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Investigation of the Relationship Between HbA1c Levels and Inflammatory Markers

Year 2025, Volume: 12 Issue: 2, 135 - 144, 28.08.2025
https://doi.org/10.47572/muskutd.1628895

Abstract

The purpose of our study is to evaluate the possible complications and treatment process in diabetic patients by examining the relationship between neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), C-reactive protein (CRP), sedimentation and Systemic Immun Inflamation Index (SII). The study included who had HbA1c tests taken from the outpatient and in hospital patients of Aydin Adnan Menderes University Hospital between January-August 2023. The demographic data and HbA1c, NLR, PLR, SII, sedimentation, CRP were recorded. Patients were divided into 3 groups as non-diabetic (HbA1c<6%), prediabetes (6–6.4%) and (≥6.5%) diabetic. The levels of various inflammation markers were compared between different patient groups. A statistically significant relation was identified between HbA1c levels and albumin (p<0.001), CRP (p=0.003), sedimentation (p<0.001), and NLR (p=0.021). Upon examination of the HbA1c groups as discrete categories, namely non-diabetes (<6), prediabetes (6-6.4) and diabetes (>6.5), at the level of non-diabetes and prediabetes a notable relation was observed between albumin (p=0.028), CRP (p=0.013) and sedimentation (p=0.014). Once more, a statistically significant relationship was identified between albumin (p<0.0001), CRP (p=0.013), sedimentation (p<0.0001) and NLR (p=0.020) in the non-diabetic and diabetic groups. No notable relation was identified between the prediabetes and diabetes groups and any of the inflammatory markers under investigation (p>0.05). The findings of our study indicate that in patients with diabetic (>6.5) or non-diabetic (<6) HbA1c, the use of NLR and SII as inexpensive and readily accessible inflammatory markers is a viable proposition.

Ethical Statement

The ethics committee approval for the study was obtained X University Clinical Research Ethics Committee (2023/183).

