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Alcohol consumption and the risk of diabetes by body mass index levels in a cohort of 5,636 Japanese
Diabetes Research and Clinical Practice 57 (2002) 191– 197 www.elsevier.com/locate/diabres
Alcohol consumption and the risk of diabetes by body mass index levels in a cohort of 5,636 Japanese Makoto Watanabe a,*, Federica Barzi b, Bruce Neal b, Hirotsugu Ueshima a, Yuji Miyoshi c, Akira Okayama d, Sohel Reza Choudhury a a
Department of Health Science, Shiga Uni6ersity of Medical Science, Seta-tsukinowa-cho, Otsu-shi, Shiga-ken 520 -2192, Japan b Institute for International Health, Uni6ersity of Sydney, Sydney, Australia c Meiji Mutual Life Insurance Company, Tokyo, Japan d Department of Hygiene and Pre6enti6e Medicine, Iwate Medical Uni6ersity, Iwate, Japan Received 18 October 2001; received in revised form 28 March 2002; accepted 4 April 2002
Abstract The association between alcohol consumption and the risk of diabetes in Japanese with a low-body mass index (BMI) (522.0 kg/m2), middle-BMI (22.1–24.9 kg/m2) and high-BMI (]25.0 kg/m2) was investigated among a cohort of 5,636 employees of a Japanese insurance company. Participants were free of diabetes at baseline and were followed up for a mean of 5.7 years with annual assessments of fasting plasma glucose (FPG). The outcome was a clinical diagnosis of diabetes on the basis of a questionnaire administered at each follow-up assessment or a follow-up FPG level of 7.8 mmol/l or more. Relative risks and 95% confidence intervals (95% CIs) were estimated by fitting pooled logistic regression models, which included age, gender, BMI, baseline FPG level, current tobacco use and current alcohol consumption. A total of 264 outcome events were recorded. The relative risk of diabetes associated with current alcohol consumption was 3.19 (95% CI 1.09– 9.37) among low-BMI individuals, 0.41 (0.23– 0.73) among middle-BMI individuals and 0.74 (0.44–1.25) among high-BMI individuals. In this study, current alcohol consumption was associated with an increased risk of diabetes among low-BMI individuals and a decreased risk of diabetes among middle-BMI individuals. A tendency for an association of alcohol consumption with a decreased risk of diabetes among high-BMI individuals was noted, although without statistical significance. © 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Diabetes; Alcohol consumption; BMI; Cohort study
1. Introduction
* Corresponding author. Tel.: +81-77-548-2191; fax: + 8177-543-9732 E-mail address: [email protected] (M. Watanabe).
In 1995 there were about 135 million individuals with diabetes worldwide, and this number is expected to increase to about 300 million by 2025 [1]. A similar increase is anticipated in Japan (from 6.3 to 8.5 million) [1].
0168-8227/02/$ - see front matter © 2002 Elsevier Science Ireland Ltd. All rights reserved. PII: S0168-8227(02)00083-9
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M. Watanabe et al. / Diabetes Research and Clinical Practice 57 (2002) 191–197
Age, obesity, physical inactivity, heredity and tobacco use are established determinants of the risk of diabetes [2– 8]. However, the association between alcohol consumption and the risk of developing diabetes is uncertain since previous studies have variously reported inverse [8– 12], null [13– 15] and positive associations [16]. Data from a Japanese study has provided some evidence that the effects of alcohol consumption on the risk of diabetes may vary by BMI [17] although similar analyses of a cohort of participants in a study conducted in the US identified no such interaction [11]. Reliable data on the effects of alcohol consumption on the risk of diabetes are important because alcohol consumption is both widespread and potentially modifiable. In Japan about half of all males and one in ten of all females consume alcohol every week [18]. It is uncertain whether the reported differences between the findings of previous studies with regard to the effects of alcohol on diabetes reflect true differences in response to alcohol according to BMI or are simply a function of the limited statistical power of subgroup analyses. To further address this issue, we report here the association of alcohol consumption with the risk of diabetes both overall and separately in low-, middle- and high-BMI individuals in a cohort of middle-aged Japanese men and women.
2. Materials and methods
2.1. Participants The study was conducted among employees of a Japanese insurance company that participated in a legislated system of annual health checks for employees aged 35 years or over. Participants were recruited from a network of 206 company offices located in major cities around Japan with baseline assessments made between 1991 and 1998. Follow-up assessments were scheduled annually, with the final assessments made in 1999. To be eligible for inclusion in these analyses, participants were required to have completed at least one follow-up assessment, to have no clinical
diagnosis of diabetes at baseline, to have a baseline FPG level of B 7.8 mmol/l and to have no history of chronic pancreatitis at baseline and during follow-up [19,20].
2.2. Data collection At each annual assessment, nurses administered a questionnaire, conducted a brief physical examination and collected a venous blood sample. Participants were asked to fast overnight prior to each assessment to enable measurement of FPG levels. In this study standardization of the method for glucose measurement across centers and over time was not possible. However, all laboratories were regulated by the Japan Medical Association, which reported that four major methods have been used since 1991 in 98.8% of laboratories and that the measurement errors among methods and among laboratories were minimal [21]. The questionnaire consisted of questions about demographics, lifestyle and medical history, including a clinical diagnosis of diabetes. Average daily alcohol consumption was calculated by participants themselves and self-reported as either no alcohol consumption, alcohol consumption 5 21 g/day, alcohol consumption \ 21 but 5 42 g/day, or alcohol consumption \ 42 g/day (the traditional Japanese measurement of alcohol consumption, ‘1 gou’, contains 21 g of alcohol). Body weight and height were measured with the participant wearing light clothing and with shoes removed. In this study we collaborated with the company’s industrial doctor, who was in charge of promoting employee health through the use of information gained during health check-ups. To ensure confidentiality, the identities of these participants were not revealed to those other than the authors and data collectors with whom we collaborated.
2.3. Outcomes The outcome for the study was diabetes, defined as either a first clinical diagnosis of diabetes on the basis of the questionnaire at each follow-up assessment or a follow-up FPG level of 7.8 mmol/l or more [22].
