Research Blog

May 17, 2023

Blood Glucose Regulation: Triglyceride-Glucose Index

Optimal Takeaways  

The Triglyceride-Glucose (TyG) Index is a valuable tool of prevention that can be used to identify insulin resistance and its associated complications early on. An increased TyG Index reflects glucose dysregulation and metabolic dysfunction and is directly associated with an increased risk of cardiometabolic disorders, including diabetes, cardiovascular disease, and stroke.

An elevated TyG Index increases the risk of cardiovascular disease in initially healthy individuals and the risk of adverse cardiac events in those with suspected CVD, as well as those with type 2 diabetes. Higher TyG Index is also associated with greater risk and severity of non-alcoholic metabolic fatty liver disease.

Standard Range: Below 4.5

The ODX Range: Below 4.4 calculated with the modified formula Ln [fasting triglycerides (mg/dL) x fasting blood glucose (mg/dL)]/2

Low TyG Index is associated with a reduced risk of insulin resistance and related cardiometabolic disorders, including diabetes, metabolic syndrome, cardiovascular disease, and cerebrovascular disease.

High TyG index is associated with type 2 diabetes (Chamroonkiadtikun 2020, Low 2018, Navarro 2016), insulin resistance (Guerrero 2010, Salazar 2017), risk of metabolic syndrome, cardiovascular disease, cerebrovascular disease (Salazar 2017), coronary artery calcification (Low 2018), CVD events in initially healthy individuals (Li 2022, Tian 2021), cardiovascular events in high-risk individuals (Neglia 2021, Su 2019, Jin 2018), ischemic stroke (Shi 2020), and non-alcoholic metabolic fatty liver disease (Beran 2022, Zhang 2017).

Overview    

The triglyceride-glucose index (TyG Index or TGI) is a measurement used to identify insulin resistance (IR) and predict the risk of complications associated with it, including metabolic syndrome, diabetes, and cardiovascular and cerebrovascular disease. It is based on fasting triglycerides and fasting glucose. Emerging research suggests that the TyG Index is a better predictor of IR than leptin, the visceral adiposity index, Apo-B/ApoA-1 ratio, TG/HDL-C ratio, and other lipid parameters, and a better predictor of type 2 diabetes incidence than triglycerides, HOMA-IR, TG/HDL-C, and weight gain (Salazar 2017).

Evaluation of metabolic data from a set of 227 revealed a closer association between TyG Index and atherogenic sdLDLs, nephropathy, BMI, and HbA1C than other commonly assessed cardiometabolic biomarkers including fasting triglycerides, HOMA-IR, HDL-C, and nonHDL-C (Khan 2018). However, another study of 4,419 individuals found fasting glucose and HOMA-IR to be better predictors of type 2 diabetes incidence than the TyG Index (Tohidi 2018).

It is imperative that insulin resistance be identified and addressed early due to its wide-ranging metabolic complications, including defective glucose uptake, decreased glycogen synthesis, reduced suppression of lipid oxidation, increased oxidative stress, increased inflammation, glucotoxicity, and lipotoxicity. The TyG Index is a valuable tool that is more convenient and cost-effective than the euglycemic-hyperinsulinemic clamp or HOMA calculations. There is an established association between increased TyG Index and adverse cardiometabolic outcomes, diabetes, hypertension, arterial stiffness, CVD, stroke, and obesity-related cancer (Liu 2021).

In one cross-sectional randomized population study of 2,004 subjects, a TyG Index of 4.5 or above was significantly associated with a higher average HOMA2-IR of 2.48 versus a TyG Index below 4.5, which was associated with a lower HOMA2-IR of 1.74. Nutrition and lifestyle changes can improve triglyceride and glucose levels and, therefore, the triglyceride-glucose index. The modified TyG Index calculation was used in the study, i.e., In [fasting TG (mg/dl) x fasting glucose (mg/dl)]/2 (Salazar 2017).

