read and answer the following in two or three sentences:
1. In Paragraph 1, the authors provided one important statistic for this problem. What was that statistic and where did it come from?
2. In your own words, what are some limitations of their study that the authors identified?
Smoking and Risk for Diabetes Incidence
and Mortality in Korean Men and Women
SUN HA JEE, PHD1,2
ATHENA W. FOONG, BSC3
NAM WOOK HUR, PHD4
JONATHAN M. SAMET, MD, MS3
OBJECTIVE — Mounting evidence suggests that smoking is a cause of type 2 diabetes. We
explored the association of cigarette smoking with diabetes incidence and mortality in a large
cohort of Koreans.
RESEARCH DESIGN AND METHODS — A 14-year prospective cohort study was
performed on 1,236,443 Korean men and women, aged 30 –95 years at baseline, who underwent
standardized biennial medical examinations provided by the National Health Insurance Corpo-
ration (NHIC). Incident diabetes was identified on the basis of outpatient visits, hospitalization,
or prescription medication treatment for diabetes, as captured in the NHIC database. Diabetes
mortality was obtained through the national statistical office. Cox proportional hazards models
were used to investigate associations of smoking with indicators of diabetes and diabetes
mortality.
RESULTS — Smoking was significantly associated with increased risk for diabetic outpatient
treatment, hospitalization, and mortality among both men and women, and the risk among
current smokers increased modestly with the number of cigarettes smoked daily (Ptrend �
0.0001 for all associations). Compared with never smokers, current male smokers who smoked
�20 cigarettes/day had increased risk for incident diabetes defined by outpatient treatment
(adjusted hazard ratio 1.55 [1.51–1.60]), incident diabetes defined by �3 prescription medi-
cations for diabetes (1.71 [1.63–1.80]), and death from diabetes (1.60 [1.25–2.06]). The risks
for outpatient treatment among smokers were higher in men than in women with evidence for
effect modification by sex and age (Pinteraction � 0.0001).
CONCLUSIONS — Our study provides longitudinal evidence that smoking increases the
risk of incident diabetes and mortality.
Diabetes Care 33:2567–2572, 2010
T
obacco smoking is well established as
a causal risk factor for multiple dis-
eases (1). Since the early 1990s, active
smoking has been assessed as a risk factor
for type 2 diabetes in multiple cohort stud-
ies (2,3). In a 2007 systematic review, Willi
et al. (2) found that active smoking was as-
sociated with a higher incidence of type 2
diabetes based on evidence from 25 cohort
studies. The pooled adjusted relative risk
(RR) was 1.44 (95% CI 1.31–1.58), and
there was an indication of a dose-response
relationship with amount smoked. The hy-
pothesis that smoking increases risk for in-
cident type 2 diabetes draws plausibility
from the general inflammation caused by
smoking and the increased insulin resis-
tance and greater abdominal obesity in
smokers (1,4). Given the immediate meta-
bolic consequences of smoking, current
smokers may be at greater risk than former
smokers (4). With regard to mortality, it is
well established that diabetic individuals
who smoke are at greatly increased risk for
dying because of the increased risk for car-
diovascular disease caused by smoking (1,5).
Since the meta-analysis by Willi et al.
(2), three more cohort studies on smok-
ing and diabetes have been reported (6 –
8). Two were in Korea, the location of our
study. Hur et al. (6) followed a cohort of
27,635 men through the Korean Medical
Insurance Corporation and found that
sustained active smoking was associated
with a 60% increase in risk, whereas risk
declined with increasing duration of ces-
sation. In a cohort study of 4,041 men in
urban and rural Korea, former and cur-
rent smokers had significantly increased
risk for type 2 diabetes, and the risk in-
creased among current smokers with
number of cigarettes smoked (7). The
third study, conducted in New York,
showed that current smokers had more
than a twofold increased risk for onset of
impaired fasting glucose after 6 years of
follow-up among those who were normo-
glycemic at baseline (8).
Smoking has not yet been designated
as a cause of diabetes in reports of the U.S.
