Effect of 6-months’ vitamin D supplementation on residual beta cell function in children with type 1 diabetes: a case control interventional study

2016 ◽  
Vol 29 (4) ◽  
Author(s):  
Atindra Mishra ◽  
Devi Dayal ◽  
Naresh Sachdeva ◽  
Savita Verma Attri
Keyword(s):  
Vitamin D ◽  
Type 1 Diabetes ◽  
Beta Cell Function ◽  
Cell Function ◽  
Intervention Group ◽  
Vitamin D Supplementation ◽  
Control Group ◽  
Short Term ◽  
C Peptide

AbstractThe aim of this study was to evaluate the effect of short-term vitamin D supplementation on the decline of residual beta cell function (RBCF) in children with type 1 diabetes (T1D).The study involved an intervention group (cholecalciferol 2000 IU/day and calcium 25 mg/kg/day for 6 months) comprising 15 children aged 6–12 years and within 1–2 years of diagnosis of T1D. Fifteen age-matched T1D patients were followed up as controls. Stimulated C-peptide levels were estimated at baseline and 6 months.: The mean decrease in stimulated C-peptide levels in the intervention group was lower (–0.048±0.15 ng/mL) as compared with the controls (–0.107±0.23 ng/mL) but did not reach statistical significance (p=0.472). The percent decrease in stimulated C-peptide from baseline to endpoint (8.3% vs. 20.3%, p=0.357) and the monthly decrease (0.008 ng/mL vs. 0.017 ng/mL, p=0.22) were non-significantly lower in the intervention group compared with the control group. Three (20%) patients progressed to undetectable stimulated C-peptide (≤0.01 ng/mL) over the study period in the control group as compared with one (6%) in the intervention group (p-value 0.260).There was a trend towards lesser decline of RBCF with short term cholecalciferol supplementation in children with T1D. Further larger studies are urgently needed to explore the beneficial effects of the relatively inexpensive vitamin D supplementation on RBCF.

scholarly journals Circulating Levels of MicroRNA from Children with Newly Diagnosed Type 1 Diabetes and Healthy Controls: Evidence That miR-25 Associates to Residual Beta-Cell Function and Glycaemic Control during Disease Progression

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Lotte B. Nielsen ◽  
Cheng Wang ◽  
Kaspar Sørensen ◽  
Claus H. Bang-Berthelsen ◽  
Lars Hansen ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Glycaemic Control ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Control Group ◽  
Healthy Controls ◽  
Newly Diagnosed ◽  
New Onset

This study aims to identify key miRNAs in circulation, which predict ongoing beta-cell destruction and regeneration in children with newly diagnosed Type 1 Diabetes (T1D). We compared expression level of sera miRNAs from new onset T1D children and age-matched healthy controls and related the miRNAs expression levels to beta-cell function and glycaemic control. Global miRNA sequencing analyses were performed on sera pools from two T1D cohorts (n= 275 and 129, resp.) and one control group (n= 151). We identified twelve upregulated human miRNAs in T1D patients (miR-152, miR-30a-5p, miR-181a, miR-24, miR-148a, miR-210, miR-27a, miR-29a, miR-26a, miR-27b, miR-25, miR-200a); several of these miRNAs were linked to apoptosis and beta-cell networks. Furthermore, we identified miR-25 as negatively associated with residual beta-cell function (est.: −0.12,P= 0.0037), and positively associated with glycaemic control (HbA1c) (est.: 0.11,P= 0.0035) 3 months after onset. In conclusion this study demonstrates that miR-25 might be a “tissue-specific” miRNA for glycaemic control 3 months after diagnosis in new onset T1D children and therefore supports the role of circulating miRNAs as predictive biomarkers for tissue physiopathology and potential intervention targets.

Assessment of preservation of beta-cell function in children with long-standing type 1 diabetes with „ultrasensitive c-peptide” method

2017 ◽  
Vol 23 (3) ◽  
pp. 130-138 ◽  
Author(s):  
Agnieszka Kalinowska ◽  
◽  
Barbara Orlińska ◽  
Mateusz Panasiuk ◽  
Milena Jamiołkowska ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
C Peptide

scholarly journals Phase II multicentre, double-blind, randomised trial of ustekinumab in adolescents with new-onset type 1 diabetes (USTEK1D): trial protocol

BMJ Open ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. e049595
Author(s):  
John W Gregory ◽  
Kymberley Carter ◽  
Wai Yee Cheung ◽  
Gail Holland ◽  
Jane Bowen-Morris ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cell ◽  
Research Ethics ◽  
Beta Cells ◽  
Beta Cell Function ◽  
Cell Function ◽  
Double Blind ◽  
C Peptide ◽  
New Onset

IntroductionMost individuals newly diagnosed with type 1 diabetes (T1D) have 10%–20% of beta-cell function remaining at the time of diagnosis. Preservation of residual beta-cell function at diagnosis may improve glycaemic control and reduce longer-term complications.Immunotherapy has the potential to preserve endogenous beta-cell function and thereby improve metabolic control even in poorly compliant individuals. We propose to test ustekinumab (STELARA), a targeted and well-tolerated therapy that may halt T-cell and cytokine-mediated destruction of beta-cells in the pancreas at the time of diagnosis.Methods and analysisThis is a double-blind phase II study to assess the safety and efficacy of ustekinumab in 72 children and adolescents aged 12–18 with new-onset T1D.Participants should have evidence of residual functioning beta-cells (serum C-peptide level >0.2nmol/L in the mixed-meal tolerance test (MMTT) and be positive for at least one islet autoantibody (GAD, IA-2, ZnT8) to be eligible.Participants will be given ustekinumab/placebo subcutaneously at weeks 0, 4 and 12, 20, 28, 36 and 44 in a dose depending on the body weight and will be followed for 12 months after dose 1.MMTTs will be used to measure the efficacy of ustekinumab for preserving C-peptide area under the curve at week 52 compared with placebo. Secondary objectives include further investigations into the efficacy and safety of ustekinumab, patient and parent questionnaires, alternative methods for measuring insulin production and exploratory mechanistic work.Ethics and disseminationThis trial received research ethics approval from the Wales Research Ethics Committee 3 in September 2018 and began recruiting in December 2018.The results will be disseminated using highly accessed, peer-reviewed medical journals and presented at conferences.Trial registration numberISRCTN14274380.

