The Relationship between Frailty, Hemoglobin-Albumin-lymphocyte-Platelet (HALP) Score, and Systemic Inflammatory Index (SII) in Elderly Type 2 Diabetic Patients

Authors

  • Gulali Aktas Abant Izzet Baysal University Hospital, Department of Internal Medicine, Bolu, Turkey Author
  • Murat Pehlivan Hacettepe University Hospital, Department of Geriatrics, Ankara, Turkey Author
  • Burcin Meryem Atak Tel Abant Izzet Baysal University Hospital, Department of Internal Medicine, Bolu, Turkey Author
  • Satilmis Bilgin Abant Izzet Baysal University Hospital, Department of Internal Medicine, Bolu, Turkey Author
  • Elif Basaran Ankara Liv Hospital, Department of Internal Medicine, Ankara, Turkey Author
  • Atiqa Khalid Woman Medical Officer, Gynaecology and Obstetrics Department, Tehsil Headquarter Hospital, Jahanian, Pakistan Author
  • Emre Cimenden Abant Izzet Baysal University Hospital, Department of Internal Medicine, Bolu, Turkey Author
  • Tuba Taslamacioglu Duman Abant Izzet Baysal University Hospital, Department of Internal Medicine, Bolu, Turkey Author

DOI:

https://doi.org/10.64229/tygtab29

Keywords:

Frailty, HALP score, Inflammation, SII, Type 2 diabetes mellitus, Elderly

Abstract

Aim: Frailty, a clinical syndrome of reduced physiological reserves and increased vulnerability, is a key concern in managing type 2 diabetes mellitus (T2DM). Biomarkers like the systemic inflammatory index (SII) and the hemoglobin-albumin-lymphocyte-platelet (HALP) score have shown promise in understanding the inflammatory and nutritional factors underlying frailty. Present study explored the relationship between frailty, HALP, and SII in elderly diabetic patients.

Method: We included diabetic patients aged 65 years and older who visited the institutional outpatient clinics. Participants were classified as frail or non-frail using the Edmonton Frail Scale. The SII and HALP score of the frail and non-frail diabetic subjects were compared.

Results: There were 112 and 189 subjects in frail and non-frail groups, respectively. Mean SII level of the frail patients was significantly higher than that of the non-frail diabetic subjects (911 ± 322 vs 568 ± 286), (p<0.001). Median HALP score of the frail group (35 [7-142]) was significantly lower than the HALP score of the non-frail group (54 [6-143]), (p<0.001). According to the ROC analyses, the sensitivity and specificity of HALP score (when lower than 38.7) in detecting frailty in diabetic patients were 76% and 59%, respectively. The sensitivity and specificity of SII (when higher than 652) in detecting frailty were 60% and 73%, respectively. Multivariate analyses revealed that both SII and HALP score were independent risk factors for frailty.

Conclusion: HALP and SII may serve as potential screening markers and warrant validation in larger longitudinal studies. We suggest that elevated SII and decreased HALP score in patients with T2DM should alert physicians for possible frailty.

References

[1]Khan KT, Hemati K, Donovan AL. Geriatric Physiology and the Frailty Syndrome. Anesthesiology Clinics, 2019; 37(3), 453-474. DOI: 10.1016/j.anclin.2019.04.006

[2]Keegan GL, Bhardwaj N, Abdelhafiz AH. The outcome of frailty in older people with diabetes as a function of glycaemic control and hypoglycaemic therapy: a review. Expert Review of Endocrinology & Metabolism, 2023, 18(5), 361-375. DOI: 10.1080/17446651.2023.2239907

[3]Lee YJ, Kim MH, Lim DJ, Lee JM, Chang SA, Lee J. Exploring the Association between Thyroid Function and Frailty: Insights from Representative Korean Data. Endocrinology and Metabolism (Seoul, Korea), 2023, 38(6), 729-738. DOI: 10.3803/EnM.2023.1769

[4]Akan S, Aktas G. Relationship between frailty, according to three frail scores, and clinical and laboratory parameters of the geriatric patients with type 2 Diabetes Mellitus. Revista da Associacao Medica Brasileira (1992), 2022, 68(8), 1073-1077. DOI: 10.1590/1806-9282.20220271

[5]Zheng Z, Luo HH, Xue QY. U-shaped association of systemic immune-inflammation index levels with cancer-related and all-cause mortality in middle-aged and older individuals with frailty. Archives of Gerontology and Geriatrics, 2023, 116, 105228. DOI: 10.1016/j.archger.2023.105228

