scholarly journals A Phase IIb Randomized Controlled Trial Investigating the Effects of Tocotrienol-Rich Vitamin E on Diabetic Kidney Disease

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 258
Author(s):  
Yan Yi Koay ◽  
Gerald Chen Jie Tan ◽  
Sonia Chew Wen Phang ◽  
J-Ian Ho ◽  
Pei Fen Chuar ◽  
...  
Keyword(s):  
Vitamin E ◽  
Kidney Disease ◽  
Serum Creatinine ◽  
Diabetic Kidney Disease ◽  
Controlled Trial ◽  
Intervention Group ◽  
Serum Biomarkers ◽  
Double Blind ◽  
Diabetic Kidney ◽  
Vitamin E Supplementation

Diabetic kidney disease (DKD) is a debilitating complication of diabetes, which develops in 40% of the diabetic population and is responsible for up to 50% of end-stage renal disease (ESRD). Tocotrienols have shown to be a potent antioxidant, anti-inflammatory, and antifibrotic agent in animal and clinical studies. This study evaluated the effects of 400 mg tocotrienol-rich vitamin E supplementation daily on 59 DKD patients over a 12-month period. Patients with stage 3 chronic kidney disease (CKD) or positive urine microalbuminuria (urine to albumin creatinine ratio; UACR > 20–200 mg/mmol) were recruited into a randomized, double-blind, placebo-controlled trial. Patients were randomized into either intervention group (n = 31) which received tocotrienol-rich vitamin E (Tocovid SupraBioTM; Hovid Berhad, Ipoh, Malaysia) 400 mg daily or a placebo group which received placebo capsules (n = 28) for 12 months. HbA1c, renal parameters (i.e., serum creatinine, eGFR, and UACR), and serum biomarkers were collected at intervals of two months. Tocovid supplementation significantly reduced serum creatinine levels (MD: −4.28 ± 14.92 vs. 9.18 ± 24.96), p = 0.029, and significantly improved eGFR (MD: 1.90 ± 5.76 vs. −3.29 ± 9.24), p = 0.011 after eight months. Subgroup analysis of 37 patients with stage 3 CKD demonstrated persistent renoprotective effects over 12 months; Tocovid improved eGFR (MD: 4.83 ± 6.78 vs. −1.45 ± 9.18), p = 0.022 and serum creatinine (MD: −7.85(20.75) vs. 0.84(26.03), p = 0.042) but not UACR. After six months post washout, there was no improvement in serum creatinine and eGFR. There were no significant changes in the serum biomarkers, TGF-β1 and VEGF-A. Our findings verified the results from the pilot phase study where tocotrienol-rich vitamin E supplementation at two and three months improved kidney function as assessed by serum creatinine and eGFR but not UACR.

scholarly journals Antioxidant, Anti-Inflammatory, and Metabolic Properties of Tocopherols and Tocotrienols: Clinical Implications for Vitamin E Supplementation in Diabetic Kidney Disease

2019 ◽  
Vol 20 (20) ◽  
pp. 5101 ◽  
Author(s):  
Angelo Di Vincenzo ◽  
Claudio Tana ◽  
Hamza El Hadi ◽  
Claudio Pagano ◽  
Roberto Vettor ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Vitamin E ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Vascular Complications ◽  
High Morbidity ◽  
Diabetic Kidney ◽  
Anti Inflammatory ◽  
Vitamin E Supplementation

Diabetes mellitus is a metabolic disorder characterized by the development of vascular complications associated with high morbidity and mortality and the consequent relevant costs for the public health systems. Diabetic kidney disease is one of these complications that represent the main cause of end-stage renal disease in Western countries. Hyperglycemia, inflammation, and oxidative stress contribute to its physiopathology, and several investigations have been performed to evaluate the role of antioxidant supplementation as a complementary approach for the prevention and control of diabetes and associated disturbances. Vitamin E compounds, including different types of tocopherols and tocotrienols, have been considered as a treatment to tackle major cardiovascular outcomes in diabetic subjects, but often with conflicting or even negative results. However, their effects on diabetic nephropathy are even less clear, despite several intervention studies that showed the improvement of renal parameters after supplementation in patients with diabetic kidney disease. Then we performed a review of the literature about the role of vitamin E supplementation on diabetic nephropathy, also describing the underlying antioxidant, anti-inflammatory, and metabolic mechanisms to evaluate the possible use of tocopherols and tocotrienols in clinical practice.

