Cargando…
The majority of patients with long-duration type 1 diabetes are insulin microsecretors and have functioning beta cells
AIMS/HYPOTHESIS: Classically, type 1 diabetes is thought to proceed to absolute insulin deficiency. Recently developed ultrasensitive assays capable of detecting C-peptide under 5 pmol/l now allow very low levels of C-peptide to be detected in patients with long-standing type 1 diabetes. It is not k...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855529/ https://www.ncbi.nlm.nih.gov/pubmed/24121625 http://dx.doi.org/10.1007/s00125-013-3067-x |
_version_ | 1782294933492727808 |
---|---|
author | Oram, Richard A. Jones, Angus G. Besser, Rachel E. J. Knight, Bridget A. Shields, Beverley M. Brown, Richard J. Hattersley, Andrew T. McDonald, Timothy J. |
author_facet | Oram, Richard A. Jones, Angus G. Besser, Rachel E. J. Knight, Bridget A. Shields, Beverley M. Brown, Richard J. Hattersley, Andrew T. McDonald, Timothy J. |
author_sort | Oram, Richard A. |
collection | PubMed |
description | AIMS/HYPOTHESIS: Classically, type 1 diabetes is thought to proceed to absolute insulin deficiency. Recently developed ultrasensitive assays capable of detecting C-peptide under 5 pmol/l now allow very low levels of C-peptide to be detected in patients with long-standing type 1 diabetes. It is not known whether this low-level endogenous insulin secretion responds to physiological stimuli. We aimed to assess how commonly low-level detectable C-peptide occurs in long-duration type 1 diabetes and whether it responds to a meal stimulus. METHODS: We performed a mixed-meal tolerance test in 74 volunteers with long-duration (>5 years) type 1 diabetes, i.e. with age at diagnosis 16 (9–23) years (median [interquartile range]) and diabetes duration of 30 (19–41) years. We assessed fasting and stimulated serum C-peptide levels using an electrochemiluminescence assay (detection limit 3.3 pmol/l), and also the urinary C-peptide:creatinine ratio (UCPCR). RESULTS: Post-stimulation serum C-peptide was detectable at very low levels (>3.3 pmol/l) in 54 of 74 (73%) patients. In all patients with detectable serum C-peptide, C-peptide either increased (n = 43, 80%) or stayed the same (n = 11) in response to a meal, with no indication of levels falling (p < 0.0001). With increasing disease duration, absolute C-peptide levels fell although the numbers with detectable C-peptide remained high (68%, i.e. 25 of 37 patients with >30 years duration). Similar results were obtained for UCPCR. CONCLUSIONS/INTERPRETATION: Most patients with long-duration type 1 diabetes continue to secrete very low levels of endogenous insulin, which increase after meals. This is consistent with the presence of a small number of still functional beta cells and implies that beta cells are either escaping immune attack or undergoing regeneration. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-013-3067-x) contains peer-reviewed but unedited supplementary material, which is available to authorised users. |
format | Online Article Text |
id | pubmed-3855529 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-38555292013-12-11 The majority of patients with long-duration type 1 diabetes are insulin microsecretors and have functioning beta cells Oram, Richard A. Jones, Angus G. Besser, Rachel E. J. Knight, Bridget A. Shields, Beverley M. Brown, Richard J. Hattersley, Andrew T. McDonald, Timothy J. Diabetologia Article AIMS/HYPOTHESIS: Classically, type 1 diabetes is thought to proceed to absolute insulin deficiency. Recently developed ultrasensitive assays capable of detecting C-peptide under 5 pmol/l now allow very low levels of C-peptide to be detected in patients with long-standing type 1 diabetes. It is not known whether this low-level endogenous insulin secretion responds to physiological stimuli. We aimed to assess how commonly low-level detectable C-peptide occurs in long-duration type 1 diabetes and whether it responds to a meal stimulus. METHODS: We performed a mixed-meal tolerance test in 74 volunteers with long-duration (>5 years) type 1 diabetes, i.e. with age at diagnosis 16 (9–23) years (median [interquartile range]) and diabetes duration of 30 (19–41) years. We assessed fasting and stimulated serum C-peptide levels using an electrochemiluminescence assay (detection limit 3.3 pmol/l), and also the urinary C-peptide:creatinine ratio (UCPCR). RESULTS: Post-stimulation