Proinsulin Secretion Is a Persistent Feature of Type 1 Diabetes
dc.contributor.author | Sims, Emily K. | |
dc.contributor.author | Bahnson, Henry T. | |
dc.contributor.author | Nyalwidhe, Julius | |
dc.contributor.author | Haataja, Leena | |
dc.contributor.author | Davis, Asa K. | |
dc.contributor.author | Speake, Cate | |
dc.contributor.author | DiMeglio, Linda A. | |
dc.contributor.author | Blum, Janice | |
dc.contributor.author | Morris, Margaret A. | |
dc.contributor.author | Mirmira, Raghavendra G. | |
dc.contributor.author | Nadler, Jerry | |
dc.contributor.author | Mastracci, Teresa L. | |
dc.contributor.author | Marcovina, Santica | |
dc.contributor.author | Qian, Wei-Jun | |
dc.contributor.author | Yi, Lian | |
dc.contributor.author | Swensen, Adam C. | |
dc.contributor.author | Yip-Schneider, Michele | |
dc.contributor.author | Schmidt, C. Max | |
dc.contributor.author | Considine, Robert V. | |
dc.contributor.author | Arvan, Peter | |
dc.contributor.author | Greenbaum, Carla J. | |
dc.contributor.author | Evans-Molina, Carmella | |
dc.contributor.author | T1D Exchange Residual C-peptide Study Group | |
dc.contributor.department | Pediatrics, School of Medicine | en_US |
dc.date.accessioned | 2020-04-13T19:15:49Z | |
dc.date.available | 2020-04-13T19:15:49Z | |
dc.date.issued | 2019-02 | |
dc.description.abstract | OBJECTIVE: Abnormally elevated proinsulin secretion has been reported in type 2 and early type 1 diabetes when significant C-peptide is present. We questioned whether individuals with long-standing type 1 diabetes and low or absent C-peptide secretory capacity retained the ability to make proinsulin. RESEARCH DESIGN AND METHODS: C-peptide and proinsulin were measured in fasting and stimulated sera from 319 subjects with long-standing type 1 diabetes (≥3 years) and 12 control subjects without diabetes. We considered three categories of stimulated C-peptide: 1) C-peptide positive, with high stimulated values ≥0.2 nmol/L; 2) C-peptide positive, with low stimulated values ≥0.017 but <0.2 nmol/L; and 3) C-peptide <0.017 nmol/L. Longitudinal samples were analyzed from C-peptide-positive subjects with diabetes after 1, 2, and 4 years. RESULTS: Of individuals with long-standing type 1 diabetes, 95.9% had detectable serum proinsulin (>3.1 pmol/L), while 89.9% of participants with stimulated C-peptide values below the limit of detection (<0.017 nmol/L; n = 99) had measurable proinsulin. Proinsulin levels remained stable over 4 years of follow-up, while C-peptide decreased slowly during longitudinal analysis. Correlations between proinsulin with C-peptide and mixed-meal stimulation of proinsulin were found only in subjects with high stimulated C-peptide values (≥0.2 nmol/L). Specifically, increases in proinsulin with mixed-meal stimulation were present only in the group with high stimulated C-peptide values, with no increases observed among subjects with low or undetectable (<0.017 nmol/L) residual C-peptide. CONCLUSIONS: In individuals with long-duration type 1 diabetes, the ability to secrete proinsulin persists, even in those with undetectable serum C-peptide. | en_US |
dc.eprint.version | Final published version | en_US |
dc.identifier.citation | Sims, E. K., Bahnson, H. T., Nyalwidhe, J., Haataja, L., Davis, A. K., Speake, C., DiMeglio, L. A., Blum, J., Morris, M. A., Mirmira, R. G., Nadler, J., Mastracci, T. L., Marcovina, S., Qian, W. J., Yi, L., Swensen, A. C., Yip-Schneider, M., Schmidt, C. M., Considine, R. V., Arvan, P., … T1D Exchange Residual C-peptide Study Group (2019). Proinsulin Secretion Is a Persistent Feature of Type 1 Diabetes. Diabetes care, 42(2), 258–264. https://doi.org/10.2337/dc17-2625 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/22558 | |
dc.language.iso | en_US | en_US |
dc.publisher | American Diabetes Association | en_US |
dc.relation.isversionof | 10.2337/dc17-2625 | 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 | Cohort Studies | en_US |
dc.subject | Diabetes Mellitus, Type 1 | en_US |
dc.subject | Fasting | en_US |
dc.subject | Insulin | en_US |
dc.subject | Meals | en_US |
dc.subject | Proinsulin | en_US |
dc.subject | Time Factors | en_US |
dc.title | Proinsulin Secretion Is a Persistent Feature of Type 1 Diabetes | en_US |
dc.type | Article | en_US |
ul.alternative.fulltext | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341288/ | en_US |