Class I and II HLA Genes Are Associated with Susceptibility and Age at Onset in Finnish Families with Type 1 Diabetes

2004 ◽  
Vol 57 (2) ◽  
pp. 69-79 ◽  
Author(s):  
Janne Pitkäniemi ◽  
Timo Hakulinen ◽  
Jurkka Näsänen ◽  
Eva Tuomilehto-Wolf ◽  
Jaakko Tuomilehto
Keyword(s):  
Type 1 Diabetes ◽  
Age At Onset ◽  
Class I ◽  
Hla Genes

scholarly journals Use of class I and class II HLA loci for predicting age at onset of type 1 diabetes in multiple populations

Diabetologia ◽  
2012 ◽  
Vol 55 (9) ◽  
pp. 2394-2401 ◽  
Author(s):  
A. M. Valdes ◽  
H. A. Erlich ◽  
J. Carlson ◽  
M. Varney ◽  
P. V. Moonsamy ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Age At Onset ◽  
Class Ii ◽  
Class I ◽  
Multiple Populations

scholarly journals What the HLA-I!—Classical and Non-classical HLA Class I and Their Potential Roles in Type 1 Diabetes

2019 ◽  
Vol 19 (12) ◽  
Author(s):  
Rebecca C. Wyatt ◽  
Giacomo Lanzoni ◽  
Mark A. Russell ◽  
Ivan Gerling ◽  
Sarah J. Richardson
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Immune Cells ◽  
Age At Onset ◽  
Hla Class I ◽  
Class I ◽  
Β Cells ◽  
Disease Etiology ◽  
Recent Onset

Abstract Purpose of Review Hyperexpression of classical HLA class I (HLA-I) molecules in insulin-containing islets has become a widely accepted hallmark of type 1 diabetes pathology. In comparison, relatively little is known about the expression, function and role of non-classical subtypes of HLA-I. This review focuses on the current understanding of the non-classical HLA-I subtypes: HLA-E, HLA-F and HLA-G, within and outside the field of type 1 diabetes, and considers the possible impacts of these molecules on disease etiology. Recent Findings Evidence is growing to suggest that non-classical HLA-I proteins are upregulated, both at the RNA and protein levels in the pancreas of individuals with recent-onset type 1 diabetes. Moreover, associations between non-classical HLA-I genotypes and age at onset of type 1 diabetes have been reported in some studies. As with classical HLA-I, it is likely that hyperexpression of non-classical HLA-I is driven by the release of diffusible interferons by stressed β cells (potentially driven by viral infection) and exacerbated by release of cytokines from infiltrating immune cells. Summary Non-classical HLA-I proteins predominantly (but not exclusively) transduce negative signals to immune cells infiltrating at the site of injury/inflammation. We propose a model in which the islet endocrine cells, through expression of non-classical HLA-I are fighting back against the infiltrating immune cells. By inhibiting the activity and function on NK, B and select T cells, the non-classical HLA-I, proteins will reduce the non-specific bystander effects of inflammation, while at the same time still allowing the targeted destruction of β cells by specific islet-reactive CD8+ T cells.

scholarly journals HLA class I genes modulate disease risk and age at onset together with DR-DQ in Chinese patients with insulin-requiring type 1 diabetes

Diabetologia ◽  
2021 ◽  
Author(s):  
Ziyu Jiang ◽  
Wenqian Ren ◽  
Hua Liang ◽  
Jinhua Yan ◽  
Daizhi Yang ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Disease Risk ◽  
Hla Class I ◽  
Class I ◽  
Chinese Patients ◽  
Onset Age ◽  
Disease Heterogeneity ◽  
Negatively Associated ◽  
Healthy Control

Abstract Aims/hypothesis The study aimed to investigate the effects of HLA class I genes on susceptibility to type 1 diabetes with different onset ages, in addition to the well-established effects of HLA class II genes. Methods A total of 361 patients with type 1 diabetes (192 patients with onset <18 years and 169 patients with onset ≥18 years) and 500 healthy control participants from China were enrolled and genotyped for the HLA-A, -B, -C, -DQA1, -DQB1 and -DRB1 genes using next-generation sequencing. Results The susceptible DR3 (β = −0.09, p = 0.0009) and DR4-DQ8 (β = −0.13, p = 0.0059) haplotypes were negatively associated with onset age, while the protective DR11 (β = 0.21, p = 0.0314) and DR12 (β = 0.27, p < 0.0001) haplotypes were positively associated with onset age. After adjustment for linkage disequilibrium with DR-DQ haplotypes, A*11:01:01 was positively associated with onset age (β = 0.06, p = 0.0370), while the susceptible C*15:02:01 was negatively associated with onset age (β = −0.21, p = 0.0050). The unit for β was double square-root (fourth root) transformed years of change in onset age associated with per copy of the HLA haplotype/allele. In addition, B*46:01:01 was protective (OR 0.41, 0.46; pc [corrected for multiple comparisons] = 0.0044, 0.0040), whereas A*24:02:01 (OR 2.71, 2.25; pc = 0.0003, 0.0002) and B*54:01:01 (OR 3.96, 3.79; pc = 0.0018, 0.0004) were predisposing in both the <18 group and the ≥18 group compared with healthy control participants. In the context of DR4-DQ4, A*11:01:01 (61.29% vs 28.26%, pc = 0.0144) was increased while the predisposing A*24:02:01 (19.35% vs 47.83%, pc = 0.0403) was decreased in patients with onset ≥18 years when compared with patients with onset <18 years. Conclusions/interpretation In addition to DR-DQ haplotypes, novel HLA class I alleles were detected to play a role in susceptibility to type 1 diabetes with different onset ages, which could improve the understanding of disease heterogeneity and has implications for the design of future studies. Graphical abstract

Negative association between type 1 diabetes and HLA DQB1*0602-DQA1*0102 is attenuated with age at onset

1999 ◽  
Vol 26 (2-3) ◽  
pp. 117-127
Author(s):  
Jinko Graham ◽  
Ingrid Kockum ◽  
Carani B. Sanjeevi ◽  
Mona Landin-Olsson ◽  
Lennarth Nyström ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Age At Onset ◽  
Negative Association

Discordant association of islet autoantibodies with high-risk HLA genes in Chinese type 1 diabetes

2011 ◽  
Vol 27 (8) ◽  
pp. 899-905 ◽  
Author(s):  
Yong Gu ◽  
Mei Zhang ◽  
Heng Chen ◽  
Zhixiao Wang ◽  
Chunyan Xing ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
High Risk ◽  
Islet Autoantibodies ◽  
Hla Genes

Vestibular Function in Children with Type 1 Diabetes: Videonystagmography Testing

2021 ◽  
pp. 1-9
Author(s):  
Sherifa A. Hamed ◽  
Ali F. ElHadad ◽  
Amira M. Oseily
Keyword(s):  
Type 1 Diabetes ◽  
Diabetic Complications ◽  
Multiple Logistic Regression Analysis ◽  
Age At Onset ◽  
Vestibular Function ◽  
Multiple Logistic Regression ◽  
Duration Of Illness ◽  
Control And Prevention ◽  
Hba1c Levels

<b><i>Background:</i></b> Vestibular system is critical for maintaining balance and learning complex tasks. This study aimed to determine the frequencies, types, and predictors of vestibular dysfunctions (VDs) in children with type 1 diabetes (T1D) using videonystagmography (VNG). <b><i>Patients and Methods:</i></b> This study included 65 patients (children with T1D = 40; controls = 25). The patients underwent VNG. <b><i>Results:</i></b> Patients (boys = 15; girls = 25) had a mean age of 14.05 ± 1.82 years and duration of illness of 6.30 ± 2.84 years. The majority had frequent attacks of diabetic ketoacidosis (DKA) (65%) and hypoglycemia (40%). Dizziness was reported in 20%. VNG abnormalities were reported in 70% (<i>n</i> = 28), of them 71.43 and 28.57% had central and peripheral VDs, respectively. Dizziness was associated with peripheral VD. Compared to patients without VDs, those with VDs were older and had earlier age at onset and longer duration of diabetes (&#x3e;5 years), higher levels of HbA1c (&#x3e;7%), higher frequencies of DKA and hypoglycemic attacks, comorbid medical conditions, and diabetic complications. Multiple logistic regression analysis showed that presence of VNG abnormalities (VDs) was independently correlated with diabetes duration &#x3e;5 years (odds ratio [OR] = 4.52 [95% confidence interval [CI] = 3.55–7.04], <i>p</i> = 0.001), HbA1c% levels &#x3e;7% (OR = 3.42 [95% CI = 2.84–5.75], <i>p</i> = 0.001), and presence of hypoglycemic attacks (OR = 4.65 [95% CI = 2.85–7.55]). <b><i>Conclusions:</i></b> -VDs are prevalent in children with T1D and correlated with the duration and severity of diabetes and the occurrence of hypoglycemic attacks. Therefore, optimizing glycemic control and prevention and treatment of diabetic complications and comorbidities are important. Multidisciplinary follow-ups are required for early detection and management of diabetic VDs.

Partial remission in children and adolescents with type 1 diabetes: an analysis based on the insulin dose-adjusted hemoglobin A1c

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Emine Ayça Cimbek ◽  
Aydın Bozkır ◽  
Deniz Usta ◽  
Nazım Ercüment Beyhun ◽  
Ayşenur Ökten ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Partial Remission ◽  
Hemoglobin A1c ◽  
Insulin Dose ◽  
Age At Onset ◽  
Insulin Requirement ◽  
C Peptide ◽  
Factors Associated ◽  
Daily Insulin

Abstract Objectives Most patients with type 1 diabetes (T1D) experience a transient phase of partial remission (PR). This study aimed to identify the demographic and clinical factors associated with PR. Methods This was a longitudinal retrospective cohort study of 133 children and adolescents with T1D. PR was defined by the gold standard insulin dose-adjusted hemoglobin A1c (HbA1c) (IDAA1c) of ≤9. Results Remission was observed in 77 (57.9%) patients. At diagnosis, remitters had significantly higher pH (7.3 ± 0.12 vs. 7.23 ± 0.15, p=0.003), higher C-peptide levels (0.45 ± 0.31 ng/mL vs. 0.3 ± 0.22, p=0.003), and they were significantly older (9.3 ± 3.6 years vs. 7.3 ± 4.2, p=0.008) compared with non-remitters. PR developed more frequently in patients without diabetic ketoacidosis (DKA) (p=0.026) and with disease onset after age 5 (p=0.001). Patients using multiple daily insulin regimen were more likely to experience PR than those treated with a twice daily regimen (63.9 vs. 32%, p=0.004). Only age at onset was an independent predictor of PR (OR: 1.12, 95% CI: 1-1.25; p=0.044). Remitters had lower HbA1c levels and daily insulin requirement from diagnosis until one year after diagnosis (p<0.001). PR recurred in 7 (9%) patients. The daily insulin requirement at three months was lower in remitters with PR recurrence compared to those without (0.23 ± 0.14 vs. 0.4 ± 0.17 U/kg/day, p=0.014). Conclusions Addressing factors associated with the occurrence of PR could provide a better comprehension of metabolic control in T1D. The lack of DKA and higher C-peptide levels may influence PR, but the main factor associated with PR presence was older age at onset. PR may recur in a small proportion of patients.

Higher age at onset of type 1 diabetes increases risk of macular oedema

2012 ◽  
Vol 91 (8) ◽  
pp. 709-715 ◽  
Author(s):  
Kustaa Hietala ◽  
Carol Forsblom ◽  
Paula Summanen ◽  
Per-Henrik Groop ◽  
Keyword(s):  
Type 1 Diabetes ◽  
Macular Oedema ◽  
Age At Onset
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