Association of the triglyceride glucose index as a measure of insulin resistance with mortality and cardiovascular disease in populations from five continents (PURE study): a prospective cohort study

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Abstract

The triglyceride glucose (TyG) index is an easily accessible surrogate marker of insulin resistance, an important pathway in the development of type 2 diabetes and cardiovascular diseases. However, the association of the TyG index with cardiovascular diseases and mortality has mainly been investigated in Asia, with few data available from other regions of the world. We assessed the association of insulin resistance (as determined by the TyG index) with mortality and cardiovascular diseases in individuals from five continents at different levels of economic development, living in urban or rural areas. We also examined whether the associations differed according to the country's economical development.

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Association between insulin resistance and the development of cardiovascular disease

Valeska Ormazabal, Soumyalekshmi Nair, Omar Elfeky … (2018)

For many years, cardiovascular disease (CVD) has been the leading cause of death around the world. Often associated with CVD are comorbidities such as obesity, abnormal lipid profiles and insulin resistance. Insulin is a key hormone that functions as a regulator of cellular metabolism in many tissues in the human body. Insulin resistance is defined as a decrease in tissue response to insulin stimulation thus insulin resistance is characterized by defects in uptake and oxidation of glucose, a decrease in glycogen synthesis, and, to a lesser extent, the ability to suppress lipid oxidation. Literature widely suggests that free fatty acids are the predominant substrate used in the adult myocardium for ATP production, however, the cardiac metabolic network is highly flexible and can use other substrates, such as glucose, lactate or amino acids. During insulin resistance, several metabolic alterations induce the development of cardiovascular disease. For instance, insulin resistance can induce an imbalance in glucose metabolism that generates chronic hyperglycemia, which in turn triggers oxidative stress and causes an inflammatory response that leads to cell damage. Insulin resistance can also alter systemic lipid metabolism which then leads to the development of dyslipidemia and the well-known lipid triad: (1) high levels of plasma triglycerides, (2) low levels of high-density lipoprotein, and (3) the appearance of small dense low-density lipoproteins. This triad, along with endothelial dysfunction, which can also be induced by aberrant insulin signaling, contribute to atherosclerotic plaque formation. Regarding the systemic consequences associated with insulin resistance and the metabolic cardiac alterations, it can be concluded that insulin resistance in the myocardium generates damage by at least three different mechanisms: (1) signal transduction alteration, (2) impaired regulation of substrate metabolism, and (3) altered delivery of substrates to the myocardium. The aim of this review is to discuss the mechanisms associated with insulin resistance and the development of CVD. New therapies focused on decreasing insulin resistance may contribute to a decrease in both CVD and atherosclerotic plaque generation.

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The product of triglycerides and glucose, a simple measure of insulin sensitivity. Comparison with the euglycemic-hyperinsulinemic clamp.

Fernando Guerrero-Romero, Luis E Simental-Mendía, Manuel González-Ortiz … (2010)

To meet the worldwide challenge of emerging diabetes, accessible and inexpensive tests to identify insulin resistance are needed. To evaluate the sensitivity and specificity of the product of fasting, we compared the triglycerides and glucose (TyG) index, a simple measure of insulin resistance, with the euglycemic-hyperinsulinemic clamp test. We conducted a cross-sectional study of the general population and outpatients of the Internal Medicine Department at the Medical Unit of High Specialty of the Specialty Hospital at the West National Medical Center in Guadalajara, Mexico. Eleven nonobese healthy subjects, 34 obese normal glucose tolerance individuals, 22 subjects with prediabetes, and 32 diabetic patients participated in the study. We performed a euglycemic-hyperinsulinemic clamp test. Sensitivity and specificity of the TyG index [Ln(fasting triglycerides) (mg/dl) x fasting glucose (mg/dl)/2] were measured, as well as the area under the curve of the receiver operating characteristic scatter plot and the correlation between the TyG index and the total glucose metabolism (M) rates. Pearson's correlation coefficient between the TyG index and M rates was -0.681 (P < 0.005). Correlation between the TyG index and M rates was similar between men (-0.740) and women (-0.730), nonobese (-0.705) and obese (-0.710), and nondiabetic (-0.670) and diabetic (-0.690) individuals. The best value of the TyG index for diagnosis of insulin resistance was 4.68, which showed the highest sensitivity (96.5%) and specificity (85.0%; area under the curve + 0.858). The TyG index has high sensitivity and specificity, suggesting that it could be useful for identification of subjects with decreased insulin sensitivity.

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The product of fasting glucose and triglycerides as surrogate for identifying insulin resistance in apparently healthy subjects.

Martha Mendoza-Rodríguez, Fernando Guerrero, Luis Simental-Mendía (2008)

Because the insulin test is expensive and is not available in most laboratories in the cities of undeveloped countries, we tested whether the product of fasting triglycerides and glucose levels (TyG) is a surrogate for estimating insulin resistance compared with the homeostasis model assessment of insulin resistance (HOMA-IR) index. We performed a population-based cross-sectional study. Sampling strategy was based on a randomized two-stage cluster sampling procedure. Only apparently healthy subjects, men and nonpregnant women aged 18-65 years, with newly diagnosed impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or IFG + IGT were enrolled. Renal disease, malignancy, and diabetes were exclusion criteria. Sensitivity, specificity, predictive values, and the probability of disease given a positive test were calculated. The optimal TyG index for estimating insulin resistance was established using a receiver operating characteristic scatter plot analysis. A total of 748 apparently healthy subjects aged 41.4 +/- 11.2 years were enrolled. Insulin resistance was identified in 241 (32.2%) subjects (HOMA-IR index 4.4 +/- 1.6). New diagnoses of IFG, IGT, and IFG + IGT were established in 145 (19.4%), 54 (7.2%), and 75 (10.0%) individuals. respectively. The best TyG index for diagnosis of insulin resistance was Ln 4.65, which showed the highest sensitivity (84.0%) and specificity (45.0%) values. The positive and negative predictive values were 81.1% and 84.8%, and the probability of disease, given a positive test, was 60.5%. The TyG index could be useful as surrogate to identify insulin resistance in apparently healthy subjects.