Flushing Response Modifies the Association of Alcohol Consumption with Markers of Glucose Metabolism in Japanese Men and Women

Kuwahara, Keisuke; Kochi, Takeshi; Nanri, Akiko; Tsuruoka, Hiroko; Kurotani, Kayo; Pham, Ngoc Minh; Akter, Shamima; Kabe, Isamu; Mizoue, Tetsuya

doi:10.1111/acer.12323

Cited by 7 publications

(3 citation statements)

References 42 publications

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“…Of note is that about 40% of the Eastern Asian populations carry the mutation phenotype [16]. Additionally, it is well known that acetaldehyde, rather than ethanol, is highly toxic, carcinogenic, and mutagenic, and has been determined as the cause of "Asian flush syndrome"unpleasant symptoms after alcohol intake with nausea, facial flushing, muscle weakness, tachycardia, palpitation, perspiration, headache, and sleepiness [17]. Furthermore, a recent review proposed that the differential ALDH2 expression may dedicate to a wide variety of human diseases, including cardiovascular diseases, diabetes, and cancers [18].…”

Section: Ivyspringmentioning

confidence: 99%

The Defective Allele of Aldehyde Dehydrogenase 2 Gene is Associated with Favorable Postoperative Prognosis in Hepatocellular Carcinoma

Huang¹,

Hu²,

Chien³

et al. 2019

J. Cancer

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Background: The Aldehyde dehydrogenase 2 (ALDH2) mutant genotypes contain an allele encoding defective ALDH2 with reduced efficacy of alcohol metabolism leading to accumulation of highly toxic and carcinogenic acetaldehyde. It can induce unpleasant "Asian flush syndrome" and associate with increased risk of cancers. However, to date, little is known about ALDH2 genotypes in relation to the postoperative prognosis of hepatocellular carcinoma (HCC). Methods: From 2002 to 2012, 419 HCC patients receiving surgical resection of HCC were enrolled for ALDH2-rs671 genotyping and outcome correlation. Results: Of the patients included, 202 were ALDH2-rs671 "GG" (wild type) and 217 were mutant (defective) "AA" + "GA" genotype. Kaplan-Meier analysis indicated that "GG" genotype significantly associated with shorter metastasis-free (P = 0.034) and overall (P = 0.005) survival, but not recurrence-free survival (P = 0.281). Univariate followed by multivariate Cox proportional hazard analysis showed that "GG" genotype was an independent clinical predictor for shorter time-to-distant metastasis (adjusted P = 0.019) and shorter overall survival (adjusted P = 0.001). Subgroup analysis showed that in patients with negative hepatitis B surface antigen, Edmonson's histology grade < 3, and aspartate transaminase > alanine transaminase, the ALDH2-rs671-GG genotype was associated with both shorter time-to-metastasis and shorter overall survival. Conclusions: HCC patients carrying a defective allele of ALDH2 had a favorable postoperative outcome.

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Section: Ivyspringmentioning

confidence: 99%

The Defective Allele of Aldehyde Dehydrogenase 2 Gene is Associated with Favorable Postoperative Prognosis in Hepatocellular Carcinoma

Huang¹,

Hu²,

Chien³

et al. 2019

J. Cancer

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“…However, the effect of alcohol on insulin also remains unclear. Several cross-sectional studies have reported a negative association of alcohol consumption with beta cell function but a positive association with insulin sensitivity [9, 10]. In a prospective study in Japan [11], the researchers concluded that alcohol was positively associated with the incidence of both impaired BC and IR but showed no significant effect on type 2 diabetes.…”

Section: Introductionmentioning

confidence: 99%

Alcohol consumption and its interaction with genetic variants are strongly associated with the risk of type 2 diabetes: a prospective cohort study

Wang

Zhang

et al. 2019

Nutr Metab (Lond)

