Kinetic Models for Insulin Disappearance from Plasma in Type I Diabetic Patients

Abstract

We have tested whether our previous finding in normal subjects that the disappearance of insulin from plasma obeys saturation kinetics alone also applies to type I diabetic patients. In six long-term diabetic patients steady state plasma insulin concentrations resulting from constant insulin infusion at different rates were compared with the predictions of three models for the kinetics of insulin in plasma. The models allowed the existence of non-saturable (first order equation) or saturable (Michaëlis-Menten equation) mechanisms, or both. The minimal acceptable model included saturation kinetics alone in four subjects and first order kinetics alone in two subjects. The clearance of insulin in diabetic patients, calculated from the best fitting model, was 18.0 (median, range 10.0-23.7) ml X kg-1 X min.-1 versus 25.0 (18.6-47.1) ml X kg-1 X min.-1 in six normal subjects (2p = 0.008). Insulin thus disappears from plasma at a lower rate in diabetic patients than in normal subjects at physiological plasma concentrations.

A physiological Intensive Control Insulin-Nutrition-Glucose (ICING) model validated in critically ill patients

“…Therefore its concentration is several folds higher than insulin in plasma. If the diffusion process is to any level saturable [50], the rates determined using C-peptide measurements will not be reflective of insulin. In addition, the plasma concentration achieved in critically ill patients is very different to that in EIC experiments or otherwise healthy diabetic individuals.…”

“…This model also has relatively simple insulin kinetics compared to other more extensive models [50,51,52,53]. It does not explicitly express different routes of insulin clearance and transport from plasma.…”

Interstitial insulin kinetic parameters for a 2-compartment insulin model with saturable clearance

“…Therefore, its concentration is several folds higher than insulin in plasma. If the diffusion process is to any level saturable [18], the rates determined using Cpeptide measurements would not be reflective of insulin.…”

Adaptive Bolus-Based Set-Point Regulation of Hyperglycemia in Critical Care

“…First order plasma insulin disappearance rate at low insulin concentration, n, is set to 0.16 min -1 , a value that is fairly consistent across many studies (e.g. [14,15]). The value of I is set to 0.0017 L/mU, which is also consistent across many studies (e.g.…”