Impact of disease-modifying therapy on β-cell function and metabolic control in newly diagnosed type 1 diabetes

Type 1 diabetes is an immune-mediated disease and therefore immunotherapy is a potential modality for halting β-cell destruction and attenuating C-peptide loss after the diagnosis of clinical diabetes. From the beginning of this century, a series of intervention trials have been done to assess whether immunotherapy could affect the loss of β-cell function and metabolic control in people with newly diagnosed type 1 diabetes. As part of the Trial Outcome Markers Initiative, Peter Taylor and colleagues 2 Taylor PN Collins KS Lam A et al. C-peptide and metabolic outcomes in trials of disease modifying therapy in new-onset type 1 diabetes: an individual participant meta-analysis. Lancet Diabetes Endocrinol. 2023; (published online Nov 3.)https://doi.org/10.1016/S2213-8587(23)00267-X Summary Full Text Full Text PDF Scopus (1) Google Scholar have now carried out an individual participant meta-analysis of C-peptide and metabolic outcomes in 21 trials of disease-modifying therapy including 1315 adults (ie, those 18 years and older) and 1396 children (ie, those younger than 18 years). The article 2 Taylor PN Collins KS Lam A et al. C-peptide and metabolic outcomes in trials of disease modifying therapy in new-onset type 1 diabetes: an individual participant meta-analysis. Lancet Diabetes Endocrinol. 2023; (published online Nov 3.)https://doi.org/10.1016/S2213-8587(23)00267-X Summary Full Text Full Text PDF Scopus (1) Google Scholar represents a laudable attempt to explore the relationship between C-peptide secretion as an indicator of β-cell function and metabolic outcomes assessed by a series of different measures such as HbA1c, insulin use, hypoglycaemic events, IDAA1c, BETA-2 score, and the Suito index. The authors defined studies meeting their primary endpoint as positive, whereas the remaining trials were considered negative. A 24·8% greater C-peptide preservation was associated with a 0·55% lower HbA1c after treatment for 6 months in the positive studies. The merit of this meta-analysis is based on the observation that the improvement in HbA1c across the first 2 years of clinical disease is directly proportional to the degree of C-peptide preservation. It remains, however, open whether this is a long-term effect, as the difference in HbA1c between those on active treatment and the controls decreased after 12 months of follow-up and there was only a weak significant difference between the two groups at 24 months. Therefore, to show that immunotherapy slows down the loss of β-cell function beyond the first 2 years of clinical disease would be important. It has recently been shown that a considerable proportion of adolescents and adults (ie, those 10 years and older) affected by type 1 diabetes retain some degree of insulin secretion even decades after the diagnosis and that this residual β-cell function is inversely associated with HbA1c, cholesterol, and hypertension. 3 Harsunen M Haukka J Harjutsalo V et al. Residual insulin secretion in individuals with type 1 diabetes in Finland: longitudinal and cross-sectional analyses. Lancet Diabetes Endocrinol. 2023; 11: 465-473 Summary Full Text Full Text PDF PubMed Scopus (4) Google Scholar In addition, residual β-cell function is associated with a reduced risk of nephropathy and retinopathy. C-peptide and metabolic outcomes in trials of disease modifying therapy in new-onset type 1 diabetes: an individual participant meta-analysisInterventions 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. Full-Text PDF Open Access