Introduction and Objective: The reduction of the insulin Fractional Clearance Rate (FCR) is an early marker of insulin resistance and/or beta-cell disfunction that may be observed before prediabetes arises. Here we aim to investigate whether such reduction is associated with easily measurable anthropometric characteristics, like body mass index (BMI), age and gender.Methods: We studied 204 healthy individuals (87 F; Median [IQR]: age=65 [27-71] y, BMI=27 [23-31] kg/m²) who received a mixed meal containing 0.02 g/kg of glucose. Plasma glucose, insulin and C-peptide concentrations were frequently measured for 420 min after the meal and interpreted with a model describing glucose control on insulin secretion, hepatic extraction and FCR. This was identified in a nonlinear mixed-effects framework to quantify the influence of BMI, age and gender on key model parameters.Results: The model well fitted the data and reproduced the observed variability (R2 = 0.93). Both BMI and gender are significantly associated with FCR. In particular, a proportionally inverse relationship was found with BMI, by a factor equal to 26.4/BMI, while males exhibited a further 27% reduction in FCR with respect to female (Fig. 1).Conclusion: Our results indicates that elevated BMI (especially in males) is strongly associated with FCR reduction, which, in turn, is an early marker of diabetes.
J. Bonet: None. M. Schiavon: Research Support; Current; Sanofi. C. Dalla Man: Other – Webinar provider; Ended; Sanofi. Other – Joint research project; Current; Sanofi-Aventis Deutschland GmbH.
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