High dose amino acid administration achieves an anabolic response in type 2 diabetic patients that is independent of glycaemic control: A randomized clinical trial

Abstract

Surgical stress provokes protein catabolism and hyperglycaemia that is enhanced in patients with type 2 diabetes (T2DM), and increases perioperative morbidity. This study hypothesized that perioperative administration of high dose intravenous (IV) amino acids (AA) will augment protein balance in T2DM patients receiving tight plasma glucose control via continuous IV insulin compared to standard plasma glucose control via subcutaneous (SC) insulin sliding scale. Eighteen patients with well-controlled T2DM (HbA1C%<7.1) undergoing colorectal surgery were assigned randomly to receive standard glucose control (6-10mmol/l, SC insulin, n=9) or tight glucose control (4-6mmol/l, IV insulin, n=9). Both groups received general anaesthesia and epidural analgesia. AA (1ml/kgh Aminoven™ 10%, ∼2.4g/kgd) were infused via a peripheral vein for two 3-hperiods: at the beginning of surgery and in the post-operative care unit. Whole-body protein and glucose kinetics were assessed by stable isotope tracers, L-[1-13C]leucine and [6,6-2H2]glucose. Whole-body protein balance was positive after surgery in all patients. Since protein synthesis, breakdown and leucine oxidation were comparable in both groups, whole body protein balance was not different (p=0.605). Tight glucose control suppressed endogenous glucose production (EGP, p<0.001) and increased glucose clearance (p<0.001) compared to standard glucose control during both study periods. No episode of hypoglycaemia occurred in either group. High-dose perioperative AA administration under optimal anti-catabolic care with epidural analgesia was effective in achieving a positive protein balance in T2DM patients undergoing surgery that was independent of glycaemic control strategy. Continuous IV insulin maintained normoglycaemia by inhibiting EGP and increasing glucose clearance. Improved glucose control, without a pronounced increase in protein balance with the intravenous insulin regimen, suggests perioperative protein metabolism may be less sensitive to insulin than is glucose.