IgG4 subclass glutamic acid decarboxylase antibodies (GADA) are associated with a reduced risk of developing type 1 diabetes as well as increased C-peptide levels in GADA positive gestational diabetes

Dereke, Jonatan; Nilsson, Charlotta; Strevens, Helena; Landin‐Olsson, Mona; Hillman, Magnus

doi:10.1016/j.clim.2015.11.001

Cited by 5 publications

(4 citation statements)

References 24 publications

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“…In our study, an increased level of HbA1c correlated well with the increased absolute number of the intermediate subset. The levels of insulin and C-peptide are reliable clinical indicators for the competent function of β-cell 45 . Our data demonstrated that the absolute number of intermediate monocytes was negatively correlated with the concentrations of C-peptide and insulin.…”

Section: Discussionmentioning

confidence: 99%

Increase in Peripheral Blood Intermediate Monocytes is Associated with the Development of Recent-Onset Type 1 Diabetes Mellitus in Children

Ren¹,

Mou²,

Su³

et al. 2017

Int. J. Biol. Sci.

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Monocytes play important roles in antigen presentation and cytokine production to achieve a proper immune response, and are therefore largely implicated in the development and progression of autoimmune diseases. The aim of this study was to analyze the change in the intermediate (CD14+CD16+) monocyte subset in children with recent-onset type 1 diabetes mellitus (T1DM) and its possible association with clinical parameters reflecting islet β-cell dysfunction. Compared with age- and sex-matched healthy controls, intermediate monocytes were expanded in children with T1DM, which was positively associated with hemoglobin A1C and negatively associated with serum insulin and C-peptide. Interestingly, the intermediate monocytes in T1DM patients expressed higher levels of human leukocyte antigen-DR and CD86, suggesting better antigen presentation capability. Further analysis revealed that the frequency of CD45RO+CD4+ memory T cells was increased in the T1DM patients, and the memory T cell content was well correlated with the increase in intermediate monocytes. These results suggest that expanded intermediate monocytes are a predictive factor for the poor residual islet β-cell function in children with recent-onset T1DM.

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Section: Discussionmentioning

confidence: 99%

Increase in Peripheral Blood Intermediate Monocytes is Associated with the Development of Recent-Onset Type 1 Diabetes Mellitus in Children

Ren¹,

Mou²,

Su³

et al. 2017

Int. J. Biol. Sci.

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“…Prevalence of autoantibodies in women with GDM has been previously described in several studies, including our own 6-year follow-up study of the same study population ( 15 ). Most studies have investigated the autoantibodies during pregnancy ( 7 , 11 , 13 , 15 , 17 , 20 , 21 , 23 – 25 ), however, some studies investigated them after pregnancy ( 5 , 14 , 22 ) and one study both during and after the GDM pregnancy ( 12 ). Overall, GADA has been the most frequently assessed autoantibody, however, its prevalence (0-10.8%) and association to the progression to T1DM has varied considerably in different populations ( 5 , 6 , 8 – 10 , 12 , 13 , 19 , 21 , 27 – 32 ), which probably at least partly reflects the differences of β-cell autoimmunity in various ethnic groups.…”

Section: Discussionmentioning

confidence: 99%

Autoantibodies predict type 1 diabetes after gestational diabetes – a 23-year cohort study

Luiro,

Auvinen,

Auvinen

et al. 2023

Front. Endocrinol.

