Genetic Influences on Serum LDL Levels and on Type 1 Diabetes Incidence in Sardinia

2001 ◽  
pp. 76-82 ◽  
Author(s):  
S. Muntoni ◽  
S. Muntoni
Keyword(s):  
Type 1 Diabetes ◽  
Genetic Influences ◽  
Diabetes Incidence

scholarly journals DR15-DQ6 remains dominantly protective against type 1 diabetes throughout the first five decades of life

Diabetologia ◽  
2021 ◽  
Author(s):  
Nicholas J. Thomas ◽  
John M. Dennis ◽  
Seth A. Sharp ◽  
Akaal Kaur ◽  
Shivani Misra ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Major Type ◽  
Diabetes Incidence ◽  
Diabetes Diagnosis ◽  
Risk Haplotype ◽  
Adult Onset ◽  
Uk Biobank ◽  
Onset Type ◽  
Increased Risk

Abstract Aims/hypothesis Among white European children developing type 1 diabetes, the otherwise common HLA haplotype DR15-DQ6 is rare, and highly protective. Adult-onset type 1 diabetes is now known to represent more overall cases than childhood onset, but it is not known whether DR15-DQ6 is protective in older-adult-onset type 1 diabetes. We sought to quantify DR15-DQ6 protection against type 1 diabetes as age of onset increased. Methods In two independent cohorts we assessed the proportion of type 1 diabetes cases presenting through the first 50 years of life with DR15-DQ6, compared with population controls. In the After Diabetes Diagnosis Research Support System-2 (ADDRESS-2) cohort (n = 1458) clinician-diagnosed type 1 diabetes was confirmed by positivity for one or more islet-specific autoantibodies. In UK Biobank (n = 2502), we estimated type 1 diabetes incidence rates relative to baseline HLA risk for each HLA group using Poisson regression. Analyses were restricted to white Europeans and were performed in three groups according to age at type 1 diabetes onset: 0–18 years, 19–30 years and 31–50 years. Results DR15-DQ6 was protective against type 1 diabetes through to age 50 years (OR < 1 for each age group, all p < 0.001). The following ORs for type 1 diabetes, relative to a neutral HLA genotype, were observed in ADDRESS-2: age 5–18 years OR 0.16 (95% CI 0.08, 0.31); age 19–30 years OR 0.10 (0.04, 0.23); and age 31–50 years OR 0.37 (0.21, 0.68). DR15-DQ6 also remained highly protective at all ages in UK Biobank. Without DR15-DQ6, the presence of major type 1 diabetes high-risk haplotype (either DR3-DQ2 or DR4-DQ8) was associated with increased risk of type 1 diabetes. Conclusions/interpretation HLA DR15-DQ6 confers dominant protection from type 1 diabetes across the first five decades of life. Graphical abstract

scholarly journals pH of Drinking Water Influences the Composition of Gut Microbiome and Type 1 Diabetes Incidence

Diabetes ◽  
2013 ◽  
Vol 63 (2) ◽  
pp. 632-644 ◽  
Author(s):  
M. H. Sofi ◽  
R. Gudi ◽  
S. Karumuthil-Melethil ◽  
N. Perez ◽  
B. M. Johnson ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Drinking Water ◽  
Gut Microbiome ◽  
Diabetes Incidence

Thiazolidinediones May Not Reduce Diabetes Incidence in Type 1 Diabetes

2006 ◽  
Vol 1079 (1) ◽  
pp. 365-368 ◽  
Author(s):  
T. SHIGIHARA ◽  
Y. OKUBO ◽  
Y. KANAZAWA ◽  
Y. OIKAWA ◽  
A. SHIMADA
Keyword(s):  
Type 1 Diabetes ◽  
Diabetes Incidence

scholarly journals Proinsulin peptide promotes autoimmune diabetes in a novel HLA-DR3-DQ2-transgenic murine model of spontaneous disease

Diabetologia ◽  
2019 ◽  
Vol 62 (12) ◽  
pp. 2252-2261 ◽  
Author(s):  
Johan Verhagen ◽  
Norkhairin Yusuf ◽  
Emma L. Smith ◽  
Emily M. Whettlock ◽  
Kerina Naran ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Autoimmune Diabetes ◽  
Diabetes Incidence ◽  
Human Type ◽  
Insulin Promoter ◽  
Human Type 1 Diabetes ◽  
Hla Dr3 ◽  
Peptide Region

