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https://doi.org/10.53941/ijctm.2025.1000012
Jialal, I., & Adams-Huet, B. Circulating Neutrophil and Monocyte Ratios to High Density Lipoprotein-Cholesterol Are Elevated with Increased Triglyceride-Glucose Index. International Journal of Clinical and Translational Medicine. 2025. doi: https://doi.org/10.53941/ijctm.2025.1000012
Volume 1, Issue 2, 2025
Copyright (c) 2025 by the authors.
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This work is licensed under a Creative Commons Attribution 4.0 International License.

Original Research Articles

Circulating Neutrophil and Monocyte Ratios to High Density Lipoprotein-Cholesterol Are Elevated with Increased Triglyceride-Glucose Index

Ishwarlal Jialal 1,*,† and Beverley Adams-Huet 2

1 UC Davis School of Medicine, 2616 Hepworth Drive, Davis, CA 95618, USA

2 UT Southwestern Medical Center, Dallas, TX 75390, USA

* Correspondence: kjialal@gmail.com; Tel.: +1-530-902-0125

† Retired Distinguished Professor of Internal Medicine and Pathology.

Received: 15 March 2025; Accepted: 28 March 2025; Published: 8 April 2025

Abstract: The triglyceride-glucose (TyG) index, is a promising biomarker of Metabolic Syndrome (MetS), Type-2 Diabetes (T2DM) and premature atherosclerotic cardiovascular diseases (ASCVD). Whilst increased inflammation is a crucial mechanism in the pathogenesis of these disorders there is a general paucity of data on the association of the TyG index and inflammation. Accordingly, in the present report we investigated the relationship between tertiles of TyG index and accepted measures of inflammation, the ratios of Neutrophil (PMN):HDL-C and Monocyte(Mono):HDL-C in a cohort of 99 individuals (41 controls and 58 patients with MetS). Both PMN:HDL-C and Mono:HDL-C ratios increased significantly with increasing tertiles of the TyG index and both ratios correlated significantly with the TyG index. Also there was a significant correlation with certain biomarkers of inflammation which also increased over tertiles of PMN:HDL-C and Mono:HDL-C. In conclusion, in this cross-sectional study, we provide further support for a pro-inflammatory phenotype with an increase in the TyG index as manifest by increases in the ratio of the professional phagocytes (neutrophils and monocytes) to HDL-C, as a potential mechanism to explain the increase risk for cardio-metabolic syndromes. 

Keywords:

triglyceride-glucose index inflammation monocytes neutrophils insulin resistance

References

  1. Gounden, V.; Devaraj, S.; Jialal, I. The role of the triglyceride-glucose index as a biomarker of cardio-metabolic syndromes. Lipids Health Dis. 2024, 23, 416. https://doi.org/10.1186/s12944-024-02412-6.
  2. Tao, L.C.; Xu, J.N.; Wang, T.T.; et al. Triglyceride-glucose index as a marker in cardiovascular diseases: Landscape and limitations. Cardiovasc. Diabetol. 2022, 21, 68. https://doi.org/10.1186/s12933-022-01511-.
  3. Guerrero-Romero, F.; Simental-Mendía, L.E.; González-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.
  4. Nayak, S.S.; Kuriyakose, D.; Polisetty, L.D.; et al. Diagnostic and prognostic value of triglyceride glucose index: A comprehensive evaluation of meta-analysis. Cardiovasc. Diabetol. 2024, 23, 310. https://doi.org/10.1186/s12933-024-02392.
  5. Adams-Huet, B.; Jialal, I. An Increasing Triglyceride-Glucose Index Is Associated with a Pro-Inflammatory and Pro-Oxidant Phenotype. J. Clin. Med. 2024, 13, 3941. https://doi.org/10.3390/jcm13133941.
  6. Mildner, A.; Kim, K.W.; Yona, S. Unravelling monocyte functions: From the guardians of health to the regulators of disease. Discov. Immunol. 2024, 3, kyae014. https://doi.org/10.1093/discim/kyae014.
  7. Libby, P.; Nahrendorf, M.; Swirski, F.K. Monocyte heterogeneity in cardiovascular disease. Semin. Immunopathol. 2013, 35, 553–562. https://doi.org/10.1007/s00281-013-0387-3.
  8. Aroca-Crevillén, A.; Vicanolo, T.; Ovadia, S.; et al. Neutrophils in Physiology and Pathology. Annu. Rev. Pathol. 2024, 19, 227–259. https://doi.org/10.1146/annurev-pathmechdis-051222-015009.
  9. He, W.; Yan, L.; Hu, D.; et al. Neutrophil heterogeneity and plasticity: Unveiling the multifaceted roles in health and disease. MedComm 2025, 6, e70063. https://doi.org/10.1002/mco2.70063.
  10. Jialal, I.; Jialal, G.; Adams-Huet, B.; et al. Neutrophil and monocyte ratios to high-density lipoprotein-cholesterol and adiponectin as biomarkers of nascent metabolic syndrome. Horm. Mol. Biol. Clin. Investig. 2020, 41. https://doi.org/10.1515/hmbci-2019-0070.
  11. Jialal, I.; Huet, B.A.; Kaur, H.; et al. Increased toll-like receptor activity in patients with metabolic syndrome. Diabetes Care 2012, 35, 900–904.
  12. Ganjali, S.; Gotto, A.M., Jr.; Ruscica, M.; et al. Monocyte-to-HDL-cholesterol ratio as a prognostic marker in cardiovascular diseases. J. Cell. Physiol. 2018, 233, 9237–9246. https://doi.org/10.1002/jcp.27028.
  13. Vahit, D.; Akboga, M.K.; Samet, Y.; et al. Assessment of monocyte to high density lipoprotein cholesterol ratio and lymphocyte-to-monocyte ratio in patients with metabolic syndrome. Biomark. Med. 2017, 11, 535–540. https://doi.org/10.2217/bmm-2016-0380.
  14. Li, Y.; Guo, X.; Ge, J.; et al. Sex differences in associations of metabolic inflammation and insulin resistance with incident type 2 diabetes mellitus: A retrospective cohort of adults with annual health examinations. Lipids Health Dis. 2025, 24, 50. https://doi.org/10.1186/s12944-025-02473-1.
  15. Boughanem, H.; Torres-Peña, J.D.; Arenas-de Larriva, A.P.; et al. Mediterranean diet, neutrophil count, and carotid intima-media thickness in secondary prevention: The CORDIOPREV study. Eur. Heart J. 2025, 46, 719–729. https://doi.org/10.1093/eurheartj/ehae836.
  16. Pirillo, A.; Catapano, A.L.; Norata, G.D. Biological Consequences of Dysfunctional HDL. Curr. Med. Chem. 2019, 26, 1644–1664. https://doi.org/10.2174/0929867325666180530110543.
  17. Nazir, S.; Jankowski, V.; Bender, G.; et al. Interaction between high-density lipoproteins and inflammation: Function matters more than concentration! Adv. Drug Deliv. Rev. 2020, 159, 94–119. https://doi.org/10.1016/j.addr.2020.10.006.
  18. Brotfain, E.; Hadad, N.; Shapira, Y.; et al. Neutrophil functions in morbidly obese subjects. Clin. Exp. Immunol. 2015, 181, 156–163. https://doi.org/10.1111/cei.12631.
  19. Nijhuis, J.; Rensen, S.S.; Slaats, Y.; et al. Neutrophil activation in morbid obesity, chronic activation of acute inflammation. Obesity 2009, 17, 2014–2018. https://doi.org/10.1038/oby.2009.113.
  20. Jialal, I.; Devaraj, S. Subcutaneous adipose tissue biology in metabolic syndrome. Horm. Mol. Biol. Clin. Investig. 2018, 33, 20170074. https://doi.org/10.1515/hmbci-2017-0074.
  21. Wang, Z.; Qian, H.; Zhong, S.; et al. The relationship between triglyceride-glucose index and albuminuria in United States adults. Front. Endocrinol. 2023, 14, 1215055. https://doi.org/10.3389/fendo.2023.1215055.
  22. Jung, C.Y.; Yoo, T.H. Pathophysiologic Mechanisms and Potential Biomarkers in Diabetic Kidney Disease. Diabetes Metab. J. 2022, 46, 181–197. https://doi.org/10.4093/dmj.2021.0329.