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

• Background 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. Methods We used the TyG index as a surrogate measure for insulin resistance. Fasting triglycerides and fasting plasma glucose were measured at the baseline visit in 141 243 individuals aged 35-70 years from 22 countries in the Prospective Urban Rural Epidemiology (PURE) study. The TyG index was calculated as Ln (fasting triglycerides [mg/dL] x fasting plasma glucose [mg/dL]/2). We calculated hazard ratios (HRs) using a multivariable Cox frailty model with random effects to test the associations between the TyG index and risk of cardiovascular diseases and mortality. The primary outcome of this analysis was the composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, and non-fatal myocardial infarction, or stroke). Secondary outcomes were non-cardiovascular mortality, cardiovascular mortality, all myocardial infarctions, stroke, and incident diabetes. We also did subgroup analyses to examine the magnitude of associations between insulin resistance (ie, the TyG index) and outcome events according to the income level of the countries. Findings During a median follow-up of 13 center dot 2 years (IQR 11 center dot 9-14 center dot 6), we recorded 6345 composite cardiovascular diseases events, 2030 cardiovascular deaths, 3038 cases of myocardial infarction, 3291 cases of stroke, and 5191 incident cases of type 2 diabetes. After adjusting for all other variables, the risk of developing cardiovascular diseases increased across tertiles of the baseline TyG index. Compared with the lowest tertile of the TyG index, the highest tertile (tertile 3) was associated with a greater incidence of the composite outcome (HR 1 center dot 21; 95% CI 1 center dot 13-1 center dot 30), myocardial infarction (1 center dot 24; 1 center dot 12-1 center dot 38), stroke (1 center dot 16; 1 center dot 05-1 center dot 28), and incident type 2 diabetes (1 center dot 99; 1 center dot 82-2 center dot 16). No significant association of the TyG index was seen with non-cardiovascular mortality. In low-income countries (LICs) and middle-income countries (MICs), the highest tertile of the TyG index was associated with increased hazards for the composite outcome (LICs: HR 1 center dot 31; 95% CI 1 center dot 12-1 center dot 54; MICs: 1 center dot 20; 1 center dot 11-1 center dot 31; p(interaction)=0 center dot 01), cardiovascular mortality (LICs: 1 center dot 44; 1 center dot 15-1 center dot 80; p(interaction)=0 center dot 01), myocardial infarction (LICs: 1 center dot 29; 1 center dot 06-1 center dot 56; MICs: 1 center dot 26; 1 center dot 10-1 center dot 45; p(interaction)=0 center dot 08), stroke (LICs: 1 center dot 35; 1 center dot 02-1 center dot 78; MICs: 1 center dot 17; 1 center dot 05-1 center dot 30; p interaction=0 center dot 19), and incident diabetes (LICs: 1 center dot 64; 1 center dot 38-1 center dot 94; MICs: 2 center dot 68; 2 center dot 40-2 center dot 99; p(interaction) <0 center dot 0001). In contrast, in high-income countries, higher TyG index tertiles were only associated with an increased hazard of incident diabetes (2 center dot 95; 2 center dot 25-3 center dot 87; p(interaction)<0 center dot 0001), but not of cardiovascular diseases or mortality. Interpretation The TyG index is significantly associated with future cardiovascular mortality, myocardial infarction, stroke, and type 2 diabetes, suggesting that insulin resistance plays a promoting role in the pathogenesis of cardiovascular and metabolic diseases. Potentially, the association between the TyG index and the higher risk of cardiovascular diseases and type 2 diabetes in LICs and MICs might be explained by an increased vulnerability of these populations to the presence of insulin resistance. Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.

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MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Geriatrik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Geriatrics (hsv//eng)

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beta-cell function

high-income

middle

countries

risk

strength

product

Geriatrics & Gerontology

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