[6]Tian MK, Li YF, Wang X, Tian X, Pei LL, Wang X, et al. The Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) Score Is Associated With Poor Outcome of Acute Ischemic Stroke. Frontiers in Neurology, 2020, 11, 610318. DOI: 10.3389/fneur.2020.610318

[7]Bilgin S, Aktas G, Zahid Kocak M, Atak BM, Kurtkulagi O, Taslamacioglu Duman T, et al. Association between novel inflammatory markers derived from hemogram indices and metabolic parameters in type 2 diabetic men.The Aging Male, 2020, 23(5), 923-927. DOI: 10.1080/13685538.2019.1632283

[8]Bilgin S, Aktas G, Kahveci G, Atak BM, Kurtkulagi O, Taslamacioglu Duman T. Does mean platelet volume/lymphocyte count ratio associate with frailty in type 2 diabetes mellitus? Bratislavske Lekarske Listy, 2021, 122(2), 116-119. DOI: 10.4149/bll_2021_017

[9]Taslamacioglu Duman T, Ozkul FN, Balci B. Could Systemic Inflammatory Index Predict Diabetic Kidney Injury in Type 2 Diabetes Mellitus? Diagnostics (Basel), 2023, 13(12), 2063. DOI: 10.3390/diagnostics13122063

[10]Ustaoglu M, Aktas G, Kucukdemirci O, Goren I, Bas B. Could a reduced hemoglobin, albumin, lymphocyte, and platelet (HALP) score predict autoimmune hepatitis and degree of liver fibrosis? Revista da Associacao Medica Brasileira (1992), 2024, 70(1), e20230905. DOI: 10.1590/1806-9282.20230905

[11]Rolfson DB, Majumdar SR, Tsuyuki RT, Tahir A, Rockwood K. Validity and reliability of the Edmonton Frail Scale. Age and Ageing, 2006, 35(5), 526-529. DOI: 10.1093/ageing/afl041

[12]Puts MT, Visser M, Twisk JW, Deeg DJ, Lips P. Endocrine and inflammatory markers as predictors of frailty. Clinical Endocrinology (Oxf), 2005, 63(4), 403-411. DOI: 10.1111/j.1365-2265.2005.02355.x

[13] Soysal P, Stubbs B, Lucato P, Luchini C, Solmi M, Peluso R, et al. Inflammation and frailty in the elderly: A systematic review and meta-analysis. Ageing Reseach Reviews, 2016, 31, 1-8. DOI: 10.1016/j.arr.2016.08.006

[14]Ferrucci L, Fabbri E. Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nature Reviews Cardiology, 2018, 15, 505-522. DOI: 10.1038/s41569-018-0064-2

[15] Yang YL, Wu CH, Hsu PF, Chen SC, Huang SS, Chan WL, et al. Systemic immune-inflammation index (SII) predicted clinical outcome in patients with coronary artery disease. European Journal of Clinical Investigation, 2020, 50(5), e13230. DOI: 10.1111/eci.13230

[16]Huang YW, Yin XS, Li ZP. Association of the systemic immune-inflammation index (SII) and clinical outcomes in patients with stroke: A systematic review and meta-analysis. Frontiers in Immunology, 2022, 13, 1090305. DOI: 10.3389/fimmu.2022.1090305

[17]Fu HY, Zheng J, Cai JY, Zeng KN, Yao J, Chen L, et al. Systemic Immune-Inflammation Index (SII) is Useful to Predict Survival Outcomes in Patients After Liver Transplantation for Hepatocellular Carcinoma within Hangzhou Criteria. Celularl Physiology and Biochemistry, 2018, 47(1), 293-301. doi:10.1159/000489807

[18]Uchmanowicz I. Oxidative Stress, Frailty and Cardiovascular Diseases: Current Evidence. Advance in Experimental Medicine Biology, 2020, 1216, 65-77. DOI: 10.1007/978-3-030-33330-0_8

[19]Mir R, Jha CK, Khullar N, Maqbool M, Dabla PK, Mathur S, et al. The Role of Inflammatory and Cytokine Biomarkers in the Pathogenesis of Frailty Syndrome. Endocrine Metabolic and Immune Disorders Drug Targets, 2022, 22(14), 1357-1366. DOI: 10.2174/1871530322666220304220522

[20]Wang G, Han BH, Zhang RX, Liu Q, Wang XD, Huang XT, et al. C1q/TNF-Related Protein 9 Attenuates Atherosclerosis by Inhibiting Hyperglycemia-Induced Endothelial Cell Senescence Through the AMPKα/KLF4 Signaling Pathway. Frontiers in Pharmacology, 2021, 12, 758792. DOI: 10.3389/fphar.2021.758792

