Impaired beta cell glucose sensitivity and whole-body insulin sensitivity as predictors of hyperglycaemia in non-diabetic subjects |
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Authors: | M Walker A Mari M K Jayapaul S M A Bennett E Ferrannini |
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Institution: | (1) Diabetes Research Group, University of Newcastle upon Tyne, Newcastle upon Tyne, UK;(2) CNR Institute of Biomedical Engineering, Padova, Italy;(3) University of Pisa School of Medicine, Pisa, Italy;(4) School of Clinical Medical Sciences, The Medical School, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK |
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Abstract: | Aims/hypothesis The aim of this prospective study was to investigate predictors of deteriorating glucose tolerance in subjects of British
extraction.
Methods A total of 156 non-diabetic subjects (86 with a family history of type 2 diabetes) underwent a 75-g OGTT and anthropometric
assessment at baseline and 5 years later. Pancreatic beta cell function and whole-body insulin sensitivity were studied by
model assessment. Subjects were classified as progressors if glucose tolerance moved one or more steps from normal, impaired
fasting glucose, impaired glucose tolerance and diabetes over the follow-up period.
Results At baseline, the progressors (n=22) had increased adiposity and a higher proportion of familial diabetes and abnormal glucose tolerance than non-progressors.
Baseline pancreatic beta cell sensitivity to changes in glucose (p<0.02) and whole-body insulin sensitivity (p<0.0001) were decreased in the progressors. Logistic regression revealed that baseline and follow-up changes in beta cell
glucose sensitivity and insulin sensitivity, rather than the classical clinical predictors (adiposity, familial diabetes and
glucose levels), were the key independent predictors of progression (explaining over 50% of the progression).
Conclusions/interpretation Impaired pancreatic beta cell glucose sensing and whole-body insulin sensitivity predict progression to hyperglycaemia. Strikingly,
these pathophysiological changes override the importance of the clinical risk factors and highlight potential metabolic targets
for prevention strategies.
An erratum to this article can be found at |
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Keywords: | Beta cell glucose sensitivity Disposition index Impaired glucose tolerance Impaired fasting glucose Insulin secretion Insulin sensitivity Oral glucose tolerance test |
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