) | 140.8 (51.1) | <.001 |
| Triglyceride, mg/dL | 159.1 (118.6) | 148.1 (101.5) | 179.0 (134.2) | 203.7 (166.3) | <.001 |
| HDL, mg/dL | 51.6 (25.7) | 52.5 (28.0) | 49.5 (16.4) | 48.3 (14.2) | <.001 |
| LDL, mg/dL | 110.4 (40.6) | 111.9 (40.0) | 104.5 (46.2) | 105.3 (41.3) | <.001 |
| Total cholesterol, mg/dL | 192.8 (43.2) | 193.5 (42.2) | 187.3 (49.4) | 191.5 (45.1) | <.001 |
| eGFR, mL/min/1.73 m2 | 85.7 (18.1) | 84.5 (17.8) | 87.4 (18.4) | 90.5 (18.4) | <.001 |
| AST, median (IQR), U/L | 24.0 (20.0-31.0) | 24.0 (20.0-30.0) | 26.0 (21.0-35.0) | 25.0 (20.0-33.0) | <.001 |
| ALT, median (IQR), U/L | 23.0 (17.0-33.0) | 22.0 (17.0-31.0) | 28.0 (20.0-41.0) | 27.0 (19.0-40.0) | <.001 |
| γ-GTP, median (IQR), U/L | 27.0 (18.0-44.0) | 24.0 (17.0-36.0) | 42.0 (27.0-71.0) | 48.0 (30.0-83.0) | <.001 |
| Pack-years | |||||
| <10 | 168 022 (80.1) | 162 861 (100) | 1600 (13.5) | 3561 (10.2) | <.001 |
| 10 to <20 | 11 384 (5.4) | NA | 2723 (23.0) | 8661 (24.8) | |
| 20 to <30 | 11 730 (5.6) | NA | 2753 (23.2) | 8977 (25.7) | |
| >30 | 18 562 (8.8) | NA | 4772 (40.3) | 13 790 (39.4) | |
| Smoking cessation duration, y | |||||
| None | 197 850 (94.3) | 162 861 (100) | NA | 34 989 (100) | <.001 |
| <2 | 4523 (2.2) | NA | 4523 (38.2) | NA | |
| 2-3 | 3215 (1.5) | NA | 3215 (27.1) | NA | |
| 4-5 | 2137 (1.0) | NA | 2137 (18.0) | NA | |
| 6-7 | 1166 (0.6) | NA | 1166 (9.8) | NA | |
| ≥8 | 807 (0.4) | NA | 807 (6.8) | NA | |
| Alcohol consumption, d/wk | |||||
| 0-1 | 172 654 (82.4) | 149 245 (91.7) | 6593 (55.7) | 16 816 (48.1) | <.001 |
| 2-7 | 36 953 (17.6) | 13 541 (8.3) | 5252 (44.3) | 18 160 (51.9) | |
| Exercise, d/wk | |||||
| 0-3 d/wk | 151 363 (72.3) | 118 340 (72.7) | 7397 (62.5) | 25 626 (73.3) | <.001 |
| 4-7 d/wk | 58 120 (27.7) | 44 350 (27.3) | 4434 (37.5) | 9336 (26.7) | |
| Duration of diabetes, mean (SD), y | 4.6 (2.9) | 4.6 (2.9) | 4.2 (2.9) | 4.4 (2.8) | .06 |
| Hypertension | |||||
| No | 91 988 (43.9) | 66 389 (40.8) | 6212 (52.4) | 19 387 (55.4) | <.001 |
| Yes | 117 710 (56.1) | 96 472 (59.2) | 5636 (47.6) | 15 602 (44.6) | |
| Diabetic microvascular complication | |||||
| All | 54 767 (26.1) | 42 414 (26.0) | 3060 (25.8) | 9293 (26.6) | .10 |
| Diabetic nephropathy | 20 596 (9.8) | 15 454 (9.5) | 1345 (11.3) | 3797 (10.8) | <.001 |
| Diabetic retinopathy | 6844 (3.3) | 5286 (3.2) | 371 (3.1) | 1187 (3.4) | .26 |
| Diabetic neuropathy | 34 520 (16.5) | 27 127 (16.7) | 1775 (15.0) | 5618 (16.1) | <.001 |
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); GTP, glutamyl transferase; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; NA, not applicable.