[21]Bilgin S, Aktas G, Kurtkulagi O, Atak BM, Duman TT, et al. Edmonton frail score is associated with diabetic control in elderly type 2 diabetic subjects. Journal of Diabetes Metabolic Disorders, 2020, 19(1), 511-514. DOI: 10.1007/s40200-020-00542-z

[22]Tel BMA, Bilgin S, Kurtkulagi O, Kahveci G, Duman TT, Sagdic T, et al. Frailty in diabetic subjects during COVID-19 and its association with HbA1c, mean platelet volume and monocyte/lymphocyte ratio. Clinical Diabetology, 2022, 11(2), 119-126. DOI: 10.5603/DK.a2022.0015

[23]Güç ZG, Alacacıoğlu A, Kalender ME, Oflazoğlu U, Ünal S, Yıldız Y, et al. HALP score and GNRI: Simple and easily accessible indexes for predicting prognosis in advanced stage NSCLC patients. The İzmir oncology group (IZOG) study. Frontiers in Nutrition, 2022, 9, 905292. DOI: 10.3389/fnut.2022.905292

[24]Zhang HR, Wei XJ, Chen XT, Sun XD. Mortality from all-cause and cause-specific in the elderly: Joint implications of anemia and frailty. Archives of Gerontology and Geriatrics, 2023, 115, 105213. DOI: 10.1016/j.archger.2023.105213

[25]Yamamoto M, Adachi H, Enomoto M, Fukami A, Nakamura S, Nohara Y, et al. Lower albumin levels are associated with frailty measures, trace elements, and an inflammation marker in a cross-sectional study in Tanushimaru. Environmental Health and Preventive Medicine, 2021, 26(1), 25. DOI: 10.1186/s12199-021-00946-0

[26]Buigues C, Navarro-Martínez R, Sánchez-Martínez V, Serrano-Carrascosa M, Rubio-Briones J, Cauli O. Interleukin-6 and Lymphocyte Count Associated and Predicted the Progression of Frailty Syndrome in Prostate Cancer Patients Undergoing Antiandrogen Therapy. Cancers (Basel), 2020, 12. DOI: 10.3390/cancers12071716

[27]Arauna D, García F, Rodríguez-Mañas L, Marrugat J, Sáez C, Alarcón M, et al. Older adults with frailty syndrome present an altered platelet function and an increased level of circulating oxidative stress and mitochondrial dysfunction biomarker GDF-15. Free Radical Biology & Medicine, 2020, 149: 64-71. DOI: 10.1016/j.freeradbiomed.2020.01.007

[28]Sciacchitano S, Carola V, Nicolais G, Sciacchitano S, Napoli C, Mancini R, et al. To Be Frail or Not to Be Frail: This Is the Question-A Critical Narrative Review of Frailty. Journal of Clinical Medicine, 2024, 13(3). DOI: 10.3390/jcm13030721

[29]Bhatti JS, Sehrawat A, Mishra J, Sidhu IS, Navik U, Khullar N, et al. Oxidative stress in the pathophysiology of type 2 diabetes and related complications: Current therapeutics strategies and future perspectives. Free Radical Biology & Medicine, 2022, 184, 114-134. DOI: 10.1016/j.freeradbiomed.2022.03.019

[30]Thuluvath AJ, Verna EC. Deciphering an expanding array of clinical and research frailty measures. Clinical Liver Disease (Hoboken), 2024, 23(1), e0180. DOI: 10.1097/cld.0000000000000180

[31]Moradell A, Fernández-García ÁI, Navarrete-Villanueva D, Sagarra-Romero L, Gesteiro E, Pérez-Gómez J, et al. Functional Frailty, Dietary Intake, and Risk of Malnutrition. Are Nutrients Involved in Muscle Synthesis the Key for Frailty Prevention? Nutrients, 2021, 13(4). DOI: 10.3390/nu13041231

[32]Eckart A, Struja T, Kutz A, Baumgartner A, Baumgartner T, Zurfluh S, et al. Relationship of Nutritional Status, Inflammation, and Serum Albumin Levels During Acute Illness: A Prospective Study. The American Journal of Medicine, 2020, 133(6), 713-722.e717. DOI: 10.1016/j.amjmed.2019.10.031

[33]Shevyrev D, Tereshchenko V, Berezina TN, Rybtsov S. Hematopoietic Stem Cells and the Immune System in Development and Aging. International Journal of Molecular Sciences, 2023, 24(6). DOI: 10.3390/ijms24065862

[34]Baechle JJ, Chen N, Makhijani P, Winer S, Furman D, Winer DA. Chronic inflammation and the hallmarks of aging. Molecular Metabolish, 2023, 74, 101755. DOI: 10.1016/j.molmet.2023.101755

