Association of genetically determined aldehyde dehydrogenase 2 activity with diabetic complications in relation to alcohol consumption in Japanese patients with type 2 diabetes mellitus: The fukuoka diabetes registry

Yasuhiro Idewaki, Masanori Iwase, Hiroki Fujii, Toshiaki Ohkuma, Hitoshi Ide, Shinako Kaizu, Tamaki Jodai, Yohei Kikuchi, Atsushi Hirano, Udai Nakamura, Michiaki Kubo, Takanari Kitazono

Research output: Contribution to journalArticle

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Abstract

Aldehyde dehydrogenase 2 (ALDH2) detoxifies aldehyde produced during ethanol metabolism and oxidative stress. A genetic defect in this enzyme is common in East Asians and determines alcohol consumption behaviors. We investigated the impact of genetically determined ALDH2 activity on diabetic microvascular and macrovascular complications in relation to drinking habits in Japanese patients with type 2 diabetes mellitus. An ALDH2 singlenucleotide polymorphism (rs671) was genotyped in 4,400 patients. Additionally, the relationship of clinical characteristics with ALDH2 activity (ALDH2 1/1 active enzyme activity vs. 1/2 or 2/2 inactive enzyme activity) and drinking habits (lifetime abstainers vs. former or current drinkers) was investigated cross-sectionally (n = 691 in 1/1 abstainers, n = 1,315 in abstainers with 2, n = 1,711 in 1/1 drinkers, n = 683 in drinkers with 2). The multiple logistic regression analysis for diabetic complications was adjusted for age, sex, current smoking habits, leisure-time physical activity, depressive symptoms, diabetes duration, body mass index, hemoglobin A1c, insulin use, high-density lipoprotein cholesterol, systolic blood pressure and renin-angiotensin system inhibitors use. Albuminuria prevalence was significantly lower in the drinkers with 2 than that of other groups (odds ratio [95% confidence interval (CI)]: 1/1 abstainers as the referent, 0.94 [0.76-1.16] in abstainers with 2, 1.00 [0.80-1.26] in 1/1 drinkers, 0.71 [0.54-0.93] in drinkers with 2). Retinal photocoagulation prevalence was also lower in drinkers with ALDH2 2 than that of other groups. In contrast, myocardial infarction was significantly increased in ALDH2 2 carriers compared with that in ALDH2 1/1 abstainers (odds ratio [95% CI]: 1/1 abstainers as the referent, 2.63 [1.28-6.13] in abstainers with 2, 1.89 [0.89-4.51] in 1/1 drinkers, 2.35 [1.06-5.79] in drinkers with 2). In summary, patients with type 2 diabetes and ALDH2 2 displayed a lower microvascular complication prevalence associated with alcohol consumption but a higher macrovascular complication prevalence irrespective of alcohol consumption.

Original languageEnglish
Article numbere0143288
JournalPLoS One
Volume10
Issue number11
DOIs
Publication statusPublished - 01-11-2015
Externally publishedYes

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aldehyde dehydrogenase
Aldehyde Dehydrogenase
Diabetes Complications
Medical problems
noninsulin-dependent diabetes mellitus
Alcohol Drinking
Type 2 Diabetes Mellitus
diabetes
Registries
Alcohols
Habits
Drinking
Enzyme activity
Enzymes
drinking
Odds Ratio
odds ratio
Confidence Intervals
Blood Pressure
confidence interval

