Autoimmune polyglandular syndrome type 2 shows the same HLA class II pattern as type 1 diabetes†

ABSTRACT Whereas the genetic risk for type 1 diabetes is linked to human leukocyte antigen (HLA) class II genes, the HLA association in type 2 (non-insulin-dependent) diabetes is less clear. The association between HLA class II genotypes and type 2 diabetes was examined in adult Bahrainis, an Arab population with a high prevalence of type 2 diabetes. HLA-DRB1* and -DQB1* genotyping of 86 unrelated type 2 diabetes patients (age, 51.6 ± 8.2 years; mean duration of diabetes, 7.7 ± 7.1 years) who had a strong family history of diabetes (52 of 72 versus 0 of 89 for controls, P < 0.001) and 89 healthy subjects was done by PCR-sequence-specific priming. DRB1*040101 (0.1221 versus 0.0562, P = 0.019) and DRB1*070101 (0.2151 versus 0.0843, P < 0.001) were positively associated, while DRB1*110101 (0.0698 versus 0.1461, P = 0.014) and DRB1*160101 (0.0640 versus 0.1236, P = 0.038) were negatively associated with type 2 diabetes. DRB1*040101-DQB1*0302 (0.069 versus 0.0007; P = 0.004), DRB1*070101-DQB1*0201 (0.178 versus 0.0761, P = 0.007), DRB1*070101-DQB1*050101 (0.125 versus 0.0310, P = 0.002), and DRB1*150101-DQB1*060101 (0.0756 versus 0.0281, P = 0.008) were more prevalent among patients, while DRB1*160101-DQB1*050101 (0.0702 versus 0.0349, P = 0.05) was more prevalent among controls, conferring disease susceptibility or protection, respectively. In Bahrainis with type 2 diabetes, there is a significant association with select HLA class II genotypes, which were distinct from those in type 1 diabetes.

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HLA Class II Allele Analyses Implicate Common Genetic Components in Type 1 and Non–Insulin-Treated Type 2 Diabetes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa027 ◽

2020 ◽

Vol 105 (3) ◽

pp. e245-e254 ◽

Cited By ~ 1

Author(s):

Thomas Jacobi ◽

Lucas Massier ◽

Nora Klöting ◽

Katrin Horn ◽

Alexander Schuch ◽

...

Keyword(s):

Type 2 Diabetes ◽

Type 1 Diabetes ◽

Class Ii ◽

Hla Class Ii ◽

Risk Haplotype ◽

Genetic Components ◽

Hla Genotypes ◽

Increased Risk

Abstract Context Common genetic susceptibility may underlie the frequently observed co-occurrence of type 1 and type 2 diabetes in families. Given the role of HLA class II genes in the pathophysiology of type 1 diabetes, the aim of the present study was to test the association of high density imputed human leukocyte antigen (HLA) genotypes with type 2 diabetes. Objectives and Design Three cohorts (Ntotal = 10 413) from Leipzig, Germany were included in this study: LIFE-Adult (N = 4649), LIFE-Heart (N = 4815) and the Sorbs (N = 949) cohort. Detailed metabolic phenotyping and genome-wide single nucleotide polymorphism (SNP) data were available for all subjects. Using 1000 Genome imputation data, HLA genotypes were imputed on 4-digit level and association tests for type 2 diabetes, and related metabolic traits were conducted. Results In a meta-analysis including all 3 cohorts, the absence of HLA-DRB5 was associated with increased risk of type 2 diabetes (P = 0.001). In contrast, HLA-DQB*06:02 and HLA-DQA*01:02 had a protective effect on type 2 diabetes (P = 0.005 and 0.003, respectively). Both alleles are part of the well-established type 1 diabetes protective haplotype DRB1*15:01~DQA1*01:02~DQB1*06:02, which was also associated with reduced risk of type 2 diabetes (OR 0.84; P = 0.005). On the contrary, the DRB1*07:01~DQA1*02:01~DQB1*03:03 was identified as a risk haplotype in non–insulin-treated diabetes (OR 1.37; P = 0.002). Conclusions Genetic variation in the HLA class II locus exerts risk and protective effects on non–insulin-treated type 2 diabetes. Our data suggest that the genetic architecture of type 1 diabetes and type 2 diabetes might share common components on the HLA class II locus.

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Insulin Administration May Trigger Type 1 Diabetes in Japanese Type 2 Diabetes Patients With Type 1 Diabetes High-Risk HLA Class II and the Insulin Gene VNTR Genotype

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2014-1759 ◽

2014 ◽

Vol 99 (9) ◽

pp. E1793-E1797 ◽

Cited By ~ 3

Author(s):

Wataru Nishida ◽

Masao Nagata ◽

Akihisa Imagawa ◽

Toshiaki Hanafusa ◽

Jun Ohashi ◽

...

Keyword(s):

Type 2 Diabetes ◽

Type 1 Diabetes ◽

High Risk ◽

Class Ii ◽

Hla Class Ii ◽

Insulin Gene ◽

Insulin Administration ◽

Diabetes Patients

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Autoimmune Polyglandular Syndrome Type 3 with Anorexia

Case Reports in Endocrinology ◽

10.1155/2012/657156 ◽

2012 ◽

Vol 2012 ◽

pp. 1-4

Author(s):

Toshio Kahara ◽

Hitomi Wakakuri ◽

Juri Takatsuji ◽

Iori Motoo ◽

Kosuke R. Shima ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Pernicious Anemia ◽

Cobalamin Deficiency ◽

Syndrome Type ◽

Autoimmune Polyglandular Syndrome ◽

Autoimmune Polyglandular Syndrome Type ◽

Type 3

A 71-year-old man with diabetes mellitus visited our hospital with complaints of anorexia and weight loss (12 kg/3 months). He had megaloblastic anemia, cobalamin level was low, and autoantibody to intrinsic factor was positive. He was treated with intramuscular cyanocobalamin, and he was able to consume meals. GAD autoantibody and ICA were positive, and he was diagnosed with slowly progressive type 1 diabetes mellitus (SPIDDM). Thyroid autoantibodies were positive. According to these findings, he was diagnosed with autoimmune polyglandular syndrome type 3 with SPIDDM, pernicious anemia, and Hashimoto's thyroiditis. Extended periods of cobalamin deficiency can cause serious complications such as ataxia and dementia, and these complications may not be reversible if replacement therapy with cobalamin is delayed. Although type 1 diabetes mellitus with coexisting pernicious anemia is very rare in Japan, physicians should consider the possibility of pernicious anemia when patients with diabetes mellitus have cryptogenic anorexia with the finding of significant macrocytosis (MCV > 100 fL).

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Autoimmune polyglandular syndrome type 3 variant in rheumatoid arthritis

Romanian Journal of Internal Medicine ◽

10.2478/rjim-2019-0024 ◽

2020 ◽

Vol 58 (1) ◽

pp. 40-43 ◽

Cited By ~ 1

Author(s):

Taro Horino ◽

Masami Ogasawara ◽

Osamu Ichii ◽

Yoshio Terada

Keyword(s):

Rheumatoid Arthritis ◽

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Clinical Course ◽

Syndrome Type ◽

Autoimmune Polyglandular Syndrome ◽

History Of ◽

Autoimmune Polyglandular Syndrome Type ◽

Type 3

AbstractIntroduction. Although type 1 diabetes mellitus is largely associated with autoimmune thyroid disease and this entity has been recently referred to as autoimmune polyglandular syndrome type 3 variant, the autoimmune polyglandular syndrome type 3 variant in patients with rheumatoid arthritis has not been reported so far. We herein describe the first case of rheumatoid arthritis that was associated with autoimmune polyglandular syndrome type 3 variant.Case report. A 77-year-old woman with a 15-year history of rheumatoid arthritis (RA) and a 10-year history of type 2 diabetes mellitus (T2D) presented with polyarthralgia and hyperglycaemia. Methotrexate 16 mg/week had been started from the onset and was continued, and adalimumab 40 mg/day was started for RA. Insulin treatment was also started for the diabetes. Laboratory examinations revealed high levels of C-reactive protein (CRP), rheumatoid factor, anti-cyclic citrullinated peptide antibody, and matrix metalloprotease 3. She was admitted multiple times as the symptoms recurred after treatment. Subsequently, based on the clinical course and investigations, she was diagnosed with type 1 diabetes mellitus and Graves’ disease occurring during the course of RA and T2D. Her clinical course improved after reinforcement of insulin therapy and the addition of thiamazole therapy.Conclusion. In patients with rheumatoid arthritis, the autoimmune polyglandular syndrome type 3 variant should be considered as the cause of the deterioration.

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