Abstract Aims/hypothesis The molecular basis for the pathological impact of specific HLA molecules on autoimmune diseases such as type 1 diabetes remains unclear. Recent natural history studies in children have indicated a link between specific HLA genotypes and the first antigenic target against which immune responses develop. We set out to examine this link in vivo by exploring the diabetogenicity of islet antigens on the background of a common diabetes-associated HLA haplotype. Methods We generated a novel HLA-transgenic mouse model that expresses high-risk genes for type 1 diabetes (DRB1*03:01-DQA1*05:01-DQB1*02:01) as well as human CD80 under the rat insulin promoter and human CD4, on a C57BL/6 background. Adjuvanted antigen priming was used to reveal the diabetogenicity of candidate antigens and peptides. Results HLA-DR3-DQ2+huCD4+IA/IE−/−RIP.B7.1+ mice spontaneously developed autoimmune diabetes (incidence 46% by 35 weeks of age), accompanied by numerous hallmarks of human type 1 diabetes (autoantibodies against GAD65 and proinsulin; pancreatic islet infiltration by CD4+, CD8+ B220+, CD11b+ and CD11c+ immune cells). Disease was markedly accelerated and had deeper penetrance after adjuvanted antigen priming with proinsulin (mean onset 11 weeks and incidence 100% by 20 weeks post challenge). Moreover, the diabetogenic effect of proinsulin located to the 15-residue B29-C11 region. Conclusions/interpretation Our study identifies a proinsulin-derived peptide region that is highly diabetogenic on the HLA-DR3-DQ2 background using an in vivo model. This approach and the peptide region identified may have wider implications for future studies of human type 1 diabetes.

scholarly journals An Increase in Serum 25-Hydroxyvitamin D Concentrations Preceded a Plateau in Type 1 Diabetes Incidence in Finnish Children

2014 ◽  
Vol 99 (11) ◽  
pp. E2353-E2356 ◽  
Author(s):  
Marjaana Mäkinen ◽  
Ville Simell ◽  
Juha Mykkänen ◽  
Jorma Ilonen ◽  
Riitta Veijola ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Diabetes Incidence ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D

Exposure to DDT metabolitep,p′-DDE increases autoimmune type 1 diabetes incidence in NOD mouse model

2015 ◽  
Vol 13 (1) ◽  
pp. 108-118 ◽  
Author(s):  
Marina Cetkovic-Cvrlje ◽  
Marin Olson ◽  
Broc Schindler ◽  
Hwee Kiat Gong
Keyword(s):  
Type 1 Diabetes ◽  
Mouse Model ◽  
Nod Mouse ◽  
Diabetes Incidence

scholarly journals Knockout of the Amino Acid Transporter SLC6A19 and Autoimmune Diabetes Incidence in Female Non-Obese Diabetic (NOD) Mice

Metabolites ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 665
Author(s):  
Matthew F. Waters ◽  
Viviane Delghingaro-Augusto ◽  
Kiran Javed ◽  
Jane E. Dahlstrom ◽  
Gaetan Burgio ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Amino Acid ◽  
Confidence Interval ◽  
Autoimmune Diabetes ◽  
Nod Mice ◽  
Amino Acid Transporter ◽  
Diabetes Incidence ◽  
Amino Acid Availability ◽  
Acid Transporter

High protein feeding has been shown to accelerate the development of type 1 diabetes in female non-obese diabetic (NOD) mice. Here, we investigated whether reducing systemic amino acid availability via knockout of the Slc6a19 gene encoding the system B(0) neutral amino acid transporter AT1 would reduce the incidence or delay the onset of type 1 diabetes in female NOD mice. Slc6a19 gene deficient NOD mice were generated using the CRISPR-Cas9 system which resulted in marked aminoaciduria. The incidence of diabetes by week 30 was 59.5% (22/37) and 69.0% (20/29) in NOD.Slc6a19+/+ and NOD.Slc6a19−/− mice, respectively (hazard ratio 0.77, 95% confidence interval 0.41–1.42; Mantel-Cox log rank test: p = 0.37). The median survival time without diabetes was 28 and 25 weeks for NOD.Slc6a19+/+ and NOD.Slc6a19−/− mice, respectively (ratio 1.1, 95% confidence interval 0.6–2.0). Histological analysis did not show differences in islet number or the degree of insulitis between wild type and Slc6a19 deficient NOD mice. We conclude that Slc6a19 deficiency does not prevent or delay the development of type 1 diabetes in female NOD mice.

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