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. 2014 Mar 26;9(3):e93053.
doi: 10.1371/journal.pone.0093053. eCollection 2014.

High plasma levels of islet amyloid polypeptide in young with new-onset of type 1 diabetes mellitus

Johan F Paulsson  1 , Johnny Ludvigsson  1 , Annelie Carlsson  2 , Rosaura Casas  1 , Gun Forsander  3 , Sten A Ivarsson  4 , Ingrid Kockum  5 , Åke Lernmark  6 , Claude Marcus  7 , Bengt Lindblad  3 , Gunilla T Westermark  8
Affiliations

High plasma levels of islet amyloid polypeptide in young with new-onset of type 1 diabetes mellitus

Johan F Paulsson et al. PLoS One. .

Abstract

Aims/hypothesis: Islet amyloid polypeptide (IAPP) is a beta cell hormone secreted together with insulin upon glucose stimulation. IAPP participates in normal glucose regulation, but IAPP is also known for its ability to misfold and form islet amyloid. Amyloid fibrils form through smaller cell toxic intermediates and deposited amyloid disrupts normal islet architecture. Even though IAPP and amyloid formation are much discussed in type 2 diabetes, our aim was to study the significance of IAPP in type 1 diabetes.

Results: Plasma IAPP levels in children and adolescents with newly diagnosed type 1 diabetes (n = 224) were analysed and concentrations exceeding 100 pmol/L (127.2-888.7 pmol/L) were found in 11% (25/224). The IAPP increase did not correlate with C-peptide levels.

Conclusions/interpretation: Plasma levels of IAPP and insulin deviate in a subpopulation of young with newly-diagnosed type 1 diabetes. The determined elevated levels of IAPP might increase the risk for IAPP misfolding and formation of cell toxic amyloid in beta cells. This finding add IAPP-aggregation to the list over putative pathological factors causing type 1 diabetes.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Elevated IAPP values in Day1 samples remain elevated in Day 3 samples.
Comparison of IAPP concentrations in plasma taken at diagnosis (day 1) and three days after diagnosis (day 3). Red circles designate day 1 samples and blue circles day 3 samples.
Figure 2
Figure 2. Comparison of IAPP and C-peptide concentrations in plasma from young with newly diagnosed T1D.
Figure 3
Figure 3. There is no correlation between presence of insulin autoantibodies and plasma IAPP concentration.
Analysis of insulin autoantibodies in plasma from children and adolescent newly diagnosed with T1D.
Figure 4
Figure 4. Analysis of autoantibody reactivity against NIAPP, IAPP and IAPPC in plasma from newly diagnosed T1D.
High IAPP values are represented by blue bars and low IAPP values are represented by purple bars.
See this image and copyright information in PMC

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