ALDH2 rs671 Is Associated With Elevated FPG, Reduced Glucose Clearance and Hepatic Insulin Resistance in Japanese Men.

Autor:	Kageumi Takeno, Yoshifumi Tamura, Saori Kakehi, Hideyoshi Kaga, Ryuzo Kawamori, Hirotaka Watada, Takeno, Kageumi, Tamura, Yoshifumi, Kakehi, Saori, Kaga, Hideyoshi, Kawamori, Ryuzo, Watada, Hirotaka
Předmět:	JAPANESE people GLUCOSE INSULIN resistance HIGH density lipoproteins INSULIN sensitivity HDL cholesterol ASPARTATE aminotransferase BLOOD pressure RESEARCH GLUCOSE clamp technique SEQUENCE analysis SKELETAL muscle LIVER RESEARCH methodology BLOOD sugar NUCLEAR magnetic resonance spectroscopy GENETIC disorders MAGNETIC resonance imaging MEDICAL cooperation EVALUATION research COMPARATIVE studies ALCOHOL drinking GENOTYPES RESEARCH funding LIPID metabolism disorders LONGITUDINAL method ADIPOSE tissues
Zdroj:	Journal of Clinical Endocrinology & Metabolism; Sep2021, Vol. 106 Issue 9, pe3573-e3581, 9p
Abstrakt:	Context: A recent meta-analysis of genome-wide association studies data from East Asians identified aldehyde dehydrogenase 2 (ALDH2) rs671 as a susceptibility variant for type 2 diabetes in males.Objective: To investigate the association between ALDH2 rs671 and metabolic characteristics.Methods: We studied 94 nonobese, nondiabetic, Japanese men. Using a 2-step hyperinsulinemic-euglycemic clamp, we evaluated insulin sensitivity in muscle and liver. Intrahepatic lipid and fat distribution were measured using 1H-magnetic resonance spectroscopy and magnetic resonance imaging, respectively. We divided participants into a risk-carrying group with ALDH2 rs671 G/G (n = 53) and a nonrisk-carrying group with ALDH2 rs671 G/A or A/A (n = 41).Results: The risk-carrying group had significantly higher levels of alcohol consumption (18.4 [interquartile range, IQR, 10.4-48.9]) vs 12.1 (IQR, 1.3-29.0) g/day; P = .003), elevated fasting plasma glucose (FPG) (97.5 ± 7.9 vs 93.5 ± 6.2 mg/dL; P = .010), lower hepatic insulin sensitivity (61.7 ± 20.5% vs 73.1 ± 15.9%; P = .003), and lower fasting glucose clearance (0.84 ± 0.8 dL·m-2·min-1 vs 0.87 ± 0.09 dL·m-2·min-1; P = .047) than the nonrisk-carrying group, while insulin resistance in muscle and body fat distribution were similar. The single linear correlation analysis revealed significant correlations between alcohol consumption and hepatic insulin sensitivity (r = -0.262, P = .011), fasting glucose clearance (r = -0.370, P < .001), or FPG (r = 0.489, P < .001). The multiple regression analysis revealed that both ALDH2 rs671 G/G genotype and alcohol consumption were significant independent correlates for hepatic insulin sensitivity, whereas only alcohol consumption was a significant independent correlate for fasting glucose clearance.Conclusion: Our data suggest that high-alcohol intake-dependent and independent hepatic insulin resistance and reduced fasting glucose clearance due to high alcohol intake could be a relatively upstream metabolic abnormality in ALDH2 rs671 G/G carriers. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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