The major findings of this study were as follows: Alcohol consumption at the level of 0 < to < 22 g/day and 22 to < 39 g/day were associated with reduced risk of type 2 diabetes in middle-aged Japanese. In participants with BMI < 25 kg/m2, alcohol consumption level of 39 to < 66 g/day and ≥ 66 g/day were associated with an increased risk of type 2 diabetes. In the participants with BMI ≥ 25 kg/m2, alcohol consumption could reduce the risk of type 2 diabetes. No interaction effects were found between alcohol consumption, and FPG category and sex on the onset of type 2 diabetes.
Although the mechanism through which alcohol consumption affects the risk of developing diabetes remains unknown, some studies have reported an association between alcohol consumption and insulin resistance. Alcohol consumption can improve insulin resistance 23–26. Alcohol consumption increases insulin sensitivity by increasing the adiponectin and leptin levels27,28. Previous studies showed that high levels of adiponectin are closely associated with increased insulin sensitivity 29–31. A previous study demonstrated that low fasting plasma adiponectin levels are linked with reduced insulin-stimulated skeletal muscle insulin receptor tyrosine phosphorylation, which could be a potential cause of decreased insulin sensitivity 32. Alcohol has also anti-inflammatory properties. A previous study found that alcohol consumption had a U-shaped association with C-reactive protein levels33. Furthermore, moderate ethanol consumption inhibits interleukin-6 production or activity 34. Inflammation is also associated with insulin resistance35. Moreover, alcohol consumption may indirectly affect adipocytes because it has long been known that acetate, the chief circulating metabolite of alcohol, has an antilipolytic effect on adipocytes34,36. The ability of alcohol consumption to acutely lower free fat acid levels 37,38 presumably reflects the generation of hepatic acetate. Therefore, alcohol consumption may prevent insulin resistance by suppressing adipocyte lipolysis, resulting in reduced levels of circulating free fatty acids. On the other hand, alcohol consumption was associated with a significant decrease in the insulin secretion level at the alcohol consumption level of ≥ 40 g/day 39. Excessive alcohol consumption can lead to pancreatic fibrosis 40 and, depending on the amount, may potentially result in decreased insulin secretion due to alcohol intake.
In this study, different results were obtained after stratification according to BMI. In participants with BMI < 25 kg/m2, moderate-to-high alcohol consumption increased the risk of type 2 diabetes. In participants with BMI ≥ 25 kg/m2, alcohol consumption reduced the risk of type 2 diabetes. As mentioned earlier, alcohol consumption is associated with improving insulin resistance. Therefore, it might exert a protective effect against the onset of diabetes in individuals with BMI ≥ 25 kg/m2, who are anticipated to have higher insulin resistance. Conversely, individuals with BMI < 25 kg/m2 who are not anticipated to have high insulin resistance may be less likely to benefit from this effect and may even face an increased risk of developing diabetes due to decreased insulin secretion caused by alcohol consumption. Previous reports have suggested that the impact of alcohol on type 2 diabetes may vary depending on the BMI in Japanese individuals 41–44. Waki. et al. 42 reported that moderate to high alcohol consumption increased the risk of type 2 diabetes in the participants with BMI ≤ 22 kg/m2, but not in the participants with BMI ≥ 22 kg/m2. Tsumura et al. 43 reported that moderate to high alcohol consumption reduced the risk of type 2 diabetes in the participants with BMI ≥ 22 kg/m2, but not in the participants with BMI < 22 kg/m2. Watanabe et al. 44 reported that alcohol consumption increased the risk of type 2 diabetes in the individuals with BMI < 22 kg/m2, but not in those with BMI ≥ 25 kg/m2. In summary, alcohol consumption might pose a risk of developing type 2 diabetes in the individuals with a BMI ≤ 22 kg/m2, but may not have an impact on those with ≥ 25 kg/m2. However, previous reports had serious limitations, including a small sample size, studies with short observation periods, no consideration of blood test data, and failure to consider the observation period in the analysis.
The present study included only Japanese people and showed results different from the association between alcohol consumption and the onset of type 2 diabetes in Western populations. There were several reasons for this observation. Even among obese individuals, the BMI of Japanese people tends to be lower than that of Western people. Therefore, the impact of alcohol consumption may differ between Japanese and Western populations. Ethanol, which is the main component of alcoholic beverages, decomposes into acetaldehyde. Aldehyde dehydrogenase 2 (ALDH2) is required for acetaldehyde decomposition. The ALDH2 allele appears to be most prevalent in Japanese, Chinese-American, Taiwanese, Han Chinese, Koreans, and many Japanese people who are unable to metabolize alcohol adequately compared to other racial groups, such as Western people 45. Differences in ethanol metabolism might be involved in the variations in the effects of alcohol consumption on the onset of diabetes. Moreover, a unique Japanese food culture has evolved, comprising Japanese cuisine and sake. In particular, ethyl-α-D-glucoside, which is present in sake, has been found to prevent product of interleukin 6 and liver injury 46. A previous study showed that the intake of sake lees extract improved insulin resistance via the improvement of hepatic inflammation in an animal model 47. Therefore, alcohol consumption, including sake, might have inhibited the development of type 2 diabetes in the Japanese participants with BMI ≥ 25 kg/m2.
In previous reports, it has been suggested that hypertension and dyslipidemia are implicated in the onset of type 2 diabetes 48. However, in the current study, hypertension and dyslipidemia were not included as covariates. This decision was made because we believe that alcohol consumption may also impact blood pressure and lipid levels, suggesting blood pressure and lipid levels could serve as intermediate factors in the onset of type 2 diabetes in our analyses.
The present study had certain limitations. First, it was an observational study. Consequently, unknown confounding factors may have existed. Second, the data on dietary intake were not considered. A previous study reported that significantly more food was consumed in the alcohol condition than that in the no-alcohol condition 49. Third, we were unable to sufficiently investigate the risk of type 2 diabetes associated with alcohol consumption exceeding 66 g/day. Fourth, this study did not consider the type of alcohol consumed, such as sake, beer, or wine. Fifth, previous report suggested that the ALDH2 was associated with glucose metabolism in non-obese non-diabetic Japanese 50. Unfortunately, however, we have no data about the ALDH2. Finally, this study included only Japanese middle-aged employees. Therefore, it is unclear whether our results are applicable to other ethnic groups or populations. However, excessive alcohol consumption should be avoided, and when consuming alcohol, responsible intake is recommended because excess alcohol consumption may induce alcoholic steatohepatitis, pancreatitis, dementia, cerebral hemorrhage, and mental disorders.
This large-scale and long-term study identified that light alcohol consumption might decrease the risk of developing type 2 diabetes in middle-aged Japanese people. Moderate-to-high alcohol consumption might increase the risk of developing type 2 diabetes in Japanese people with a BMI < 25 kg/m2. Alcohol consumption might prevent the development of type 2 diabetes in Japanese people with BMI ≥ 25 kg/m2.