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Copyright © 2001 by the Johns Hopkins University Bloomberg School of Public Health Printed in U.S.A.
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W. H. Linda Kao,1 Ian B. Puddey,2 Lori L. Boland,3 Robert L. Watson,4 and Frederick L. Brancati1,5
Evidence regarding the association between alcohol consumption and type 2 diabetes risk remains
inconsistent, particularly with regard to male-female differences. The authors conducted a prospective study of
type 2 diabetes risk associated with alcohol consumption in a cohort of 12,261 middle-aged participants of the
Atherosclerosis Risk in Communities Study (1990–1998), who were followed between 3 and 6 years. Alcohol
consumption at baseline was characterized into lifetime abstainers, former drinkers, and current drinkers of
various levels. Incident diabetes was determined by blood glucose measurements and self-report. After
adjustment for potential confounders, an increased risk of diabetes was found in men who drank >21
drinks/week when compared with men who drank ≤1 drink/week (odds ratio = 1.50, 95% confidence interval:
1.02, 2.20) while no significant association was found in women. This increased diabetes risk among men who
drank >21 drinks/week was predominantly related to spirits rather than to beer or wine consumption. The relative
odds of incident diabetes in a comparison of men who drank >14 drinks of spirits per week with men who were
Type 2 diabetes mellitus affects over 15 million tion of pancreatitis, disturbance of carbohydrate and glucose
Americans and leads to excess risk of cardiovascular dis- metabolism, and impairment of liver function (5–7).
eases and other morbidities (1–3). Aside from obesity and However, the association between alcohol and diabetes or
physical inactivity, there are few other well-established other diabetes-related physiologic endpoints has been incon-
modifiable risk factors for type 2 diabetes. Alcohol con- sistent in previous small clinical studies (8–16), animal stud-
sumption represents a potentially important, modifiable risk ies (17, 18), and larger cross-sectional epidemiologic stud-
factor of type 2 diabetes, especially given that more than ies (5, 19–24).
half of the adults in the United States are current drinkers Prospective epidemiologic studies have yielded similarly
(4). equivocal results; furthermore, results of these studies sug-
The hypothesized diabetogenic effects of alcohol include gest a potential difference in the association of alcohol and
its contribution to excess caloric intake and obesity, induc- incident type 2 diabetes between women and men (25–32).
The Atherosclerosis Risk in Communities (ARIC) Study
Received for publication March 21, 2000, and accepted for publi- offers a unique opportunity to examine the association
cation May 10, 2001. between alcohol consumption and the risk of type 2 diabetes
Abbreviation: ARIC, Atherosclerosis Risk in Communities. mellitus in a large community-based cohort of middle-aged
1
Department of Epidemiology, Bloomberg School of Public
Health, Johns Hopkins University, Baltimore, MD.
women and men.
2
Department of Medicine, University of Western Australia, Perth,
Australia. MATERIALS AND METHODS
3
Division of Epidemiology, School of Public Health, University of
Minnesota, Minneapolis, MN. Study population
4
Division of Epidemiology, University of Mississippi Medical
Center, Jackson, MS.
5 The ARIC Study is an ongoing prospective study that
Department of Medicine, School of Medicine, Johns Hopkins
University, Baltimore, MD. examines clinical and subclinical atherosclerotic diseases in
Reprint requests to Dr. Frederick L. Brancati, Welch Center for a cohort of 15,792 persons, aged 45–64 years at baseline
Prevention, Epidemiology, and Clinical Research, the Johns Hopkins examination, selected by probability sampling from four US
Medical Institutions, 2024 East Monument St., Suite 2-600, communities. The sampling procedure and methods used in
Baltimore, MD 21205 (e-mail: fbrancat@welch.jhu.edu).
This study was presented in part at the 31st Annual Meeting of the ARIC Study have been described in detail elsewhere
the Society for Epidemiologic Research, Chicago, IL, June 24–26, (33). This analysis was based on information obtained over
1998. 6 years of follow-up, which included two clinic visits sched-
748
Alcohol Consumption and the Risk of Diabetes Mellitus 749
uled at 3 (visit 2) and 6 (visit 3) years after baseline. We history of diabetes was defined as having either biologic par-
excluded participants who reported ethnicity other than ent with diabetes. Body mass index (weight (kg)/height (m)2)
Black or White (n 48), had diabetes at visit 1 (n 1,867), and waist/hip ratio were determined by the anthropometric
had missing exposure information (n 89), had missing measurements taken at the baseline clinic visit.
diabetes information at visit 1 or were lost to follow-up Measurements were made with the participants wearing
before visit 2 of the study took place (n 1,022), and had light-weight, nonconstricting underwear and no shoes. Waist
missing information on the potential confounders (n 315), and hip measurements were taken at the level of the umbili-
as well as persons in whom total caloric intake was within cus and the level of maximal protrusion of the gluteal mus-
the top 1 percent or bottom 1 percent of the entire cohort due cles, respectively. Intrareader and interreader correlations
to probable reporting error (n 190). After these exclu- between repeated waist/hip ratio measures were 0.94 and
sions, 12,261 participants (6,838 women and 5,423 men) 0.91, respectively (34). Physical activity was assessed using
remained. a modified interviewer-administered version of the question-
naire developed by Baecke et al. (35). Results from the
questionnaire concerning physical activity were further con-
Exposure assessment densed to a sport-related physical activity index with scores
ranging from 1 to 5, with 1 indicating the lowest level of
Alcohol consumption was assessed using five questions.
activity and 5 the highest level. Total caloric intake was
The following two questions were used to determine the
derived from an interviewer-administered, modified version
current drinking status of the persons: “Do you presently
of the 61-item food frequency questionnaire developed by
drink alcoholic beverages?” and “Have you ever consumed
Willett et al. (36). Smoking status was categorized into never,
alcoholic beverages?” Persons were classified as lifetime
former, and current smokers. Hypertension was defined by
abstainers if they answered “no” to both questions. Persons
the presence of any of the following: 1) systolic blood pres-
who answered “no” to the first question and “yes” to the sec-
sure of ≥140 mmHg, 2) diastolic blood pressure of ≥90
ond question were classified as former drinkers. Persons
0.001
<0.001
<0.001
were censored at 3 years after the baseline visit.
trend†
0.10
0.05
0.87
0.95
p
The independent association between baseline alcohol
TABLE 1. Means (SDs*) and frequencies of selected baseline characteristics of 6,838 female ARIC* Study participants by alcohol consumption group, 1990–1998
consumption and subsequent incident diabetes was exam-
ined using logistic regression models. Alcohol consumption
<0.001
0.001
0.001
0.001
<0.001
<0.001
<0.001
<0.001
0.001
0.001
<0.001
overall
0.04
p
was treated both nominally and continuously (for trend
among current drinkers). Multiple linear regression analysis
was also performed to examine the association between
0.914 (0.069)
59.58 (38.58)
25.61 (4.73)
2.16 (0.83)
5.42 (0.56)
baseline alcohol consumption and fasting glucose levels at
53.3 (5.3)
347 (107)
1,793 (630)
visit 2 or visit 3 among persons who did not have diagnosed
58 (0.8)
>21
15.5
19.0
50.0
31.0
19.0
60.3
25.9
13.8
32.8
diabetes by the time of the visit. All statistical analyses were
performed using a SAS statistical package (Cary, North
Carolina) (37).
