Usefulness of uric acid-to-high-density lipoprotein cholesterol ratio for the evaluation of insulin resistance in healthy normoglycaemic and normoinsulinaemic men

Abstract

Background

Uric acid-to-high-density lipoprotein cholesterol ratio (UHR) is a novel and promising marker for metabolic abnormalities. Recent studies have demonstrated that UHR is related to a number of diseases that are caused by insulin resistance. However, only a few studies have investigated the association between UHR and insulin resistance. The aim of this study was to evaluate the diagnostic ability of UHR to detect insulin resistance in healthy normoglycaemic and normoinsulinaemic men.

Methods

A total of 209 healthy men (aged 23–57 years) with normoglycaemia and normoinsulinaemia were included in this study. Anthropometric and biochemical data were collected. Insulin resistance was assessed by original homeostasis model assessment of insulin resistance (HOMA-IR) and its computerized updated version (HOMA2-IR), the fasting glucose/insulin ratio (FGIR), the McAuley index, and the triglyceride-glucose (TyG) index. A receiver operating characteristic (ROC) curve analysis was conducted to evaluate the ability of UHR to predict insulin resistance.

Results

UHR was significantly correlated with HOMA-IR (r_s=0.23; p=0.001) and HOMA2-IR (r_s=0.20; p=0.003). There were no correlations between UHR and other insulin resistance indices. The prevalence of insulin resistance among the participants was 21.5% and 9.6% according to HOMA-IR (>2.7) and HOMA2-IR (>1.8) cut-off values, respectively. ROC curve analysis revealed the diagnostic ability of UHR to determine insulin resistance assessed by HOMA2-IR (area under the ROC (AUROC) curve: 0.680; p=0.005). However, UHR did not predict insulin resistance assessed by HOMA-IR (AUROC curve: 0.584; p=0.087).

Conclusion

UHR is not a reliable marker of insulin resistance in healthy men with normoglycaemia and normoinsulinaemia.

Keywords

uric acid-to-high-density lipoprotein cholesterol ratio - insulin resistance - homeostasis model assessment of insulin resistance (HOMA-IR) - normoglycaemia - normoinsulinaemia

