• KAMALESH D. R. Drug Testing Laboratory, Bangalore 560001, Karnataka, India, College of Pharmaceutical, Sciences, Dayanand Sagar University, Shavige Malleshwara Hills, 1st Stage, Kumaraswamy Layout, Bengaluru, Karnataka 560078
  • GEETHA K. M. College of Pharmaceutical, Sciences, Dayanand Sagar University, Shavige Malleshwara Hills, 1st Stage, Kumaraswamy Layout, Bengaluru, Karnataka 560078




Insulin, Diabetes mellitus, Biomarker, Glycated haemoglobin, Fructosamine, Ferritin


Diabetes mellitus is one of the leading metabolic disorders in the last few decades, affecting the larger population of the world in both developed and developing countries.

In diabetes mellitus there is reduced secretion and/or action leading to disturbance in the metabolism of glucose. The prolonged hyperglycemia causes several microvascular and macrovascular complications, which are the leading cause of death. Although the prevalence of diabetes is high, the majority of the people remain undiagnosed, which leads to complications. The diagnosis of diabetes involves the measurement of blood glucose levels. Several biochemical and body components regulate the secretion and action of insulin. Therefore, they serve as biomarkers for the diagnosis of diabetes mellitus. The biomarkers like HbA1C, glycated albumin, fructosamine, ferritin, fetuin-A, ceramides, HDL cholesterol, calprotectin, Acylcarnitine and micro RNA are some of the important biomarkers for diabetes mellitus. Through this review, we have made an attempt to describe the role and significance of biomarkers for diabetes mellitus.


Download data is not yet available.


Deepthi B, Sowjanya K, Lidiya B, Bhargavi RS, Babu PS. A modern review of diabetes mellitus: an uninhilatory metabolic disorder. J In Silico In Vitro Pharmacol. 2017;3(1):1-5.

Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLOS Med. 2006;3(11):442. doi: 10.1371/journal.pmed.0030442.

Tiwari N. Therapeutic targets for diabetes mellitus: an update. Clinic Pharmacol Biopharm 2014;3(1). doi: 10.4172/2167-065X.1000117.

Johnson L, Strich H, Taylor A, Timmermann B, Malone D, Teufel Shone N, Drummond R, Woosley R, Pereira E, Martinez A. Use of herbal remedies by diabetic Hispanic women in the southwestern United States. Phytother Res. 2006;20(4):250-5. doi: 10.1002/ptr.1820. PMID 16557605.

Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Invest. 2005;115(5):1111-9. doi: 10.1172/JCI25102.

Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2018;14(2):88-98. doi: 10.1038/nrendo.2017.151, PMID 29219149.

Lacro CRM, Barengo NC, Flores LA, Rauner M. Update on the impact of type 2 diabetes mellitus on bone metabolism and material properties. Endocr Connect. 2019;8(3):R55-70.

Khawandanah J. Double or hybrid diabetes: A systematic review on disease prevalence, characteristics and risk factors. Nutr Diabetes. 2019;9(1):33. doi: 10.1038/s41387-019-0101-1, PMID 31685799.

Mishra BK, Shukla P, Aslam M, Siddiqui AA, Madhu SV. Prevalence of double diabetes in youth onset diabetes patients from east Delhi and neighboring NCR region. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2018;12(6):839-42. doi: 10.1016/j.dsx.2017.08.016.

Merger SR, Kerner W, Stadler M, Zeyfang A, Jehle P, Muller Korbsch M, Holl RW. Prevalence and comorbidities of double diabetes. Diabetes Res Clin Pract. 2016;119:48-56. doi: 10.1016/j.diabres.2016.06.003.

Braham R, Alzaid A, Robert AA, Mujammami M, Ahmad RA, Zitouni M, Sobki SH, Al Dawish MA. Double diabetes in Saudi Arabia: A new entity or an underestimated condition. World J Diabetes. 2016;7(20):621-6. doi: 10.4239/wjd.v7.i20.621, PMID 28031780.

Kamalesh DR, Geetha KM, Harish M. Target treatment in diabetic and microvascular complications: an updated review. Int J Pharm Sci Res. 2020;11(8):1000-8.

Lyons TJ, Basu A. Biomarkers in diabetes: hemoglobin A1c, vascular and tissue markers. Transl Res. 2012;159(4):303-12. doi: 10.1016/j.trsl.2012.01.009, PMID 22424433.