Surgeon General or other authoritative
groups. To obtain additional evidence on
smoking as a potential cause of type 2
diabetes, we explored the association of
smoking with diabetes in a cohort study
of 1.3 million Koreans, the Korean Cancer
Prevention Study (KCPS) (9,10). Because
of the richness of the clinical data avail-
able in the KCPS and the high prevalence
of smoking among Korean men, we were
able to assess smoking as a risk factor for
incident diabetes ascertained using clini-
cal indicators based on outpatient visit
and hospitalization diagnoses and on
medication prescriptions.
RESEARCH DESIGN AND
METHODS — The design and base-
line characteristics of the KCPS have been
described previously (9). It includes
1,329,525 Korean men and women aged
30 –95 years who participated in a Na-
tional Health Insurance Corporation
(NHIC) medical evaluation between 1992
and 1995 with biennial follow-up evalu-
ations through 2006. The numbers of
baseline enrollees by year were 784,870
in 1992, 367,903 in 1993, 98,417 in
1994, and 78,335 in 1995. All enrollees
in the NHIC underwent standardized ex-
aminations at local hospitals.
We excluded 904 participants who
● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●
From the 1Department of Epidemiology and Health Promotion and Institute for Health Promotion, Graduate
School of Public Health, Yonsei University, Seoul, Korea; the 2Department of Epidemiology, Johns
Hopkins Bloomberg School of Public Health, Baltimore, Maryland; the 3Department of Preventive Med-
icine and Institute for Global Health, Keck School of Medicine, University of Southern California, Los
Angeles, California; and the 4Department of Preventive Medicine, Yonsei College of Medicine, Seoul,
Korea.
Corresponding author: Sun Ha Jee, jsunha@yuhs.ac.
Received 9 February 2010 and accepted 29 August 2010. Published ahead of print at http://care.
diabetesjournals.org on 7 September 2010. DOI: 10.2337/dc10-0261.
© 2010 by the American Diabetes Association. Readers may use this article as long as the work is properly
cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.
org/licenses/by-nc-nd/3.0/ for details.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby
marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
E p i d e m i o l o g y / H e a l t h S e r v i c e s R e s e a r c h
O R I G I N A L A R T I C L E
care.diabetesjournals.org DIABETES CARE, VOLUME 33, NUMBER 12, DECEMBER 2010 2567
died before 1993 along with 64,507 par-
ticipants who reported having diabetes on
enrollment. Also excluded were 27,671
participants with missing information on
smoking, BMI, or alcohol consumption at
enrollment. The final sample for this anal-
ysis included 1,236,443 participants. For
the analyses of incident diabetes as as-
sessed by prescriptions during the win-
dow 2001–2005, those with diabetes
before 2000 (n � 53,639), without a fol-
low-up survey or missing data on BMI or
alcohol consumption (n � 397,582), or
with inconsistent smoking data between
baseline and follow-up (n � 76,961) were
excluded. Therefore, the final sample size
for the analysis of incident diabetes based
on prescription medication was 708,261
participants.
Informed consent was not specifically
obtained because the study involved rou-
tinely collected data. The institutional re-
view boards of Yonsei University and the
Johns Hopkins Bloomberg School of Pub-
lic Health approved the study.
Data collection
Standardized questionnaire. During
the biennial visits at both baseline and fol-
low-up examinations, participants re-
ported their smoking habits, including
number of cigarettes smoked per day and
duration of cigarette smoking in years for
current smokers, along with other health
information including alcohol consump-
tion and exercise. History of past or prev-
alent diabetes was also included in the
baseline questionnaire.
Medical examination. Fasting serum
glucose measurements were obtained
during medical evaluations for routine
clinical purposes. Each hospital had inter-
nal and external quality control proce-
dures directed by the Korean Association
of Laboratory Quality Control (9). Data
for weight and height were also obtained.
Outpatient visit and hospitalization.
All outpatient and hospitalization
records
from 1993 through 2006 were captured by
the NHIC. Outpatient treatment and hospi-
talization due to diabetes were defined ac-
cording to ICD-10 codes (E11–E11x and
E14 –E14x). Outpatient records were not
complete for 1993 through 1996.
History of prescription medication for
diabetes. Between 2001 and 2005, 16
diabetes-related medications and the in-
sulin pump were listed in the medication
database at the Health Insurance Review
and Assessment Service; the medications
included insulin, acarbose, glibenclamide,
gliclazide, glimepiride, glipizide, gliqui-
done, repaglinide, nateglinide, metformin,
voglibose, rosiglitazone, pioglitazone, com-
bination sulfonyl and metformin, and com-
bination thiazolidinedione and metformin.
