Investigation of insulin clearance in septic patients with glucose intolerance: analysis under strict blood glucose control by means of artificial pancreas

Purpose

Analysis of insulin metabolism in severely ill patients with glucose intolerance is important for appropriate nutritional support. Significance of the measurement of insulin clearance (IC) and the factors which influence IC in septic patients were investigated.

Method

Twenty septic patients in whom blood glucose (BG) levels were strictly controlled by means of bedside-type artificial pancreas (AP) (STG-22: manufactured by NIKKISO corporation in Japan) were studied. IC was calculated from the data obtained by euglycemic hyperinsulinemic glucose clamp method performed by means of AP twice for each patient (first measurement was done in acute condition or within 3 days after admission, second measurement was done 1 week after the first measurement basically. Clamped BG level: 80 mg/dl. Insulin infusion rate [IIR]: 1.12 and 3.36 mU/kg min. I1/I3 and C1/C3, the blood insulin levels, and the C-peptide reactivity levels, when IIR is 1.12/3.36 mU/kg min respectively. Glucose disposal rate: Mvalue [mg/kg min]). IC was calculated from the following formula: IC = (3.36 – 1.12) × 1000/(I3 – I1), normal value of IC: 10–15 ml/kg min. Relationships between IC and the following factors were investigated: (1) M value, (2) daily mean BG (BGm), (3) diabetes mellitus (DM), (4) degree of organ dysfunction/ failure (MOF score: calculated from the MOF criteria of Japanese Association for Critical Care Medicine), (5) cardiac output/body weight (C/B), (6) serum fat (triglyceride, free fatty acid, total cholesterol) levels (SF), and (7) blood stress hormone levels (SH).

Results

The results are as follows (shown in mean ± SD): (a) C1–C3: 0.52 ± 0.88 ng/ml (n = 40), (b) I1: 53 ± 26, I3: 191 ± 75 μU/ml, IC: 20 ± 10 ml/kg min (n = 40), (c) IC in comparison between the patients (1) with liver dysfunction (-)/(+): 23 ± 11 ml/kg min (n = 25)/15 ± 5 ml/kg min (n = 15) (P < 0.025), (2) with the MOF score 0 or 1/more than 5: 24 ± 14 ml/kg min (n = 15)/16 ± 4 ml/kg min (n = 14) (P < 0.05), (d) There was positive correlation between IC and C/B (y=0.11x + 5.0, n = 23, r = 0.59, P < 0.003), (e) There was no definite relationship between IC and organ dysfunction except liver dysfunction, M value, BGm, DM, SF, and SH.

Interpretation and conclusions

(1) IC calculated from our method seemed to be reliable because there seemed no significant influence of the intrinsic insulin which was apparent from the small amount of (C1-C3) value. (2) Insulin clearance was elevated in most patients with hyperdynamic state, although the degree of the elevation was suppressed in patients with liver dysfunction and multiple organ dysfunction. (3) The results suggest the justification of sufficient insulin therapy.