In the present study, we examined whether liver markers (e.g., GGT, ALT, AST, and ALT/AST ratio) as well as gender, age, BMI, smoking status, alcohol consumption, SBP, lipid profiles, uric acid, and serum HMW adiponectin were associated with insulin resistance in Japanese adults, categorized by body mass index. Most fundamental is the fact that not all overweight or obese persons are insulin resistant. In non-obese subjects, 6.2% of them were insulin resistant, and the best marker of insulin resistance was ALT/AST ratio, but serum HMW adiponectin, ALT, and hsCRP also discriminated insulin resistance. In the overweight subjects, areas of the ALT/AST ratio and ALT were greater than those of the other parameters. The optimal cut-off point to identifying insulin resistance for these markers yielded the following values: ALT/AST ratio of ≥0.82 in the non-obese, and ≥1.02 in the overweight subjects. The positive likelihood ratio was greatest for ALT/AST ratio in the non-obese subjects. ALT/AST ratio, an inexpensive and routinely measured clinical variable, might be used as an integrated parameter and measure to evaluate insulin resistance in community-dwelling persons, especially non-obese subjects.
Insulin resistance is common and when clustered with glucose intolerance, dyslipidemia and high blood pressure, and present in type 2 diabetes it play a key role in the occurrence of hyperglycemia. Resistance to insulin-mediated glucose disposal is distributed continuously through the general population , and we have no criterion with which to identify a participant as being insulin resistance. However, we classified a participant with a HOMA-IR of >2.5 as insulin resistance . Some previous studies have demonstrated that HOMA-IR strongly correlates with glucose clamp–assessed insulin resistance [5, 20] and has the advantage of requiring only a single plasma sample assayed for insulin and glucose. However, HOMA-IR is less accurate and precise than the glucose clamp method in measuring insulin resistance, but this limitation is now mitigated, because the HOMA model has become a widely used clinical and epidemiological tool, as in our study [22, 23]. Thus, we used HOMA-IR as a marker of insulin resistance in this study.
In previous studies, several lipid ratios have been proposed as simple and useful clinical indicators of insulin resistance. The TG/HDL-C, the T-C/HDL-C, and the LDL-C/HDL-C ratio have shown similar potential for insulin resistance, though the reports are not entirely consistent [24–27]. Also in our study, both LDL-C/HDL-C and TG/HDL-C ratio were useful markers of insulin resistance, especially in all subjects or non-obese subjects. However, these markers were weaker in overweight subjects . ALT/AST ratio as well as LDL-C/HDL-C and the TG/HDL-C ratio were also strongly related to insulin resistance. Several studies have reported a significant association of ALT with HOMA-IR [15, 29, 30]. Moreover, Hanley et al. [30, 31] reported that ALT/AST ratio predicts metabolic syndrome independently of potential confounding variables, including directly measured insulin sensitivity and acute insulin response. ALT/AST ratio that includes information on at least two measures might have a more integrated explanation than single measures such as ALT or TG.
There are a number of possible mechanisms that can explain the association between the ALT/AST ratio and insulin resistance. Fat accumulation in the liver is characterized by several features of insulin resistance in normal weight and moderately overweight subjects, independent of BMI and intra-abdominal and overall obesity . Increased liver fat content, a disorder that has detrimental effects on components of the metabolic syndrome, is known to be significantly correlated with these markers . Nanji et al.  reported a significant correlation between ALT/AST ratio and the degree of fatty infiltration of the liver. Moreover, non-alcoholic fatty liver disease (NAFLD), which has recently been proposed as a feature of the metabolic syndrome , was also characterized by chronic elevations in liver transaminase levels, including ALT, AST, and GGT [36, 37]. ALT/AST ratio and ALT per se along with the cut-off points might be reflecting NAFLD, but in this study, we have not evaluated ultrasound liver findings. Although, this study is of interest because liver transaminase markers, which are inexpensive and routinely collected in clinical settings, may provide a simple and accurate enhancement to models currently used to identify subjects with insulin resistance.
Some limitations of this study must be considered. First, the cross-sectional study design is limited in its ability to eliminate causal relationships between ALT/AST ratio and HOMA-IR. Second, our definition of HOMA-IR is based on a single assessment of FBS and IRI, which may introduce misclassification bias, although common to most epidemiological studies. However, random errors due to the fluctuations of laboratory measurements usually lead to a reduced estimate of the associated strength. Third, our study participants might include patients with subclinical liver diseases (i.e., chronic viral hepatitis, or drug–induced liver injury). These liver diseases are present in community-dwelling persons and are usually asymptomatic. Therefore the demographics and referral source may limit generalizability.