{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sims EK"],"funding":["NCATS NIH HHS","National Institute of Diabetes and Digestive and Kidney Diseases","NIDDK NIH HHS","Juvenile Diabetes Research Foundation International","John Templeton Foundation"],"pagination":["2283-2291"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10914155"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["66(12)"],"pubmed_abstract":["<h4>Aims/hypothesis</h4>Tractable precision biomarkers to identify immunotherapy responders are lacking in type 1 diabetes. We hypothesised that proinsulin:C-peptide (PI:C) ratios, a readout of beta cell stress, could provide insight into type 1 diabetes progression and responses to immunotherapy.<h4>Methods</h4>In this post hoc analysis, proinsulin and C-peptide levels were determined in baseline serum samples from 63 participants with stage 2 type 1 diabetes in the longitudinal TrialNet Teplizumab Prevention Study (n=41 in the teplizumab arm; n=22 in the placebo arm). In addition, previously tested demographic, C-peptide, glucose and proinsulin data were used for the new data analyses. The ratio of intact (unprocessed) proinsulin to C-peptide was analysed and relationships with progression to stage 3 diabetes were investigated.<h4>Results</h4>Elevated baseline PI:C was strongly associated with more rapid progression of diabetes in both the placebo and teplizumab treatment groups, but teplizumab abrogated the impact of high pre-treatment PI:C on type 1 diabetes progression. Differential responses of drug treatment in those with high vs low PI:C ratios were independent of treatment effects of teplizumab on the PI:C ratio or on relevant immune cells.<h4>Conclusions/interpretation</h4>High pre-treatment PI:C identified individuals with stage 2 type 1 diabetes who were exhibiting rapid progression to stage 3 disease and who displayed benefit from teplizumab treatment. These data suggest that readouts of active disease, such as PI:C ratio, could serve to identify optimal candidates or timing for type 1 diabetes disease-modifying therapies."],"journal":["Diabetologia"],"pubmed_title":["High proinsulin:C-peptide ratio identifies individuals with stage 2 type 1 diabetes at high risk for progression to clinical diagnosis and responses to teplizumab treatment."],"pmcid":["PMC10914155"],"funding_grant_id":["U01 DK061042","R01DK129523","U01 DK085476","U01 DK085453","R01 DK057846","U01 DK085499","UL1 TR001863","U01 DK103180","U01 DK085509","R01DK057846","R01 DK129523","UC4 DK106993","U01 DK106993","U01 DK106994","U01 DK103266","R01 DK133881","R01 DK121929","U01DK127382","U01 DK103282","U01 DK061010","U01 DK085461","U01 DK061034","U01 DK085465","62288","R01 DK121843","P30DK097512","U01 DK085466","U01 DK061058","P30 DK097512","U01 DK085504","SRA-2019-833-S-B","R01DK121929","U01 DK107013","U01 DK107014","UC4 DK097835","U01 DK106984","U01 DK103153","U01 DK127382","R01DK133881"],"pubmed_authors":["Herold KC","Long SA","Geyer SM","Sims EK"],"additional_accession":[]},"is_claimable":false,"name":"High proinsulin:C-peptide ratio identifies individuals with stage 2 type 1 diabetes at high risk for progression to clinical diagnosis and responses to teplizumab treatment.","description":"<h4>Aims/hypothesis</h4>Tractable precision biomarkers to identify immunotherapy responders are lacking in type 1 diabetes. We hypothesised that proinsulin:C-peptide (PI:C) ratios, a readout of beta cell stress, could provide insight into type 1 diabetes progression and responses to immunotherapy.<h4>Methods</h4>In this post hoc analysis, proinsulin and C-peptide levels were determined in baseline serum samples from 63 participants with stage 2 type 1 diabetes in the longitudinal TrialNet Teplizumab Prevention Study (n=41 in the teplizumab arm; n=22 in the placebo arm). In addition, previously tested demographic, C-peptide, glucose and proinsulin data were used for the new data analyses. The ratio of intact (unprocessed) proinsulin to C-peptide was analysed and relationships with progression to stage 3 diabetes were investigated.<h4>Results</h4>Elevated baseline PI:C was strongly associated with more rapid progression of diabetes in both the placebo and teplizumab treatment groups, but teplizumab abrogated the impact of high pre-treatment PI:C on type 1 diabetes progression. Differential responses of drug treatment in those with high vs low PI:C ratios were independent of treatment effects of teplizumab on the PI:C ratio or on relevant immune cells.<h4>Conclusions/interpretation</h4>High pre-treatment PI:C identified individuals with stage 2 type 1 diabetes who were exhibiting rapid progression to stage 3 disease and who displayed benefit from teplizumab treatment. These data suggest that readouts of active disease, such as PI:C ratio, could serve to identify optimal candidates or timing for type 1 diabetes disease-modifying therapies.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Dec","modification":"2026-06-03T00:44:51.745Z","creation":"2025-04-06T15:08:50.184Z"},"accession":"S-EPMC10914155","cross_references":{"pubmed":["37667106"],"doi":["10.1007/s00125-023-06003-5"]}}