M. Watanabe et al. / Diabetes Research and Clinical Practice 57 (2002) 191–197
Sensitivity analyses were also conducted using variations of the definition of outcome measures (a first clinical diagnosis of diabetes on the basis of the questionnaire at each follow-up assessment or a follow-up FPG level of 7.0 mmol/l or more, excluding participants with a baseline FPG level of 7.0 mmol/l or more) [23].
2.4. Statistical analysis The associations between exposures and study outcomes were determined by fitting multivariate pooled logistic regression models [24]. The unit of exposure fitted was person years with the exposure level for each period defined by the measurements made at the end of each year of follow-up. Each person-year of exposure was treated as an independent observation. Participants were censored upon the first occurrence of an outcome. Relative risks and 95% CIs were calculated. The independent variables included in each model were age, gender, BMI, baseline FPG level, current tobacco use and current alcohol consumption. Evidence for an interaction between BMI status and the effects of alcohol consumption on diabetes was investigated by adding an interaction term to the model. For each independent variable, missing data were complemented from the last known measurement. Overall models were fitted to determine the association of exposures with the risk of diabetes and then separate models were fitted for three subgroups of participants defined by BMI (5 22.0 kg/m2 (low-BMI), 22.1– 24.9 kg/m2 (middle-BMI) and ]25.0 kg/m2 (high-BMI)). The BMI cut-off point of 22.0 kg/m2 was based on the cut-off point adopted in a previous Japanese study [17], and the BMI cut-off point of 25.0 kg/m2 was based on the definition of obesity by the Japan Society for the Study of Obesity [25]. We pooled men and women in this analysis because the number of outcomes among women was too small to investigate in detail and because the interaction term between gender and alcohol consumption was not significant in each model. Alcohol consumption was dichotomized into no alcohol consumption and current alcohol consumption. No alcohol consumption was taken as
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a reference group to estimate the relative risk for current alcohol consumption. We pooled the three current alcohol consumption categories because when separating alcohol consumption into three categories, relative risk of each current alcohol consumption category showed a similar value with a very wide 95% CI and without a clear dose–response relationship. Sensitivity analyses were conducted, first, without a baseline FPG level, and, second, with the addition of total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride and systolic blood pressure.
3. Results A total of 6,106 individuals were enrolled in the study. Of these, 470 (7.7%) were deemed ineligible for the analyses based on a clinical history of diabetes (N= 44), a baseline FPG of 7.8 mmol/l or more (N=162) or failure to attend any followup visit (total N= 264), death (N= 2), retirement (N= 158), and no available data (N= 104) (Fig. 1). Almost 99% of the employees participated in a health check each year from 1991 to 1999. Of the 5,636 eligible participants, 28% were female and the mean age was 44 years (range 35–68 years), 47% were regular smokers and 78% regularly consumed alcohol (Table 1). Among these individuals, during the mean 5.7 years of
Fig. 1. Flow chart of composition of participants, Japan, 1991 – 1999. FPG: Fasting plasma glucose.
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Table 1 Baseline characteristics of participants overall and by body mass index levels, Japan, 1991–1999 Overall
N Age (years) Male (%)
5636 449 7 72
Low BMIa
Middle BMIa
High BMIa
522.0 (kg/m2)
22.1–24.9 (kg/m2)
25.05(kg/m2)
2304 44 96 56
2003 469 7 81
1329 4597 84
71 45 19 7 33 23.3 5.2 5.3 1.4 1.4 122 77
71 43 19 9 33 27.0 5.3 5.5 1.3 1.9 128 81
Age, gender adjusted Current alcohol consumption (%) Alcohol consumption521 g/day (%) 21Balcohol consumption542 g/day (%) 42 g/dayBalcohol consumption (%) Current tobacco use (%) BMIa (kg/m2) Fasting plasma glucose (mmol/l) Total cholesterol (mmol/l) HDLb- cholesterol (mmol/l) Triglyceride (mmol/l) Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg)
78 41 26 10 47 22.9 9 3.1 5.29 0.6 5.39 0.9 1.49 0.4 1.59 1.4 122 9 15 78 911
68 41 21 6 39 20.1 5.0 5.0 1.5 1.1 117 74
Mean9 S.D. a BMI, body mass index. b HDL, high density lipoprotein.
follow-up, 264 outcome events were recorded (17 clinical diagnoses of diabetes and 247 FPG levels of 7.8 mmol/l or more) (Fig. 1). Of the total person years, the proportion of complemented data was 1.4%. On the basis of baseline assessment of BMI, 2,304 individuals were classified as low-BMI, 2,003 as middle-BMI and 1,329 as high-BMI, (Table 1). Among low-BMI individuals the proportion of male was lower and the proportion of current tobacco use was higher than middle- or high-BMI individuals. Mean total cholesterol, triglyceride and systolic and diastolic blood pressure increased with increase in BMI level. In the overall analyses of outcome, factors that were significantly associated with the risk of diabetes were: female gender (relative risk= 0.57, 95% CI 0.33– 0.96), BMI (per kg/m2) (1.11, 1.07– 1.16), baseline FPG (per mmol/l) (6.98, 5.92– 8.22) and current tobacco use (1.50, 1.15– 1.95). In the analysis with the inclusion of total cholesterol, HDL- cholesterol, triglyceride and systolic blood pressure, HDL-cholesterol and triglyceride
were also significantly associated with the risk of diabetes (HDL-cholesterol [per mmol/l] 0.47, 0.29–0.76; triglyceride [per mmol/l] 1.11, 1.05– 1.18) (Table not presented). Among current alcohol drinkers compared with non-drinkers, the relative risk of diabetes was 3.19 (1.09–9.37) in the low-BMI individuals, 0.41 (0.23–0.73) in the middle-BMI individuals and 0.74 (0.44–1.25) in the high-BMI individuals (Table 2). The P value for the interaction term between BMI categories and current alcohol consumption was 0.05. These findings were similar to those of the sensitivity analyses conducted using variations of the definition of outcome measures (a first clinical diagnosis of diabetes on the basis of the questionnaire at each follow-up assessment or a follow-up FPG level of 7.0 mmol/l or more, excluding participants with a baseline FPG level of 7.0 mmol/l or more): relative risk of diabetes among lowBMI individuals was 1.85 (0.84–4.07), among middle-BMI individuals was 0.55 (0.34– 0.89) and among high-BMI individuals was 0.89 (0.57–
M. Watanabe et al. / Diabetes Research and Clinical Practice 57 (2002) 191–197
1.40). The exclusion of FPG from the models and the inclusion of total cholesterol, HDL-cholesterol, triglyceride and systolic blood pressure in the models did not appreciably change the findings (Table not presented).
