HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nakanishi, N. Articles by Tatara, K. Search for Related Content PubMed PubMed Citation Articles by Nakanishi, N. Articles by Tatara, K. Social Bookmarking                What's this?

Alcohol Consumption and Risk for Development of Impaired Fasting Glucose or Type 2 Diabetes in Middle-Aged Japanese Men

¹ Department of Social and Environmental Medicine, Course of Social Medicine, Osaka University Graduate School of Medicine F2, Osaka, Japan
² Japan Labor and Welfare Association, Tokyo, Japan

	ABSTRACT

TOP ABSTRACT INTRODUCTION RESEARCH DESIGN AND METHODS RESULTS CONCLUSIONS References

 
OBJECTIVE—To investigate the association between alcohol consumption and risk for development of diabetes.

RESEARCH DESIGN AND METHODS—We examined 2,953 Japanese male office workers aged 35–59 years who did not have impaired fasting glucose (IFG) (a fasting plasma glucose concentration of 6.1–6.9 mmol/l), type 2 diabetes (a fasting plasma glucose concentration of 7.0 mmol/l or receipt of hypoglycemic medication), medication for hypertension, or a history of cardiovascular disease. Fasting plasma glucose concentrations were measured at periodic annual health examinations from May 1994 through May 2001.

RESULTS—There was a U-shaped association between alcohol consumption and the incidence of IFG or type 2 diabetes during 7 years of follow-up, with the lowest incidence at alcohol intake of 23.0–45.9 g ethanol/day. After controlling for age, family history of diabetes, BMI, cigarette smoking, and physical activity, the relative risk for development of IFG or type 2 diabetes compared with alcohol consumption of 23.0–45.9 g ethanol/day was 1.51 (95% CI, 1.07–2.13), 1.31 (95% CI, 0.93–1.84), 1.18 (95% CI, 0.87–1.61), and 1.43 (95% CI, 1.01–2.02) with alcohol consumption of 0, 0.1–22.9, 46.0–68.9, and 69.0 g ethanol/day, respectively (P for quadratic trend = 0.016). Analyses by presence or absence of a risk factor revealed that a U-shaped association was more evident in older men, men without a family history of diabetes, and nonsmokers.

CONCLUSIONS—These results indicate that moderate alcohol consumption among apparently healthy Japanese men is associated with reduced risk for development of IFG or type 2 diabetes.

Abbreviations: CVD, cardiovascular disease • IFG, impaired fasting glucose

	INTRODUCTION

TOP ABSTRACT INTRODUCTION RESEARCH DESIGN AND METHODS RESULTS CONCLUSIONS References

 
Type 2 diabetes, which affects 7 million Japanese individuals, is characterized by impaired insulin secretion and insulin resistance. Aside from obesity, reduced physical activity, and cigarette smoking, there are few other well-established modifiable risk factors for type 2 diabetes (1–6). Alcohol consumption represents a potentially important, modifiable risk factor of type 2 diabetes and may be related to the risk for type 2 diabetes through its effects on insulin secretion and sensitivity (7–10).

Several studies have been performed to study the effect of alcohol consumption on the incidence of type 2 diabetes in men (1,5,11–17). In some of these studies, the association was U- or J-shaped, with the lowest incidence of type 2 diabetes in subjects with moderate alcohol consumption (5,11–13), whereas others observed overall positive (14,15), null (1,16), or inverse (17) associations. These inconclusive results may have resulted in part from ethnic or lifestyle differences in the study populations but also may have been strongly influenced by different methods used to investigate the association between alcohol intake and type 2 diabetes. In addition, participants with preexisting diabetes were enrolled in some studies and biased populations in others, and these confounders may have influenced the results. Therefore, it is necessary to conduct a longitudinal study in subjects free of diabetes at baseline to clarify the relation between alcohol intake and risk for diabetes.

Using data from serial annual health examinations at the workplace, we carried out a longitudinal population study to examine prospectively the association of alcohol intake with development of impaired fasting glucose (IFG) or type 2 diabetes (as diagnosed with the newly revised criteria of American Diabetes Association in 1997 [18] for epidemiological studies) in normoglycemic middle-aged Japanese men.