scholarly journals Tocotrienol-Rich Vitamin E from Palm Oil (Tocovid) and Its Effects in Diabetes and Diabetic Nephropathy: A Pilot Phase II Clinical Trial

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1315 ◽  
Author(s):  
Suzanne Tan ◽  
Yilynn Chiew ◽  
Badariah Ahmad ◽  
Khalid Kadir
Keyword(s):  
Blood Pressure ◽  
Diabetic Nephropathy ◽  
Vitamin E ◽  
Serum Creatinine ◽  
Palm Oil ◽  
Controlled Trial ◽  
Intervention Group ◽  
Serum Biomarkers ◽  
Control Group ◽  
Potential Biomarker

Tocotrienol-rich vitamin E from palm oil (Tocovid) has been shown to ameliorate diabetes through its superior antioxidant, antihyperglycemic, and anti-inflammatory properties in diabetic rats. This study aimed to investigate the effects of Tocovid on diabetic nephropathy in patients with type 2 diabetes. Baseline parameters of potential subjects such as HbA1c, blood pressure, Advanced Glycation Endproduct (AGE), soluble receptor for AGE (sRAGE), Nε-Carboxymethyllysine (Nε-CML), and Cystatin C were assessed for possible correlation with diabetic nephropathy. Only subjects with diabetic nephropathy or urine microalbuminuria-positive defined as Urine Albumin to Creatinine Ratio (UACR) >10 mg/mmol were recruited into a prospective, randomized, double-blinded, placebo-controlled trial. The intervention group (n = 22) received Tocovid 200 mg twice a day while the control group (n = 23) received placebo twice a day for 8 weeks. Changes in Hemoglobin A1c (HbA1c), blood pressure, serum biomarkers and renal parameters such as UACR, serum creatinine, and estimated Glomerular Filtration Rate (eGFR) were compared between the two groups. It was found that serum Nε-CML significantly correlated to the severity of microalbuminuria. For every 1 ng/mL increase in serum Nε-CML, the odds of diabetic nephropathy increased by 1.476 times. Tocovid, compared to placebo, significantly reduced serum creatinine but not eGFR, UACR, HbA1c, blood pressure, and serum biomarkers. In conclusion, serum Nε-CML is a potential biomarker for diabetic nephropathy. Treatment with Tocovid significantly reduced serum creatinine; therefore Tocovid may be a useful addition to the current treatment for diabetic nephropathy.

scholarly journals Effects of Dapagliflozin on Circulating Markers of Phosphate Homeostasis

2018 ◽  
Vol 14 (1) ◽  
pp. 66-73 ◽  
Author(s):  
Maarten A. de Jong ◽  
Sergei I. Petrykiv ◽  
Gozewijn D. Laverman ◽  
Antonius E. van Herwaarden ◽  
Dick de Zeeuw ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Early Stage ◽  
Glycosylated Hemoglobin ◽  
Fibroblast Growth Factor 23 ◽  
Serum Phosphate ◽  
Phosphate Homeostasis ◽  
Double Blind ◽  
Diabetic Kidney ◽  
Albumin Excretion

