Τίτλος:
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
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2020 Elsevier Inc.
Συγγραφείς:
Mengozzi, A.
Tricò, D.
Nesti, L.
Petrie, J.
Højlund, K.
Mitrakou, A.
Krebs, M.
Mari, A.
Natali, A.
RISC Investigators
Περιοδικό:
Metabolism: Clinical and Experimental
Λέξεις-κλειδιά:
glucose, adult; Article; cell function; cohort analysis; controlled study; cross-sectional study; fasting; female; follow up; glucose blood level; glucose homeostasis; human; insulin resistance; insulin sensitivity; longitudinal study; major clinical study; male; non insulin dependent diabetes mellitus; oral glucose tolerance test; pancreas islet beta cell; priority journal
DOI:
10.1016/j.metabol.2020.154185
