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 autoantibodies (Ab⁻) versus those with T2DM and positive autoantibodies (Ab⁺) to examine whether differences in β-cell function can be detected between the 2 groups.

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 [ΔI₃₀/ΔG₃₀] and C-peptide [ΔC₃₀/ΔG₃₀]), and oDI were calculated.

Indices of insulin secretion were ∼40%-50% lower in patients with Ab⁺ T2DM compared with those with Ab⁻ T2DM. After controlling for body mass index, ΔI₃₀/ΔG₃₀, ΔC₃₀/ΔG₃₀, 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 × ΔI₃₀/ΔG₃₀ (0.04 ± 0.02 vs 0.12 ± 0.02 mg/dL⁻¹; P = .005), and 1/fasting C-peptide × ΔC₃₀/ΔG₃₀ (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 ΔC₃₀/ΔG₃₀ <0.075 ng/mL per mg/dL had 93% sensitivity and 80% specificity for identifying youth with Ab⁺ T2DM.

During a liquid mixed-meal test, indices of β-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 β-cell function in therapeutic trials of β-cell restoration in youth with T2DM.