Type 1 diabetes patients born to immigrants to Sweden increase their native diabetes risk and differ from Swedish patients in HLA types and islet autoantibodies

Delli, Ahmed J.; Lindblad, Bengt; Carlsson, Annelie; Forsander, Gun; Ivarsson, Sten-A.; Ludvigsson, Johnny; Marcus, Claude; Lernmark, Åke

doi:10.1111/j.1399-5448.2010.00637.x

Cited by 52 publications

(67 citation statements)

References 37 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Patients-Serum samples were from 304 (54% male) patients with newly diagnosed T1D in the Better Diabetes Diagnosis study (10,35). Patient sera were selected at random to represent one group of 152 patients with clinical onset at 1-5 years of age and another group of 152 patients at 15-18 years of age ( Table 1).…”

Section: Methodsmentioning

confidence: 99%

“…Patient sera were selected at random to represent one group of 152 patients with clinical onset at 1-5 years of age and another group of 152 patients at 15-18 years of age ( Table 1). The classification of diabetes was clinically confirmed 6 months after onset with T1D (10,35). HLA-DQ typing and analyses of islet autoantibodies against GAD65, insulin, IA-2, and ZnT8 (Table 1) were described in detail elsewhere (28,35).…”

Section: Methodsmentioning

confidence: 99%

“…Insulin autoantibodies (IAA) may be the first islet autoantibodies to appear (8,9). However, it is the least frequent (10) as IAA are particularly common in patients at a younger age of diagnosis (11). Persistent IAA in combination with any other islet autoantibody predicts T1D (12).…”

Section: Type 1 Diabetes (T1d)mentioning

confidence: 99%

See 2 more Smart Citations

Autoimmunity against INS-IGF2 Protein Expressed in Human Pancreatic Islets*

Kanatsuna

Taneera

Vaziri-Sani

et al. 2013

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background: Islet INS-IGF2 was examined as a possible autoantigen in type 1 diabetes. Results: INS-IGF2 expression was inversely related to donor HbA1c and glucose-stimulated insulin release. Autoantibodies doubly reactive with INS-IGF2 and insulin were more common in patients with type 1 diabetes than controls. Conclusion: INS-IGF2 is recognized by autoantibodies in type 1 diabetes. Significance: Autoantibodies doubly reactive with both INS-IGF2 and insulin may contribute to type 1 diabetes.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Autoimmunity against INS-IGF2 Protein Expressed in Human Pancreatic Islets*

Kanatsuna

Taneera

Vaziri-Sani

et al. 2013

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…This is very much consistent with T1D being an autoimmune disease, and the number of genes involved in T1D pathogenesis highlights the complex interplay in which multiple pathways may be essential for developing autoimmunity. Very high and high risk HLA alleles are more prevalent among Swedish children with T1D, while moderate and low risk alleles are more common among immigrants with T1D in Sweden, illustrating differences in genetic risk depending on ethnicity [22].…”

Section: Genetic Risk Factorsmentioning

confidence: 99%

Regin in Blood Immune Regulation in Type 1 Diabetes

Pihl¹

2013

View full text Add to dashboard Cite

Type 1 Diabetes (T1D) is an autoimmune disease resulting in insulin deficiency as a result of autoimmune destruction of pancreatic β-cells. Preserving β-cell function in patients with T1D would be of great benefit since patients with sustained endogenous insulin secretion are known to suffer less from secondary complications due to hyperglycemia. Glutamic acid decarboxylase 65 (GAD 65 ) is a major autoantigen targeted by self-reactive lymphocytes in T1D, and has been used in several attempts at treating T1D by inducing tolerance to β-cell antigens. We showed positive clinical effects of GAD 65 formulated with aluminium hydroxide (GAD-alum) on preservation of C-peptide secretion in a phase II clinical trial. Unfortunately, a phase III clinical trial in a larger population failed to confirm this finding. Regulatory T cells (Treg) are instrumental in maintaining peripheral tolerance to self-antigens. Deficiencies in Treg function are thought to influence the pathogenesis of autoimmune diseases, including T1D. One proposed mechanism of achieving tolerance to β-cell antigens in T1D is the induction of antigen-specific Treg through immunomodulation. The general aim of this thesis was to study immune regulation in T1D, the role of Treg and immunomodulatory effects of GAD-alum treatment in particular. Our hypothesis was that Treg biology is altered in T1D and pre-diabetes, and that an induction of GAD 65 -specific Treg contributes to the clinical efficacy of GAD-alum treatment. We demonstrated that T cells expressing Treg-associated markers were increased in number in patients with recent-onset T1D, as well as in children with high risk of developing T1D. We found that antigen recall 4 years after GAD-alum treatment induced cells with both regulatory and effector phenotypes in GAD-alum treated patients. Furthermore there was no effect on Treg-mediated suppression in GAD-alum treated patients, while patients with T1D, regardless of treatment, exhibited deficient Treg-mediated suppression of Teff that was intrinsic to the Treg population. We followed patients participating in a phase III trial of GAD-alum, and using an extended antibody panel we risk, but found no effects of variant alleles on the risk of developing T1D, or on the efficacy of GAD-alum treatment. We show small effects on C-peptide secretion and autoantibody positivity in patients with T1D. In conclusion, we find that while Treg are deficient in patients with T1D, induction of Treg is an unlikely mechanism of action of GAD-alum treatment. SUPERVISOR

