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Hyperproinsulinemia segregates young adult patients with newly diagnosed autoimmune (type 1) and non-autoimmune (type 2) diabetes

Bolinder, J; Fernlund, Per LU ; Borg, Henrik LU ; Arnqvist, HJ; Bjork, E; Blohme, G; Eriksson, JW; Nystrom, L; Ostman, J and Sundkvist, G (2005) In Scandinavian Journal of Clinical & Laboratory Investigation 65(7). p.585-594
Abstract
Objective. To investigate whether measurements of proinsulin and/or intermediate proinsulin degradation products could be used to differentiate between autoimmune (type 1) and non-autoimmune (type 2) diabetes in young adults. Material and methods. Total proinsulin, intact proinsulin and 32,33 split proinsulin concentrations were measured in 25 patients aged 15-34 years with type 1 diabetes, as defined by the presence of at least two positive islet autoantibodies, and in 23 antibody-negative patients of similar age with type 2 diabetes, at the time of clinical onset of diabetes and at 3-4 months thereafter. Comparisons were made with data from 25 healthy subjects matched for gender and age. Results. Plasma levels of total proinsulin, intact... (More)
Objective. To investigate whether measurements of proinsulin and/or intermediate proinsulin degradation products could be used to differentiate between autoimmune (type 1) and non-autoimmune (type 2) diabetes in young adults. Material and methods. Total proinsulin, intact proinsulin and 32,33 split proinsulin concentrations were measured in 25 patients aged 15-34 years with type 1 diabetes, as defined by the presence of at least two positive islet autoantibodies, and in 23 antibody-negative patients of similar age with type 2 diabetes, at the time of clinical onset of diabetes and at 3-4 months thereafter. Comparisons were made with data from 25 healthy subjects matched for gender and age. Results. Plasma levels of total proinsulin, intact proinsulin and 32,33 split proinsulin were significantly increased 2-3-fold in the patients with newly diagnosed type 2 diabetes as compared with the controls, both in absolute terms (p<0.0001) and when related to circulating insulin (p<0.01-0.0002). In contrast, absolute proinsulin and 32,33 split proinsulin concentrations were significantly lower in patients with onset of type 1 diabetes than in controls. When proinsulin and split proinsulin release were related to plasma insulin, however, similar ratios were found in the type 1 diabetes patients and in controls. Using the 90th percentile for total proinsulin in the control group as the cut-off, the sensitivity and specificity for differentiation between autoimmune and non-autoimmune diabetes were 87% and 92%, respectively. At 3-4 months after clinical onset of diabetes, proinsulin secretion was still 2-3 times higher in type 2 than in type 1 diabetes patients (p<0.001). Conclusions. Young adult patients with newly diagnosed type 2 diabetes display disproportionate hyperproinsulinemia, whereas proinsulin secretion appears to be normal in patients with clinical onset of type 1 diabetes. Evaluation of proinsulin and 32,33 split proinsulin concentrations may be useful as a diagnostic tool in differentiating between autoimmune and non-autoimmune diabetes in young adults, particularly in those lacking islet autoantibodies at diagnosis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
IA-2A, diabetes classification, GADA, ICA, split proinsulin
in
Scandinavian Journal of Clinical & Laboratory Investigation
volume
65
issue
7
pages
585 - 594
publisher
Informa Healthcare
external identifiers
  • wos:000233021100008
  • scopus:31544468414
ISSN
1502-7686
DOI
10.1080/00365510500261869
language
English
LU publication?
yes
id
dd3432d7-c019-478d-aa87-f146143b534f (old id 214128)
date added to LUP
2007-08-14 12:50:51
date last changed
2017-03-19 04:08:07
@article{dd3432d7-c019-478d-aa87-f146143b534f,
  abstract     = {Objective. To investigate whether measurements of proinsulin and/or intermediate proinsulin degradation products could be used to differentiate between autoimmune (type 1) and non-autoimmune (type 2) diabetes in young adults. Material and methods. Total proinsulin, intact proinsulin and 32,33 split proinsulin concentrations were measured in 25 patients aged 15-34 years with type 1 diabetes, as defined by the presence of at least two positive islet autoantibodies, and in 23 antibody-negative patients of similar age with type 2 diabetes, at the time of clinical onset of diabetes and at 3-4 months thereafter. Comparisons were made with data from 25 healthy subjects matched for gender and age. Results. Plasma levels of total proinsulin, intact proinsulin and 32,33 split proinsulin were significantly increased 2-3-fold in the patients with newly diagnosed type 2 diabetes as compared with the controls, both in absolute terms (p&lt;0.0001) and when related to circulating insulin (p&lt;0.01-0.0002). In contrast, absolute proinsulin and 32,33 split proinsulin concentrations were significantly lower in patients with onset of type 1 diabetes than in controls. When proinsulin and split proinsulin release were related to plasma insulin, however, similar ratios were found in the type 1 diabetes patients and in controls. Using the 90th percentile for total proinsulin in the control group as the cut-off, the sensitivity and specificity for differentiation between autoimmune and non-autoimmune diabetes were 87% and 92%, respectively. At 3-4 months after clinical onset of diabetes, proinsulin secretion was still 2-3 times higher in type 2 than in type 1 diabetes patients (p&lt;0.001). Conclusions. Young adult patients with newly diagnosed type 2 diabetes display disproportionate hyperproinsulinemia, whereas proinsulin secretion appears to be normal in patients with clinical onset of type 1 diabetes. Evaluation of proinsulin and 32,33 split proinsulin concentrations may be useful as a diagnostic tool in differentiating between autoimmune and non-autoimmune diabetes in young adults, particularly in those lacking islet autoantibodies at diagnosis.},
  author       = {Bolinder, J and Fernlund, Per and Borg, Henrik and Arnqvist, HJ and Bjork, E and Blohme, G and Eriksson, JW and Nystrom, L and Ostman, J and Sundkvist, G},
  issn         = {1502-7686},
  keyword      = {IA-2A,diabetes classification,GADA,ICA,split proinsulin},
  language     = {eng},
  number       = {7},
  pages        = {585--594},
  publisher    = {Informa Healthcare},
  series       = {Scandinavian Journal of Clinical & Laboratory Investigation},
  title        = {Hyperproinsulinemia segregates young adult patients with newly diagnosed autoimmune (type 1) and non-autoimmune (type 2) diabetes},
  url          = {http://dx.doi.org/10.1080/00365510500261869},
  volume       = {65},
  year         = {2005},
}