Despite the incidence of diabetes is increasing worldwide and its prevalence is higher in developing countries, no studies have examined the relationship between elevated liver enzymes and T2D risk in Yemeni patients. Our study, therefore, was focused on the liver as the vital organ contributing to glucose homeostasis during fasting and postprandial stage. Serum ALT, AST, and GGT were taken from each participant and used for this work. Additionally, most people aged ≥45 years in developing countries suffer from diabetes . These findings were convenient with our study showed that T2D patients had significantly higher mean age compared to healthy control subjects (Table 1).
Besides, our present findings also observed significantly increased BMI, systolic BP, and diastolic BP in T2D patients than healthy control subjects. Besides, the present study also showed that serum FBG, total cholesterol, and LDL-C were significantly higher in T2D patients than healthy control subjects, while, no significant difference was found among both groups for serum triglyceride. In contrast, HDL-C was significantly lower in T2D patients. Our study further revealed higher levels of GGT in T2D patients. While AST was significantly lower in T2D patients. Besides, no significant difference was found among both groups for ALT. Such a positive relationship between liver enzymes and blood lipids profile in T2D patients has been observed in previous studies  20]   .
This finding supports the role of hepatic insulin resistance in the pathogenesis of NAFLD in patients with T2D  . Moreover, Cho et al. reported a correlation between ALT activity and increased fatty liver . The impairment of the normal process of synthesis and elimination of triglycerides may progress to fibrosis, cirrhosis, and hepatocellular carcinoma  .
In addition to its effect on lipid metabolism, insulin also contributes a proinflammatory effect to liver abrasion . Thus, inflammation contributes to IR. Pro-inflammatory cytokines and transcription factors are highly expressed in white adipose tissue and liver. Obesity, which is a state of chronic low-grade inflammation and a risk factor for IR and NAFLD, is induced by the overnutrition and is a primary cause of decreased insulin sensitivity. Obesity leads to lipid accumulation and activates the c-Jun N-terminal kinase (JNK) and nuclear factor-kappa B (NF-κB) signaling pathways, which consequently increase the production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) . Besides, various adipose tissue-derived proteins, such as adiponectin and leptin, are considered to be major links between obesity, IR, and related inflammatory disorders .
GGT is known as a marker of hepatobiliary disorders and is associated with other pathological conditions like diabetes. Free radicals generated by diabetes consume glutathione which induces the increased expression of GGT in hepatocytes. Various studies have suggested the association of GGT concentrations with T2D    , and hyperlipidemia . These findings are in agreement with our study; GGT was significantly associated with the hyperglycemic and hyperlipidemic profile. We observed ALT and GGT together were positively correlated. Moreover, some data also reported elevated GGT levels with ALT in T2D patients with dyslipidemia   . Although we did not confirm the presence of fatty liver by ultrasound techniques, we showed the relationship of ALT, AST, and GGT with the predictors of diabetes and lipid profile parameters, presenting hepatocellular injury.
A study of male Korean workers found that AST was independently associated with diabetes , while in a study of male Japanese office workers AST was not associated with T2D risk . Some studies also reported that ALT is a significant predictor of diabetes while AST is not . These findings are in agreement with our findings as AST does not show considerable relationship with the studied parameters. Besides, Clark et al. also suggested that mild or chronic elevations of these aminotransferases may be due to NAFLD  .
The strength of the present study included adjustment for well-established diabetes risk factors including BMI, blood lipids, and hypertension. However, there are some limitations. First, our sample size may be small and thus underpowered to detect the interaction with ALT and GGT. Second, we measured liver enzymes only once and may not represent a long-term profile. Third, we did not measure hepatitis B and C infection, which could result in elevated liver enzymes. Fourth, we did not measure insulin, CRP, leptin, and, adiponectin as the predictive biomarkers links between obesity, hepatic IR, and related inflammatory disorders in T2D patients. Thus, a further large sample size with measurement of insulin, CRP, leptin, adiponectin, and interleukins are required to confirm these correlations. We conclude that higher levels of ALT and GGT are used as the predictive biomarkers for NAFLD in T2D patients with hyperlipidemia.