Evaluation of the prognostic significance of leptin, adiponectin and resistin in the development of diabetic retinopathy in type 2 diabetes mellitus patients

Main Article Content

M.L. Kyryliuk


Background. There is evidence of the participation of adipose tissue hormones leptin, adiponectin and resistin in the formation of metabolic disorders in the retina, retinal neovascularization, and diabetic microangiopathy. The development of methods for the mathematical evaluation of the prognosis of diabetic retinopathy (DR) formation with the participation of adipokines is a relevant problem in modern diabetology. Aim. Elaboration of a mathematical model for assessing the prognostic significance of serum leptin, adiponectin and resistin to study the likelihood of deve­loping and progressing DR in patients with type 2 diabetes mellitus (DM). Materials and methods. An open observational single-center one-stage selective study was conducted among patients with type 2 DM and DR. The blood serum concentration of leptin, adiponectin and resistin, HbA1с, lipid metabolism findings were determined, the results of an instrumental examination of the fundus were analyzed. The diagnostic predictive value of serum leptin, adiponectin and resistin was assessed using discriminant analysis. Statistical analyses were conducted using Statistica 9.0 (StatSoft, Tulsa, OK, USA) software. The differences were considered statistically signifi­cant at p < 0.05. A model with linear combinations of the serum leptin, adiponectin and resistin, triglyceride (TG), HbA1с, type of antihyperglycemic therapy (oral anti-hyperglycemic medication or insulin therapy) were developed, and, subsequently, formulas for classification-relevant discriminant functions were derived. Results. Fifty-nine patients (107 eyes) with type 2 DM and DR (men and women; mean age, 58.20 ± 0.18 years; mean diabetes duration, 9.19 ± 0.46 years; mean HbA1с 9.10 ± 0.17 %) were assigned to the basic group and underwent the study. They were divided into three DR groups based on the stage of DR. When performing the ran­king of patients for discriminant analysis, the stage 2 DR group was aggregated with the stage 3 DR group for convenience to form the stage 2 + 3 DR group based on the pathognomonic sign (portents of proliferation or actual proliferation). Anti-diabetic therapy (ADT) included metformin, either alone (type 1 ADT) or in combination with oral anti-hyperglycemic medication (metformin + OAHGM, type 2 ADT) or insulin therapy (metformin + IT, type 3 ADT). Inclusion criteria were informed consent, age above 18 years, pre­sence of T2DM and DR. Exclusion criteria were endocrine or body system disorders leading to obesity (Cushing’s syndrome, hypothyroidism, hypogonadism, polycystic ovarian syndrome, or other endocrine disorders, including hereditary disorders, and hypothalamic obesity), type 1 DM, acute infectious disorders, history of or current cancer, decompensation of comorbidities, mental disorders, treatment with neuroleptics or antidepressants, proteinuria, clinically significant maculopathy, glaucoma or cataract. The study followed the ethical standards stated in the Declaration of Helsinki and was approved by the Local Ethics Committee. The formulas for classification-relevant discriminant functions were derived based on the results of physical examination, imaging and laboratory tests, and subsequent assessment of clinical signs of DM (HbA1с), DR stage and serum leptin, adiponectin, resistin, TG concentrations and taking into account the type of antihyperglycemic therapy. The classification functions (CF) computed based on the variables found from the above developed models provided the basis for predicting the development of DR. The formulas for CF from model are as follows: CF1 = 0.29 • TG + 1.55 • HbA1С + 1.81 • ADT_Type + 0.04 • Leptin + 0,34 • Adiponectin + 0,91 • Resistin – 13,82. CF2= 0.05 • TG + 1.36 • HbA1С + 3.01 • ADT_Type + 0.08 • Leptin + 0,35 • Adiponectin + 1,01 • Resistin – 15.95. A step-by-step approach to a diagnostic decision should be used. First, blood samples are tested for serum leptin, adiponectin and resistin, TG, blood HbA1c, and the patient is assigned a code for ADT Type (metformin only, 1; metformin + OAHGM, 2; or metformin + IT, 3). Second, CF1 and CF2 values are calculated based on clinical and laboratory data. Finally, the two values are compared to determine which is greater. The predictive decision is made by selecting the classification function with the greater value. Thus, if CF1 > CF2, the process can be stabilized at this stage given adequate glycemic control (through compensation of carbohydrate metabolism) and body mass control as well as patient compliance. If CF1 < CF2, the pathological process may progress to the next stage or even within stage 3, and there is an urgent need to reduce BMI, and to correct the ADT and the blood lipid profile. Conclusions. The informative value and statistical significance of the model were 71.4 % and p = 0.040, respectively. Using the formulas, one can determine the probability of progression of DR.