Mortality data. Vital status of all partici-
pants was tracked from 1993 through 2006
and the underlying cause of death was ob-
tained as reported to the national statistical
office. Data for mortality from diabetes
(ICD-10 codes E11–E11x and E14 –E14x)
were captured, and mortality ascertainment
was complete for all Korean residents.
Follow-up and outcome
classification
The primary outcome variables were inci-
dent diabetes defined by outpatient treat-
ment for diabetes (at least three visits for
diabetes care per 365 days), hospitaliza-
tion due to diabetes (at least one hospital-
ization for diabetes during the study
period), use of prescription medication
for diabetes management or treatment,
and mortality due to diabetes. For analy-
ses related to indicators of incident diabe-
tes, we excluded individuals with
prevalent diabetes at baseline, defined as
self-reported history of diabetes or fasting
serum glucose �125 mg/dl.
Baseline smoking status (Fig. 1A) was
used for analyses of hospitalization, mor-
tality, and outpatient data. Hospitaliza-
tion and mortality data were available for
the entire study period, and complete
outpatient data were available from 1997
to 2006.
Medication data were limited to
2001–2005. In the analysis of medication
data, we used the follow-up smoking sta-
tus reported between 1997 and 2000
(Fig. 1B), because the medication data
were available only from 2001 through
2005.
Statistical analysis
Smoking status was classified as never,
current, and former, and current smokers
were further classified as smoking 1–9,
10 –19, or �20 cigarettes/day. Self-
reported smokers at entry who reported
never smoking at follow-up (n � 76,961,
17.1% of current and former smokers at
baseline) were not reclassified and were
excluded from the analysis. Alcohol con-
sumption was categorized as 0, 1–24, 25–
49, 50 –99, and �100 g/day. BMI was
categorized as �18.5, 18.5–19.9, 20.0 –
21.4, 21.5–22.9, 23.0 –24.9, 25.0 –26.4,
26.5–27.9, 28.0 –29.9, 30 –31.9, and
�32.0 kg/m2. Indicator variables, corre-
sponding to these categories, were used
Figure 1—Timeline for the Korean Cancer Prevention Study data collection, 1992–2006. A: Data used for analysis by baseline smoking status. B:
Data used for analysis by follow-up smoking status.
Smoking and diabetes
2568 DIABETES CARE, VOLUME 33, NUMBER 12, DECEMBER 2010 care.diabetesjournals.org
for the analysis. Medication history was
categorized by the number of prescrip-
tions for diabetes given within any 365-
day span during the follow-up period of
2001–2005 and stratified as �1 prescrip-
tions/365 days or �3 prescriptions/365
days.
Analyses were stratified by sex and
adjusted for age at enrollment (using age
and the square of age [age2]), alcohol con-
sumption, BMI, and exercise. Cox pro-
portional hazards models were used to
evaluate the association of smoking with
risk for the various diabetes indicators. All
Cox models were tested for and met the
proportional hazards assumption. In a
sensitivity analysis for mortality, we ex-
cluded the first 2 years of follow-up to
assess the potential role of reverse causal-
ity, i.e., that smoking status changed be-
c a u s e o f a d i a b e t e s d i a g n o s i s .
Modification of the effect of smoking was
assessed by inclusion of interaction terms
of smoking category indicators with indi-
cator variables for age, sex, BMI, and al-
cohol drinking. All analyses were
conducted using SAS (version 9.1; SAS
Institute, Cary, NC).
RESULTS — For diabetes hospitaliza-
tion and mortality, the full study popula-
tion of 1,236,443 individuals (787,764
men and 448,679 women) was largely
middle-aged on enrollment (median age
45 years; interquartile range 37–55
years). Consistent with national data at
that time, the majority of men were smok-
ers (58.6% current smokers and 20.6%
former smokers among those without di-
abetes). Among current male smokers
without diabetes, 27.2% smoked 1–9 cig-
arettes daily, 42.0% smoked 10 –19 ciga-
rettes daily, and 30.8% smoked �20
cigarettes daily. In contrast, �6.0% of
women without diabetes reported smok-
ing cigarettes (4.0% current smokers and
2.0% former smokers). Over the fol-
low-up period, which was as long as 14
years, there were 1,185 deaths (748 men
and 737 women) from diabetes, 11,398
individuals met the hospitalization crite-
ria for incident diabetes, and 89,422 met
the outpatient visit criteria. Among those
meeting the hospitalization criteria,
79.2% also met the outpatient criteria.