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Idewaki, Yasuhiro ; Iwase, Masanori ; Fujii, Hiroki ; Ohkuma, Toshiaki ; Ide, Hitoshi ; Kaizu, Shinako ; Jodai, Tamaki ; Kikuchi, Yohei ; Hirano, Atsushi ; Nakamura, Udai ; Kubo, Michiaki ; Kitazono, Takanari. / Association of genetically determined aldehyde dehydrogenase 2 activity with diabetic complications in relation to alcohol consumption in Japanese patients with type 2 diabetes mellitus : The fukuoka diabetes registry. In: PLoS One. 2015 ; Vol. 10, No. 11.
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abstract = "Aldehyde dehydrogenase 2 (ALDH2) detoxifies aldehyde produced during ethanol metabolism and oxidative stress. A genetic defect in this enzyme is common in East Asians and determines alcohol consumption behaviors. We investigated the impact of genetically determined ALDH2 activity on diabetic microvascular and macrovascular complications in relation to drinking habits in Japanese patients with type 2 diabetes mellitus. An ALDH2 singlenucleotide polymorphism (rs671) was genotyped in 4,400 patients. Additionally, the relationship of clinical characteristics with ALDH2 activity (ALDH2 ∗1/∗1 active enzyme activity vs. ∗1/∗2 or ∗2/∗2 inactive enzyme activity) and drinking habits (lifetime abstainers vs. former or current drinkers) was investigated cross-sectionally (n = 691 in ∗1/∗1 abstainers, n = 1,315 in abstainers with ∗2, n = 1,711 in ∗1/∗1 drinkers, n = 683 in drinkers with ∗2). The multiple logistic regression analysis for diabetic complications was adjusted for age, sex, current smoking habits, leisure-time physical activity, depressive symptoms, diabetes duration, body mass index, hemoglobin A1c, insulin use, high-density lipoprotein cholesterol, systolic blood pressure and renin-angiotensin system inhibitors use. Albuminuria prevalence was significantly lower in the drinkers with ∗2 than that of other groups (odds ratio [95{\%} confidence interval (CI)]: ∗1/∗1 abstainers as the referent, 0.94 [0.76-1.16] in abstainers with ∗2, 1.00 [0.80-1.26] in ∗1/∗1 drinkers, 0.71 [0.54-0.93] in drinkers with ∗2). Retinal photocoagulation prevalence was also lower in drinkers with ALDH2 ∗2 than that of other groups. In contrast, myocardial infarction was significantly increased in ALDH2 ∗2 carriers compared with that in ALDH2 ∗1/∗1 abstainers (odds ratio [95{\%} CI]: ∗1/∗1 abstainers as the referent, 2.63 [1.28-6.13] in abstainers with ∗2, 1.89 [0.89-4.51] in ∗1/∗1 drinkers, 2.35 [1.06-5.79] in drinkers with ∗2). In summary, patients with type 2 diabetes and ALDH2 ∗2 displayed a lower microvascular complication prevalence associated with alcohol consumption but a higher macrovascular complication prevalence irrespective of alcohol consumption.",
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Association of genetically determined aldehyde dehydrogenase 2 activity with diabetic complications in relation to alcohol consumption in Japanese patients with type 2 diabetes mellitus : The fukuoka diabetes registry. / Idewaki, Yasuhiro; Iwase, Masanori; Fujii, Hiroki; Ohkuma, Toshiaki; Ide, Hitoshi; Kaizu, Shinako; Jodai, Tamaki; Kikuchi, Yohei; Hirano, Atsushi; Nakamura, Udai; Kubo, Michiaki; Kitazono, Takanari.

In: PLoS One, Vol. 10, No. 11, e0143288, 01.11.2015.

Research output: Contribution to journalArticle

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T1 - Association of genetically determined aldehyde dehydrogenase 2 activity with diabetic complications in relation to alcohol consumption in Japanese patients with type 2 diabetes mellitus

