Plasma ascorbic acid and the risk of islet autoimmunity and type 1 diabetes: the TEDDY study

Abstract Aims/hypothesis We studied the association of plasma ascorbic acid with the risk of developing islet autoimmunity and type 1 diabetes and examined whether SNPs in vitamin C transport genes modify these associations. Furthermore, we aimed to determine whether the SNPs themselves are associated with the risk of islet autoimmunity or type 1 diabetes. Methods We used a risk set sampled nested case–control design within an ongoing international multicentre observational study: The Environmental Determinants of Diabetes in the Young (TEDDY). The TEDDY study followed children with increased genetic risk from birth to endpoints of islet autoantibodies (350 cases, 974 controls) and type 1 diabetes (102 cases, 282 controls) in six clinical centres. Control participants were matched for family history of type 1 diabetes, clinical centre and sex. Plasma ascorbic acid concentration was measured at ages 6 and 12 months and then annually up to age 6 years. SNPs in vitamin C transport genes were genotyped using the ImmunoChip custom microarray. Comparisons were adjusted for HLA genotypes and for background population stratification. Results Childhood plasma ascorbic acid (mean ± SD 10.76 ± 3.54 mg/l in controls) was inversely associated with islet autoimmunity risk (adjusted OR 0.96 [95% CI 0.92, 0.99] per +1 mg/l), particularly islet autoimmunity, starting with insulin autoantibodies (OR 0.94 [95% CI 0.88, 0.99]), but not with type 1 diabetes risk (OR 0.93 [95% Cl 0.86, 1.02]). The SLC2A2 rs5400 SNP was associated with increased risk of type 1 diabetes (OR 1.77 [95% CI 1.12, 2.80]), independent of plasma ascorbic acid (OR 0.92 [95% CI 0.84, 1.00]). Conclusions/interpretation Higher plasma ascorbic acid levels may protect against islet autoimmunity in children genetically at risk for type 1 diabetes. Further studies are warranted to confirm these findings. Data availability The datasets generated and analysed during the current study will be made available in the NIDDK Central Repository at https://www.niddkrepository.org/studies/teddy.

Download Full-text

Diabetic Retinopathy May Indicate an Increased Risk of Cardiovascular Disease in Patients With Type 1 Diabetes—A Nested Case-Control Study in Brazil

Frontiers in Endocrinology ◽

10.3389/fendo.2019.00689 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 1

Author(s):

Laura Gomes Nunes Melo ◽

Paulo Henrique Morales ◽

Karla Rezende Guerra Drummond ◽

Deborah Conte Santos ◽

Marcela Haas Pizarro ◽

...

Keyword(s):

Cardiovascular Disease ◽

Type 1 Diabetes ◽

Diabetic Retinopathy ◽

Case Control Study ◽

Case Control ◽

Increased Risk ◽

Nested Case Control ◽

Control Study

Download Full-text

Associations of growth patterns and islet autoimmunity in children with increased risk for type 1 diabetes: a functional analysis approach

Pediatric Diabetes ◽

10.1111/pedi.12368 ◽

2016 ◽

Vol 18 (2) ◽

pp. 103-110 ◽

Cited By ~ 5

Author(s):

Christina Yassouridis ◽

Friedrich Leisch ◽

Christiane Winkler ◽

Anette-Gabriele Ziegler ◽

Andreas Beyerlein

Keyword(s):

Functional Analysis ◽

Type 1 Diabetes ◽

Growth Patterns ◽

Analysis Approach ◽

Islet Autoimmunity ◽

Increased Risk

Download Full-text

Primary Dietary Intervention Study to Reduce the Risk of Islet Autoimmunity in Children at Increased Risk for Type 1 Diabetes: The BABYDIET study

Diabetes Care ◽

10.2337/dc10-2456 ◽

2011 ◽

Vol 34 (6) ◽

pp. 1301-1305 ◽

Cited By ~ 141

Author(s):