[35]Zhang LX, Yang PP, Yin FR, Zhang JB, Zhao BL, Zhou JM. Association between frailty and hypoproteinaemia in older patients: meta-analysis and systematic review. BMC Geriatrics, 2024, 24(1), 689. DOI: 10.1186/s12877-024-05275-9

[36]Fulop T, Larbi A, Pawelec G, Khalil A, Cohen AA, Hirokawa K, et al. Immunology of Aging: the Birth of Inflammaging. Clinical Reviews in Allergy & Immunology, 2023, 64(2), 109-122. DOI: 10.1007/s12016-021-08899-6

[37]Lewis ED, Wu DY, Meydani SN. Age-associated alterations in immune function and inflammation. Progress in Neuro-psychopharmacol & Biological Psychiatry, 2022, 118, 110576. DOI: 10.1016/j.pnpbp.2022.110576

[38]Johnson J, Jaggers RM, Gopalkrishna S, Dahdah A, Murphy AJ, Hanssen NMJ, et al. Oxidative Stress in Neutrophils: Implications for Diabetic Cardiovascular Complications. Antioxidants & Redox Signaling, 2022, 36(10-12), 652-666. DOI: 10.1089/ars.2021.0116

[39]Guo WC, Song YC, Sun Y, Du HS, Cai Y,You QQ, et al. Systemic immune-inflammation index is associated with diabetic kidney disease in Type 2 diabetes mellitus patients: Evidence from NHANES 2011-2018. Frontiers in Endocrinology (Lausanne), 2022, 13, 1071465. DOI: 10.3389/fendo.2022.1071465

[40]Zhao Y, Shao WY, Zhu QH, Zhang R, Sun T, Wang BJ, et al. Association between systemic immune-inflammation index and metabolic syndrome and its components: results from the National Health and Nutrition Examination Survey 2011-2016. Journal of Translational Medicine, 2023, 21(1), 691. DOI: 10.1186/s12967-023-04491-y

[41]Ye CL, Yuan L, Wu KL, Shen BZ, Zhu CL. Association between systemic immune-inflammation index and chronic obstructive pulmonary disease: a population-based study. BMC Pulmonary Medicine, 2023, 23(1), 295. DOI: 10.1186/s12890-023-02583-5

[42]Olson ME, Hornick MG, Stefanski A, Albanna HR, Gjoni A, Hall GD, et al. A biofunctional review of C-reactive protein (CRP) as a mediator of inflammatory and immune responses: differentiating pentameric and modified CRP isoform effects. Frontiers in Immunology, 2023, 14, 1264383. DOI: 10.3389/fimmu.2023.1264383

[43]Molinari P, Caldiroli L, Abinti M, Nardelli L, Armelloni S, Cesari M, et al. Frailty Is Associated with Malnutrition-Inflammation Syndrome in Older CKD Patients. Nutrients, 2024, 16(16), 2626. DOI: 10.3390/nu16162626

[44]Chen Y, Yu CY, Deng WM. The role of pro-inflammatory cytokines in lipid metabolism of metabolic diseases. International Reviews of Immunology, 2019, 38(6), 249-266. DOI: 10.1080/08830185.2019.1645138

[45]Jiménez-Valverde A. Threshold-dependence as a desirable attribute for discrimination assessment: implications for the evaluation of species distribution models. Biodiversity and Conservation, 2014, 23, 369-385. DOI: 10.1007/s10531-013-0606-1

[46]Zhou J, Yang DF. Prognostic Significance of Hemoglobin, Albumin, Lymphocyte and Platelet (HALP) Score in Hepatocellular Carcinoma. Journal of Hepatocellular Carcinoma, 2023, 10, 821-831. DOI: 10.2147/jhc.s411521

[47]Zhang FP, Li LH, Shi TT, Liu Y, Xie J, Yu L. The hemoglobin, albumin, lymphocyte, and platelet (HALP) is a potent indicator for the prognosis in hemodialysis patients. Medicine (Baltimore) 2023; 102: e33650. doi:10.1097/md.0000000000033650

[48]Bayram F, Ozgen G, Karasın SS, Ozgen L. The predictive value of HALP score and systemic immune inflammation (SII) index in hyperemesis gravidarum. Journal of Obstetrics and Gynaecology Research, 2023, 49(7), 1729-1735. DOI: 10.1111/jog.15666

[49]Günaydın FE. The predictive value of HALP score and systemic immune inflammation (SII) index in patients with asthma. The Annals of Clinical and Analytical Medicine, 2023, 14, S357-360. DOI: 10.4328/ACAM.21945

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2025-11-20

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