Herder C, Karakas M, Koenig W. Biomarkers for the prediction of type 2diabetes and cardiovascular disease. Clin Pharmacol Ther. 2011;90(1):52-66. doi: 10.1038/clpt.2011.93, PMID 21654741.

Lima N, Cavaliere H, Tomimori E, Knobel M, Medeiros-Neto G. Prognostic value of serial serum thyroglobulin determinations after total thyroidectomy for differentiated thyroid cancer. J Endocrinol Invest. 2002;25(2):110-5. doi: 10.1007/ BF03343973, PMID 11929080.

Chien HY, Lee T, Chen C, Chiu Y, Lin Y, Lee L, Li W. Circulating microRNA as a diagnostic marker in populations with type 2 diabetes mellitus and diabetic complications. Journal of the Chinese Medical Association. 2015;78(4):204-11. doi: 10.1016/j.jcma.2014.11.002.

Schnedl WJ, Liebminger A, Roller RE, Lipp RW, Krejs GJ. Hemoglobin variants and determination of glycated hemoglobin (HbA1c). Diabetes Metab Res Rev. 2001;17(2):94-8. doi: 10.1002/dmrr.186. PMID 11307174.

Sherwani SI, Khan HA, Ekhzaimy A, Masood A, Sakharkar MK. Significance of HbA1c test in diagnosis and prognosis of diabetic patients. Biomark Insights. 2016;11:95-104. doi: 10.4137/BMI.S38440, PMID 27398023.

English E, Milosevich E, John WG. In vitro determination of haemoglobin A1c for diabetes diagnosis and management: technology update. Pathol Lab Med Int. 2014;6:21-31.

Radchenko OM, Korolyuk OY. Glycated hemoglobin: mechanisms of formation and clinical significance (literature review and own researches). IEJ 2020;16(1):69-75. doi: 10.22141/2224-0721.16.1.2020.199131.

Guo W, Zhou Q, Jia Y, Xu J. Increased levels of glycated hemoglobin A1c and Iron deficiency Anemia: a review. Med Sci Monit. 2019;25:8371-8. doi: 10.12659/MSM.916719, PMID 31696865.

Weykamp C, John WG, Mosca A. A review of the challenge in measuring haemoglobin. J Diabet Sci Technol. 2009;3(A1c):439-45.

Ozçelik F. Comparison of three methods for measurement of HbA1c. Turk J Biochem. 2010;35:344-9.

Lin CN, Emery TJ, Little RR, Hanson SE, Rohlfing CL, Jaisson S, Gillery P, Roberts WL. Effects of hemoglobin C, D, E, and S traits on measurements of HbA1c by six methods. Clin Chim Acta. 2012;413(7-8):819-21. doi: 10.1016/j.cca.2011.12.019.

Rathod SD. Glycated haemoglobinA1c (HbA1c) for detection of diabetes mellitus and impaired fasting glucose in Malawi: a diagnostic accuracy study. BMJ. 2018;8:e020972.

Khan HA, Sobki SH, Khan SA. Association between glycaemic control and serum lipids profile in type 2 diabetic patients: HbA1c predicts dyslipidaemia. Clin Exp Med. 2007;7(1):24-9. doi: 10.1007/s10238-007-0121-3, PMID 17380302.

Radin MS. Pitfalls in hemoglobin A1c measurement: when results may be misleading. J Gen Intern Med. 2014;29(2):388-94. doi: 10.1007/s11606-013-2595-x, PMID 24002631.

Qatanani M, Lazar MA. Mechanisms of obesity-associated insulin resistance: many choices on the menu. Genes Dev. 2007;21(12):1443-55. doi: 10.1101/gad.1550907, PMID 17575046.

Mori K, Emoto M, Yokoyama H, Araki T, Teramura M, Koyama H, Shoji T, Inaba M, Nishizawa Y. Association of serum fetuin-a with insulin resistance in type 2 diabetic and nondiabetic subjects. Diabet Care. 2006;29(2):468. doi: 10.2337/diacare.29.02.06.dc05-1484.

Mori K, Emoto M, Inaba M. Fetuin-A: A multifunctional protein. Recent Pat Endocr Metab Immune Drug Discov. 2011;5(2):124-46. doi: 10.2174/187221411799015372, PMID 22074587.

Pal D, Dasgupta S, Kundu R, Maitra S, Das G, Mukhopadhyay S, Ray S, Majumdar SS, Bhattacharya S. Fetuin-a acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance. Nat Med. 2012;18(8):1279-85. doi: 10.1038/nm.2851, PMID 22842477.