Publication History

Received: 03 July 2025

Accepted after revision: 22 December 2025

Article published online:
11 February 2026

• References

• 1 Xie Y, Huang K, Zhang X. et al. Association of serum uric acid-to-high-density lipoprotein cholesterol ratio with non-alcoholic fatty liver disease in American adults: a population-based analysis. Front Med (Lausanne) 2023; 10: 1164096
• 2 Kocak MZ, Aktas G, Erkus E. et al. Serum uric acid to HDL-cholesterol ratio is a strong predictor of metabolic syndrome in type 2 diabetes mellitus. Rev Assoc Med Bras (1992) 2019; 65: 9-15
• 3 Balci SB, Atak BM, Duman T. et al. A novel marker for prediabetic conditions: Uric acid-to-HDL cholesterol ratio. Bratisl Lek Listy 2024; 125: 145-148
• 4 Aktas G, Khalid A, Kurtkulagi O. et al. Poorly controlled hypertension is associated with elevated serum uric acid to HDL-cholesterol ratio: a cross-sectional cohort study. Postgrad Med 2022; 134: 297-302
• 5 Park B, Jung DH, Lee YJ. Predictive value of serum uric acid to HDL cholesterol ratio for incident ischemic heart disease in non-diabetic Koreans. Biomedicines 2022; 10: 1422
• 6 Cheng Y, Zhang H, Zheng H. et al. Association between serum uric acid/HDL-cholesterol ratio and chronic kidney disease: a cross-sectional study based on a health check-up population. BMJ Open 2022; 12: e066243
• 7 Zhen R, Wang S, Chen S. The relationship between UA/HDL and diabetic peripheral neuropathy: A cross-sectional analysis. Diabetes Metab Syndr Obes 2024; 17: 969-980
• 8 Kurtkulagi O, Tel BMA, Kahveci G. et al. Hashimoto's thyroiditis is associated with elevated serum uric acid to high density lipoprotein-cholesterol ratio. Rom J Intern Med 2021; 59: 403-408
• 9 Metin Z, Tur K, Durmaz K. et al. A comprehensive investigation of novel and traditional inflammatory and metabolic markers as predictive indicators in psoriasis. Int J Dermatol 2023; 62: 1272-1280
• 10 Kalfaoglu ME. Could serum uric acid to HDL cholesterol ratio predict sacroiliitis?. PLoS One 2023; 18: e0289624
• 11 Uzeli U, Doğan AG. The relationship between diabetic neuropathy and uric acid/high-density lipoprotein ratio in patients with type-2 diabetes mellitus. Cureus 2023; 15: e45151
• 12 Rohani-Rasaf M, Ghavidel F, Hosseini H. et al. The predictive significance of uric acid to high density lipoprotein- cholesterol ratio and uric acid for the severity and mortality of coronavirus disease-19. BMC Res Notes 2024; 17: 277
• 13 Li Z, Liu Q, Yao Z. The serum uric acid-to-high-density lipoprotein cholesterol ratio is a predictor for all-cause and cardiovascular disease mortality: a cross-sectional study. Front Endocrinol (Lausanne) 2024; 15: 1417485
• 14 Aktas G, Kocak MZ, Bilgin S. et al. Uric acid to HDL cholesterol ratio is a strong predictor of diabetic control in men with type 2 diabetes mellitus. Aging Male 2020; 23: 1098-1102
• 15 Wang H, Ba Y, Gao X. et al. Association between serum uric acid to high density lipoprotein-cholesterol ratio and arterial stiffness in a Japanese population. Medicine (Baltimore) 2023; 102: e34182
• 16 Deng F, Jia F, Sun Y. et al. Predictive value of the serum uric acid to high-density lipoprotein cholesterol ratio for culprit plaques in patients with acute coronary syndrome. BMC Cardiovasc Disord 2024; 24: 155
• 17 Sun H, Su H, Zheng R. et al. Serum uric acid to high‑density lipoprotein cholesterol ratio is associated with visceral fat in patients with type 2 diabetes. Diabetes Metab Syndr Obes 2023; 16: 959-967
• 18 Li G, Zhao Q, Zhang X. et al. Association between the uric acid to high density lipoprotein cholesterol ratio and alanine transaminase in Chinese short stature children and adolescents: A cross-sectional study. Front Nutr 2023; 10: 1063534
• 19 DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 1979; 237: E214-E223
• 20 Aktas G, Alcelik A, Ozlu T. et al. Association between omentin levels and insulin resistance in pregnancy. Exp Clin Endocrinol Diabetes 2014; 122: 163-166
• 21 Dikker O, Aktaş A, Şahin M. et al. The association of serum uric acid levels and various uric acid-related ratios with insulin resistance and obesity: A preliminary study in adolescents. Children (Basel) 2023; 10: 1493
• 22 Zhou X, Xu J. Association between serum uric acid-to-high-density lipoprotein cholesterol ratio and insulin resistance in patients with type 2 diabetes mellitus. J Diabetes Investig 2024; 15: 113-120
• 23 Zhou X, Xu J. Association between serum uric acid-to-high-density lipoprotein cholesterol ratio and insulin resistance in an American population: A population-based analysis. J Diabetes Investig 2024; 15: 762-771
• 24 Simental-Mendía LE, Guerrero-Romero F. The correct formula for the triglycerides and glucose index. Eur J Pediatr 2020; 179: 1171
• 25 Bello-Chavolla OY, Almeda-Valdes P, Gomez-Velasco D. et al. METS-IR, a novel score to evaluate insulin sensitivity, is predictive of visceral adiposity and incident type 2 diabetes. Eur J Endocrinol 2018; 178: 533-544
• 26 Matthews DR, Hosker JP, Rudenski AS. et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419
• 27 Legro RS, Finegood D, Dunaif A. A fasting glucose to insulin ratio is a useful measure of insulin sensitivity in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1998; 83: 2694-2698
• 28 McAuley KA, Williams SM, Mann JI. et al. Diagnosing insulin resistance in the general population. Diabetes Care 2001; 24: 460-464
• 29 Levy JC, Matthews DR, Hermans MP. Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care 1998; 21: 2191-2192
• 30 Yu W, Xie D, Yamamoto T. et al. Mechanistic insights of soluble uric acid-induced insulin resistance: Insulin signaling and beyond. Rev Endocr Metab Disord 2023; 24: 327-343
• 31 Li C, Hsieh MC, Chang SJ. Metabolic syndrome, diabetes, and hyperuricemia. Curr Opin Rheumatol 2013; 25: 210-216
• 32 Van Linthout S, Spillmann F, Schultheiss HP. et al. High-density lipoprotein at the interface of type 2 diabetes mellitus and cardiovascular disorders. Curr Pharm Des 2010; 16: 1504-1516
• 33 von Eckardstein A, Sibler RA. Possible contributions of lipoproteins and cholesterol to the pathogenesis of diabetes mellitus type 2. Curr Opin Lipidol 2011; 22: 26-32
• 34 Caporaso NE, Jones RR, Stolzenberg-Solomon RZ. et al. Insulin resistance in healthy U.S. adults: Findings from the National Health and Nutrition Examination Survey (NHANES). Cancer Epidemiol Biomarkers Prev 2020; 29: 157-168
• 35 Lee JA, Laurson KR. Obesity and insulin resistance screening tools in American adolescents: National Health and nutrition examination survey (NHANES) 1999–2010. Can J Diabetes 2016; 40: 311-317
• 36 Sumner AE, Cowie CC. Ethnic differences in the ability of triglyceride levels to identify insulin resistance. Atherosclerosis 2008; 196: 696-703
• 37 Geloneze B, Vasques AC, Stabe CF. et al. HOMA1-IR and HOMA2-IR indexes in identifying insulin resistance and metabolic syndrome: Brazilian Metabolic Syndrome Study (BRAMS). Arq Bras Endocrinol Metabol 2009; 53: 281-287
• 38 Ryoo JH, Hong HP, Park SK. et al. The risk for insulin resistance according to the degree of non-alcoholic fatty liver disease in Korean men. J Korean Med Sci 2016; 31: 1761-1767
• 39 Carvalho CA, Silva AAM, Assunção MCF. et al. The dietary inflammatory index and insulin resistance or metabolic syndrome in young adults. Nutrition 2019; 58: 187-193
• 40 Kazukauskiene N, Podlipskyte A, Varoneckas G. et al. Insulin resistance in association with thyroid function, psychoemotional state, and cardiovascular risk factors. Int J Environ Res Public Health 2021; 18: 3388
• 41 Podlipskyte A, Kazukauskiene N, Varoneckas G. et al. Association of insulin resistance with cardiovascular risk factors and sleep complaints: A 10-year follow-up. Front Public Health 2022; 10: 848284