Autoantibodies against ZnT8 are rare in Central-European LADA patients and absent in MODY patients, including those positive for other autoantibodies

Heneberg, Petr; Šimčíková, Daniela; Čecháková, Marie; Rypáčková, Blanka; Kučera, Petr; Andĕl, M

doi:10.1016/j.jdiacomp.2018.10.004

Cited by 7 publications

(5 citation statements)

References 39 publications

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“…This represents a non-negligible percentage, close to 15% of patients (4/27), who were diagnosed properly as T1D. The absence of pathogenic variants in the four patients with only ZnT8A positive, supports recently published data confirming ZnT8A as a marker for excluding patients from genetic testing for monogenic diabetes [42,43].…”

Section: Discussionsupporting

confidence: 82%

Negative autoimmunity in a Spanish pediatric cohort suspected of type 1 diabetes, could it be monogenic diabetes?

et al. 2019

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Objective Monogenic diabetes can be misdiagnosed as type 1 or type 2 diabetes in children. The right diagnosis is crucial for both therapeutic choice and prognosis and influences genetic counseling. The main objective of this study was to search for monogenic diabetes in Spanish pediatric patients suspected of type 1 diabetes with lack of autoimmunity at the onset of the disease. We also evaluated the extra value of ZnT8A in addition to the classical IAA, GADA and IA2A autoantibodies to improve the accuracy of type 1 diabetes diagnosis. Methods Four hundred Spanish pediatric patients with recent-onset diabetes (mean age 8.9 ± 3.9 years) were analyzed for IAA, GADA, IA2A and ZnT8A pancreatic-autoantibodies and HLA-DRB1 alleles. Patients without autoimmunity and those with only ZnT8A positive were screened for 12 monogenic diabetes genes by next generation sequencing. Results ZnT8A testing increased the number of autoantibody-positive patients from 373 (93.3%) to 377 (94.3%). An isolated positivity for ZnT8A allowed diagnosing autoimmune diabetes in 14.8% (4/27) of pediatric patients negative for the rest of the antibodies tested. At least 2 of the 23 patients with no detectable autoimmunity (8%) carried heterozygous pathogenic variants: one previously reported missense variant in the INS gene (p.Gly32Ser) and one novel frameshift variant (p.Val264fs) in the HNF1A gene. One variant of uncertain significance was also found. Carriers of pathogenic variants had HLA-DRB1 risk alleles for autoimmune diabetes and clinical characteristics compatible with type 1 diabetes except for the absence of autoimmunity. Conclusion ZnT8A determination improves the diagnosis of autoimmune diabetes in pediatrics. At least 8% of pediatric patients suspected of type 1 diabetes and with undetectable autoimmunity have monogenic diabetes and can benefit from the correct diagnosis of the disease by genetic study.

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Section: Discussionsupporting

confidence: 82%

Negative autoimmunity in a Spanish pediatric cohort suspected of type 1 diabetes, could it be monogenic diabetes?

et al. 2019

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“…In one study performed in a selected adult Czech population with LADA, confirmed maturity-onset diabetes of the young, and healthy controls, a high prevalence of ZnT8-A positivity of 23.7% was noted in 59 participants with study-defined LADA. All of these participants were positive for GADA and IA-2A [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Islet autoantibody positivity in an adult population with recently diagnosed diabetes in Uganda

