Recent epidemiological data show an enhancement in the prevalence of type 1 diabetes mellitus (T1DM), which is characterized by autoimmune destruction by CD4+ and CD8+ T cells of insulin-producing β cells in the pancreas, with further infiltration of the pancreatic islets by the macrophages. T1DM accounts for about 10% of all cases of diabetes, affecting around 2 million of people in Europe and North America [1].
DR is the most common ocular complication of diabetes mellitus, as well as the most prevalent cause for irreversible vision loss in working-age population [2].
Vision-threatening DR is rarely present at the moment of T1DM diagnosis, but after 20 years, 99% of patients with T1DM develop DR having different complex symptoms. On the other hand, in diabetic patients with type 2 diabetes mellitus (T2DM), DR can be found at the time of diagnosis and 20 years afterwards, approx. 60% of patients having different manifestations of DR [3].
The pathophysiology of the DR is considered more or less known, being mostly described the role of hyperglycemia and altered metabolic pathways in the development of oxidative stress and neurodegeneration in the initial stage. As early hallmarks of non‐proliferative diabetic retinopathy (NPDR) are remarked: vascular endothelial damage, the development of microaneurysms, and dot intraretinal hemorrhage. Continuously, under fundoscopy is observed the disruption of the blood–retinal barrier, with further leakage of multiple inflammatory cytokines and plasma proteins that explains the appearance of the hard exudates. Tortured capillaries and retinal ischemia are explained by the vasoconstriction and capillary occlusions. In the last stage of DR, marked hypoxia induce neovascularization, vitreous hemorrhage, and retinal detachment [2, 4].
Many different classifications have been proposed in order to simplify the approach to the diagnostic and treatment of DR. In order to ease the communication between doctors has been developed an International Clinical Disease Severity Scale, which is based on the findings of the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) and the Early Treatment Diabetic Retinopathy Study (ETDRS). There are five stages of DR that are recognized [5].
An increase in the frequency of the disease and its complications, underlines the need of a better understanding of the pathophysiology of DR, in order to be able to identify it in the first stage, the high-risk patients and at the same time to assure a personalized tailored therapy with a minimization of further negative consequences [6].
Nowadays a series of biomarkers of DR related to the visualization of the retinal vasculature and measuring of glycemia, lipids, blood pressure, body weight are used for diagnostic and treatment purpose. Moreover, novel biomarkers and mediators of DR, as for example the one related to inflammation and angiogenesis, have influenced the development of extra therapeutics, especially for late-stage retinopathy, like intra-ocular corticosteroids and intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') agents. Unfortunately, in spite of a range of treatments, a lot of patients still are underdiagnosed [7].
Many studies have demonstrated that intensive control of the risk factors for DR is essential in reducing the onset and progression of DR. At present, the relationship between lipid profile and DR remains unclear. But lipid metabolic abnormalities have emerged as potential risk factors for the onset and progression of diabetic complications, including DR [8, 9].
Enhanced lipid levels were incriminated to induce endothelial dysfunction (ED) as a result of reduced bioavailability of nitric oxide. Hence, it has been suggested that ED plays a role in retinal degeneration in DR [10]. However, a disturbance in metabolism of lipids cannot be fully responsible for all pathological changes that lead to the development of retinopathy, there is still a lot of evidence to be rechecked and examined, due to interesting new data that are arriving continuously. Large epidemiologic studies imply an inconsistent association between serum TG or major cholesterol species and the severity of DR, but certain specific lipoprotein species are proved to have a stronger association with DR severity, suggesting a pathological role for lipoproteins, which are modified in the intraretinal environment, creating substantial local damage [11].
Nevertheless, there is a huge gap in the research of lipid markers, especially in DR at the patients with T1DM. Mostly all the recent data are based on T2DM population [12]. Also, only few studies have specifically explained the role of lipids and lipoproteins in different retinal diseases [13]. Therefore, we consider that it would be of much interest to search for how conventional biomarkers of lipid status as well as lipoproteins can contribute to the development and progression of DR.
The aim of the study was to analyze the association between DR in patients with T1DM, and lipid biomarkers changes, as well as to highlight possible existing correlations.