β-Cell Function and Insulin Sensitivity in Youth With Early Type 1 Diabetes From a 2-Hour 7-Sample OGTT

Abstract

Context: The oral minimal model is a widely accepted noninvasive tool to quantify both β-cell responsiveness and insulin sensitivity (SI) from glucose, C-peptide, and insulin concentrations during a 3-hour 9-point oral glucose tolerance test (OGTT).

Objective: Here, we aimed to validate a 2-hour 7-point protocol against the 3-hour OGTT and to test how variation in early sampling frequency impacts estimates of β-cell responsiveness and SI.

Methods: We conducted a secondary analysis on 15 lean youth with stage 1 type 1 diabetes (T1D; ≥ 2 islet autoantibodies with no dysglycemia) who underwent a 3-hour 9-point OGTT. The oral minimal model was used to quantitate β-cell responsiveness (φtotal) and insulin sensitivity (SI), allowing assessment of β-cell function by the disposition index (DI = φtotal × SI). Seven- and 5-point 2-hour OGTT protocols were tested against the 3-hour 9-point gold standard to determine agreement between estimates of φtotal and its dynamic and static components, SI, and DI across different sampling strategies.

Results: The 2-hour estimates for the disposition index exhibited a strong correlation with 3-hour measures (r = 0.975; P < .001) with similar results for β-cell responsiveness and SI (r = 0.997 and r = 0.982; P < .001, respectively). The agreement of the 3 estimates between the 7-point 2-hour and 9-point 3-hour protocols fell within the 95% CI on the Bland-Altman grid with a median difference of 16.9% (-35.3 to 32.5), 0.2% (-0.6 to 1.3), and 14.9% (-1.4 to 28.3) for DI, φtotal, and SI. Conversely, the 5-point protocol did not provide reliable estimates of φ dynamic and static components.

Conclusion: The 2-hour 7-point OGTT is reliable in individuals with stage 1 T1D for assessment of β-cell responsiveness, SI, and DI. Incorporation of these analyses into current 2-hour diabetes staging and monitoring OGTTs offers the potential to more accurately quantify risk of progression in the early stages of T1D.

Keywords: insulin sensitivity; islet autoimmunity; oral minimal model; prediabetes; type 1 diabetes; β-cell function.