4. Discussion In this study, current alcohol consumption was associated with an increased risk of diabetes among low-BMI individuals and a decreased risk of diabetes among middle-BMI individuals. A tendency for an association of alcohol consumption with a decreased risk of diabetes among high-BMI individuals was noted, although without statistical significance. The interaction between the effects of BMI and alcohol consumption on the risk of diabetes observed in this study is directly in line with a similar interaction observed in a prior study of Japanese men [17]. The finding is, however, discrepant with findings of a large study conducted among US physicians [11] that showed no such interaction. In that
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study there was an inverse association between alcohol consumption and diabetes among individuals both above and below the median BMI. Inverse associations also have been observed in several other large prospective studies conducted among predominantly Western populations [8– 12]. While differences between findings of the US physicians study, the current study and the previous Japanese study may simply reflect chance, other characteristics of the study populations may be responsible for the observed differences. The mean BMI of the participants in the US physicians study was about 25 kg/m2 compared with 23 kg/m2 in the current study and 22.5 kg/m2 in the prior Japanese study. Accordingly, the BMI levels at which possible interactions between BMI and alcohol consumption were investigated were markedly lower in this and the prior Japanese study (22 kg/m2) than in the US physicians study (24.4 kg/m2). If a modifying effect of BMI occurred only among low-BMI individuals, this might explain why an interaction between the effects of BMI and alcohol consumption on the
Table 2 Association of alcohol consumption with risk of clinical diagnosis of diabetes or fasting plasma glucose of 7.8 mmol/l or more overall and by body mass index levels, Japan, 1991–1999 Alcohol consumption
Total person-years
Cases
O6erall None Current
6296 22 944
43 221 4 43
Low BMI (BMI522.0 kg/m 2)b None 2970 Current 7652
Age, gender adjusted incidence rate/1000 person-years
Multivariate relative riska
95% Confidence interval
7.9 7.6
1.00 0.79
0.55–1.13
2.3 6.1
1.00 3.19
1.09–9.37
9.2 6.1
1.00 0.41
0.23–0.73
13.6 11.7
1.00 0.74
0.44–1.25
2 b
Middle BMI (22.15BMI524.9 kg/m ) None 1985 19 Current 8875 73 High BMI (25.0 kg/m 5BMI) None 1341 20 Current 6417 105 (P value for interaction termc = 0.05) 2
a
b
Model included age, gender, BMI, baseline fasting plasma glucose level, current tobacco use and current alcohol consumption. BMI: body mass index. c P value for interaction term between BMI categories and current alcohol consumption was estimated by adding interaction term to the overall model. b
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M. Watanabe et al. / Diabetes Research and Clinical Practice 57 (2002) 191–197
risk of diabetes were observed in this and the prior Japanese study, but not in the US physicians study. It is possible that imperfect measurement of dependent and independent variables may have resulted in underestimation or overestimation of the importance of some of the risk factors studied. For example, non-standardized FPG measurements across centers and over time may have resulted in underestimation of the strengths of the observed associations although the reported broad consistency in laboratory techniques and standards [21] suggests that attenuation of the associations attributable to this cause is likely to have been small. The absence of information about a family history of diabetes, physical activity and diet makes it impossible to determine either the separate effects of these exposures on the risk of diabetes or to investigate their possible modifying effects on the associations reported. There is a well-established association between obesity, insulin resistance and diabetes [26– 28] and several cross-sectional studies conducted among Western populations have suggested a beneficial effect of alcohol consumption on insulin resistance [29– 32]. Such studies provide a possible physiological explanation of the inverse association between alcohol consumption and diabetes observed among Western populations and Japanese individuals having a BMI 22 kg/m2 or greater [8,10–12,17]. However, clear data about the effects of alcohol on insulin resistance among individuals with a low BMI are not available and a clear physiological explanation for the apparent increased risk of diabetes with increasing alcohol consumption among low-BMI individuals has not been established. In conclusion, the observed inverse association between current alcohol consumption and the risk of diabetes among middle- or high-BMI individuals in this study is in line with evidence provided by several previous studies conducted among predominantly middle- or high-BMI individuals. However, the increased risk of diabetes associated with current alcohol consumption among lowBMI individuals observed in this study decreases the likelihood that the corresponding observation in the prior study of Japanese men was a chance
finding. Definitive information about the effects of alcohol consumption on the risk of diabetes among low-BMI individuals might be obtained by overview analyses of existing datasets. Reliable information about the effects of alcohol among such individuals is required to properly formulate health policy and will be particularly important in countries, such as Japan, where a large proportion of the population has a low BMI.
Acknowledgements The authors thanks the industrial nurses of the Meiji Mutual Life Insurance Company for their collaboration, and thanks Professor MacMahon S. and Professor Woodward M. at the Institute for International Health (University of Sydney) for their methodological and statistical suggestion.
References [1] H. King, R.E. Aubert, W.H. Herman, Global burden of diabetes 1995 – 2025, Diabetes care 21 (1998) 1414 – 1431. [2] E. Barrett-Connor, Epidemiology obesity, and non-insulin-dependent diabetes mellitus, Epidemiol. Rev. 11 (1989) 172 – 181. [3] R.D. Morris, D.L. Rimm, A.J. Hartz, R.K. Kalkhoff, A.A. Rimm, Obesity and heredity in the etiology of non-insulin dependent diabetes mellitus in 32,662 adult white women, Am. J. Epidemiol. 130 (1989) 112 – 121. [4] G.A. Colditz, W.C. Willett, A. Rotnitzky, J.E. Manson, Weight gain as a risk factor for clinical diabetes in women, Ann. Intern. Med. 122 (1995) 481 – 486. [5] S.P. Helmrich, D.R. Ragland, R.W. Leung, R.S. Paffenbarger, Physical activity and reduced occurrence of noninsulin-dependent diabetes mellitus, New Engl. J. Med. 325 (1991) 147 – 152. [6] X.R. Pan, G.W. Li, Y.H. Hu, et al., Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance: The Da Quing IGT and Diabetes Study, Diabetes care 20 (1997) 537 – 544. [7] E.B. Rimm, J.E. Manson, M.J. Stampfer, et al., Cigarette smoking and the risk of diabetes in women, Am. J. Public Health 83 (1993) 211 – 214. [8] E.B. Rimm, J. Chan, M.J. Stampfer, G.A. Colditz, W.C. Willett, Prospective study of cigarette smoking, alcohol use, and the risk of diabetes in men, Br. Med. J. 310 (1995) 555 – 559.