SI conversion factors: To convert fasting blood glucose to millimoles per liter, multiply by 0.0555; AST, ALT, and γ-GTP to microkatals per liter, multiply by 0.0167; HDL, LDL, and total cholesterol to millimoles per liter, multiply by 0.0259; triglyceride to millimoles per liter, multiply by 0.0113.
The crude incidence rate of all diabetic microvascular complications was 287.6 per 10 000 PYs among never smokers and 301.9 per 10 000 PYs among continuous smokers. Among quitters, the incidence rate was highest for cessation of less than 2 years (312.8 per 10 000 PYs) and decreased progressively with longer cessation duration, to 237.6 per 10 000 PYs for 8 or more years (Table 2).
Table 2. Outcome Incidence Rates by Smoking Status and Duration of Smoking Cessation.
| Smoking status | No. | Incident events | PYs | IR per 10 000 PYs |
|---|---|---|---|---|
| All diabetic microvascular complications | ||||
| Never smokers | 162 861 | 42 414 | 1 474 962.5 | 287.6 (287.6-287.6) |
| Quitters by duration, y | ||||
| <2 | 4523 | 1209 | 38 650.3 | 312.8 (312.7-312.9) |
| 2-3 | 3215 | 834 | 28 277.3 | 294.9 (294.8-295.1) |
| 4-5 | 2137 | 562 | 19 037.2 | 295.2 (295.0-295.4) |
| 6-7 | 1166 | 278 | 10 645.6 | 261.1 (260.8-261.4) |
| ≥8 | 807 | 177 | 7449.2 | 237.6 (237.2-238.0) |
| Continuous smokers | 34 989 | 9293 | 307 795.9 | 301.9 (301.9-301.9) |
| Diabetic nephropathy | ||||
| Never smokers | 162 861 | 15 454 | 1 625 272.8 | 95.1 (95.1-95.1) |
| Quitters by duration, y | ||||
| <2 | 4523 | 537 | 42 652.6 | 125.9 (125.9-126.0) |
| 2-3 | 3215 | 354 | 30 867.1 | 114.7 (114.6-114.8) |
| 4-5 | 2137 | 246 | 20 749.9 | 118.6 (118.5-118.7) |
| 6-7 | 1166 | 137 | 11 438.00 | 119.8 (119.6-120.0) |
| ≥8 | 807 | 71 | 7957.12 | 89.2 (89.0-89.5) |
| Continuous smokers | 34 989 | 3797 | 337 712.24 | 112.4 (112.4-112.4) |
| Diabetic retinopathy | ||||
| Never smokers | 162 861 | 5286 | 1 684 104.2 | 31.4 (31.4-31.4) |
| Quitters by duration, y | ||||
| <2 | 4523 | 138 | 44 943.4 | 30.7 (30.7-30.7) |
| 2-3 | 3215 | 109 | 32 318.4 | 33.7 (33.7-33.8) |
| 4-5 | 2137 | 69 | 21 709.3 | 31.8 (31.7-31.8) |
| 6-7 | 1166 | 39 | 12 007.2 | 32.5 (32.4-32.6) |
| ≥8 | 807 | 16 | 8242.1 | 19.4 (19.3-19.5) |
| Continuous smokers | 34 989 | 1187 | 352 220.8 | 33.7 (33.7-33.7) |
| Diabetic neuropathy | ||||
| Never smokers | 162 861 | 27 127 | 1 568 895.2 | 172.9 (172.9-172.9) |
| Quitters by duration, y | ||||
| <2 | 4523 | 721 | 41 691.02 | 172.9 (172.9-173.0) |
| 2-3 | 3215 | 477 | 30 369.82 | 157.1 (157.0-157.2) |
| 4-5 | 2137 | 332 | 20 447.93 | 162.4 (162.2-162.5) |
| 6-7 | 1166 | 143 | 11 496.5 | 124.4 (124.2-124.6) |
| ≥8 | 807 | 102 | 7859.7 | 129.78 (129.5-130.1) |
| Continuous smokers | 34 989 | 5618 | 329 192.7 | 170.66 (170.7-170.7) |
Abbreviations: IR, incidence rate; PY, person-years.