The TyG Index is significantly higher in type 2 diabetics. An elevated TyG Index can help assess the risk of T2DM in those not yet diagnosed better than HOMA-IR or the triglyceride/HDL-C ratio can (Chamroonkiadtikun 2020). In those with established type 2 diabetes, an elevated TyG Index was better able to predict CVD events than either hemoglobin A1C or serum triglycerides (Su 2019).

Data from NHANES research 1999-2014 confirmed the association between increased TyG Index, insulin resistance, cardiovascular disease, and increased all-cause mortality. Those at the highest risk had a mean fasting blood glucose of 197.8 mg/dL (10.98 mmol/L) and fasting triglycerides of 484.1 mg/dL (5.47 mmol/L). Those at the lowest risk had a mean fasting glucose of 90.7 mg/dL (5.03 mmol/L) and fasting triglycerides of 51.8 mg/dL (0.59 mmol/L). The TyG Index was 5.73 for those at highest risk and 4.23 for those at the lowest risk, using the modified TyG Index equation, and 10.49 versus 7.73, respectively, using the original equation (Liu 2021).

An increased TyG index independently predicted cardiac events in a group of 1,097 subjects with established or suspected coronary artery disease. Those with the greatest risk had a mean fasting glucose of 99.6 mg/dL (5.53 mmol/L) and a fasting triglyceride level of 240.3 mg/dL (2.72 mmol/L), while those at lowest risk had a mean fasting glucose of 91.4 mg/dL (5.0 mmol/L) and a fasting triglyceride level of 63.7 mg/dL (0.72 mmol/L). Results using the modified TyG Index formula indicate that a TyG Index of 5.05 was associated with the highest risk of a cardiac event, and a TyG Index of 4.33 was associated with the lowest risk; results were 9.33 versus 7.95 using the original equation (Neglia 2021). An increase in the TyG Index, as well as its increased variability over time, also predicted the incidence of cardiovascular disease in those with no prior history or suspicion of CVD in a prospective cohort study of 49,579 individuals (Li 2022).

Meta-analysis of 17 observational studies comprising 121,975 subjects confirms that an elevated TyG Index is also associated with the increased risk and severity of non-alcoholic metabolic fatty liver disease (NAFLD). The analysis concludes that the TyG Index is also useful for screening for liver dysfunction, including steatosis and non-alcoholic steatohepatitis. Higher results should prompt further diagnostic steps and lifestyle intervention (Beran 2022). A cross-sectional cohort study of 761 subjects found that the TyG Index was superior to the biomarker alanine aminotransferase (ALT) in predicting NAFLD (Zhang 2017).

Note: The modified TyG Index calculation of Ln [fasting glucose (mg/dL) x fasting triglycerides (mg/dL)]/2 is an update from the original equation and yields lower values for assessing insulin resistance and disease risk than the original formula (Hosseini 2017).

  • Original Ln [fasting glucose (mg/dL) x fasting triglycerides (mg/dL)/2]
  • Modified Ln [fasting glucose (mg/dL) x fasting triglycerides (mg/dL)] /2

Contemporary research frequently uses the modified equation, the same calculation utilized in the ODX software and related resources.

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References

Beran, Azizullah et al. “Triglyceride-Glucose Index for Early Prediction of Nonalcoholic Fatty Liver Disease: A Meta-Analysis of 121,975 Individuals.” Journal of clinical medicine vol. 11,9 2666. 9 May. 2022, doi:10.3390/jcm11092666

Chamroonkiadtikun, Panya et al. “The triglyceride-glucose index, a predictor of type 2 diabetes development: A retrospective cohort study.” Primary care diabetes vol. 14,2 (2020): 161-167. doi:10.1016/j.pcd.2019.08.004

Guerrero-Romero, Fernando et al. “The product of triglycerides and glucose, a simple measure of insulin sensitivity. Comparison with the euglycemic-hyperinsulinemic clamp.” The Journal of clinical endocrinology and metabolism vol. 95,7 (2010): 3347-51. doi:10.1210/jc.2010-0288

Hosseini, S. Mehran. "Triglyceride-glucose index simulation." Journal of Clinical and Basic Research 1.1 (2017): 11-16.

