Biomarkers used in the diagnosis of type 2 Diabetes mellitus: A systematic review
DOI:
https://doi.org/10.33448/rsd-v14i11.49983Keywords:
Type 2 Diabetes Mellitus, Biomarkers, Diagnosis.Abstract
Type 2 Diabetes Mellitus (DM2) is a chronic metabolic disease with increasing global prevalence, characterized by insulin resistance and pancreatic cell dysfunction. Early diagnosis and adequate monitoring are essential to prevent micro- and macrovascular complications. This systematic review aimed to synthesize recent scientific evidence on biomarkers used in the diagnosis, prognosis, and follow-up of DM2. Articles published between 2011 and 2025, in Portuguese and English, indexed in databases such as PubMed, SciELO, and American Diabetes Association (ADA) guidelines were included. The results highlight the importance of classic biomarkers, such as fasting blood glucose, glycated hemoglobin (HbA1c), and lipid profile, which remain fundamental in clinical practice due to their accessibility and correlation with glycemic control and cardiovascular risk. Additionally, inflammatory (IL-6, TNF-α, CRP), hormonal (C-peptide, leptin, adiponectin), genetic (TCF7L2, SLC30A8), and immunological (anti-GAD autoantibodies) biomarkers have demonstrated complementary value in risk stratification, identification of specific phenotypes (such as LADA), and therapeutic personalization. It is concluded that the integration of multiple classes of biomarkers allows for a more precise and individualized approach in the management of type 2 diabetes mellitus (DM2), reinforcing the trend towards precision medicine.
References
Adolfsson, P., Taplin, C. E., Zaharieva, D. P., Pemberton, J., Davis, E. A., Riddell, M. C., McGavock, J., Moser, O., Szadkowska, A., Lopez, P., Santiprabhob, J., Frattolin, E., Griffiths, G., & DiMeglio, L. A. (2022). ISPAD Clinical Practice Consensus Guidelines 2022: Exercise in children and adolescents with diabetes. Pediatric diabetes, 23(8), 1341–1372. https://doi.org/10.1111/pedi.13452
Alzamil, H. (2020). Elevated Serum TNF-α Is Related to Obesity in Type 2 Diabetes Mellitus and Is Associated with Glycemic Control and Insulin Resistance. Journal of Obesity, 2020, 1–5. https://doi.org/10.1155/2020/5076858
American Diabetes Association Professional Practice Committee (2022). 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2022. Diabetes care, 45(Suppl 1), S17–S38. https://doi.org/10.2337/dc22-S002
American Diabetes Association (2020). 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2020. Diabetes care, 43(Suppl 1), S14–S31. https://doi.org/10.2337/dc20-S002
Andrade, R. L. M., Callo, G., & Horta, B. L. (2019). Peptídeo C e mortalidade cardiovascular: revisão sistemática e metanálise [C-peptide and cardiovascular mortality: systematic review and meta-analysisPéptido C y mortalidad cardiovascular: revisión sistemática y metanálisis]. Revista panamericana de salud publica = Pan American journal of public health, 43, e23. https://doi.org/10.26633/RPSP.2019.23
Assunção, R. G. et al. (2023). Diagnóstico diferencial do diabetes mellitus tipo 1, tipo 2 e LADA. In: Gonçalves, H. M. L.; Santos, J. A.; Pereira, R. A. (org.). Compilado de Ciências Biomédicas. v. 2. São Luís: Editora Pascal, 2023. p. 165-176. https://doi.org/10.29327/5296579
Artha, I. M. J. R., Bhargah, A., Dharmawan, N. K., Pande, U. W., Triyana, K. A., Mahariski, P. A., Yuwono, J., Bhargah, V., Prabawa, I. P. Y., Manuaba, I. B. A. P., & Rina, I. K. (2019). High level of individual lipid profile and lipid ratio as a predictive marker of poor glycemic control in type-2 diabetes mellitus. Vascular health and risk management, 15, 149–157. https://doi.org/10.2147/VHRM.S209830
Benak, D., Sevcikova, A., Holzerova, K., & Hlavackova, M. (2024). FTO in health and disease. Frontiers in cell and developmental biology, 12, 1500394. https://doi.org/10.3389/fcell.2024.1500394
Bosma, K. J., Syring, K. E., Oeser, J. K., Lee, J. D., Benninger, R. K. P., Pamenter, M. E., & O'Brien, R. M. (2019). Evidence that Evolution of the Diabetes Susceptibility Gene SLC30A8 that Encodes the Zinc Transporter ZnT8 Drives Variations in Pancreatic Islet Zinc Content in Multiple Species. Journal of molecular evolution, 87(4-6), 147–151. https://doi.org/10.1007/s00239-019-09898-0
BRASIL. Ministério da Saúde. Diretrizes para o diagnóstico e tratamento do diabetes mellitus tipo 2. Brasília, 2024.
