Top

Diabetology International

Published in:

07-01-2022 | Type 1 Diabetes | Original Article

Leukocytic dysregulation in children with type 1 diabetes: relation to diabetic vascular complications

Authors: Nouran Yousef Salah, Nesrine Radwan, Heba Mohamed Atif

Published in: Diabetology International | Issue 3/2022

Abstract

Background

Growing evidences highlight the role of the innate immune response in the pathogenesis of type 1 diabetes (T1D) vascular complications. Neutrophil lymphocytic ratio (NLR) and platelet lymphocytic ratio (PLR) are inexpensive but novel markers of chronic inflammation might have prognostic value in children with T1D.

Aim

To study NLR and PLR levels in children with T1D in comparison to matched controls and correlate them with fraction-C of glycosylated hemoglobin (HbA1C) and micro-vascular complications.

Methodology

Hundred children with T1D were compared to 100 matched healthy controls. History included diabetes duration, insulin dose and frequency of hypoglycemic attacks. Fundus examination and the simple rapid neuropathy disability score were done. HbA1C, fasting lipids, urinary albumin excretion and complete blood count were measured with assessment of NLR and PLR

Results

NLR was significantly higher (p = 0.008) and PLR was significantly lower (p = 0.007) in children with T1D than controls. NLR was positively correlated while PLR was negatively correlated with HbA1C, diabetes duration, fasting cholesterol, triglycerides and LDL. NLR was significantly higher (p < 0.001) and PLR was significantly lower (p = 0.005) in children with microvascular complications than those without. Moreover, multivariate logistic regression revealed that microvascular complications were independently associated with NLR (p = 0.013) and PLR (p = 0.004).

Conclusion

Children with T1D had significantly higher NLR and lower PLR compared to controls. These changes were more evident in those with diabetic microvascular complications than those without. Furthermore, NLR was positively correlated and PLR was negatively correlated to HbA1C, diabetes duration and hyperlipidemia. Hence, NLR and PLR can be a potential indicator for the risk of development of diabetic microvascular complications in children with T1D.

Gliwiński M, Iwaszkiewicz-Grześ D, Wołoszyn-Durkiewicz A, Tarnowska M, Żalińska M, Hennig M, Zielińska H, Dukat-Mazurek A, Zielkowska-Dębska J, Zieliński M, Jaźwińska-Curyłło A, Owczuk R, Jarosz-Chobot P, Bossowski A, Szadkowska A, Młynarski W, Marek-Trzonkowska N, Moszkowska G, Siebert J, Myśliwiec M, Trzonkowski P. Proinsulin-specific T regulatory cells may control immune responses in type 1 diabetes: implications for adoptive therapy. BMJ Open Diabetes Res Care. 2020;8:e000873. https://doi.org/10.1136/bmjdrc-2019-000873.CrossRefPubMedPubMedCentral

Graves L, Donaghue K. Vascular complication in adolescents with diabetes mellitus. Front Endocrinol. 2020;11:340. https://doi.org/10.3389/fendo.2020.00370.CrossRef

Sun B, Luo Z, Zhou J. Comprehensive elaboration of glycemic variability in diabetic macrovascular and microvascular complications. Cardiovasc Diabetol. 2021;20:9. https://doi.org/10.1186/s12933-020-01200-7.CrossRefPubMedPubMedCentral

Mendes B, Oliveira A, Alcântara K. Comparison of the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in normoglycemic and hyperglycemic subjects. Einstein (Sao Paulo). 2019;17(1):eAO4403. https://doi.org/10.31744/einstein_journal/2019AO4403.CrossRef

Oguntibeju O. Type 2 diabetes mellitus, oxidative stress and inflammation: examining the links. Int J Physiol Pathophysiol Pharmacol. 2019;11(3):45–63.PubMedPubMedCentral

Paolisso P, Foà A, Bergamaschi L, Donati F, Fabrizio M, Chiti C, Angeli F, Toniolo S, Stefanizzi A, Armillotta M, Rucci P, Iannopollo G, Casella G, Marrozzini C, Galiè N, Pizzi C. Hyperglycemia, inflammatory response and infarct size in obstructive acute myocardial infarction and MINOCA. Cardiovasc Diabetol. 2021;20(1):33. https://doi.org/10.1186/s12933-021-01222-9.PMID:33530978;PMCID:PMC7856791.CrossRefPubMedPubMedCentral

Yang M, Weng H, Pei Q, Jing F, Yi Q. The relationship between retinol-binding protein 4 and markers of inflammation and thrombogenesis in children with Kawasaki disease. Mediators Inflamm. 2021;11(2021):7029514. https://doi.org/10.1155/2021/7029514.PMID:33505217;PMCID:PMC7814943.CrossRef

Pian G, Li H, Piao Y. Clinical significance of inflammation markers in predicting the severity of acute pancreatitis. Pancreas. 2021;50(2):201–5. https://doi.org/10.1097/MPA.0000000000001749 (PMID: 33565796).CrossRefPubMed

Liu J, Liu X, Li Y, Quan J, Wei S, An S, Yang R, Liu J. The association of neutrophil to lymphocyte ratio, mean platelet volume, and platelet distribution width with diabetic retinopathy and nephropathy: a meta-analysis. Biosci Rep. 2018;38(3):BSR20180172. https://doi.org/10.1042/BSR20180172.CrossRefPubMedPubMedCentral

10.