Table 1 summarizes the baseline charac-
teristics of study participants without di-
abetes at enrollment.
We first assessed the relationship of
baseline smoking status with indicators of
incident diabetes and diabetes mortality
(Table 2). In both men and women,
smoking was associated with increased
risk for �3 outpatient visits for diabetes,
hospitalization due to diabetes, and death
of diabetes. The risks were higher in cur-
Table 1—Baseline characteristics of participants without diabetes at enrollment in the Korean Cancer Prevention Study, 1992–2006
Men Women
Never smoker Former smoker Current smoker Never smoker Former smoker Current smoker
n 163,838 162,548 461,378 421,847 9,079 17,753
Age (years) 45.2 � 11.1 47.1 � 11.6 44.0 � 10.7 48.4 � 11.6 63.2 � 11.8 62.7 � 10.1
Weight (kg) 66.3 � 8.5 66.5 � 8.5 65.8 � 8.7 55.8 � 7.8 53.8 � 8.7 52.2 � 9.0
BMI (kg/m2) 23.4 � 2.6 23.4 � 2.5 23.1 � 2.6 23.2 � 3.1 23.5 � 3.3 22.7 � 3.4
Alcohol drinking (g/day) 10.7 � 24.4 13.0 � 26.2 20.7 � 35.4 0.2 � 1.7 0.4 � 2.8 0.6 � 4.4
Fasting serum glucose (mg/dl) 89.2 � 12.8 89.5 � 12.8 88.6 � 13.1 87.0 � 12.3 89.0 � 13.3 88.5 � 13.3
Data are means � SD.
Table 2—Adjusted hazard ratios (95% CI) for indicators of incident diabetes and for diabetes mortality by baseline smoking status, alcohol
intake, and exercise in men and women in the Korean Cancer Prevention Study, 1992–2006
Baseline characteristics
Men Women
Incident diabetes
Death of diabetes
Incident diabetes
Death of diabetesOutpatient visits
Hospitalization
records Outpatient visits
Hospitalization
records
Never smoker 1.0 1.0 1.0 1.0 1.0 1.0
Former smoker 1.10 (1.07–1.13) 1.12 (1.03–1.21) 0.96 (0.76–1.22) 1.19 (1.10–1.28) 1.31 (1.11–1.55) 1.33 (0.93–1.90)
Current smoker (cigarettes
smoked daily)*
1–9 1.30 (1.25–1.32) 1.50 (1.38–1.62) 1.63 (1.29–2.07) 1.34 (1.25–1.44) 1.43 (1.21–1.68) 1.86 (1.35–2.58)
10–19 1.37 (1.34–1.41) 1.58 (1.47–1.71) 1.44 (1.14–1.82) 1.26 (1.14–1.38) 1.65 (1.35–2.02) 1.91 (1.26–2.89)
�20 1.55 (1.51–1.60) 1.79 (1.66–1.93) 1.60 (1.25–2.06) 1.33 (1.15–1.53) 1.57 (1.14–2.16) 3.38 (2.03–5.63)
Alcohol intake (g/day)
0 1.0 1.0 1.0 1.0 1.0 1.0
1–24 0.95 (0.93–0.97) 0.86 (0.82–0.91) 0.85 (0.72–0.99) 0.90 (0.87–0.93) 0.83 (0.76–0.92) 0.94 (0.72–1.23)
25–49 0.99 (0.96–1.02) 0.94 (0.86–1.02) 1.01 (0.74–1.38)
50–99 1.05 (1.01–1.08) 1.11 (1.01–1.23) 1.02 (0.66–1.56) 1.85 (0.77–4.43) 3.05 (0.43–21.7) NE
�100 1.04 (0.99–1.10) 1.28 (1.10–1.48) 1.12 (0.57–2.19)
Exercise 0.94 (0.92–0.96) 0.98 (0.93–1.03) 0.89 (0.76–1.04) 1.03 (1.00–1.06) 1.02 (0.94–1.10) 0.95 (0.74–1.22)
Hazard ratios were adjusted for age, age2, alcohol drinking, BMI, and exercise. Data collection periods for outpatient visits, hospitalization, and death were 1997
through 2006, 1993 through 2006, and 1993 through 2006, respectively. NE, not estimated due to small of number of instances. *Ptrend � 0.0001 for all associations.