serum C-peptide was detectable at very low levels (>3.3 pmol/l) in 54 of 74 (73%) patients. In all patients with detectable serum C-peptide, C-peptide either increased (n = 43, 80%) or stayed the same (n = 11) in response to a meal, with no indication of levels falling (p < 0.0001). With increasing disease duration, absolute C-peptide levels fell although the numbers with detectable C-peptide remained high (68%, i.e. 25 of 37 patients with >30 years duration). Similar results were obtained for UCPCR. CONCLUSIONS/INTERPRETATION: Most patients with long-duration type 1 diabetes continue to secrete very low levels of endogenous insulin, which increase after meals. This is consistent with the presence of a small number of still functional beta cells and implies that beta cells are either escaping immune attack or undergoing regeneration. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-013-3067-x) contains peer-reviewed but unedited supplementary material, which is available to authorised users. Springer Berlin Heidelberg 2013-10-12 2014 /pmc/articles/PMC3855529/ /pubmed/24121625 http://dx.doi.org/10.1007/s00125-013-3067-x Text en © The Author(s) 2013 https://creativecommons.org/licenses/by/2.0/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Article Oram, Richard A. Jones, Angus G. Besser, Rachel E. J. Knight, Bridget A. Shields, Beverley M. Brown, Richard J. Hattersley, Andrew T. McDonald, Timothy J. The majority of patients with long-duration type 1 diabetes are insulin microsecretors and have functioning beta cells |
title | The majority of patients with long-duration type 1 diabetes are insulin microsecretors and have functioning beta cells |
title_full | The majority of patients with long-duration type 1 diabetes are insulin microsecretors and have functioning beta cells |
title_fullStr | The majority of patients with long-duration type 1 diabetes are insulin microsecretors and have functioning beta cells |
title_full_unstemmed | The majority of patients with long-duration type 1 diabetes are insulin microsecretors and have functioning beta cells |
title_short | The majority of patients with long-duration type 1 diabetes are insulin microsecretors and have functioning beta cells |
title_sort | majority of patients with long-duration type 1 diabetes are insulin microsecretors and have functioning beta cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855529/ https://www.ncbi.nlm.nih.gov/pubmed/24121625 http://dx.doi.org/10.1007/s00125-013-3067-x |
work_keys_str_mv | AT oramricharda themajorityofpatientswithlongdurationtype1diabetesareinsulinmicrosecretorsandhavefunctioningbetacells AT jonesangusg themajorityofpatientswithlongdurationtype1diabetesareinsulinmicrosecretorsandhavefunctioningbetacells AT besserrachelej themajorityofpatientswithlongdurationtype1diabetesareinsulinmicrosecretorsandhavefunctioningbetacells AT knightbridgeta themajorityofpatientswithlongdurationtype1diabetesareinsulinmicrosecretorsandhavefunctioningbetacells AT shieldsbeverleym themajorityofpatientswithlongdurationtype1diabetesareinsulinmicrosecretorsandhavefunctioningbetacells AT brownrichardj themajorityofpatientswithlongdurationtype1diabetesareinsulinmicrosecretorsandhavefunctioningbetacells AT hattersleyandrewt themajorityofpatientswithlongdurationtype1diabetesareinsulinmicrosecretorsandhavefunctioningbetacells AT mcdonaldtimothyj themajorityofpatientswithlongdurationtype1diabetesareinsulinmicrosecretorsandhavefunctioningbetacells AT oramricharda majorityofpatientswithlongdurationtype1diabetesareinsulinmicrosecretorsandhavefunctioningbetacells AT jonesangusg majorityofpatientswithlongdurationtype1diabetesareinsulinmicrosecretorsandhavefunctioningbetacells AT besserrachelej majorityofpatientswithlongdurationtype1diabetesareinsulinmicrosecretorsandhavefunctioningbetacells AT knightbridgeta majorityofpatientswithlongdurationtype1diabetesareinsulinmicrosecretorsandhavefunctioningbetacells AT shieldsbeverleym majorityofpatientswithlongdurationtype1diabetesareinsulinmicrosecretorsandhavefunctioningbetacells AT brownrichardj majorityofpatientswithlongdurationtype1diabetesareinsulinmicrosecretorsandhavefunctioningbetacells AT hattersleyandrewt majorityofpatientswithlongdurationtype1diabetesareinsulinmicrosecretorsandhavefunctioningbetacells AT mcdonaldtimothyj majorityofpatientswithlongdurationtype1diabetesareinsulinmicrosecretorsandhavefunctioningbetacells |