Association of the apoptotic markers Apo1/Fas and cCK-18 and the adhesion molecule ICAM-1 with Type 1 diabetes mellitus in children and adolescents.
Apo1/Fas
Children
ICAM-1
Type 1 diabetes mellitus
cCK-18
Journal
BMC pediatrics
ISSN: 1471-2431
Titre abrégé: BMC Pediatr
Pays: England
ID NLM: 100967804
Informations de publication
Date de publication:
02 Aug 2024
02 Aug 2024
Historique:
received:
27
11
2023
accepted:
02
07
2024
medline:
3
8
2024
pubmed:
3
8
2024
entrez:
2
8
2024
Statut:
epublish
Résumé
Type 1 diabetes mellitus (T1DM) is characterized by immune and metabolic dysregulation. Apo1/Fas is implicated in maintaining homeostasis of the immune system. Cytokeratin-18 (cCK-18) is a predictive marker of liver disorders in T2DM. Intercellular adhesion molecule-1 (ICAM-1) is considered to increase susceptibility to diabetes mellitus. All three markers are associated with endothelial function, apoptosis and diabetes-related complications. The possible role of Apo1/Fas, cCK-18 and ICAM-1 was investigated in children and adolescents with T1DM. Forty-nine (49) children and adolescents with T1DM and 49 controls were included in the study. Somatometric measurements were obtained and the Body Mass Index (BMI) of the participants was calculated. Biochemical parameters were measured by standard laboratory methods and Apo1/Fas, cCK-18 and ICAM-1 were measured using appropriate ELISA kits. The statistical analysis was performed using the IBM SPSS Statistics 23 program. Apo1/Fas (p = 0.001), cCK-18 (p < 0.001) and ICAM-1 (p < 0.001) were higher in patients with T1DM compared to the controls. Apo1Fas was negatively correlated with glucose (p = 0.042), uric acid (p = 0.026), creatinine (p = 0.022), total cholesterol (p = 0.023) and LDL (p = 0.005) in the controls. In children and adolescents with T1DM, Apo1/Fas was positively correlated with total cholesterol (p = 0.013) and LDL (p = 0.003). ICAM-1 was negatively correlated with creatinine (p = 0.019) in the controls, whereas in patients with T1DM it was negatively correlated with HbA1c (p = 0.05). Apo1/Fas, cCK-18 and ICAM-1 may be useful as serological markers for immune and metabolic dysregulation in children and adolescents with T1DM. Also, Apo1/Fas may have a protective role against metabolic complications in healthy children.
Sections du résumé
BACKGROUND
BACKGROUND
Type 1 diabetes mellitus (T1DM) is characterized by immune and metabolic dysregulation. Apo1/Fas is implicated in maintaining homeostasis of the immune system. Cytokeratin-18 (cCK-18) is a predictive marker of liver disorders in T2DM. Intercellular adhesion molecule-1 (ICAM-1) is considered to increase susceptibility to diabetes mellitus. All three markers are associated with endothelial function, apoptosis and diabetes-related complications. The possible role of Apo1/Fas, cCK-18 and ICAM-1 was investigated in children and adolescents with T1DM.
METHOD
METHODS
Forty-nine (49) children and adolescents with T1DM and 49 controls were included in the study. Somatometric measurements were obtained and the Body Mass Index (BMI) of the participants was calculated. Biochemical parameters were measured by standard laboratory methods and Apo1/Fas, cCK-18 and ICAM-1 were measured using appropriate ELISA kits. The statistical analysis was performed using the IBM SPSS Statistics 23 program.
RESULTS
RESULTS
Apo1/Fas (p = 0.001), cCK-18 (p < 0.001) and ICAM-1 (p < 0.001) were higher in patients with T1DM compared to the controls. Apo1Fas was negatively correlated with glucose (p = 0.042), uric acid (p = 0.026), creatinine (p = 0.022), total cholesterol (p = 0.023) and LDL (p = 0.005) in the controls. In children and adolescents with T1DM, Apo1/Fas was positively correlated with total cholesterol (p = 0.013) and LDL (p = 0.003). ICAM-1 was negatively correlated with creatinine (p = 0.019) in the controls, whereas in patients with T1DM it was negatively correlated with HbA1c (p = 0.05).