M. Watanabe et al. / Diabetes Research and Clinical Practice 57 (2002) 191–197 [9] M.J. Stampfer, G.A. Colditz, W.C. Willett, et al., A prospective study of moderate alcohol drinking and risk of diabetes in women, Am. J. Epidemiol. 128 (1988) 549 – 558. [10] I.J. Perry, S.G. Wannamethee, M.K. Walker, A.G. Thomson, P.H. Whincup, A.G. Shaper, Prospective study of risk factors for development of non-insulin dependent diabetes in middle aged British men, Br. Med. J. 310 (1995) 560 – 564. [11] U.A. Ajani, C.H. Hennekens, A. Spelsberg, J.E. Manson, Alcohol consumption and risk of type 2 diabetes mellitus among US male physicians, Arch. Intern. Med. 160 (2000) 1025 – 1030. [12] M. Wei, L.W. Gibbons, T.L. Mitchell, J.B. Kampert, S.N. Blair, Alcohol intake and incidence of type 2 diabetes in men, Diabetes care 23 (2000) 18 – 22. [13] E.J.M. Feskens, D. Kromhout, Cardiovascular risk factors and the 25-year incidence of diabetes mellitus in middle-aged men. The Zutphen Study, Am. J. Epidemiol. 130 (1989) 1101 – 1108. [14] L.O. Ohlson, B. Larsson, P. Bjorntorp, et al., Risk factors for Type 2 (non-insulin-dependent) diabetes mellitus, Thirteen and one-half years of follow-up of the participants in a study of Swedish men born in 1913, Diabetologia 31 (1988) 798 – 805. [15] A.M. Hodge, G.K. Dowse, V.R. Collins, P.Z. Zimmet, Abnormal glucose tolerance and alcohol consumption in three populations at high risk of non-insulin-dependent diabetes mellitus, Am. J. Epidemiol. 137 (1993) 178 –189. [16] T.L. Holbrook, E. Barrett-Connor, D.L. Wingard, A Prospective Population-based study of alcohol use and non-insulin-dependent diabetes mellitus, Am. J. Epidemiol. 132 (1990) 902 – 909. [17] K. Tsumura, T. Hayashi, C. Suematsu, G. Endo, S. Fujii, K. Okada, Daily alcohol consumption and the risk of type 2 diabetes in Japanese men: The Osaka Health Survey, Diabetes care 22 (1999) 1432 –1437. [18] Ministry of Health and Welfare, Kokumin eiyou no genjou (Results of National Nutrition Survey in 1998), Tokyo, Daiichi Shuppan, 2000, p. 57 (Japanese). [19] S. Larsen, J. Hilsted, B. Tronier, H. Worning, Metabolic control and B cell function in patients with insulin-dependent diabetes mellitus secondary to chronic pancreatitis, Metabolism 36 (1987) 964 –967. [20] M. Koizumi, Y. Yoshida, N. Abe, T. Shimosegawa, T. Toyota, Pancreatic diabetes in Japan, Pancreas 16 (1998) 385 – 391.
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[21] Japan Medical Association, Wagakuni no rinshoukensa seidokanri-30 nen no ayumi (Management of quality in clinical examination-progress in 30 years), Tokyo, Nihonijishinpousha, 1998, pp. 76 – 106 (Japanese). [22] World Health Organization, Diabetes Mellitus; Report of a WHO study Group, World Health Organization, Geneva, 1985 (Technical Report Series No.727). [23] The expert committee on the diagnosis and classification of diabetes mellitus, Report of the expert committee on the diagnosis and classification of diabetes mellitus, Diabetes care 20 (1997) 1183 – 1197. [24] R.B. D’Agostino, M.L. Lee, A.J. Belanger, L.A. Cupples, K. Anderson, W.B. Kannel, Relation of pooled logistic regression to time dependent Cox regression analysis: the Framingham Heart Study, Stat. Med. 9 (1990) 1501 – 1515. [25] Y. Matuzawa, S. Inoue, Y. Ikeda, et al., (The committee on the diagnosis and classification criteria of obesity, Japan Society for the Study of Obesity), Atarashii himan no hantei to himanshou no shindankijun (The new diagnosis and classification of obesity), J. Jap. Soc. Study Obes. 6 (2000) 18 – 28 (Japanese). [26] G.M. Reaven, Role of insulin resistance in human disease, Diabetes 37 (1988) 1595 – 1607. [27] N.M. Kaplan, The deadly quartet. Upper-body obesity glucose intolerance hypertriglyceridemia and hypertension, Arch. Intern. Med. 149 (1989) 1514 – 1520. [28] R.A. DeFronzo, E. Ferrannini, Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity hypertension dyslipidemia and atherosclerotic cardiovascular disease, Diabetes Care 14 (1991) 173 – 194. [29] E.J. Mayer, B. Newman, C.P. Quesenberry Jr, G.D. Friedman, J.V. Selby, Alcohol consumption and insulin concentrations. Role of insulin in associations of alcohol intake with high-density lipoprotein cholesterol and triglycerides, Circulation 88 (part 1) (1993) 2190 – 2197. [30] F. Facchini, Y.D.I. Chen, G.M. Reaven, Light-to-moderate alcohol intake is associated with enhanced insulin sensitivity, Diabetes care 17 (1994) 115 – 119. [31] R. Lazarus, D. Sparrow, S.T. Weiss, Alcohol intake and insulin levels. The Normative Aging Study, Am. J. Epidemiol. 145 (1997) 909 – 916. [32] R.A. Bell, E.J. Mayer-Davis, M.A. Martin, R.B. D’Agostino Jr, S.M. Haffner, Associations between alcohol consumption and insulin sensitivity and cardiovascular disease risk factors: the insulin resistance and atherosclerosis study, Diabetes Care 23 (2000) 1630 – 1636.
