Elevations in the Fasting Serum Proinsulin–to–C-Peptide Ratio Precede the Onset of Type 1 Diabetes
dc.contributor.author | Sims, Emily K. | |
dc.contributor.author | Chaudhry, Zunaira | |
dc.contributor.author | Watkins, Renecia | |
dc.contributor.author | Syed, Farooq | |
dc.contributor.author | Blum, Janice | |
dc.contributor.author | Ouyang, Fangqian | |
dc.contributor.author | Perkins, Susan M. | |
dc.contributor.author | Mirmira, Raghavendra G. | |
dc.contributor.author | Sosenko, Jay | |
dc.contributor.author | DiMeglio, Linda A. | |
dc.contributor.author | Evans-Molina, Carmella | |
dc.contributor.department | Medicine, School of Medicine | en_US |
dc.date.accessioned | 2018-03-12T16:19:45Z | |
dc.date.available | 2018-03-12T16:19:45Z | |
dc.date.issued | 2016-09 | |
dc.description.abstract | OBJECTIVE We tested whether an elevation in the serum proinsulin–to–C-peptide ratio (PI:C), a biomarker of β-cell endoplasmic reticulum (ER) dysfunction, was associated with progression to type 1 diabetes. RESEARCH DESIGN AND METHODS Fasting total PI and C levels were measured in banked serum samples obtained from TrialNet Pathway to Prevention (PTP) participants, a cohort of autoantibody-positive relatives without diabetes of individuals with type 1 diabetes. Samples were obtained ∼12 months before diabetes onset from PTP progressors in whom diabetes developed (n = 60), and were compared with age-, sex-, and BMI-matched nonprogressors who remained normoglycemic (n = 58). PI:C ratios were calculated as molar ratios and were multiplied by 100% to obtain PI levels as a percentage of C levels. RESULTS Although absolute PI levels did not differ between groups, PI:C ratios were significantly increased in antibody-positive subjects in whom there was progression to diabetes compared with nonprogressors (median 1.81% vs. 1.17%, P = 0.03). The difference between groups was most pronounced in subjects who were ≤10 years old, where the median progressor PI:C ratio was nearly triple that of nonprogressors; 90.0% of subjects in this age group within the upper PI:C quartile progressed to the development of diabetes. Logistic regression analysis, adjusted for age and BMI, demonstrated increased odds of progression for higher natural log PI:C ratio values (odds ratio 1.44, 95% CI 1.02, 2.05). CONCLUSIONS These data suggest that β-cell ER dysfunction precedes type 1 diabetes onset, especially in younger children. Elevations in the serum PI:C ratio may have utility in predicting the onset of type 1 diabetes in the presymptomatic phase. | en_US |
dc.eprint.version | Final published version | en_US |
dc.identifier.citation | Sims, E. K., Chaudhry, Z., Watkins, R., Syed, F., Blum, J., Ouyang, F., … Evans-Molina, C. (2016). Elevations in the Fasting Serum Proinsulin–to–C-Peptide Ratio Precede the Onset of Type 1 Diabetes. Diabetes Care, 39(9), 1519–1526. https://doi.org/10.2337/dc15-2849 | en_US |
dc.identifier.issn | 0149-5992 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/15438 | |
dc.language.iso | en_US | en_US |
dc.publisher | American Diabetes Association | en_US |
dc.relation.isversionof | 10.2337/dc15-2849 | en_US |
dc.relation.journal | Diabetes Care | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | C-peptide | en_US |
dc.subject | proinsulin | en_US |
dc.subject | endoplasmic reticulum dysfunction | en_US |
dc.subject | diabetes | en_US |
dc.subject | presymptomatic phase | en_US |
dc.title | Elevations in the Fasting Serum Proinsulin–to–C-Peptide Ratio Precede the Onset of Type 1 Diabetes | en_US |
dc.type | Article | en_US |
ul.alternative.fulltext | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5001142/ | en_US |