Continuous smokers had a significantly higher risk of all diabetic microvascular complications (adjusted HR [aHR], 1.03; 95% CI, 1.01-1.05) and diabetic neuropathy (aHR, 1.09; 95% CI, 1.04-1.14) than never smokers, whereas quitters showed no significant association with any outcome (Table 3). With continuous smokers as the reference group (Table 4), smoking cessation for 6 to 7 years (aHR, 0.88; 95% CI, 0.78-0.99) and 8 or more years (aHR, 0.81; 95% CI, 0.70-0.95) was associated with a significantly lower risk of all diabetic microvascular complications. For diabetic nephropathy, cessation for less than 2 years was associated with a higher risk (aHR, 1.12; 95% CI, 1.03-1.23) and cessation for 8 or more years with a lower risk (aHR, 0.79; 95% CI, 0.64-0.94). Cessation for 8 or more years was also associated with a lower risk of diabetic retinopathy (aHR, 0.59; 95% CI, 0.36-0.97), and cessation for 6 to 7 years (aHR, 0.76; 95% CI, 0.64-0.89) and 8 or more years (aHR, 0.80; 95% CI, 0.66-0.98) were associated with a lower risk of diabetic neuropathy.
Table 3. Hazard of Diabetic Microvascular Complications According to Smoking Status.
| Smoking status | Hazard ratio (95% CI) | |
|---|---|---|
| Unadjusted | Adjusteda | |
| All diabetic microvascular complications | ||
| Never smokers | 1 [Reference] | 1 [Reference] |
| Quitters | 1.14 (1.07-1.22)b | 1.01 (0.96-1.07) |
| Continuous smokers | 1.19 (1.15-1.24)b | 1.03 (1.01-1.05)b |
| Diabetic nephropathy | ||
| Never smokers | 1 [Reference] | 1 [Reference] |
| Quitters | 1.38 (1.25-1.52)b | 1.06 (0.98-1.15) |
| Continuous smokers | 1.32 (1.24-1.41)b | 1.00 (0.94-1.07) |
| Diabetic retinopathy | ||
| Never smokers | 1 [Reference] | 1 [Reference] |
| Quitters | 1.01 (0.84-1.22) | 0.92 (0.80-1.06) |
| Continuous smokers | 1.23 (1.11-1.36)b | 0.95 (0.85-1.07) |
| Diabetic neuropathy | ||
| Never smokers | 1 [Reference] | 1 [Reference] |
| Quitters | 1.01 (0.93-1.10) | 0.99 (0.94-1.04) |
| Continuous smokers | 1.11 (1.05-1.17)b | 1.09 (1.04-1.14)b |
Adjusted for age, sex, body mass index, systolic blood pressure, γ-glutamyl transferase, total cholesterol, alcohol consumption, exercise, pack-years, hypertension, and duration of diabetes.
Indicates statistical significance (P < .05).
Table 4. Hazard of Diabetic Microvascular Complications According to Smoking Cessation Duration vs Continuous Smokers.
