Association Between Triglyceride-Glucose Index and Diabetic Retinopathy: A Meta-Analysis

Abstract

The objective of this study was to assess the relationship between the triglyceride-glucose (TyG) index, a recently proposed marker of insulin resistance, and the occurrence of diabetic retinopathy (DR), a complication associated with cardiovascular risk. This systematic review and meta-analysis aimed to evaluate the association between the TyG index and DR. To achieve the objective of the meta-analysis, an extensive search was conducted on databases such as PubMed, Embase, and Web of Science to identify observational studies with longitudinal follow-up. Random-effects models were employed to combine the findings, taking into account the potential influence of heterogeneity. Twelve observational studies from 11 reports were included in the meta-analysis, which involved 16 259 patients with type 2 diabetes (T2D). Among them, 4302 (26.5%) were diagnosed as DR. Pooled results showed that a higher TyG index was associated with a higher risk of DR [odds ratio (OR) for the fourth versus the first quartile of TyG index: 1.91, 95% confidence interval (CI): 1.44 to 2.53, p<0.001; I2=72%]. Meta-analysis of TyG index analyzed in continuous variable showed consistent results (OR for per 1 unit increment of TyG index: 1.41, 95% CI: 1.08 to 1.86, p=0.01; I2=82%). Subgroup analysis showed that adjustment of HbA1c or the duration of diabetes did not significantly affect the results (p for subgroup difference all>0.05). In conclusion, a high TyG index was associated with the risk of DR in T2D patients.

Keywords

triglyceride-glucose index - diabetic retinopathy - type 2 diabetes - microvascular - meta-analysis