CONCLUSIONS
CONCLUSIONS
Apo1/Fas, cCK-18 and ICAM-1 may be useful as serological markers for immune and metabolic dysregulation in children and adolescents with T1DM. Also, Apo1/Fas may have a protective role against metabolic complications in healthy children.
Identifiants
pubmed: 39095736
doi: 10.1186/s12887-024-04926-5
pii: 10.1186/s12887-024-04926-5
doi:
Substances chimiques
Intercellular Adhesion Molecule-1
126547-89-5
Biomarkers
0
Keratin-18
0
fas Receptor
0
FAS protein, human
0
ICAM1 protein, human
0
Apolipoprotein A-I
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
493Informations de copyright
© 2024. The Author(s).
Références
Pugliese A. Autoreactive T cells in type 1 diabetes. J Clin Invest. 2017;127:2881–91. https://doi.org/10.1172/jci94549 .
doi: 10.1172/jci94549
pubmed: 28762987
pmcid: 5531393
Turner SJ, La Gruta NL. A subset of immune-system T cells branded as seeds foe Type 1 Diabetes. Nature. 2022;602:35–6. https://doi.org/10.1038/d41586-021-03800-z .
doi: 10.1038/d41586-021-03800-z
pubmed: 35079168
Pugliese A. Insulitis in the pathogenesis of type 1 diabetes. Pediatr Diabetes. 2016;22:31–6. https://doi.org/10.1111/pedi.12388 .
doi: 10.1111/pedi.12388
Ferraro A, Socci C, Stabilini A, Valle A, Monti P, Piemonti L, Nano R, Olek S, Maffi P, Scavini M, et al. Expansion of Th17 cells and functional defects in T regulatory cells are key features of the pancreatic lymph nodes in patients with type 1 diabetes. Diabetes. 2011;60:2903–13. https://doi.org/10.2337/db11-0090 .
doi: 10.2337/db11-0090
pubmed: 21896932
pmcid: 3198077
Katsa ME, Kostopoulou E, Magana M, Ioannidis A, Chatzipanagiotou S, Sachlas A, Dimopoulos I, Spiliotis B, Rojas Gil AP. Association of the apoptotic marker APO1/Fas with childen’s predisposing factors for metabolic syndrome and with mean platelet volume. J Pediatr Endocrinol Metab. 2021;34(11):1393–400. https://doi.org/10.1515/jpem-2021-0352 .
doi: 10.1515/jpem-2021-0352
pubmed: 34332515
DeFranco S, Bonissoni S, Cerutti F, Bona G, Bottarel F, Cadario F, Brusco A, Loffredo G, Rabbone I, Corrias A, et al. Defective function of Fas in patients with type 1 diabetes associated with other autoimmune diseases. Diabetes. 2001;50:483–8. https://doi.org/10.2337/diabetes.50.3.483 .
doi: 10.2337/diabetes.50.3.483
pubmed: 11246866
Nagata S, Golstein P. The Fas death factor. Science. 1995;267:1449–56. https://doi.org/10.1126/science.7533326 .
doi: 10.1126/science.7533326
pubmed: 7533326
Cryns VL, Bergeron L, Zhu H, Li H, Yuan J. Specific cleavage of α-Fodrin during Fas- and Tumor Necrosis Factor-induced Apoptosis is mediated by an Interleukin-1β-converting enzyme/Ced-3 protease distinct from the Poly(ADP-ribose) polymerase protease. J Biol Chem. 1996;271:31277–82. https://doi.org/10.1074/jbc.271.49.31277 .
doi: 10.1074/jbc.271.49.31277
pubmed: 8940132
Sia C, Hänninen A. Apoptosis in autoimmune diabetes: the fate of beta-cells in the cleft between life and death. Rev Diabet Stud. 2006;3(1):39–46. https://doi.org/10.1900/RDS.2006.3.39 . Spring.
doi: 10.1900/RDS.2006.3.39
pubmed: 17491711
pmcid: 1783572
Kostopoulou E, Kalaitzopoulou E, Papadea P, et al. Oxidized lipid-associated protein damage in children and adolescents with type 1 diabetes mellitus: New diagnostic/prognostic clinical markers. Pediatr Diabetes. 2021;22(8):1135–42. https://doi.org/10.1111/pedi.13271 .
