Sökning: WFRF:(Gottlieb Peter A.) >
C-peptide and metab...
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Taylor, Peter NDepartment of Infection and Immunity, Cardiff University School of Medicine, Cardiff University, Cardiff, UK
(författare)
C-peptide and metabolic outcomes in trials of disease modifying therapy in new-onset type 1 diabetes: an individual participant meta-analysis
- Artikel/kapitelEngelska2023
Förlag, utgivningsår, omfång ...
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Elsevier,2023
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:liu-201566
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-201566URI
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https://doi.org/10.1016/S2213-8587(23)00267-XDOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Background: Metabolic outcomes in type 1 diabetes remain suboptimal. Disease modifying therapy to prevent β-cell loss presents an alternative treatment framework but the effect on metabolic outcomes is unclear. We, therefore, aimed to define the relationship between insulin C-peptide as a marker of β-cell function and metabolic outcomes in new-onset type 1 diabetes.Methods: 21 trials of disease-modifying interventions within 100 days of type 1 diabetes diagnosis comprising 1315 adults (ie, those 18 years and older) and 1396 children (ie, those younger than 18 years) were combined. Endpoints assessed were stimulated area under the curve C-peptide, HbA1c, insulin use, hypoglycaemic events, and composite scores (such as insulin dose adjusted A1c, total daily insulin, U/kg per day, and BETA-2 score). Positive studies were defined as those meeting their primary endpoint. Differences in outcomes between active and control groups were assessed using the Wilcoxon rank test.Findings: 6 months after treatment, a 24·8% greater C-peptide preservation in positive studies was associated with a 0·55% lower HbA1c (p<0·0001), with differences being detectable as early as 3 months. Cross-sectional analysis, combining positive and negative studies, was consistent with this proportionality: a 55% improvement in C-peptide preservation was associated with 0·64% lower HbA1c (p<0·0001). Higher initial C-peptide levels and greater preservation were associated with greater improvement in HbA1c. For HbA1c, IDAAC, and BETA-2 score, sample size predictions indicated that 2-3 times as many participants per group would be required to show a difference at 6 months as compared with C-peptide. Detecting a reduction in hypoglycaemia was affected by reporting methods.Interpretation: Interventions that preserve β-cell function are effective at improving metabolic outcomes in new-onset type 1 diabetes, confirming their potential as adjuncts to insulin. We have shown that improvements in HbA1c are directly proportional to the degree of C-peptide preservation, quantifying this relationship, and supporting the use of C-peptides as a surrogate endpoint in clinical trials.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Collins, Kimberly SCritical Path Institute, Tucson, AZ, USA
(författare)
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Lam, AnnaAlberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada
(författare)
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Karpen, Stephen RCritical Path Institute, Tucson, AZ, USA
(författare)
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Greeno, BriannaCritical Path Institute, Tucson, AZ, USA
(författare)
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Walker, FrankCritical Path Institute, Tucson, AZ, USA
(författare)
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Lozano, AlejandroCritical Path Institute, Tucson, AZ, USA
(författare)
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Atabakhsh, ElnazCritical Path Institute, Tucson, AZ, USA
(författare)
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Ahmed, Simi TThe New York Stem Cell Foundation Research Institute, New York, NY, USA
(författare)
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Marinac, MarjanaJDRF, New York, NY, USA
(författare)
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Latres, EstherJDRF, New York, NY, USA
(författare)
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Senior, Peter AAlberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada
(författare)
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Rigby, MarkCritical Path Institute, Tucson, AZ, USA
(författare)
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Gottlieb, Peter AUniversity of Colorado School of Medicine, Aurora, CO, USA
(författare)
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Dayan, Colin MDepartment of Infection and Immunity, Cardiff University School of Medicine, Cardiff University, Cardiff, UK
(författare)
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Ludvigsson, Johnny,Professor,1943-Linköpings universitet,Avdelningen för barns och kvinnors hälsa,Medicinska fakulteten,Region Östergötland, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus,Trial Outcome Markers Initiative collaboration(Swepub:liu)johlu29
(bidragsgivare)
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Department of Infection and Immunity, Cardiff University School of Medicine, Cardiff University, Cardiff, UKCritical Path Institute, Tucson, AZ, USA
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:The Lancet Diabetes and Endocrinology: Elsevier11:12, s. 915-9252213-85872213-8595
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Taylor, Peter N
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Collins, Kimberl ...
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Lam, Anna
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Karpen, Stephen ...
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Greeno, Brianna
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Walker, Frank
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visa fler...
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Lozano, Alejandr ...
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Atabakhsh, Elnaz
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Ahmed, Simi T
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Marinac, Marjana
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Latres, Esther
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Senior, Peter A
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Rigby, Mark
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Gottlieb, Peter ...
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Dayan, Colin M
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Ludvigsson, John ...
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