Calcium Insufficiency Accelerates Type 1 Diabetes in Vitamin D Receptor-Deficient Nonobese Diabetic (NOD) Mice

Vitamin D exerts important regulatory effects on the endocrine and immune systems. Autoimmune type 1 diabetes (T1D) development in the inbred NOD mouse strain can be accelerated by vitamin D insufficiency or suppressed by chronic treatment with high levels of 1α,25-dihydroxyvitamin D3. Consequently, a report that T1D development was unaffected in NOD mice genetically lacking the vitamin D receptor (VDR) was unexpected. To further assess this result, the mutant stock was imported to The Jackson Laboratory, backcrossed once to NOD/ShiLtJ, and progeny rederived through embryo transfer. VDR-deficient NOD mice of both sexes showed significant acceleration of T1D. This acceleration was not associated with alterations in immune cells targeting pancreatic β-cells. Rather, the capacity of β-cells to produce and/or secrete insulin was severely impaired by the hypocalcaemia developing in VDR-deficient NOD mice fed a standard rodent chow diet. Feeding a high-lactose calcium rescue diet that circumvents a VDR requirement for calcium absorption from the intestine normalized serum calcium levels, restored β-cell insulin secretion, corrected glucose intolerance, and eliminated accelerated T1D in VDR-deficient NOD mice. These findings suggest that calcium and/or vitamin D supplementation may improve disease outcomes in some T1D-prone individuals that are calcium deficient.

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Vitamin D Supplementation Modulates ICOS+ and ICOS− Regulatory T Cell in Siblings of Children With Type 1 Diabetes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa588 ◽

2020 ◽

Vol 105 (12) ◽

pp. e4767-e4777

Author(s):

Silvia Savastio ◽

Francesco Cadario ◽

Sandra D’Alfonso ◽

Marta Stracuzzi ◽

Erica Pozzi ◽

...

Keyword(s):

Vitamin D ◽

Type 1 Diabetes ◽

Human Leukocyte ◽

Protective Role ◽

Vitamin D Insufficiency ◽

Vitamin D Supplementation ◽

25 Oh Vitamin D ◽

Hla Haplotypes ◽

The Impact

Abstract Objectives Vitamin D plays an immunoregulatory activity. The aim of this study was to assess the correlation between blood serum 25(OH)D levels and Th17 and Treg circulating subsets, mainly Treg/inducible costimulatory-positive (ICOS+), which seems to have a protective role in autoimmunity, in children with type 1 diabetes mellitus (T1D) and their healthy siblings (S). The secondary aim was to evaluate the impact of vitamin D supplementation on these subsets. Patients and Methods 22 T1D and 33 S were enrolled. Glucose, hemoglobin A1c, 25 OH vitamin D (25[OH]D), T helper type 17 (Th17; CD4+CCR6+), regulatory T cells (Treg; CD4+CD25+Foxp3+), and Treg/ICOS+ cells were evaluated. According to human leukocyte antigen (HLA) haplotypes, subjects were classified as “at risk” (HLA+), “protective haplotypes” (HLA−; “nested controls”), and “undetermined” (HLAUND). T1D and S subjects were supplemented with cholecalciferol 1000 IU/die and evaluated after 6 months. Results Vitamin D insufficiency (74.4%) and deficiency (43%) were frequent. S subjects with 25(OH)D levels <25 nmol/L had Th17, Treg (p < 0.01), and Treg/ICOS+ (P < 0.05) percentages higher than subjects with 25(OH)D >75 nmol/L. Treg/ICOS+ percentages (P < 0.05) were higher in HLA− S subjects compared to percentages observed in S with T1D. At baseline, in S subjects, a decreasing trend in Th17 and Treg/ICOS+ values (P < 0.05) from vitamin D deficiency to sufficiency was observed; 25(OH)D levels were negative predictors of Treg/ICOS+ (R2 = 0.301) and Th17 percentages (R2 = 0.138). After 6 months, supplemented S subjects showed higher 25(OH)D levels (P < 0.0001), and lower Th17 (P < 0.0001) and Treg/ICOS+ (P < 0.05) percentages than at baseline; supplemented T1D patients only had a decrease in Th17 levels (P < 0.05). Conclusion Serum 25(OH)D levels seem to affect Th17 and Treg cell subsets in S subjects, consistent with its immunomodulating role. HLA role should be investigated in a larger population.

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Diabetes and osteoporosis

Orvosi Hetilap ◽

10.1556/oh.2011.29154 ◽

2011 ◽

Vol 152 (29) ◽

pp. 1161-1166 ◽

Cited By ~ 4

Author(s):

Zsuzsanna Valkusz

Keyword(s):

Vitamin D ◽

Type 1 Diabetes ◽

Bone Mass ◽

Fragility Fractures ◽

Vitamin D Supplementation ◽

Bone Collagen ◽

Skeletal Changes ◽

Glucagon Like Peptide 1 ◽

Bone Quantity

Over the last decades a considerable amount of data has accumulated to indicate that metabolic and endocrine alterations of diabetes affect bone quantity and quality. These skeletal changes may increase the risk of bone fracture. There is strong evidence that in type 1 diabetes the decreased bone mass, lack of insulin and insulin-like growth factor-1, dysregulation of adipokines, and increased levels of proinflammatory cytokines are in the background of fragility fractures. In type 2 diabetes hyperinsulinemia, insulin resistance and increased body weight may result in an increase of bone mass; however, accumulation of advanced glycation end products within the bone collagen driven by glucotoxicity may increase the cortical porosity. There is a higher incidence of falls resulting from diabetes-related co-morbidities such as diabetic retinopathy, peripheral neuropathy, hypoglycemic episodes and sometimes from the medications. Vitamin D deficiency has special impact on glucose metabolism and the prevalence of diabetes. Vitamin D supplementation in childhood can decrease incidence of type 1 diabetes by 80%. The effect of thiazolidinediones, glucagon-like peptide-1 agonists and metformin, agents for treatment of diabetes open a new connection between bone, carbohydrate and fat metabolism. Orv. Hetil., 2011, 152, 1161–1166.

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Association between a Protein Polymorphism in the Start Codon of the Vitamin D Receptor Gene and Severe Diabetic Retinopathy in C-Peptide-Negative Type 1 Diabetes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2004-2407 ◽

2005 ◽

Vol 90 (8) ◽

pp. 4803-4808 ◽

Cited By ~ 42

Author(s):

Mariano J. Taverna ◽

Jean-Louis Selam ◽

Gérard Slama

Keyword(s):

Vitamin D ◽

Type 1 Diabetes ◽

Diabetic Retinopathy ◽

Vitamin D Receptor ◽

Receptor Gene ◽

Start Codon ◽

Vitamin D Receptor Gene ◽

C Peptide ◽

Negative Type

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Vitamin D and Omega-3 Polyunsaturated Fatty Acids in Type 1 Diabetes modulation

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530322666220103114450 ◽

2022 ◽

Vol 22 ◽

Author(s):

Thais Sibioni Berti Bastos ◽

Tárcio Teodoro Braga ◽

Mariana Rodrigues Davanso

Keyword(s):

Fatty Acids ◽

Vitamin D ◽

Type 1 Diabetes ◽

Polyunsaturated Fatty Acids ◽

Immune Cell ◽

Omega 3 ◽

Β Cells ◽

Potential Benefits ◽

Chronic Autoimmune Disease

Background: Type 1 diabetes (T1D) is a chronic autoimmune disease that affects people globally. Usually developed during childhood, T1D is characterized by the destruction of pancreatic β-cells due to immune cell attack and the establishment of an inflammatory process. Objective: The study aimed to investigate the effects of vitamin D through its nuclear receptor and the ω-3 polyunsaturated fatty acids (PUFAs) through their lipid derivatives in T1D modulation. Both components exert anti-inflammatory activity and act directly on cells of the immune system, attenuating the destruction of insulin-producing cells. Furthermore, they lead to a better glycemic level, reducing the need for insulin and a normal immune state, such as C-peptide maintenance. Method: Presently, our review highlights the significant studies that evaluated the supplementation of vitamin D and ω-3 PUFAs in humans and animal models in the modulation of T1D. Conclusion: The data collected suggests that supplementation can provide potential benefits, mainly when done early in the diagnosis, since it reduces the need for insulin and the risk of complications generated by the disease.

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