The impact of a modified carbohydrate formula, and its constituents, on glycaemic control and inflammatory markers: A nested mechanistic sub-study.

BACKGROUND: Hyperglycaemia occurs frequently in the critically ill. Dietary intake of advanced glycation end-products (AGEs), specifically Nε-(carboxymethyl)lysine (CML), may exacerbate hyperglycaemia through perturbation of insulin sensitivity. The present study aimed to determine whether the use of nutritional formulae, with varying AGE loads, affects the amount of insulin administered and inflammation. METHODS: Exclusively tube fed patients (n = 35) were randomised to receive Nutrison Protein Plus Multifibre®, Diason® or Glucerna Select®. Insulin administration was standardised according to protocol based on blood glucose (<10 mmol L-1 ). Samples were obtained at randomisation and 48 h later. AGEs in nutritional formula, plasma and urine were measured using mass spectrometry. Plasma inflammatory markers were measured using an enzyme-linked immunosorbent assay and multiplex bead-based assays. RESULTS: AGE concentrations of CML in nutritional formulae were greatest with delivery of Nutrison Protein Plus® (mean [SD]; 6335 pmol mol-1 [2436]) compared to Diason® (4836 pmol mol-1 [1849]) and Glucerna Select® (4493 pmol mol-1 [1829 pmol mol-1 ]) despite patients receiving similar amounts of energy (median [interquartile range]; 12 MJ [8.2-13.7 MJ], 11.5 MJ [8.3-14.5 MJ], 11.5 MJ [8.3-14.5 MJ]). More insulin was administered with Nutrison Protein Plus® (2.47 units h-1 [95% confidence interval (CI) = 1.57-3.37 units h-1 ]) compared to Diason® (1.06 units h-1 [95% CI = 0.24-1.89 units h-1 ]) or Glucerna Select® (1.11 units h-1 [95% CI = 0.25-1.97 units h-1 ]; p = 0.04). Blood glucose concentrations were similar. There were associations between greater insulin administration and reductions in circulating interleukin-6 (r = -0.46, p < 0.01), tumour necrosis factor-α (r = -0.44, p < 0.05), high sensitivity C-reactive protein (r = -0.42, p < 0.05) and soluble receptor for advanced glycation end-products (r = -0.45, p < 0.01) concentrations. CONCLUSIONS: The administration of greater AGE load in nutritional formula potentially increases the amount of insulin required to maintain blood glucose within a normal range during critical illness. There was an inverse relationship between exogenous insulin and plasma inflammatory markers.

The effect of a low carbohydrate formula on glycaemia in critically ill enterally-fed adult patients with hyperglycaemia: A blinded randomised feasibility trial.

BACKGROUND: Enteral nutrition is a source of carbohydrate that may exacerbate hyperglycaemia. Its treatment, insulin, potentially exacerbates glycaemic variability. METHODS: This was a prospective, parallel group, blinded, randomised feasibility trial. Patients were eligible if 18 years or over when admitted to the intensive care unit and receiving enteral nutrition (EN) exclusively with two consecutive blood glucose > 10 mmol/L. A standardized glucose management protocol determined administration of insulin. Key outcome measures were insulin administered and glycaemic variability (coefficient of variation) over the first 48 h. RESULTS: 41 patients were randomized to either standard EN (14.1 g/100 mL carbohydrate; n = 20) or intervention EN (7.4 g/100 mL carbohydrate; n = 21). Overall 59% were male, mean (±SD) age of 62.3 years ± 10.4, APACHE II score of 16.5 ± 7.8 and a median (IQR) Body Mass Index 29.0 kg/m2 (25.2-35.5). Most patients (73%) were mechanically ventilated. Approximately half (51%) were identified as having diabetes prior to ICU admission. Patients in the intervention arm received less insulin over the 48 h study period than those in the control group (mean insulin units over study period (95% CI) 45.0 (24.4-68.7) vs. 107 (56.1-157.9) units; p = 0.02) and had lower mean glycaemic variability (12.6 vs. 15.9%, p = 0.01). There was a small difference in the mean percentage of energy requirements met (intervention: 72.9 vs. control: 79.1%; p = 0.4) or protein delivered (78.2 vs. 85.4%; p = 0.3). CONCLUSIONS: A low carbohydrate formula was associated with reduced insulin use and glycaemic variability in enterally-fed critically ill patients with hyperglycaemia. Further large trials are required to determine the impact of this formula on clinical outcomes. Registered under Australian and New Zealand Clinical Trials Registry, ANZCTR number: 12614000166673.