Jin, Jing-Lu et al. “Triglyceride glucose index for predicting cardiovascular outcomes in patients with coronary artery disease.” Journal of thoracic disease vol. 10,11 (2018): 6137-6146. doi:10.21037/jtd.2018.10.79

Khan, Sikandar Hayat et al. “Metabolic clustering of risk factors: evaluation of Triglyceride-glucose index (TyG index) for evaluation of insulin resistance.” Diabetology & metabolic syndrome vol. 10 74. 5 Oct. 2018, doi:10.1186/s13098-018-0376-8

Kim, Min Kyung et al. “Relationship between the triglyceride glucose index and coronary artery calcification in Korean adults.” Cardiovascular diabetology vol. 16,1 108. 23 Aug. 2017, doi:10.1186/s12933-017-0589-4

Li, Haibin et al. “Triglyceride-glucose index variability and incident cardiovascular disease: a prospective cohort study.” Cardiovascular diabetology vol. 21,1 105. 10 Jun. 2022, doi:10.1186/s12933-022-01541-5

Liu, Xiao-Cong et al. “The Triglyceride-Glucose Index, an Insulin Resistance Marker, Was Non-linear Associated With All-Cause and Cardiovascular Mortality in the General Population.” Frontiers in cardiovascular medicine vol. 7 628109. 14 Jan. 2021, doi:10.3389/fcvm.2020.628109

Low, Serena et al. “The role of triglyceride glucose index in development of Type 2 diabetes mellitus.” Diabetes research and clinical practice vol. 143 (2018): 43-49. doi:10.1016/j.diabres.2018.06.006

Navarro-González, David et al. “Triglyceride-glucose index (TyG index) in comparison with fasting plasma glucose improved diabetes prediction in patients with normal fasting glucose: The Vascular-Metabolic CUN cohort.” Preventive medicine vol. 86 (2016): 99-105. doi:10.1016/j.ypmed.2016.01.022

Neglia, Danilo et al. “Triglyceride-glucose index predicts outcome in patients with chronic coronary syndrome independently of other risk factors and myocardial ischaemia.” European heart journal open vol. 1,1 oeab004. 24 Jul. 2021, doi:10.1093/ehjopen/oeab004

Salazar, Juan et al. “Optimal cutoff for the evaluation of insulin resistance through triglyceride-glucose index: A cross-sectional study in a Venezuelan population.” F1000Research vol. 6 1337. 7 Aug. 2017, doi:10.12688/f1000research.12170.3

Shi, Wenrui et al. “Value of triglyceride-glucose index for the estimation of ischemic stroke risk: Insights from a general population.” Nutrition, metabolism, and cardiovascular diseases : NMCD vol. 30,2 (2020): 245-253. doi:10.1016/j.numecd.2019.09.015

Su, Wei-Yu et al. “Comparison of the Effects of Fasting Glucose, Hemoglobin A1c, and Triglyceride-Glucose Index on Cardiovascular Events in Type 2 Diabetes Mellitus.” Nutrients vol. 11,11 2838. 19 Nov. 2019, doi:10.3390/nu11112838

Tian, Xue et al. “Triglyceride-glucose index is associated with the risk of myocardial infarction: an 11-year prospective study in the Kailuan cohort.” Cardiovascular diabetology vol. 20,1 19. 12 Jan. 2021, doi:10.1186/s12933-020-01210-5

Tohidi, Maryam et al. “Fasting plasma glucose is a stronger predictor of diabetes than triglyceride-glucose index, triglycerides/high-density lipoprotein cholesterol, and homeostasis model assessment of insulin resistance: Tehran Lipid and Glucose Study.” Acta diabetologica vol. 55,10 (2018): 1067-1074. doi:10.1007/s00592-018-1195-y

Zhang, Shujun et al. “The triglyceride and glucose index (TyG) is an effective biomarker to identify nonalcoholic fatty liver disease.” Lipids in health and disease vol. 16,1 15. 19 Jan. 2017, doi:10.1186/s12944-017-0409-6

 

Tag(s): Biomarkers

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