Positivity for Zinc Transporter 8 Autoantibodies at Diagnosis Is Subsequently Associated With Reduced β-Cell Function and Higher Exogenous Insulin Requirement in Children and Adolescents With Type 1 Diabetes

Juusola, Matilda; Parkkola, Anna; Härkönen, Taina; Siljander, Heli; Ilonen, Jorma; Åkerblom, Hans K.; Knip, Mikael

doi:10.2337/dc15-1027

Cited by 31 publications

(31 citation statements)

References 13 publications

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“…Low levels of zinc in drinking water has been associated with high risk of type 1 diabetes [T1D] in children in Finland and England, which was supported by the data from Sardinia Island [2][3][4]. In line with these findings, the presence of an antibody against Zn-transport 8 has been well documented as a diagnostic consideration for T1D [5][6][7]. This may explain the importance of zinc dyshomeostasis, resulting from insufficient dietary intake or genetic causes, in the development of T1D.…”

Section: Introductionmentioning

confidence: 58%

Preventing Diabetes and Diabetic Cardiovascular Diseases with Dietary Zinc

Cai¹

2017

J Microb Biochem Technol

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Section: Introductionmentioning

confidence: 58%

Preventing Diabetes and Diabetic Cardiovascular Diseases with Dietary Zinc

Cai¹

2017

J Microb Biochem Technol

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“…Multiple islet autoantibodies have been reported to be associated with the rapid loss of beta cell function [27]. The detection of TSPAN7A in individuals with LADA increased the number of multiple-antibody-positive individuals detected, raising the question of whether TSPAN7A are associated with the poor beta cell function in individuals with LADA.…”

Section: Discussionmentioning

confidence: 99%

Tetraspanin 7 autoantibodies predict progressive decline of beta cell function in individuals with LADA

et al. 2018

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Aims/hypothesis The aim of this work was to investigate whether tetraspanin 7 autoantibodies (TSPAN7A) are valuable in predicting poor beta cell function in individuals with latent autoimmune diabetes in adults (LADA). Methods The cross-sectional study involved participants with LADA (n = 173), type 1 diabetes (n = 158), type 2 diabetes (n = 204) and healthy control participants (n = 170). The longitudinal study involved 53 participants with LADA, with a 3-year follow-up. In both cohorts, TSPAN7A in the sera were measured by a luciferase immunoprecipitation system assay, and physical and clinical characteristics were recorded. Results The prevalence of TSPAN7A in LADA, type 1 diabetes, type 2 diabetes and healthy control participants was 21.4% (37/ 173), 26% (41/158), 0.5% (1/204) and 1.2% (2/170), respectively. Importantly, measurement of TSPAN7A significantly increased the number of individuals with LADA found to be positive for multiple antibodies (32.4% vs 22%; p < 0.001). Further logistic regression analysis demonstrated that positivity for TSPAN7A (OR 2.87, p = 0.034), disease duration (OR 1.83, p = 0.019) and GAD antibody titre (OR 2.67, p = 0.009) were risk factors for beta cell function in LADA, while BMI (OR 0.34, p = 0.001) was a protective factor. In the prospective study in individuals with LADA, the median annual decrease in rates of fasting C-peptide and 2 h postprandial C-peptide in individuals who were positive for TSPAN7A was significantly higher when compared with the decrease in those who were negative for TSPAN7A (34.6% vs 7.9%, p = 0.043 and 33.2% vs 11%, p = 0.041, respectively). Conclusions/interpretation TSPAN7A are valid islet autoantibodies for use in East Asian populations with autoimmune diabetes and can discriminate individuals with LADA who have lower beta cell function after disease progression.

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“…These results might be influenced by several factors, including the time elapsed between the diagnosis of DM and the clinical evaluation, variations in sensitivity and specificity of the assays, a relatively lower prevalence of autoimmunity in this population,[27] and the lack of measurement of antibodies against ZnT8, a parameter that has been recently reported to be an indicator of autoimmunity. [28]…”

Section: Discussionmentioning

confidence: 99%

Clinical and Metabolic Characteristics among Mexican Children with Different Types of Diabetes Mellitus

Guardado-Mendoza

Rodea-Montero

2016

PLoS ONE

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BackgroundCurrent classification of diabetes mellitus (DM) is based on etiology and includes type 1 (T1DM), type 2 (T2DM), gestational, and other. Clinical and pathophysiological characteristics of T1DM and T2DM in the same patient have been designated as type 1.5 DM (T1.5DM).ObjectivesThe aim of this study was to classify pediatric patients with DM based on pancreatic autoimmunity and the presence or absence of overweight/obesity, and to compare the clinical, anthropometric, and biochemical characteristics between children in the different classes of DM.MethodsA sample of 185 patients, recruited (March 2008-April 2015) as part of the Cohort of Mexican Children with DM (CMC-DM); ClinicalTrials.gov, identifier: NCT02722655. The DM classification was made considering pancreatic autoimmunity (via antibodies GAD-65, IAA, and AICA) and the presence or absence of overweight/obesity. Clinical, anthropometric and biochemical variables, grouped by type of DM were compared (Kruskal-Wallis or chi-squared test).ResultsThe final analysis included 140 children; 18.57% T1ADM, 46.43% T1BDM, 12.14% T1.5DM, and 22.86% T2DM. Fasting C-Peptide (FCP), and hs-CRP levels were higher in T1.5DM and T2DM, and the greatest levels were observed in T1.5DM (p<0.001 and 0.024 respectively).ConclusionsWe clearly identified that the etiologic mechanisms of T1DM and T2DM are not mutually exclusive, and we detailed why FCP levels are not critical for the classification system of DM in children. The findings of this study suggest that T1.5DM should be considered during the classification of pediatric DM and might facilitate more tailored approaches to treatment, clinical care and follow-up.

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Positivity for Zinc Transporter 8 Autoantibodies at Diagnosis Is Subsequently Associated With Reduced β-Cell Function and Higher Exogenous Insulin Requirement in Children and Adolescents With Type 1 Diabetes

Cited by 31 publications

References 13 publications

Preventing Diabetes and Diabetic Cardiovascular Diseases with Dietary Zinc

Preventing Diabetes and Diabetic Cardiovascular Diseases with Dietary Zinc

Tetraspanin 7 autoantibodies predict progressive decline of beta cell function in individuals with LADA

Clinical and Metabolic Characteristics among Mexican Children with Different Types of Diabetes Mellitus

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