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Progress in the Relationship between Vitamin D Deficiency and the Incidence of Type 1 Diabetes Mellitus in Children.

ABSTRACT: Type 1 diabetes mellitus (T1DM) is an autoimmune disease, due to a large number of islet β cells damaged, resulting in an absolute lack of insulin, ultimately relying on insulin therapy. Vitamin D is a fat-soluble sterol derivative that not only participates in calcium and phosphorus metabolism but also acts as an immunomodulatory role by binding to nuclear vitamin D receptors to regulate the expression of transcription factors. Increasing evidence has shown that vitamin D has immunoregulation and anti-inflammatory effects, and it may play a role in T cell regulatory responses due to downregulation in the expression of cathepsin G and inhibition of CD4+ T cell activation and protection of β cells from immune attack and is beneficial in decreasing oxidative stress in T1DM patients. Epidemiologic evidence demonstrates involvement of vitamin D deficiency in T1DM pathogenesis, with the immune system improperly targeting and destroying its own islet β cells. In addition, polymorphisms in genes critical for vitamin D metabolism may increase the risk of islet autoimmunity and T1DM. In this paper, the relationship between vitamin D deficiency and the molecular mechanism of T1DM was discussed.

SUBMITTER: He LP

PROVIDER: S-EPMC9463035 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Progress in the Relationship between Vitamin D Deficiency and the Incidence of Type 1 Diabetes Mellitus in Children.

He Lian-Ping LP Song Yu-Xin YX Zhu Ting T Gu Wei W Liu Chang-Wei CW

Journal of diabetes research 20220902

Type 1 diabetes mellitus (T1DM) is an autoimmune disease, due to a large number of islet <i>β</i> cells damaged, resulting in an absolute lack of insulin, ultimately relying on insulin therapy. Vitamin D is a fat-soluble sterol derivative that not only participates in calcium and phosphorus metabolism but also acts as an immunomodulatory role by binding to nuclear vitamin D receptors to regulate the expression of transcription factors. Increasing evidence has shown that vitamin D has immunoregul ...[more]

PMID: 36090587

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Project description:BackgroundThe incidence of type 1 diabetes mellitus (T1DM) in Kuwait is amongst the highest in the world. Vitamin D is considered to be involved in immune modulation and its deficiency contribute to autoimmune destruction of insulin producing beta cells in T1DM patients. Vitamin D has been shown to exert its effects via a nuclear vitamin D receptor (VDR) and therefore, VDR gene may be considered a candidate for T1DM susceptibility.MethodsThe genotypes of four VDR gene polymorphisms were determined in 253 Kuwaiti Arab T1DM patients and 214 healthy controls by PCR-RFLP analysis. Serum concentrations of three autoantibodies i.e. ICA (Islet cell autoantibody), GADA (Glutamic acid decarboxylase) and INS (Insulin autoantibody) were determined by radio-immunoassays.ResultsStatistically significant differences were detected between the genotypes of two VDR gene polymorphisms (FokI, C > T, rs10735810 and TaqI, C > T, rs731236) between T1DM patients and controls (P < 0.0001). In both, the frequency of variant alleles was considerably high in T1DM than in the controls. In contrast, the VDR gene ApaI (G > T, rs7975232) and BsmI (A > G, rs1544410) polymorphisms did not show association with T1DM. The homozygous variant genotypes of FokI, ApaI and TaqI polymorphisms show significant differences between various age-of-onset subgroups while no such association was detected in the case of BsmI polymorphism. Significant differences were also noted between heterozygous genotypes of all four polymorphisms especially between 4-6y and > 6y age-of-onset subgroups of T1DM patients. Three autoantibodies, ICA (Islet cell), GADA (glutamate decarboxylase) and INS (insulin) were positively associated to, varying degrees, with T1DM in Kuwaiti Arabs harboring different VDR gene polymorphism genotypes.ConclusionsOur results demonstrate a significant effect of two VDR gene polymorphisms (FokI and TaqI) and three autoantibodies on genetic susceptibility of T1DM in Kuwaiti Arabs along with other factors.

Project description:IntroductionVitamin D has a significant correlation with type 2 diabetes. Insufficient levels of vitamin D can cause insulin resistance, which impairs the ability of cells to respond to insulin and worsens the progression of diseases. Furthermore, vitamin D has the potential to enhance the release of insulin, enhance the regulation of blood sugar levels, and reduce the glycemic index. Research has indicated that insufficient levels of vitamin D may elevate the likelihood of experiencing complications related to type 2 diabetes, including cardiovascular disease and neuropathy. This study employed bibliometric analysis to investigate recent advancements in research about the relationship between vitamin D and type 2 diabetes.MethodsWe searched for articles on the topic of vitamin D and type 2 diabetes published between January 1, 2004, and December 31, 2023. The search was performed on February 20, 2024, using the Web of Science Core Collection (WoSCC). Utilizing VOSviewer and CiteSpace, we conducted bibliometric analysis and visualization.ResultsA comprehensive study was conducted on a total of 1362 papers pertaining to the relationship between vitamin D and type 2 diabetes. The United States had the biggest number of publications and the highest effect among these articles. Within the top 10 most published journals, the journal "DIABETES CARE" has the highest H-index, indicating its significant influence in this field of study. Currently, there is an extensive body of research on the supplementation of vitamin D for the improvement of type 2 diabetes and prevention of complications in type 2 diabetes, as well as its related mechanisms. Research related to bone turnover and peripheral neuropathy represents a promising area for future studies.ConclusionOverall, bibliometrics may assist researchers in comprehending the trajectory, significant themes, and scholarly influence of the field concerning vitamin D and type 2 diabetes. This, in turn, offers substantial backing for future studies that delve further into the subject matter.