S. Hummel ◽

M. Pfluger ◽

M. Hummel ◽

E. Bonifacio ◽

A.-G. Ziegler

Keyword(s):

Type 1 Diabetes ◽

Intervention Study ◽

Dietary Intervention ◽

Islet Autoimmunity ◽

Dietary Intervention Study ◽

Increased Risk

Download Full-text

Pandemrix® vaccination is not associated with increased risk of islet autoimmunity or type 1 diabetes in the TEDDY study children

Diabetologia ◽

10.1007/s00125-017-4448-3 ◽

2017 ◽

Vol 61 (1) ◽

pp. 193-202 ◽

Cited By ~ 5

Author(s):

Helena Elding Larsson ◽

◽

Kristian F. Lynch ◽

Maria Lönnrot ◽

Michael J. Haller ◽

...

Keyword(s):

Type 1 Diabetes ◽

Islet Autoimmunity ◽

Increased Risk

Download Full-text

Evidence of Stage- and Age-Related Heterogeneity of Non-HLA SNPs and Risk of Islet Autoimmunity and Type 1 Diabetes: The Diabetes Autoimmunity Study in the Young

Clinical and Developmental Immunology ◽

10.1155/2013/417657 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 16

Author(s):

Brittni N. Frederiksen ◽

Andrea K. Steck ◽

Miranda Kroehl ◽

Molly M. Lamb ◽

Randall Wong ◽

...

Keyword(s):

Type 1 Diabetes ◽

Cox Regression ◽

Islet Autoimmunity ◽

Candidate Snps ◽

Age Related ◽

Increased Risk ◽

Restricted Cubic Splines ◽

Candidate Loci ◽

Hispanic White

Previously, we examined 20 non-HLA SNPs for association with islet autoimmunity (IA) and/or progression to type 1 diabetes (T1D). Our objective was to investigate fourteen additional non-HLA T1D candidate SNPs for stage- and age-related heterogeneity in the etiology of T1D. Of 1634 non-Hispanic white DAISY children genotyped, 132 developed IA (positive for GAD, insulin, or IA-2 autoantibodies at two or more consecutive visits); 50 IA positive children progressed to T1D. Cox regression was used to analyze risk of IA and progression to T1D in IA positive children. Restricted cubic splines were used to model SNPs when there was evidence that risk was not constant with age.C1QTNF6(rs229541) predicted increased IA risk (HR: 1.57, CI: 1.20–2.05) but not progression to T1D (HR: 1.13, CI: 0.75–1.71). SNP (rs10517086) appears to exhibit an age-related effect on risk of IA, with increased risk before age 2 years (age 2 HR: 1.67, CI: 1.08–2.56) but not older ages (age 4 HR: 0.84, CI: 0.43–1.62).C1QTNF6(rs229541), SNP (rs10517086), andUBASH3A(rs3788013) were associated with development of T1D. This prospective investigation of non-HLA T1D candidate loci shows that some SNPs may exhibit stage- and age-related heterogeneity in the etiology of T1D.

Download Full-text

Maternal Vitamin C and Iron Intake during Pregnancy and the Risk of Islet Autoimmunity and Type 1 Diabetes in Children: A Birth Cohort Study

Nutrients ◽

10.3390/nu13030928 ◽

2021 ◽

Vol 13 (3) ◽

pp. 928

Author(s):

Markus Mattila ◽

Leena Hakola ◽

Sari Niinistö ◽

Heli Tapanainen ◽

Hanna-Mari Takkinen ◽

...