T2 - The fukuoka diabetes registry

AU - Idewaki, Yasuhiro

AU - Iwase, Masanori

AU - Fujii, Hiroki

AU - Ohkuma, Toshiaki

AU - Ide, Hitoshi

AU - Kaizu, Shinako

AU - Jodai, Tamaki

AU - Kikuchi, Yohei

AU - Hirano, Atsushi

AU - Nakamura, Udai

AU - Kubo, Michiaki

AU - Kitazono, Takanari

PY - 2015/11/1

Y1 - 2015/11/1

N2 - Aldehyde dehydrogenase 2 (ALDH2) detoxifies aldehyde produced during ethanol metabolism and oxidative stress. A genetic defect in this enzyme is common in East Asians and determines alcohol consumption behaviors. We investigated the impact of genetically determined ALDH2 activity on diabetic microvascular and macrovascular complications in relation to drinking habits in Japanese patients with type 2 diabetes mellitus. An ALDH2 singlenucleotide polymorphism (rs671) was genotyped in 4,400 patients. Additionally, the relationship of clinical characteristics with ALDH2 activity (ALDH2 ∗1/∗1 active enzyme activity vs. ∗1/∗2 or ∗2/∗2 inactive enzyme activity) and drinking habits (lifetime abstainers vs. former or current drinkers) was investigated cross-sectionally (n = 691 in ∗1/∗1 abstainers, n = 1,315 in abstainers with ∗2, n = 1,711 in ∗1/∗1 drinkers, n = 683 in drinkers with ∗2). The multiple logistic regression analysis for diabetic complications was adjusted for age, sex, current smoking habits, leisure-time physical activity, depressive symptoms, diabetes duration, body mass index, hemoglobin A1c, insulin use, high-density lipoprotein cholesterol, systolic blood pressure and renin-angiotensin system inhibitors use. Albuminuria prevalence was significantly lower in the drinkers with ∗2 than that of other groups (odds ratio [95% confidence interval (CI)]: ∗1/∗1 abstainers as the referent, 0.94 [0.76-1.16] in abstainers with ∗2, 1.00 [0.80-1.26] in ∗1/∗1 drinkers, 0.71 [0.54-0.93] in drinkers with ∗2). Retinal photocoagulation prevalence was also lower in drinkers with ALDH2 ∗2 than that of other groups. In contrast, myocardial infarction was significantly increased in ALDH2 ∗2 carriers compared with that in ALDH2 ∗1/∗1 abstainers (odds ratio [95% CI]: ∗1/∗1 abstainers as the referent, 2.63 [1.28-6.13] in abstainers with ∗2, 1.89 [0.89-4.51] in ∗1/∗1 drinkers, 2.35 [1.06-5.79] in drinkers with ∗2). In summary, patients with type 2 diabetes and ALDH2 ∗2 displayed a lower microvascular complication prevalence associated with alcohol consumption but a higher macrovascular complication prevalence irrespective of alcohol consumption.

AB - Aldehyde dehydrogenase 2 (ALDH2) detoxifies aldehyde produced during ethanol metabolism and oxidative stress. A genetic defect in this enzyme is common in East Asians and determines alcohol consumption behaviors. We investigated the impact of genetically determined ALDH2 activity on diabetic microvascular and macrovascular complications in relation to drinking habits in Japanese patients with type 2 diabetes mellitus. An ALDH2 singlenucleotide polymorphism (rs671) was genotyped in 4,400 patients. Additionally, the relationship of clinical characteristics with ALDH2 activity (ALDH2 ∗1/∗1 active enzyme activity vs. ∗1/∗2 or ∗2/∗2 inactive enzyme activity) and drinking habits (lifetime abstainers vs. former or current drinkers) was investigated cross-sectionally (n = 691 in ∗1/∗1 abstainers, n = 1,315 in abstainers with ∗2, n = 1,711 in ∗1/∗1 drinkers, n = 683 in drinkers with ∗2). The multiple logistic regression analysis for diabetic complications was adjusted for age, sex, current smoking habits, leisure-time physical activity, depressive symptoms, diabetes duration, body mass index, hemoglobin A1c, insulin use, high-density lipoprotein cholesterol, systolic blood pressure and renin-angiotensin system inhibitors use. Albuminuria prevalence was significantly lower in the drinkers with ∗2 than that of other groups (odds ratio [95% confidence interval (CI)]: ∗1/∗1 abstainers as the referent, 0.94 [0.76-1.16] in abstainers with ∗2, 1.00 [0.80-1.26] in ∗1/∗1 drinkers, 0.71 [0.54-0.93] in drinkers with ∗2). Retinal photocoagulation prevalence was also lower in drinkers with ALDH2 ∗2 than that of other groups. In contrast, myocardial infarction was significantly increased in ALDH2 ∗2 carriers compared with that in ALDH2 ∗1/∗1 abstainers (odds ratio [95% CI]: ∗1/∗1 abstainers as the referent, 2.63 [1.28-6.13] in abstainers with ∗2, 1.89 [0.89-4.51] in ∗1/∗1 drinkers, 2.35 [1.06-5.79] in drinkers with ∗2). In summary, patients with type 2 diabetes and ALDH2 ∗2 displayed a lower microvascular complication prevalence associated with alcohol consumption but a higher macrovascular complication prevalence irrespective of alcohol consumption.

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