Lessons From the Mixed-Meal Tolerance Test Use of 90-minute and fasting C-peptide in pediatric diabetes

• 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-minMMTT-stimulated CP andgt;= 0.2 nmol/L (90CP) is related to improved clinical outcomes, and CP andgt;= 0.1 nmol/L is the equivalent fasting measure (FCP). We assessed whether 90CP or FCP are alternatives to a full MMTT. less thanbrgreater than less thanbrgreater thanRESEARCH 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 andgt;= 0.2 nmol/L and FCP andgt;= 0.1 nmol/L to detect peak CP andgt;= 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. less thanbrgreater than less thanbrgreater thanRESULTS-AUC CP was highly correlated to 90CP (r(s) = 0.96; P andlt; 0.0001) and strongly correlated to FCP (r(s) = 0.84; P andlt; 0.0001). AUC CP andgt;= 23 nmol/L/150 min was the equivalent cutoff for peak CP andgt;= 0.2 nmol/L (98% sensitivity/97% specificity). A 90CP andgt;= 0.2 nmol/L correctly classified 96% patients using AUC or peak CP, whereas FCP andgt;= 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). less thanbrgreater than less thanbrgreater thanCONCLUSIONS-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. Diabetes Care 36:195-201, 2013

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