| Smoking status | Hazard ratios (95% CI) | |
|---|---|---|
| Unadjusted | Adjusteda | |
| All diabetic microvascular complications | ||
| Continuous smokers | 1 [Reference] | 1 [Reference] |
| Quitters by duration, y | ||
| <2 | 1.01 (0.99-1.22) | 1.03 (0.97-1.09) |
| 2-3 | 1.00 (0.88-1.14) | 0.99 (0.92-1.06) |
| 4-5 | 0.84 (0.72-0.99) | 0.99 (0.91-1.08) |
| 6-7 | 0.82 (0.66-1.02) | 0.88 (0.78-0.99)b |
| ≥8 | 0.64 (0.49-0.85)b | 0.81 (0.70-0.95)b |
| Never smokers | 0.84 (0.81-0.87)b | 0.97 (0.95-0.99)b |
| Diabetic nephropathy | ||
| Continuous smokers | 1 [Reference] | 1 [Reference] |
| Quitters by duration, y | ||
| <2 | 1.17 (1.00-1.37)b | 1.12 (1.03-1.23)b |
| 2-3 | 1.12 (0.93-1.35) | 1.03 (0.93-1.15) |
| 4-5 | 0.90 (0.71-1.15) | 1.01 (0.91-1.11) |
| 6-7 | 0.97 (0.71-1.33) | 1.02 (0.88-1.16) |
| ≥8 | 0.54 (0.33-0.86)b | 0.79 (0.64-0.94)b |
| Never smokers | 0.76 (0.71-0.80)b | 1.00 (0.94-1.06) |
| Diabetic retinopathy | ||
| Continuous smokers | 1 [Reference] | 1 [Reference] |
| Quitters by duration, y | ||
| <2 | 0.96 (0.72-1.28) | 0.96 (0.80-1.14) |
| 2-3 | 0.99 (0.71-1.38) | 1.07 (0.88-1.30) |
| 4-5 | 0.69 (0.44-1.10) | 0.99 (0.78-1.26) |
| 6-7 | 0.60 (0.31-1.16) | 0.97 (0.70-1.34) |
| ≥8 | 0.27 (0.09-0.82)b | 0.59 (0.36-0.97)b |
| Never smokers | 0.81 (0.73-0.90)b | 1.05 (0.94-1.18) |
| Diabetic neuropathy | ||
| Continuous smokers | 1 [Reference] | 1 [Reference] |
| Quitters by duration, y | ||
| <2 | 1.10 (0.96-1.25) | 0.99 (0.92-1.07) |
| 2-3 | 0.89 (0.75-1.06) | 0.93 (0.85-1.02) |
| 4-5 | 0.80 (0.65-0.99)b | 0.97 (0.86-1.08) |
| 6-7 | 0.72 (0.53-0.97)b | 0.76 (0.64-0.89)b |
| ≥8 | 0.72 (0.51-1.01) | 0.80 (0.66-0.98)b |
| Never smokers | 0.90 (0.85-0.94)b | 0.96 (0.93-0.99)b |
Adjusted for age, sex, body mass index, systolic blood pressure, γ-glutamyl transferase, total cholesterol, alcohol consumption, exercise, pack-years, hypertension, and duration of diabetes.
Indicates statistical significance (P < .05).
Associations were more evident among males, whereas female-specific analyses were limited by small sample size (Table 5). Among men, smoking cessation for 6 to 7 years (aHR, 0.88; 95% CI, 0.78-1.00) and 8 or more years (aHR, 0.82; 95% CI, 0.70-0.95) were associated with lower risk of all microvascular complications. Cessation for 8 or more years was associated with a lower risk of diabetic retinopathy (aHR, 0.56; 95% CI, 0.34-0.94). Cessation for 6 to 7 years (aHR, 0.77; 95% CI, 0.65-0.91) and 8 or more years (aHR, 0.79; 95% CI, 0.66-0.90) were associated with a lower risk of diabetic neuropathy.
Table 5. Sex-Specific Adjusted Hazard of Diabetic Microvascular Complications According to Smoking Cessation Duration, Compared With Continuous Smokers.
