Evidence map›Paper›PMID 40654035›Full record

ArticleDiabetes, obesity & metabolism2025

Persisting plasma proinsulin levels in a cohort of 482 individuals with long-standing type 1 diabetes mellitus.

Douwe Frank de Wit, Coco Marjolein Fuhri Snethlage, Rana Minab, Elena Rampanelli, Pleun de Groen, Manon Balvers, Timothy James McDonald, Richard A Oram, Bart O Roep, Daniel H van Raalte and 3 more

Abstract read
In one paragraph

Article in Diabetes, obesity & metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Douwe Frank de WitDepartment of Experimental Vascular Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.ORCID 0000-0002-2124-4915
Coco Marjolein Fuhri SnethlageDepartment of Experimental Vascular Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.ORCID 0009-0009-4166-5045
Rana MinabDepartments of Surgery and Pathology and Laboratory Medicine, Centre for Molecular Medicine and Therapeutics, Faculty of Medicine, University of British Columbia, and BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.ORCID 0000-0002-8679-5339
Elena RampanelliDepartment of Experimental Vascular Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.ORCID 0000-0002-7742-0092
Pleun de GroenDepartment of Experimental Vascular Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.ORCID 0009-0008-4604-2755
Manon BalversDepartment of Experimental Vascular Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.ORCID 0000-0003-4094-5087
Timothy James McDonaldPeninsula College of Medicine and Dentistry, Department of Clinical and Biomedical Sciences, University of Exeter, Exeter, UK.ORCID 0000-0003-3559-6660
Richard A OramPeninsula College of Medicine and Dentistry, Department of Clinical and Biomedical Sciences, University of Exeter, Exeter, UK.ORCID 0000-0003-3581-8980
Bart O RoepInternal Medicine, Leids Universitair Medisch Centrum, Leiden, the Netherlands.ORCID 0000-0002-3110-7391
Daniel H van RaalteDepartment of Endocrinology and Metabolism, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands.ORCID 0000-0003-2894-6124
Cameron Bruce VerchereDepartments of Surgery and Pathology and Laboratory Medicine, Centre for Molecular Medicine and Therapeutics, Faculty of Medicine, University of British Columbia, and BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.ORCID 0000-0002-9262-0586
Max NieuwdorpDepartment of Experimental Vascular Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.ORCID 0000-0002-1926-7659
Nordin M J HanssenDepartment of Experimental Vascular Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.ORCID 0000-0001-9541-7244

Funding

Aspasia 015.022.031AUMC StarterCIHR PJT-153156CIHR PJT-185912DON-DFN 2020.10.002Dutch Diabetes FoundationDutch Heart FoundationDutch Kidney Foundation 2021T055ERC 101141346Novo Nordisk Foundation CAMIT 23130NWO VICI 09150182010020NWO VIDI 09150172210019NWO VIDI 09150172210050
6 · The paper itself

Abstract

aimsAs compared with C-peptide, plasma proinsulin levels in individuals with long-standing type 1 diabetes mellitus are relatively understudied, but may serve as a marker of stressed, yet alive β-cells. MATERIALS AND

methodsWe measured proinsulin and C-peptide levels (detection limit <0.15 pmol/L and <0.05 nmol/L, respectively) in a cross-sectional cohort of 482 individuals with type 1 diabetes mellitus and measured associations with diabetes duration, HLA haplotype and autoantibodies.

resultsProinsulin showed a biphasic decline with an initial decrease over 15 years followed by a stabilisation period, whereas C-peptide showed a similar pattern but with an inflection point at ~8 years. Proinsulin and the proinsulin-to-C-peptide ratio did not associate with variables associated with insulin resistance (BMI, triglyceride levels, insulin/day/kg). Higher proinsulin- and C-peptide levels correlated with higher levels of anti-GAD antibodies (Spearman ρ = 0.18 and 0.23 respectively, p < 0.05), but not with anti-IA2. A high-risk DR3/3 HLA genotype associated with complete loss of C-peptide (OR 0.34, 95% CI 0.14-0.79) and proinsulin(OR 0.44, 95% CI 0.20-0.92). CONCLUSIONS/

interpretationIn type 1 diabetes mellitus, proinsulin levels remain detectable long after diagnosis, also in the absence of C-peptide, implying the presence of stressed, yet alive β-cells.

Indexed as

C-PeptideDiabetes Mellitus, Type 1ProinsulinAdultAutoantibodiesBiomarkersCohort StudiesCross-Sectional StudiesFemaleHumansInsulin ResistanceInsulin-Secreting CellsMaleMiddle AgedYoung AdultAutoantibodiesBiomarkersC-PeptideProinsulinautoantibodiesHLA haplotypeproinsulintype 1 diabetes mellitus

Identifiers

PMID40654035
PMCPMC12409225

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.