Forget P, Khalifa C, Defour J, Latinne D, Van Pel M, De Kock M. What is the normal value of the neutrophil-to-lymphocyte ratio? BMC Res Notes. 2017;10(1):12.

11.

Lee J, Kim N, Na S, Youn Y, Shin C. Reference values of neutrophil–lymphocyte ratio, lymphocytemonocyte ratio, platelet-lymphocyte ratio, and mean platelet volume in healthy adults in South Korea. Medicine. 2018;97(26):e11138.CrossRef

12.

Duman T, Aktas G, Atak B, Kocak M, Erkus E, Savli H. Neutrophil to lymphocyte ratio as an indicative of diabetic control level in type 2 diabetes mellitus. Afr Health Sci. 2019;19(1):1602–6. https://doi.org/10.4314/ahs.v19i1.35.CrossRefPubMedPubMedCentral

13.

Hasan K, Mustari M, Asaduzzaman M, Gaffar A, Chanda P, Rahman M, Hannan M, Akter F, Saifudddin M, Selim S. Evaluation of neutrophil–lymphocyte ratio and platelet–lymphocyte ratio as markers of diabetic kidney disease in Bangladeshi patients with type 2 diabetes mellitus. J Diabetol. 2020;12:58–62. https://doi.org/10.4103/jod.jod_4_20.CrossRef

14.

Wang J, Chen Z, Yang K, Yang H, Tao W, Li Y, Jiang Z, Bai C, Yin Y, Duan J, Zhou Y, Geng X, Yang Y. Association between neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and diabetic retinopathy among diabetic patients without a related family history. Diabetol Metab Syndr. 2020;12:55. https://doi.org/10.1186/s13098-020-00562-y.CrossRefPubMedPubMedCentral

15.

Liu W, Lin S, Wang L, Fang C, Lin Y, Braddock M, Zhu G, Zhang Z, Zheng M, Shen F. Platelet-to-lymphocyte ratio: a novel prognostic factor for prediction of 90-day outcomes in critically ill patients with diabetic ketoacidosis. Medicine. 2016;95(4):1–7.

16.

Ilhan C, Citirik M, Uzel MM, Kiziltoprak H, Tekin K. The usefulness of systemic inflammatory markers as diagnostic indicators of the pathogenesis of diabetic macular edema. Arq Bras Oftalmol. 2020;83(4):299–304. https://doi.org/10.5935/0004-2749.20200051 (Epub 2020 Jul 29 PMID: 32756784).CrossRefPubMed

17.

Tsalamandris S, Antonopoulos A, Oikonomou E, Papamikroulis G, Vogiatzi G, Papaioannou S, Deftereos S, Tousoulis D. The role of inflammation in diabetes: current concepts and future perspectives. Eur Cardiol Rev. 2019;14(1):50–9. https://doi.org/10.15420/ecr.2018.33.1.CrossRef

18.

Baghersalimi A, Koohmanaee S, Darbandi B, Farzamfard V, Hassanzadeh Rad A, Zare R, Tabrizi M, Dalili S. Platelet indices alterations in children with type 1 diabetes mellitus. J Pediatr Hematol Oncol. 2019;41(4):e227–32. https://doi.org/10.1097/MPH.0000000000001454.CrossRefPubMed

19.

Herrera B, Rosas X, Pérez M, Castañeda M, Paulín L, Díaz R. Comparison of neutrophil/lymphocyte ratio according to degree of glycemic control in children with recent-onset type 1 and type 2 diabetes. ESPE Abstr. 2016;86:P-P2-274.

20.

Mayer-Davis E, Kahkoska A, Jefferies C, Dabelea D, Balde N, Gong C, Craig M. ISPAD clinical practice consensus guidelines 2018: definition, epidemiology, and classification of diabetes in children and adolescents. Pediatr Diabetes. 2018;19:7–19.CrossRef

21.

Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005;5. https://doi.org/10.1186/1471-2288-5-13

22.

Hozo S, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2015;5:13. https://doi.org/10.1186/1471-2288-5-13.CrossRef

23.

Bolster NM, Bastawrous A. Chapter 25: Examining the optic fundus and assessing visual acuity and visual fields using mobile technology. Revolutionizing Tropical Medicine: Point-of-Care Tests, New Imaging Technologies and Digital Health. Wiley; 2019.

24.

Yang Z, Chen R, Zhang Y, Huang Y, Hong T, Sun F, Ji L, Zhan. Scoring systems to screen for diabetic peripheral neuropathy Cochrane Database Syst Rev. 2014;2018(7):CD010974.

25.

Balder J, Lansberg P, Hof M, Wiegman A, Hutten B, Kuivenhoven J. Pediatric lipid reference values in the general population: the Dutch lifelines cohort study. J Clin Lipidol. 2018;12(5):1208–16. https://doi.org/10.1016/j.jacl.2018.05.011.CrossRefPubMed

26.

