C-peptide and metabolic outcomes in trials of disease modifying therapy in new-onset type 1 diabetes: an individual participant meta-analysis

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 funct...

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Veröffentlicht in:The lancet. Diabetes & endocrinology Jg. 11; H. 12; S. 915
Hauptverfasser: Taylor, Peter N, Collins, Kimberly S, Lam, Anna, Karpen, Stephen R, Greeno, Brianna, Walker, Frank, Lozano, Alejandro, Atabakhsh, Elnaz, Ahmed, Simi T, Marinac, Marjana, Latres, Esther, Senior, Peter A, Rigby, Mark, Gottlieb, Peter A, Dayan, Colin M
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England 01.12.2023
Schlagworte:
Adult
C-Peptide - therapeutic use
Child
Cross-Sectional Studies
Diabetes Mellitus, Type 1 - complications
Diabetes Mellitus, Type 1 - drug therapy
Glycated Hemoglobin
Humans
Hypoglycemic Agents - therapeutic use
Insulin - therapeutic use
ISSN:2213-8595, 2213-8595
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Zusammenfassung: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. 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, HbA , insulin use, hypoglycaemic events, and composite scores (such as insulin dose adjusted A , 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. 6 months after treatment, a 24·8% greater C-peptide preservation in positive studies was associated with a 0·55% lower HbA (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 HbA (p<0·0001). Higher initial C-peptide levels and greater preservation were associated with greater improvement in HbA . For HbA , 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. 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 HbA 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. JDRF and Diabetes UK.
Bibliographie:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
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ISSN:2213-8595
2213-8595
DOI:10.1016/S2213-8587(23)00267-X