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1 Metabolic Unit, Institute of Biomedical Engineering, National Research Council, Padova, Italy
2 Division of Endocrinology and Metabolism, Department of Medicine 3, University of Vienna Medical School, Vienna, Austria
* To whom correspondence should be addressed. E-mail: Karl.Thomaseth{at}ladseb.pd.cnr.it.
The fasting proinsulin/insulin ratio is a currently used marker of B-cell dysfunction. This ratio is calculated at basal, while its behavior in dynamic conditions, i.e. during glucose stimulation, could be more informative. Given the different kinetics of the peptides, a mathematical model was necessary to analyze OGTT data of insulin, C-peptide and proinsulin in 55 healthy (NGT), 30 impaired glucose tolerant (IGT) and 31 type 2 diabetic (T2DM) subjects. The model provided secretion and disappearance of the peptides, and an index of B-cell function under dynamic conditions. Total proinsulin secretion during OGTT was not different (P>0.053) among NGT (0.17±0.01 mmol/l in 3h), IGT (0.22±0.02) and T2DM (0.21±0.02). The proinsulin/insulin molar ratio measured from basal samples was higher (P<0.0001) in T2DM (0.39±0.05) than in NGT (0.14±0.01) and IGT (0.13±0.02), and similar results (P<0.003) were found by the dynamic index (0.27±0.04, 0.14±0.01, 0.15±0.01 in T2DM, NGT, IGT, respectively). Basal ratio significantly correlated with the dynamic index and regression line slope was lower than 1 (0.43±0.08, 0.61±0.10, 0.56±0.03, in NGT, IGT, T2DM, respectively, P<0.0001). Impaired beta cell function in T2DM could then be indicated by proinsulin/insulin indexes both at basal and during the dynamic phase.
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