0.878 (0.072)
54.52 (40.25)
24.75 (4.09)
2.41 (0.85)
5.45 (0.47)
14.1–21
53.3 (6.1)
RESULTS
1,490 (512)
130 (1.9)
202 (22)
6.2
7.7
51.5
40.8
16.2
44.6
36.2
19.2
30.8
Baseline characteristics
0.872 (0.078)
56.70 (37.11)
24.76 (4.46)
2.45 (0.77)
5.43 (0.49)
lifetime abstainers, and roughly half identified themselves
52.9 (5.6)
7.1–14
1,545 (502)
395 (5.8)
as current drinkers, of whom roughly half reported an aver-
117 (25)
age weekly consumption of ≤1 drink/week. Both lifetime
11.6
9.1
44.8
46.1
20.8
41.8
31.1
27.1
25.8
* SD, standard deviation; ARIC, Atherosclerosis Risk in Communities; BMI, body mass index (weight (kg)/height (m)2).
to each other than to current drinkers. There was also a
0.874 (0.080)
64.77 (49.00)
26.02 (4.89)
2.48 (0.80)
5.39 (0.47)
greater proportion of Blacks, positive family history of dia-
53.2 (5.6)
1,316 (19.2)
1.1–7
1,487 (522)
betes, and hypertension among lifetime abstainers and for-
40 (20)
15.5
11.2
47.0
41.8
20.4
29.2
31.3
39.5
24.1
mer drinkers. Among current drinkers, total caloric intake
and prevalence of hypertension were positively associated
with alcohol consumption, while educational level, family
history of diabetes, and body mass index were inversely
0.880 (0.078)
68.95 (52.24)
26.54 (5.17)
2.41 (0.76)
5.36 (0.47)
associated with alcohol consumption. Persons who drank
53.2 (5.6)
1,736 (25.4)
1,484 (546)
more than 21 drinks per week had a noticeably higher
≤1
1 (3)
10.6
49.9
39.5
22.5
22.4
24.9
52.7
23.2
activity. As expected, smoking and alcohol consumption
were highly associated. Although the fasting serum glucose
level was slightly positively associated with alcohol con-
0.902 (0.076)
86.47 (70.87)
28.32 (6.42)
2.29 (0.76)
5.40 (0.51)
sumption among current drinkers, the fasting serum insulin
drinkers
Former
53.9 (5.6)
980 (14.3)
1,549 (598)
32.8
42.4
24.8
26.9
29.0
30.5
40.5
35.5
87.48 (64.94)
28.48 (6.14)
2.24 (0.70)
5.39 (0.53)
54.1 (5.8)
2,223 (32.5)
1,498 (549)
28.0
44.1
27.9
26.6
14.7
12.2
73.1
38.6
Hypertension (%)
Smoking (%)
BMI* (kg/m2)
Current
Former
Black (%)
<0.001
<0.001
<0.001
trend†
0.79
0.04
0.01
Type 2 diabetes incidence rates of the seven alcohol con-
p
<0.001
0.001
0.001
<0.001
<0.001
<0.001
0.001
0.001
<0.001
<0.001
overall
0.59
0.27
dence rates were found in lifetime abstainers and former
p
0.966 (0.052)
72.62 (57.23)
decreased from 11.40 per 1,000 person-years to 6.41 per
26.88 (4.30)
2.46 (0.83)
5.67 (0.59)
1,000 person-years as alcohol consumption increased. The
54.0 (5.7)
402 (182)
1,992 (635)
439 (8.1)
>21
17.3
43.5
39.2
20.0
47.6
42.1
10.3
38.3
appeared inverse and by grade, but the incidence rates of the
higher consumption groups (>14 drinks/week) were based
on very few cases. In men, although the risks for lifetime
Current drinkers by alcohol consumption group (drinks/week)
0.961 (0.050)
74.03 (51.34)
27.18 (4.20)
2.78 (0.85)
5.68 (0.51)
the reference group (≤1 drink/week), and to their female
14.1–21
54.4 (5.6)
1,795 (586)
313 (5.8)
205 (24)
16.0
31.3
52.7
19.8
32.3
54.0
13.7
29.7
2.74 (0.80)
5.61 (0.48)
725 (13.4)
1,723 (589)
124 (25)
15.4
35.2
49.4
20.0
27.2
49.4
23.4
30.5
1,000 person-years).