BRASIL. Ministério da Saúde. Diretrizes para prevenção e tratamento de dislipidemias. Brasília: Ministério da Saúde, 2017.
Cardim, Edna da Silva et al. (2024). Diabetes mellitus tipos 1 e 2 e aspectos imunológicos. Revista Ibero-Americana de Humanidades, Ciências e Educação – REASE, São Paulo, 10(10), 927–945, out. 2024. Disponível em: https://doi.org/10.51891/rease.v10i10.16003.
Cao, J., Yan, W., Ma, X., Huang, H., & Yan, H. (2021). Insulin-like Growth Factor 2 mRNA-Binding Protein 2-a Potential Link Between Type 2 Diabetes Mellitus and Cancer. The Journal of clinical endocrinology and metabolism, 106(10), 2807–2818. https://doi.org/10.1210/clinem/dgab391
Costacou, T., Evans, R. W., & Orchard, T. J. (2011). High-density lipoprotein cholesterol in diabetes: is higher always better?. Journal of clinical lipidology, 5(5), 387–394. https://doi.org/10.1016/j.jacl.2011.06.011
De George, D. J., Ge, T., Krishnamurthy, B., Kay, T. W. H., & Thomas, H. E. (2023). Inflammation versus regulation: how interferon-gamma contributes to type 1 diabetes pathogenesis. Frontiers in cell and developmental biology, 11, 1205590. https://doi.org/10.3389/fcell.2023.1205590
Duncan, Bruce Bartholow et al. The burden of diabetes and hyperglycemia in Brazil and its states: findings from the Global Burden of Disease Study 2015. Revista Brasileira de Epidemiologia [online]. 2017, v. 20, n. Suppl 01 [Accessed 1 November 2025] , pp. 90-101. Available from: https://doi.org/10.1590/1980-5497201700050008. ISSN 1980-5497.
Dludla, P. V., Mabhida, S. E., Ziqubu, K., Nkambule, B. B., Mazibuko-Mbeje, S. E., Hanser, S., Basson, A. K., Pheiffer, C., & Kengne, A. P. (2023). Pancreatic β-cell dysfunction in type 2 diabetes: Implications of inflammation and oxidative stress. World journal of diabetes, 14(3), 130–146. https://doi.org/10.4239/wjd.v14.i3.130
Freeman, A. M., Acevedo, L. A., & Pennings, N. (2023). Insulin Resistance. In StatPearls. StatPearls Publishing.
