Vitamin B complex supplementation as a homocysteine-lowering therapy for early stage diabetic nephropathy in pediatric patients with type 1 diabetes: A randomized controlled trial

Elbarbary, Nancy Samir; Ismail, Eman Abdel Rahman; Zaki, Manal M.; Darwish, Yasser W.; Ibrahim, Marwa Zaki; El‐Hamamsy, Manal

doi:10.1016/j.clnu.2019.01.006

Cited by 22 publications

(8 citation statements)

References 42 publications

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“…Some studies associated low B6 levels to diabetic complications, such as neuropathy and retinopathy, in T1D and T2D patients [29,105]. While others reported a significant reduction in neuropathy, after vitamin B6 supplementation [106] and reduced progression of diabetic nephropathy [107,108]. Horikawa and coworkers [109] found a high vitamin B6 intake associated with a lower incidence of diabetic retinopathy, in a cohort of T2D Japanese patients.…”

Section: Vitamin B6 and Diabetes Complicationsmentioning

confidence: 99%

Vitamin B6 and Diabetes: Relationship and Molecular Mechanisms

Mascolo

Vernı̀

2020

IJMS

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Vitamin B6 is a cofactor for approximately 150 reactions that regulate the metabolism of glucose, lipids, amino acids, DNA, and neurotransmitters. In addition, it plays the role of antioxidant by counteracting the formation of reactive oxygen species (ROS) and advanced glycation end-products (AGEs). Epidemiological and experimental studies indicated an evident inverse association between vitamin B6 levels and diabetes, as well as a clear protective effect of vitamin B6 on diabetic complications. Interestingly, by exploring the mechanisms that govern the relationship between this vitamin and diabetes, vitamin B6 can be considered both a cause and effect of diabetes. This review aims to report the main evidence concerning the role of vitamin B6 in diabetes and to examine the underlying molecular and cellular mechanisms. In addition, the relationship between vitamin B6, genome integrity, and diabetes is examined. The protective role of this vitamin against diabetes and cancer is discussed.

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Section: Vitamin B6 and Diabetes Complicationsmentioning

confidence: 99%

Vitamin B6 and Diabetes: Relationship and Molecular Mechanisms

Mascolo

Vernı̀

2020

IJMS

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“…However, whether elevated Hcy level in humans is the cause or consequence of insulin resistance and type 2 diabetes remains controversial (Yang et al, 2015;Zhang et al, 2018). Several studies have shown that Hcy elevation is the cause of type 2 diabetes; for example, results from in vivo and in vitro experiments have shown that elevation in the Hcy level causes insulin resistance (Li et al, 2008(Li et al, , 2013 and that Hcy-lowering therapy is beneficial for patients with type 2 diabetes (Elbarbary et al, 2020). However, the causality between Hcy and insulin resistance is still controversial, as the underlying mechanism remains elusive so far.…”

Section: Introductionmentioning

confidence: 99%

Homocysteine inhibits pro-insulin receptor cleavage and causes insulin resistance via protein cysteine-homocysteinylation

et al. 2021

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Elevation in homocysteine (Hcy) level is associated with insulin resistance; however, the causality between them and the underlying mechanism remain elusive. Here, we show that Hcy induces insulin resistance and causes diabetic phenotypes by protein cysteine-homocysteinylation (C-Hcy) of the pro-insulin receptor (pro-IR). Mechanistically, Hcy reacts and modifies cysteine-825 of pro-IR in the endoplasmic reticulum (ER) and abrogates the formation of the original disulfide bond. C-Hcy impairs the interaction between pro-IR and the Furin protease in the Golgi apparatus, thereby hindering the cleavage of pro-IR. In mice, an increase in Hcy level decreases the mature IR level in various tissues, thereby inducing insulin resistance and the type 2 diabetes phenotype. Furthermore, inhibition of C-Hcy in vivo and in vitro by overexpressing protein disulfide isomerase rescues the Hcy-induced phenotypes. In conclusion, C-Hcy in the ER can serve as a potential pharmacological target for developing drugs to prevent insulin resistance and increase insulin sensitivity.

