Glucose uptake saturation explains glucose kinetics profiles measured by different tests

Area of Science:

• Metabolic Research
• Mathematical Modeling
• Endocrinology

Background:

• Glucose clearance is known to depend on insulin levels, but a quantitative model for combined hyperinsulinemia and hyperglycemia is missing.
• Existing methods for assessing glucose tolerance, like euglycemic and hyperglycemic clamps, lack a unifying mathematical framework.

Purpose of the Study:

• To develop and validate a mathematical model describing glucose utilization under varying glucose and insulin concentrations.
• To quantitatively represent the effects of hyperinsulinemia and hyperglycemia on glucose clearance across different testing conditions.

Main Methods:

• Collected data from five studies involving 123 subjects undergoing various glucose tolerance tests (euglycemic/hyperglycemic clamps, oral tests) with glucose tracers.
• Developed a mathematical model using Michaelis-Menten kinetics for glucose utilization, with insulin-controlled Vmax.
• Estimated model parameters using a population approach and validated against experimental data.

Main Results:

• The model accurately fitted tracer data across all tested conditions.
• The estimated Michaelis constant (Km) for glucose was 3.88 mmol/l.
• Model simulations showed reduced glucose clearance with increasing glucose levels under hyperinsulinemia, consistent with experimental observations.

Conclusions:

• A unifying mathematical model can describe glucose clearance in diverse testing scenarios, aligning with glucose transport principles.
• The model successfully reproduces the suppressive effect of hyperglycemia on glucose clearance in the presence of hyperinsulinemia.
• This model has potential applications in designing accurate glucose homeostasis simulators.