2.68 (0.83)
5.58 (0.48)
1,742 (621)
43 (22)
14.1
37.3
48.6
22.2
24.3
46.9
28.8
26.7
2.67 (0.82)
5.55 (0.48)
1,719 (653)
1 (3)
7.7
14.1
36.6
49.3
21.6
20.0
43.4
36.6
27.2
2.52 (0.81)
5.57 (0.51)
1,096 (20.2)
Former
1,749 (661)
33.2
37.0
29.8
20.7
28.7
50.8
20.5
30.5
85.63 (62.52)
27.26 (4.10)
2.47 (0.78)
5.52 (0.49)
55.1 (5.5)
669 (12.3)
1,706 (580)
29.3
36.2
34.5
23.6
12.7
27.6
59.6
34.5
Subsidiary analyses
‡ Based on 5,281 fasting participants.
Attended college
Hypertension (%)
Smoking (%)
BMI* (kg/m2)
Current
Former
Black (%)
TABLE 3. Incidence of type 2 diabetes in the 12,261 ARIC* Study participants by sex and alcohol consumption groups,
1990–1998
Women
Incident diabetes (no.) 236 108 110 90 18 5 2
Total person-years 11,868 5,133 9,651 7,275 2,196 728 312
Incidence rate 19.88 21.04 11.40 12.37 8.20 6.87 6.41 <0.001
Rate ratio 1.74 1.85 1.00 (reference) 1.08 0.72 0.62 0.56
Men
Incident diabetes (no.) 69 118 74 139 55 32 60
Total person-years 3,602 5,703 4,353 7,352 3,959 1,665 2,259
Incidence rate 19.16 20.69 17.00 18.91 13.89 19.22 26.56 0.08
Rate ratio 1.13 1.22 1.00 (reference) 1.11 0.82 1.13 1.56
* ARIC, Atherosclerosis Risk in Communities.
† p value for overall difference.
group at baseline). In contrast, adjustment for the fasting visits 2 and 3; however, neither association was statistically
serum glucose level at baseline weakened the association significant at the 0.05 level.
between alcohol consumption and the risk of diabetes in The last set of analyses was conducted using continuous
men but strengthened the association in women. Because the serum glucose at either visit 2 or visit 3 as the outcome among
TABLE 4. Adjusted relative odds (95% confidence intervals) of incident type 2 diabetes mellitus in a comparison of alcohol
consumption groups in 12,261 ARIC* Study participants by sex, 1990–1998
>21 0.41 (0.10, 1.77) 0.52 (0.12, 2.26) 0.33 (0.08, 1.48) 1.50 (1.02, 2.20) 1.64 (1.10, 2.42) 1.22 (0.80, 1.85)
14.1–21 0.64 (0.25, 1.64) 0.77 (0.29, 2.00) 0.54 (0.20, 1.43) 1.07 (0.68, 1.69) 1.19 (0.75, 1.88) 0.91 (0.56, 1.48)
7.1–14 0.81 (0.47, 1.37) 0.88 (0.52, 1.51) 0.63 (0.36, 1.11) 0.80 (0.55, 1.17) 0.88 (0.60, 1.28) 0.84 (0.56, 1.25)
1.1–7 1.09 (0.80, 1.49) 1.14 (0.84, 1.56) 0.98 (0.71, 1.36) 1.12 (0.82, 1.52) 1.15 (0.84, 1.57) 1.12 (0.81, 1.56)
≤1 1.00 (reference) 1.00 (reference) 1.00 (reference) 1.00 (reference) 1.00 (reference) 1.00 (reference)
Former drinkers 1.10 (0.81, 1.49) 1.09 (0.79, 1.48) 1.18 (0.85, 1.65) 1.06 (0.77, 1.47) 1.06 (0.76, 1.46) 1.06 (0.75, 1.51)
Lifetime abstainers 1.10 (0.84, 1.43) 1.08 (0.82, 1.43) 1.15 (0.86, 1.54) 1.14 (0.79, 1.65) 1.09 (0.75, 1.58) 1.18 (0.80, 1.76)
overall difference). The corresponding numbers from visit 3 current drinkers but reported no regular weekly consump-
were 100.0, 101.2, 101.2, 101.2, and 102.8 (p 0.06 for tion of wine, beer, or spirits. Table 5 shows the adjusted rel-
overall difference). At both visits 2 and 3, men who drank >21 ative odds of diabetes from multiple logistic regression,
drinks/week at baseline had the highest fasting serum glucose which adjusted for intakes of other types of alcoholic bever-
level at subsequent visits. ages; that is, nine dummy variables were included in the
regression to adjust for intake of other alcoholic beverages,
Consumption of specific alcoholic beverages and the in addition to the potential confounders mentioned previ-
risk of type 2 diabetes ously. In the fully adjusted model, persons who drank >14
drinks of spirits per week were still at higher risk for devel-
To assess whether the discrepancy between women and oping diabetes (odds ratio 1.82, 95 percent confidence
men might have been explained by differences in alcoholic interval: 1.14, 2.92). There was no statistically significant
beverage preference, we characterized the beverage preference association between wine intake and the risk of diabetes at
of current drinkers. Figure 1 shows the mean percentage of the conventional 0.05 level.
