Investigation of the factors which influence insulin sensitivity in septic patients with glucose intolerance: analysis with glucose clamp method by means of artificial pancreas

Purpose

Insulin Sensitivity (IS) is often impaired in septic patients and its evaluation is important in terms of the nutritional support for those patients. However, accurate measurement of IS is not easy, partly because Insulin Clearance (IC) is usually increased in septic patients as we reported at this congress last year. We investigated IS excluding the influence of IC and the factors which affect IS in septic patients with glucose intolerance.

Method

Twenty-one septic patients without diabetes mellitus were investigated. IS was measured by Glucose Clamp method (GC) by means of bedside-type artificial pancreas (STG-22: manufactured by NIKKISO corporation in Japan). GC was performed twice for each patient basically (first measurement was done in acute condition or within 3 days after admission, and second measurement was done 1 week after the first measurement). GC was performed with clamped blood glucose level of 80 mg/dl and Insulin Infusion Rate (IIR) of 1.12 and 3.36 mU/kg min. I1/I3 and M1/M3 indicates the blood insulin level (μU/ml) and glucose disposal rate: M value (mg/kg min), when IIR is 1.12/3.36 mU/kg min respectively. IC was calculated from the following formula: IC = (3.36 – 1.12) × 1000/(I3 – I1) (normal value of IC: 10–15 ml/kg min). M/I: M1/I1 (M1/I1 × 1000) and M3/I3 (M3/I3 × 1000) (ml l/kg min μU) were calculated as the parameter of IS. Relationships between M/I and the following factors were investigated: (1) blood stress hormone levels (SH) (adrenaline, noradrenaline, glucagon, cortisol, growth hormone), (2) serum fat levels (SF) (triglyceride, free fatty acid, total cholesterol), (3) blood endotoxin and β-D glucan levels, (4) degree of organ dysfunction/failure (MOF score: calculated from the MOF criteria of Japanese Association for Critical Care Medicine), and (5) blood IL-6 level.

Results

The results are as follows (shown in mean ± SD [n]). (1) (maximum, minimum, mean) of I1, I3, and IC were I1 (133, 23, 62 ± 31 [28]), I3 (705, 19, 209 ± 121 [36]), IC (26, 4, 16 ± 6 [27]) respectively. (2) Mean of M3/I3 of the patients with MOF score more than 7 was significantly lower than that of the patients with MOF score = 0 (29 ± 18 [10] vs 57 ± 20 [7], P < 0.025). The same tendency was found as for M1/I1 (44 ± 54 [12] vs 102 ± 76 [7], P < 0.10). (3) Platelet count was positively correlated with M3/I3 (n = 35, r = 0.62, P < 0.002) and M1/I1 (n = 35, r = 0.45, P < 0.006). (4) As IL-6 increased, M/I decreased in one patient, but increased in another patient. (5) There was no definite relationship between M/I and SH, SF, endotoxin, and β-D glucan.

Interpretation and conclusions

M/I seemed to be one of the useful indicators of IS in septic patients, because IC was variable in those patients. Multiple organ dysfunction and coagulopathy with thrombocytopenia were the factors which decreased IS. Difference of the influence of blood IL-6 level to M/I among the patients might be related to the balance of the type of glucose transporters affected by the inflammatory cytokines (ex. activation of glucose transporter-1, suppression of glucose transporter-4, etc.).