Fuhr, J. C., Ramos, M. E. K., Piovesan, F., Renner, L. de O., and Siqueira, L. de O.. (2022). Relationship of advanced glycation end-products in hypertension in diabetic patients: a systematic review. Brazilian Journal of Nephrology, 44(4), 557–572. https://doi.org/10.1590/2175-8239
Grant S. F. A. (2019). The TCF7L2 Locus: A Genetic Window Into the Pathogenesis of Type 1 and Type 2 Diabetes. Diabetes care, 42(9), 1624–1629. https://doi.org/10.2337/dci19-0001
Guyton, A. C.; & Hall, J. E. (2002). Tratado de fisiologia médica. 10. ed. Rio de Janeiro: Guanabara Koogan, 2002. ISBN: 9788527707138
Hoong, C., Farr, J.N., Monroe, D.G., White, T.A., Atkinson, E.J., Tweed, A., Palmer, A.K., LeBrasseur, N.K., Sfeir, J.G. and Khosla, S. (2025), Biomarkers of Cellular Senescence in Type 2 Diabetes Mellitus. Aging Cell, 24. https://doi.org/10.1111/acel.70120
Moser, O., Riddell, MC, Eckstein, ML et al. Controle da glicose durante o exercício utilizando monitoramento contínuo de glicose (MCG) e sistemas de MCG com leitura intermitente (MCGi) no diabetes tipo 1: declaração de posicionamento da Associação Europeia para o Estudo do Diabetes (EASD) e da Sociedade Internacional de Diabetes Pediátrico e do Adolescente (ISPAD), endossada pela JDRF e apoiada pela Associação Americana de Diabetes (ADA). Diabetologia 63 , 2501–2520 (2020). https://doi.org/10.1007/s00125-020-05263-9
Ito, R., Kimura, A., Hirose, Y., Hatano, Y., Mima, A., Mae, S. I., Keidai, Y., Nakamura, T., Fujikura, J., Nishi, Y., Ohta, A., Toyoda, T., Inagaki, N., & Osafune, K. (2023). Elucidation of HHEX in pancreatic endoderm differentiation using a human iPSC differentiation model. Scientific reports, 13(1), 8659. https://doi.org/10.1038/s41598-023-35875-1
Justi, A.; Tatsch, P.; & Siqueira, L. O. (2019). Ferritina: um biomarcador de doenças cardiovasculares em pacientes diabéticos. ABCS Health Sciences, 44(1), 2019. https://doi.org/10.7322/abcshs.v44i1.1145
Kim, J., Oh, C. M., & Kim, H. (2023). The Interplay of Adipokines and Pancreatic Beta Cells in Metabolic Regulation and Diabetes. Biomedicines, 11(9), 2589. https://doi.org/10.3390/biomedicines11092589
Kong, Y., Sharma, R. B., Nwosu, B. U., & Alonso, L. C. (2016). Islet biology, the CDKN2A/B locus and type 2 diabetes risk. Diabetologia, 59(8), 1579–1593. https://doi.org/10.1007/s00125-016-3967-7
Langenberg, C., Pascoe, L., Mari, A., Tura, A., Laakso, M., Frayling, T. M., Barroso, I., Loos, R. J., Wareham, N. J., Walker, M., & RISC Consortium (2009). Common genetic variation in the melatonin receptor 1B gene (MTNR1B) is associated with decreased early-phase insulin response. Diabetologia, 52(8), 1537–1542. https://doi.org/10.1007/s00125-009-1392-x
Lima, R. A. D., Fernandes, D. R., Garcia, R. A. C., Carvalho, L. A. da R., Silveira, R. C. de C. P., & Teixeira, C. R. de S.. (2023). Correlación entre tiempo en rango y hemoglobina glicosilada en personas con diabetes mellitus: revisión sistemática . Revista Latino-americana De Enfermagem, 31, e4088. https://doi.org/10.1590/1518-8345.6655.4088
Liu, C., Feng, X., Li, Q., Wang, Y., Li, Q., & Hua, M. (2016). Adiponectin, TNF-α and inflammatory cytokines and risk of type 2 diabetes: A systematic review and meta-analysis. Cytokine, 86, 100–109. https://doi.org/10.1016/j.cyto.2016.06.028
Maddaloni, E., Bolli, G. B., Frier, B. M., Little, R. R., Leslie, R. D., Pozzilli, P., & Buzzetti, R. (2022). C‐peptide determination in the diagnosis of type of diabetes and its management: a clinical perspective. Diabetes, Obesity and Metabolism. https://doi.org/10.1111/dom.14785
Martins AM, Brati LP. Tratamento para o diabetes mellitus gestacional: uma revisão de literatura. Femina. 2021;49(4):251-6.