	RESEARCH DESIGN AND METHODS

TOP ABSTRACT INTRODUCTION RESEARCH DESIGN AND METHODS RESULTS CONCLUSIONS References

 
Study cohort
Our study is an ongoing cohort investigation, designed to clarify risk factors for major diseases, including hypertension, dyslipidemia, and diabetes among Japanese men who were office workers at one of the biggest building contractors in Japan. The Industrial Safety and Health Law in Japan requires the employer to conduct annual health examinations of all employees, and employees are required by law to participate. A signed self-administered questionnaire is a part of this examination, and the employee data, which are anonymous, are available for research with the approval of the employer. To evaluate the association of alcohol intake with development of IFG or type 2 diabetes, a survey of the incidence of IFG or type 2 diabetes was done between 1994 and 2001. All Japanese male office workers aged 35–59 years in May 1994 were invited to take a survey (n = 3,694); the participation rate was 99.6% (n = 3,681).

Of 3,681 potential participants, 663 (18.0%) were excluded: 175 (4.8%) had IFG, 282 (7.7%) had type 2 diabetes, 253 (6.9%) were taking antihypertensive medication, and 32 (0.9%) had a history of either coronary heart disease or stroke. Thus, the baseline population consisted of 3,018 men. We also excluded 65 men who did not participate in consecutive annual health examinations during follow-up. The final study population for analysis therefore consisted of 2,953 men. Men in whom IFG or type 2 diabetes was found during repeated surveys through May 2001 were classified as having IFG or type 2 diabetes. To determine the incidence of type 2 diabetes, incidental cases of IFG were followed and considered type 2 diabetes if they reached that end point. Altogether, 39 participants who started taking medication for diabetes during the observation period were considered to have type 2 diabetes. Owing to the age range of the study population, all cases of IFG or type 2 diabetes were diagnosed after 35 years of age.

Study design
Fasting plasma glucose concentrations were measured at annual health examinations in May from 1994 to 2001. The participants were asked to fast for at least 8 h and to avoid smoking and heavy physical activity for more than 2 h before the examinations. Blood samples were drawn from an antecubital vein. Glucose was measured using hexokinase-glucose dehydrogenase method (Shino-Test, Tokyo, Japan) with Olympus AU-5000 in 1994 and Olympus AU-5200 in 1995 to 2001 (Olympus Japan, Tokyo, Japan) at FALCO Biosystems Tokyo (Tokyo, Japan). Quality control of the laboratory was done internally, and the coefficients of variation between and within assays for plasma glucose were no more than 3% from 1994 to 2001. Normal fasting glucose, IFG, and type 2 diabetes were defined using the criteria of the American Diabetes Association (18). Normal fasting glucose was defined as fasting plasma glucose concentration of <6.1 mmol/l. IFG was defined as fasting plasma glucose concentration of 6.1–6.9 mmol/l. Type 2 diabetes was defined as fasting plasma glucose concentration of 7.0 mmol/l or receipt of hypoglycemic medications, because an oral glucose tolerance test was not done for every subject.

Annual health examinations at study entry included medical history, physical examination, anthropometric measurements, biochemical measurements, and a questionnaire on health-related behaviors, such as alcohol consumption, smoking, and physical activity. Medical history and history of use of prescription drugs were assessed by the examining physicians. After a 5-min rest in a quiet room, systolic and diastolic blood pressures were measured in the right arm using a standard mercury sphygmomanometer. Serum total cholesterol was determined by the Olympus AU-5000 using the enzymatic method with a commercial reagents kit (Wako, Osaka, Japan), and HDL cholesterol was assayed using the same enzymatic method after precipitation by polyethylene glycol. Enzyme activities for -glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase were measured by the Olympus AU-5000 using commercial reagents (International Reagents, Kobe, Japan) based on the principles recommended by the Japan Society of Clinical Chemistry (19).

For health-related behaviors, the questions about alcohol intake included items about frequency of alcohol consumption per week, type of alcoholic beverage, and usual amount consumed daily in units of "go" (a traditional Japanese unit of measurement, by volume, corresponding to 23 g ethanol). Weekly alcohol intake was calculated and then converted to daily alcohol consumption using standard Japanese tables. One go is 180 ml of sake, and it corresponds to one bottle (663 ml) of beer, two single shots (75 ml) of whiskey, or two glasses (180 ml) of wine. Subjects were classified as nondrinkers or current drinkers who averaged 0.1–22.9, 23.0–45.9, 46.0–68.9, or 69.0 g ethanol/day. The questionnaires were also used to ask about smoking habits (never, past, or current smoker); past or current smokers were asked about the number of cigarettes smoked per day and the duration of smoking in years. Participants were asked about the type and weekly frequency of leisure-time physical activity. Physical exercise was defined as participation in any physical activity, such as jogging, bicycling, swimming, or tennis, that was performed long enough to sweat.