Project description:BackgroundDiabetes mellitus (DM) stands as the most prevalent endocrine abnormality affecting the physiological systems and organs and impairing the male reproductive functions. Type 2 Diabetes Mellitus (T2DM), accounting for about 90-95% of DM, is closely associated with male infertility. However, the magnitude of the causal relationships between T2DM and male infertility remains unclear. The current investigation was to explore the causal relationship between T2DM and male infertility utilizing the Mendelian Randomization (MR) analysis.MethodsA two-sample MR (2SMR) analysis was conducted to investigate the causal relationship between T2DM and male infertility in the European population from the genome-wide association study (GWAS) summary data that was publicly accessible. GWAS for T2DM and male infertility were extracted from the IEU Open GWAS Project database, with the resulting data encompassing 680 cases and 72,799 controls as the outcome data. Five MR methods were employed for the 2SMR analyses, namely the MR-Egger, weighted median estimation (WME), weighted mode (WM), inverse-variance weighted (IVW), and simple mode. The primary analytical technique utilized in this study was the IVW method, and a multivariate MR analysis was executed to examine the potential mediating influences of T2DM on male infertility.ResultsFollowing were the odds ratios (ORs) and associated 95% CIs derived from IVW (fixed effects), MR-Egger, WM, WME, and simple mode approaches: 0.824 (95% CI 0.703-0.966), 0.726 (95% CI 0.527-1.001), 0.827 (95% CI 0.596-1.150), 0.841 (95% CI 0.654-1.082), and 0.875 (95% CI 0.544-1.405), respectively. The outcomes of the heterogeneity tests were P=0.378 and P=0.384, respectively, implying no heterogeneity. Egger-intercept outcomes were P=0.374, highlighting the absence of pleiotropy. The stability of the results was affirmed through the leave-one-out analysis. Notably, all F-values surpassed 10, indicating the absence of weak bias attributed to instrument variables(IVs).ConclusionsThis research furnishes evidence supporting a causal association between T2DM and male infertility. These insights offer a foundation for future investigations aiming to establish the association between genetically predicted T2DM and male infertility. These outcomes suggest the significance of active monitoring and proactive measures for preventing infertility in male individuals with T2DM. Furthermore, careful consideration is required for individuals of reproductive age to prevent and treat T2DM.

Project description:ObjectiveInflammation plays a major role in albuminuria in type 2 diabetes mellitus (T2DM). Our previous studies have shown that the expression of vitamin D receptor (VDR) is downregulated in T2DM which is closely associated with the severity of albuminuria. In this study, we investigated the expression of anti-inflammatory cytokine protein tyrosine phosphatase nonreceptor type 2 (PTPN2) in T2DM and explored its relationship to albuminuria and VDR.Methods101 T2DM patients were divided into three groups based on urinary albumin-to-creatinine ratio (uACR): normal albuminuria (uACR < 30 mg/g, n = 29), microalbuminuria (30 mg/g ≤ uACR < 300 mg/g, n = 34), and macroalbuminuria (uACR ≥ 300 mg/g, n = 38). Thirty healthy individuals were included as controls. Serum was analyzed for PTPN2 and IL-6 expression, and peripheral blood mononuclear cells (PBMCs) were analyzed for PTPN2 and VDR expression. THP-1 cells were incubated with high glucose and further treated with or without paricalcitol, a vitamin D analog. The levels of PTPN2, VDR, IL-6, TNFα, and MCP-1 were analyzed. In addition, anti-inflammatory activities of PTPN2 were further explored in THP-1 cells stimulated with high glucose after PTPN2 silencing or overexpression.ResultsPTPN2 expression was downregulated in T2DM with the lowest level observed in macroalbuminuria patients. PTPN2 level positively correlated with VDR but negatively correlated with uACR and IL-6. When stimulated with high glucose, there was an increase in inflammatory factors and a decrease in PTPN2 expression. Treatment with paricalcitol reversed these effects. However, paricalcitol failed to exert anti-inflammatory effects in the setting of PTPN2 knockdown. Thus, low levels of PTPN2 aggravated glucose-stimulated inflammation, while high levels of PTPN2 reduced it.ConclusionPTPN2, an anti-inflammatory factor regulated by VDR, was reduced in T2DM CKD stages 1-2. Taken together, our results suggest that therapeutic strategies that enhance PTPN2 may be beneficial for controlling inflammation in T2DM.

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Progress in the Relationship between Vitamin D Deficiency and the Incidence of Type 1 Diabetes Mellitus in Children.

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Progress in the Relationship between Vitamin D Deficiency and the Incidence of Type 1 Diabetes Mellitus in Children.

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