Melanie Rodacki, Roberta A. Cobas, Lenita Zajdenverg, Wellington Santana da Silva Júnior, Luciano Giacaglia, Luis Eduardo Calliari, Renata Maria Noronha, Cynthia Valerio, Joaquim Custódio, Mauro Scharf, Cristiano Roberto Grimaldi Barcellos, Maithe Pimentel Tomarchio, Maria Elizabeth Rossi da Silva, Rosa Ferreira dos Santos, Bianca de Almeida-Pitito, Carlos Antonio Negrato, Monica Gabbay, Marcello Bertoluci | Diagnóstico de diabetes mellitus. Diretriz Oficial da Sociedade Brasileira de Diabetes (2024). https://doi.org/10.29327/5412848.2024-1
Menetski, J. P., Hoffmann, S. C., Cush, S. S., Kamphaus, T. N., Austin, C. P., Herrling, P. L., & Wagner, J. A. (2019). The Foundation for the National Institutes of Health Biomarkers Consortium: Past Accomplishments and New Strategic Direction. Clinical pharmacology and therapeutics, 105(4), 829–843. https://doi.org/10.1002/cpt.1362
Mir, M. M., Mir, R., Alghamdi, M. A. A., Wani, J. I., Sabah, Z. U., Jeelani, M., Marakala, V., Sohail, S. K., O'haj, M., Alharthi, M. H., & Alamri, M. M. S. (2022). Differential Association of Selected Adipocytokines, Adiponectin, Leptin, Resistin, Visfatin and Chemerin, with the Pathogenesis and Progression of Type 2 Diabetes Mellitus (T2DM) in the Asir Region of Saudi Arabia: A Case Control Study. Journal of personalized medicine, 12(5), 735. https://doi.org/10.3390/jpm12050735
Mustafa, H. A., Albkrye, A. M. S., AbdAlla, B. M., Khair, M. A. M., Abdelwahid, N., & Elnasri, H. A. (2020). Computational determination of human PPARG gene: SNPs and prediction of their effect on protein functions of diabetic patients. Clinical and translational medicine, 9(1), 7. https://doi.org/10.1186/s40169-020-0258-1
National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (2002). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation, 106(25), 3143–3421.
Oliveira, L. M. L. de ., Barbosa, L. M., Negreiros, J. H. C. N., Penteado, L. A. M., & Lima, V. V. R. da S. S.. (2020). Cuidado integrado do paciente periodontal diabético tipo 2 na Atenção Básica: revisão scoping. Physis: Revista De Saúde Coletiva, 30(3), e300327. https://doi.org/10.1590/S0103-73312020300327
Pereira, A. S. et al. (2018). Metodologia da pesquisa científica. [e-book]. Ed. UAB/NTE/UFSM.
Ramasamy, R., Yan, S. F., & Schmidt, A. M. (2011). Receptor for AGE (RAGE): signaling mechanisms in the pathogenesis of diabetes and its complications. Annals of the New York Academy of Sciences, 1243, 88–102. https://doi.org/10.1111/j.1749-6632.2011.06320.x
SANTOS, Keila Marina da Silva; SILVA, Tamylle Monte da; SANT’ ANNA, Carla de Castro. Aspectos atuais sobre diagnóstico laboratorial da Diabetes mellitus: mini revisão de literatura. Research, Society and Development, v. 11, n. 7, e40611730105, 2022. ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v11i7.30105
Saucedo, Renata & Peña-Cano, María & García, Yolanda & Reynoso, Rebeca & Díaz-Velázquez, Mary & Valencia-Ortega, Jorge. (2023). Relación de adipocinas con marcadores de función hepática en diabetes gestacional y embarazo normoglucémico. Acta Universitaria. 33. 1-14. 10.15174/au.2023.3711.
Sercelik, A., Tanrıverdi, O., Askin, L., & Turkmen, S.. (2021). A Associação da Relação Proteína C-Reativa/Albumina em Pacientes com Ectasia da Artéria Coronária Isolada. Arquivos Brasileiros De Cardiologia, 116(1), 48–54. https://doi.org/10.36660/abc.20190476
SILVA, A. R. A. da et al. Biomarcadores na detecção precoce das complicações do diabetes mellitus. Revista Brasileira de Análises Clínicas, v. 52, n. 2, p. 145–151, 2020.
Snyder, H. (2019). Literature review as a research methodology: An overview and guidelines. Journal of Business Research. 104, 333-9. https://doi.org/10.1016/j.jbusres.2019.07.039.
SUM Q, Song K, Shen X, Cai Y. The association between KCNQ1 gene polymorphism and type 2 diabetes risk: a meta-analysis. PLoS One. 2012;7(11):e48578. https://doi.org/10.1371/journal.pone.0048578.
Talbot, IC (1985), Bases patológicas das doenças. SL Robbins, RS Cotran e V. Kumar. 3ª edição. WB Saunders, Filadélfia, Londres, Toronto, Cidade do México, Rio de Janeiro, Sydney, Tóquio, 1984. Número de páginas: x+1467. Preço: £49,50. ISBN: 0 7216 7597 2. J. Pathol., 147: 305-305. https://doi.org/10.1002/path.1711470413
Ullah, A., Ali, N., Ahmad, S., Rahman, S. U., Alghamdi, S., Bannunah, A. M., Ali, R., Aman, A., Khan, J., Hussain, H., & Sahibzada, M. U. K.. (2023). Glycogen synthase kinase-3 (GSK-3) a magic enzyme: it’s role in diabetes mellitus and glucose homeostasis, interactions with fluroquionlones. A mini-review. Brazilian Journal of Biology, 83, e250179. https://doi.org/10.1590/1519-6984.250179
Weinert, L. S., Silveiro, S. P., Oppermann, M. L., Salazar, C. C., Simionato, B. M., Siebeneichler, A., & Reichelt, A. J.. (2011). Diabetes gestacional: um algoritmo de tratamento multidisciplinar. Arquivos Brasileiros De Endocrinologia & Metabologia, 55(7), 435–445. https://doi.org/10.1590/S0004-27302011000700002
Wolf, S. J., Melvin, W. J., & Gallagher, K. (2021). Macrophage-mediated inflammation in diabetic wound repair. Seminars in cell & developmental biology, 119, 111–118. https://doi.org/10.1016/j.semcdb.2021.06.013
Yaghini, N., Mahmoodi, M., Asadikaram, G. R., Hassanshahi, G. H., Khoramdelazad, H., & Kazemi Arababadi, M. (2011). Serum levels of interleukin 10 (IL-10) in patients with type 2 diabetes. Iranian Red Crescent medical journal, 13(10), 752.
Yameny, A. (2024). Visão geral do diabetes mellitus em 2024. Journal of Bioscience and Applied Research , 10 (3), 641-645. https://doi.org/10.21608/jbaar.2024.382794
Yin, R., Zhang, Y., Fang, X., Zhang, Y., Miao, R., Yao, Y., Guan, H., & Tian, J. (2025). Discovering diabetes complications-related microRNAs: meta-analyses and pathway modeling approach. BMC medical genomics, 18(1), 86. https://doi.org/10.1186/s12920-025-02144-1
Yao, Y., Li, R., Du, J., Long, L., Li, X., & Luo, N. (2019). Interleukin-6 and Diabetic Retinopathy: A Systematic Review and Meta-Analysis. Current eye research, 44(5), 564–574. https://doi.org/10.1080/02713683.2019.1570274
Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2018 Feb;14(2):88-98. https://doi.org/10.1038/nrendo.2017.151.
Zhu, M., Huang, Q., Li, H., Zhao, Y., Guo, H., Wang, T., Liu, X., Huang, Y., Hu, J., Fang, C., & Huang, J. (2024). The impact of site-specific DNA methylation in KCNJ11 promoter on type 2 diabetes. Heliyon, 10(22), e39934. https://doi.org/10.1016/j.heliyon.2024.e39934
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Natália Conceição dos Santos, André Santos Carvalho, João Pedro Cunha Lima, Carla Cristina dos Santos Cardoso, Leonardo Guedes Rodrigues, Denilson de Araújo e Silva
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