ethanol contributed by specific alcoholic beverages for each One possible explanation for the excess risk associated
consumption group (total alcohol intake) in women and men. with spirits might be differences in underlying health behav-
In the reference groups (≤1 drink/week), although all persons iors as compared with wine drinkers, particularly with
identified themselves as current drinkers, only 11 percent of regard to diet. To investigate this possibility, we examined
the women and 8 percent of the men reported regular weekly the correlation between the percentage of ethanol con-
alcohol consumption (the remaining persons in the reference tributed by each alcoholic beverage and measures that were
group identified themselves as current alcohol drinkers but thought to indicate healthy behavior. In general, the
reported no regular weekly alcohol consumption), and in those increased percentage of ethanol from wine was associated
persons who reported regular use of alcohol, wine accounted with healthier behaviors, such as increased physical activity
for 100 percent for ethanol consumed. In general, the contri- and total intake of dietary fiber and decreased total fat
FIGURE 1. Mean percentage of ethanol contributed by specific alcoholic beverage in 12,261 participants by sex and consumption group,
Atherosclerosis Risk in Communities Study, 1990–1998.
TABLE 5. Adjusted* relative odds (95% confidence intervals) of incident type 2 diabetes mellitus in
5,423 male ARIC† Study participants by alcoholic beverage type and alcohol consumption groups,
1990–1998
Servings of
alcohol Spirits Beer Wine
per week‡
>14 servings/week 1.82 (1.14, 2.92) 1.19 (0.77, 1.85) 0.63 (0.08, 4.95)
8–14 servings/week 1.02 (0.67, 1.56) 0.74 (0.48, 1.14) 0.84 (0.29, 2.44)
1–7 servings/week 1.00 (0.77, 1.29) 0.88 (0.68, 1.13) 1.10 (0.82, 1.50)
None 1.00 (reference) 1.00 (reference) 1.00 (reference)
and men who consumed a moderate amount of alcohol edge, this study is the first study to present a more compre-
subjects, and worsen insulin resistance in diabetic patients, risk of diabetes seen in ARIC Study male participants who
while chronic alcohol consumption has also been implicated drank >21 drinks/week is consistent with results reported by
to induce beta-cell dysfunction (10, 14, 15). Similarly con- two of these studies, the Rancho Bernardo Study and the
tradictory results arise from animal studies. In rats, acute San Antonio Heart Study (25, 31). However, an inverse
alcohol administration can attenuate basal and hormone- association was found in the other two studies, the Health
induced glucose utilization by skeletal muscles while, in Professionals’ Follow-up Study and the British Regional
obese mice, chronic ethanol consumption can lower blood Heart Study (26, 30). Given the unique nature of the Health
glucose and insulin (17, 18). The exact relation between Professionals’ cohort, it is conceivable that these persons
alcohol and diabetes-related endpoints may depend on the had different beverage preference and drinking patterns
nature of alcohol exposure, that is, acute versus chronic and from those of ARIC Study men or that they had healthier
alcohol administration versus alcohol ingestion. behaviors, which were not measured and were associated
Since 1965, eight prospective studies have examined the with increased consumption of alcohol. Furthermore, the
association between alcohol consumption and the risk of type association between the waist/hip ratio and alcohol con-
2 diabetes (25, 26, 28–32, 43, 44). Five are comparable with sumption, which was positive in the ARIC Study, was
the present study, while significant differences in the study unknown in the Health Professionals’ Study and therefore
methodology and study population exist between the other was not included in their multivariate analyses. The main
three studies and the present study. Of these three, two difference between the present study and the British
showed no association between alcohol intake and the risk of Regional Heart Study may lie in the populations studied.