Aroner SA, St-Jules DE, Mukamal KJ, Katz R, Shlipak MG, Criqui MH, Kestenbaum B, Siscovick DS, de Boer IH, Jenny NS, Budoff MJ, Ix JH, Jensen MK. Fetuin-A, glycemic status, and risk of cardiovascular disease: the multi-ethnic study of atherosclerosis. Atherosclerosis. 2016;248:224-9. doi: 10.1016/j.atherosclerosis.2016.03.029, PMID 27038419.

Youssef D, El Abbassi A, Jordan RM, Peiris AN. Fructosamine-an underutilized tool in diabetes management: case report and literature review. Tenn Med. 2008;101(11):31-3. PMID 19024248.

Lee JE. Alternative biomarkers for assessing glycemic control in diabetes: fructosamine, glycated albumin, and 1,5-anhydroglucitol. Ann Pediatr Endocrinol Metab. 2015;20(2):74-8. doi: 10.6065/apem.2015.20.2.74, PMID 26191510.

Ribeiro RT, Macedo MP, Raposo JF. HbA1c, fructosamine, and glycated albumin in the detection of dysglycaemic conditions. Curr Diabetes Rev. 2016;12(1):14-9. doi: 10.2174/1573399811666150701143112, PMID 26126638.

Shimizu L, Kohzuma T, Koga M. A proposed glycemic control marker for future. J Lab Prec Med. 2019;4:23.

Koga M, Hashimoto K, Murai J, Saito H, Mukai M, Ikegame K, Ogawa H, Kasayama S. Usefulness of glycated albumin as an indicator of glycemic control status in patients with hemolytic anemia. Clin Chim Acta. 2011;412(3-4):253-7. doi: 10.1016/j.cca.2010.10.014.

Huang Y, Hu Y, Ma YU, Ye G. Glycated albumin is an optimal biomarker for gestational diabetes mellitus. Exp Ther Med. 2015;10(6):2145-9. doi: 10.3892/etm.2015.2808, PMID 26668607.

Dozio E, Di Gaetano N, Findeisen P, Corsi Romanelli MM. Glycated albumin: from biochemistry and laboratory medicine to clinical practice. Endocrine. 2017;55(3):682-90. doi: 10.1007/s12020-016-1091-6. PMID 27623968.

Haus JM. Plasma ceramides are elevated in obese subjects with type2 diabetes and correlates with the severity of insulin resistance. Diabetes. 2009;58(1):337-43.

Summers SA. Ceramides in insulin resistance and lipotoxicity. Prog Lipid Res. 2006;45(1):42-72. doi: 10.1016/j.plipres.2005.11.002, PMID 16445986.

Haase CL, Tybjærg Hansen A, Nordestgaard BG, Frikke Schmidt R. HDL cholesterol and risk of type 2 diabetes: a mendelian randomization study. Diabetes. 2015;64(9):3328-33. doi: 10.2337/db14-1603, PMID 25972569.

Femlak M, Gluba Brzozka A, Ciałkowska Rysz A, Rysz J. The role and function of HDL in patients with diabetes mellitus and the related cardiovascular risk. Lipids Health Dis. 2017;16(1):207. doi: 10.1186/s12944-017-0594-3. PMID 29084567.

Gilad S, Meiri E, Yogev Y, Benjamin S, Lebanony D, Yerushalmi N, Benjamin H, Kushnir M, Cholakh H, Melamed N, Bentwich Z, Hod M, Goren Y, Chajut A. Serum microRNAs are promising novel biomarkers. PLOS ONE. 2008;3(9):e3148. doi: 10.1371/journal.pone.0003148, PMID 18773077.

Etheridge A, Gomes CP, Pereira RW, Galas D, Wang K. The complexity, function and applications of RNA in circulation. Front Genet. 2013;4:115. doi: 10.3389/fgene.2013.00115, PMID 23785385.

Lu TX, Rothenberg ME. MicroRNA. J Allergy Clin Immunol. 2018;141(4):1202-07. doi: 10.1016/j.jaci.2017.08.034.

Vasu S, Kumano K, Darden CM, Rahman I, Lawrence MC, Naziruddin B. MicroRNA signatures as future biomarkers for diagnosis of diabetes states. Cells. 2019;8(12):1533. doi: 10.3390/cells8121533, PMID 31795194.

Beltrami C, Angelini TG, Emanueli C. Noncoding RNAs in diabetes vascular complications. J Mol Cell Cardiol. 2015;89(A):42-50. doi: 10.1016/j.yjmcc.2014.12.014, PMID 25536178.

