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DB23-0613 BCFI_comparison_R1_FINAL_supplement_only.pdf (748.51 kB)

Critical assessment of indices used to assess beta-cell function

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posted on 2023-11-28, 17:50 authored by Chao Cao, Han-Chow E. Koh, Dominic N. Reeds, Bruce W. Patterson, Samuel Klein, Bettina Mittendorfer

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.


ARTICLE HIGHLIGHTS

· We evaluated differences in beta-cell function—insulin secretion rate (ISR) in relationship to plasma glucose—among normoglycemic lean people and people with obesity and different glycemic status (normal, prediabetes, type 2 diabetes) by using an oral glucose tolerance test in conjunction with popular beta-cell function indices. Additionally, we plotted the ISR-plasma glucose relationship and evaluated group differences in this relationship with a statistical mixed effects model.

· Beta-cell function indices produced results that did not reflect the observed group differences in the ISR-glucose relationship, presumably because of incorrect mathematical assumptions involved in computing indices.

· Beta-cell function indices should be used cautiously.

Funding

American Diabetes Association 1-18-ICTS-119

Longer Life Foundation 2019-011

NIH x R01 DK115400

Washington University School of Medicine Diabetes Research Center x P30 DK020579

Washington University School of Medicine Institute of Clinical and Translational Sciences x UL1 TR002345

Washington University School of Medicine Nutrition Obesity Research Center x P30 DK056341

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