Investigation of insulin clearance in severely acutely ill patients with glucose intolerance evaluated by means of bedside-type artificial pancreas

Background and purpose

Glucose intolerance in acutely ill patients is one of the risk factors of their morbidity and mortality, and glucose control with insulin therapy improves the outcome. We investigated relationships among insulin clearance (IC), which is considered to be one of the factors related to effectiveness of insulin therapy, and glucose tolerance, glucose intolerance, and severity of the diseases, in order to clarify the significance of IC on the severity of the diseases including glucose intolerance and on the therapies.

Materials and methods

Twenty-three ICU patients with glucose intolerance in whom strict blood glucose control was performed by means of a bedside-type artificial pancreas (NIKKISO Corp., Japan) were investigated. The diabetics were excluded. The items investigated were IC (ml/kg/min) measured by the glucose clamp method, daily mean blood glucose level as a parameter of glucose intolerance (BGm, mg/dl), proportion of septic patients (%), SOFA score and mortality (%) as indicators of the severity of the diseases, and blood concentration of free fatty acid (FFA) and stress hormones (glucagon, growth hormone, cortisol, adrenalin, noradrenalin) as factors that might affect glucose intolerance. The method of investigation involved patients being classified into four groups according to IC, and those groups were compared with each other; low IC group (group L: IC < 9, n = 2), normal IC group (group N: 9 < IC < 15, n = 13), high IC group (group H: 15 < IC, n = 8), and severely high IC group (group S: 19 < IC, n = 5) (group S was a subgroup of group H).

Results

• (1) FFA values were low or normal in all groups. (2) There were no significant differences in stress hormones among group N, group H, and group S. Those hormones in group L were significantly higher than, or had a tendency to be higher than, those in group N, group H, and group S. (3) The mean values of BGm in the groups had a tendency to be higher in the order of group S (179 ± 30), group H (172 ± 25), group N (162 ± 26), and group L (153 ± 8). (4) The severities of the diseases (sepsis (%)/SOFA score/mortality (%)) in the groups were significantly higher in the order group L (100%/20.0 ± 1.4/100%), group S (100%/9.6 ± 7.0/40%), group H (88%/7.0 ± 6.5/25%), and group N (54%/5.8 ± 5.2/15%).

Interpretation and conclusions

The increase of IC was related to glucose intolerance. IC increased and glucose intolerance became severe as the severity of the diseases progressed. In the most severe state, or in a near-terminal state, however, IC decreased and glucose intolerance improved, although stress hormones increased significantly. Therapies focused on the improvement of IC were considered important in acutely ill severe patients with glucose intolerance as well as blood glucose control by insulin therapy.