Alcohol consumption and the risk of diabetes by body mass index levels in a cohort of 5,636 Japanese Makoto Watanabe a,*, Federica Barzi b, Bruce Neal b, Hirotsugu Ueshima a, Yuji Miyoshi c, Akira Okayama d, Sohel Reza Choudhury a a
Department of Health Science, Shiga Uni6ersity of Medical Science, Seta-tsukinowa-cho, Otsu-shi, Shiga-ken 520 -2192, Japan b Institute for International Health, Uni6ersity of Sydney, Sydney, Australia c Meiji Mutual Life Insurance Company, Tokyo, Japan d Department of Hygiene and Pre6enti6e Medicine, Iwate Medical Uni6ersity, Iwate, Japan Received 18 October 2001; received in revised form 28 March 2002; accepted 4 April 2002
Abstract The association between alcohol consumption and the risk of diabetes in Japanese with a low-body mass index (BMI) (522.0 kg/m2), middle-BMI (22.1–24.9 kg/m2) and high-BMI (]25.0 kg/m2) was investigated among a cohort of 5,636 employees of a Japanese insurance company. Participants were free of diabetes at baseline and were followed up for a mean of 5.7 years with annual assessments of fasting plasma glucose (FPG). The outcome was a clinical diagnosis of diabetes on the basis of a questionnaire administered at each follow-up assessment or a follow-up FPG level of 7.8 mmol/l or more. Relative risks and 95% confidence intervals (95% CIs) were estimated by fitting pooled logistic regression models, which included age, gender, BMI, baseline FPG level, current tobacco use and current alcohol consumption. A total of 264 outcome events were recorded. The relative risk of diabetes associated with current alcohol consumption was 3.19 (95% CI 1.09– 9.37) among low-BMI individuals, 0.41 (0.23– 0.73) among middle-BMI individuals and 0.74 (0.44–1.25) among high-BMI individuals. In this study, current alcohol consumption was associated with an increased risk of diabetes among low-BMI individuals and a decreased risk of diabetes among middle-BMI individuals. A tendency for an association of alcohol consumption with a decreased risk of diabetes among high-BMI individuals was noted, although without statistical significance. © 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Diabetes; Alcohol consumption; BMI; Cohort study
1. Introduction
* Corresponding author. Tel.: +81-77-548-2191; fax: + 8177-543-9732 E-mail address: [email protected] (M. Watanabe).
In 1995 there were about 135 million individuals with diabetes worldwide, and this number is expected to increase to about 300 million by 2025 [1]. A similar increase is anticipated in Japan (from 6.3 to 8.5 million) [1].
0168-8227/02/$ - see front matter © 2002 Elsevier Science Ireland Ltd. All rights reserved. PII: S0168-8227(02)00083-9
192
M. Watanabe et al. / Diabetes Research and Clinical Practice 57 (2002) 191–197
Age, obesity, physical inactivity, heredity and tobacco use are established determinants of the risk of diabetes [2– 8]. However, the association between alcohol consumption and the risk of developing diabetes is uncertain since previous studies have variously reported inverse [8– 12], null [13– 15] and positive associations [16]. Data from a Japanese study has provided some evidence that the effects of alcohol consumption on the risk of diabetes may vary by BMI [17] although similar analyses of a cohort of participants in a study conducted in the US identified no such interaction [11]. Reliable data on the effects of alcohol consumption on the risk of diabetes are important because alcohol consumption is both widespread and potentially modifiable. In Japan about half of all males and one in ten of all females consume alcohol every week [18]. It is uncertain whether the reported differences between the findings of previous studies with regard to the effects of alcohol on diabetes reflect true differences in response to alcohol according to BMI or are simply a function of the limited statistical power of subgroup analyses. To further address this issue, we report here the association of alcohol consumption with the risk of diabetes both overall and separately in low-, middle- and high-BMI individuals in a cohort of middle-aged Japanese men and women.
2. Materials and methods
2.1. Participants The study was conducted among employees of a Japanese insurance company that participated in a legislated system of annual health checks for employees aged 35 years or over. Participants were recruited from a network of 206 company offices located in major cities around Japan with baseline assessments made between 1991 and 1998. Follow-up assessments were scheduled annually, with the final assessments made in 1999. To be eligible for inclusion in these analyses, participants were required to have completed at least one follow-up assessment, to have no clinical
diagnosis of diabetes at baseline, to have a baseline FPG level of B 7.8 mmol/l and to have no history of chronic pancreatitis at baseline and during follow-up [19,20].
2.2. Data collection At each annual assessment, nurses administered a questionnaire, conducted a brief physical examination and collected a venous blood sample. Participants were asked to fast overnight prior to each assessment to enable measurement of FPG levels. In this study standardization of the method for glucose measurement across centers and over time was not possible. However, all laboratories were regulated by the Japan Medical Association, which reported that four major methods have been used since 1991 in 98.8% of laboratories and that the measurement errors among methods and among laboratories were minimal [21]. The questionnaire consisted of questions about demographics, lifestyle and medical history, including a clinical diagnosis of diabetes. Average daily alcohol consumption was calculated by participants themselves and self-reported as either no alcohol consumption, alcohol consumption 5 21 g/day, alcohol consumption \ 21 but 5 42 g/day, or alcohol consumption \ 42 g/day (the traditional Japanese measurement of alcohol consumption, ‘1 gou’, contains 21 g of alcohol). Body weight and height were measured with the participant wearing light clothing and with shoes removed. In this study we collaborated with the company’s industrial doctor, who was in charge of promoting employee health through the use of information gained during health check-ups. To ensure confidentiality, the identities of these participants were not revealed to those other than the authors and data collectors with whom we collaborated.
2.3. Outcomes The outcome for the study was diabetes, defined as either a first clinical diagnosis of diabetes on the basis of the questionnaire at each follow-up assessment or a follow-up FPG level of 7.8 mmol/l or more [22].
