Lessons From the Mixed Meal Tolerance Test
Use of 90-minute and fasting C-peptide in pediatric diabetes
- Rachel E.J. Besser, PHD1⇓,
- Beverley M. Shields, PHD1,
- Rosaura Casas, PHD2,
- Andrew T. Hattersley, DM1 and
- Johnny Ludvigsson, MD, PHD2
- 1Peninsula National Institute of Health Research Clinical Research Facility, Peninsula Medical School, University of Exeter, Exeter, United Kingdom
- 2Department of Clinical and Experimental Medicine, Division of Pediatrics, Faculty of Health Sciences, Linköping University, Linköping, Sweden
- Corresponding author: Rachel E.J. Besser, .
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.
- © 2012 by the American Diabetes Association.
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