Prognostic effect of triglyceride glucose-related parameters on all-cause and cardiovascular mortality in the United States adults with metabolic dysfunction-associated steatotic liver disease

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Abstract

Backgrounds

Insulin resistance (IR) plays a vital role in the pathogenesis of the metabolic dysfunction-associated steatotic liver disease (MASLD). However, it remains unclear whether triglyceride–glucose (TyG) related parameters, which serve as useful biomarkers to assess IR, have prognostic effects on mortality outcomes of MASLD.

Methods

Participants in the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2018 years were included. TyG and its related parameters [TyG-waist circumference (TyG-WC) and TyG-waist to height ratio (TyG-WHtR)] were calculated. Kaplan–Meier curves, Cox regression analysis, and restricted cubic splines (RCS) were conducted to evaluate the association between TyG-related indices with the all-cause and cardiovascular mortality of adults with MASLD. The concordance index (C-index) was used to evaluate the prediction accuracy of TyG-related indices.

Results

A total of 8208 adults (4209 men and 3999 women, median age 49.00 years) with MASLD were included in this study. Multivariate-adjusted Cox regression analysis revealed that high quartile levels of TyG-related indices were significantly associated with the all-cause mortality of participants with MASLD [ _TyGadjusted hazard ratio (aHR) = 1.25, 95% confidence interval (CI) 1.05–1.50, P = 0.014; _TyG-WCaHR for all-cause mortality = 1.28, 95% CI 1.07–1.52, P = 0.006; _TyG-WHtRaHR for all-cause mortality = 1.50, 95% CI 1.25–1.80, P < 0.001; _TyG-WCaHR for cardiovascular mortality = 1.81, 95% CI 1.28–2.55, P = 0.001; _TyG-WHtRaHR for cardiovascular mortality = 2.22, 95% CI 1.55–3.17, P < 0.001]. The C-index of TyG-related indices for predicting all-cause mortality was 0.563 for the TyG index, 0.579 for the TyG-WC index, and 0.585 for the TyG-WHtR index, respectively. Regarding cardiovascular mortality, the C-index was 0.561 for the TyG index, 0.607 for the TyG-WC index, and 0.615 for the TyG-WHtR index, respectively. Nonlinear trends were observed between TyG and TyG-WC indices with all-cause mortality of MASLD ( P < 0.001 and = 0.012, respectively). A non-linear relationship was observed between the TyG index and cardiovascular mortality of MASLD ( P = 0.025). Subgroup analysis suggested that adults aged < 65 years old and those without comorbidities were more sensitive to the mortality prediction of TyG-related indices.

Conclusion

Findings of this study highlight the predictive value of TyG-related indices, especially the TyG-WHtR index, in the mortality outcomes of adults with MASLD. TyG-related indices would be surrogate biomarkers for the clinical management of MASLD.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12933-024-02287-y.

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Most cited references 65

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Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.

D. Matthews, J Hosker, A Rudenski … (1985)

The steady-state basal plasma glucose and insulin concentrations are determined by their interaction in a feedback loop. A computer-solved model has been used to predict the homeostatic concentrations which arise from varying degrees beta-cell deficiency and insulin resistance. Comparison of a patient's fasting values with the model's predictions allows a quantitative assessment of the contributions of insulin resistance and deficient beta-cell function to the fasting hyperglycaemia (homeostasis model assessment, HOMA). The accuracy and precision of the estimate have been determined by comparison with independent measures of insulin resistance and beta-cell function using hyperglycaemic and euglycaemic clamps and an intravenous glucose tolerance test. The estimate of insulin resistance obtained by homeostasis model assessment correlated with estimates obtained by use of the euglycaemic clamp (Rs = 0.88, p less than 0.0001), the fasting insulin concentration (Rs = 0.81, p less than 0.0001), and the hyperglycaemic clamp, (Rs = 0.69, p less than 0.01). There was no correlation with any aspect of insulin-receptor binding. The estimate of deficient beta-cell function obtained by homeostasis model assessment correlated with that derived using the hyperglycaemic clamp (Rs = 0.61, p less than 0.01) and with the estimate from the intravenous glucose tolerance test (Rs = 0.64, p less than 0.05). The low precision of the estimates from the model (coefficients of variation: 31% for insulin resistance and 32% for beta-cell deficit) limits its use, but the correlation of the model's estimates with patient data accords with the hypothesis that basal glucose and insulin interactions are largely determined by a simple feed back loop.

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The Global Epidemic of the Metabolic Syndrome

Mohammad G. Saklayen (2018)