Jee and Associates
care.diabetesjournals.org DIABETES CARE, VOLUME 33, NUMBER 12, DECEMBER 2010 2569
rent smokers than in former smokers, and
there was an indication of increasing risk
with increasing number of cigarettes
smoked daily among current smokers
(Ptrend � 0.0001). For outpatient visits for
diabetes, risks among smokers were
higher in men than in women, with evi-
dence for effect modification by sex and
age (Pinteraction � 0.0001). There was
some indication of increased risk for inci-
dent diabetes with alcohol drinking
among men but without a dose response.
Exercise, as reported at baseline, was mar-
ginally associated with decreased risk for
incident outpatient visit for diabetes in
men.
For the analysis of the association of
smoking with prescription medications
for diabetes, the sample included
708,261 individuals. Compared with the
full cohort, this group tended to be
younger, reflecting the start of the win-
dow with medication data �7 years after
enrollment. Over the follow-up period of
2001 through 2005, there were 6,815
cases of incident diabetes based on �1
prescriptions and 2,427 based on �3 pre-
scriptions. Among men, smoking was as-
sociated with increased risk for incident
diabetes defined by use of prescription
medication for diabetes (Table 3). Risk in-
creased with increasing number of ciga-
rettes smoked daily. The association was
stronger for those given �3 prescriptions
annually than for those given �1 pre-
scription annually. A similar association
was observed among women who were cur-
rent smokers. There was evidence of effect
modification by sex and age (Pinteraction �
0.0001). Alcohol drinking was not signifi-
cantly associated with use of diabetes med-
ication among men, but the risk was
significantly higher among women who
consumed �50 g of alcohol/day. Exercise
decreased the risk for incident diabetes.
Among current male smokers, the in-
creasing risk of incident diabetes with in-
creasing amount of cigarettes smoked daily,
as reported at entry, persisted with control
for duration of smoking. We did not find an
indication that risk increased as duration in-
creased, after controlling for amount
smoked. Mortality was not associated with
either amount smoked or duration of smok-
ing in the fully adjusted model (supplemen-
tary Table 1, available in an online appen-
dix at http://care.diabetesjournals.org/cgi/
content/full/dc10-0261/DC1).
We also explored modification of the
effect of smoking on risk for diabetes by
alcohol consumption and BMI. For both,
the data did not indicate that their pres-
ence modified the risks of smoking.
CONCLUSIONS — Using a large co-
hort and multiple indicators for the oc-
currence of type 2 diabetes, we have
shown that cigarette smoking is associ-
ated with incident diabetes and with mor-
tality from diabetes. The effect was greater
among current smokers than among
former smokers. Among current smokers,
the risk for incident diabetes increased
slightly with amount smoked, but not
with duration of smoking. The associa-
tion of smoking with diabetes was robust
to control for potential confounding fac-
tors including age, BMI, alcohol drinking,
and exercise. The association was stron-
ger in men and at younger ages and was
not modified by alcohol consumption or
BMI.
The association of smoking with type
2 diabetes has been examined previously
in multiple studies. The 2007 meta-
analysis by Willi et al. (2) included 25
cohort studies with 45,844 cases of inci-
dent diabetes. All but one of the individ-
ual studies demonstrated a positive
association with smoking. As observed in
the KCPS cohort, there was evidence of a
dose-response relationship among cur-
rent smokers with amount smoked. Our
confirmatory findings from a single co-
hort of 1.3 million are based on a far larger
number of cases of incident diabetes than
in the meta-analysis and add greatly to the
evidence from Asian populations.