M. Watanabe et al. / Diabetes Research and Clinical Practice 57 (2002) 191–197
Sensitivity analyses were also conducted using variations of the definition of outcome measures (a first clinical diagnosis of diabetes on the basis of the questionnaire at each follow-up assessment or a follow-up FPG level of 7.0 mmol/l or more, excluding participants with a baseline FPG level of 7.0 mmol/l or more) [23].
2.4. Statistical analysis The associations between exposures and study outcomes were determined by fitting multivariate pooled logistic regression models [24]. The unit of exposure fitted was person years with the exposure level for each period defined by the measurements made at the end of each year of follow-up. Each person-year of exposure was treated as an independent observation. Participants were censored upon the first occurrence of an outcome. Relative risks and 95% CIs were calculated. The independent variables included in each model were age, gender, BMI, baseline FPG level, current tobacco use and current alcohol consumption. Evidence for an interaction between BMI status and the effects of alcohol consumption on diabetes was investigated by adding an interaction term to the model. For each independent variable, missing data were complemented from the last known measurement. Overall models were fitted to determine the association of exposures with the risk of diabetes and then separate models were fitted for three subgroups of participants defined by BMI (5 22.0 kg/m2 (low-BMI), 22.1– 24.9 kg/m2 (middle-BMI) and ]25.0 kg/m2 (high-BMI)). The BMI cut-off point of 22.0 kg/m2 was based on the cut-off point adopted in a previous Japanese study [17], and the BMI cut-off point of 25.0 kg/m2 was based on the definition of obesity by the Japan Society for the Study of Obesity [25]. We pooled men and women in this analysis because the number of outcomes among women was too small to investigate in detail and because the interaction term between gender and alcohol consumption was not significant in each model. Alcohol consumption was dichotomized into no alcohol consumption and current alcohol consumption. No alcohol consumption was taken as
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a reference group to estimate the relative risk for current alcohol consumption. We pooled the three current alcohol consumption categories because when separating alcohol consumption into three categories, relative risk of each current alcohol consumption category showed a similar value with a very wide 95% CI and without a clear dose–response relationship. Sensitivity analyses were conducted, first, without a baseline FPG level, and, second, with the addition of total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride and systolic blood pressure.
3. Results A total of 6,106 individuals were enrolled in the study. Of these, 470 (7.7%) were deemed ineligible for the analyses based on a clinical history of diabetes (N= 44), a baseline FPG of 7.8 mmol/l or more (N=162) or failure to attend any followup visit (total N= 264), death (N= 2), retirement (N= 158), and no available data (N= 104) (Fig. 1). Almost 99% of the employees participated in a health check each year from 1991 to 1999. Of the 5,636 eligible participants, 28% were female and the mean age was 44 years (range 35–68 years), 47% were regular smokers and 78% regularly consumed alcohol (Table 1). Among these individuals, during the mean 5.7 years of
Fig. 1. Flow chart of composition of participants, Japan, 1991 – 1999. FPG: Fasting plasma glucose.
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Table 1 Baseline characteristics of participants overall and by body mass index levels, Japan, 1991–1999 Overall
N Age (years) Male (%)
5636 449 7 72
Low BMIa
Middle BMIa
High BMIa
522.0 (kg/m2)
22.1–24.9 (kg/m2)
25.05(kg/m2)
2304 44 96 56
2003 469 7 81
1329 4597 84
71 45 19 7 33 23.3 5.2 5.3 1.4 1.4 122 77
71 43 19 9 33 27.0 5.3 5.5 1.3 1.9 128 81
Age, gender adjusted Current alcohol consumption (%) Alcohol consumption521 g/day (%) 21Balcohol consumption542 g/day (%) 42 g/dayBalcohol consumption (%) Current tobacco use (%) BMIa (kg/m2) Fasting plasma glucose (mmol/l) Total cholesterol (mmol/l) HDLb- cholesterol (mmol/l) Triglyceride (mmol/l) Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg)
78 41 26 10 47 22.9 9 3.1 5.29 0.6 5.39 0.9 1.49 0.4 1.59 1.4 122 9 15 78 911
68 41 21 6 39 20.1 5.0 5.0 1.5 1.1 117 74
Mean9 S.D. a BMI, body mass index. b HDL, high density lipoprotein.
follow-up, 264 outcome events were recorded (17 clinical diagnoses of diabetes and 247 FPG levels of 7.8 mmol/l or more) (Fig. 1). Of the total person years, the proportion of complemented data was 1.4%. On the basis of baseline assessment of BMI, 2,304 individuals were classified as low-BMI, 2,003 as middle-BMI and 1,329 as high-BMI, (Table 1). Among low-BMI individuals the proportion of male was lower and the proportion of current tobacco use was higher than middle- or high-BMI individuals. Mean total cholesterol, triglyceride and systolic and diastolic blood pressure increased with increase in BMI level. In the overall analyses of outcome, factors that were significantly associated with the risk of diabetes were: female gender (relative risk= 0.57, 95% CI 0.33– 0.96), BMI (per kg/m2) (1.11, 1.07– 1.16), baseline FPG (per mmol/l) (6.98, 5.92– 8.22) and current tobacco use (1.50, 1.15– 1.95). In the analysis with the inclusion of total cholesterol, HDL- cholesterol, triglyceride and systolic blood pressure, HDL-cholesterol and triglyceride
were also significantly associated with the risk of diabetes (HDL-cholesterol [per mmol/l] 0.47, 0.29–0.76; triglyceride [per mmol/l] 1.11, 1.05– 1.18) (Table not presented). Among current alcohol drinkers compared with non-drinkers, the relative risk of diabetes was 3.19 (1.09–9.37) in the low-BMI individuals, 0.41 (0.23–0.73) in the middle-BMI individuals and 0.74 (0.44–1.25) in the high-BMI individuals (Table 2). The P value for the interaction term between BMI categories and current alcohol consumption was 0.05. These findings were similar to those of the sensitivity analyses conducted using variations of the definition of outcome measures (a first clinical diagnosis of diabetes on the basis of the questionnaire at each follow-up assessment or a follow-up FPG level of 7.0 mmol/l or more, excluding participants with a baseline FPG level of 7.0 mmol/l or more): relative risk of diabetes among lowBMI individuals was 1.85 (0.84–4.07), among middle-BMI individuals was 0.55 (0.34– 0.89) and among high-BMI individuals was 0.89 (0.57–
M. Watanabe et al. / Diabetes Research and Clinical Practice 57 (2002) 191–197
1.40). The exclusion of FPG from the models and the inclusion of total cholesterol, HDL-cholesterol, triglyceride and systolic blood pressure in the models did not appreciably change the findings (Table not presented).
