Jung SH, et al. - The aim of this study was to quantify the relative contributions of increased insulin secretion rate (ISR) and decreased insulin clearance rate (ICR) in the compensatory hyperinsulinaemia characteristic of insulin-resistant individuals without diabetes. Decreases in ICR could provide the first adaptation to decreased insulin sensitivity while both increases in ISR and decreases in ICR compensated for insulin resistance.

Methods

• The researchers identified obese (BMI ≥30 kg/m²) individuals without diabetes (n = 91) from a registry of volunteers.
• For this study, subjects underwent the following measurements: oral glucose tolerance; insulin resistance (steady-state plasma glucose [SSPG] concentration during the insulin suppression test [IST]); ISR (using the graded glucose infusion test [GGIT]); and ICR (using the IST and GGIT).
• They stratified participants into tertiles based on SSPG concentration: SSPG-1(insulin-sensitive); SSPG-2 (intermediate); and SSPG-3 (insulin-resistant).

Results

• Among the SSPG tertiles, no differences in BMI and waist circumference were observed.
• In the SSPG-2 and SSPG-3 groups, serum alanine aminotransferase concentrations were higher compared with the SSPG-1 group (p=0.02).
• There was a progressive increase in the total integrated insulin response from the most insulin-sensitive to the most insulin-resistant tertiles (p < 0.001) following an oral glucose challenge.
• The SSPG-3 group had significantly greater integrated glucose (median [interquartile range], 32.9 [30.8-36.3] mmol/l × h) and insulin responses (1711 [1476–2223] mmol/l × h) compared with the SSPG-1 group (30.3 [28.8-32.9] mmol/l × h, p=0.04, and 851 [600-1057] pmol/l × h, p < 0.001, respectively) following intravenous glucose.
• Moreover, significant changes in both ISR and ICR were observed only in the SSPG-3 group (p < 0.001).
• Only the ICR was significantly decreased in the SSPG-2 group compared with the SSPG-1 group.
• Thus, during the IST with increasing insulin resistance (SSPG-1, 0.48 [0.41-0.59]; SSPG-2, 0.43 [0.39-0.50]; SSPG-3, 0.34 [0.31–0.40]), ICR progressively declined.