title: Lessons from the mixed-meal tolerance test: use of 90-minute and fasting C-peptide in pediatric diabetes.
abstract: OBJECTIVE
  Mixed-meal tolerance test (MMTT) area under the curve C-peptide (AUC CP) is the gold-standard measure of endogenous insulin secretion in type 1 diabetes but is intensive and invasive to perform. The 90-min MMTT-stimulated CP ≥0.2 nmol/L (90CP) is related to improved clinical outcomes, and CP ≥0.1 nmol/L is the equivalent fasting measure (FCP). We assessed whether 90CP or FCP are alternatives to a full MMTT.
  
  
  METHODS
  CP was measured during 1,334 MMTTs in 421 type 1 diabetes patients aged <18 years at 3, 9, 18, 48, and 72 months duration. We assessed: 1) correlation between mean AUC CP and 90CP or FCP; 2) sensitivity and specificity of 90CP ≥0.2 nmol/L and FCP ≥ 0.1 nmol/L to detect peak CP ≥0.2 nmol/L and the equivalent AUC CP; and 3) how the time taken to reach the CP peak varied with age of diagnosis and diabetes duration.
  
  
  RESULTS
  AUC CP was highly correlated to 90CP (r(s) = 0.96; P < 0.0001) and strongly correlated to FCP (r(s) = 0.84; P < 0.0001). AUC CP ≥23 nmol/L/150 min was the equivalent cutoff for peak CP ≥0.2 nmol/L (98% sensitivity/97% specificity). A 90CP ≥0.2 nmol/L correctly classified 96% patients using AUC or peak CP, whereas FCP ≥0.1 nmol/L classified 83 and 85% patients, respectively. There was only a small difference seen between peak and 90CP (median 0.02 nmol/L). The CP peak occurred earlier in patients with longer diabetes duration (6.1 min each 1-year increase in duration) and younger age (2.5 min each 1-year increase).
  
  
  CONCLUSIONS
  90CP is a highly sensitive and specific measure of AUC and peak CP in children and adolescents with type 1 diabetes and offers a practical alternative to a full MMTT.
authors.affiliation: Peninsula National Institute of Health Research Clinical Research Facility, Peninsula Medical School, University of Exeter, Exeter, United Kingdom. rachel.besser@nhs.net
authors.forename: Rachel E J
authors.initials: RE
authors.lastname: Besser
authors.forename: Beverley M
authors.initials: BM
authors.lastname: Shields
authors.forename: Rosaura
authors.initials: R
authors.lastname: Casas
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
authors.forename: Johnny
authors.initials: J
authors.lastname: Ludvigsson
mesh_terms: D000293:Adolescent; D002096:C-Peptide / Q000097:blood*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005215:Fasting / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D019518:Postprandial Period
chemical_list: D002096:C-Peptide