Proinsulin secretion is a persistent feature of type 1 diabetes

Emily K. Sims, Henry T. Bahnson, Julius Nyalwidhe, Leena Haataja, Asa K. Davis, Cate Speake, Linda DiMeglio, Janice Blum, Margaret A. Morris, Raghu Mirmira, Jerry Nadler, Teresa L. Mastracci, Santica Marcovina, Wei Jun Qian, Lian Yi, Adam C. Swensen, Michele Yip-Schneider, C. Schmidt, Robert Considine, Peter ArvanCarla J. Greenbaum, Carmella Evans-Molina

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)258-264
Number of pages7
JournalDiabetes Care
Volume42
Issue number2
DOIs
StatePublished - Feb 1 2019

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Proinsulin
C-Peptide
Type 1 Diabetes Mellitus
Aptitude
Meals
Serum
Limit of Detection
Fasting

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

Sims, E. K., Bahnson, H. T., Nyalwidhe, J., Haataja, L., Davis, A. K., Speake, C., ... Evans-Molina, C. (2019). Proinsulin secretion is a persistent feature of type 1 diabetes. Diabetes Care, 42(2), 258-264. https://doi.org/10.2337/dc17-2625

Proinsulin secretion is a persistent feature of type 1 diabetes. / Sims, Emily K.; Bahnson, Henry T.; Nyalwidhe, Julius; Haataja, Leena; Davis, Asa K.; Speake, Cate; DiMeglio, Linda; Blum, Janice; Morris, Margaret A.; Mirmira, Raghu; Nadler, Jerry; Mastracci, Teresa L.; Marcovina, Santica; Qian, Wei Jun; Yi, Lian; Swensen, Adam C.; Yip-Schneider, Michele; Schmidt, C.; Considine, Robert; Arvan, Peter; Greenbaum, Carla J.; Evans-Molina, Carmella.

In: Diabetes Care, Vol. 42, No. 2, 01.02.2019, p. 258-264.

Research output: Contribution to journalArticle

Sims, EK, Bahnson, HT, Nyalwidhe, J, Haataja, L, Davis, AK, Speake, C, DiMeglio, L, Blum, J, Morris, MA, Mirmira, R, Nadler, J, Mastracci, TL, Marcovina, S, Qian, WJ, Yi, L, Swensen, AC, Yip-Schneider, M, Schmidt, C, Considine, R, Arvan, P, Greenbaum, CJ & Evans-Molina, C 2019, 'Proinsulin secretion is a persistent feature of type 1 diabetes', Diabetes Care, vol. 42, no. 2, pp. 258-264. https://doi.org/10.2337/dc17-2625
Sims EK, Bahnson HT, Nyalwidhe J, Haataja L, Davis AK, Speake C et al. Proinsulin secretion is a persistent feature of type 1 diabetes. Diabetes Care. 2019 Feb 1;42(2):258-264. https://doi.org/10.2337/dc17-2625
Sims, Emily K. ; Bahnson, Henry T. ; Nyalwidhe, Julius ; Haataja, Leena ; Davis, Asa K. ; Speake, Cate ; DiMeglio, Linda ; Blum, Janice ; Morris, Margaret A. ; Mirmira, Raghu ; Nadler, Jerry ; Mastracci, Teresa L. ; Marcovina, Santica ; Qian, Wei Jun ; Yi, Lian ; Swensen, Adam C. ; Yip-Schneider, Michele ; Schmidt, C. ; Considine, Robert ; Arvan, Peter ; Greenbaum, Carla J. ; Evans-Molina, Carmella. / Proinsulin secretion is a persistent feature of type 1 diabetes. In: Diabetes Care. 2019 ; Vol. 42, No. 2. pp. 258-264.
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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.",
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AU - Sims, Emily K.

AU - Bahnson, Henry T.

AU - Nyalwidhe, Julius

AU - Haataja, Leena

AU - Davis, Asa K.

AU - Speake, Cate

AU - DiMeglio, Linda

AU - Blum, Janice

AU - Morris, Margaret A.

AU - Mirmira, Raghu

AU - Nadler, Jerry

AU - Mastracci, Teresa L.

AU - Marcovina, Santica

AU - Qian, Wei Jun

AU - Yi, Lian

AU - Swensen, Adam C.

AU - Yip-Schneider, Michele

AU - Schmidt, C.

AU - Considine, Robert

AU - Arvan, Peter

AU - Greenbaum, Carla J.

AU - Evans-Molina, Carmella

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N2 - 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.

AB - 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.

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