The effect of supplementation of hydroalcoholic extract of okra fruit on lipid profile, renal function indices, expression of RAGE, ICAM-1, Il-1ß genes and serum level of sRAGE in patients with diabetic nephropathy: A triple-blind randomized controlled clinical trial

Abstract

bstract

Background: Diabetic nephropathy (DN) is one of the microvascular problems as well as a common complication of disease progression in people with type 2 diabetes. The anti-diabretic characteristic of Okra (Abelmoscus Escalntus L.) has been approved in several studies. However, no clinical trial has been conducted on the effects of okra on renal indices, inflammatory parameters, and the related genes, the present study aimed to investigate the effects of okra hydroalcoholic powdered extract supplementation on lipid profile, renal function indices, expression of RAGEs, ICAM, Il-1ß genes and serum level of sRAGE in patients with diabetic nephropathy (DN). Methods: This study is a triple-blind randomized controlled clinical trial in which eligible individuals were recruited through public announcement as well as the clinic of Imam Reza Hospital and Tabriz Diabetes Association. Patients with DN in stage шA were diagnosed by the excretion of more than 0.3 g of protein in 24-hour urine for more than 3 months or glomerular filtration (GFR) of 45-60 ml/min/m 2 with a history of retinopathy. After considering the inclusion and exclusion criteria, 64 patients were randomly assigned to either the intervention (125-mg okra) or placebo (125-mg carboxy methyl cellulose) groups (n=32) for 10 weeks, using the random block method, based on gender. In addition, the two study groups received DN-related dietary recommendations. Serum levels of lipid profile and sRAGE were assessed before and after supplementation. The expression of RAGE, ICAM-1, and lL-1ß genes in peripheral blood mononuclear cells (PBMCs) was evaluated, using Real-Time PCR technique. Also, three statistical models were applied for adjusting the effect of baseline values as well as confounding factors, as below: model 1 (baseline values), model 2 (baseline values, age, and changes in physical activity, energy intake, and body mass index (BMI)), and model 3 (baseline values, age, and changes in physical activity, energy intake, BMI, GFR, and HOMA-IR). Statistical analyses were performed using SPSS 21 and STATA 16 softwares. Results: At the end of the study, there was a remarkable decrease in systolic blood pressure (P= 0.056), MD [95% CI]: -8.3 (-16.8 , 0.21) and energy intake (P=0.04), MD [95% CI]: -214.56 (-425.87, -3.25) within the intervention group. However, there were no significant differences in terms of energy intake and systolic or diastolic blood pressure between the two groups. Also, after the intervention, serum levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-c) decreased in the intervention group, while no statistically significant difference was observed between the two groups. At the end of the study, serum level of high-density lipoprotein cholesterol (HDL-c) increased significantly in the intervention group, compared to the baseline (P<0.01); although the difference between the two groups was not significant. No significant difference was found in terms of sRAGE between the two groups, even after controlling for confounders. The expression levels of RAGE, ICAM-1, and Il-1ß genes as well as proteinuria and GFR state did not show a statistically significant difference between the two groups. Conclusion: The findings of the present study showed that probably due to the progressive nature of DN, dried okra extract supplement could not cause significant changes in renal function indices and lipid profile between the two groups, though intra-group changes were observed in some indices. Numerous factors such as geographical differences in growing areas, harvesting time, and size of okra can affect the components of okra, especially the amount of polyphenols and antioxidants which can affect the results of the study. Keywords: Diabetic nephropathy, Okra (Abelmoscus Escalntus L.), Receptor for Advanced glycation end products, soluble Receptor for Advanced glycation end products, Intercellular adhesion molecules, Interleukin 1 beta