USING SERUM BIOMARKERS FOR THE EARLY DIAGNOSIS AND PREDICTION OF TYPE 1 DIABETES

Year 2022, Volume: 3 Issue: 1, 7 - 17, 30.01.2022

Merita Rumano , Romina Meçaj

Abstract

Diabetes mellitus type 1 (T1D) is an autoimune disease where the pancreas fails to insulin production. This is a cronic disorder observed mainly in young ages and is caused by an autoimune response against pancreatic β cells, leading to reduced levels or lack of insulin in circulation. There are different factors, such as genetic, epigenetic, immunologic and environmental factors, leading to the development of type 1 diabetes.
Clinical similarity to type 2 diabetes (T2D) and the lack of clinical symptoms at the beginning of the disease, makes its diagnosis more difficult and this is one of the main reasons leading to late diagnosis of the disease. Monitoring specific parameters like C-peptide, HbA1c, fasting glucose and autoantibodies is of great importance in prediction and evaluation of individuals predisposed to develop diabetes mellitus type1.
Based on the importance of these autoimune markers for type 1 diabetes, the aim of our work, was to study the laboratory parameters related to the early diagnosis of type 1 diabetes as well as to evaluate the relationship between these parameters in a group of individuals diagnosed with type 1 diabetes. After blood tests and data analysis, the results showed that the increase of positive autoantibodies affects the reduction of C-peptide levels, which means that pancreatic β cells have begun to lose their functionality, as a result of cell death which comes after the autoimmune attack. Based on these results we can say that low C-peptide levels and high blood glucose are an indicator of type 1 diabetes. A significant correlation between C-peptide level and age, as well as between high glicemic level and high triglicerides is present. High levels of urea and electrolite disbalance is observed. Taking into consideration these facts, clinical testing for the presence of specific serum biomarkers, helps in the early detection of the disease.