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ObjectiveTo study the predictive value of autoantibodies for type 1 (T1DM) and type 2 (T2DM) diabetes morbidity after gestational diabetes (GDM) in a 23-year follow-up study.DesignProspective population-based cohort study.MethodsWe studied 391 women with GDM, and 391 age- and parity-matched controls, who delivered in 1984–1994. Four autoantibodies were analysed in first-trimester blood samples: islet cell autoantibodies (ICAs), glutamic acid decarboxylase autoantibodies (GADAs), insulin autoantibodies (IAAs) and insulinoma-associated antigen-2 autoantibodies (IA-2As). Two follow-up questionnaires (1995–1996, 2012–2013) were sent to assess development of T1DM and T2DM. Predictive value of autoantibodies and clinical factors were analysed by conditional linear regression and ROC analyses.ResultsSingle autoantibody positivity was detected in 12% (41/342) of the GDM cohort and in 2.3% (8/353) of the control cohort. In the GDM cohort, 2.6% (9/342) tested positive for two autoantibodies and 2.3% (8/342) for three autoantibodies, whereas only one subject in the control cohort had two autoantibodies. ICA positivity was found in 12.5% of the cases, followed by GADA (6.0%), IA-2A (4.9%) and IAA (1.2%). In the control cohort, GADA positivity was found in 1.4%, IA-2A in 0.8%, IAA in 0.6%, and ICA in 0.3% of the subjects. Detection of ICA, GADA and/or IA-2A autoantibodies decreased T1DM-free survival time and time to diagnosis. All subjects with three positive autoantibodies developed T1DM within seven years from the GDM pregnancy. Development of T2DM after GDM occurred independent of autoantibody positivity.ConclusionDevelopment of T1DM can be reliably predicted with GADA and ICA autoantibodies during early pregnancy.

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“…We do not have any data on the presence of antibodies in women who developed diabetes postpartum. Since approximately 1% of women with diabetes postpartum are diagnosed with type 1 diabetes in Sweden [ 44 ], the vast majority of women included in this study were expected to have been diagnosed with type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

Association of single nucleotide polymorphisms with insulin secretion, insulin sensitivity, and diabetes in women with a history of gestational diabetes mellitus

et al. 2021

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Background This study investigated whether single nucleotide polymorphisms (SNPs) reported by previous genome-wide association studies (GWAS) to be associated with impaired insulin secretion, insulin resistance, and/or type 2 diabetes are associated with disposition index, the homeostasis model assessment of insulin resistance (HOMA-IR), and/or development of diabetes following a pregnancy complicated by gestational diabetes mellitus (GDM). Methods Seventy-two SNPs were genotyped in 374 women with previous GDM from Southern Sweden. An oral glucose tolerance test was performed 1–2 years postpartum, although data on the diagnosis of diabetes were accessible up to 5 years postpartum. HOMA-IR and disposition index were used to measure insulin resistance and secretion, respectively. Results The risk A-allele in the rs11708067 polymorphism of the adenylate cyclase 5 gene (ADCY5) was associated with decreased disposition index (beta = − 0.90, SE 0.38, p = 0.019). This polymorphism was an expression quantitative trait loci (eQTL) in islets for both ADCY5 and its antisense transcript. The risk C-allele in the rs2943641 polymorphism, near the insulin receptor substrate 1 gene (IRS1), showed a trend towards association with increased HOMA-IR (beta = 0.36, SE 0.18, p = 0.050), and the T-allele of the rs4607103 polymorphism, near the ADAM metallopeptidase with thrombospondin type 1 motif 9 gene (ADAMTS9), was associated with postpartum diabetes (OR = 2.12, SE 0.22, p = 0.00055). The genetic risk score (GRS) of the top four SNPs tested for association with the disposition index using equal weights was associated with the disposition index (beta = − 0.31, SE = 0.29, p = 0.00096). In addition, the GRS of the four SNPs studied for association with HOMA-IR using equal weights showed an association with HOMA-IR (beta = 1.13, SE = 0.48, p = 9.72874e−11). All analyses were adjusted for age, body mass index, and ethnicity. Conclusions This study demonstrated the genetic susceptibility of women with a history of GDM to impaired insulin secretion and sensitivity and, ultimately, to diabetes development.

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IgG4 subclass glutamic acid decarboxylase antibodies (GADA) are associated with a reduced risk of developing type 1 diabetes as well as increased C-peptide levels in GADA positive gestational diabetes

Cited by 5 publications

References 24 publications

Increase in Peripheral Blood Intermediate Monocytes is Associated with the Development of Recent-Onset Type 1 Diabetes Mellitus in Children

Increase in Peripheral Blood Intermediate Monocytes is Associated with the Development of Recent-Onset Type 1 Diabetes Mellitus in Children

Autoantibodies predict type 1 diabetes after gestational diabetes – a 23-year cohort study

Association of single nucleotide polymorphisms with insulin secretion, insulin sensitivity, and diabetes in women with a history of gestational diabetes mellitus

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