Statistical analyses
The ² test and one-way ANOVA were used to analyze the statistical differences among characteristics of the study participants at enrollment according to alcohol intake. For each participant, person-years of follow-up were calculated from the date of enrollment to the date of the development of IFG or type 2 diabetes or the date of last follow-up, whichever came first. The follow-up rate was 92.6% of the total potential person-years of follow-up. Cox’s proportional hazards models were used to evaluate the association between alcohol intake and development of IFG or type 2 diabetes. Data were adjusted first for age alone and then for the following multiple covariables: age, family history of diabetes, BMI, cigarette smoking, and physical activity. Potential confounding factors were treated as categorical variables: age and BMI (graded from 1 through 5 [first through fifth quintiles]); family history of diabetes (no or yes); cigarette smoking (graded as 1 [none] or as quartile 1 [grade of 2] to quartile 4 [grade of 5] for current smokers); and regular physical exercise (graded from 1 to 3 [hardly ever, once a week, or twice or more a week]). To assess nonlinearity between alcohol intake and the risk for IFG or type 2 diabetes, the estimated quantitative median value for each category of alcohol intake was included as a linear and quadratic term in the model.

Data were analyzed using the SPSS/PC statistical package (SPSS, Chicago, IL). All reported P values are two-tailed, and those <0.05 were considered to be statistically significant.

	RESULTS

TOP ABSTRACT INTRODUCTION RESEARCH DESIGN AND METHODS RESULTS CONCLUSIONS References

 
The baseline characteristics of the study sample according to alcohol intake are shown in Table 1. Tests for differences in baseline characteristics across drinking groups were significant except for family history of diabetes and fasting plasma glucose. Current cigarette smoking, regular physical activity, systolic and diastolic blood pressures, HDL cholesterol, and -glutamyltransferase showed a linear trend related to alcohol intake.

View larger version (39K): [in this window] [in a new window]   Figure 1— Incidence rates per 1,000 person-years for IFG and type 2 diabetes according to alcohol intake among 2,953 Japanese male office workers during 7 years of follow-up.

	CONCLUSIONS

TOP ABSTRACT INTRODUCTION RESEARCH DESIGN AND METHODS RESULTS CONCLUSIONS References

However, the lower relative risk for development of IFG or type 2 diabetes associated with moderate alcohol intake in men with a family history of diabetes and in current smokers does not really mean that genetic predisposition and cigarette smoking improve the risk for development of IFG or type 2 diabetes in moderate drinkers. As shown in Table 3, men with a family history of diabetes and current smokers had higher incidence rates of IFG or type 2 diabetes than those without a family history of diabetes and nonsmokers, respectively. Furthermore, in moderate drinkers (23.0–45.9 g ethanol/day), these differences were more pronounced (incidence rate of IFG or type diabetes: 13.9 and 32.9 per 1,000 person-years for those without and with family history of diabetes, respectively, and 9.0 and 23.2 per 1,000 person-years for nonsmokers and current smokers, respectively). Thus, the influence of alcohol on development of IFG or type 2 diabetes might be obscured by genetic predisposition and cigarette smoking.

