Lessons From the Mixed Meal Tolerance Test

Use of 90-minute and fasting C-peptide in pediatric diabetes

  1. Johnny Ludvigsson, MD, PHD2
  1. 1Peninsula National Institute of Health Research Clinical Research Facility, Peninsula Medical School, University of Exeter, Exeter, United Kingdom
  2. 2Department of Clinical and Experimental Medicine, Division of Pediatrics, Faculty of Health Sciences, Linköping University, Linköping, Sweden
  1. Corresponding author: Rachel E.J. Besser, rachel.besser{at}


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.

RESEARCH DESIGN AND 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 (rs = 0.96; P < 0.0001) and strongly correlated to FCP (rs = 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.

  • Received May 1, 2012.
  • Accepted July 15, 2012.

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