Introduction and Objective: To investigate how β-cell glucose sensitivity, insulin clearance, and insulin sensitivity interact to determine glucose tolerance.Methods: We analyzed data from 54 healthy individuals (age 44 years IQR 27-56, 63% females, BMI 24.5 kg/m² IQR 21.9-28.7, HbA1c 33.26 mmol/mol IQR 32.13-35.51) undergoing a 3-hour OGTT. β-cell glucose sensitivity, insulin clearance, and insulin sensitivity were assessed via modeling of OGTT data. Their relationship with glucose tolerance was evaluated through linear regression models.Results: β-cell glucose sensitivity strongly predicted glucose tolerance during the OGTT (IQR increase effect: -87 mg/dL; 95% CI -141, -32; p = 0.003), but not fasting glucose (p = 0.4). Patients with low β-cell glucose sensitivity showed the widest range of glucose tolerance during the OGTT, some approaching diabetic levels despite others tolerating glucose well. Insulin sensitivity was the strongest determinant of this variance (IQR increase effect: -49 mg/dL; 95% CI -68, -31; p <0.001), and significantly influenced the relationship between β-cell glucose sensitivity and glucose tolerance (interaction term p = 0.035). Conversely, higher clearance (i.e. lower insulin levels) tended towards worse tolerance, though the effect was minor and the relationship not statistically significant. Among patients with low β-cell glucose sensitivity, comparing those with high vs. low insulin sensitivity showed that the former tended to be younger, female, with lower BMI and waist circumference, and produced less insulin while fasting. They also tended to produce less insulin during the OGTT, but this was not statistically significant. Fasting glycemic control and HbA1c were similar between the two groups.Conclusion: β-cell glucose sensitivity is key for glucose tolerance after a glucose challenge. While high β-cell glucose sensitivity often overcomes low insulin sensitivity, the latter becomes crucial when β-cell glucose sensitivity is low.
A. Foppiani: None. F. Sileo: None. G. Pozzi: None. S. Gallosti: None. A. Mari: Consultant; Lilly USA LLC, Novo Nordisk, Sanofi. A. Battezzati: None.
Project funded under the National Recovery and Resilience Plan (NRRP), Mission 4 Component 2 Investment 1.3 – Call for proposals No. 341 of 15 March 2022 of Italian Ministry of University and Research funded by the European Union – NextGenerationEU; Award Number: Project code PE00000003, Concession Decree No. 1550 of 11 October 2022 adopted by the Italian Ministry of University and Research, CUP D93C22000890001, Project title “ON Foods – Research and innovation network on food and nutrition Sustainability, Safety and Security – Working ON Foods.
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