Our results are consistent with those of other studies (5,11–13) and indicate that moderate alcohol consumption is associated with a reduced risk for IFG or type 2 diabetes. Although the mechanism of how moderate drinking decreases the risk for diabetes remains to be elucidated, the findings that light-to-moderate alcohol intake is associated with a lower risk of diabetes and high alcohol intake is associated with a high risk are biologically plausible. Several studies have suggested that moderate alcohol consumption may increase insulin sensitivity and lower insulin resistance (7–10). Increased insulin secretory responses and enhanced glucose disposal rates have been observed after moderate alcohol ingestion in subjects without diabetes as well as in subjects with type 2 diabetes (20,21). This increased secretory response may be a result of the alcohol-induced stimulation of insulin secretion by gastrointestinal secretogogues or an insulinogenic effect of corticotropin peptides present in cells of the gastroentero-pancreatic system (22,23,24,25). On the other hand, diabetogenic effects of high alcohol intake include its contribution to excess caloric intake and obesity, induction of pancreatitis, disturbance of carbohydrate and glucose metabolism, and impairment of liver function (7,26). Large amounts of alcohol decrease insulin-mediated glucose uptake, and alcoholics have decreased glucose tolerance (25,27,28). In vitro studies indicate that exposure of ß-cells to alcohol is associated with decreased insulin secretion (29,30) and that metabolites of alcohol such as ethanol 2,3-butanediol and 1,2-propanediol inhibit basal and insulin-stimulated adipocyte metabolism (31). In an experimental study, atrophy of ß-cells and reduction of absolute pancreatic islet volume have been observed in ethanol-treated rats (32). In addition, gross ultrastructural alterations are seen in most ß-cells of ethanol-treated rats: irregularity of the nuclear envelope with deep invagination, margination of heterochromatin, and many empty granules or granules without clear electrodense crystals of insulin. These conditions may be attributable to a direct toxic effect of alcohol on pancreatic islet cells or to inhibition of insulin secretion and increase in insulin resistance, and large amounts of alcohol may be relevant to the pathogenesis of a high incidence of type 2 diabetes.

As for the association between alcohol consumption and mortality, previous studies reveal a J- or U-shaped relationship between alcohol consumption and total mortality in men (33–36). The reduction in total mortality at light-to-moderate levels is due to a reduction in cardiovascular disease (CVD), without significant increases in other causes of mortality. Biological mechanisms that might explain the association between light-to-moderate alcohol consumption and mortality might be increased insulin sensitivity and decreased insulin resistance (7,8,9,10) as well as the increase in HDL cholesterol, decreased platelet aggregation, and enhanced fibrinolysis (37,38,39).

Our study had several limitations. First, we estimated alcohol intake from a questionnaire of self-reported drinking habits, and misreporting of alcohol consumption could be sources of bias. In this study, there was a clear dose-response relation between alcohol intake and biological markers of alcohol consumption such as HDL cholesterol and -glutamyl transpeptidase, suggesting that little misclassification of alcohol intake had occurred.

Second, bias in case-finding could have occurred. Specifically, heavy drinkers are more likely to visit a doctor for reasons other than diabetes; thus diabetes could have been found by chance. However, because all incidental cases were found by periodic annual screening in our study, such bias is unlikely to have occurred. Furthermore, participants in our normoglycemic cohort, particularly those in the older age-groups, might not be typical of the general population. Those whose plasma glucose concentration was already above borderline values or who reported taking drugs for hypertension or having a history of CVD during the initial examination were excluded. Because hypertension is a recognized risk factor for diabetes (40,41), exclusion of hypertensive persons would bias the study toward a particularly healthy study population at a low risk for diabetes. The selection of men with rigorously normal fasting plasma glucose concentration at study entry could have had an effect on the observations.

Third, an assessment of IFG or type 2 diabetes entirely dependent on fasting plasma glucose concentration may underestimate overt longer-term diabetes. HbA_1c was measured using high-performance liquid chromatography (Sekisui Chemical, Osaka, Japan) with Olympus AU-5000 in 1994 and Olympus AU-5200 in 1995 to 2001. From the distribution of fasting plasma glucose and HbA_1c, the cut-off points of 6.1 and 7.0 mmol/l for fasting plasma glucose were compatible with those of 5.9% and 6.5% for HbA_1c, respectively. Among 3,140 men who had HbA_1c <5.9%, were not taking medication for diabetes or hypertension, and had no history of CVD at study entry, a U-shaped association was found between alcohol consumption and development of the elevated HbA_1c of both 5.9–6.4% and 6.5% over a 7-year period, with the lowest incidence at alcohol intake of 23.0–45.9 g ethanol/day. The multivariate adjusted relative risk for development of the elevated HbA_1c level of 5.9% compared with alcohol consumption of 23.0–45.9 g ethanol/day was 1.70 (95% CI, 1.21–2.38), 1.55 (95% CI, 1.12–2.15), 1.32 (95% CI, 0.98–1.79), and 1.67 (95% CI, 1.20–2.32) with alcohol consumption of 0, 0.1–22.9, 46.0–68.9, and 69.0 g ethanol/day, respectively (P for quadratic trend <0.001). These results are consistent with those of the analyses using fasting plasma glucose, and the rise in fasting plasma glucose observed in this normoglycemic cohort may express the development of diabetes during the follow-up period.

