Elevations in markers of liver injury and risk of type 2 diabetes - The insulin resistance atherosclerosis study
Elevations in markers of liver injury and risk of type 2 diabetes - The insulin resistance atherosclerosis study
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DOI：
10.2337/diabetes.53.10.2623
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发表时间：
2004-10-01
期刊：
影响因子：
7.7
通讯作者：
Haffner, SM
中科院分区：
文献类型：
--
作者：
Hanley, AJG;Williams, K;Haffner, SM
有限数量的研究报告了肝损伤标志物（包括天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）浓度升高）与2型糖尿病预期风险的相关性。然而，只有一项研究调整了胰岛素敏感性的详细测量（胰岛素敏感性指数[S-i]），考虑到肥胖和Si与非酒精性脂肪肝的相关性，这一点很重要。非酒精性脂肪肝（NAFLD）。我们的目的是调查906名胰岛素抵抗动脉粥样硬化研究中基线时无糖尿病的参与者中AST和ALT升高与2型糖尿病发病的关系。在40-69岁的黑人、西班牙裔和非西班牙裔白色受试者中，直接从频繁采样的静脉内葡萄糖耐量试验中测量S-i和急性胰岛素反应（AIR）。5.2年后，148人患上了2型糖尿病。基线AST和ALT与空腹胰岛素（分别为r = 0.22和r = 0.35）、腰围（r = 0.18和r = 0.34）和空腹血糖（r = 0.13和r = 0.29）呈正相关，与S-i呈负相关（r = -0.18和r = -0.30;均P < 0.0001）。在调整了年龄、性别、种族、临床中心和饮酒量的单独logistic回归模型中，AST和ALT最高四分位数（Q4）的参与者与最低三个四分位数（Q1-Q3）的参与者相比，2型糖尿病发病风险显著增加：AST：比值比（OR）1.73（95% CI 1.17-2.57）; ALT：OR 2.32（1.36-3.75）。在进一步调整吸烟、腰围、甘油三酯、HDL、糖耐量受损、S-i和AIR后，AST和ALT均与2型糖尿病发病率显著相关：AST，Q4 vs. Q1-Q3：OR 1.98（1.23-3.17）; ALT，Q4 vs. Q1-Q3：OR 2.00（1.22-3.28）。性别、种族、肥胖、糖耐量异常或Si与AST或ALT在预测2型糖尿病中没有相互作用。当进入相同的模型并调整人口统计学变量时，C-反应蛋白和ALT都能独立预测2型糖尿病。此外，在排除既往和中度至重度饮酒者后，AST和ALT与2型糖尿病发病呈正相关。总之，AST和ALT独立预测2型糖尿病。这些标志物的基线升高可能反映NAFLD或相关病理。
A limited number of studies have reported associations of markers of liver injury, including elevated concentrations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), with prospective risk of type 2 diabetes. However, only one study has adjusted for a detailed measure of insulin sensitivity (insulin sensitivity index [S-i]), which is important given associations of obesity and Si with nonalcoholic fatty liver. disease (NAFLD). Our objective was to investigate the associations of elevated AST and ALT with incident type 2 diabetes among 906 participants in the Insulin Resistance Atherosclerosis Study who were nondiabetic at baseline. S-i and acute insulin response (AIR) were measured directly from the frequently sampled intravenous glucose tolerance test among black, Hispanic, and non-Hispanic white participants aged 40-69 years. After 5.2 years, 148 individuals had developed type 2 diabetes. Baseline AST and ALT were positively correlated with fasting insulin (r = 0.22 and r = 0.35, respectively), waist circumference (r = 0.18 and r = 0.34), and fasting glucose (r = 0.13 and r = 0.29) and inversely with S-i (r = -0.18 and r = -0.30; all P < 0.0001). In separate logistic regression models adjusting for age, sex, ethnicity, clinical center, and alcohol consumption, participants in the highest quartiles (Q4) of AST and ALT were at significantly increased risk of incident type 2 diabetes compared with those in the lowest three quartiles (Q1-Q3): AST: odds ratio (OR) 1.73 (95% CI 1.17-2.57); ALT: OR 2.32 (1.36-3.75). After further adjustment for smoking, waist circumference, triglyceride, HDL, impaired glucose tolerance, S-i, and AIR, both AST and ALT remained significantly associated with incident type 2 diabetes: AST, Q4 vs. Q1-Q3: OR 1.98 (1.23-3.17); ALT, Q4 vs. Q1-Q3: OR 2.00 (1.22-3.28). There were no interactions of sex, ethnicity, obesity, impaired glucose tolerance, or Si with AST or ALT in the prediction of type 2 diabetes. When entered into the same model with adjustment for demographic variables, both C-reactive protein and ALT independently predicted type 2 diabetes. In addition, AST and ALT were positively associated with incident type 2 diabetes after excluding former and moderate to heavy drinkers. In conclusion, AST and ALT independently predict type 2 diabetes. Baseline elevations of these markers may reflect NAFLD or related pathologies.