et al. 2022

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Aims This study aimed to investigate the frequency of islet autoantibody positivity in adult patients with recently diagnosed diabetes in Uganda and its associated characteristics. Methods Autoantibodies to glutamic acid decarboxylase-65 (GADA), zinc transporter 8 (ZnT8-A), and tyrosine phosphatase (IA-2A) were measured in 534 adult patients with recently diagnosed diabetes. Islet autoantibody positivity was defined based on diagnostic thresholds derived from a local adult population without diabetes. The socio-demographic, clinical, and metabolic characteristics of islet autoantibody-positive and negative participants were then compared. The differences in these characteristics were analysed using the x2 test for categorical data and the Kruskal Wallis test for continuous data. Multivariate analysis was performed to identify predictors of islet autoantibody positivity. Results Thirty four (6.4%) participants were positive for ≥1 islet autoantibody. GADA, IA-2A and ZnT8-A positivity was detected in 17 (3.2%), 10 (1.9%), and 7 (1.3%) participants, respectively. Compared with those negative for islet autoantibodies, participants positive for islet autoantibodies were more likely to live in a rural area (n = 18, 52.9% Vs n = 127, 25.5%, p = 0.005), to be initiated on insulin therapy (n = 19, 55.9% Vs n = 134, 26.8%, p<0.001), to have a lower median waist circumference (90 [80–99] cm Vs 96 [87–104.8], p = 0.04), waist circumference: height ratio (0.55 [0.50–0.63] vs 0.59 [0.53–0.65], p = 0.03), and fasting C-peptide concentration (0.9 [0.6–1.8] Vs 1.4 [0.8–2.1] ng/ml, p = 0.01). On multivariate analysis, living in a rural area (odds ratio or OR 3.62, 95%CI 1.68–7.80, p = 0.001) and being initiated on insulin therapy (OR 3.61, 95% CI 1.67–7.83, p = 0.001) were associated with islet autoantibody positivity. Conclusion The prevalence of islet autoantibody positivity was relatively low, suggesting that pancreatic autoimmunity is a rare cause of new-onset diabetes in this adult Ugandan population. Living in a rural area and being initiated on insulin therapy were independently associated with islet autoantibody positivity in this study population.

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“…Type 1 diabetes is basically an autoimmune disease. Autoimmunity is also present in patients with a phenotype of type 2 diabetes but with detectable autoantibodies against pancreatic beta-cells ( 1 , 2 , 3 , 4 , 5 ). This form of diabetes, latent autoimmune diabetes in adults (LADA), constitutes 4–10% of what was formerly regarded as type 2 diabetes ( 6 , 7 ).…”

Section: Introductionmentioning

confidence: 99%

Small RNAs are differentially expressed in autoimmune and non-autoimmune diabetes and controls

Sørgjerd

Mjelle

Beisvåg

et al. 2022

European Journal of Endocrinology

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Objective Diabetes is a heterogeneous disease and precise diagnosis of diabetes subgroups is necessary to initiate proper early treatment and clinical management of the disease. Circulating small RNAs (sRNAs) are potentially diagnostic biomarkers in diseases, including diabetes. Here we aimed to examine whether profiles of circulating sRNAs differed between patients with autoimmune and non-autoimmune diabetes and non-diabetic controls. Design This cross-sectional case-control study included participants from the third survey of the HUNT study. Methods We performed sRNA sequencing in serum from adult-onset type 1 diabetes (n=51), type 2 diabetes (n=50) and Latent Autoimmune Diabetes in Adult (LADA, n=51), as well as non-diabetic HUNT3 participants as control group (n=51). Differential expression analysis of the sRNAs were performed in R using limma-voom. Results We identified differences in sRNA expression between autoimmune (type 1 diabetes and LADA) and non-autoimmune diabetes (type 2 diabetes) and between patients with diabetes and non-diabetic controls. Focusing on microRNAs (miRNAs), we identified 10 differentially expressed mature miRNAs and 30 differentially expressed miRNA variants (isomiRs). We also identified significant changes within other sRNA classes, including a pronounced up-regulation of a transfer RNA-fragment in patients with diabetes compared to non-diabetic controls. We created cross-validated sRNA signatures based on the significant sRNAs that distinguished patients with diabetes from non-diabetic controls, and autoimmune from non-autoimmune diabetes, with high specificity and sensitivity. sRNA profiles did not distinguish between type 1 diabetes and LADA. Conclusions Circulating sRNAs are differentially expressed between patients with diabetes and non-diabetic controls and between autoimmune and non-autoimmune diabetes.

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Autoantibodies against ZnT8 are rare in Central-European LADA patients and absent in MODY patients, including those positive for other autoantibodies

Cited by 7 publications

References 39 publications

Negative autoimmunity in a Spanish pediatric cohort suspected of type 1 diabetes, could it be monogenic diabetes?

Negative autoimmunity in a Spanish pediatric cohort suspected of type 1 diabetes, could it be monogenic diabetes?

Islet autoantibody positivity in an adult population with recently diagnosed diabetes in Uganda

Small RNAs are differentially expressed in autoimmune and non-autoimmune diabetes and controls

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