Deteriorating beta-cell function in type 2 diabetes: a long-term model.
BACKGROUND
Type 2 diabetes is characterized by insulin resistance and the progressive loss of islet beta-cell function. Although the former is already established at diagnosis and changes little thereafter, beta-cell function continues to decline, leading to secondary failure of anti-hyperglycaemic therapies.


OBJECTIVE
To develop a quantitative model of the process of beta-cell function decay over time, using trial data.


METHODS
Re-analysis of published data.


METHODS
The results of the Belfast Diet Study were re-analysed. Assuming patients are diagnosed at different stages in the disease process, time displacement of data was used to obtain a bi-partite spline model describing loss of insulin secretion over a 6-year period.


RESULTS
The model was developed combining two phases, in which a long slow gradual loss of beta-cell function leads to a crisis in metabolic regulation, precipitating a much more rapid decay phase. This paradigm was consistent with a previous non-linear model of beta-cell mass regulation.


CONCLUSIONS
This model may have important implications for targeting appropriate therapy to patients in each phase: delaying or avoiding full clinical type 2 diabetes in the first phase; and preventing the development of diabetic complications in the second phase.
Bagust
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A
York Health Economics Consortium, University of York, Heslington, UK. ab13@york.ac.uk
Beale
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D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000178:diet therapy / Q000503:physiopathology*; D006801:Humans; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000503:physiopathology*; D008875:Middle Aged; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin