title: Demonstration of an intrinsic relationship between endogenous C-peptide concentration and determinants of glycemic control in type 1 diabetes following islet transplantation.
abstract: OBJECTIVE
  Maintenance of endogenous pancreatic β-cell function could be an important goal in the management of type 1 diabetes. However, the impact of stimulated C-peptide level on overall glycemic control is unknown. The relationship between C-peptide and parameters of glucose control was therefore characterized in a cohort with rapidly changing β-cell function following islet transplantation.
  
  
  METHODS
  Standardized mixed-meal tolerance test was undertaken in 12 consecutive islet recipients at 1-6-month intervals, with graft function determined by 90-min stimulated C-peptide. Continuous glucose monitoring was undertaken in the week preceding each assessment and the relationship between C-peptide and glucose control evaluated by mixed Poisson regression.
  
  
  RESULTS
  Recipients completed 5 (1-14) [median (range)] clinical assessments over 18 (1-51) months posttransplant encompassing a wide range of stimulated C-peptide levels (7-2,622 pmol/L). Increasing β-cell function across predefined C-peptide groups was associated with reduced insulin dose, HbA1c, mean glucose (low [<200 pmol/L] 10.7 vs. excellent [>1,000 pmol/L] 7.5 mmol/L), and glucose SD (low, 4.4 vs. excellent, 1.4 mmol/L). Highly statistically significant continuous associations between stimulated C-peptide and mean interstitial glucose (lower by 2.5% [95% CI 1.5-3.5%] per 100 pmol/L higher C-peptide), glucose SD, time outside glucose target range, and measures of hyper-/hypoglycemia risk were confirmed.
  
  
  CONCLUSIONS
  Repeated assessment of islet transplant recipients has enabled modeling of the relationship between endogenous β-cell function and measures of glycemic control providing quantitative estimates of likely impact of an acute change in β-cell function in individuals with type 1 diabetes.
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle, United Kingdom.
authors.forename: Augustin M
authors.initials: AM
authors.lastname: Brooks
authors.affiliation: Peninsula NIHR Clinical Research Facility, Exeter, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Oram
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle, United Kingdom.
authors.forename: Philip
authors.initials: P
authors.lastname: Home
authors.affiliation: Department of Statistics, Newcastle University, Newcastle, United Kingdom.
authors.forename: Nick
authors.initials: N
authors.lastname: Steen
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle, United Kingdom jim.shaw@ncl.ac.uk.
authors.forename: James A M
authors.initials: JA
authors.lastname: Shaw
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000601:surgery*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000188:drug therapy; D007328:Insulin / Q000627:therapeutic use; D016381:Islets of Langerhans Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D006442:Glycated Hemoglobin; D007328:Insulin