Analysis of the relationship between body mass index, insulin resistance, and beta-cell function: A cross-sectional study using the minimal model

Abstract

The objective of our research was to identify the mathematical model that would best define the relationship between obesity, insulin resistance (IR), and β-cell function. Eighty-seven healthy subjects with a wide range of body mass index (BMI) were studied. Insulin sensitivity (IS) was calculated using Bergman’s minimal model. Acute insulin response (AIRg) was calculated as the secretion of insulin during the first 10 minutes following a glucose bolus. IS × AIRg was used as an index of insulin-mediated glucose uptake (IMGU). The relationships among BMI, IS, fasting plasma insulin (FPI), and AIRg were studied in linear relationship terms and in terms of the hyperbolic function. Where the best fit was linear, the Jones and Molitoris method was used to investigate whether the 2-line fit was significantly better. The division of the population into BMI quartiles shows that from the third quartile, IS (12.4 ± 6.0 v 11.0 ± 6.4 v 4.8 ± 1.8 v 3.2 ± 2.0 E-5 min−1[pmol/L]−1, P < .01) diminishes. Nevertheless, a plateau was established between the last 3 quartiles for IS × AIRg. AIRg related to BMI via a breakpoint of 29.3 kg · m−2. The best fits for both the BMI/IS and BMI/FPI relationships were hyperbolic. Our data indicate that obesity represents a continuum of IR, with severity increasing as BMI increases. Nevertheless, above a value of 29 kg · m−2 and despite great increases in adiposity, IS tends to descend slowly. Moreover, there seems to be an IMGU threshold at a BMI value of approximately 27 kg · m−2, above which an increase in adiposity leads to a greater fall in IS × AIRg. Furthermore, this threshold also appears to affect pancreatic response to a glucose stimulus.