Article Details

How to Cite
Kyryliuk, M. “Evaluation of the Prognostic Significance of Leptin, Adiponectin and Resistin in the Development of Diabetic Retinopathy in Type 2 Diabetes Mellitus Patients”. INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), vol. 17, no. 3, June 2021, pp. 209-13, doi:10.22141/2224-0721.17.3.2021.232649.
Original Researches


Joyal JS, Sun Y, Gantner ML, et al. Retinal lipid and glucose metabolism dictates angiogenesis through the lipid sensor Ffar1. Nat Med. 2016 Apr;22(4):439-445. doi:10.1038/nm.4059.

Afarid M, Attarzadeh A, Farvardin M, Ashraf H. The Association of Serum Leptin Level and Anthropometric Measures With the Severity of Diabetic Retinopathy in Type 2 Diabetes Mellitus. Med Hypothesis Discov Innov Ophthalmol. 2018 Winter;7(4):156-162.

Fu Z, Gong Y, Löfqvist C, Hellström A, Smith LE. Review: adiponectin in retinopathy. Biochim Biophys Acta. 2016 Aug;1862(8):1392-1400. doi:10.1016/j.bbadis.2016.05.002.

Malachkova NV, Kyryliuk ML, Komarovska IV. Association between serum resistin level and diabetic retinopathy in obese patients with type 2 diabetes mellitus. J Ophthalmol (Ukraine). 2017;(477):9-13. doi:10.31288/oftalmolzh201753944. (in Russian).

Mao D, Peng H, Li Q, et al. Aqueous humor and plasma adiponectin levels in proliferative diabetic retinopathy patients. Curr Eye Res. 2012 Sep;37(9):803-808. doi:10.3109/02713683.2012.676700.

Kuo JZ, Guo X, Klein R, et al. Adiponectin, Insulin Sensitivity and Diabetic Retinopathy in Latinos With Type 2 Diabetes. J Clin Endocrinol Metab. 2015 Sep;100(9):3348-3355. doi:10.1210/jc.2015-1221.

Kohner EM, Porta M. Protocols for screening and treatment of diabetic retinopathy in Europe. Eur J Ophthalmol. 1991 Jan-Mar;1(1):45-54.

Wang W, Lo ACY. Diabetic Retinopathy: Pathophysiology and Treatments. Int J Mol Sci. 2018 Jun 20;19(6):1816. doi:10.3390/ijms19061816.

Whitehead M, Wickremasinghe S, Osborne A, Van Wijngaarden P, Martin KR. Diabetic retinopathy: a complex pathophysiology requiring novel therapeutic strategies. Expert Opin Biol Ther. 2018 Dec;18(12):1257-1270. doi:10.1080/14712598.2018.1545836.

Eisma JH, Dulle JE, Fort PE. Current knowledge on diabetic retinopathy from human donor tissues. World J Diabetes. 2015 Mar 15;6(2):312-320. doi:10.4239/wjd.v6.i2.312.

Nittala MG, Keane PA, Zhang K, Sadda SR. Risk factors for proliferative diabetic retinopathy in a Latino American population. Retina. 2014 Aug;34(8):1594-1599. doi:10.1097/IAE.0000000000000117.

Khan A, Petropoulos IN, Ponirakis G, Malik RA. Visual complications in diabetes mellitus: beyond retinopathy. Diabet Med. 2017 Apr;34(4):478-484. doi:10.1111/dme.13296.

Schreur V, van Asten F, Ng H, et al. Risk factors for development and progression of diabetic retinopathy in Dutch patients with type 1 diabetes mellitus. Acta Ophthalmol. 2018 Aug;96(5):459-464. doi:10.1111/aos.13815.

Zhao C, Wang W, Xu D, Li H, Li M, Wang F. Insulin and risk of diabetic retinopathy in patients with type 2 diabetes mellitus: data from a meta-analysis of seven cohort studies. Diagn Pathol. 2014 Jun 27;9:130. doi:10.1186/1746-1596-9-130.

Simó-Servat O, Hernández C, Simó R. Diabetic Retinopathy in the Context of Patients with Diabetes. Ophthalmic Res. 2019;62(4):211-217. doi:10.1159/000499541.

Duh EJ, Sun JK, Stitt AW. Diabetic retinopathy: current understanding, mechanisms, and treatment strategies. JCI Insight. 2017 Jul 20;2(14):e93751. doi:10.1172/jci.insight.93751.

Serdiuk VN, Kyryliuk ML, Ishchenko VA. Mathematical substantiation of the method for assessing the risk of progression of diabetic retinopathy with serum leptin determination in patients with metabolic syndrome and diabetes mellitus. J Ophthalmol (Ukraine). 2018;(481):17-22. doi:10.31288/oftalmolzh/2018/2/1721. (in Russian).

Most read articles by the same author(s)