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: 8.47). 10/2004; 53(10):2623-32. DOI: 10.2337/diabetes.53.10.2623
Source: PubMed

ABSTRACT 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.
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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.:
    Obesity Research & Clinical Practice 02/2014; 8(1):e1-e114. DOI:10.1016/j.orcp.2012.08.191 · 0.70 Impact Factor
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    • "In the late 1980s ALAT increase significantly predicted diabetes in Swedish men (Ohlson et al., 1988). Recently, the connection between ALAT and the risk of diabetes has been shown in Pima Indians (Sattar et al., 2004), and non- Hispanic blacks and whites in the United States (Hanley et al., 2004). Only one study, performed with Japanese subjects, reported no correlations between ALAT and the risk of diabetes (Nakanishi et al., 2004). "
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    ABSTRACT: Nonalcoholic fatty liver disease is commonly associated with obesity, insulin resistance, dyslipidemia and type 2 diabetes, and can thus be regarded as the hepatic manifestation of metabolic syndrome. In this study we compared the effects of lifestyle intervention with and without industrial berry products, on risk factors associated with metabolic syndrome on slightly overweight women. Sixty-one female volunteers (average age 42.9 years) were recruited and randomized for a 20-week dietary intervention trial with two parallel treatment groups, one lifestyle intervention group with berry products equaling with an average daily dose of 163 g of northern berries (berry group, diet 1, N=31, of which 28 completed the study) and the other group with lifestyle intervention only (control group, diet 2, N=30, of which 22 completed the study). Increased berry consumption as part of the normal daily diet was the only lifestyle difference between the two intervention groups. The major effects achieved by diet 1 were changes in the levels of alanine aminotransferase (ALAT) and adiponectin (at P-values <0.001 and 0.002, respectively). A statistically significant difference between the two intervention groups was the higher decrease in the ALAT value in the berry group (P=0.003). The 23% decrease in the ALAT value, from 20.29 to 15.66 U/l in the berry group may be regarded as nutritionally significant by enhancing the liver function. This may contribute positively to the low-grade systemic inflammation in body and decrease the risk of cardiovascular diseases.
    European journal of clinical nutrition 03/2010; 64(6):614-21. DOI:10.1038/ejcn.2010.27 · 2.95 Impact Factor
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