Finally, we could not include several confounding variables in this study, such as visceral adiposity (waist-to-hip ratio) and fasting insulin level. The central pattern of fat distribution, with its increased waist-to-hip ratio, is associated with more insulin resistance than is the peripheral pattern of distribution (42,43). Individuals with the central pattern are more likely to have glucose intolerance and hyperinsulinemia resulting from insulin resistance (44,45). Therefore, visceral adiposity and fasting insulin level should be included in future studies.

Despite these potential limitations, our findings, which were obtained from a cohort of middle-aged Japanese men, support the conclusion that moderate alcohol consumption is associated with a lower risk for development of IFG or type 2 diabetes. As moderate alcohol consumption might lower the risks for CVD and diabetes, it may well be that the effects of moderate alcohol consumption on CVD are related to the changes in insulin and glucose metabolism.

	Acknowledgments

 
This study was supported in part by a grant-in-aid from the Japan Arteriosclerosis Prevention Fund (JAPF), Tokyo, Japan.

	Footnotes

 
Address correspondence and reprint requests to Noriyuki Nakanishi, Department of Social and Environmental Medicine, Course of Social Medicine, Osaka University Graduate School of Medicine F2, 2–2 Yamada-oka, Suita-shi, Osaka 565-0871, Japan. E mail: noriyuki{at}pbhel.med.osaka-u.ac.jp.

Received for publication 1 August 2002 and accepted in revised form 26 September 2002.

A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

	References

TOP ABSTRACT INTRODUCTION RESEARCH DESIGN AND METHODS RESULTS CONCLUSIONS References

 

1. Feskens EJ, Kromhout D: Cardiovascular risk factors and the 25-year incidence of diabetes mellitus in middle-aged men. The Zutphen Study. Am J Epidemiol 130:1101–1108, 1989[Abstract/Free Full Text]
   
2. Helmrich SP, Ragland DR, Leung RW, Paffenbarger RS Jr: Physical activity and reduced occurrence of non-insulin-dependent diabetes mellitus. N Engl J Med 325:147–152, 1991[Abstract]
   
3. Colditz GA, Willett WC, Rotnitzky A, Manson JE: Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med 122:481–486, 1995[Abstract/Free Full Text]
   
4. Pan XR, Li GW, Hu YH, Wang JX, Yang WY, An ZX, Hu ZX, Lin J, Xiao JZ, Cao HB, Liu PA, Jiang XG, Jiang YY, Wang JP, Zheng H, Zhang H, Bennett PH, Howard BV: Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care 20:537–544, 1997[Abstract]
   
5. Rimm EB, Chan J, Stampfer MJ, Colditz GA, Willett WC: Prospective study of cigarette smoking, alcohol use, and the risk of diabetes in men. BMJ 310:555–559, 1995[Abstract/Free Full Text]
   
6. Nakanishi N, Nakamura K, Matsuo Y, Suzuki K, Tatara K: Cigarette smoking and risk for impaired fasting glucose and type 2 diabetes in middle-aged Japanese men. Ann Intern Med 133:183–191, 2000[Abstract/Free Full Text]
   
7. Bell DS: Alcohol and the NIDDM patient. Diabetes Care 19:509–513, 1996[Abstract]
   
8. Facchini F, Chen YD, Reaven GM: Light-to-moderate alcohol intake is associated with enhanced insulin sensitivity. Diabetes Care 17:115–119, 1994[Abstract]
   
9. Mayer EJ, Newman B, Quesenberry CP Jr, Friedman GD, Selby JV: Alcohol consumption and insulin concentrations: role of insulin in associations of alcohol intake with high-density lipoprotein cholesterol and triglycerides. Circulation 88:2190–2197, 1993[Abstract/Free Full Text]
   
10. Lazarus R, Sparrow D, Weiss ST: Alcohol intake and insulin levels. The Normative Aging Study. Am J Epidemiol 145:909–916, 1997[Abstract/Free Full Text]
    
11. Perry IJ, Wannamethee SG, Walker MK, Thomson AG, Whincup PH, Shaper AG: Prospective study of risk factors for development of non-insulin dependent diabetes in middle aged British men. BMJ 310:560–564, 1995[Abstract/Free Full Text]
    
