NEW PREDICTIVE FACTORS OF DIABETIC MACULOPATHY DEVELOPMENT IN DIABETES MELLITUS TYPE 2
Article PDF

Keywords

diabetes mellitus type 2, diabetic maculopathy, endothelin-1, TNFα

How to Cite

Panchenko, Y., Mogilevskyy, S., Ziablitsev, S., & Chernobrivtsev, O. (2018). NEW PREDICTIVE FACTORS OF DIABETIC MACULOPATHY DEVELOPMENT IN DIABETES MELLITUS TYPE 2. Medical Science of Ukraine (MSU), 14(3-4), 60-65. https://doi.org/10.32345/2664-4738.3-4.2018.08

Abstract

Relevance. In diabetes mellitus (DM), a cascade of pathological reactions unfolds in the vascular endothelium with the formation of endothelial dysfunction (EDF). Its main factors are endothelium hormone – endothelin-1 (ET1), nitric oxide (NO), endothelial NO-synthase (eNOS), and also tumor necrosis factor-α (TNFα). But the unexplored question remains whether EDFs can be used as prognostic markers for the development of diabetic maculopathy.

Objective: to find out the prognostic value of EDF factors in the development of diabetic maculopathy (DM) in type 2 diabetes.

Material and methods. This study included 152 patients (304 eyes) with type 2 diabetes, which were divided into groups according to the degree of diabetic retinopathy (DR): 1st – initial non-proliferative DR, 2nd – moderate or severe non-proliferative DR and 3rd – proliferative DR. DM was determined by the presence of specific diabetic retinal changes in the macular area according to the International Clinical Gravity Scale of the American Academy of Ophthalmology (2002). The control group consisted of 95 people. The content of ET1, eNOS and TNFα was determined by ELISA; the content of the final NO metabolites (NOx) was determined spectrophotometrically. Statistical data processing was performed using Statistica 10 (StatSoft, Inc., USA).

Results. With the progression of DR, there was an increase in the frequency and severity level of DM (p=2.0e-06), which was accompanied by an increase in the blood levels ET1 (3.7-4.7 times), NOx (1.4-1.5  times) and TNFα (4.2-6.5 times), with a progressive decrease in the level of eNOS (P<0.01). Multifactorial logistic regression analysis (GLZ package; StatSoft, Inc., USA) showed that pathogenetic factors for the DM development were multiple increase in blood levels of ET1 and TNFα, which was confirmed by building a logistic regression model with satisfactory results of adequacy (p=0.039).

Conclusions. This study confirmed the significant role of EDF in type 2 diabetes and proved the prognostic value of ET1 and TNFα blood levels for the development of DM.

https://doi.org/10.32345/2664-4738.3-4.2018.08
Article PDF

References

Balashevich L.I., Izmailov A.S. Diabeticheskaya oftalomopatiya [Diabetic ophthalmopathy]. SPb.: Man. 2012. 396 p. [in Russian]

Ziablitsev S.V., Chernobrivtsev OP, Ziablitsev D.S. Znachennya factoru nekrozu puhlin alfa u mehanizmah rozvitku nefropatii pri cukrovomu diabeti 2 tipu [The importance of the Tumor Necrotic Factor alpha in mechanisms of the nephropathy development in diabetus mellitus 2 type] // Clіn endocr and endocr surg. 2019. 65 (1): 72-80. [in Ukrainian]

Pasechnikova N.V. Diabeticheskaya makulopatiya. Sovremennie aspecti patogeneza, kliniki, diagnostiki, lechenia [Diabetic maculopathy. Modern aspects of pathogenesis, clinic, diagnosis, treatment]. Kiev: publishing house LLC "Carbon LTD." 2010. 154 p. [in Russian]

Babik B., Peták F., Agócs S., Blaskovics I., Alács E., Bodó K., et al. Diabetes mellitus: endothelial dysfunction and changes in hemostasis // OrvHetil. 2018. 159 (33): 1335-1345. DOI: 10.1556/650.2018.31130.

Blum A, Socea D, Sirchan R. Vascular responsiveness in type 2 diabetes mellitus (T2DM) // QJM. 2016. 109 (12): 791-796. DOI: 10.1093/qjmed/hcw081

Bregar D., Cilenšek I., Mankoč S., Reschner A., Petrovič D., Globočnik Petrovič M. The joint effect of the endothelin receptor B gene (EDNRB) polymorphism rs10507875 and nitric oxide synthase 3 gene (NOS3) polymorphism rs869109213 in Slovenian patients with type 2 diabetes mellitus and diabetic retinopathy // Bosn J Basic Med Sci. 2018. 18 (1): 80-86. DOI: 10.17305/bjbms.2017.2244.

Copps K.D., White M.F. Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2 // Diabetologia. 2012. 55 (10): 2565-2582. DOI:10.1007/s00125-012-2644-8.

Georgianos P.I., Agarwal R. Endothelin A receptor antagonists in diabetic kidney disease // Curr Opin Nephrol Hypertens. 2017. 26 (5): 338-344. DOI: 10.1097/MNH.0000000000000342.

IRS1 – Insulin receptor substrate 1 – Homo sapiens (Human) – IRS1 gene & protein". www.uniprot.org. Retrieved 2016-04-21.

Kaur R., Kaur M., Singhcorresponding J. Endothelial dysfunction and platelet hyperactivity in type 2 diabetes mellitus: molecular insights and therapeutic strategies // Cardiovasc Diabetol. 2018. 17: 121. DOI: [10.1186/s12933-018-0763-3].

Knapp M., Tu X., Wu R. Vascular endothelial dysfunction, a major mediator in diabetic cardiomyopathy // ActaPharmacol Sin. 2018. DOI: 10.1038/s41401-018-0042-6.

Li W., Abdul Y., Ward R., Ergul A. Endothelin and diabetic complications: a brain-centric view. Physiol Res. 2018. 67 (Supplementum 1): S83-S94.

Lian K., Guo X., Huang Q., Tan Z., Xia C., Wang R., et al. Reduction Levels and the Effects of High-Molecular-Weight Adiponectin via AMPK/eNOS in Chinese Type 2 Diabetes // Exp Clin Endocrinol Diabetes. 2016. 124 (9): 541-547. DOI: 10.1055/s-0042-109262.

Liu C., Feng X., Li Q., Wang Y., Li Q., Hua M. Adiponectin, TNF-α and inflammatory cytokines and risk of type 2 diabetes: A systematic review and meta-analysis // Cytokine. 2016. 86: 100-109. DOI: 10.1016/j.cyto.2016.06.028.

Pi X., Xie L., Patterson C. Emerging Roles of Vascular Endothelium in Metabolic Homeostasis // Circ Res. 2018. 123 (4): 477-494. DOI: 10.1161/CIRCRESAHA.118.313237.

Polovina M.M., Potpara T.S. Endothelial dysfunction in metabolic and vascular disorders // Postgrad Med. 2014. 126 (2): 38-53. DOI: 10.3810/pgm.2014.03.2739.

Takaguri A. Elucidation of a new mechanism of onset of insulin resistance: effects of statins and tumor necrosis factor-α on insulin signal transduction // Yakugaku Zasshi. 2018. 138 (11): 1329-1334. DOI: 10.1248/yakushi.18-00116. [In Japanese]

Zanatta C.M., Crispim D., Sortica D.A., Klassmann L.P., Gross J.L., Gerchman F., Canani L.H. Endothelin-1 gene polymorphisms and diabetic kidney disease in patients with type 2 diabetes mellitus // Diabetol Metab Syndr. 2015. 7: 103. DOI: 10.1186/s13098-015-0093-5.

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.