| Smoking status | Adjusted hazard ratios (95% CI)a | |
|---|---|---|
| Male | Female | |
| All microvascular complications | ||
| Continuous smokers | 1 [Reference] | 1 [Reference] |
| Quitters by duration, y | ||
| <2 | 1.03 (0.97-1.09) | 0.98 (0.68-1.43) |
| 2-3 | 0.99 (0.92-1.06) | 1.36 (0.84-2.19) |
| 4-5 | 0.98 (0.90-1.07) | 0.99 (0.52-1.45) |
| 6-7 | 0.88 (0.78-1.00)b | 0.69 (0.17-2.79) |
| ≥8 | 0.82 (0.70-0.95)b | NA |
| Never smoker | 0.96 (0.92-1.01) | 0.96 (0.80-1.15) |
| Diabetic nephropathy | ||
| Continuous smokers | 1 [Reference] | 1 [Reference] |
| Quitters by duration, y | ||
| <2 | 1.13 (1.04-1.24) | 1.67 (0.77-3.63) |
| 2-3 | 1.02 (0.91-1.14) | NA |
| 4-5 | 1.05 (0.92-1.20) | NA |
| 6-7 | 1.04 (0.88-1.24) | NA |
| ≥8 | 0.81 (0.64-1.02) | NA |
| Never smoker | 0.92 (0.86-0.98)b | 0.95 (0.67-1.36) |
| Diabetic retinopathy | ||
| Continuous smokers | 1 [Reference] | 1 [Reference] |
| Quitters by duration, y | ||
| <2 | 0.97 (0.81-1.16) | 3.05 (0.68-5.41) |
| 2-3 | 1.07 (0.88-1.31) | NA |
| 4-5 | 0.98 (0.77-1.26) | NA |
| 6-7 | 0.99 (0.71-1.36) | NA |
| ≥8 | 0.56 (0.34-0.94)b | NA |
| Never smoker | 1.05 (0.93-1.19) | 0.62 (0.36-1.08) |
| Diabetic neuropathy | ||
| Continuous smokers | 1 [Reference] | 1 [Reference] |
| Quitters by duration, y | ||
| <2 | 0.99 (0.92-1.07) | 1.09 (0.72-1.66) |
| 2-3 | 0.93 (0.85-1.02) | 1.41 (0.82-2.42) |
| 4-5 | 0.97 (0.87-1.08) | 0.57 (0.08-4.07) |
| 6-7 | 0.77 (0.65-0.91)b | 1.37 (0.68-2.79) |
| ≥8 | 0.79 (0.66-0.90)b | NA |
| Never smoker | 0.96 (0.90-1.01) | 0.92 (0.75-1.13) |
Abbreviation: NA, not available because of the small number of events.
Adjusted for age, body mass index, systolic blood pressure, γ-glutamyl transferase, total cholesterol, alcohol consumption, exercise, pack-years, hypertension, and duration of diabetes.
Indicates statistical significance (P < .05).
With never smokers as the reference group (eTable 1 in Supplement 1), smoking cessation for 8 or more years was associated with a significantly lower risk of all microvascular complications (aHR, 0.81; 95% CI, 0.70-0.94) and diabetic retinopathy (aHR, 0.56; 95% CI, 0.34-0.93), and cessation for 6 to 7 years with a lower risk of diabetic neuropathy (aHR, 0.78; 95% CI, 0.66-0.92). Measured continuously, each 1-year increase in cessation duration was associated with decreased risk for all microvascular complications (aHR, 0.99; 95% CI, 0.98-0.99) and for diabetic neuropathy (aHR, 0.98; 95% CI, 0.97-0.99) (eTable 2 in Supplement 1).
Compared with excluded participants, included participants differed significantly across most characteristics (eTable 3 in Supplement 1), so a sensitivity analysis using a less restrictive inclusion criterion of at least 3 health checkups was performed (eTable 4 in Supplement 1). Smoking cessation for 8 or more years remained associated with a lower risk of all diabetic microvascular complications (aHR, 0.80; 95% CI, 0.69-0.93), diabetic nephropathy (aHR, 0.80; 95% CI, 0.64-0.95), diabetic retinopathy (aHR, 0.59; 95% CI, 0.36-0.96), and diabetic neuropathy (aHR, 0.78; 95% CI, 0.64-0.95).
