PMID- 30412637 OWN - NLM STAT- MEDLINE DCOM- 20190415 LR - 20190415 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 13 IP - 11 DP - 2018 TI - Comparison of proinsulin and C-peptide secretion in healthy versus long-standing type 1 diabetes mellitus cohorts: A pilot study. PG - e0207065 LID - 10.1371/journal.pone.0207065 [doi] LID - e0207065 AB - AIMS: Increased proinsulin (PI) compared to C-peptide (CP) concentrations have been reported, both prior to type 1 diabetes mellitus (T1D) onset, as well as early in disease. In this pilot study, we sought to define the normal PI secretion in a healthy cohort and compare this to a local T1D cohort and a separate well-defined nationally representative T1D cohort with measurable CP. METHODS: Thirteen healthy subjects and 12 T1D subjects with T1D >3 years from the local T1D cohort completed mixed meal tolerance tests (MMTT) with PI and CP measured over 90 and 240 minutes. The change in CP (maximum versus baseline, DeltaCP) during MMTT in the T1D Exchange T1D cohort was stratified according to non-fasting PI concentrations, based on a fasting PI threshold, as defined by the healthy control group. RESULTS: The maximum fasting PI in the control group was 6 pmol/L. Individuals from the T1D Exchange with a non-fasting PI >/= 6 pmol/L had a lower DeltaCP during a MMTT, compared to those with a PI < 6 pmol/L. While only three individuals from the local T1D cohort had measurable CP and PI during the MMTT, those with a greater DeltaCP had lower PI secretion. CONCLUSION: While all T1D subjects from the T1D Exchange secreted measurable non-fasting PI, those with a greater non-fasting PI demonstrated a decrease in DeltaCP during the MMTT. PI may be preferentially secreted compared to CP in some individuals with long standing T1D. FAU - Sullivan, Catherine A AU - Sullivan CA AUID- ORCID: 0000-0003-1035-5828 AD - Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, Boston, MA, United States of America. FAU - Cacicedo, Jose M AU - Cacicedo JM AD - Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, Boston, MA, United States of America. FAU - Rajendran, Iniya AU - Rajendran I AD - School of Public Health, Boston University, Boston, MA, United States of America. FAU - Steenkamp, Devin W AU - Steenkamp DW AD - Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, Boston, MA, United States of America. LA - eng GR - UL1 TR001430/TR/NCATS NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20181109 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Blood Glucose) RN - 0 (C-Peptide) RN - 9035-68-1 (Proinsulin) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Blood Glucose/metabolism MH - C-Peptide/*metabolism MH - Case-Control Studies MH - Cohort Studies MH - Diabetes Mellitus, Type 1/*metabolism MH - Female MH - Humans MH - Male MH - Middle Aged MH - Pilot Projects MH - Proinsulin/*metabolism MH - Young Adult PMC - PMC6226191 COIS- The authors have declared that no competing interests exist. EDAT- 2018/11/10 06:00 MHDA- 2019/04/16 06:00 PMCR- 2018/11/09 CRDT- 2018/11/10 06:00 PHST- 2018/09/07 00:00 [received] PHST- 2018/10/24 00:00 [accepted] PHST- 2018/11/10 06:00 [entrez] PHST- 2018/11/10 06:00 [pubmed] PHST- 2019/04/16 06:00 [medline] PHST- 2018/11/09 00:00 [pmc-release] AID - PONE-D-18-26317 [pii] AID - 10.1371/journal.pone.0207065 [doi] PST - epublish SO - PLoS One. 2018 Nov 9;13(11):e0207065. doi: 10.1371/journal.pone.0207065. eCollection 2018.