doi: 10.1111/pedi.13271
pubmed: 34633133
Chang J, Zhang G, Zhang L, Hou YP, Liu XL, Zhang L. High admission glucose levels increase Fas apoptosis and mortality in patients with acute ST-elevation myocardial infarction: a prospective cohort study. Cardiovasc Diabetol. 2013;15(12):171. https://doi.org/10.1186/1475-2840-12-171 .
doi: 10.1186/1475-2840-12-171
Leers MP, Kolgen W, Bjorklund V, Bergman T, Tribbick G, Persson B, Bjorklund P, Ramaekers FC, Bjorklund B, Nap M, et al. Immunocytochemical detection and mapping of a cytokeratin 18 neo-epitope exposed during early apoptosis. J Pathol. 1999;187:567–72 https://doi.org/10.1002/(sici)1096-9896(199904)187:5%3C567::aid-path288%3E3.0.co;2-j.
doi: 10.1002/(SICI)1096-9896(199904)187:5<567::AID-PATH288>3.0.CO;2-J
pubmed: 10398123
Chang YH, Lin HC, Hwu DW, Chang DM, Lin KC, Lee YJ. Elevated serum cytokeratin-18 concentration in patients with type 2 diabetes mellitus and non0alcoholic fatty liver disease. Ann Clin Biochem. 2019;56(1):141–7. https://doi.org/10.1177/0004563218796259 .
doi: 10.1177/0004563218796259
pubmed: 30089409
Ueno T, Toi M, Linder S. Detection of epithelial cell death in the body by cytokeratin 18 measurement. Biomed Pharmacother. 2005;59(2):359–62. https://doi.org/10.1016/s0753-3322(05)80078-2 .
doi: 10.1016/s0753-3322(05)80078-2
Morling JR, Fallowfield JA, Williamson RM, Nee LD, Jackson AP, Glancy S, Reynolds RM, Hayes PC, Guha IN, Strachan MW, Price JF. Non-invasive hepatic biomarkers (ELF and CK18) in people with type 2 diabetes: the Edinburgh type 2 diabetes study. Liver Int. 2014;34:1267–77. https://doi.org/10.1111/liv.12385 .
doi: 10.1111/liv.12385
pubmed: 24237940
Ramljak S, Hermanns I, Demircik F, Pfutzner A. Assessment of hepatic disorders in patients with type 2 diabetes by means of a panel of specific biomarkers for liver injury. Clin Lab. 2015;61:1687–93. https://doi.org/10.7754/clin.lab.2015.140522 .
doi: 10.7754/clin.lab.2015.140522
pubmed: 26731994
Pagano S, Bakker SJL, Juillard C, Dullaart RPF, Vuilleumier N. Serum Level of Cytokeratin 18 (M65) as a Prognostic Marker of High Cardiovascular Disease Risk in Individuals with Non-Alcoholic Fatty Liver Disease. Biomolecules. 2023;13(7):1128. https://doi.org/10.3390/biom13071128 .
doi: 10.3390/biom13071128
pubmed: 37509164
pmcid: 10377236
Kumari V, Sarangapani S, Krishnamurthy P, Vaitheeswaran K, Sathyabaarathi R, Rajesh M, Amali J, Umashankar V, Kumaramanickavel G, Pal SS, et al. ICAM-1K469E polymorphism is a genetic determinant for the clinical risk factors of T2D subjects with retinopathy in Indians: a population-based case–control study. BMJ Open. 2012;2(4). https://doi.org/10.1136/bmjopen-2012-001036 .
Gu HF, Ma J, Gu KT, Brismar K. Association of intercellular adhesion molecule 1 (ICAM1) with diabetes and diabetic nephropathy. Front Endocrinol (Lausanne). 2013;3:179. https://doi.org/10.3389/fendo.2012.00179 .
doi: 10.3389/fendo.2012.00179
pubmed: 23346076
Frørup C, Gerwig R, Svane CAS, Mendes Lopes de Melo J, Henriksen K, Fløyel T, Pociot F, Kaur S, Størling J. Characterization of the functional and transcriptomic effects of pro-inflammatory cytokines on human EndoC-βH5 beta cells. Front Endocrinol (Lausanne). 2023;14:1128523. https://doi.org/10.3389/fendo.2023.1128523 .
doi: 10.3389/fendo.2023.1128523
pubmed: 37113489
Committee ADAPP. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2024. Diabetes Care. 2024;47(1):S20–42. https://doi.org/10.2337/dc24-S002 .
doi: 10.2337/dc24-S002
Marcovecchio ML, de Giorgis T, Di Giovanni I, Chiavaroli V, Chiarelli F, Mohn A. Association between markers of endothelial dysfunction and early signs of renal dysfunction in pediatric obesity and type 1 diabetes. Pediatr Diabetes. 2017;18(4):283–9. https://doi.org/10.1111/pedi.12391 .
doi: 10.1111/pedi.12391
pubmed: 27246625
Ogden CL, Flegal KM. Changes in terminology for childhood overweight and obesity. Natl Health Stat Report. 2010;25:1–5 PMID: 20939253.
Amrani A, Verdaguer J, Thiessen S, Bou S, Santamaria P. IL-1alpha, IL-1beta, and IFN-gamma mark beta cells for Fas-dependent destruction by diabetogenic CD4(+) T lymphocytes. J Clin Invest. 2000;105:459–68. https://doi.org/10.1172/jci8185 .
doi: 10.1172/jci8185
pubmed: 10683375
pmcid: 289158
Chervonsky AV, Wang Y, Wong FS, Visintin I, Flavell RA, Janeway CA Jr, Matis LA. The role of Fas in autoimmune diabetes. Cell. 1997;89(1):17–24. https://doi.org/10.1016/s0092-8674(00)80178-6 .
doi: 10.1016/s0092-8674(00)80178-6
pubmed: 9094710
Apostolou I, Hao Z, Rajewsky K, von Boehmer H. Effective destruction of Fas-deficient insulin-producing beta cells in type 1 diabetes. J Exp Med. 2003;198(7):1103–6. https://doi.org/10.1084/jem.20030698 .
doi: 10.1084/jem.20030698
pubmed: 14530378
pmcid: 2194221
Burger K, Gimpl G, Fahrenholz F. Regulation of receptor function by cholesterol. Cell Mol Life Sci. 2000;57:1577–92. https://doi.org/10.1007/pl00000643 .
doi: 10.1007/pl00000643
pubmed: 11092453
pmcid: 11146861
Westover EJ, Covey DF, Brockman HL, Brown RE, Pike LJ. Cholesterol depletion results in site-specific increases in epidermal growth factor receptor phosphorylation due to membrane level effects. Studies with cholesterol enantiomers. J Biol Chem. 2003;278:51125–33. https://doi.org/10.1074/jbc.m304332200 .
doi: 10.1074/jbc.m304332200
pubmed: 14530278
Gniadecki R. Depletion of membrane cholesterol causes ligand-independent activation of Fas and apoptosis. Biochem Biophys Res Commun. 2004;320:165–9. https://doi.org/10.1016/j.bbrc.2004.05.145 .
doi: 10.1016/j.bbrc.2004.05.145
pubmed: 15207716
Cooper RA, Diloy Puray M, Lando P, Greenverg MS. An analysis of lipoproteins, bile acids, and red cell membranes associated with target cells and spur cells in patients with liver disease. J Clin Invest. 1972;51:3182–92. https://doi.org/10.1172/jci107145 .
doi: 10.1172/jci107145
pubmed: 4640953
pmcid: 333000
Thomas WA, Kim DN, Lee KT, Reiner JM, Schmee J. Population dynamics of arterial cells during atherogenesis. XIII. Mitogenic and cytotoxic effects of a hyperlipidemic (HL) diet on cells in advanced lesions in the abdominal aortas of swine fed an HL diet for 270–345 days. Exp Mol Pathol. 1983;39:257–70. https://doi.org/10.1016/0014-4800(83)90056-4 .
doi: 10.1016/0014-4800(83)90056-4
pubmed: 6641917
Cernea S, Dobreanu M. Diabetes and beta cell function: from mechanisms to evaluation and clinical implications. Biochem Med (Zagreb). 2013;23(3):266–80. https://doi.org/10.11613/bm.2013.033 .
doi: 10.11613/bm.2013.033
pubmed: 24266296
Chen CH, Jiang T, Yang JH, Jiang W, Lu J, Marathe GK, Pownall HJ, Ballantyne CM, McIntyre TM, Henry PD, Yang CY. Low-density lipoprotein in hypercholesterolemic human plasma induces vascular endothelial cell apoptosis by inhibiting fibroblast growth factor 2 transcription. Circulation. 2003;107:2102–8. https://doi.org/10.1161/01.cir.0000065220.70220.f7 .
doi: 10.1161/01.cir.0000065220.70220.f7
pubmed: 12695302
Norata GD, Tonti L, Roma P, Catapano AL. Apoptosis and proliferation of endothelial cells in early atherosclerotic lesions: possible role of oxidised LDL. Nutr Metab Cardiovasc Dis. 2002;12:297–305.
pubmed: 12616810
Choi JW, Kim SK. Relationships of soluble APO-1 (Fas/CD95) concentrations, obesity, and serum lipid parameters in healthy adults. Ann Clin Lab Sci. 2005;35:290–6 PMID: 16081586.
pubmed: 16081586
Hoffmanova I, Sanchez D, Habova V, Andel M, Tuckova L, Tlaskalova-Honova H. Serological markers of enterocyte damage and apoptosis in patients with celiac disease, autoimmune diabetes mellitus and diabetes mellitus type 2. Physiol Res. 2015;64:537–46. https://doi.org/10.33549/physiolres.932916 .
doi: 10.33549/physiolres.932916
pubmed: 25470519
Vos MB, Barve S, Joshi-Barve S, Carew JD, Whitington PF, et al. Cytokeratin 18, a marker of cell death, is increased in children with suspected nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr. 2008;47:481–5. https://doi.org/10.1097/MPG.0b013e31817e2bfb .
doi: 10.1097/MPG.0b013e31817e2bfb
pubmed: 18852641
pmcid: 2628810
Fitzpatrick E, Mitry RR, Quaglia A, Hussain MJ, DeBruyne R, et al. Serum levels of CK18 M30 and leptin are useful predictors of steatohepatitis and fibrosis in paediatric NAFLD. J Pediatr Gastroenterol Nutr. 2010;51:500–6. https://doi.org/10.1097/MPG.0b013e3181e376be .
doi: 10.1097/MPG.0b013e3181e376be
pubmed: 20808246
Feldstein AE, Alkhouri N, de Vito R, Alisi A, Lopez R, et al. Serum cytokeratin-18 fragment levels are useful biomarkers for nonalcoholic steatohepatitis in children. Am J Gastroenterol. 2013;108:1526–31. https://doi.org/10.1038/ajg.2013.168 .
doi: 10.1038/ajg.2013.168
pubmed: 23752877
Nurten E, Vogel M, Kapellen TM, Richter S, Garten A, Penke M, Schuster S, Korner A, Kiess W, Kratzsch J. Omentin-1 and NAMPT serum concentrations are higher and CK-18 levels are lower in children and adolescents with type 1 diabetes when compared to healthy age, sex and BMI matched controls. J Pediatr Endocrinol Metab. 2018;31:959–69. https://doi.org/10.1515/jpem-2018-0353 .
doi: 10.1515/jpem-2018-0353
pubmed: 30179852
Rostampour N, Fekri K, Hashemi-Dehkordi E, Obodiat M. Association between vascular endothelial markers and carotid intima-media thickness in children and adolescents with Type 1 diabetes mellitus. J Clin Diagn Res. 2017;11(9):SC01–5. https://doi.org/10.7860/JCDR/2017/26623.10541 .
doi: 10.7860/JCDR/2017/26623.10541
pubmed: 29207795
pmcid: 5713817
Noda K, Nakao S, Zandi S, Sun D, Hayes KC, Hafezi-Moghadam A. Retinopathy in a novel model of metabolic syndrome and type 2 diabetes: new insight on the inflammatory paradigm. FASEB J. 2014;28:2038–46. https://doi.org/10.1096/fj.12-215715 .
doi: 10.1096/fj.12-215715
pubmed: 24571922
pmcid: 3986844
Martin TM, Burke SJ, Wasserfall CH, Collier JJ. Islet beta-cells and intercellular adhesion molecule-1 (ICAM-1): Integrating immune responses that influence autoimmunity and graft rejection. Autoimmun Rev. 2023;22. https://doi.org/10.1016/j.autrev.2023.103414 .
