Determinants of glycemic control in youth with type 2 diabetes at randomization in the TODAY study

Objective: To investigate insulin sensitivity and secretion indices and determinants of glycemic control in youth with recent-onset type 2 diabetes (T2DM) at randomization in the TODAY study, the largest study of youth with T2DM to date. Methods: We examined estimates of insulin sensitivity [1/fasting insulin (1/I_F), fasting glucose/insulin (G_F/I_F), 1/fasting C-peptide (1/C_F), G_F/C_F], β-cell function [insulinogenic index (ΔI₃₀/ΔG₃₀), and ΔC₃₀/ΔG₃₀], and disposition index (DI) in the TODAY cohort of 704 youth (14.0 ± 2.0 yr; diabetes duration 7.8 ± 5.8 months; 64.9% female; 41.1% Hispanic, 31.5% Black, 19.6% White, 6.1% American Indian, and 1.7% Asian) according to hemoglobin A1c (HbA1c) quartiles at study randomization. The randomization visit followed a run-in period (median 71 d) during which glycemic control (HbA1c ≤ 8% for at least 2 months) was achieved with metformin alone. These measures were also examined in relation to screening HbA1c levels before run-in. Results: Insulin secretion indices declined with increasing HbA1c quartiles, at randomization (ΔC₃₀/ΔG₃₀: 0.11 ± 0.09, 0.10 ± 0.19, 0.07 ± 0.06, and 0.03 ± 0.03 ng/mL per mg/dL, p < 0.0001; DI: 0.03 ± 0.03, 0.03 ± 0.05, 0.02 ± 0.02, and 0.01 ± 0.01 mg/dL^-1, p < 0.0001) and at screening, with no significant difference in insulin sensitivity. There were no significant differences in estimates of insulin sensitivity or secretion between genders or across the different racial groups. At randomization and screening, HbA1c correlated with DI (r = -0.3, p < 0.001), with ΔC₃₀/ΔG₃₀, but not with insulin sensitivity estimates. Conclusions: In youth with recent-onset T2DM treated with metformin, glycemic control, as measured by HbA1c, appears to be associated with residual β-cell function and not insulin sensitivity.