Circulating vitamin E, transforming growth factor β1, and the association with renal disease susceptibility in two racial groups with type 2 diabetes

Zitouni, Karima; Harry, David; Nourooz‐Zadeh, Jaffar; Betteridge, D. J.; Earle, Kenneth

doi:10.1111/j.1523-1755.2005.00300.x

Cited by 13 publications

(6 citation statements)

References 37 publications

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“…Increasing evidence suggests that circulating TGF-b1 levels are linked to vascular target organ damage in both diabetic and nondiabetic populations. 30,31 Although urinary TGF-b1 levels are believed to reflect intrarenal production of TGF-b1, circulating levels may be both a risk factor and risk marker for more severe or progressive CKD. In a small substudy including 63 patients from the Collaborative Study Group Captopril Trial in patients with type 1 diabetes mellitus and overt nephropathy, participants with an increased urinary TGF-b1 level showed the greatest GFR decline over the ensuing 2 years.…”

Section: Discussionmentioning

confidence: 99%

Circulating bone morphogenetic protein-7 and transforming growth factor-β1 are better predictors of renal end points in patients with type 2 diabetes mellitus

Wong

Perkovic

Woodward

et al. 2013

Kidney International

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Albuminuria and a reduced glomerular filtration rate are conventional predictors of a future decline in kidney function in patients with type 2 diabetes mellitus. Using a nested case-control study we assessed whether circulating transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-7 (BMP-7) levels more accurately predict renal end points than the conventional markers. Cases were defined as those who developed a renal end point (doubling of serum creatinine to at least 200 μmol/l, the need for renal replacement therapy, or death due to renal disease) during the study. Using propensity scoring, two controls were selected for each of 281 cases. Participants who developed renal end points had significantly higher total TGF-β1, lower BMP-7 levels, and a higher total TGF-β1 to BMP-7 ratio at baseline. A graded increase in risk was found in individuals with lower BMP-7 levels (odds ratio 24.07, for the lowest to the highest tertile), or significantly higher TGF-β1 levels (odds ratio for the highest to the lowest tertile, 8.43). The area under the receiver operating characteristic curve (c-statistic) for the conventional predictors was 0.73. Using BMP-7 and total and active TGF-β1, the c-statistic was 0.94 (significantly higher to conventional predictors). Thus, our results suggest these novel kidney markers are better predictors of renal progression than the conventional predictors in patients with type 2 diabetes mellitus.

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Section: Discussionmentioning

confidence: 99%

Circulating bone morphogenetic protein-7 and transforming growth factor-β1 are better predictors of renal end points in patients with type 2 diabetes mellitus

Wong

Perkovic

Woodward

et al. 2013

Kidney International

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“…However, a genome-wide analysis has not shown consistent relationships between VEGF polymorphisms and circulating protein in different populations suggesting that other non-heritable, modulating factors contribute to differences in circulating levels (16). We reported increased oxidative stress in African-Caribbean patients with type 2 diabetes compared to Caucasian patients as assessed by lipid peroxidation product, antioxidant nutrients and antioxidant enzyme activities (17)(18)(19). The reasons for this observation or the mechanisms that could account for these differences are unclear.…”

Section: Introductionmentioning

confidence: 74%

Lipopolysaccharide-induced VEGF production and ambient oxidative stress in type 2 diabetes

Earle

Zitouni

Nourooz‐Zadeh

2018

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…Potentially, this change could be due to chronic antifibrotic effects. Vitamin E concentrations in the renal cortex were associated with downregulation of TGF-β1 levels and reduction in glomerular expansion [24][25][26]. Pathological matrix collection, fibrotic contraction and replacement of structural function lead to the demise of organ function.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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.

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Circulating vitamin E, transforming growth factor β1, and the association with renal disease susceptibility in two racial groups with type 2 diabetes

Abstract: In these patients with type 2 diabetes, vitamin E is a determinant of renal function, and may explain some of the racial differences in renal disease susceptibility that precedes the divergence in incidence of end-stage renal disease.

Cited by 13 publications

References 37 publications

Circulating bone morphogenetic protein-7 and transforming growth factor-β1 are better predictors of renal end points in patients with type 2 diabetes mellitus

Circulating bone morphogenetic protein-7 and transforming growth factor-β1 are better predictors of renal end points in patients with type 2 diabetes mellitus

Lipopolysaccharide-induced VEGF production and ambient oxidative stress in type 2 diabetes

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

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