Background and objectivesThe sodium glucose cotransporter 2 (SGLT-2) inhibitor dapagliflozin is a novel drug for the treatment of diabetes mellitus. Recent studies suggest that SGLT-2 inhibitors affect phosphate homeostasis, but their effects on phosphate-regulating hormones in patients with diabetic kidney disease are still unclear.Design, setting, participants, & measurementsWe performed a post-hoc analysis of a double-blind, randomized, crossover trial in patients with type 2 diabetes with early-stage diabetic kidney disease on stable renin–angiotensin–aldosterone system blockade, with an albumin-to-creatinine ratio between 100 and 3500 mg/g, eGFR≥45 ml/min per 1.73 m2, and glycosylated hemoglobin≥7.2% and <11.4%. Patients were randomized to dapagliflozin 10 mg/d or placebo during consecutive 6-week study periods, separated by a 6-week wash-out. We investigated effects on circulating phosphate, calcium, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D (25[OH]D), and 1,25-dihydroxyvitamin D (1,25[OH]2D) levels.ResultsThirty-one patients (age 62 years; 23% female) were analyzed. Compared with placebo, dapagliflozin increased serum phosphate by 9% (95% confidence interval, 4% to 15%; P=0.002), PTH increased by 16% (3% to 30%; P=0.01), FGF23 increased by 19% (0.3% to 42%; P=0.05), and serum 1,25(OH)2D decreased by −12% (−25% to 4%; P=0.12). Calcium and 25(OH)D were unaffected. We found no correlation between changes in markers of phosphate homeostasis and changes in eGFR or 24-hour albumin excretion during dapagliflozin treatment.ConclusionsDapagliflozin increases serum phosphate, plasma PTH, and FGF23. This effect was independent of concomitant changes in eGFR or 24-hour albumin excretion.

scholarly journals The Effects of Tocotrienol-Rich Vitamin E (Tocovid) on Diabetic Neuropathy: A Phase II Randomized Controlled Trial

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1522
Author(s):  
Yeek Tat Ng ◽  
Sonia Chew Wen Phang ◽  
Gerald Chen Jie Tan ◽  
En Yng Ng ◽  
Nevein Philip Botross Henien ◽  
...  
Keyword(s):  
Vitamin E ◽  
Nerve Conduction ◽  
Controlled Trial ◽  
Intervention Group ◽  
Serum Biomarkers ◽  
Control Group ◽  
Controlled Clinical Trial ◽  
Diabetic Patients ◽  
Chronic Hyperglycemia ◽  
Conduction Velocities

Chronic hyperglycemia increases oxidative stress, activates inflammatory pathways and reduces nerve growth factor (NGF) among diabetic patients, which contribute to development of diabetic peripheral neuropathy (DPN). Tocotrienol-Rich Vitamin E (Tocovid) possesses potent antioxidant and anti-inflammatory properties which are postulated to target these pathogeneses in order to ameliorate DPN. This study aims to evaluate the effects of Tocovid on nerve conduction parameters and serum biomarkers among diabetic patients. This multicenter, prospective, randomized, double-blind, placebo-controlled clinical trial was conducted on 80 eligible participants. The intervention group (n = 39) was randomly allocated to receive 200 mg of Tocovid twice a day, and the control group (n = 41) received placebo twice a day. At the end of eight weeks, the nerve conduction parameters, as assessed by nerve conduction study, as well as serum biomarkers (NGF, malondialdehyde, vascular cell adhesion molecule 1, tumor necrosis factor receptor 1 and thromboxane B2) were compared between the two groups. Compared to placebo, Tocovid significantly improves the nerve conduction velocities of all nerves (+1.25 m/s, interquartile range [IQR] 3.35, p < 0.001, median nerve; +1.60 m/s, IQR 1.80, p < 0.001, sural nerve; +0.75 m/s, IQR 2.25, p < 0.001, tibial nerve). Meanwhile, the levels of serum NGF were significantly higher in the Tocovid group as compared to placebo at eight weeks post-intervention. Participants receiving Tocovid illustrated highly significant improvement in terms of nerve conduction velocities for all nerves tested after eight weeks of supplementation. In addition, Tocovid supplementation elevated the levels of serum NGF, in which its increase is postulated to reflect enhanced neuronal functions. This novel finding suggests that Tocovid could be a disease-modifying agent targeting serum NGF to improve nerve conduction velocities.

