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

Patricio Lopez-Jaramillo, Masira Research Institute, Universidad de Santander, Bucaramanga, Colombia. Electronic address: jplopezj@gmail.com.
Diego Gomez-Arbelaez, Masira Research Institute, Universidad de Santander, Bucaramanga, Colombia.
Daniel Martinez-Bello, Masira Research Institute, Universidad de Santander, Bucaramanga, Colombia.
Marc Evans Abat, Division of Adult Medicine, Department of Medicine, Philippine General Hospital, Manila, Philippines.Follow
Khalid F. Alhabib, Department of Cardiac Sciences, King Fahad Cardiac Center, College of Medicine, King Saud Medical City, King Saud University, Riyadh, Saudi Arabia.Follow
Álvaro Avezum, International Research Center, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil.Follow
Olga Barbarash, Federal State Budgetary Institution Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, Russia.Follow
Jephat Chifamba, Physiology Unit, Department of Biomedical Sciences, University of Zimbabwe, Harare, Zimbabwe.Follow
Maria L. Diaz, Estudios Clínicos Latinoamérica and Instituto Cardiovascular de Rosario, Rosario, Argentina.
Sadi Gulec, Cardiology Department, Ankara University School of Medicine, Ankara, Türkiye.
Noorhassim Ismail, Department of Community Health, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Romaina Iqbal, Department of Community Health Sciences, Aga Khan University, Karachi, Pakistan.
Roya Kelishadi, Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.
Rasha Khatib, Advocate Aurora HealthFollow
Fernando Lanas, Universidad de La Frontera, Temuco, Chile.
Naomi S. Levitt, Chronic Disease Initiative for Africa, University of Cape Town, Cape Town, South Africa.
Yang Li, Medical Research & Biometrics Center, National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China.
Viswanathan Mohan, Madras Diabetes Research Foundation, and Dr Mohan's Diabetes Specialities Centre, Chennai, India.
Prem K. Mony, Division of Epidemiology & Population Health, St John's Medical College & Research Institute, Bangalore, India.
Paul Poirier, Faculté de Pharmacie, Université Laval, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec City, QC, Canada.
Annika Rosengren, Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.
Biju Soman, Health Action by People, Medical College, and Sree Chitra Tirunal Institute for Medical Sciences and Technology, Kerala, India.
Chuangshi Wang, Medical Research & Biometrics Center, National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China.
Yang Wang, Medical Research & Biometrics Center, National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China.
Karen Yeates, Department of Medicine, Queen's University, Kingston, ON, Canada.
Rita Yusuf, Independent University, Dhaka, Bangladesh.
Afzalhussein Yusufali, Tamani Foundation, Matemwe, Zanzibar, Tanzania.
Katarzyna Zatonska, Department of Population Health, Wroclaw Medical University, Wroclaw, Poland.
Sumathy Rangarajan, Population Health Research Institute, McMaster University, Hamilton Health Sciences, Hamilton, ON, Canada.
Salim Yusuf, Population Health Research Institute, McMaster University, Hamilton Health Sciences, Hamilton, ON, Canada.

Affiliations

Advocate Aurora Research Institute

Abstract

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 13·2 years (IQR 11·9-14·6), 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 1·21; 95% CI 1·13-1·30), myocardial infarction (1·24; 1·12-1·38), stroke (1·16; 1·05-1·28), and incident type 2 diabetes (1·99; 1·82-2·16). 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 1·31; 95% CI 1·12-1·54; MICs: 1·20; 1·11-1·31; p interaction=0·01), cardiovascular mortality (LICs: 1·44; 1·15-1·80; pinteraction=0·01), myocardial infarction (LICs: 1·29; 1·06-1·56; MICs: 1·26; 1·10-1·45; pinteraction=0·08), stroke (LICs: 1·35; 1·02-1·78; MICs: 1·17; 1·05-1·30; p interaction=0·19), and incident diabetes (LICs: 1·64; 1·38-1·94; MICs: 2·68; 2·40-2·99; pinteractioninteraction

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.

Funding: Full funding sources are listed at the end of the paper (see Acknowledgments).

Document Type

Article

PubMed ID

36521498

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