Disruption of fasting and post-load glucose homeostasis are largely independent and sustained by distinct and early major beta-cell function defects: a cross-sectional and longitudinal analysis of the relationship between insulin sensitivity and cardiovascular risk (RISC) study cohort

Mengozzi, A., Tricò, D., Nesti, L., Petrie, J. , Højlund, K., Mitrakou, A., Krebs, M., Mari, A. and Natali, A. (2020) Disruption of fasting and post-load glucose homeostasis are largely independent and sustained by distinct and early major beta-cell function defects: a cross-sectional and longitudinal analysis of the relationship between insulin sensitivity and cardiovascular risk (RISC) study cohort. Metabolism, 105, 154185. (doi: 10.1016/j.metabol.2020.154185) (PMID:32061908)

Abstract

Background/aims: Uncertainty still exists on the earliest beta-cell defects at the bases of the type 2 diabetes. We assume that this depends on the inaccurate distinction between fasting and post-load glucose homeostasis and aim at providing a description of major beta-cell functions across the full physiologic spectrum of each condition. Methods: In 1320 non-diabetic individuals we performed an OGTT with insulin secretion modeling and a euglycemic insulin clamp, coupled in subgroups to glucose tracers and IVGTT; 1038 subjects underwent another OGTT after 3.5 years. Post-load glucose homeostasis was defined as mean plasma glucose above fasting levels (δOGTT). The analysis was performed by two-way ANCOVA. Results: Fasting plasma glucose (FPG) and δOGTT were weakly related variables (stβ = 0.12) as were their changes over time (r = −0.08). Disruption of FPG control was associated with an isolated and progressive decline (approaching 60%) of the sensitivity of the beta-cell to glucose values within the normal fasting range. Disruption of post-load glucose control was characterized by a progressive decline (approaching 60%) of the slope of the full beta-cell vs glucose dose-response curve and an early minor (30%) decline of potentiation. The acute dynamic beta-cell responses, neither per se nor in relation to the degree of insulin resistance appeared to play a relevant role in disruption of fasting or post-load homeostasis. Follow-up data qualitatively and quantitatively confirmed the results of the cross-sectional analysis. Conclusion: In normal subjects fasting and post-load glucose homeostasis are largely independent, and their disruption is sustained by different and specific beta-cell defects.

• Item Type: Articles
• Additional Information: The RISC Study was partly supported by EU grant QLG1-CT-2001-01252. DT is funded by the European Foundation for the Study of Diabetes (EFSD) Mentorship Programme.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Petrie, Professor John
• Authors: Mengozzi, A., Tricò, D., Nesti, L., Petrie, J., Højlund, K., Mitrakou, A., Krebs, M., Mari, A., and Natali, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Metabolism
• Publisher: Elsevier
• ISSN: 0026-0495
• ISSN (Online): 1532-8600
• Published Online: 14 February 2020
• Copyright Holders: Copyright © 2020 Elsevier Inc.
• First Published: First published in Metabolism 105: 154185
• Publisher Policy: Reproduced in accordance with the publisher copyright policy