After PSM, the characteristics are presented in eTable 5 in Supplement 1, and all covariates included in PSM were well balanced, with standardized mean differences less than 0.10 (eTable 6 in Supplement 1). Smoking cessation for 8 or more years remained associated with a significantly lower risk of all diabetic microvascular complications (aHR, 0.82; 95% CI, 0.71-0.96), diabetic nephropathy (aHR, 0.81; 95% CI, 0.70-0.92), diabetic retinopathy (aHR, 0.62; 95% CI, 0.38-0.86), and diabetic neuropathy (aHR, 0.80; 95% CI, 0.66-0.98) (eTable 7 in Supplement 1). In competing risk analyses accounting for death as a competing event (eTable 8 in Supplement 1), smoking cessation for 2 to 3 years was associated with a higher risk of diabetic nephropathy (aHR, 1.12; 95% CI, 1.02-1.22), and smoking cessation for 8 or more years was associated with a significantly lower risk of diabetic neuropathy (aHR, 0.78; 95% CI, 0.66-0.93).
Discussion
In this nationwide cohort study of patients with type 2 diabetes, longer smoking cessation duration was associated with a lower risk of diabetic microvascular complications. Smoking cessation for 8 or more years was associated with lower risk of all diabetic microvascular complications, diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy. However, in sex-stratified analyses, these associations were significant only among male participants.
A 2025 meta-analysis reported an increased risk of diabetic nephropathy among smokers with type 2 diabetes (HR, 1.31; 95% CI, 1.01-1.67),23 but prior cohorts in Japan (1407 participants) and Sweden (6513 participants) classified smoking status as a binary variable combining never smokers and quitters and found no significant association with renal outcomes.24,25 By classifying participants into 3 distinct categories based on repeated assessments, our study minimized misclassification and enabled more precise evaluation. The association between smoking and diabetic retinopathy in patients with diabetes also remains uncertain. A meta-analysis of studies published before 2017 reported a lower risk of diabetic retinopathy among smokers with type 2 diabetes than among never smokers (risk ratio, 0.92; 95% CI, 0.86-0.98).26 However, several studies published after 2017 have suggested that smoking may increase the risk of diabetic retinopathy.27 Our previous study did not identify a significant association between heavy smoking and diabetic retinopathy.11
The association between smoking and diabetic neuropathy remains inconclusive, although recent evidence has tended to support a positive association. Earlier meta-analyses reported no significant associations,28,29 whereas a 2025 meta-analysis found a significantly increased risk (pooled OR, 1.14; 95% CI, 1.03-1.25).30 Consistent with these findings, our study showed that continuous smokers had a significantly higher risk of diabetic neuropathy than never smokers.
Although smoking cessation provides significant benefits for macrovascular complications, its role in microvascular complications remains less well understood. In a scoping review of 26 publications, Walicka et al27 concluded that the most consistent evidence for a beneficial association of smoking cessation was observed for diabetic nephropathy, whereas evidence regarding retinopathy and neuropathy was limited.27 Our finding of a lower risk of diabetic retinopathy and neuropathy after 8 or more years of cessation extends this evidence beyond nephropathy, although this estimate was based on a small number of events and should be interpreted with caution.
Our findings have important clinical implications for the management of type 2 diabetes. Despite guidelines recommending smoking cessation in all patients with diabetes, the pooled prevalence of current smoking among individuals with type 2 diabetes remains approximately 20.8% globally.31 The American Diabetes Association recommends routine tobacco assessment with cessation counseling and pharmacotherapy.32 Our finding that microvascular benefits associated with cessation became more apparent with longer abstinence may enhance risk communication during cessation counseling.
Strengths and Limitations
Our study has several notable strengths. To our knowledge, this is the first large-scale cohort study to systematically evaluate smoking cessation duration and the risk of all 3 diabetic microvascular complications among patients with type 2 diabetes. Unlike most prior studies relying on a single smoking assessment, we classified smoking behavior longitudinally using repeated health checkups, requiring quitters to demonstrate sustained abstinence across all follow-up examinations, which reduced misclassification and recall bias. Excluding participants with unstable smoking patterns and applying detailed cessation duration categories further allowed us to precisely characterize temporal changes in risk.
