liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
Low C-peptide levels and decreased expression of TNF and CD45 in children with high risk of type 1 diabetes
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
2013 (English)In: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 148, no 1Article in journal (Refereed) Published
Abstract [en]

Type 1 diabetes (T1D) patients have numeral and functional defects in peripheral immune cells, but the pre-diabetic period is fairly uncharacterized. Our aim was to analyze expression of immunological markers in T1D high risk children and relate it to clinical/immunological parameters. Children from ABIS (All Babies in Southeast Sweden) with greater than= 2 diabetes related autoantibodies were considered at high risk. Age-matched controls and new-onset T1D patients were included. Expression of genes related to immune cell function and different arms of the immune system was assessed in peripheral blood mononuclear cells using PCR array. Risk children had lower TNF and CD45, and although there were few differences between the groups, expression of many genes differed when comparing children with regard to residual insulin secretion. Hence, expression of immune related genes seemed related not only to the autoimmune process but rather to residual beta-cell function, which was decreased already during the pre-diabetic phase.

Place, publisher, year, edition, pages
Elsevier , 2013. Vol. 148, no 1
Keyword [en]
Type 1 diabetes; Gene expression; PBMC; T1D high risk; T1D autoantibodies; PCR array
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-96458DOI: 10.1016/j.clim.2013.03.011ISI: 000320427300002OAI: diva2:642935
Available from: 2013-08-23 Created: 2013-08-20 Last updated: 2016-10-19
In thesis
1. Aspects of the Pre-Diabetic Period in Type 1 Diabetes
Open this publication in new window or tab >>Aspects of the Pre-Diabetic Period in Type 1 Diabetes
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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 risk-individuals 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.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. 101 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1529
National Category
Endocrinology and Diabetes Neurology Pediatrics Gastroenterology and Hepatology Rheumatology and Autoimmunity Clinical Science
urn:nbn:se:liu:diva-132171 (URN)10.3384/disss.diva-132171 (DOI)9789176857113 (Print) (ISBN)
Public defence
2016-11-18, Hasselquistsalen, Campus US, Linköping, 13:00 (English)
Available from: 2016-10-19 Created: 2016-10-19 Last updated: 2016-10-24Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Åkerman, LindaLudvigsson, JohnnyCasas, Rosaura
By organisation
Division of Clinical SciencesFaculty of Health SciencesDepartment of Paediatrics in Linköping
In the same journal
Clinical Immunology
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 354 hits
ReferencesLink to record
Permanent link

Direct link