Evaluation of glucose intolerance in acutely ill severe patients by means of an artificial pancreas

Purpose

To verify the importance of both the M value (glucose disposal rate measured by the glucose clamp method [GC]) and the I/E ratio (administered insulin/energy [glucose] ratio) measured by means of a bedside-type artificial pancreas (STG-22) in acutely ill severe patients.

Materials and methods

Thirty-four patients in whom blood glucose (BG) levels were controlled by means of the artificial pancreas (aim of BG control: 150 mg/dl) were investigated. The first measurement of GC was performed in acute conditions for all the patients, and the second measurement was done 1 week after the first measurement for 20 patients. GC was performed with a clamped BG level of 80 mg/dl and an insulin infusion rate (IIR) of 1.12 and 3.36 mU/kg/min. M1/M3 and I1/I3 indicate the M value (mg/kg/min) and blood insulin level (μU/ml) when the IIR is 1.12/3.36, respectively (normal value of M1: 5–10). M1/I1 and M3/I3 were calculated as the indicator of insulin sensitivity (IS). Patients were classified in four groups (A, B, C, D) according to M1 and the I/E ratio (mU/kcal): A, M1 < 5 and 30 < I/E ratio; B, M1 < 5 and I/E ratio < 30; C, 5 < M1 and I/E ratio < 30; D, 5 < M1 and 30 < I/E ratio. The following parameters were studied: (1) administered energy (glucose) (E), (2) administered insulin (I), (3) SOFA score, (4) M value, (5) daily mean BG level (BGm), (6) blood C-peptide reactivity (CPR), (7) IS, (5) insulin clearance (IC) (ml/kg/min).

Results

(1) There was negative correlation between the I/E ratio and M1/M3 (r = -0.31/r = -0.44). (2) Comparison between A (M1, 3.3 ± 1.1; I/E ratio, 55 ± 20; n = 23) and B (M1, 3.5 ± 0.8; I/E ratio, 18 ± 9; n = 11): there was significant difference in I (P < 0.005), BGm (183 ± 16 vs 153 ± 18, P < 0.005), and IC (19 ± 7 vs 14 ± 4, P < 0.05), but no significant difference in E, M1, CPR, IS, and SOFA score. (3) Comparison between C (M1, 7.3 ± 1.7; I/E ratio, 12 ± 8; n = 15) and D (M1, 7.8 ± 2.2; I/E ratio, 62 ± 44; n = 5): there was a significant difference in I (P < 0.005) and BGm (145 ± 21 vs 168 ± 16, P < 0.05), but no significant difference in E, M1, M3, CPR, IS, IC, and SOFA score.

Interpretation

The I/E ratio was a daily measurable indicator of glucose tolerance. However, there was discrepancy between the M value and the I/E ratio in some patients (groups B, D). the mechanism of the discrepancy was unclear, but the influence of IC and/or an increase of glucose metabolism by BG itself (ex. mass action effect, activation of glucose transporter-2, etc.) in group B, and a decrease of that in group D was speculated, because the M value was measured under a BG level of 80 mg/dl, while the I/E ratio was under BG control aiming at 150 mg/dl.

Conclusions

Measurement of both the M value and the I/E ratio was considered to be useful not only for the evaluation of glucose tolerance, but also for further understanding of the mechanism of glucose intolerance in acutely ill severe patients.