Proinsulin Secretion Is a Persistent Feature of Type 1 Diabetes

• DOI: 10.2337/dc17-2625
• Publication Date: 2018-12-10T20:05:11Z
• Authors: Emily K. Sims; Henry T. Bahnson; Julius Nyalwidhe; Leena Haataja; Asa K. Davis; Cate Speake; Linda A. DiMeglio; Janice Blum; Margaret A. Morris; Raghavendra G. Mi...; Jerry Nadler; Teresa L. Mastracci; Santica Marcovina; Wei-Jun Qian; Lian Yi; Adam C. Swensen; Michele Yip-Schne...; C. Max Schmidt; Robert V. Considine; Peter Arvan; Carla J. Greenbaum; Carmella Evans-Mo...; ; Steven Willi; Tammy Calvano; Georgeanna Klinge...; Heidi Haro; Ruth Weinstock; Suzan Bzdick; Robin Goland; Ellen Greenberg; Joyce Lee; Ashley Eason; Linda DiMeglio; Stephanie Woerner; Andrew Ahmann; Rebecca Fitch; Kathleen Bethin; Michelle Ecker; Irl Hirsch; Christina Peterson; David Liljenquist; Brandon Robison; Richard Bergenstal; Beth Olson; Eda Cengiz; Amy Steffen; Anne Peters; Perez Hinton; Janet McGill; Lori Buechler; Eva Tsalikian; Joanne Cabbage; Mark Clements; Lois Hester; Davida Kruger; Heather Remtema; Desmond Schatz; Jamie Thomas; William Zipf; Diane Seiple; Henry Rodriguez; Danielle Henson; Jill Simmons; Faith Brendle; Brandon Nathan; Kara Schmid; Kathleen Arnold; Sharon Sellers; David Harlan; Lisa Hubacz; John Buse; Julie Tricome; Michael Rickels; Cornelia Dalton-B...; Leroy Schroeder; Amanda Roark; Amy Potter; Faith Brendle
• Keywords: Proinsulin; C-peptide

OBJECTIVE Abnormally elevated proinsulin secretion has been reported in type 2 and early 1 diabetes when significant C-peptide is present. We questioned whether individuals with long-standing low or absent secretory capacity retained the ability to make proinsulin. RESEARCH DESIGN AND METHODS were measured fasting stimulated sera from 319 subjects (≥3 years) 12 control without diabetes. considered three categories of C-peptide: 1) positive, high values ≥0.2 nmol/L; 2) ≥0.017 but <0.2 3) <0.017 nmol/L. Longitudinal samples analyzed C-peptide–positive after 1, 2, 4 years. RESULTS Of diabetes, 95.9% had detectable serum (>3.1 pmol/L), while 89.9% participants below limit detection (<0.017 n = 99) measurable Proinsulin levels remained stable over years follow-up, decreased slowly during longitudinal analysis. Correlations between mixed-meal stimulation found only (≥0.2 nmol/L). Specifically, increases present group values, no observed among undetectable nmol/L) residual C-peptide. CONCLUSIONS In long-duration secrete persists, even those