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

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.

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

Endocrinology ◽  
2011 ◽  
Vol 152 (12) ◽  
pp. 4620-4629 ◽  
Author(s):  
John P. Driver ◽  
Deanna J. Lamont ◽  
Conny Gysemans ◽  
Chantal Mathieu ◽  
David V. Serreze
Keyword(s):  
Vitamin D ◽  
Type 1 Diabetes ◽  
Vitamin D Receptor ◽  
Calcium Absorption ◽  
Nod Mice ◽  
Vitamin D Insufficiency ◽  
Vitamin D Supplementation ◽  
Chow Diet ◽  
Β Cells

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.

Diabetes and osteoporosis

2011 ◽  
Vol 152 (29) ◽  
pp. 1161-1166 ◽  
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.

scholarly journals A pilot interventional study to evaluate the impact of cholecalciferol treatment on HbA1c in type 1 diabetes (T1D)

2017 ◽  
Vol 6 (4) ◽  
pp. 225-231 ◽  
Author(s):  
R Perchard ◽  
L Magee ◽  
A Whatmore ◽  
F Ivison ◽  
P Murray ◽  
...  
Keyword(s):  
Vitamin D ◽  
Type 1 Diabetes ◽  
South Asian ◽  
Negative Relationship ◽  
Late Winter ◽  
Vitamin D Levels ◽  
Significant Difference ◽  
Before And After ◽  
The Impact

Background Higher 25(OH)D3 levels are associated with lower HbA1c, but there are limited UK interventional trials assessing the effect of cholecalciferol on HbA1c. Aims (1) To assess the baseline 25(OH)D3 status in a Manchester cohort of children with type 1 diabetes (T1D). (2) To determine the effect of cholecalciferol administration on HbA1c. Methods Children with T1D attending routine clinic appointments over three months in late winter/early spring had blood samples taken with consent. Participants with a 25(OH)D3 level <50 nmol/L were treated with a one-off cholecalciferol dose of 100,000 (2–10 years) or 160,000 (>10 years) units. HbA1c levels before and after treatment were recorded. Results Vitamin D levels were obtained from 51 children. 35 were Caucasian, 11 South Asian and 5 from other ethnic groups. 42 were vitamin D deficient, but 2 were excluded from the analysis. All South Asian children were vitamin D deficient, with mean 25(OH)D3 of 28 nmol/L. In Caucasians, there was a negative relationship between baseline 25(OH)D3 level and HbA1c (r = −0.484, P < 0.01). In treated participants, there was no significant difference in mean HbA1c at 3 months (t = 1.010, P = 0.328) or at 1 year (t = −1.173, P = 0.248) before and after treatment. One-way ANCOVA, controlling for age, gender, ethnicity, BMI and diabetes duration showed no difference in Δ HbA1c level. Conclusion We report important findings at baseline, but in children treated with a stat dose of cholecalciferol, there was no effect on HbA1c. Further studies with larger sample sizes and using maintenance therapy are required.

scholarly journals Vitamin D insufficiency, preterm delivery and preeclampsia in women with type 1 diabetes - an observational study

2017 ◽  
Vol 96 (10) ◽  
pp. 1197-1204 ◽  
Author(s):  
Marianne Vestgaard ◽  
Anna L. Secher ◽  
Lene Ringholm ◽  
Jens-Erik B. Jensen ◽  
Peter Damm ◽  
...  
Keyword(s):  
Vitamin D ◽  
Type 1 Diabetes ◽  
Observational Study ◽  
Preterm Delivery ◽  
Vitamin D Insufficiency

Association of HLA-DRB1 and -DQ Alleles and Haplotypes with Type 1 Diabetes in Jordanians

2020 ◽  
Vol 20 (6) ◽  
pp. 895-902 ◽  
Author(s):  
Sawsan I. Khdair ◽  
Wassan Jarrar ◽  
Yazun Bashir Jarrar ◽  
Safa’a Bataineh ◽  
Omar Al-Khaldi
Keyword(s):  
Type 1 Diabetes ◽  
Human Leukocyte ◽  
Positive Association ◽  
Insulin Dependent Diabetes Mellitus ◽  
Class Ii ◽  
Protective Role ◽  
Hla Class Ii ◽  
Dependent Diabetes Mellitus ◽  
Risk Alleles

Background: The Human Leukocyte Antigen (HLA) class II genes, particularly the HLADR and -DQ loci, have been shown to play a crucial role in Type 1 Diabetes (T1D) development. Objective: This study is the first to examine the contribution of the HLA-DR/DQ alleles and haplotypes to T1D susceptibility in Jordanians. Methods: Polymerase chain reaction sequence-specific primers (PCR-SSP) were used to genotype 41 Jordanian healthy controls and 50 insulin-dependent diabetes mellitus (IDDM) patients. Results: The following alleles were found to be significant high risk alleles in T1D Jordanian patients: DRB1*04 (OR=3.95, p<0.001), DRB1*0301(OR=5.27, p<0.001), DQA1*0301 (OR=5.67, p<0.001), DQA1*0501(OR=3.18, p=0.002), DQB1*0201(OR=2.18, p=0.03), DQB1*0302 (OR=5.67, p<0.001). However, Jordanians harboring the DRB1*0701 (OR=0.37, p=0.01), DRB1*1101 (OR=0.2, p=0.01), DQA1*0505 (OR=0.31, p=0.02), DQA1*0103 (OR=0.33, p=0.04), DQA1*0201 (OR=0.45, p=0.04), DQB1*0301 (OR=0.23, p=0.001), DQB1*0501 (OR=0.18, p=0.009) alleles had a significantly lower risk of developing T1D. Conclusion: A strong positive association of DRB1*04-DQA1*0301-DQBl*0302 (OR=5.67, p<0.001) and DRB1*0301-DQA1*0501-DQB1*0201 (OR=6.24, p<0.001) putative haplotypes with IDDM was evident in Jordanian IDDM patients whereas DRB1*1101-DQA1*0505- DQB1*0301 (OR=0.23, p=0.03) was shown to have a protective role against T1D in Jordanians. Our findings show that specific HLA class II alleles and haplotypes are significantly associated with susceptibility to T1D in Jordanians.

Sign in / Sign up

Export Citation Format

Share Document