title: Characterization of residual β cell function in long-standing type 1 diabetes.
abstract: BACKGROUND
  Some patients with long-standing type 1 diabetes (T1D) maintain detectable levels of C-peptide. The quantitative and qualitative aspects of insulin secretion in these subjects have not been assessed, but may shed light on the basis for maintained β cell function. Our objective was to characterize insulin secretion in subjects with varying duration of T1D.
  
  
  METHODS
  Data from mixed-meal tolerance tests were collected in this cross-sectional study. We screened 58 subjects with T1D <1 year and 34 subjects with T1D >2 years, 20 of whom had previously participated in trials of anti-CD3 monoclonal antibody. Data from 38 historical non-diabetic controls were utilized. Insulin secretory rates were calculated from C-peptide levels from mixed-meal tolerance tests. Patterns and rates of insulin secretion were characterized along with relationships between insulin secretion and clinical parameters.
  
  
  RESULTS
  C-peptide was detected in 68% of subjects with T1D duration >2 years. Insulin secretion was negatively correlated with HgbA(1c) and insulin use. A decline in total insulin secretion was seen with increasing disease duration (p < 0.0001). More subjects with long duration of T1D had a delayed time to peak secretion compared with those with new onset T1D or non-diabetic subjects. Insulin and glucagon secretory responses appeared unrelated.
  
  
  CONCLUSIONS
  Meal-stimulated insulin secretory responses are seen in those with long-standing T1D and detectable C-peptide. Delayed insulin secretory responses are more common in individuals with longer disease duration. Residual insulin secretory responses are associated with improved clinical parameters.
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Sherr
authors.forename: Tara
authors.initials: T
authors.lastname: Ghazi
authors.forename: Anna
authors.initials: A
authors.lastname: Wurtz
authors.forename: Linda
authors.initials: L
authors.lastname: Rink
authors.forename: Kevan C
authors.initials: KC
authors.lastname: Herold
mesh_terms: D000293:Adolescent; D000328:Adult; D002096:C-Peptide / Q000097:blood; D002648:Child; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D018450:Disease Progression; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005934:Glucagon / Q000378:metabolism; D050416:Glucagon-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism* / Q000627:therapeutic use; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019518:Postprandial Period; D055815:Young Adult
chemical_list: D002096:C-Peptide; D005934:Glucagon; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; C517652:hemoglobin A1c protein, human
keywords: insulin secretion rates; long duration; type 1 diabetes