Critical Evaluation of Indices Used to Assess b-Cell Function

The assessment of b-cell function, defined as the relationship between insulin secretion rate (ISR) and plasma glucose, is not standardized and often involves any of a number of b-cell function indices. We compared b-cell function by using popular indices obtained during basal conditions and after glucose ingestion, including the HOMA-B index, the basal ISR (or plasma insulin)-to-plasma glucose concentration ratio, the insulinogenic and ISRogenic indices, the ISR (or plasma insulin)-to-plasma glucose concentration areas (or incremental areas) under the curve ratio, and the disposition index, which integrates a specific b-cell function index value with an estimate of insulin sensitivity, between lean people with normal fasting glucose (NFG) and normal glucose tolerance (NGT) (n = 50) and four groups of people with obesity (n = 188) with 1) NFG-NGT, 2) NFG and impaired glucose tolerance (IGT), 3) impaired fasting glucose (IFG) and IGT, and 4) type 2 diabetes. We also plotted the ISR-plasma glucose relationship before and after glucose ingestion and used a statistical mixed-effects model to evaluate group differences in this relationship (i.e., b-cell function). Index-based group differences in b-cell function produced contradicting results and did not reflect the group differences of the actual observed ISR-glucose relationship or, in the case of the disposition index, group differences in glycemic status. The discrepancy in results is likely due to incorrect mathe-matical assumptions that are involved in computing indices, which can be overcome by evaluating the relationship between ISR and plasma glucose with an appro-priate statistical model. Data obtained with common b-cell function indices should be interpreted cautiously.