Publication History

Received: 17 November 2023

Accepted after revision: 26 February 2024

Article published online:
26 April 2024

• References

• 1 Li X, Tan TE, Wong TY. et al. Diabetic retinopathy in China: Epidemiology, screening and treatment trends-A review. Clin Exp Ophthalmol 2023; 51: 607-626
• 2 Lin KY, Hsih WH, Lin YB. et al. Update in the epidemiology, risk factors, screening, and treatment of diabetic retinopathy. J Diabetes Investig 2021; 12: 1322-1325
• 3 Guo VY, Cao B, Wu X. et al. Prospective association between diabetic retinopathy and cardiovascular disease - a systematic review and meta-analysis of cohort studies. J Stroke Cerebrovasc Dis 2016; 25: 1688-1695
• 4 Xie J, Ikram MK, Cotch MF. et al. Association of diabetic macular edema and proliferative diabetic retinopathy with cardiovascular disease: a systematic review and meta-analysis. JAMA Ophthalmol 2017; 135: 586-593
• 5 Xu XH, Sun B, Zhong S. et al. Diabetic retinopathy predicts cardiovascular mortality in diabetes: a meta-analysis. BMC Cardiovasc Disord 2020; 20: 478
• 6 Perais J, Agarwal R, Evans JR. et al. Prognostic factors for the development and progression of proliferative diabetic retinopathy in people with diabetic retinopathy. Cochrane Database Syst Rev 2023; 2: CD013775
• 7 Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006; 444: 840-846
• 8 Lee SH, Park SY, Choi CS. Insulin resistance: from mechanisms to therapeutic strategies. Diabetes Metab J 2022; 46: 15-37
• 9 Yaribeygi H, Farrokhi FR, Butler AE. et al. Insulin resistance: review of the underlying molecular mechanisms. J Cell Physiol 2019; 234: 8152-8161
• 10 Yue T, Shi Y, Luo S. et al. The role of inflammation in immune system of diabetic retinopathy: Molecular mechanisms, pathogenetic role and therapeutic implications. Front Immunol 2022; 13: 1055087
• 11 Haydinger CD, Oliver GF, Ashander LM. et al. Oxidative stress and its regulation in diabetic retinopathy. Antioxidants (Basel) 2023; 12: 1649
• 12 Tahapary DL, Pratisthita LB, Fitri NA. et al. Challenges in the diagnosis of insulin resistance: Focusing on the role of HOMA-IR and Tryglyceride/glucose index. Diabetes Metab Syndr 2022; 16: 102581
• 13 Ramdas Nayak VK, Satheesh P, Shenoy MT. et al. Triglyceride glucose (TyG) index: a surrogate biomarker of insulin resistance. J Pak Med Assoc 2022; 72: 986-988
• 14 Liu X, Tan Z, Huang Y. et al. Relationship between the triglyceride-glucose index and risk of cardiovascular diseases and mortality in the general population: a systematic review and meta-analysis. Cardiovasc Diabetol 2022; 21: 124
• 15 Ding X, Wang X, Wu J. et al. Triglyceride-glucose index and the incidence of atherosclerotic cardiovascular diseases: a meta-analysis of cohort studies. Cardiovasc Diabetol 2021; 20: 76
• 16 Stroup DF, Berlin JA, Morton SC. et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000; 283: 2008-2012
• 17 Higgins J, Thomas J, Chandler J. et al. Cochrane handbook for systematic reviews of interventions version 6.2. The Cochrane Collaboration. 2021 www.training.cochrane.org/handbook
• 18 Tao LC, Xu JN, Wang TT. et al. Triglyceride-glucose index as a marker in cardiovascular diseases: landscape and limitations. Cardiovasc Diabetol 2022; 21: 68
• 19 Wells GA, Shea B, O’Connell D. et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2010 http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp
• 20 Higgins J, Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0. The Cochrane Collaboration. 2011 www.cochranehandbook.org
• 21 Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539-1558
• 22 Egger M, Davey Smith G, Schneider M. et al. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629-634
• 23 Hameed EK, Abdul-Qahar ZH, Kadium TE. The association of triglycerides glucose index with diabetic retinopathy in patients with type 2 diabetes mellitus. Indian J Pub Health Res Develop 2019; 10: 1885-1890
• 24 Chiu H, Tsai HJ, Huang JC. et al. Associations between triglyceride-glucose index and micro- and macro-angiopathies in type 2 diabetes mellitus. Nutrients 2020; 12: 328
• 25 Pan Y, Zhong S, Zhou K. et al. Association between diabetes complications and the triglyceride-glucose index in hospitalized patients with type 2 diabetes. J Diabetes Res 2021;
• 26 Srinivasan S, Singh P, Kulothungan V. et al. Relationship between triglyceride glucose index, retinopathy and nephropathy in Type 2 diabetes. Endocrinol Diabetes Metab 2021; 4: e00151
• 27 Yao L, Wang X, Zhong Y. et al. The triglyceride-glucose index is associated with diabetic retinopathy in Chinese patients with type 2 diabetes: a hospital-based, nested, case-control study. Diabetes Metab Syndr Obes 2021; 14: 1547-1555
• 28 Li CH, Ning LL, Wang J. Relationship between the triglyceride glucose index and diabetic retinopathy in patients with type 2 diabetes mellitus: a cohort study. Chin J Diabetes Mellitus 2022; 14: 1051-1056
• 29 Shan Y, Wang Q, Zhang Y. et al. High remnant cholesterol level is relevant to diabetic retinopathy in type 2 diabetes mellitus. Lipids Health Dis 2022; 21: 12
• 30 Wang J, Zhang HF, Li CH. Triglyceride and glucose index as a predictive factor for diabetic retinopathy in Type 2 diabetic patients. Int Eye Sci 2022; 22: 1385-1390
• 31 Kassab HS, Osman NA, Elrahmany SM. Assessment of triglyceride-glucose index and ratio in patients with type 2 diabetes and their relation to microvascular complications. Endocr Res 2023; 48: 94-100
• 32 Neelam K, Aung KCY, Ang K. et al. Association of triglyceride glucose index with prevalence and incidence of diabetic retinopathy in a Singaporean population. Clin Ophthalmol 2023; 17: 445-454
• 33 Zhou Y, Lu Q, Zhang M. et al. The U-shape relationship between triglyceride-glucose index and the risk of diabetic retinopathy among the US population. J Pers Med 2023; 13: 495
• 34 Mjwara M, Khan M, Kruse CH. et al. Significance of HbA1c levels in diabetic retinopathy extremes in South Africa. S Afr Med J 2021; 111: 886-890
• 35 Foo V, Quah J, Cheung G. et al. HbA1c, systolic blood pressure variability and diabetic retinopathy in Asian type 2 diabetics. J Diabetes 2017; 9: 200-207
• 36 Ghamdi AHA. Clinical predictors of diabetic retinopathy progression; a systematic review. Curr Diabetes Rev 2020; 16: 242-247
• 37 Muniyappa R, Lee S, Chen H. et al. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab 2008; 294: E15-E26
• 38 Guerrero-Romero F, Simental-Mendia LE, Gonzalez-Ortiz M. et al. The product of triglycerides and glucose, a simple measure of insulin sensitivity. Comparison with the euglycemic-hyperinsulinemic clamp. J Clin Endocrinol Metab 2010; 95: 3347-3351
• 39 Vasques AC, Novaes FS, de Oliveira Mda S. et al. TyG index performs better than HOMA in a Brazilian population: a hyperglycemic clamp validated study. Diabetes Res Clin Pract 2011; 93: e98-e100
• 40 Simental-Mendia LE, Rodriguez-Moran M, Guerrero-Romero F. The product of fasting glucose and triglycerides as surrogate for identifying insulin resistance in apparently healthy subjects. Metab Syndr Relat Disord 2008; 6: 299-304
• 41 Khan SH, Sobia F, Niazi NK. et al. Metabolic clustering of risk factors: evaluation of Triglyceride-glucose index (TyG index) for evaluation of insulin resistance. Diabetol Metab Syndr 2018; 10: 74
• 42 Gasmi A, Noor S, Menzel A. et al. Obesity and insulin resistance: associations with chronic inflammation, genetic and epigenetic factors. Curr Med Chem 2021; 28: 800-826
• 43 Rubsam A, Parikh S, Fort PE. Role of inflammation in diabetic retinopathy. Int J Mol Sci 2018; 19: 942
• 44 Andreadi A, Bellia A, Di Daniele N. et al. The molecular link between oxidative stress, insulin resistance, and type 2 diabetes: a target for new therapies against cardiovascular diseases. Curr Opin Pharmacol 2022; 62: 85-96
• 45 Kang Q, Yang C. Oxidative stress and diabetic retinopathy: Molecular mechanisms, pathogenetic role and therapeutic implications. Redox Biol 2020; 37: 101799