12. Wei M, Gibbons LW, Mitchell TL, Kampert JB, Blair SN: Alcohol intake and incidence of type 2 diabetes in men. Diabetes Care 23:18–22, 2000[Abstract]
    
13. Wannamethee SG, Shaper AG, Perry IJ, Alberti KG: Alcohol consumption and the incidence of type II diabetes. J Epidemiol Community Health 56:542–548, 2002[Abstract/Free Full Text]
    
14. Holbrook TL, Barrett-Connor E, Wingard DL: A prospective population-based study of alcohol use and non-insulin-dependent diabetes mellitus. Am J Epidemiol 132:902–909, 1990[Abstract/Free Full Text]
    
15. Kao WH, Puddey IB, Boland LL, Watson RL, Brancati FL: Alcohol consumption and the risk of type 2 diabetes melli-tus: atherosclerosis risk in communities study. Am J Epidemiol 154:748–757, 2001[Abstract/Free Full Text]
    
16. Hodge AM, Dowse GK, Collins VR, Zimmet PZ: Abnormal glucose tolerance and alcohol consumption in three populations at high risk of non-insulin-dependent diabetes mellitus. Am J Epidemiol 137:178–189, 1993[Abstract/Free Full Text]
    
17. Ajani UA, Hennekens CH, Spelsberg A, Manson JE: Alcohol consumption and risk of type 2 diabetes mellitus among US male physicians. Arch Intern Med 160:1025–1030, 2000[Abstract/Free Full Text]
    
18. 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 20:1183–1197, 1997[Medline]
    
19. Japan Society of Clinical Chemistry: Recommendation for measuring enzyme activity in human serum [in Japanese with English abstract]. Jpn J Clin Chem 18:211–262, 1989
    
20. McMonagle J, Felig P: Effects of ethanol ingestion on glucose tolerance and insulin secretion in normal and diabetic subjects. Metabolism 24:625–632, 1975[Medline]
    
21. Metz R, Berger S, Mako M: Potentiation of the plasma insulin response to glucose by prior administration of alcohol: an apparent islet-priming effect. Diabetes 18:517–22, 1969[Medline]
    
22. Shapiro H, Wruble LD, Estes JW: Pancreatic secretion stimulated by the action of alcohol on the gastric antrum. Am J Dig Dis 13:536–539, 1968[Medline]
    
23. Unger RH, Ketterer H, Dupre J, Eisentraut AM: The effects of secretin, pancreozymin, and gastrin on insulin and glucagon secretion in anesthetized dogs. J Clin Invest 46:630–645, 1967
    
24. Sussman KE, Vaughan GD, Timmer RF: An in vitro method for studying insulin secretion in the perfused isolated rat pancreas. Metabolism 15:466–476, 1966[Medline]
    
25. Yki-Jarvinen H, Nikkila EA: Ethanol decreases glucose utilization in healthy man. J Clin Endocrinol Metab 61:941–945, 1985[Abstract]
    
26. Avogaro A, Tiengo A: Alcohol, glucose metabolism and diabetes. Diabete Metab Rev 9:129–146, 1993
    
27. Shelmet JJ, Reichard GA, Skutches CL, Hoeldtke RD, Owen OE, Boden G: Ethanol causes acute inhibition of carbohydrate, fat, and protein oxidation and insulin resistance. J Clin Invest 81:1137–1145, 1988
    
28. Yki-Jarvinen H, Koivisto VA, Ylikahri R, Taskinen MR: Acute effects of ethanol and acetate on glucose kinetics in normal subjects. Am J Physiol 254:E175–E180, 1988[Abstract/Free Full Text]
    
29. Tiengo A, Valerio A, Molinari M, Meneghel A, Lapolla A: Effect of ethanol, acetaldehyde, and acetate on insulin and glucagon secretion in the perfused rat pancreas. Diabetes 30:705–709, 1981[Abstract]
    
30. Holley DC, Bagby GJ, Curry DL: Ethanol-insulin interrelationships in the rat studied in vitro and in vivo: evidence for direct ethanol inhibition of biphasic glucose-induced insulin secretion. Metabolism 30:894–899, 1981[Medline]
    
31. Lomeo F, Khokher MA, Dandona P: Ethanol and its novel metabolites inhibit insulin action on adipocytes. Diabetes 37:912–915, 1988[Abstract]
    
