Original ArticlesSerum 1,25 dihydroxy vitamin D (1,25(OH)2D3), 25 hydroxy vitamin D (25(OH)D) and parathormone levels in diabetic retinopathy
Introduction
S erum concentration of 1,25(OH)2D3 is important in the regulation of calcium metabolism. The etiology of type 2 diabetes is likely to involve defects of both insulin secretion and insulin signaling. In experimental animals, vitamin D is neccesary for normal insulin release and maintenance of glucose tolerance. The β cell possesses specific receptors for the activated hormone 1,25(OH)2D3 and vitamin D-dependent calcium-binding proteins (1). Insulin secretion is impaired by vitamin D deficiency and restored by 1,25(OH)2D3 administration (2).
Diabetic retinopathy (DR) is one of the most common causes of blindness in individuals between the ages of 20 and 65 years. Neovascularization is the hallmark of proliferative DR (PDR), which is a severe form of DR, and until the onset of vitreous hemorrhage, PDR can be completely asymptomatic and can only be detected by examinations of the optic fundus (3). Related to diagnosis, some studies reported that vitreous levels of insulinlike growth factor-1 (IGF-1) were found elevated in patients with PDR relative to those in controls (4) and the association of the serum IGF-1 concentration with PDR has been determined (5). In contrast, Nardelli et al. (6) could not show the increased levels of IGF-1 in diabetics with retinopathy. Human hepatocyte growth factor (hHGF) is a powerful inducer of angiogenesis 7, 8. One study suggested that diabetic patients whose serum hHGF concentrations are high may have PDR and need detailed ophthalmologic examination, although low concentrations of serum hHGF does not necessarily exclude the existence of PDR (9).
It has been realized from the findings of some studies that 1,25(OH)2D3 inhibits proliferation of breast cancer cell in vitro and in animal models in vivo 10, 11, 12. In addition to its effects on tumor cell proliferation and differentiation, the hormone also has potent inhibitory effects on angiogenesis in embryos and in transgenic murine retinoblastoma (13) and, therefore, low serum levels of 1,25(OH)2D3 may lead to increased, uncontrolled angiogenesis with the progression of breast cancer (14).
Although there are several studies demonstrating lower 1,25(OH)2D3 concentrations in children and adolescents with type 1 diabetes, patients admitted with diabetic ketoacidosis, and patients with type 2 diabetes 1, 15, 16, we could not find any study related to relationship of DR and 1.25(OH)2D3 in the literature. Therefore, we aimed to investigate the relationship, if present, of DR and levels of 1,25(OH)2D3, being an inhibitor of angiogenesis.
Section snippets
Subjects and methods
Sixty-six patients with the diagnosis of noninsulin dependent diabetes mellitus were included in this study: 24 men and 42 women (57.3 ± 7.37 years). Patients were examined to determine the degree of DR by a specialist in the ophthalmology department. Patients were classified as following: no diabetic retinopathy (NDR), n = 20; background diabetic retinopathy (BDR), n = 15; preproliferative diabetic retinopathy (pre-PDR), n = 14; and proliferative diabetic retinopathy (PDR), n = 17.
Following
Results
The mean serum concentration of 1,25 (OH)2D3 was lower in the diabetic patients than in nondiabetic healthy subjects (57.3 ± 21.44 vs. 89.4 ± 18.01 pmol/L, respectively; p < 0.001). From the findings of the present study it can be stated that there was an inverse relationship between the severity of DR and serum 1,25(OH)2D3 concentrations, that is, serum 1,25(OH)2D3 concentrations were found increased as the grade of DR was worsened (for BDR, 63.4 ± 17.26 pmol/L; for pre-PDR, 47.7 ± 13.27
Discussion
1,25(OH)2D3 is neccesary for normal insulin release, but the mechanism has not been clarified, yet. On the other hand, there is evidence that 1,25(OH)2D3 directly influences insulin secretion in the β cell through a rise in intracellular channel (1). It was found that plasma 1,25(OH)2D3 concentrations were decreased in diabetic rats (18), in vitamin D-deficient animals (19), and in subjects with gestational DM (20). The administration of 1,25(OH)2D3 increases insulin secretion and improves
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