4. Discussion In this study, current alcohol consumption was associated with an increased risk of diabetes among low-BMI individuals and a decreased risk of diabetes among middle-BMI individuals. A tendency for an association of alcohol consumption with a decreased risk of diabetes among high-BMI individuals was noted, although without statistical significance. The interaction between the effects of BMI and alcohol consumption on the risk of diabetes observed in this study is directly in line with a similar interaction observed in a prior study of Japanese men [17]. The finding is, however, discrepant with findings of a large study conducted among US physicians [11] that showed no such interaction. In that
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study there was an inverse association between alcohol consumption and diabetes among individuals both above and below the median BMI. Inverse associations also have been observed in several other large prospective studies conducted among predominantly Western populations [8– 12]. While differences between findings of the US physicians study, the current study and the previous Japanese study may simply reflect chance, other characteristics of the study populations may be responsible for the observed differences. The mean BMI of the participants in the US physicians study was about 25 kg/m2 compared with 23 kg/m2 in the current study and 22.5 kg/m2 in the prior Japanese study. Accordingly, the BMI levels at which possible interactions between BMI and alcohol consumption were investigated were markedly lower in this and the prior Japanese study (22 kg/m2) than in the US physicians study (24.4 kg/m2). If a modifying effect of BMI occurred only among low-BMI individuals, this might explain why an interaction between the effects of BMI and alcohol consumption on the
Table 2 Association of alcohol consumption with risk of clinical diagnosis of diabetes or fasting plasma glucose of 7.8 mmol/l or more overall and by body mass index levels, Japan, 1991–1999 Alcohol consumption
Total person-years
Cases
O6erall None Current
6296 22 944
43 221 4 43
Low BMI (BMI522.0 kg/m 2)b None 2970 Current 7652
Age, gender adjusted incidence rate/1000 person-years
Multivariate relative riska
95% Confidence interval
7.9 7.6
1.00 0.79
0.55–1.13
2.3 6.1
1.00 3.19
1.09–9.37
9.2 6.1
1.00 0.41
0.23–0.73
13.6 11.7
1.00 0.74
0.44–1.25
2 b
Middle BMI (22.15BMI524.9 kg/m ) None 1985 19 Current 8875 73 High BMI (25.0 kg/m 5BMI) None 1341 20 Current 6417 105 (P value for interaction termc = 0.05) 2
a
b
Model included age, gender, BMI, baseline fasting plasma glucose level, current tobacco use and current alcohol consumption. BMI: body mass index. c P value for interaction term between BMI categories and current alcohol consumption was estimated by adding interaction term to the overall model. b
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risk of diabetes were observed in this and the prior Japanese study, but not in the US physicians study. It is possible that imperfect measurement of dependent and independent variables may have resulted in underestimation or overestimation of the importance of some of the risk factors studied. For example, non-standardized FPG measurements across centers and over time may have resulted in underestimation of the strengths of the observed associations although the reported broad consistency in laboratory techniques and standards [21] suggests that attenuation of the associations attributable to this cause is likely to have been small. The absence of information about a family history of diabetes, physical activity and diet makes it impossible to determine either the separate effects of these exposures on the risk of diabetes or to investigate their possible modifying effects on the associations reported. There is a well-established association between obesity, insulin resistance and diabetes [26– 28] and several cross-sectional studies conducted among Western populations have suggested a beneficial effect of alcohol consumption on insulin resistance [29– 32]. Such studies provide a possible physiological explanation of the inverse association between alcohol consumption and diabetes observed among Western populations and Japanese individuals having a BMI 22 kg/m2 or greater [8,10–12,17]. However, clear data about the effects of alcohol on insulin resistance among individuals with a low BMI are not available and a clear physiological explanation for the apparent increased risk of diabetes with increasing alcohol consumption among low-BMI individuals has not been established. In conclusion, the observed inverse association between current alcohol consumption and the risk of diabetes among middle- or high-BMI individuals in this study is in line with evidence provided by several previous studies conducted among predominantly middle- or high-BMI individuals. However, the increased risk of diabetes associated with current alcohol consumption among lowBMI individuals observed in this study decreases the likelihood that the corresponding observation in the prior study of Japanese men was a chance
finding. Definitive information about the effects of alcohol consumption on the risk of diabetes among low-BMI individuals might be obtained by overview analyses of existing datasets. Reliable information about the effects of alcohol among such individuals is required to properly formulate health policy and will be particularly important in countries, such as Japan, where a large proportion of the population has a low BMI.
Acknowledgements The authors thanks the industrial nurses of the Meiji Mutual Life Insurance Company for their collaboration, and thanks Professor MacMahon S. and Professor Woodward M. at the Institute for International Health (University of Sydney) for their methodological and statistical suggestion.
References [1] H. King, R.E. Aubert, W.H. Herman, Global burden of diabetes 1995 – 2025, Diabetes care 21 (1998) 1414 – 1431. [2] E. Barrett-Connor, Epidemiology obesity, and non-insulin-dependent diabetes mellitus, Epidemiol. Rev. 11 (1989) 172 – 181. [3] R.D. Morris, D.L. Rimm, A.J. Hartz, R.K. Kalkhoff, A.A. Rimm, Obesity and heredity in the etiology of non-insulin dependent diabetes mellitus in 32,662 adult white women, Am. J. Epidemiol. 130 (1989) 112 – 121. [4] G.A. Colditz, W.C. Willett, A. Rotnitzky, J.E. Manson, Weight gain as a risk factor for clinical diabetes in women, Ann. Intern. Med. 122 (1995) 481 – 486. [5] S.P. Helmrich, D.R. Ragland, R.W. Leung, R.S. Paffenbarger, Physical activity and reduced occurrence of noninsulin-dependent diabetes mellitus, New Engl. J. Med. 325 (1991) 147 – 152. [6] X.R. Pan, G.W. Li, Y.H. Hu, et al., Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance: The Da Quing IGT and Diabetes Study, Diabetes care 20 (1997) 537 – 544. [7] E.B. Rimm, J.E. Manson, M.J. Stampfer, et al., Cigarette smoking and the risk of diabetes in women, Am. J. Public Health 83 (1993) 211 – 214. [8] E.B. Rimm, J. Chan, M.J. Stampfer, G.A. Colditz, W.C. Willett, Prospective study of cigarette smoking, alcohol use, and the risk of diabetes in men, Br. Med. J. 310 (1995) 555 – 559.