Several limitations should be considered. First, as in any observational study, residual confounding by unmeasured factors cannot be excluded, indicating associations rather than causality. In particular, hemoglobin A1c was not available in our dataset. Although we adjusted for duration of diabetes as a marker of cumulative exposure to hyperglycemia, residual confounding by glycemic control cannot be fully excluded. Second, the possibility of sick quitter bias cannot be excluded, as some participants may have stopped smoking because of worsening health status or early manifestations of diabetic complications. This possibility is supported by our finding that quitters who had quit smoking for less than 2 years showed a higher risk of diabetic nephropathy compared with continuous smokers. Third, healthy quitter bias may also be present, because individuals who maintained long-term smoking cessation may have been more likely than continuous smokers to adopt other healthy behaviors, such as abstaining from alcohol and exercising regularly. Consistent with this possibility, quitters were more likely to exercise regularly and less likely to drink frequently than continuous smokers. Fourth, participants in our main analyses were required to have at least 4 health checkups with intervals shorter than 37 months, which may introduce selection bias. These participants may be more health-conscious than the general population of patients with diabetes. However, a sensitivity analysis restricting the requirement to 3 visits yielded results similar to those of the main analysis, and the national general health checkup participation rate in Korea is relatively high (65.3% in 2008 and 72.1% in 2013).33 Fifth, covariates were assessed at the index date rather than at the time of smoking cessation. Sixth, since health checkup data were only available starting in 2002, we were unable to determine smoking history prior to 2002. Seventh, smoking status and cessation duration were fixed at the index date and were not updated during follow-up. Participants who quit smoking or relapsed after the index date could not be identified.
Conclusions
In this cohort study of patients with type 2 diabetes, the risk of diabetic microvascular complications declined progressively with longer smoking cessation duration. These findings suggest that microvascular risk reduction associated with smoking cessation required sustained, long-term cessation rather than appearing soon after quitting. Because these associations were observed mainly among male participants, the results may not be generalizable to female patients, and further studies with adequate power in women are warranted.
eMethods.
eFigure 1. Timeline for cohort enrollment and follow-up
eFigure 2. Flowchart of the study participants
eFigure 3. Schematic illustrating the classification of never smokers, quitters, continuous smokers, and excluded participants based on repeated health checkups
eFigure 4. Cumulative incidence of all diabetic microvascular complications according to smoking cessation duration category and continuous smoking status
eTable 1. Hazard of diabetic microvascular complications according to smoking cessation duration referenced to never smokers
eTable 2. Hazard of diabetic microvascular complications per 1-year increase in cessation duration
eTable 3. Baseline characteristics of included and excluded participants.
eTable 4. Hazard of diabetic microvascular complications according to smoking cessation duration referenced to continuous smokers, restricted to participants with at least 3 health checkups
eTable 5. Baseline characteristics of the propensity score-matched study population according to smoking status
eTable 6. Covariate balance before and after propensity score matching
eTable 7. Hazard of diabetic microvascular complications according to smoking cessation duration referenced to continuous smokers after propensity score matching
eTable 8. Subdistribution hazards of diabetic microvascular complications according to smoking cessation duration referenced to continuous smokers in competing risk analyses
Data Sharing Statement
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
eMethods.
eFigure 1. Timeline for cohort enrollment and follow-up
eFigure 2. Flowchart of the study participants
eFigure 3. Schematic illustrating the classification of never smokers, quitters, continuous smokers, and excluded participants based on repeated health checkups
eFigure 4. Cumulative incidence of all diabetic microvascular complications according to smoking cessation duration category and continuous smoking status
eTable 1. Hazard of diabetic microvascular complications according to smoking cessation duration referenced to never smokers
eTable 2. Hazard of diabetic microvascular complications per 1-year increase in cessation duration
eTable 3. Baseline characteristics of included and excluded participants.
eTable 4. Hazard of diabetic microvascular complications according to smoking cessation duration referenced to continuous smokers, restricted to participants with at least 3 health checkups
eTable 5. Baseline characteristics of the propensity score-matched study population according to smoking status
eTable 6. Covariate balance before and after propensity score matching
eTable 7. Hazard of diabetic microvascular complications according to smoking cessation duration referenced to continuous smokers after propensity score matching
eTable 8. Subdistribution hazards of diabetic microvascular complications according to smoking cessation duration referenced to continuous smokers in competing risk analyses
Data Sharing Statement
