Critical assessment of indices used to assess beta-cell function

Abstract

The assessment of beta-cell function—defined as insulin secretion rate (ISR) in relationship to plasma glucose—is not standardized and often involves any of a number of beta-cell function indices. We compared beta-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 beta-cell function index value with an estimate of insulin sensitivity, in 50 lean people with normal fasting glucose (NFG) and normal glucose tolerance (NGT) and four groups of people with obesity (n=188) with: i) NFG-NGT; ii) NFG and impaired glucose tolerance (IGT); iii) impaired fasting glucose and IGT, and iv) 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. beta-cell function). Index-based group differences in beta-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 mathematical assumptions that are involved in computing indices, which can be overcome by evaluating the relationship between ISR and plasma glucose with an appropriate statistical model. Data obtained with common beta-cell function indices should be interpreted cautiously.