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Proinsulin Secretion Is a Persistent Feature of Type 1 Diabetes

2018; American Diabetes Association; Volume: 42; Issue: 2 Linguagem: Inglês

10.2337/dc17-2625

1935-5548

Emily K. Sims, Henry T. Bahnson, Julius O. Nyalwidhe, Leena Haataja, Asa K. Davis, Cate Speake, Linda A. DiMeglio, Janice S. Blum, Margaret Morris, Raghavendra G. Mirmira, Jerry L. Nadler, Teresa L. Mastracci, Santica M. Marcovina, Weijun Qian, Lian Yi, Adam Swensen, Michele Yip-Schneider, C. Schmidt, Robert V. Considine, Peter Arvan, Carla J. Greenbaum, Carmella Evans‐Molina, Steven M. Willi, Tammy Calvano, Georgeanna J. Klingensmith, Heidi Haro, Ruth S. Weinstock, Suzan Bzdick, Robin Goland, Ellen Greenberg, Joyce Lee, Ashley Eason, Linda A. DiMeglio, Stephanie L. Woerner, Andrew Ahmann, Rebecca Fitch, Kathleen E. Bethin, Michelle Ecker, Irl B. Hirsch, Christina Peterson, David R. Liljenquist, Brandon Robison, Richard M. Bergenstal, Beth A. Olson, Eda Cengiz, Amy Steffen, Anne L. Peters, Perez Hinton, Janet B. McGill, Lori Buechler, Eva Tsalikian, Joanne Cabbage, Mark A. Clements, Lois Hester, Davida F. Kruger, Heather Remtema, Desmond Schatz, Jamie Thomas, William B. Zipf, Diane Seiple, Henry Rodriguez, Danielle Henson, Jill H. Simmons, Faith Brendle, Brandon M. Nathan, Kara Schmid, Kathleen Arnold, Sharon Sellers, David M. Harlan, Lisa Hubacz, John B. Buse, Julie Tricome, Michael R. Rickels, Cornelia Dalton-Bakes, Leroy Schroeder, Amanda Roark, Amy Potter, Faith Brendle,

Diabetes Management and Research

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.