Keyword(s):

Type 1 Diabetes ◽

Vitamin C ◽

Birth Cohort ◽

Islet Autoimmunity ◽

Birth Cohort Study ◽

Iron Intake ◽

Family History Of Diabetes ◽

Maternal Vitamin ◽

Prediction And Prevention

Our aim was to study the associations between maternal vitamin C and iron intake during pregnancy and the offspring’s risk of developing islet autoimmunity and type 1 diabetes. The study was a part of the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) prospective birth cohort including children genetically at risk of type 1 diabetes born between 1997–2004. The diets of 4879 mothers in late pregnancy were assessed with a validated food frequency questionnaire. The outcomes were islet autoimmunity and type 1 diabetes. Cox proportional hazards regression analysis adjusted for energy, family history of diabetes, human leukocyte antigen (HLA) genotype and sex was used for statistical analyses. Total intake of vitamin C or iron from food and supplements was not associated with the risk of islet autoimmunity (vitamin C: HR 0.91: 95% CI (0.80, 1.03), iron: 0.98 (0.87, 1.10)) or type 1 diabetes (vitamin C: 1.01 (0.87, 1.17), iron: 0.92 (0.78, 1.08)), neither was the use of vitamin C or iron supplements associated with the outcomes. In conclusion, no association was found between maternal vitamin C or iron intake during pregnancy and the risk of islet autoimmunity or type 1 diabetes in the offspring.

Download Full-text

Study of oxidative stress biomarkers in obese children

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20184042 ◽

2018 ◽

Vol 6 (10) ◽

pp. 3335

Author(s):

Avni Kanji Fariya ◽

Bina F. Dias

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Ascorbic Acid ◽

Childhood Obesity ◽

Vitamin C ◽

Low Grade ◽

Obese Children ◽

Oxidative Stress Biomarkers ◽

Plasma Ascorbic Acid ◽

Increased Risk

Background: The objective is to study the oxidative stress in obese and non-obese children by assessing the biomarkers of lipid peroxidation and antioxidant status, Malondialdehyde (MDA) and Ascorbic acid (vitamin C) respectively. Childhood obesity is a growing global epidemic that requires attention due to the burden placed on the healthcare system for children and adults. Consumption of fatty foods and a high sugar, fat diet, and no exercise qualify as the main reasons for obesity among children and adults. Childhood obesity is connected with an increased risk of various diseases such as diabetes, cardiovascular, stroke, certain types of cancer later in life, social problems and depression among youths. Obesity is also characterized by chronic low grade inflammation with permanently increased oxidative stress (OS). Over-expression of oxidative stress damages cellular structures together with under-production of anti-oxidant mechanisms, leading to the development of obesity-related complications.Methods: The study involved 25 obese children for Vitamin C, 20 obese children for Malondialdehyde (MDA) and 18 non obese children for both Vitamin C and MDA in the age group of 5-14 years, without any complications. This study was conducted at L.T.M.M College. Plasma Ascorbic Acid was estimated colorimetrically by using 2,6- dicholrophenol indophenol dye and similarly Malondialdehyde was estimated colorimetrically by MDA-TBA colored complex.Results: The study showed significantly higher values of MDA and lower level of Vitamin C in obese children as compared with non-obese children.Conclusions: The levels of lipid peroxidation marker Malondialdehyde (MDA) is higher and level of antioxidant marker Ascorbic Acid (Vitamin C) is lower in obese children as compared with non-obese children. Thereby increasing oxidative stress and hence the oxidative damage to cells.

Download Full-text

Omega-3 Polyunsaturated Fatty Acid Intake and Islet Autoimmunity in Children at Increased Risk for Type 1 Diabetes

JAMA ◽

10.1001/jama.298.12.1420 ◽

2007 ◽

Vol 298 (12) ◽

pp. 1420 ◽

Cited By ~ 182

Author(s):

Jill M. Norris ◽

Xiang Yin ◽

Molly M. Lamb ◽

Katherine Barriga ◽

Jennifer Seifert ◽

...

Keyword(s):

Type 1 Diabetes ◽

Fatty Acid ◽

Polyunsaturated Fatty Acid ◽

Islet Autoimmunity ◽

Fatty Acid Intake ◽

Omega 3 ◽

Acid Intake ◽

Increased Risk

Download Full-text

Telomere Length is Not a Main factor for the Development of Islet Autoimmunity and Type 1 Diabetes in the TEDDY Study

10.21203/rs.3.rs-1018251/v1 ◽

2021 ◽

Author(s):

Hemang Parikh ◽

Carina Törn ◽

Xiang Liu ◽

Suna Onengut-Gumuscu ◽

Kevin Counts ◽

...