Metabolic syndrome, variously known also as syndrome X, insulin resistance, etc., is defined by WHO as a pathologic condition characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. Though there is some variation in the definition by other health care organization, the differences are minor. With the successful conquest of communicable infectious diseases in most of the world, this new non-communicable disease (NCD) has become the major health hazard of modern world. Though it started in the Western world, with the spread of the Western lifestyle across the globe, it has become now a truly global problem. The prevalence of the metabolic syndrome is often more in the urban population of some developing countries than in its Western counterparts. The two basic forces spreading this malady are the increase in consumption of high calorie-low fiber fast food and the decrease in physical activity due to mechanized transportations and sedentary form of leisure time activities. The syndrome feeds into the spread of the diseases like type 2 diabetes, coronary diseases, stroke, and other disabilities. The total cost of the malady including the cost of health care and loss of potential economic activity is in trillions. The present trend is not sustainable unless a magic cure is found (unlikely) or concerted global/governmental/societal efforts are made to change the lifestyle that is promoting it. There are certainly some elements in the causation of the metabolic syndrome that cannot be changed but many are amenable for corrections and curtailments. For example, better urban planning to encourage active lifestyle, subsidizing consumption of whole grains and possible taxing high calorie snacks, restricting media advertisement of unhealthy food, etc. Revitalizing old fashion healthier lifestyle, promoting old-fashioned foods using healthy herbs rather than oil and sugar, and educating people about choosing healthy/wholesome food over junks are among the steps that can be considered.

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The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population

Giorgio Bedogni, Stefano Bellentani, Lucia Miglioli … (2006)

Background Fatty liver (FL) is the most frequent liver disease in Western countries. We used data from the Dionysos Nutrition & Liver Study to develop a simple algorithm for the prediction of FL in the general population. Methods 216 subjects with and 280 without suspected liver disease were studied. FL was diagnosed by ultrasonography and alcohol intake was assessed using a 7-day diary. Bootstrapped stepwise logistic regression was used to identify potential predictors of FL among 13 variables of interest [gender, age, ethanol intake, alanine transaminase, aspartate transaminase, gamma-glutamyl-transferase (GGT), body mass index (BMI), waist circumference, sum of 4 skinfolds, glucose, insulin, triglycerides, and cholesterol]. Potential predictors were entered into stepwise logistic regression models with the aim of obtaining the most simple and accurate algorithm for the prediction of FL. Results An algorithm based on BMI, waist circumference, triglycerides and GGT had an accuracy of 0.84 (95%CI 0.81–0.87) in detecting FL. We used this algorithm to develop the "fatty liver index" (FLI), which varies between 0 and 100. A FLI < 30 (negative likelihood ratio = 0.2) rules out and a FLI ≥ 60 (positive likelihood ratio = 4.3) rules in fatty liver. Conclusion FLI is simple to obtain and may help physicians select subjects for liver ultrasonography and intensified lifestyle counseling, and researchers to select patients for epidemiologic studies. Validation of FLI in external populations is needed before it can be employed for these purposes.

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Author and article information

Contributors

Xin Zhao: zhaoxintjdx@163.com

Yi Lei: leiyilyfy@163.com

Journal

Journal ID (nlm-ta): Cardiovasc Diabetol

Journal ID (iso-abbrev): Cardiovasc Diabetol

Title: Cardiovascular Diabetology

Publisher: BioMed Central (London )

ISSN (Electronic): 1475-2840

Publication date (Electronic): 1 June 2024

Publication date PMC-release: 1 June 2024

Publication date Collection: 2024

Volume: 23

Electronic Location Identifier: 188

Affiliations

[1 ]GRID grid.13291.38, ISNI 0000 0001 0807 1581, Department of Biotherapy, West China Hospital, , Sichuan University, ; Chengdu, 610041 People’s Republic of China

[2 ]GRID grid.13291.38, ISNI 0000 0001 0807 1581, Department of Head and Neck Oncology, West China Hospital, , Sichuan University, ; Chengdu, 610041 People’s Republic of China

[3 ]Department of Urology, The Affiliated Hospital of Southwest Medical University, ( https://ror.org/0014a0n68) Luzhou, 646000 Sichuan People’s Republic of China

[4 ]Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, ( https://ror.org/0014a0n68) Luzhou, 646000 Sichuan People’s Republic of China

[5 ]Sichuan Clinical Research Center for Nephropathy, Luzhou, 646000 Sichuan People’s Republic of China

[6 ]Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, 646000 Sichuan People’s Republic of China

Article

Publisher ID: 2287

DOI: 10.1186/s12933-024-02287-y

PMC ID: 11144336

PubMed ID: 38824550

SO-VID: 23538e6f-1b5c-4ad7-81c0-24e65637dae6

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 28 March 2024

Date accepted : 24 May 2024

Funding

Funded by: Youth Medical Innovation Research Project of Sichuan Province

Award ID: No. Q23068

Award Recipient : Xin Zhao

Custom metadata

ScienceOpen disciplines: Endocrinology & Diabetes

Keywords: masld,insulin resistance,tyg index,tyg-wc index,tyg-whtr index,all-cause mortality,cardiovascular mortality

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ScienceOpen disciplines: Endocrinology & Diabetes

Keywords: masld, insulin resistance, tyg index, tyg-wc index, tyg-whtr index, all-cause mortality, cardiovascular mortality

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Association between triglyceride-glucose related indices and mortality among individuals with non-alcoholic fatty liver disease or metabolic dysfunction-associated steatotic liver disease
Authors: Qingling Chen, Pingping Hu, Xiaoxue Hou …

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Prognostic effect of triglyceride glucose-related parameters on all-cause and cardiovascular mortality in the United States adults with metabolic dysfunction-associated steatotic liver disease

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Abstract

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Supplementary Information

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Society for Endocrinology

Most cited references 65

Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.

The Global Epidemic of the Metabolic Syndrome

The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population

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