Septic Patients in Multiple Organ Failure Can Oxidize Infused Glucose, but Non-Oxidative Disposal (Storage) is Impaired

Abstract

1. Patients suffering trauma and sepsis are insulin resistant, but no studies have specifically been made of patients suffering multiple organ failure. 2. We have studied exogenous glucose utilization in multiple organ failure using a combination of the hyperglycaemic glucose clamp and indirect calorimetry to quantify glucose utilization in multiple organ failure, partitioning it into oxidative and nonoxidative disposal (storage). 3. Fourteen septic patients with multiple organ failure were studied. APACHE II (Acute Physiological and Chronic Health Evaluation Mark II) scores on the day of the study ranged from 11 to 31 (median 16). Twenty percent D-glucose was infused and blood glucose was clamped at 12 mmol/l for 3 h. The results were compared with those obtained on seven healthy control subjects. 4. Glucose utilization and energy expenditure were similar in the two groups for the first 90 min of the clamp, after which glucose utilization and energy expenditure increased steadily in the control subjects but did not change in the patients. Respiratory exchange ratio rose in both groups; considered over the whole of the clamp period, respiratory exchange ratio was slightly lower in the patients than in the control subjects (P < 0.05) but not at any specific time point. Glucose oxidation rose in both groups but non-oxidative glucose disposal (storage) rose only in the control subjects. Glucose oxidation was slightly lower in the patients (P < 0.05) but not at any specific time point and there was no difference between the groups in the amount by which glucose oxidation increased. Non-oxidative disposal in the patients fell significantly (P < 0.01) over the course of the clamp and was significantly lower than in the control subjects (P < 0.01). 5. Growth hormone increased in response to glucose infusion in the patients but not in the control subjects. 6. Like patients suffering uncomplicated sepsis or trauma, patients with multiple organ failure are also insulin resistant. The defect appears to lie in an impairment of the ability to store glucose rather than oxidize it, and this may be due in part to the increase in growth hormone in patients with multiple organ failure.

Stress hyperglycaemia

“…69 Additionally, impaired non-oxidative glucose disposal probably results from reduced skeletal muscle glycogen synthesis. 70 Both excess cortisol 71 and epinephrine 72 reduce insulin-mediated glucose uptake. Cytokines such as TNFα, 73 and interleukin 1 74 inhibit postreceptor insulin signalling.…”

Effect of a 2-h hyperglycemic–hyperinsulinemic glucose clamp to promote glucose storage on endurance exercise performance

“…Other studies with subjects at rest, and under conditions of hyperglycemia or euglycemic-hyperinsulinemia, have confirmed increases in glucose oxidation, as well as nonoxidative glucose disposal. Peripheral tissues, probably muscle, are primarily responsible for the disposal of most of the infused glucose load (DeFronzo et al 1981;Ferrannini et al 1989;Green et al 1995;Shulman et al 1990). Studies using indirect calorimetry in combination with hepatic and femoral-vein cannulation, and the euglycemic insulin clamp, have shown that the major site of non-oxidative disposal of glucose given intravenously in normal subjects is muscle (DeFronzo et al 1981).…”

Untitled

“…Insulin levels are usually within the normal or mildly elevated range, but are not sufficiently elevated to prevent hyperglycaemia. Hyperglycaemia may also be due to reduced nonoxidative glucose disposal that results from decreased muscle glycogen synthetase activity [2,3]. The hyperglycaemia is thought to ensure a ready supply of glucose to predominantly glucose-consuming cells, such as the wound, inflammatory cells and immune cells [4].…”

“…Insulin resistance occurred after both elective open and laparoscopic cholecystectomy, and persisted for at least 5 days [6,7]. The overall amount of glucose oxidized may be decreased, despite a glucose oxidization pathway that is thought to be intact, because of the reduced rate of glucose uptake into the cell [3]. The incremental response to increases in insulin concentration is maintained [8], but the ability to reduce blood glucose concentrations per insulin concentration is markedly diminished [9].…”