Biomarkers of Blood Glucose Regulation: The ALT:AST ratio

Optimal Takeaways

The ratio of the transferase enzymes ALT and AST can be used to gauge metabolic dysfunction. Increased release of these enzymes in the blood suggests tissue damage. An increasing ratio may be indicative of worsening blood glucose regulation, insulin resistance, metabolic syndrome, undiagnosed diabetes, or non-alcoholic fatty liver disease. An increasing ratio can also be associated with increased CVD risk.

Standard Range: 0 – 0.80 Ratio

The ODX Range: 0.10 - 0.78 Ratio

Low ALT:AST ratio in frail older adults may reflect a decrease in ALT which creates a decreased ratio of ALT to AST (Liu 2014).

High ALT:AST ratio correlates with impaired fasting glucose, insulin resistance, undiagnosed type 2 diabetes, and declining metabolic health (Kwon 2019).

An increasing ratio is also associated with decreased muscle mass in type 2 diabetics (Ma 2022), metabolic syndrome, non-alcoholic fatty liver disease, and cardiovascular disease (Sg 2017, Vonbank 2016, Ohgo 2009).

Overview

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are enzymes involved in gluconeogenesis, the production of “new” glucose from the amino acids alanine and aspartate. ALT is found in high concentrations in the liver and lower concentrations in the brain, intestines, muscle, adipose tissue, and prostate. Elevated serum levels of ALT tend to be more specific to liver injury. AST is found in the liver, muscle, brain, kidneys, pancreas, lungs, and white and red blood cells (Lala 2020). Increased release of ALT and AST into the bloodstream is a sign of tissue damage which can eventually lead to loss of function.

An increasing ratio of ALT to AST is associated with declining glucose regulation, metabolic impairment, and organ dysfunction, including non-alcoholic fatty liver disease and cardiovascular disease (Sg 2017, Vonbank 2016). A health survey of 16,371 adults revealed that increasing ALT:AST ratios correlated with impaired fasting glucose, insulin resistance/HOMA-IR, undiagnosed type 2 diabetes, and declining metabolic health (Kwon 2019).

Increasing ALT:AST is independently associated with insulin resistance and may provide early clues to its presence. Researchers in a large cross-sectional study of 8,398 adults suggested a cut-off point for ALT:AST of 0.80 in non-centrally obese individuals and 0.78 in the centrally obese for identifying insulin resistance, especially above these levels. An increasing ratio of 0.82 or above may also indicate insulin resistance even in those who maintain a normal BMI below 25 (Kawamoto 2012, Zhao 2017).

The health of the liver is closely tied to blood glucose regulation and insulin resistance, as the liver is responsible for clearing insulin from the bloodstream (Kwon 2019). As can be expected, insulin resistance is closely tied to non-alcoholic fatty liver disease. An increased ALT:AST ratio is considered a surrogate marker for NAFLD, an all-too-common phenomenon associated with the accumulation of fat in the liver (hepatosteatosis) (Zhao 2017).

Increases in ALT:AST may also help gauge cardiovascular risk. In 1,063 subjects with coronary artery disease, an ALT:AST of 1.1 or greater strongly and significantly predicted an adverse cardiac event in those with insulin resistance (Vonbank 2016).

References

Kawamoto R, Kohara K, Kusunoki T, et al. Alanine aminotransferase/aspartate aminotransferase ratio is the best surrogate marker for insulin resistance in non-obese Japanese adults. Cardiovasc Diabetol. 2012 Oct 1;11:117,

Kwon SS, Lee SG. A High Alanine Aminotransferase/Aspartate Aminotransferase Ratio Determines Insulin Resistance and Metabolically Healthy/Unhealthy Obesity in a General Adult Population in Korea: The Korean National Health and Nutritional Examination Survey 2007-2010. Exp Clin Endocrinol Diabetes. 2019 Oct;127(10):677-684.

Lala V, Goyal A, Bansal P, Minter DA. Liver Function Tests. 2020 Mar 27. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 

Liu Z, Que S, Xu J, Peng T. Alanine aminotransferase-old biomarker and new concept: a review. Int J Med Sci. 2014 Jun 26;11(9):925-35.

Ma, Wenjie et al. “Association between ALT/AST and Muscle Mass in Patients with Type 2 Diabetes Mellitus.” Mediators of inflammation vol. 2022 9480228. 14 Oct. 2022, doi:10.1155/2022/9480228

Ohgo, Hideki, et al. "Significance of ALT/AST ratio for specifying subjects with metabolic syndrome in its silent stage." Diabetes & metabolic syndrome: Clinical research & reviews 3.1 (2009): 3-6.

Sg, R., Dhamija, R., Gurtoo, A., & Singh, R. (2017). Correlation Of Alt/ast Ratio With Insulin Resistance In Metabolic Syndrome. International Journal of Advanced Research, 5(3), 1677-1684. 

Vonbank, Alexander, et al. "The alanine aminotransferase/aspartate aminotransferase ratio predicts future cardiovascular events in patients with established coronary artery disease and homa insulin resistance." Atherosclerosis 252 (2016): e64-e65.

Zhao L, Cheng J, Chen Y, et al. Serum alanine aminotransferase/aspartate aminotransferase ratio is one of the best markers of insulin resistance in the Chinese population. Nutr Metab (Lond). 2017 Oct 10;14:64.