Guja C, Todd JA, Welsh K, Marshall, Ionescu-Tirgoviste C. Increased transmission of intercellular adhesion-molecule 1, 469E allele in type 1 Romanian diabetic families. Diabetologia. 1999;42:A90.
Nishimura M, Obayashi H, Maruya E, Ohta M, Tegoshi H, Fukui M, Hasegawa G, Shigeta H, Kitagawa Y, Nakano K, Saji H. Nakamura N (2000) Association between type 1 diabetes age-at-onset and intercellular adhesion molecule-1 (ICAM-1) gene polymorphism. Hum Immunol. 2000;61(5):507–10. https://doi.org/10.1016/s0198-8859(00)00101-4 .
doi: 10.1016/s0198-8859(00)00101-4
pubmed: 10773353
Nejentsev S, Laine AP, Simell O, Ilonen J. Intercellular adhesion molecule-1 (ICAM-1) K469E polymorphism: no association with type 1 diabetes among Finns. Tissue Antigens. 2000;55(6):568–70. https://doi.org/10.1034/j.1399-0039.2000.550608.x .
doi: 10.1034/j.1399-0039.2000.550608.x
pubmed: 10902613
Kristiansen OP, Nolsoe RL, Holst H, Reker S, Larsen ZM, Johannesen J, et al. The intercellular adhesion molecule-1 K469E polymorphism in type 1 diabetes. Immunogenetics. 2000;52:107–11. https://doi.org/10.1007/s002510000258 .
doi: 10.1007/s002510000258
pubmed: 11132145
Lin J, Glynn RJ, Rifai N, Manson JE, Ridker PM, Nathan DM, Schaumberg DA. Inflammation and progressive nephropathy in type 1 diabetes in the diabetes control and complications trial. Diabetes Care. 2008;31(12):2338–43. https://doi.org/10.2337/dc08-0277 .
doi: 10.2337/dc08-0277
pubmed: 18796620
pmcid: 2584192
Lv Z, Li Y, Wu Y, Qu Y. Association of ICAM-1 and HMGA1 gene variants with retinopathy in type 2 diabetes mellitus among Chinese individuals. Curr Eye Res. 2016;41(8):1118–22. https://doi.org/10.3109/02713683.2015.1094093 .
doi: 10.3109/02713683.2015.1094093
pubmed: 26717491
Sun H, Cong X, Sun R, Wang C, Wang X, Liu Y. Association between the ICAM-1 K469E polymorphism and diabetic retinopathy in type 2 diabetes mellitus: a meta-analysis. Diabetes Res Clin Pract. 2014;104(2):46–9. https://doi.org/10.1016/j.diabres.2014.01.028 .
doi: 10.1016/j.diabres.2014.01.028
Ma J, Möllsten A, Prázny M, Falhammar H, Brismar K, Dahlquist G, Efendic S, Gu HF. Genetic influences of the intercellular adhesion molecule 1 (ICAM-1) gene polymorphisms in development of type 1 diabetes and diabetic nephropathy. Diabetes Med. 2006;23(10):1093–9. https://doi.org/10.1111/j.1464-5491.2006.01948.x .
doi: 10.1111/j.1464-5491.2006.01948.x
Astrup AS, Tarnow L, Pietraszek L, Schalkwijk CG, Stehouwer CD, Parving HH, Rossing P. kers of endothelial dysfunction and inflammation in type 1 diabetic patients with or without diabetic nephropathy followed for 10 years: association with mortality and decline of glomerular filtration rate. Diabetes Care. 2008;31(6):1170–6. https://doi.org/10.2337/dc07-1960 .
doi: 10.2337/dc07-1960
pubmed: 18332153
Kaur P, Dahiya R, Nandave M, Sharma K, Goyal RK. Unveiling the crucial role of intercellular adhesion molecule-1 in secondary diabetic complications. Cell Biochem Funct. 2024;42:4037. https://doi.org/10.1002/cbf.4037 .
doi: 10.1002/cbf.4037