Research Article Details

Article ID: A23677
PMID: 23569998
Source: Asian Pac J Trop Biomed
Title: Elevated alanine aminotransferase activity is not associated with dyslipidemias, but related to insulin resistance and higher disease grades in non-diabetic non-alcoholic fatty liver disease.
Abstract: OBJECTIVE: To explore demographic and metabolic factors associated with increased alanine aminotransferase (ALT) activity in non-diabetic non-alcoholic fatty liver disease (NAFLD) patients. METHODS: Overall 372 patients who consecutively attended to Gastroenterology Clinic of Baqiyatallah University of Medical Sciences, Tehran, Iran awere diagnosed as NAFLD entered into analysis. Exclusion criteria were having diabetes mellitus and fasting blood glucose over 126 mg/dL, active hepatitis B virus infection, having hepatitis C virus positive serology, and to be under corticosteroid therapy. ALT levels were considered pathologically high when it was over 30 IU/L for men and over 19 IU/L for women. RESULTS: Bivariate analyses using t test and chi-square test showed that patients with pathologically augmented ALT levels had significantly higher NAFLD grades in their ultrasonographic evaluations (P=0.003). Moreover, these patients represented significantly higher homeostatic model assessment levels (P=0.003), levels of serum insulin (P=0.002), fasting blood glucose (P<0.001), and uric acid (P=0.02). The prevalence of insulin resistance was also higher in patients with increased serum ALT concentrations. Multifactorial logistic regression models showed that ultrasonographic grading of NAFLD (P=0.027) and insulin resistance (P=0.013) were the only variables significantly associated with abnormal ALT levels. CONCLUSIONS: This study shows that the associations of increased ALT serum levels in NAFLD patients are different from what are supposed before. By excluding diabetic patients from our population, we find that increased ALT levels are not associated with dyslipidemias but are independently associated with insulin resistance and NAFLD grading on ultrasonographic evaluations. Further studies are needed to confirm our results.
DOI: 10.1016/S2221-1691(12)60213-5

Strategy ID Therapy Strategy Synonyms Therapy Targets Therapy Drugs
S01 Improve insulin resistance insulin sensitizer; insulin resistance; glucose tolerance Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide Details

Target ID Target Name GENE Action Class UniProtKB ID Entry Name
T20 Fatty acid synthase FASN inhibitor Enzyme P49327 FAS_HUMAN Details

Diseases ID DO ID Disease Name Definition Class
I13 3146 Lipid metabolism disorder An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism disease of metabolism/ inherited metabolic disorder Details
I05 9352 Type 2 diabetes mellitus A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus Details

Drug ID Drug Name Type DrugBank ID Targets Category Latest Progress
D328 Serine Chemical drug DB00133 SRR Improve insulin resistance Under clinical trials Details
D316 S-adenosyl-L-methionine Chemical drug DB00118 GNMT cofactor Antiviral Under clinical trials Details
D182 Insulin Biological drug DB00030 INSR agonist; CPE modulator&product of -- Under clinical trials Details
D199 L-alanine Chemical drug DB00160 KYNU -- Failed in clinical trials Details