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“…The lifetime risk of DN in T1DM has traditionally been estimated at ~50% but may exceed 70% 7 . The initial stage of DN is characterized by the development of microalbuminuria (MA) and hyperfiltration 8 . The traditional concept of DN holds that MA (albumin excretion rate >30 mg/24 h) is the fundamental early prognostic indicator that heralds macroalbuminuria, indicating a need for additional treatments 7 .…”

Section: Introductionmentioning

confidence: 99%

“… 7 The initial stage of DN is characterized by the development of microalbuminuria (MA) and hyperfiltration. 8 The traditional concept of DN holds that MA (albumin excretion rate >30 mg/24 h) is the fundamental early prognostic indicator that heralds macroalbuminuria, indicating a need for additional treatments. 7 In light of the dynamic process of T1DM, there is a need to identify risk factors associated with MA of kidney disease.…”

Section: Introductionmentioning

confidence: 99%

Clinical study of autoantibodies in type 1 diabetes mellitus children with ketoacidosis or microalbuminuria

Zhang

Wang

et al. 2021

Clinical Laboratory Analysis

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Aims The study aimed to investigate the value of autoantibodies in predicting the risk of ketoacidosis or microalbuminuria in children with type 1 diabetes mellitus. Methods Clinical data and laboratory indicators of 80 patients with type 1 diabetes admitted to the Department of Endocrinology in Tianjin Children's Hospital, from June 2017 to March 2019, were retrospectively analyzed. The patients were divided into two groups: diabetes without ketoacidosis group (n = 20) and diabetes with ketoacidosis group (n = 60). The differences in general data, laboratory test indexes, and autoantibodies between the two groups were analyzed. Finally, ROC curves and multivariate logistic regression analysis were used to explore the value of autoantibodies in patients with ketoacidosis or microalbuminuria. Results A total of 80 children with type 1 diabetes were assessed, including 35 boys and 45 girls, ranging in age from 10 months to 15 years. The concentration of GADA, IA2A, and ZnT8A was not statistically different between the two groups, but the positive rate of ZnT8A was statistically significant (p = 0.038) and had a diagnostic value for the occurrence of ketoacidosis (p = 0.025). ZnT8A‐positive patients had a higher titer of IA2A and a more frequent prevalence of GADA and IA2A than ZnT8A‐negative patients (p < 0.01). In multivariate logistic regression analyses, the presence of positive ZnT8A was associated with a higher risk of microalbuminuria independent of age, sex, and BMI (OR = 4.184 [95% CI 1.034~16.934], p = 0.045). Conclusions The positive ZnT8A had diagnostic value for ketoacidosis in children with type 1 diabetes and had the highest specificity among the three kinds of autoantibodies. Moreover, ZnT8A positivity was related to a higher titer of IA2A and more frequent occurrence of multiple diabetes‐related autoantibodies. Besides, the presence of positive ZnT8A was an independent risk factor of microalbuminuria in children with type 1 diabetes. Therefore, we can infer that positive ZnT8A may be related to ketoacidosis and microalbuminuria, accelerating the progression of T1DM.

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Vitamin B complex supplementation as a homocysteine-lowering therapy for early stage diabetic nephropathy in pediatric patients with type 1 diabetes: A randomized controlled trial

Cited by 22 publications

References 42 publications

Vitamin B6 and Diabetes: Relationship and Molecular Mechanisms

Vitamin B6 and Diabetes: Relationship and Molecular Mechanisms

Homocysteine inhibits pro-insulin receptor cleavage and causes insulin resistance via protein cysteine-homocysteinylation

Clinical study of autoantibodies in type 1 diabetes mellitus children with ketoacidosis or microalbuminuria

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