Goldstein D, Little R, Wie-dmeyer H, England J, McKenzie E. Glycated hemoglobin: methodologies and clinical applications. Clin Chem. 1986;32(10):B64-70.PubMed

27.

Viberti G, Hill R, Jarrett R, Argyropoulos A, Mahmud U, Keen H. Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus. Lancet. 1982;1(8287):1430–2.CrossRef

28.

Xu T, Weng Z, Pei C, Yu S, Chen Y, Guo W, Wang X, Luo P, Sun J. The relationship between neutrophil-to-lymphocyte ratio and diabetic peripheral neuropathy in type 2 diabetes mellitus. Medicine. 2017;96(45):e8289. https://doi.org/10.1097/MD.0000000000008289.CrossRefPubMedPubMedCentral

29.

Hussain M, Babar M, Akhtar L, Hussain M. Neutrophil lymphocyte ratio (NLR): a well assessment tool of glycemic control in type 2 diabetic patients. Pak J Med Sci. 2017;33(6):1366–70. https://doi.org/10.12669/pjms.336.12900.CrossRefPubMedPubMedCentral

30.

Luo W, Zhang W. The relationship of blood cell-associated inflammatory indices and diabetic retinopathy: a meta-analysis and systematic review. Int J Ophthalmol. 2019;12(2):312–23. https://doi.org/10.18240/ijo.2019.02.20.CrossRefPubMedPubMedCentral

31.

Ayhan H, Kasapkara HA, Aslan AN, Durmaz T, Keleş T, Akçay M, Akar Bayram N, Baştuğ S, Bilen E, Sarı C, Bozkurt E. Relationship of neutrophil-to-lymphocyte ratio with aortic stiffness in type 1 diabetes mellitus. Can J Diabetes. 2015;39(4):317–21. https://doi.org/10.1016/j.jcjd.2015.01.004 (Epub 2015 Mar 19 PMID: 25797110).CrossRefPubMed

32.

Yu Y, Lin Q, Ye D, Wang Y, He B, Li Y, Huang G, Zhou Z, Xiao Y. Neutrophil count as a reliable marker for diabetic kidney disease in autoimmune diabetes. BMC Endocr Disord. 2020;20(1):158. https://doi.org/10.1186/s12902-020-00597-2.PMID:33092580;PMCID:PMC7580021.CrossRefPubMedPubMedCentral

33.

Devamsh N, Parvathi M, Madhumathi R, Leela R. Study of neutrophil lymphocyte ratio in patients with type 2 diabetes mellitus and its correlation with glycemic control. Int J Adv Med. 2019;6:1637. https://doi.org/10.18203/2349-3933.ijam20194233.CrossRef

34.

Liu N, Sheng J, Pan T, Wang Y. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio are associated with lower extremity vascular lesions in chinese patients with type 2 diabetes. Clin Lab. 2019. https://doi.org/10.7754/Clin.Lab.2018.180804.CrossRefPubMed

35.

Fawwad A, Butt AM, Siddiqui IA, Khalid M, Sabir R, Basit A. Neutrophil-to-lymphocyte ratio and microvascular complications in subjects with type 2 diabetes: Pakistan’s perspective. Turk J Med Sci. 2018;48(1):157–61. https://doi.org/10.3906/sag-1706-141 (PMID: 29479977).CrossRefPubMed

36.

Jaaban M, Zetoune A, Hesenow S, Hessenow R. Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as novel risk markers for diabetic nephropathy in patients with type 2 diabetes. Heliyon. 2021;7(7):e07564. https://doi.org/10.1016/j.heliyon.2021.e07564.CrossRefPubMedPubMedCentral

Title: Leukocytic dysregulation in children with type 1 diabetes: relation to diabetic vascular complications
Authors: Nouran Yousef Salah
Nesrine Radwan
Heba Mohamed Atif
Publication date: 07-01-2022
Publisher: Springer Nature Singapore
Keyword: Type 1 Diabetes
Published in: Diabetology International / Issue 3/2022
Print ISSN: 2190-1678
Electronic ISSN: 2190-1686
DOI: https://doi.org/10.1007/s13340-021-00568-5

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Aim

Methodology

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 3/2022

Metabolism-secretion coupling in glucose-stimulated insulin secretion

Incidence of interventions for diabetic retinopathy and serious lower-limb complications and its related factors in patients with type 2 diabetes using a real-world large claims database

Effect of ultra-rapid insulin aspart on glycemic control in children with type 1 diabetes: the experience of a Portuguese tertiary centre

The effectiveness of psychological interventions on mental health and quality of life in people living with type 1 diabetes: a systematic review and meta-analysis

Development of a hyperosmolar-hyperglycemic state and possible fulminant type 1 diabetes mellitus during the treatment of a case of adenocarcinoma of the lung and interstitial pneumonia

Continuity of diabetes care among elderly Japanese patients: a medical record review study in a specialized diabetes clinic

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials