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.
authors: Department of Paediatrics, Glostrup/Herlev University Hospital, Copenhagen, Denmark. annekaas@dadlnet.dk
authors: Anne
authors: A
authors: Kaas
authors: Marie Louise Max
authors: ML
authors: Andersen
authors: Siri
authors: S
authors: Fredheim
authors: Philip
authors: P
authors: Hougaard
authors: Karsten
authors: K
authors: Buschard
authors: Jacob Steen
authors: JS
authors: Petersen
authors: Carine
authors: C
authors: de Beaufort
authors: Kenneth J
authors: KJ
authors: Robertson
authors: Lars
authors: L
authors: Hansen
authors: Henrik B
authors: HB
authors: Mortensen
authors: Lotte B
authors: LB
authors: Nielsen
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000032:analysis / Q000097:blood; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D005934:Glucagon / Q000032:analysis / Q000097:blood*; D052216:Glucagon-Like Peptide 1 / Q000032:analysis / Q000097:blood*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011384:Proinsulin / Q000032:analysis / Q000097:blood*; D012075:Remission, Spontaneous
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D011384:Proinsulin