References

  • Guo H, Wu H, Li Z. The Pathogenesis of Diabetes. Int J Mol Sci. 2023;24(8):6978.
  • NCD Risk Factor. Worldwide trends in diabetes prevalence and treatment from 1990 to 2022: a pooled analysis of 1108 population-representative studies with 141 million participants. Lancet. 2024;404(10467):2077-2093.
  • Green A, Hede SM, Patterson CC, et al. Type 1 diabetes in 2017: global estimates of incident and prevalent cases in children and adults. Diabetologia. 2021;64:2741.
  • Centers for Disease Control and Prevention: National Diabetes Statistics Report, https://www.cdc.gov/diabetes/php/data-research/index.html (Accessed on October 23, 2024).
  • Fang M, Wang D, Coresh J, Selvin E. Undiagnosed Diabetes in U.S. Adults: Prevalence and Trends. Diabetes Care. 2022;45:1994.
  • TEMD Diabetes Mellitus ve Komplikasyonlarının Tanı, Tedavi ve İzlem Kılavuzu 2024, https://file.temd.org.tr/uploads/publications/guides/documents/diabetesmellitus2024.pdf, access date 26.06.2024
  • Dunn TC, Xu Y, Bergenstal RM, et al. Personalized Glycated Hemoglobin in Diabetes Management: Closing the Gap with Glucose Management Indicator. Diabetes Technol Ther. 2023;25(S3):S65-74.
  • Kurniawan LB. HbA1c As Diabetes Mellitus Biomarker and Its Methods Evolution. IJCPML. 2024;30(2):198–203.
  • Unluguzel Ustun G, Keskin A, Aci R, et al. Association between HbA1c and severity of covid 19 patients. Hemoglobin. 2021;45(2):124-8.
  • Nøst TH, Alcala K, Urbarova I, et al. Systemic inflammation markers and cancer incidence in the UK Biobank. Eur J Epidemiol. 2021;36(8):841-8.
  • Qiu Z, Jiang Y, Jiang X, et al. Relationship Between Platelet to Lymphocyte Ratio and Stable Coronary Artery Disease: Meta-Analysis of Observational Studies. Angiology. 2020;71(10):909-15.
  • Jarmuzek P, Kozlowska K, Defort P, Kot M, Zembron-Lacny A. Prognostic Values of Systemic Inflammatory Immunological Markers in Glioblastoma: A Systematic Review and Meta-Analysis. Cancers (Basel). 2023;15(13):3339.
  • Hossain N, Haque M, Karmakar P, et al. Association of serum high sensitivity c-reactive protein with insulin resistance in patirnts with type 2 diabetes mellitus. Eastern Med Coll J. 2022;7(1):15-20.
  • Cai Q, Huang D, Ou P, et al. COVID-19 in a designated infectious diseases hospital outside Hubei Province, China. Allergy. 2020;75(7):1742-52.
  • Guo W, Song Y, Sun Y, et al. Systemic immune-inflammation index is associated with diabetic kidney disease in Type 2 diabetes mellitus patients: Evidence from NHANES 2011-2018. Front Endocrinol. 2022;13:1071465.
  • Öngen İpek B, Sitar ME. HbA1c değerlerinin inflamatuar belirteçleri ile ilişkisi. Türk Klinik Biyokimya Derg. 2018;16(2):83-90.
  • Taslamacioglu Duman T, Ozkul FN, et al. Could systemic inflammatory index predict diabetic kidney injury in Type 2 Diabetes Mellitus? Diagnostics. 2023;13(12): 2063.
  • Lou M, Luo P, Tang R, et al. Relationship between neutrophil-lymphocyte ratio and insulin resistance in newly diagnosed type 2 diabetes mellitus patients. BMC Endocr Disord. 2015;15:9.
  • Sefil F, Ulutas KT, Dokuyucu R, et al. Investigation of neutrophil lymphocyte ratio and blood glucose regulation in patients with type 2 diabetes mellitus. J Int Med Res. 2014;42(2):581-8.
  • Shiny A, Bibin YS, Shanthirani CS, et al. Association of neutrophil-lymphocyte ratio with glucose intolerance: an indicator of systemic inflammation in patients with type 2 diabetes. Diabetes Technol Ther. 2014;16(8):524-30.
  • Kim JK, Lee AY, Kang JH, et al. Association of fasting glucose level with neutrophil-lymphocyte ratio compared to leukocyte count and serum c- reactive protein. Korean J Fam Med. 2018;39(1):42-50.
  • Mertoglu C, Gunay M. Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as useful predictive markers of prediabetes and diabetes mellitus. Diabetes Metab Syndr. 2017;11(1):127-31.
  • Frohlich M, Imhof A, Berg G, et al. Association between c-reactive protein and features of the metabolic syndrome: a population-based study. Diabetes Care. 2000; 23(12):1835-9.
  • Lemieux I, Pascot A, Prud'homme D, et al. Elevated c-reactive protein: another component of the atherothrombotic profile of abdominal obesity. Arterioscler Thromb Vasc Biol. 2001;21(6):961-7.
  • Pradhan AD, Manson JE, Rifai N, et al. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA. 2001;286(3):327-34.
  • Yesilyurt S, Ozsenel EB, Senat A, et al. The Relationship between hemoglobin A1c and hemogram-derived novel inflammatory indices. South Clin Ist Euras. 2024;35(1): 47-53.
  • Guo W, Song Y, Sun Y, et al. Systemic immune- inflammation index is associated with diabetic kidney disease in type 2 diabetes mellitus patients: Evidence from NHANES 2011-2018. Front Endocrinol Lausanne. 2022;13:1071465.
  • Song Y, Zhao Y, Shu Y, et al. Combination model of neutrophil to high-density lipoprotein ratio and system inflammation response index is more valuable for predicting periph- eral arterial disease in type 2 diabetic patients: A cross-sectional study. Front Endocrinol Lausanne 2023;14:1100453.
  • Kachekouche Y, Dali-Sahi M, Benmansour D, et al. Hematological profile associated with type 2 diabetes mellitus. Diabetes Metab Syndr. 2018;12(3):309-12.
  • Zhang M, Zhang Y, Li C, et al. Association between red blood cell distribution and renal function in patients with untreated type 2 diabetes mellitus. Ren Fail. 2015;37(4):659-63.
  • Muscari A, Antonelli S, Bianchi G, et al. Serum C3 is a stronger inflammatory marker of insulin resistance than C-reactive protein, leukocyte count, and erythrocyte sedimentation rate: comparison study in an elderly population. Diabetes Care. 2007;30(9):2362-8.
  • Demirkol ME, Alisik M, Yis OM. C-reactive protein to albumin ratio in patients with prediabetes and diabetes mellitus: HbA1c and Inflammation. Clin Lab. 2022;68(8):10.
  • Huang SH, Huang PJ, Li JY, et al. Hemoglobin a1c levels associated with age and gender in taiwanese adults without prior diagnosis with diabetes. Int J Environ Res Public Health. 2021;18(7):3390.
  • Brož J, Janíčková Ždárská D, Štěpánová R, Kvapil M. Addition of basal ınsulin to oral antidiabetic agents in patients with ınadequately controlled type 2 diabetes leads to ımproved HbA1c levels: metabolic control, frequency of hypoglycemia, and ınsulin titration analysis as results of a prospective observational study (BALI Study). Diabetes Ther. 2019;10(2):663-72.
  • Urakçı Z. Çok yüksek HbA1c değerlerinin diyabetik komplikasyonlarla ilişkisinin değerlendirilmesi (Uzmanlık Tezi). Dicle Üniversitesi, Tıp Fakültesi, Diyarbakır, 2009, ss 53-4.