M. Watanabe et al. / Diabetes Research and Clinical Practice 57 (2002) 191–197 [9] M.J. Stampfer, G.A. Colditz, W.C. Willett, et al., A prospective study of moderate alcohol drinking and risk of diabetes in women, Am. J. Epidemiol. 128 (1988) 549 – 558. [10] I.J. Perry, S.G. Wannamethee, M.K. Walker, A.G. Thomson, P.H. Whincup, A.G. Shaper, Prospective study of risk factors for development of non-insulin dependent diabetes in middle aged British men, Br. Med. J. 310 (1995) 560 – 564. [11] U.A. Ajani, C.H. Hennekens, A. Spelsberg, J.E. Manson, Alcohol consumption and risk of type 2 diabetes mellitus among US male physicians, Arch. Intern. Med. 160 (2000) 1025 – 1030. [12] M. Wei, L.W. Gibbons, T.L. Mitchell, J.B. Kampert, S.N. Blair, Alcohol intake and incidence of type 2 diabetes in men, Diabetes care 23 (2000) 18 – 22. [13] E.J.M. Feskens, D. Kromhout, Cardiovascular risk factors and the 25-year incidence of diabetes mellitus in middle-aged men. The Zutphen Study, Am. J. Epidemiol. 130 (1989) 1101 – 1108. [14] L.O. Ohlson, B. Larsson, P. Bjorntorp, et al., Risk factors for Type 2 (non-insulin-dependent) diabetes mellitus, Thirteen and one-half years of follow-up of the participants in a study of Swedish men born in 1913, Diabetologia 31 (1988) 798 – 805. [15] A.M. Hodge, G.K. Dowse, V.R. Collins, P.Z. Zimmet, Abnormal glucose tolerance and alcohol consumption in three populations at high risk of non-insulin-dependent diabetes mellitus, Am. J. Epidemiol. 137 (1993) 178 –189. [16] T.L. Holbrook, E. Barrett-Connor, D.L. Wingard, A Prospective Population-based study of alcohol use and non-insulin-dependent diabetes mellitus, Am. J. Epidemiol. 132 (1990) 902 – 909. [17] K. Tsumura, T. Hayashi, C. Suematsu, G. Endo, S. Fujii, K. Okada, Daily alcohol consumption and the risk of type 2 diabetes in Japanese men: The Osaka Health Survey, Diabetes care 22 (1999) 1432 –1437. [18] Ministry of Health and Welfare, Kokumin eiyou no genjou (Results of National Nutrition Survey in 1998), Tokyo, Daiichi Shuppan, 2000, p. 57 (Japanese). [19] S. Larsen, J. Hilsted, B. Tronier, H. Worning, Metabolic control and B cell function in patients with insulin-dependent diabetes mellitus secondary to chronic pancreatitis, Metabolism 36 (1987) 964 –967. [20] M. Koizumi, Y. Yoshida, N. Abe, T. Shimosegawa, T. Toyota, Pancreatic diabetes in Japan, Pancreas 16 (1998) 385 – 391.
197
[21] Japan Medical Association, Wagakuni no rinshoukensa seidokanri-30 nen no ayumi (Management of quality in clinical examination-progress in 30 years), Tokyo, Nihonijishinpousha, 1998, pp. 76 – 106 (Japanese). [22] World Health Organization, Diabetes Mellitus; Report of a WHO study Group, World Health Organization, Geneva, 1985 (Technical Report Series No.727). [23] The expert committee on the diagnosis and classification of diabetes mellitus, Report of the expert committee on the diagnosis and classification of diabetes mellitus, Diabetes care 20 (1997) 1183 – 1197. [24] R.B. D’Agostino, M.L. Lee, A.J. Belanger, L.A. Cupples, K. Anderson, W.B. Kannel, Relation of pooled logistic regression to time dependent Cox regression analysis: the Framingham Heart Study, Stat. Med. 9 (1990) 1501 – 1515. [25] Y. Matuzawa, S. Inoue, Y. Ikeda, et al., (The committee on the diagnosis and classification criteria of obesity, Japan Society for the Study of Obesity), Atarashii himan no hantei to himanshou no shindankijun (The new diagnosis and classification of obesity), J. Jap. Soc. Study Obes. 6 (2000) 18 – 28 (Japanese). [26] G.M. Reaven, Role of insulin resistance in human disease, Diabetes 37 (1988) 1595 – 1607. [27] N.M. Kaplan, The deadly quartet. Upper-body obesity glucose intolerance hypertriglyceridemia and hypertension, Arch. Intern. Med. 149 (1989) 1514 – 1520. [28] R.A. DeFronzo, E. Ferrannini, Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity hypertension dyslipidemia and atherosclerotic cardiovascular disease, Diabetes Care 14 (1991) 173 – 194. [29] E.J. Mayer, B. Newman, C.P. Quesenberry Jr, G.D. Friedman, J.V. Selby, Alcohol consumption and insulin concentrations. Role of insulin in associations of alcohol intake with high-density lipoprotein cholesterol and triglycerides, Circulation 88 (part 1) (1993) 2190 – 2197. [30] F. Facchini, Y.D.I. Chen, G.M. Reaven, Light-to-moderate alcohol intake is associated with enhanced insulin sensitivity, Diabetes care 17 (1994) 115 – 119. [31] R. Lazarus, D. Sparrow, S.T. Weiss, Alcohol intake and insulin levels. The Normative Aging Study, Am. J. Epidemiol. 145 (1997) 909 – 916. [32] R.A. Bell, E.J. Mayer-Davis, M.A. Martin, R.B. D’Agostino Jr, S.M. Haffner, Associations between alcohol consumption and insulin sensitivity and cardiovascular disease risk factors: the insulin resistance and atherosclerosis study, Diabetes Care 23 (2000) 1630 – 1636.