Elevations in Markers of Liver Injury and Risk of Type 2 Diabetes The Insulin Resistance Atherosclerosis Study

University of Texas at San Antonio, San Antonio, Texas, United States
Diabetes (Impact Factor: 8.1). 10/2004; 53(10):2623-32. DOI: 10.2337/diabetes.53.10.2623
Source: PubMed


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 S(i) 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 S(i) 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.

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    • "The relationship between concentrations of liver enzymes and the incidence of type 2 diabetes has been investigated through several studies. Some studies showed a significant relationship between serum AST and diabetes (Hanley et al., 2004; Nannipieri et al., 2005). Other studies have investigated the relationship between AST and ALT and risk of type 2 diabetes, with varied results (Doi et al., 2007; Goessling et al., 2008; Jiamjarasrangsi et al., 2008; Monami et al., 2008; Sato, Hayashi, Nadamura, 2008). "
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    ABSTRACT: Liver plays a significant role in glucose homeostasis and acts to retain normal glucose levels during fasting and in the postprandial period. The association between liver function tests and incidence of diabetes is not well established. The present study was conducted to investigate the association between liver enzymes and diabetes, and to investigate the effects of the extract of U. pilulifera and metformin on liver enzymes. Study methodology included collection of U. pilulifera, preparation of its extract, induction of diabetic model through alloxan injection. Study findings showed a positive relationship between studied liver enzymes ALT, AST, and ALP and diabetes. Treating diabetic groups using either the extract of U. pilulifera or metformin showed protection potential for liver through restoring liver enzymes to levels approximate to control groups. Taken together, the extract of U. pilulifera mimics the action of metformin in treating diabetes through restoring liver function tests to levels approximate to control group.
    Full-text · Article · Aug 2014
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    • ", portal inflammation, portal fibrosis, and perisinusoidal fibrosis [30], abnormal lipid profile [7] [15] [29], cardiometabolic risk factors [21], MetS [15] [17] [18] [42], and of type 2 diabetes [13] [22] [27]. Due to the adverse health impact, ALT should be screened in overweight and obese Mexican children. "
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    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is emerging as a component of the metabolic syndrome (MetS); Hispanics being particularly predisposed. Alanine aminotransferase (ALT) is considered a marker of NAFLD. The aim of this study was to determine the prevalence and associations between ALT elevations and MetS in normal-weight, overweight and obese Mexican children and adolescents, since data in Mexico is scarce. Body mass index (BMI), waist circumference (WC), percentage body fat, blood pressure, glucose, lipid profiles, ALT and aspartate aminotransferase (AST) were measured in 236, 6–12yo normal-weight, overweight and obese Mexicans from eight public schools. The results showed that elevated ALT (>40 IU/L) was found in 17.7% of the obese and overweight population, with no gender difference. The prevalence of elevated ALT increased linearly across BMI categories (p = 0.001), from 0.0% for the normal-weight group (95%CI 0.0–8.0) to 22.4% for the obese one (95%CI 16.2–30.2). AST/ALT ratio <1 also increased linearly, as did the prevalence of MetS (p = 0.001), from 0.0% for the normal-weight group to 40.3% for the obese one. The prevalence of MetS was strongly associated with elevated ALT (p = 0.002), 50% in the elevated ALT group (95%CI 34.1–65.9) and 24.1% in the normal ALT one (95%CI 18.1–31.3). There was also a strong association between MetS and an AST/ALT ratio <1. WC was the best predictor of elevated ALT (AOR = 7.13). Pearson correlation showed that MetS components were significantly correlated with elevated ALT. Therefore elevated ALT levels were highly prevalent and strongly associated with MetS in Mexican children, it should be screened in overweight and obese children.:
    Full-text · Article · Feb 2014 · Obesity Research & Clinical Practice
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    • "A number of prospective studies have examined the associations between concentrations of AST [5-12], ALT [5-11,13,14], or GGT [3,4,6-11,14-21] and the incidence of type 2 diabetes. A few studies have examined the association of serum AST with risk for type 2 diabetes; two of these reported a significant association between serum AST and diabetes after adjustment for potential confounders [5,9]. "
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    ABSTRACT: We examined the association between liver enzymes and development of type 2 diabetes in a general Korean population. A total of 10,667 subjects (4,201 males and 6,466 females) aged 45 to 74 years participated in a baseline examination between 2004 and 2007. Among the subjects, 8,157 (3,231 males and 4,926 females) underwent follow-up examination from 2007 to 2011, for a median follow-up period of 4.2 years. Type 2 diabetes was defined as intake of anti-diabetic agents, insulin treatment, fasting glucose concentration of more than 126 mg/dl, or hemoglobin A1c of more than 6.5% at re-examination. Associations of liver enzymes with incidence of type 2 diabetes were analyzed using logistic regression models. During the follow-up period, 548 subjects (235 males, 313 females) developed type 2 diabetes. After adjusting for comprehensive diabetes risk factor, the risk of type 2 diabetes was significantly higher in the highest alanine aminotransferase (ALT) quartile than in the lowest quartile (odds ratio (OR): 1.95, 95% confidence interval (CI): 1.18-3.21 in males; OR: 1.49, 95% CI: 1.03-2.16 in females). Similar results were observed for gamma-glutamyltransferase (GGT) quartiles, but in the fully adjusted analysis, the OR for the highest versus lowest quartiles was significant only for females (OR: 1.58, 95% CI: 0.95-2.63 in males; OR: 1.85, 95% CI: 1.23-2.79 in females). Our results suggest that serum ALT concentrations were independently associated with type 2 diabetes in both sexes, and that GGT was also independently associated but only in females.
    Full-text · Article · Feb 2014 · Diabetology and Metabolic Syndrome
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