Modeling of insulin secretion and insulin mass balance during hemodialysis in patients with and without type 2 diabetes

The secretion, distribution, and elimination of insulin in response to a bolus of glucose injected during regular hemodialysis was modeled to quantify the intra-dialytic mass balance of glucose and insulin in patients without (D0) and with type 2 diabetes (D1). A two-compartment regional blood flow model with shared compartments and dynamics for glucose, insulin and c-peptide was used to identify parameters of insulin and c-peptide co-secretion, first- and second-pass hepatic insulin extraction, as well as insulin-independent and insulin-dependent glucose utilization. Experimental data from a previous study obtained in 21 D0 and 14 D1 were used to identify kinetic model parameters and the fractions of glucose and insulin removed by dialysis. Modeled gains for insulin secretion (β1 = 0.015 vs. 0.084 L/min, β2 = 0.004 vs. 0.666 L) were lower in D1, resulting in a lower total insulin secretion (Mi = 6.40 vs. 38.0 nmol). Hepatic insulin extraction was high (Eihep = 0.558 vs. 0.638) and only slightly smaller in D1. The fraction of insulin removed by dialysis (Fid = 0.07 vs. 0.05) was small and comparable between D1 and D0. Modeled gains for insulin-dependent glucose uptake (γ = 0.38 vs. 1.34 L2/nmol/min) were lower whereas those for insulin-independent glucose uptake (λ = 0.14 vs. 0.067 L/min) were higher in D1. The fraction of glucose removed by dialysis (Fgd = 0.31 vs. 0.28) was higher in D1. Apart from expected differences in modeled secretion and glucose utilization in patients with and without diabetes an intravenous bolus of glucose causes only small differences in overall glucose and insulin balance during a typical hemodialysis treatment.