Keyword(s):

Type 1 Diabetes ◽

Telomere Length ◽

Significant Negative Correlation ◽

Paternal Age ◽

Islet Autoimmunity ◽

Degree Relative ◽

High Prevalence ◽

Nested Case Control ◽

Hla Dr3

Abstract The Environmental Determinants of Diabetes in the Young (TEDDY) study enrolled 8,676 children, 3-4 months of age, born with HLA-susceptibility genotypes for islet autoimmunity (IA) and type 1 diabetes (T1D). Whole-genome sequencing (WGS) was performed in 1,119 children in a nested case-control study design. Telomere length was estimated from WGS data using five tools: Computel, Telseq, Telomerecat, qMotif and Motif_counter. The estimated median telomere length was 5.10 kb (IQR: 4.52 kb – 5.68 kb) using Computel. The age when the blood sample was drawn had a significant negative correlation with telomere length (P = 0.003). European children, particularly those from Finland (P = 0.041) and from Sweden (P = 0.001), had shorter telomeres than children from the U.S.A. Paternal age (P = 0.019) was positively associated with telomere length. First degree relative status, presence of gestational diabetes in the mother, and maternal age did not have a significant impact on estimated telomere length. HLA-DR4/4 or HLA-DR4/X children had significantly longer telomeres compared to children with HLA-DR3/3 or HLA-DR3/9 haplogenotypes (P = 0.008). Estimated telomere length was not significantly different with respect to any IA (P = 0.377), IAA-first (P = 0.248), GADA-first (P = 0.248) or T1D (P = 0.861). These results suggest that telomere length has no major impact on the risk for IA, the first step to develop T1D. Nevertheless, telomere length was shorter in the T1D high prevalence populations, Finland and Sweden.

Download Full-text

Plasma metabolome and circulating vitamins stratified onset age of an initial islet autoantibody and progression to type 1 diabetes: the TEDDY study

10.2337/figshare.13122524 ◽

2020 ◽

Author(s):

Ada Admin ◽

Qian Li ◽

Xiang Liu ◽

Jimin Yang ◽

Iris Erlund ◽

...

Keyword(s):

Ascorbic Acid ◽

Type 1 Diabetes ◽

Early Onset ◽

Acid Decarboxylase ◽

Islet Autoantibody ◽

Differential Analysis ◽

Plasma Ascorbic Acid ◽

Hydroxyvitamin D ◽

Plasma Metabolome

Children’s plasma metabolome, especially lipidome reflects gene regulation and dietary exposures, heralding the development of islet autoantibodies (IA) and type 1 diabetes (T1D). The TEDDY study enrolled 8676 newborns by screening HLA-DR-DQ genotypes at six clinical centers in four countries; profiled metabolome and measured concentrations of ascorbic acid, 25-hydroxyvitamin D (25(OH)D), erythrocyte membrane fatty acids following birth until IA seroconversion under nested case-control design. We grouped children having an initial autoantibody only against insulin (IAA-first) or glutamic acid decarboxylase (GADA-first) by unsupervised clustering of temporal lipidome, identifying a subgroup of children having early onset of each initial autoantibody, i.e., IAA-first by 12 months and GADA-first by 21 months, consistent with population-wide early seroconversion age. Differential analysis showed that infants having reduced plasma ascorbic acid and cholesterol experienced IAA-first earlier, while early onset of GADA-first was preceded by reduced sphingomyelins at infancy. Plasma 25(OH)D prior to either autoantibody was lower in T1D progressors compared to non-progressors, with simultaneous lower diglycerides, lysophosphatidylcholines, triglycerides, alanine before GADA-first. Plasma ascorbic acid and 25(OH)D at infancy were lower in HLA-DR3/DR4 children among IA cases but not in matched controls, implying gene expression dysregulation of circulating vitamins as latent signals for IA or T1D progression.

Download Full-text