Type 2 diabetes is rapidly increasing
in Asia, driven in part by increasing obe-
sity (11). Imaging studies suggest that
Asians may have greater visceral adiposity
at any particular BMI than Caucasians and
hence a greater risk for type 2 diabetes
(11). To date there have been eight cohort
studies of smoking and diabetes in Asian
populations, involving diverse popula-
tions and various outcome measures (12–
17). Most show increased risk for type 2
diabetes in current smokers and the ma-
jority of the effect estimates indicate an
Table 3—Adjusted hazard ratios (95% CI) for diabetes medication prescription by follow-up smoking status, alcohol intake, and exercise in
men and women of the Korean Cancer Prevention Study, 1992–2006
Follow-up characteristics
Men Women
�1 prescription/
365 days
�3 prescriptions/
365 days
�1 prescription/
365 days
�3 prescriptions/
365 days
Never smoker 1.0 1.0 1.0 1.0
Former smoker 1.17 (1.14–1.21) 1.28 (1.22–1.35) 1.06 (0.94–1.19) 1.09 (0.89–1.33)
Current smoker (cigarettes
smoked daily)*
1–9 1.11 (1.07–1.15) 1.37 (1.29–1.45) 1.20 (1.09–1.31) 1.39 (1.20–1.62)
10–19 1.17 (1.14–1.20) 1.54 (1.48–1.61) 1.17 (1.04–1.32) 1.61 (1.35–1.93)
�20 1.25 (1.21–1.29) 1.71 (1.63–1.80) 1.09 (0.85–1.39) 1.61 (1.12–2.30)
Alcohol intake (g/day)
0 1.0 1.0 1.0 1.0
1–24 0.96 (0.94–0.98) 0.96 (0.93–1.00) 0.98 (0.95–1.02) 0.96 (0.90–1.03)
25–49 0.99 (0.96–1.03) 1.01 (0.96–1.07)
50–99 1.02 (0.98–1.06) 1.09 (1.02–1.16) 2.21 (0.92–5.32) 5.61 (1.81–17.40)
�100 0.95 (0.89–1.02) 1.00 (0.90–1.11)
Exercise 0.93 (0.91–0.95) 0.86 (0.83–0.89) 0.98 (0.94–1.01) 0.93 (0.87–0.99)
Hazard ratios were adjusted for age, age2, alcohol drinking, BMI, and exercise. Data collection period for prescription medication was 2001 through 2005. *Ptrend �
0.0001 for any prescriptions in men and �3 prescriptions in women; P � 0.0062 for �1 prescription in women.
Smoking and diabetes
2570 DIABETES CARE, VOLUME 33, NUMBER 12, DECEMBER 2010 care.diabetesjournals.org
approximate doubling of risk, somewhat
higher than that observed in our study.
The lower hazard rates among former
smokers suggest that the acute effects of
smoking on insulin resistance may play a
role in the contribution of smoking to the
onset of diabetes (4).
We found that risk for incident diabe-
tes increased with amount smoked; the
magnitude of the increase was compara-
ble to the estimate made by Willi et al. (2)
(relative risk 1.61 for smokers of �20 cig-
arettes/day vs. never smokers). Risk did
not increase with duration of smoking in
our study. We did not identify other re-
ports providing similar estimates. Several
found that risk increased with pack-years
of smoking, but this cumulative measure
combines amount smoked with duration
of smoking (14,18,19).
We found strong evidence for effect
modification by age, with significantly
lower risks at older ages, regardless of the
outcome indicator. This pattern could re-
flect a depletion of susceptible individuals
at older ages, lower amount smoked by
older individuals, and possibly greater
misclassification of exposures and out-
comes in older participants. A similar pat-
tern of effect modification has been
observed for cigarette smoking and car-
diovascular disease. For example, in the
American Cancer Society’s Cancer Pre-
vention Study (CPS) I, risks for coronary
heart disease and cerebrovascular disease
declined progressively with increasing
age, such that for individuals aged �80
years, risks were not increased among
current smokers (20). Our findings are in
contrast to those presented in the meta-
analysis by Willi et al. (2). They found a
higher pooled estimate in those aged �50
years compared with younger individu-
als. However, the comparison of relative
risks by age was based on different sets of
studies for the two age strata. With regard
to BMI, Willi et al. (2) also found signifi-
cantly greater risk for individuals with
BMI of �25 kg/m2. In contrast, we found
no evidence for greater risk in those with
higher BMI. The lower risks in women are
likely to reflect the lower number of ciga-
rettes smoked per day by Korean women
(10).