Kong L, Zhu J, Han W, Jiang X, Xu M, Zhao Y, Dong Q, Pang Z, Guan Q, Gao L, Zhao J, Zhao L. Significance of serum microRNAs in pre-diabetes and newly diagnosed type 2 diabetes: a clinical study. Acta Diabetol. 2011;48(1):61-9. doi: 10.1007/s00592-010-0226-0, PMID 20857148.

Liu Y, Gao G, Yang C, Zhou K, Shen B, Liang H, Jiang X. The role of circulating micro RNA-126 (miR-126): a novel biomarker for screening prediabetes and newly diagnosed type 2 diabetes mellitus. Int J Mol Sci. 2014;15(6):10567-77. doi: 10.3390/ijms150610567, PMID 24927146.

Sun LL, Jiang BG, Li WT, Zou JJ, Shi YQ, Liu ZM. Micro RNA-15a positively regulates insulin synthesis by inhibiting uncoupling protein-2 expression. Diabetes Res Clin Pract. 2011;91(1):94-100. doi: 10.1016/j.diabres.2010.11.006, PMID 21146880.

Al-Kafaji G, Al-Mahroos G, Alsayed NA, Hasan ZA, Nawaz S, Bakhiet M. Peripheral blood microRNA-15a is a potential biomarker for type 2 diabetes mellitus and pre-diabetes. Mol Med Rep. 2015;12(5):7485-90. doi: 10.3892/mmr.2015.4416, PMID 26460159.

Burke JE, Dennis EA. Phospholipase A2 biochemistry. Cardiovascular Drugs Ther. 2009;23(1):49-59. doi: 10.1007/s10557-008-6132-9, PMID 18931897.

Triggiani M, Granata F, Giannattasio G, Marone G. Secretory phospholipases A2 in inflammatory and allergic diseases: not just enzymes. J Allergy Clin Immunol. 2005;116(5):1000-6. doi: 10.1016/j.jaci.2005.08.011, PMID 16275367.

Murakami M, Sato H, Miki Y, Yamamoto K, Taketomi Y. A new era of secreted phospholipase A₂. J Lipid Res. 2015;56(7):1248-61. doi: 10.1194/jlr.R058123, PMID 25805806.

Jones PM, Burns CJ, Belin VD, Roderigo Milne HM, Persaud SJ. The role of cytosolic phospholipase A(2) in insulin secretion. Diabetes. 2004;53Suppl 1:S172-8. doi: 10.2337/diabetes.53.2007.s172. PMID 14749284.

Striz I, Trebichavsky I. Calprotectin- a pleiotropic molecule in acute and chronic inflammation. Physiol Res. 2004; 53(3):245-53. PMID 15209531.

Brophy MB, Nolan EM. Manganese and microbial pathogenesis: sequestration by the mammalian immune system and utilization by microorganisms. ACS Chem Biol. 2015;10(3):641-51. doi: 10.1021/cb500792b, PMID 25594606.

Nakkashigeet AL, Human Nakashige TG, Zhang B, Krebs C, Nolan EM. Calprotectin is an iron sequestering host defense protein. Human calprotectin is an iron-sequestering host-defense protein. Nat Chem Biol. 2015;11(10):765-71. doi: 10.1038/nchembio.1891, PMID 26302479.

Lehmann FS, Burri E, Beglinger C. The role and utility of faecal markers in inflammatory bowel disease. Ther Adv Gastroenterol. 2015;8(1):23-36. doi: 10.1177/1756283X14553384.

Rheenen PF, Vijver EV, Fidler V. Calprotectin for screening of patients with suspected inflammatory bowel disease: a diagnostic metaanalysis. Br J 2010;341:c3369.

Tabur S, Kokmaz H, Ozkaya M, Aksoy NS, Akarsu E. Is calprotectin a novel biomarker of neuroinflammation in diabetic peripheral neuropathy? Diabetol MET Synd. 2015;7:30-6.

Ortega FJ, Sabater M, Moreno Navarrete JM, Pueyo N, Botas P, Delgado E, Ricart W, Fruhbeck G, Fernandez Real JM. Serum and urinary concentrations of calprotectin as markers of insulin resistance and type 2 diabetes. European J Endocrinology. 2012; 167(4):569-78. doi: 10.1530/EJE-12-0374.