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Background Both genetic and lifestyle factors contribute to the incidence of type 2 diabetes. It yet remains controversial whether and how alcohol consumption, one of the most prevalent lifestyle habits, influences type 2 diabetes. Moreover, whether alcohol consumption interacts with genetic risk is inconclusive. Thus, we aimed to explore the effects of alcohol, genetic risk and their potential interactions on type 2 diabetes risk. Methods The Shanghai Diabetes study (SHDS) had a total of 2546 participants with 611 incident cases of combined type 2 diabetes and impaired glucose regulation (IGR). We constructed weighted genetic risk score (GRS) for type 2 diabetes and categorized the GRS into three strata. And the homeostatic model assessment of β-cell function (HOMA-B) and insulin resistance (HOMA-IR) were calculated. Then we used logistic regression models and multiple linear regression models to examine the influence of both baseline alcohol consumption and genetic risk on blood glucose deterioration, insulin resistance (IR) and beta cell function (BC), respectively. Moreover, we investigated the interactions of alcohol intake with: (1) GRSs for type 2 diabetes, IR, BC, body mass index (BMI) and waist-to-hip ratio (WHR); and (2) each of the single nucleotide polymorphisms (SNPs) used to establish the GRSs mentioned above. Results Alcohol consumption and higher T2D-GRS both contributed to a higher incidence rate of blood glucose deterioration [odds ratio (OR), 2.24, 95% confidence interval (CI), 1.76–2.87; OR, 1.25, 95% CI, 1.11–1.42; respectively]. Alcohol reduced insulin sensitivity and compensated by enhancing beta cell function (β = 1.98, P < .0001 and β = − 1.97, P < .0001 for HOMA-IR and inverse HOMA-β, respectively). T2D-GRS deteriorated insulin secretion (β = 0.10, P = 0.0069 for inverse HOMA-B) but not insulin sensitivity (P = 0.0856). Moreover, there was a significant interaction between alcohol and T2D-GRS (Pinteraction = 0.0318), suggesting the association between alcohol and type 2 diabetes was much stronger in the lower T2D-GRS group than in the higher T2D-GRS group. And this interaction was more pronounced in men (Pinteraction = 0.0176) than in women (Pinteraction = 0.3285). No single SNP interacted strongly with alcohol intake. Conclusions/interpretation Alcohol consumption strongly increased the risk of type 2 diabetes by increasing IR, especially in men with low T2D-GRS, highlighting the importance of refraining from drinking alcohol when making recommendations for healthy lifestyle habits to prevent diabetes.

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“…23) According to another study, when drinking alcohol excessively, the flushers had higher HbA1c level than the non-drinkers, while the non-flushers had a decreased HbA1c level. 24) A difference in the process of glucose metabolism due to the alcoholinduced flushing response was observed possibly because during alcohol drinking, acetaldehyde is accumulated in the body, causing more oxidative stress reactions and hepatotoxicity. 25) Finally, obese flushers had a higher risk of pre-or T2DM, even when consuming little alcohol (over 4 drinks), than the non-flushers and non-drinkers.…”

Section: Discussionmentioning

confidence: 99%

Influence of Facial Flushing on Pre- or Type 2 Diabetes Risk according to Alcohol Consumption in Korean Male

Kim

et al. 2020

Korean J Fam Med

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Background: This study aims to examine the association between alcohol consumption and the risk of pre-or type 2 diabetes mellitus (T2DM) by alcohol-induced flushing response in Korean male adults, particularly based on their body mass index (BMI). Methods: This study selected 1,030 (158 non-drinkers, 364 flushers, and 508 non-flushers) male adults who had medical checkups. A logistic regression analysis was used to compare the association between alcohol consumption and the risk of pre-or T2DM. Results: In both the normal-weight group (BMI <23 kg/m 2 ) and the overweight group (BMI ≥23 kg/m 2 and <25 kg/ m 2 ), the flushers had a higher risk of pre-or T2DM (odds ratio, 95% confidence interval) when consuming more than 8 drinks of alcohol per week than the non-drinkers (normal-weight group: 3.43, 1.06-11.07; overweight group: 4.94, 1.56-15.67). But in the non-flushers among the normal-weight group and the overweight group, there was no significant difference compared to non-drinkers regarding the risk of pre-or T2DM. Obese flushers had a significantly higher risk of pre-or T2DM when consuming more than 4 drinks of alcohol per week than the non-drinkers (>4 and ≤8 drinks: 2.64, 1.10-6.36; >8 drinks: 2.42, 1.11-5.27). However, obese non-flushers had only a significant higher risk of pre-or T2DM when consuming more than 8 drinks of alcohol per week than the non-drinkers (2.72, 1.39-5.30) Conclusion: These results suggest that obese flushers have an increased risk of developing pre-or T2DM even with less alcohol consumption.

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Flushing Response Modifies the Association of Alcohol Consumption with Markers of Glucose Metabolism in Japanese Men and Women

Abstract: The results suggest that the alcohol flushing response may improve glucose metabolism and insulin resistance at moderate alcohol use levels in apparently healthy Japanese adults.

Cited by 7 publications

References 42 publications

The Defective Allele of Aldehyde Dehydrogenase 2 Gene is Associated with Favorable Postoperative Prognosis in Hepatocellular Carcinoma

The Defective Allele of Aldehyde Dehydrogenase 2 Gene is Associated with Favorable Postoperative Prognosis in Hepatocellular Carcinoma

Alcohol consumption and its interaction with genetic variants are strongly associated with the risk of type 2 diabetes: a prospective cohort study

Influence of Facial Flushing on Pre- or Type 2 Diabetes Risk according to Alcohol Consumption in Korean Male

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