Keywords

diabetes mellitus 1, serum biomarkers, C-peptide, autoantibody

References

• Asa K. Davis, Stephanie N. DuBose, Michael J. Haller, Kellee M. Miller, Linda A. DiMeglio, Kathleen E. Bethin, Robin S. Goland, Ellen M. Greenberg, David R. Liljenquist, Andrew J. Ahmann, Santica M. Marcovina, Anne L. Peters, Roy W. Beck, Carla J. Greenbaum (2015 Mar). Prevalence of Detectable C-Peptide According to Age at Diagnosis and Duration of Type 1 Diabetes. Diabetes Care, 38 (3) 476-481; DOI: 10.2337/dc14-1952
• Bain JR. (2013).Targeted metabolomics finds its mark in diabetes research. Diabetes. 2013;62:349–51.
• Bervoets, L., Massa, G., Guedens, W. et al. (2017). Metabolic profiling of type 1 diabetes mellitus in children and adolescents: a case–control study. Diabetol Metab Syndr 9, 48. https://doi.org/10.1186/s13098-017-0246-9
• Catherine Pihoker, Lisa K. Gilliam, Christiane S. Hampe, Åke Lernmark, Autoantibodies in Diabetes, Diabetes 2005 Dec; 54(suppl 2): S52-S61. https://doi.org/10.2337/diabetes.54.suppl_2.S52
• Cohen RM, Franco RS, Joiner CH. (2004). Is poor glycemic control associated with reduced red blood cell lifespan? Diabetes Care. 2004 Apr;27(4):1013-4. doi: 10.2337/diacare.27.4.1013. PMID: 15047667.
• Diabetes Care Jun 2015, 38 (6) 989-996; DOI: 10.2337/dc15-0101
• Ezio Bonifacio (2015). Predicting Type 1 Diabetes Using Biomarkers.
• Goitom Mebrahtu, Jayanthi Maniam, Steven James, Graham D. Ogle (2021 February 15), High incidence of type 1 diabetes in adolescents and young adults in Eritrea, Diabetic medicine, https://doi.org/10.1111/dme.14544
• Hao, G., Wang, D., Sun, Y., Yu, J., Lin, F., & Cao, H. (2017). Association of blood glucose and lipid levels with complete blood count indices to establish a regression model. Biomedical reports, 6(3), 339–345. https://doi.org/10.3892/br.2017.852
• InformedHealth.org [Internet]. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2006-. Hyperglycemia and hypoglycemia in type 1 diabetes. 2007 May 29 [Updated 2017 Jun 29, lasta update 2020].
• Jay S. Skyler (2015 Jun). Prevention and Reversal of Type 1 Diabetes—Past Challenges and Future Opportunities. Diabetes Care, 38 (6) 997-1007; DOI: 10.2337/dc15-0349
• Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group, Wilson, D. M., Xing, D., Beck, R. W., Block, J., Bode, B., Fox, L. A., Hirsch, I., Kollman, C., Laffel, L., Ruedy, K. J., Steffes, M., & Tamborlane, W. V. (2011). Hemoglobin A1c and mean glucose in patients with type 1 diabetes: analysis of data from the Juvenile Diabetes Research Foundation continuous glucose monitoring randomized trial. Diabetes care, 34(3), 540–544. https://doi.org/10.2337/dc10-1054
• Katsarou A, Gudbjornsdottir S, Rawshani A, Dabelea D, Bonifacio E, Anderson BJ, et al. Type 1 diabetes mellitus. Nat Rev Dis Primers.2017;3.
• Kawasaki E. (2014). Type 1 diabetes and autoimmunity. Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology, 23(4), 99–105. https://doi.org/10.1297/cpe.23.99
• Krzewska A, Ben-Skowronek I. Effect of Associated Autoimmune Diseases on Type 1 Diabetes Mellitus Incidence and Metabolic Control in Children and Adolescents. Biomed Res Int. 2016; 2016:6219730. doi: 10.1155/2016/6219730. Epub 2016 Jul 20. PMID: 27525273; PMCID: PMC4971288. Lanza IR, Zhang S, Ward LE, Karakelides H, Raftery D, Nair KS. (2010). Quantitative metabolomics by H-NMR and LC-MS/MS confirms altered metabolic pathways in diabetes. PLoS ONE. 2010;5:e10538.
• Leighton, E., Sainsbury, C. A., & Jones, G. C. (2017). A Practical Review of C-Peptide Testing in Diabetes. Diabetes therapy : research, treatment and education of diabetes and related disorders, 8(3), 475–487. https://doi.org/10.1007/s13300-017-0265-4
• Liamis, G., Liberopoulos, E., Barkas, F., & Elisaf, M. (2014). Diabetes mellitus and electrolyte disorders. World journal of clinical cases, 2(10), 488–496. https://doi.org/10.12998/wjcc.v2.i10.488
• Lian Yi, Adam C. Swensen, Wei-Jun Qian, “Serum biomarkers for diagnosis and prediction of type 1 diabetes”, Review article /Transl Res. 2018 November ; 201: 13–25. doi:10.1016/j.trsl.2018.07.009.
• McLaughlin KA, Richardson CC, Ravishankar A, Brigatti C, Liberati D, Lampasona V, et al. Identification of Tetraspanin-7 as a Target of Autoantibodies in Type 1 Diabetes. Diabetes. 2016; 65:1690–8. [PubMed: 26953162] P. Zhang, X. Zhang, and J. Betz Brown, “Economic impact in diabetes,” in International Diabetes Federation Diabetes Atlas, 2009, http://www.idf.org.
• Parhofer K. G. (2015). Interaction between Glucose and Lipid Metabolism: More than Diabetic Dyslipidemia. Diabetes & metabolism journal, 39(5), 353–362. https://doi.org/10.4093/dmj.2015.39.5.353
• Patel SA, Ali MK, Alam D, Yan LL, Levitt NS, Bernabe-Ortiz A, Checkley W, Wu Y, Irazola V, Gutierrez L, Rubinstein A, Shivashankar R, Li X, Miranda JJ, Chowdhury MA, Siddiquee AT, Gaziano TA, Kadir MM, Prabhakaran D. (2016). Obesity and its Relation With Diabetes and Hypertension: A Cross-Sectional Study Across 4 Geographical Regions. Glob Heart. 2016 Mar; 11(1):71-79.e4. doi: 10.1016/j.gheart.2016.01.003. PMID: 27102024; PMCID: PMC4843822.
• Pflueger M, Seppanen-Laakso T, Suortti T, Hyotylainen T, Achenbach P, Bonifacio E, et al. Age- and Islet Autoimmunity-Associated Differences in Amino Acid and Lipid Metabolites in Children at Risk for Type 1 Diabetes. Diabetes. 2011; 60:2740–7. [PubMed: 22025777]
• Pilla, S. J., Maruthur, N. M., Schweitzer, M. A., Magnuson, T. H., Potter, J. J., Clark, J. M., & Lee, C. J. (2018). The Role of Laboratory Testing in Differentiating Type 1 Diabetes from Type 2 Diabetes in Patients Undergoing Bariatric Surgery. Obesity surgery, 28(1), 25–30. https://doi.org/10.1007/s11695-017-2804-5
• Rewers, M., & Ludvigsson, J. (2016). Environmental risk factors for type 1 diabetes. Lancet (London, England), 387(10035), 2340–2348. https://doi.org/10.1016/S0140-6736(16)30507-4
• Stankov K, Benc D, Draskovic D. (2013). Genetic and epigenetic factors in etiology of diabetes mellitus type 1. Pediatrics. 2013 Dec;132(6):1112-22. doi: 10.1542/peds.2013-1652. Epub 2013 Nov 4. PMID: 24190679.
• Truyen I, Pauw P, Jorgensen PN, Van Schravendijk C, Ubani O, Decochez K, et al. Proinsulin levels and the proinsulin: C-peptide ratio complement autoantibody measurement for predicting type 1 diabetes. Diabetologia. 2005; 48:2322–9. [PubMed: 16211374]
• Wang Z, Xie Z, Lu Q, Chang C, Zhou Z.(2017). Beyond Genetics: What Causes Type 1 Diabetes. Clin Rev Allergy Immunol. 2017 Apr;52(2):273-286. doi: 10.1007/s12016-016-8592-1. PMID: 27878451.