HbA1c Düzeyleri ile İnflamatuar Belirteçler Arasındaki İlişkinin Araştırılması

Year 2025, Volume: 12 Issue: 2, 135 - 144, 28.08.2025
https://doi.org/10.47572/muskutd.1628895

Abstract

Çalışmamızın amacı, nötrofil lenfosit oranı (NLR), trombosit lenfosit oranı (PLR), C-reaktif protein (CRP), sedimantasyon ve sistemik immün inflamasyon indeksi (Sİİ) ile HbA1c düzeyleri arasındaki ilişkiyi inceleyerek diyabetli hastalarda olası komplikasyonları ve tedavi sürecini değerlendirmektir. Çalışmaya Ocak 2023 ile Ağustos 2023 tarihleri arasında Aydın Adnan Menderes Üniversitesi Hastanesi'nin ayaktan ve yatan hastalarından HbA1c testleri yaptıranlar dahil edildi. Demografik veriler ve HbA1c, NLR, PLR, SII, sedimantasyon, CRP kaydedildi. Hastalar diyabetsiz (HbA1c<6%), prediyabet (%6-6,4) ve (% ≥6,5) diyabetli olmak üzere 3 gruba ayrıldı. Çeşitli inflamasyon belirteçlerinin düzeyleri farklı hasta grupları arasında karşılaştırıldı. Bulgular: HbA1c düzeyleri ile albumin (p<0,001), CRP (p=0,003), sedimentasyon (p<0,001) ve NLR (p=0,021) arasında istatistiksel olarak anlamlı ilişki saptandı. HbA1c grupları diyabetsiz (<6), prediyabetli (6-6,4) ve diyabetli (>6,5) olmak üzere ayrı kategoriler halinde incelendiğinde diyabetsiz ve prediyabet düzeyinde albumin (p=0,028), CRP (p=0,013) ve sedimentasyon (p=0,014) arasında belirgin bir ilişki gözlendi. Yine diyabetsiz ve diyabetli gruplarda albumin (p<0,0001), CRP (p=0,013), sedimentasyon (p<0,0001) ve NLR (p=0,020) arasında istatistiksel olarak anlamlı bir ilişki saptandı. Prediyabet ve diyabet grupları ile araştırılan inflamatuar belirteçlerden herhangi biri arasında belirgin bir ilişki saptanmamıştır (p>0,05). Çalışmamızın bulguları, diyabetli (>6,5) veya diyabetli olmayan (<6) HbA1c'li hastalarda, NLR ve SII'nin ucuz ve kolay erişilebilir inflamatuar belirteçler olarak kullanılmasının uygulanabilir bir öneri olduğunu göstermektedir.

