Proinsulin, GLP-1, and glucagon are associated with partial remission in children and adolescents with newly diagnosed type 1 diabetes

A. Kaas, M. L. M. Andersen, Siri Fredheim, P. Hougaard, K. Buschard, J. S. Petersen, C. de Beaufort, K. J. Robertson, L. Hansen, H. B. Mortensen, L. B. Nielsen, Diabe Hvidoere Study Grp Childhood

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    Resumé

    Objective: Proinsulin is a marker of beta-cell distress and dysfunction in type 2 diabetes and transplanted islets. Proinsulin levels are elevated in patients newly diagnosed with type 1 diabetes. Our aim was to assess the relationship between proinsulin, insulin dose-adjusted haemoglobin A1c (IDAA1C), glucagon-like peptide-1 (GLP-1), glucagon, and remission status the first year after diagnosis of type 1 diabetes. Methods: Juvenile patients (n = 275) were followed 1, 6, and 12 months after diagnosis. At each visit, partial remission was defined as IDAA1C = 9%. The patients had a liquid meal test at the 1-, 6-, and 12-month visits, which included measurement of C-peptide, proinsulin, GLP-1, glucagon, and insulin antibodies (IA). Results: Patients in remission at 6 and 12 months had significantly higher levels of proinsulin compared to non-remitting patients (p <0.0001, p = 0.0002). An inverse association between proinsulin and IDAA1C was found at 1 and 6 months (p = 0.0008, p = 0.0022). Proinsulin was positively associated with C-peptide (p <0.0001) and IA (p = 0.0024, p = 0.0068, p <0.0001) at 1, 6, and 12 months. Glucagon (p <0.0001 and p <0.02) as well as GLP-1 (p = 0.0001 and p = 0.002) were significantly lower in remitters than in non-remitters at 6 and 12 months. Proinsulin associated positively with GLP-1 at 1 month (p = 0.004) and negatively at 6 (p = 0.002) and 12 months (p = 0.0002). Conclusions: In type 1 diabetes, patients in partial remission have higher levels of proinsulin together with lower levels of GLP-1 and glucagon compared to patients not in remission. In new onset type 1 diabetes proinsulin level may be a sign of better residual beta-cell function.
    OriginalsprogEngelsk
    TidsskriftPediatric Diabetes
    Vol/bind13
    Udgave nummer1
    Sider (fra-til)51-58
    Antal sider8
    ISSN1399-543X
    DOI
    StatusUdgivet - 2012

    Citer dette

    Kaas, A. ; Andersen, M. L. M. ; Fredheim, Siri ; Hougaard, P. ; Buschard, K. ; Petersen, J. S. ; de Beaufort, C. ; Robertson, K. J. ; Hansen, L. ; Mortensen, H. B. ; Nielsen, L. B. ; Hvidoere Study Grp Childhood, Diabe. / Proinsulin, GLP-1, and glucagon are associated with partial remission in children and adolescents with newly diagnosed type 1 diabetes. I: Pediatric Diabetes. 2012 ; Bind 13, Nr. 1. s. 51-58.
    @article{dc8f46e34e4242efb9d1e1c80411b1ce,
    title = "Proinsulin, GLP-1, and glucagon are associated with partial remission in children and adolescents with newly diagnosed type 1 diabetes",
    abstract = "Objective: Proinsulin is a marker of beta-cell distress and dysfunction in type 2 diabetes and transplanted islets. Proinsulin levels are elevated in patients newly diagnosed with type 1 diabetes. Our aim was to assess the relationship between proinsulin, insulin dose-adjusted haemoglobin A1c (IDAA1C), glucagon-like peptide-1 (GLP-1), glucagon, and remission status the first year after diagnosis of type 1 diabetes. Methods: Juvenile patients (n = 275) were followed 1, 6, and 12 months after diagnosis. At each visit, partial remission was defined as IDAA1C = 9{\%}. The patients had a liquid meal test at the 1-, 6-, and 12-month visits, which included measurement of C-peptide, proinsulin, GLP-1, glucagon, and insulin antibodies (IA). Results: Patients in remission at 6 and 12 months had significantly higher levels of proinsulin compared to non-remitting patients (p <0.0001, p = 0.0002). An inverse association between proinsulin and IDAA1C was found at 1 and 6 months (p = 0.0008, p = 0.0022). Proinsulin was positively associated with C-peptide (p <0.0001) and IA (p = 0.0024, p = 0.0068, p <0.0001) at 1, 6, and 12 months. Glucagon (p <0.0001 and p <0.02) as well as GLP-1 (p = 0.0001 and p = 0.002) were significantly lower in remitters than in non-remitters at 6 and 12 months. Proinsulin associated positively with GLP-1 at 1 month (p = 0.004) and negatively at 6 (p = 0.002) and 12 months (p = 0.0002). Conclusions: In type 1 diabetes, patients in partial remission have higher levels of proinsulin together with lower levels of GLP-1 and glucagon compared to patients not in remission. In new onset type 1 diabetes proinsulin level may be a sign of better residual beta-cell function.",
    author = "A. Kaas and Andersen, {M. L. M.} and Siri Fredheim and P. Hougaard and K. Buschard and Petersen, {J. S.} and {de Beaufort}, C. and Robertson, {K. J.} and L. Hansen and Mortensen, {H. B.} and Nielsen, {L. B.} and {Hvidoere Study Grp Childhood}, Diabe",
    year = "2012",
    doi = "10.1111/j.1399-5448.2011.00812.x",
    language = "English",
    volume = "13",
    pages = "51--58",
    journal = "Pediatric Diabetes",
    issn = "1399-543X",
    publisher = "Wiley-Blackwell Munksgaard",
    number = "1",

    }

    Kaas, A, Andersen, MLM, Fredheim, S, Hougaard, P, Buschard, K, Petersen, JS, de Beaufort, C, Robertson, KJ, Hansen, L, Mortensen, HB, Nielsen, LB & Hvidoere Study Grp Childhood, D 2012, 'Proinsulin, GLP-1, and glucagon are associated with partial remission in children and adolescents with newly diagnosed type 1 diabetes', Pediatric Diabetes, bind 13, nr. 1, s. 51-58. https://doi.org/10.1111/j.1399-5448.2011.00812.x

    Proinsulin, GLP-1, and glucagon are associated with partial remission in children and adolescents with newly diagnosed type 1 diabetes. / Kaas, A.; Andersen, M. L. M.; Fredheim, Siri; Hougaard, P.; Buschard, K.; Petersen, J. S.; de Beaufort, C.; Robertson, K. J.; Hansen, L.; Mortensen, H. B.; Nielsen, L. B.; Hvidoere Study Grp Childhood, Diabe.

    I: Pediatric Diabetes, Bind 13, Nr. 1, 2012, s. 51-58.

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    TY - JOUR

    T1 - Proinsulin, GLP-1, and glucagon are associated with partial remission in children and adolescents with newly diagnosed type 1 diabetes

    AU - Kaas, A.

    AU - Andersen, M. L. M.

    AU - Fredheim, Siri

    AU - Hougaard, P.

    AU - Buschard, K.

    AU - Petersen, J. S.

    AU - de Beaufort, C.

    AU - Robertson, K. J.

    AU - Hansen, L.

    AU - Mortensen, H. B.

    AU - Nielsen, L. B.

    AU - Hvidoere Study Grp Childhood, Diabe

    PY - 2012

    Y1 - 2012

    N2 - Objective: Proinsulin is a marker of beta-cell distress and dysfunction in type 2 diabetes and transplanted islets. Proinsulin levels are elevated in patients newly diagnosed with type 1 diabetes. Our aim was to assess the relationship between proinsulin, insulin dose-adjusted haemoglobin A1c (IDAA1C), glucagon-like peptide-1 (GLP-1), glucagon, and remission status the first year after diagnosis of type 1 diabetes. Methods: Juvenile patients (n = 275) were followed 1, 6, and 12 months after diagnosis. At each visit, partial remission was defined as IDAA1C = 9%. The patients had a liquid meal test at the 1-, 6-, and 12-month visits, which included measurement of C-peptide, proinsulin, GLP-1, glucagon, and insulin antibodies (IA). Results: Patients in remission at 6 and 12 months had significantly higher levels of proinsulin compared to non-remitting patients (p <0.0001, p = 0.0002). An inverse association between proinsulin and IDAA1C was found at 1 and 6 months (p = 0.0008, p = 0.0022). Proinsulin was positively associated with C-peptide (p <0.0001) and IA (p = 0.0024, p = 0.0068, p <0.0001) at 1, 6, and 12 months. Glucagon (p <0.0001 and p <0.02) as well as GLP-1 (p = 0.0001 and p = 0.002) were significantly lower in remitters than in non-remitters at 6 and 12 months. Proinsulin associated positively with GLP-1 at 1 month (p = 0.004) and negatively at 6 (p = 0.002) and 12 months (p = 0.0002). Conclusions: In type 1 diabetes, patients in partial remission have higher levels of proinsulin together with lower levels of GLP-1 and glucagon compared to patients not in remission. In new onset type 1 diabetes proinsulin level may be a sign of better residual beta-cell function.

    AB - Objective: Proinsulin is a marker of beta-cell distress and dysfunction in type 2 diabetes and transplanted islets. Proinsulin levels are elevated in patients newly diagnosed with type 1 diabetes. Our aim was to assess the relationship between proinsulin, insulin dose-adjusted haemoglobin A1c (IDAA1C), glucagon-like peptide-1 (GLP-1), glucagon, and remission status the first year after diagnosis of type 1 diabetes. Methods: Juvenile patients (n = 275) were followed 1, 6, and 12 months after diagnosis. At each visit, partial remission was defined as IDAA1C = 9%. The patients had a liquid meal test at the 1-, 6-, and 12-month visits, which included measurement of C-peptide, proinsulin, GLP-1, glucagon, and insulin antibodies (IA). Results: Patients in remission at 6 and 12 months had significantly higher levels of proinsulin compared to non-remitting patients (p <0.0001, p = 0.0002). An inverse association between proinsulin and IDAA1C was found at 1 and 6 months (p = 0.0008, p = 0.0022). Proinsulin was positively associated with C-peptide (p <0.0001) and IA (p = 0.0024, p = 0.0068, p <0.0001) at 1, 6, and 12 months. Glucagon (p <0.0001 and p <0.02) as well as GLP-1 (p = 0.0001 and p = 0.002) were significantly lower in remitters than in non-remitters at 6 and 12 months. Proinsulin associated positively with GLP-1 at 1 month (p = 0.004) and negatively at 6 (p = 0.002) and 12 months (p = 0.0002). Conclusions: In type 1 diabetes, patients in partial remission have higher levels of proinsulin together with lower levels of GLP-1 and glucagon compared to patients not in remission. In new onset type 1 diabetes proinsulin level may be a sign of better residual beta-cell function.

    U2 - 10.1111/j.1399-5448.2011.00812.x

    DO - 10.1111/j.1399-5448.2011.00812.x

    M3 - Journal article

    VL - 13

    SP - 51

    EP - 58

    JO - Pediatric Diabetes

    JF - Pediatric Diabetes

    SN - 1399-543X

    IS - 1

    ER -