Indices of Insulin Secretion during a Liquid Mixed-Meal Test in Obese Youth with Diabetes

Objective To compare indices of insulin secretion, insulin sensitivity (IS), and oral disposition index (oDI) during the liquid mixed-meal test in obese youth with clinically diagnosed type 2 diabetes mellitus (T2DM) and negative auto-antibodies (Ab(-)) versus those with T2DM and positive autoantibodies (Ab(+)) to examine whether differences in beta-cell function can be detected between the 2 groups. Study design Twenty-seven youth with Ab(-) and 15 youth with Ab(+) clinically diagnosed T2DM underwent a mixed-meal test (Boost; 55% carbohydrate, 25% protein, and 20% fat). Fasting and mixed-meal-derived insulin and C-peptide indices of IS, secretion (30-minute insulinogenic [Delta I-30/Delta G(30)] and C-peptide [Delta C-30/Delta G(30)]), and oDI were calculated. Results Indices of insulin secretion were similar to 40%-50% lower in patients with Ab(+) T2DM compared with those with Ab(-) T2DM. After controlling for body mass index, Delta I-30/Delta G(30), Delta C-30/Delta G(30), C-peptide area under the curve (AUC)/glucose AUC, and insulin AUC/glucose AUC were significantly (P < .05) lower in the Ab(+) group compared with the Ab(-) group. Sensitivity indices were significantly higher in the Ab(+) group. The oDI, 1/fasting insulin x Delta I-30/Delta G(30) (0.04 +/- 0.02 vs 0.12 +/- 0.02 mg/dL(-1); P = .005), and 1/fasting C-peptide x Delta C-30/Delta G(30) (0.02 +/- 0.009 vs 0.05 +/- 0.006 mg/dL(-1); P = .018) were lower in the Ab(+) group. Receiver operating characteristic curve analyses revealed that fasting C-peptide < 3.2 ng/mL had 87% sensitivity and 74% specificity and Delta C-30/Delta G(30) < 0.075 ng/mL per mg/dL had 93% sensitivity and 80% specificity for identifying youth with Ab(+) T2DM. Conclusion During a liquid mixed-meal test, indices of beta-cell function were lower and IS was higher in patients with Ab(+) T2DM versus those with Ab(-) T2DM, with high sensitivity and specificity for fasting and stimulated C-peptide as markers of Ab(+) status. Indices of insulin secretion during this standardized mixed-meal test could be used to assess beta-cell function in therapeutic trials of beta-cell restoration in youth with T2DM. (J Pediatr 2013;162:924-9).