diabetes in men even at >21 drinks/week (29, 43). We believe The prevalence of coronary heart disease was reported to be
that two methodological issues could explain the discrepancy 24 percent in the British Regional Heart Study but only
between our study and these two studies. First, both previous about 8 percent in male ARIC Study participants at baseline.
studies lacked information on potential confounders, such as Because the lower risk of diabetes seen in moderate drinkers
the waist/hip ratio, education, and hypertension, all of which was more apparent and significant only in men with preex-
afflicted with symptoms or risk factors of major illnesses, betes. Diabetes Metab Rev 1993;9:129–46.
and persons who prefer beer had intermediate traits (24). In 6. Manolio TA, Savage PJ, Burke GL, et al. Association of fast-
ing insulin with blood pressure and lipids in young adults. The
addition, we demonstrated in our study that wine consump- CARDIA Study. Arteriosclerosis 1990;10:430–6.
tion was statistically associated with healthier behaviors 7. Perry IJ, Wannamethee SG, Shaper AG. Prospective study of
while spirits and beer consumption were not. Therefore, we serum gamma-glutamyltransferase and risk of NIDDM.
cannot exclude the possibility that the differences in bever- Diabetes Care 1998;21:732–7.
age preference may simply represent differences in 8. Phillips GB, Safrit HF. Alcoholic diabetes. Induction of glu-
cose intolerance with alcohol. JAMA 1971;217:1513–19.
lifestyles, which we were not able to adequately measure 9. Dornhorst A, Ouyang A. Effect of alcohol on glucose toler-
and adjust in our regression model. Third, this difference ance. Lancet 1971;2:957–9.
could simply be a type II error due to the small number of 10. Avogaro A, Valerio A, Miola M, et al. Ethanol impairs insulin-
women who drank >14 drinks/week. mediated glucose uptake by an indirect mechanism. J Clin
Endocrinol Metab 1996;81:2285–90.
The results of the present study support the hypothesis 11. McMonagle J, Felig P. Effects of ethanol ingestion on glucose
that high alcohol intake (≥21 drinks/week) predicts type 2 tolerance and insulin secretion in normal and diabetic subjects.
diabetes mellitus among middle-aged men, specifically men Metabolism 1975;24:625–32.
who drink more than 14 drinks of spirits per week. 12. Yki-Jarvinen H, Koivisto VA, Ylikahri R, et al. Acute effects
However, more moderate levels of consumption (<21 of ethanol and acetate on glucose kinetics in normal subjects.
Am J Physiol 1988;254(2 Pt 1):E175–80.
drinks/week) do not appear to increase the risk of type 2 13. Yki-Jarvinen H, Nikkila EA. Ethanol decreases glucose uti-
diabetes in middle-aged men and women. Our results, along lization in healthy man. J Clin Endocrinol Metab 1985;61:
with those of previous studies, suggest that strategies for the 941–5.
prevention of type 2 diabetes need not target moderate alco- 14. Shelmet JJ, Reichard GA, Skutches CL, et al. Ethanol causes
acute inhibition of carbohydrate, fat, and protein oxidation and
hol consumption. In contrast, men who drink >14 drinks of insulin resistance. J Clin Invest 1988;81:1137–45.
spirits per week should be advised of the increased risk of 15. Patto RJ, Russo EK, Borges DR, et al. The enteroinsular axis
diabetes associated with heavy alcohol consumption. and endocrine pancreatic function in chronic alcohol con-