32. Koko V, Todorovic V, Nikolic JA, Glisic R, Cakic M, Lackovic V, Petronijevic L, Stojkovic M, Varagic J, Janic B, Radovanovic J, Laban A: Rat pancreatic B-cells after chronic alcohol feeding: a morphometric and fine structural study. Histol Histopathol 10:325–337, 1995[Medline]
    
33. Klatsky AL, Friedman GD, Siegelaub AB: Alcohol and mortality: a ten-year Kaiser-Permanente experience. Ann Intern Med 95:139–145, 1981
    
34. White IR: The level of alcohol consumption at which all-cause mortality is least. J Clin Epidemiol 52:967–975, 1999[Medline]
    
35. Grønbaek M, Deis A, Sørensen TI, Becker U, Borch-Johnsen K, Müller C, Schnohr P, Jensen G: Influence of sex, age, body mass index, and smoking on alcohol intake and mortality. BMJ 308:302–306, 1994[Abstract/Free Full Text]
    
36. Gaziano JM, Gaziano TA, Glynn RJ, Sesso HD, Ajani UA, Stampfer MJ, Manson JE, Hennekens CH, Buring JE: Light-to-moderate alcohol consumption and mortality in the Physicians’ Health Study enrollment cohort. J Am Coll Cardiol 35:96–105, 2000[Abstract/Free Full Text]
    
37. Gaziano JM, Buring JE, Breslow JL, Goldhaber SZ, Rosner B, VanDenburgh M, Willett W, Hennekens CH: Moderate alcohol intake, increased levels of high-density lipoprotein and its subfractions, and decreased risk of myocardial infarction. N Engl J Med 329:1829–1834, 1993[Abstract/Free Full Text]
    
38. Ridker PM, Vaughan DE, Stampfer MJ, Glynn RJ, Hennekens CH: Association of moderate alcohol consumption and plasma concentration of endogenous tissue-type plasminogen activator. JAMA 272:929–933, 1994[Abstract]
    
39. Rimm EB, Williams P, Fosher K, Criqui M, Stampfer MJ: Moderate alcohol intake and lower risk of coronary heart disease: meta-analysis of effects on lipids and haemostatic factors. BMJ 319:1523–1528, 1999[Abstract/Free Full Text]
    
40. Stolk RP, van Splunder IP, Schouten JS, Witteman JC, Hofman A, Grobbee DE: High blood pressure and the incidence of non-insulin dependent diabetes mellitus: findings in a 11.5 year follow-up study in The Netherlands. Eur J Epidemiol 9:134–139, 1993[Medline]
    
41. Morales PA, Mitchell BD, Valdez RA, Hazuda HP, Stern MP, Haffner SM: Incidence of NIDDM and impaired glucose tolerance in hypertensive subjects. The San Antonio Heart Study. Diabetes 42:154–161, 1993[Abstract]
    
42. Kissebah AH, Vydelingum N, Murray R, Evans DJ, Hartz AJ, Kalkhoff RK, Adams PW: Relation of body fat distribution to metabolic complications of obesity. J Clin Endocrinol Metab 54:254–260, 1982[Abstract]
    
43. Krotkiewski M, Bjorntorp P, Sjostrom L, Smith U: Impact of obesity on metabolism in men and women: importance of regional adipose tissue distribution. J Clin Invest 72:1150–1162, 1983
    
44. Kissebah AH, Freedman DS, Peiris AN: Health risks of obesity. Med Clin North Am 73:111–138, 1989[Medline]
    
45. Pouliot MC, Després JP, Nadeau A, Moorjani S, Prud’Homme D, Lupien PJ, Tremblay A, Bouchard C: Visceral obesity in men: associations with glucose tolerance, plasma insulin, and lipoprotein levels. Diabetes 41:826–834, 1992[Abstract]
    

CiteULike

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				A. K. Gupta, B. Dahlof, J. Dobson, P. S. Sever, H. Wedel, N.R. Poulter, and on behalf of the Anglo-Scandinavian Cardiac Outcom Determinants of New-Onset Diabetes Among 19,257 Hypertensive Patients Randomized in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm and the Relative Influence of Antihypertensive Medication Diabetes Care, May 1, 2008; 31(5): 982 - 988. [Abstract] [Full Text] [PDF]

				M. Dakeishi, K. Murata, M. Sasaki, A. Tamura, and T. Iwata Association of alcohol dehydrogenase 2 and aldehyde dehydrogenase 2 genotypes with fasting plasma glucose levels in Japanese male and female workers Alcohol Alcohol., March 1, 2008; 43(2): 143 - 147. [Abstract] [Full Text] [PDF]