scholarly journals P1033VALUE OF ADDING PENTOXIFYLLINE IN COMPARISON TO ANGIOTENSIN CONVERTING ENZYME INHIBITORS IN TYPE 2 DIABETIC PATIENTS AMONG EGYPTIAN POPULATION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Magdy ElSharkawy ◽  
Mohamed Mostafa ◽  
Mohamed Ezzat
Keyword(s):  
Kidney Disease ◽  
Serum Creatinine ◽  
Diabetic Kidney Disease ◽  
Diabetic Patients ◽  
Trial Duration ◽  
Diabetic Kidney ◽  
History Of ◽  
The Mean ◽  
Group 2 ◽  
Group 1

Abstract Background and Aims Microalbuminuria is one of the early presentations of diabetic kidney disease that may progress to macroalbuminuria, progressive loss of glomerular filtration rate and eventually end stage renal disease. Early recognition and management of microalbuminuria can avert irreversible complications. Antihypertensive medications and antihyperlipidemic medications are medications that have been used to control diabetic nephropathy, but the reports of some side effects limited the usage of some of these drugs in diabetic patients. Pentoxifylline is an anti-inflammatory medication that have been experienced for clinical trials in diabetic patients with diabetic kidney disease. Effect of Pentoxifylline on albuminuria has been evaluated in several studies with different outcomes where a significant decrease in albuminuria in the Pentoxifylline group compared with placebo was the final conclusion. The aim of our study is the assessment of the value of Pentoxifylline addition in diabetic patients. Method Of 90 patients aged between 20 and 55 years old with a history of diabetes mellites type II for more than 5 years with normal serum creatinine and had a spot urinary albumin/creatinine ratio of &gt; 300 mg/g on two consecutive measurements with HBA1C &lt; 7% and lacking any history of glomerular disease, immunological, malignant nor cardiovascular disease in the previous 6 months nor using pentoxifylline for the past 3 month attending Ain Shams University clinics in Egypt from October 2017 to September 2018, 61 patients were eligible and randomly assigned in prospective, randomized, parallel-group, non-blind study after obtaining written informed consent from studied patients into 2 groups either the Pentoxifylline group (n = 30) receiving 400 mg thrice daily for 6 months or Ramipril group (n = 31) receiving 2.5 mg once daily on the same schedule. Blood samples and single first morning void urine samples were collected before breakfast after an 8–12 hours overnight fast. Plasma glucose, HbA1c, serum Creatinine, AST, ALT, and urinary protein / Creatinine levels were measured. All biochemical analyses were performed. Participants were followed up after 1, 3 and 6 months during the treatment period to evaluate the outcome Results Highly Statistically significant differences were noted as regard the reduction of the proteinuria levels at the same measurement points in both groups where the mean ranges of proteinuria in group 1 were found to be 2.2±1, 1.8±0.7, 1.4±0.6 mg\g at the start of the study, 3 and 6 month later respectively while in group 2 the mean range was found to be 2.6±1.2, 2±0.8, 1.6±0.7 mg\g with marked reduction of 20.6% after 3 month and 37.6% after 6 month from the start of the trial in group 1 in contrast to 20.7% and 40.2% respectively in group 2, also the effect of both drugs on the level of HbA1c has been studied in both group, in group 1 there was no reduction in the level of HbA1c after 6 month of drug administration in contrary to group 2 which showed a reduction of 4% where these results were found to be statistically significant in group 2 only. we also found statistically significant differences in both groups as regard the decline in eGFR throughout the trial duration which was 4% in group 1 and 6% in group 2. Conclusion We concluded that Pentoxifylline has a promising role as an antiproteinuric agent in comparison with ACEI from our statistical analysis of the study data with a more decline in eGFR throughout the trial duration in the study population using ACEI in comparison to Pentoxifylline. Due to restrictions of the study design these observations need further confirmation by prospective studies. Figure (1) showing comparison between both groups as regard the level of proteinuria and its reduction rate over 6 months Figure (2) showing eGFR levels at 0, 6 months in both groups Figure (3) showing comparison between both groups as regard HbA1C at baseline and after 6 months.

