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>

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>

scholarly journals Efficacy of GAD-alum immunotherapy associated with HLA-DR3-DQ2 in recently diagnosed type 1 diabetes

Diabetologia ◽  
2020 ◽  
Vol 63 (10) ◽  
pp. 2177-2181 ◽  
Author(s):  
Ulf Hannelius ◽  
Craig A. Beam ◽  
Johnny Ludvigsson
Keyword(s):  
Type 1 Diabetes ◽  
Treatment Effect ◽  
Repeated Measures ◽  
C Peptide ◽  
Recent Onset ◽  
Individual Level ◽  
Onset Type ◽  
Hla Dr3 ◽  
Effect Ratio

Abstract Aims/hypothesis The aim of this study was to determine if retention of C-peptide following immunotherapy using recombinant GAD65 conjugated to aluminium hydroxide (GAD-alum) is influenced by HLA risk haplotypes DR3-DQ2 and DR4-DQ8. Methods HLA-dependent treatment effect of GAD-alum therapy on C-peptide retention in individuals with recent-onset type 1 diabetes was evaluated using individual-level patient data from three placebo-controlled, randomised clinical trials using a mixed repeated measures model. Results A significant and dose-dependent effect was observed in individuals positive for the genotypes that include HLA-DR3-DQ2 but not HLA-DR4-DQ8 and in the broader subgroup of individuals positive for all genotypes that include HLA-DR3-DQ2 (i.e. including those also positive for HLA-DR4-DQ8). Higher doses (three or four injections) showed a treatment effect ratio of 1.596 (95% CI 1.132, 2.249; adjusted p = 0.0035) and 1.441 (95% CI 1.188, 1.749; adjusted p = 0.0007) vs placebo for the two respective HLA subgroups. Conclusions/interpretation GAD65-specific immunotherapy has a significant effect on C-peptide retention in individuals with recent-onset type 1 diabetes who have the DR3-DQ2 haplotype.

Heterologous Adipose–Derived Mesenchymal Stem Cells and Vitamin D Supplementation in Patients with Recent–Onset Type 1 Diabetes Mellitus–Six Months Follow-Up

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1112-P
Author(s):  
JOANA R. DANTAS ◽  
DEBORA A. CABRAL ◽  
KARINA PEREIRA ◽  
MARIA F. PEREIRA ◽  
DEBORA L. SOUTO ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Stem Cells ◽  
Vitamin D ◽  
Type 1 Diabetes ◽  
Mesenchymal Stem Cells ◽  
Type 1 Diabetes Mellitus ◽  
Vitamin D Supplementation ◽  
Recent Onset

183-OR: Allogenic Adipose-Derived Mesenchymal Stem Cells (ASCs) and Vitamin D Supplementation in Patients with Recent-Onset Type 1 Diabetes Mellitus: A 6-Month Follow-Up Pilot Study

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 183-OR
Author(s):  
JOANA R. DANTAS ◽  
DEBORA B. ARAUJO ◽  
LEANDRA S. BAPTISTA ◽  
DEBORA L. SOUTO ◽  
KARINA PEREIRA ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Stem Cells ◽  
Vitamin D ◽  
Type 1 Diabetes ◽  
Mesenchymal Stem Cells ◽  
Pilot Study ◽  
Vitamin D Supplementation ◽  
Recent Onset

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.

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.

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