show abstract

“…The incidence increases in the migrating population, reaching rates close to those observed within the indigenous population. It has also been shown in Sweden that immigrant patients appear more prone to develop T1D when they were born and live in Sweden [39].…”

Section: Environmental Risk Factorsmentioning

confidence: 99%

Aspects of the Pre-Diabetic Perios in Type 1 Diabetes

Åkerman¹

View full text Add to dashboard Cite

Type 1 diabetes (T1D) is an autoimmune disease characterized by insulin deficiency, due to immune-mediated destruction of beta cells. Current knowledge regarding the period preceding disease onset comes, to a large extent, from studying risk cohorts based on relatives of T1D-patients, as they have an increased disease risk. Among T1D patients in general, however, few have the disease in their immediate family. It is therefore important to study risk cohorts from the general population as well. An ongoing autoimmune reaction can often be seen in the blood long before disease onset, by detection of autoantibodies directed towards beta cell antigens. By autoantibody screening among participants in the ABIS (All Babies in the South-east of Sweden) cohort, we could identify a group of children from the general population with increased risk for T1D, positive for multiple autoantibodies. They were enrolled in a 2-year prospective follow-up aiming to characterize the prediabetic period and to identify factors indicative of progression/non-progression to T1D. We assessed glucose homeostasis and autoantibody titers over time, and searched for risk-biomarkers by analyzing the expression of immune-related genes (Th1-Th2-Th3) in peripheral blood mononuclear cells (PBMC) from these children, in comparison to healthy children and newly diagnosed T1D patients. In the same groups we also compared serum micro RNA (miRNA) profiles, knowing that miRNA molecules have desirable biomarker properties. We found that two specific autoantibodies, IA2A and ZnT8A, were detected at higher concentrations in riskindividuals who progressed to overt T1D during or after the follow-up period, compared to those who still have not. We also observed disturbed glucose homeostasis long before onset in the progressors, but it was seen among those who remain symptom free as well. Further, we found support for the possible role of insulin resistance as an accelerator of the disease process. For gene expression and serum miRNA, few differences were observed between risk-individuals and healthy children overall. However, for PBMC gene expression and serum miRNA both, there were associations to beta cell function and glucose homeostasis, and for miRNA also to islet autoantibodies. Although specific profiles for prediction of disease onset or identification of risk-individuals could not be found, these results are interesting and deserve to be evaluated further. As part of another sub-study within ABIS, the effects of physical activity on glucose homeostasis were assessed in healthy schoolchildren.The level of physical activity, measured by pedometers, was related to insulin resistance and beta cell-stress, and decreased physical activity was associated with increased insulin resistance and load on the insulin-producing beta cells, already at school-age.

show abstract

Type 1 diabetes patients born to immigrants to Sweden increase their native diabetes risk and differ from Swedish patients in HLA types and islet autoantibodies

Abstract: Patients born to parents who had immigrated to the high T1DM incidence environment of Sweden have, compared with Swedish patients, more frequent HLA-DQ2 genetic markers and are diagnosed more often with GAD65Ab.

Cited by 52 publications

References 37 publications

Autoimmunity against INS-IGF2 Protein Expressed in Human Pancreatic Islets*

Autoimmunity against INS-IGF2 Protein Expressed in Human Pancreatic Islets*

Regin in Blood Immune Regulation in Type 1 Diabetes

Aspects of the Pre-Diabetic Perios in Type 1 Diabetes

Contact Info

Product

Resources

About