scholarly journals Urinary podocin level as a predictor of diabetic kidney disease

2018 ◽  
Vol 8 (3) ◽  
pp. 26-26
Author(s):  
Abdelbassit ElShaarawy ◽  
Maha Abdelmoneim Behairy ◽  
Somia Abdelhameed Bawady ◽  
Hoda Ahmed Abdelsattar ◽  
Eman Shadad
Keyword(s):  
Kidney Disease ◽  
Serum Creatinine ◽  
Diabetic Kidney Disease ◽  
Fasting Blood Glucose ◽  
University Hospital ◽  
Control Group ◽  
High Morbidity ◽  
Diabetic Kidney ◽  
Type 2 Dm

Background: Albuminuria showed to be a deteriorating condition in diabetic kidney disease (DKD) associated with high morbidity and mortality. A need for a novel marker for early detection of DKD development and progression becomes mandating. Objective: To study the clinical value of urinary podocin as an early marker of diabetic kidney disease and its association with severity of the disease. Patients and Methods: This study included 45 individuals with type 2 DM whose GFR >60 mL/min/1.73 m2 , recruited from Ain Shams University Hospital, Cairo, Egypt. Patients were further divided into three groups according to urinary albumin/creatinine ratio (ACR). In addition to, ten healthy volunteers serving as the control group was enrolled in the study. Routine chemistry including serum creatinine, fasting blood glucose (FBG), HbA1c, albumin, lipid profile, urine analysis, ACR and urinary podocin quantification were conducted for all participants (by ELISA method). Results: Podocin was higher in patients with ACR <30 mg/g, ACR 30-299 mg/g and ACR ≥ 300 mg/g versus healthy controls, respectively (P<0.001). Both GFR and serum albumin showed highly significant negative correlations with urinary podocin. Significant positive correlations were detected between urinary podocin with blood urea nitrogen (BUN), serum creatinine, FBG, HbA1c, cholesterol, and triglyceride levels. Conclusions: Urinary podocin is assumed to be a promising marker for early DKD detection in type 2 DM patients.

scholarly journals Chinese herbal medicine Tangshen Formula treatment for type 2 diabetic kidney disease in the early stage: study protocol for a randomized controlled trial

Trials ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
De Jin ◽  
Wen-Jing Huang ◽  
Xiang Meng ◽  
Fan Yang ◽  
Qi Bao ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Early Stage ◽  
Controlled Trial ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Chinese Herbal ◽  
Be The Change ◽  
Tangshen Formula

Abstract Background Diabetic kidney disease (DKD) is the main cause of end-stage kidney disease and has become a heavy economic and social burden due to its high prevalence and morbidity. The most effective strategy is that patients with DKD should be diagnosed and treated early. Preliminary studies showed that the Chinese herbal Tangshen Formula (TSF) may delay the progression of DKD, reducing microalbuminuria and macroalbuminuria and improving renal function. We designed a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of TSF in patients with DKD. Methods/design This trial is a 13-center, randomized, double-blind, placebo-controlled study. A total of 632 participants will be randomized in a 1:1 ratio to an experiment group (TSF plus losartan) and a control group (placebo plus losartan). The trial cycle will last 24 weeks. The primary outcome will be the change in the urine microalbumin–creatinine ratio from baseline to week 24. The secondary outcome will be the change in the rate of progression to the clinical proteinuria period after intervention, the rate of urine microalbumin negative conversion, the rate of normal urinary microalbumin, the doubling rate of the baseline creatinine value and the glomerular filtration rate between the two groups. Safety in medication will also be evaluated. Discussion We hypothesize that patients with type 2 diabetes in the early stage of DKD will benefit from TSF. If successful, this study will provide evidence-based recommendations for clinicians. Trial registration ClinicalTrials.gov, NCT03009864. Registered January 2017.

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