Ramsay RR, Gandour RD, van der Leij FR. Molecular enzymology of carnitine transfer and transport. Biochim Biophys Acta. 2001;1546(1):21-43. doi: 10.1016/s0167-4838(01)00147-9. PMID 11257506.

Boreen J, Taskinen MR, Olofsson SO, Levin M. Ectopic lipid storage and insulin resistance: a harmful relationship. J Intern Med. 2013;274(1):25-40. doi: 10.1111/joim.12071, PMID 23551521.

Mynatt R. L-carnitine and type 2diabetes. Diabet Met. 2009;25:S45-S49.

Morino K, Petersen KIF and, Shulman GI. Molecular mechanisms of insulin resistance in humans and their potential links with mitochondrial dysfunction. Diabetes. 2006; 55Suppl 2:S9-S15. doi: 10.2337/db06-S002, PMID 17130651.

Mihalik SJ, Goodpaster BH, Kelley DE, Chace DH, Vockley J, Toledo FGS, DeLany JP. Increased levels of plasma acylcarnitines in obesity and type 2 diabetes and identification of a marker of glucolipotoxicity. Obesity. 2010;18(9):1695-700. doi: 10.1038/oby.2009.510.

Bene J, Hadzsiev K, Melegh B. Role of carnitine and its derivatives in the development and management of type 2 diabetes. Nutr and Diabetes. 2018;8(1):8-128. doi: 10.1038/s41387-018-0017-1, PMID 29549241.

Mai M, Tonjes A, Kovacs P, Stumvol M, Fiedler GM, Leichtle. Serum levels of acyl carnitines are altered in pre diabetic conditions. Plus One. 2013;8(12):e82459.

Achari AE, Jain SK. Adiponectin, a therapeutic target for obesity, diabetes, and endothelial dysfunction. Int J Mol Sci. 2017;18(6):1321. doi: 10.3390/ijms18061321, PMID 28635626.

Ghoshal K, Ghoshal K, Bhattacharya M. Adiponectin: probe of the molecular paradigm associating diabetes and obesity. World J Diabet. 2015;6(1):151-66. doi: 10.4239/wjd.v6.i1.151.

Nedvidkova, Smitka K, Kopsky V, Hainer V. Adiponectin. Adiponectin, an adipocyte-derived protein. Physiol Res. 2005; 54(2):133-40. PMID 15544426.

Coppola A. Effect of weight loss on coronary circulation and adiponectin levels in obese women. Int J Cardiol. 2009;134(3):414-6. doi: 10.1016/j.ijcard.2007.12.087, PMID 18378021.

Hara K, Yamauchi T, kadowaki T. Adiponectin: an adipokine linking adipocytes and type 2 diabetes in humans. Curr Diab Rep. 2005;5(2):136-40. doi: 10.1007/s11892-005-0041-0, PMID 15794918.

Wang W, Knovich MA, Coffman LG, Torti FM, Torti SV. Serum ferritin: past, present and future. Biocheim Biophys Acta. 2010;1800(8):760-9. doi: 10.1016/j.bbagen.2010.03.011, PMID 20304033.

Aregbesola A, Virtanen JK, Voutilainen S, Mursu J, Lagundoye A, Kauhanen J, Tuomainen T. Serum ferritin and glucose homeostasis: change in the association by glycaemic state. Diabet Met Res Rev Diabetes Metab Res Rev. 2015;31(5):507-14. doi: 10.1002/dmrr.2628.

Sharifi SF, Nasab NM, Zadeh HJ. Elevated serum ferritin concentrations in pre-diabetic subjects. Diabetic Vasc Dis Res Diab Vasc Dis Res. 2008;5(1):1-18. doi: 10.3132/dvdr.2008.003, PMID 18398807.

Akter S, Nanri A, Kuwahara K, Matsushita Y, Nakagawa T, Konishi M, Honda T, Yamamoto S, Hayashi T, Noda M, Mizoue T. Circulating ferritin concentrations and risk of type 2 diabetes in Japanese individuals. J Diabetes Investig. 2017;8(4):462-70. doi: 10.1111/jdi.12617, PMID 28060459.



How to Cite

D. R., K., and G. K. M. “A REVIEW ON ROLE OF MARKERS IN DIABETES MELLITUS AND ASSOCIATED MICRO AND MACROVASCULAR COMPLICATIONS”. International Journal of Current Pharmaceutical Research, vol. 14, no. 1, Jan. 2022, pp. 20-26, doi:10.22159/ijcpr.2022v14i1.44108.



Review Article(s)