References

  • Guo H, Wu H, Li Z. The Pathogenesis of Diabetes. Int J Mol Sci. 2023;24(8):6978.
  • NCD Risk Factor. Worldwide trends in diabetes prevalence and treatment from 1990 to 2022: a pooled analysis of 1108 population-representative studies with 141 million participants. Lancet. 2024;404(10467):2077-2093.
  • Green A, Hede SM, Patterson CC, et al. Type 1 diabetes in 2017: global estimates of incident and prevalent cases in children and adults. Diabetologia. 2021;64:2741.
  • Centers for Disease Control and Prevention: National Diabetes Statistics Report, https://www.cdc.gov/diabetes/php/data-research/index.html (Accessed on October 23, 2024).
  • Fang M, Wang D, Coresh J, Selvin E. Undiagnosed Diabetes in U.S. Adults: Prevalence and Trends. Diabetes Care. 2022;45:1994.
  • TEMD Diabetes Mellitus ve Komplikasyonlarının Tanı, Tedavi ve İzlem Kılavuzu 2024, https://file.temd.org.tr/uploads/publications/guides/documents/diabetesmellitus2024.pdf, access date 26.06.2024
  • Dunn TC, Xu Y, Bergenstal RM, et al. Personalized Glycated Hemoglobin in Diabetes Management: Closing the Gap with Glucose Management Indicator. Diabetes Technol Ther. 2023;25(S3):S65-74.
  • Kurniawan LB. HbA1c As Diabetes Mellitus Biomarker and Its Methods Evolution. IJCPML. 2024;30(2):198–203.
  • Unluguzel Ustun G, Keskin A, Aci R, et al. Association between HbA1c and severity of covid 19 patients. Hemoglobin. 2021;45(2):124-8.
  • Nøst TH, Alcala K, Urbarova I, et al. Systemic inflammation markers and cancer incidence in the UK Biobank. Eur J Epidemiol. 2021;36(8):841-8.
  • Qiu Z, Jiang Y, Jiang X, et al. Relationship Between Platelet to Lymphocyte Ratio and Stable Coronary Artery Disease: Meta-Analysis of Observational Studies. Angiology. 2020;71(10):909-15.
  • Jarmuzek P, Kozlowska K, Defort P, Kot M, Zembron-Lacny A. Prognostic Values of Systemic Inflammatory Immunological Markers in Glioblastoma: A Systematic Review and Meta-Analysis. Cancers (Basel). 2023;15(13):3339.
  • Hossain N, Haque M, Karmakar P, et al. Association of serum high sensitivity c-reactive protein with insulin resistance in patirnts with type 2 diabetes mellitus. Eastern Med Coll J. 2022;7(1):15-20.
  • Cai Q, Huang D, Ou P, et al. COVID-19 in a designated infectious diseases hospital outside Hubei Province, China. Allergy. 2020;75(7):1742-52.
  • Guo W, Song Y, Sun Y, et al. Systemic immune-inflammation index is associated with diabetic kidney disease in Type 2 diabetes mellitus patients: Evidence from NHANES 2011-2018. Front Endocrinol. 2022;13:1071465.
  • Öngen İpek B, Sitar ME. HbA1c değerlerinin inflamatuar belirteçleri ile ilişkisi. Türk Klinik Biyokimya Derg. 2018;16(2):83-90.
  • Taslamacioglu Duman T, Ozkul FN, et al. Could systemic inflammatory index predict diabetic kidney injury in Type 2 Diabetes Mellitus? Diagnostics. 2023;13(12): 2063.
  • Lou M, Luo P, Tang R, et al. Relationship between neutrophil-lymphocyte ratio and insulin resistance in newly diagnosed type 2 diabetes mellitus patients. BMC Endocr Disord. 2015;15:9.
  • Sefil F, Ulutas KT, Dokuyucu R, et al. Investigation of neutrophil lymphocyte ratio and blood glucose regulation in patients with type 2 diabetes mellitus. J Int Med Res. 2014;42(2):581-8.
  • Shiny A, Bibin YS, Shanthirani CS, et al. Association of neutrophil-lymphocyte ratio with glucose intolerance: an indicator of systemic inflammation in patients with type 2 diabetes. Diabetes Technol Ther. 2014;16(8):524-30.
  • Kim JK, Lee AY, Kang JH, et al. Association of fasting glucose level with neutrophil-lymphocyte ratio compared to leukocyte count and serum c- reactive protein. Korean J Fam Med. 2018;39(1):42-50.
  • Mertoglu C, Gunay M. Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as useful predictive markers of prediabetes and diabetes mellitus. Diabetes Metab Syndr. 2017;11(1):127-31.
  • Frohlich M, Imhof A, Berg G, et al. Association between c-reactive protein and features of the metabolic syndrome: a population-based study. Diabetes Care. 2000; 23(12):1835-9.
  • Lemieux I, Pascot A, Prud'homme D, et al. Elevated c-reactive protein: another component of the atherothrombotic profile of abdominal obesity. Arterioscler Thromb Vasc Biol. 2001;21(6):961-7.
  • Pradhan AD, Manson JE, Rifai N, et al. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA. 2001;286(3):327-34.
  • Yesilyurt S, Ozsenel EB, Senat A, et al. The Relationship between hemoglobin A1c and hemogram-derived novel inflammatory indices. South Clin Ist Euras. 2024;35(1): 47-53.
  • Guo W, Song Y, Sun Y, et al. Systemic immune- inflammation index is associated with diabetic kidney disease in type 2 diabetes mellitus patients: Evidence from NHANES 2011-2018. Front Endocrinol Lausanne. 2022;13:1071465.
  • Song Y, Zhao Y, Shu Y, et al. Combination model of neutrophil to high-density lipoprotein ratio and system inflammation response index is more valuable for predicting periph- eral arterial disease in type 2 diabetic patients: A cross-sectional study. Front Endocrinol Lausanne 2023;14:1100453.
  • Kachekouche Y, Dali-Sahi M, Benmansour D, et al. Hematological profile associated with type 2 diabetes mellitus. Diabetes Metab Syndr. 2018;12(3):309-12.
  • Zhang M, Zhang Y, Li C, et al. Association between red blood cell distribution and renal function in patients with untreated type 2 diabetes mellitus. Ren Fail. 2015;37(4):659-63.
  • Muscari A, Antonelli S, Bianchi G, et al. Serum C3 is a stronger inflammatory marker of insulin resistance than C-reactive protein, leukocyte count, and erythrocyte sedimentation rate: comparison study in an elderly population. Diabetes Care. 2007;30(9):2362-8.
  • Demirkol ME, Alisik M, Yis OM. C-reactive protein to albumin ratio in patients with prediabetes and diabetes mellitus: HbA1c and Inflammation. Clin Lab. 2022;68(8):10.
  • Huang SH, Huang PJ, Li JY, et al. Hemoglobin a1c levels associated with age and gender in taiwanese adults without prior diagnosis with diabetes. Int J Environ Res Public Health. 2021;18(7):3390.
  • Brož J, Janíčková Ždárská D, Štěpánová R, Kvapil M. Addition of basal ınsulin to oral antidiabetic agents in patients with ınadequately controlled type 2 diabetes leads to ımproved HbA1c levels: metabolic control, frequency of hypoglycemia, and ınsulin titration analysis as results of a prospective observational study (BALI Study). Diabetes Ther. 2019;10(2):663-72.
  • Urakçı Z. Çok yüksek HbA1c değerlerinin diyabetik komplikasyonlarla ilişkisinin değerlendirilmesi (Uzmanlık Tezi). Dicle Üniversitesi, Tıp Fakültesi, Diyarbakır, 2009, ss 53-4.
There are 35 citations in total.