				V. G. Athyros, E. N. Liberopoulos, D. P. Mikhailidis, A. A. Papageorgiou, E. S. Ganotakis, K. Tziomalos, A. I. Kakafika, A. Karagiannis, S. Lambropoulos, and M. Elisaf Association of Drinking Pattern and Alcohol Beverage Type With the Prevalence of Metabolic Syndrome, Diabetes, Coronary Heart Disease, Stroke, and Peripheral Arterial Disease in a Mediterranean Cohort Angiology, January 1, 2008; 58(6): 689 - 697. [Abstract] [PDF]

				L. A. Bazzano, M. Serdula, and S. Liu Prevention of Type 2 Diabetes by Diet and Lifestyle Modification J. Am. Coll. Nutr., October 1, 2005; 24(5): 310 - 319. [Abstract] [Full Text] [PDF]

				Y. Doi, Y. Kiyohara, M. Kubo, T. Ninomiya, Y. Wakugawa, K. Yonemoto, M. Iwase, and M. Iida Elevated C-Reactive Protein Is a Predictor of the Development of Diabetes in a General Japanese Population: The Hisayama Study Diabetes Care, October 1, 2005; 28(10): 2497 - 2500. [Abstract] [Full Text] [PDF]

				K. Faerch, C. Lau, I. Tetens, O. B. Pedersen, T. Jorgensen, K. Borch-Johnsen, and C. Glumer A Statistical Approach Based on Substitution of Macronutrients Provides Additional Information to Models Analyzing Single Dietary Factors in Relation to Type 2 Diabetes in Danish Adults: the Inter99 Study J. Nutr., May 1, 2005; 135(5): 1177 - 1182. [Abstract] [Full Text] [PDF]

				P Maisonneuve, A B Lowenfels, B Mullhaupt, G Cavallini, P G Lankisch, J R Andersen, E P DiMagno, A Andren-Sandberg, L Domellof, L Frulloni, et al. Cigarette smoking accelerates progression of alcoholic chronic pancreatitis Gut, April 1, 2005; 54(4): 510 - 514. [Abstract] [Full Text] [PDF]

				L. L.J. Koppes, J. M. Dekker, H. F.J. Hendriks, L. M. Bouter, and R. J. Heine Moderate Alcohol Consumption Lowers the Risk of Type 2 Diabetes: A meta-analysis of prospective observational studies Diabetes Care, March 1, 2005; 28(3): 719 - 725. [Abstract] [Full Text] [PDF]

				N. Nakanishi and K. Suzuki Daily Life Activity and the Risk of Developing Hypertension in Middle-aged Japanese Men Arch Intern Med, January 24, 2005; 165(2): 214 - 220. [Abstract] [Full Text] [PDF]

				A. Avogaro, R. M. Watanabe, A. Dall'Arche, S. Vigili De Kreutzenberg, A. Tiengo, and G. Pacini Acute Alcohol Consumption Improves Insulin Action Without Affecting Insulin Secretion in Type 2 Diabetic Subjects Diabetes Care, June 1, 2004; 27(6): 1369 - 1374. [Abstract] [Full Text] [PDF]

				N. Nakanishi, K. Suzuki, and K. Tatara Serum {gamma}-Glutamyltransferase and Risk of Metabolic Syndrome and Type 2 Diabetes in Middle-Aged Japanese Men Diabetes Care, June 1, 2004; 27(6): 1427 - 1432. [Abstract] [Full Text] [PDF]

				A. A. Howard, J. H. Arnsten, and M. N. Gourevitch Effect of Alcohol Consumption on Diabetes Mellitus: A Systematic Review Ann Intern Med, February 3, 2004; 140(3): 211 - 219. [Abstract] [Full Text] [PDF]

				S. Carlsson, N. Hammar, V. Grill, and J. Kaprio Alcohol Consumption and the Incidence of Type 2 Diabetes: A 20-year follow-up of the Finnish Twin Cohort Study Diabetes Care, October 1, 2003; 26(10): 2785 - 2790. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nakanishi, N. Articles by Tatara, K. Search for Related Content PubMed PubMed Citation Articles by Nakanishi, N. Articles by Tatara, K. Social Bookmarking                What's this?