Potential limitations of this study pri-
marily reflect the need to rely on self-
report for tobacco and alcohol use and on
medical database information for estab-
lishing the diagnosis of diabetes, leading
to concern for potential misclassification
of exposures and outcomes. Smoking sta-
tus was updated during the follow-up
visit, however, and self-report of smoking
in Korea has been shown to be valid when
compared by use of cotinine (21). Be-
cause the follow-up data collection on
smoking occurred at various points after
enrollment, we could not update duration
of smoking for analytical purposes. Con-
sequently, our analyses could not explore
risk in relation to lengthening duration of
exposure or cessation during follow-up.
For establishing the occurrence of in-
cident diabetes, we used three different
indicators based on outcomes unlikely to
be subject to substantial misclassification
and found similar results with each. Our
definitions were intended to exclude in-
dividuals being evaluated for diabetes
who did not actually have the disease.
Consequently, for incident disease we re-
quired at least three outpatient visits or
prescription of a therapeutic agent once
or three times, the latter being less subject
to misclassification. For establishing the
diagnosis of prevalent disease, we relied
in part on self-report, which may be sub-
ject to misclassification. We do not antic-
ipate that misclassification of either
smoking or the outcome variables would
systematically induce a positive associa-
tion of smoking with diabetes.
There are limitations to the generaliz-
ability of the findings. The age range of
the population did not extend to adoles-
cents and young adults, who are now ex-
periencing type 2 diabetes because of
extreme obesity. The majority of the study
population were middle-class, employed
individuals, who may be healthier than
the general population in Korea. Al-
though incidence rates of disease proba-
bly differ by socioeconomic status, there
is little reason to suspect that the risk fac-
tor– disease relationship should markedly
differ.
The mounting evidence on smoking
and diabetes, particularly in Asians, sug-
gests that smoking should be considered
as a potentially reversible cause of diabe-
tes. Our findings greatly strengthen the
available evidence on smoking and diabe-
tes and should be considered as a further
basis for controlling tobacco use in Korea
and throughout Asia.
Acknowledgments — This study was sup-
ported by Seoul City Research and Business
Development program (10526), Seoul, Korea.
No potential conflicts of interest relevant to
this article were reported.
S.H.J. analyzed data and wrote the manu-
script. A.W.F. and J.M.S. contributed to dis-
cussion and reviewed/edited the manuscript.
N.W.H. provided input to data analysis and
reviewed/edited the manuscript.
We thank the staff of the Korean National
Health Insurance Corporation. The Johns
Hopkins Bloomberg School of Public Health is
one of five partner organizations of the
Bloomberg Initiative; its mission is to promote
freedom from smoking worldwide.
References
1. U.S. Department of Health and Human
Services. The Health Consequences of Smok-
ing. A Report of the Surgeon General. At-
lanta, GA, U.S. Department of Health and
Human Services, Centers for Disease
Control and Prevention, National Center
for Chronic Disease Prevention and
Health Promotion, Office on Smoking
and Health, 2004
2. Willi C, Bodenmann P, Ghali WA, Faris
PD, Cornuz J. Active smoking and the risk
of type 2 diabetes: a systematic review and
meta-analysis. JAMA 2007;298:2654 –
2664
3. Cassano PA, Rosner B, Vokonas PS, Weiss
ST. Obesity and body fat distribution in
relation to the incidence of non-insulin-
dependent diabetes mellitus. A prospec-
tive cohort study of men in the normative
aging study. Am J Epidemiol 1992;136:
1474 –1486
4. Berlin I. Smoking-induced metabolic dis-
orders: a review. Diabetes Metab 2008;
34(4 Pt. 1):307–314
5. Tonstad S. Cigarette smoking, smoking
cessation, and diabetes. Diabetes Res Clin
Pract 2009;85:4 –13
6. Hur NW, Kim HC, Nam CM, Jee SH, Lee
HC, Suh I. Smoking cessation and risk of
type 2 diabetes mellitus: Korea Medical
Insurance Corporation Study. Eur J Car-
diovasc Prev Rehabil 2007;14:244 –249
7. Cho NH, Chan JC, Jang HC, Lim S, Kim
HL, Choi SH. Cigarette smoking is an in-
dependent risk factor for type 2 diabetes:
a four-year community-based prospective
study. Clin Endocrinol (Oxf) 2009;71:
679 – 685
8. Rafalson L, Donahue RP, Dmochowski J,
Rejman K, Dorn J, Trevisan M. Cigarette
smoking is associated with conversion
from normoglycemia to impaired fasting
glucose: the Western New York Health
Study. Ann Epidemiol 2009;19:365–371
9. Jee SH, Ohrr H, Sull JW, Yun JE, Ji M,
Samet JM. Fasting serum glucose level
and cancer risk in Korean men and
women. JAMA 2005;293:194 –202
10. Jee SH, Golub JE, Jo J, Park IS, Ohrr H,
Samet JM. Smoking and risk of tubercu-
losis incidence, mortality, and recurrence
in South Korean men and women. Am J
Epidemiol 2009;170:1478 –1485
11. Chan JC, Malik V, Jia W, Kadowaki T, Ya-
jnik CS, Yoon KH, Hu FB. Diabetes in Asia:
epidemiology, risk factors, and pathophys-
iology. JAMA 2009;301:2129 –2140
Jee and Associates
care.diabetesjournals.org DIABETES CARE, VOLUME 33, NUMBER 12, DECEMBER 2010 2571
12. Kawakami N, Takatsuka N, Shimizu H,
Ishibashi H. Effects of smoking on the in-
cidence of non-insulin-dependent diabe-
tes mellitus. Replication and extension in
a Japanese cohort of male employees.
Am J Epidemiol 1997;145:103–109
13. Uchimoto S, Tsumura K, Hayashi T, Sue-
matsu C, Endo G, Fujii S, Okada K. Im-
pact of cigarette smoking on the incidence
of type 2 diabetes mellitus in middle-aged
Japanese men: the Osaka Health Survey.
Diabet Med 1999;16:951–955
14. Nakanishi N, Nakamura K, Matsuo Y, Su-
zuki K, Tatara K. Cigarette smoking and
risk for impaired fasting glucose and type
2 diabetes in middle-aged Japanese men.
Ann Intern Med 2000;133:183–191
15. Sawada SS, Lee IM, Muto T, Matuszaki K,
Blair SN. Cardiorespiratory fitness and
the incidence of type 2 diabetes: prospec-
tive study of Japanese men. Diabetes Care
2003;26:2918 –2922
16. Sairenchi T, Iso H, Nishimura A, Hosoda
T, Irie F, Saito Y, Murakami A, Fukutomi
H. Cigarette smoking and risk of type 2
diabetes mellitus among middle-aged and
elderly Japanese men and women. Am J
Epidemiol 2004;160:158 –162
17. Waki K, Noda M, Sasaki S, Matsumura Y,
Takahashi Y, Isogawa A, Ohashi Y, Kad-
owaki T, Tsugane S, JPHC Study Group.
Alcohol consumption and other risk fac-
tors for self-reported diabetes among
middle-aged Japanese: a population-
based prospective study in the JPHC
study cohort I. Diabet Med 2005;22:323–
331
18. Manson JE, Ajani UA, Liu S, Nathan DM,
Hennekens CH. A prospective study of
cigarette smoking and the incidence of di-
abetes mellitus among US male physi-
cians. Am J Med 2000;109:538 –542
19. Will JC, Galuska DA, Ford ES, Mokdad A,
Calle EE. Cigarette smoking and diabetes
mellitus: evidence of a positive associa-
tion from a large prospective cohort
study. Int J Epidemiol 2001;30:540 –546
20. Burns DM, Shanks TG, Choi W, Thun MJ,
Heath CW, Garfinkel L. The American
Cancer Society Cancer Prevention Study I:
12-Year Followup of 1 Million Men and
Women. Changes in Cigarette-Related Dis-
ease Risks and Their Implication for Preven-
tion and Control (Monograph 8). Bethesda,
MD, National Institutes of Health, 1997,
p. 113–304
21. Park SW, Kim JY. Validity of self-reported
smoking using urinary cotinine among
vocational high school students. J Prev
Med Public Health 2009;42:223–230
Smoking and diabetes
2572 DIABETES CARE, VOLUME 33, NUMBER 12, DECEMBER 2010 care.diabetesjournals.org