Details

Primary Language English
Subjects ​Internal Diseases
Journal Section Original Article
Authors

Murat Arı 0000-0002-1504-7050

Hakan Cengiz 0000-0002-0868-0499

Ayça Tuzcu 0000-0002-5035-9711

Publication Date August 28, 2025
Submission Date January 29, 2025
Acceptance Date March 7, 2025
Published in Issue Year 2025 Volume: 12 Issue: 2

Cite

APA Arı, M., Cengiz, H., & Tuzcu, A. (2025). Investigation of the Relationship Between HbA1c Levels and Inflammatory Markers. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi, 12(2), 135-144. https://doi.org/10.47572/muskutd.1628895
AMA Arı M, Cengiz H, Tuzcu A. Investigation of the Relationship Between HbA1c Levels and Inflammatory Markers. MMJ. August 2025;12(2):135-144. doi:10.47572/muskutd.1628895
Chicago Arı, Murat, Hakan Cengiz, and Ayça Tuzcu. “Investigation of the Relationship Between HbA1c Levels and Inflammatory Markers”. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi 12, no. 2 (August 2025): 135-44. https://doi.org/10.47572/muskutd.1628895.
EndNote Arı M, Cengiz H, Tuzcu A (August 1, 2025) Investigation of the Relationship Between HbA1c Levels and Inflammatory Markers. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi 12 2 135–144.
IEEE M. Arı, H. Cengiz, and A. Tuzcu, “Investigation of the Relationship Between HbA1c Levels and Inflammatory Markers”, MMJ, vol. 12, no. 2, pp. 135–144, 2025, doi: 10.47572/muskutd.1628895.
ISNAD Arı, Murat et al. “Investigation of the Relationship Between HbA1c Levels and Inflammatory Markers”. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi 12/2 (August2025), 135-144. https://doi.org/10.47572/muskutd.1628895.
JAMA Arı M, Cengiz H, Tuzcu A. Investigation of the Relationship Between HbA1c Levels and Inflammatory Markers. MMJ. 2025;12:135–144.
MLA Arı, Murat et al. “Investigation of the Relationship Between HbA1c Levels and Inflammatory Markers”. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi, vol. 12, no. 2, 2025, pp. 135-44, doi:10.47572/muskutd.1628895.
Vancouver Arı M, Cengiz H, Tuzcu A. Investigation of the Relationship Between HbA1c Levels and Inflammatory Markers. MMJ. 2025;12(2):135-44.