scholarly journals Faecal microbiota transplantation halts progression of human new-onset type 1 diabetes in a randomised controlled trial

Gut ◽  
2020 ◽  
Vol 70 (1) ◽  
pp. 92-105 ◽  
Author(s):  
Pieter de Groot ◽  
Tanja Nikolic ◽  
Silvia Pellegrini ◽  
Valeria Sordi ◽  
Sultan Imangaliyev ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Healthy Donor ◽  
Cell Function ◽  
Plasma Metabolites ◽  
Faecal Microbiota ◽  
C Peptide ◽  
Small Intestinal

ObjectiveType 1 diabetes (T1D) is characterised by islet autoimmunity and beta cell destruction. A gut microbiota–immunological interplay is involved in the pathophysiology of T1D. We studied microbiota-mediated effects on disease progression in patients with type 1 diabetes using faecal microbiota transplantation (FMT).DesignPatients with recent-onset (<6 weeks) T1D (18–30 years of age) were randomised into two groups to receive three autologous or allogenic (healthy donor) FMTs over a period of 4 months. Our primary endpoint was preservation of stimulated C peptide release assessed by mixed-meal tests during 12 months. Secondary outcome parameters were changes in glycaemic control, fasting plasma metabolites, T cell autoimmunity, small intestinal gene expression profile and intestinal microbiota composition.ResultsStimulated C peptide levels were significantly preserved in the autologous FMT group (n=10 subjects) compared with healthy donor FMT group (n=10 subjects) at 12 months. Small intestinal Prevotella was inversely related to residual beta cell function (r=−0.55, p=0.02), whereas plasma metabolites 1-arachidonoyl-GPC and 1-myristoyl-2-arachidonoyl-GPC levels linearly correlated with residual beta cell preservation (rho=0.56, p=0.01 and rho=0.46, p=0.042, respectively). Finally, baseline CD4 +CXCR3+T cell counts, levels of small intestinal Desulfovibrio piger and CCL22 and CCL5 gene expression in duodenal biopsies predicted preserved beta cell function following FMT irrespective of donor characteristics.ConclusionFMT halts decline in endogenous insulin production in recently diagnosed patients with T1D in 12 months after disease onset. Several microbiota-derived plasma metabolites and bacterial strains were linked to preserved residual beta cell function. This study provides insight into the role of the intestinal gut microbiome in T1D.Trial registration numberNTR3697.

scholarly journals Intralymphatic Glutamic Acid Decarboxylase With Vitamin D Supplementation in Recent-Onset Type 1 Diabetes: A Double-Blind, Randomized, Placebo-Controlled Phase IIb Trial

2021 ◽  
Author(s):  
Johnny Ludvigsson ◽  
Zdenek Sumnik ◽  
Terezie Pelikanova ◽  
Lia Nattero Chavez ◽  
Elena Lundberg ◽  
...  
Keyword(s):  
Vitamin D ◽  
Type 1 Diabetes ◽  
Treatment Effect ◽  
Vitamin D Supplementation ◽  
Double Blind ◽  
C Peptide ◽  
Recent Onset ◽  
Hla Dr3 ◽  
Effect Ratio

<b>Objectives:</b> To evaluate the efficacy of intra-lymphatic GAD-alum therapy together with vitamin D supplementation on preserving endogenous insulin secretion in all patients with Type 1 diabetes (T1D) or in a genetically pre-specified subgroup. <p><b>Research Design and Methods:</b> In a multicenter, randomized, placebo-controlled double-blind trial (NCT03345004), 109 patients aged 12-24 (16.4 ± 4.1) years with a diabetes duration of 7-193 (88.8 ± 51.4) days, elevated serum GAD65 autoantibodies (GADA) and a fasting serum C-peptide >0.12 nmol/L, were recruited. Subjects were randomized to receive either three intra-lymphatic injections (one month apart) with 4 µg GAD-alum and oral vitamin D (2000 IE daily for 120 days), or placebo. The primary outcome was the change in stimulated serum C-peptide (mean area under the curve [AUC] after a mixed-meal tolerance test) between baseline and 15-month.</p> <p><b>Results:</b> </p> <p>Primary endpoint was not met in the full analysis set (treatment effect ratio 1.091, CI 0.845-1.408, p = 0.5009). However, GAD-alum treated patients carrying HLA DR3-DQ2 (n=29, defined as DRB1*03, DQB1*02:01) showed greater preservation of C-peptide AUC (treatment effect ratio 1.557, CI 1.126-2.153, p = 0.0078) after 15 months compared to placebo individuals with the same genotype (n=17). Several secondary end points showed supporting trends and a positive effect was seen in partial remission (IDAA1c≤9, p=0.0310). Minor transient injection site reactions were reported. </p> <p><b>Conclusions:</b> Intra-lymphatic administration of GAD-alum is a simple, well-tolerated treatment that together with vitamin D supplementation seems to preserve C-peptide in patients with recent onset T1D carrying HLA DR3-DQ2. This constitutes a disease modifying treatment for T1D with a precision medicine approach.</p>

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