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

ArticleinDiabetes 53(10):2623-32 · October 2004with18 Reads
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.
    • "The liver toxicity markers are altered in diabetic condition (Elizabeth & Harris, 2005). This is due to the leakage of these enzymes from the liver to the blood stream, which indicated the hepatotoxic effect of streptozotocin in diabetic group (Hanley et al., 2004). In our study, serum toxicity markers like AST, ALT, ACP and ALP were significantly increased in diabetic rats when compared to normal. "
    [Show abstract] [Hide abstract] ABSTRACT: Hibiscus rosa sinensis L. petals have an impressive range of medicinal uses and are edible with high nutritional value. In the present study, the anti-diabetic potential of Hibiscus was evaluated. HPLC-DAD and LCMS analyses of ethyl acetate fraction of Hibiscus (EHRS) revealed the presence of eight potent phytochemicals. Anti-diabetic effect was evaluated by the intra-gastric administration of EHRS at the dose of 25 mg/kg body weight in streptozotocin-induced experimental diabetic rats and compared with metformin. Streptozotocin-induced alterations of blood glucose, glycated haemoglobin, toxicity markers and antioxidant defence system were normalised by EHRS administration. EHRS significantly modulated the expressions of marker genes involved in diabetic stress signalling pathway, such as NF-κB, P38MAPK, AKT, PI3K and Nrf2. The histopathological studies of liver reinforce our findings. The overall effect was comparable with metformin. The study reveals the efficacy of Hibiscus as a potent source of phytochemicals in ameliorating diabetic complications.
    Full-text · Article · Jan 2016
    • "Series of experimental investigations have shown that hyperglycemia-induced-oxidative stress via free radical generation and oxidative damage to cells plays a major role in these diabetic complications [1, 3] . Previous scientific investigations have shown associations between concentrations of hepatic function enzymes such as aspartate amino transferase (AST), alanine amino transferase (ALT), and the incidence of diabetes456. Wannamethee et al. [7] also suggested that elevated levels of hepatic enzymes could cause insulin resistance and other features of diabetic syndrome. "
    [Show abstract] [Hide abstract] ABSTRACT: The effects of fibre-enriched biscuit on biomarkers associated with hepatotoxicity in diabetic rats were investigated. Diabetes was induced by single intraperitoneal injection of alloxan monohydrate. Treatment lasted for 14 days after which the rats were sacrificed by cervical dislocation. Blood serum was analyzed to determine hepatic function enzymes. The liver was also analyzed to determine hepatic lipid profile and antioxidant enzymes. Induction of diabetes led to elevated levels of ALP, AST, and ALT. These were, however, significantly ( p < 0.05 ) reduced in the fibre-enriched biscuit fed (treated) group. There was no significant difference in the serum bilirubin and total protein levels of the studied groups. Reduced albumin level was observed in the diabetic group; this was further lowered on feeding with fibre-enriched biscuits. Induction of diabetes led to increased hepatic level of cholesterol, triglyceride (TG), low density lipoprotein (LDL), and lipid peroxidation and decreased activities of glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) and HDL level. These were significantly ( p < 0.05 ) reversed on feeding with fibre-enriched biscuit. This study portrays the protective effect of fibre-enriched biscuit on increased oxidative stress and hyperlipidemia in hepatic tissues of alloxan-induced diabetic rats.
    Full-text · Article · Nov 2015
    • "Studies also indicated that elevated activities of these enzymes are associated with metabolic syndrome and precedes the clinical manifestations of other metabolic derangements [11,12]. Several studies indicated that alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) are independent predictors of NAFLD [11,13]. An increased level of ALT – a glucogenic enzyme synthesized in liver demonstrates to be an indicator of impaired insulin signaling and develops hepatic IR [14]. "
    [Show abstract] [Hide abstract] ABSTRACT: Aims: Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidity and is frequently associated with insulin resistance (HOMA-IR) syndrome. Recently serum gamma glutamyl transferase (GGT) has been considered as surrogate marker of NAFLD leading to oxidative stress and hepatocellular damage. In the present study we examined the association of serum GGT and HOMA-IR with NAFLD in Bangladeshi adult subjects. Materials and methods: Under a cross-sectional analytical design a total of 110 subjects were recruited who came for their routine health check up in the BIHS Hospital, Darussalam, Dhaka, Bangladesh. After whole abdomen ultrasonography, 62 were diagnosed as non-NAFLD and 48 were NAFLD subjects. Serum glucose was measured by glucose-oxidase method, lipid profile and liver enzymes by enzymatic colorimetric method, glycosylated hemoglobin (HbA1c) was measured by high performance liquid chromatography (HPLC), serum insulin were measured by enzyme-linked immunosorbent assay. HOMA-IR was calculated by homeostasis model assessment (HOMA). Results: NAFLD subjects had significantly higher levels of GGT and HOMA-IR as compared to their non-NAFLD counterparts. Multiple linear regression analysis showed a significant positive association of HOMA-IR with GGT after adjusting the effects of waist circumference (WC) and HbA1c. In binary logistic regression analysis, HOMA-IR and GGT were found to be significant determinants of NAFLD after adjusting the effects of WC and HbA1c. CONCLUSION: These results suggest that elevated levels of GGT and insulin resistance are more likely to develop NAFLD and thus support a role of these determinants in the pathogenesis of NAFLD in Bangladeshi adult subjects.
    Full-text · Article · Oct 2015
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