Metabolic effects of intensive insulin therapy in critically ill patients

Abstract

Our aim was to investigate the effects of glycemic control and insulin concentration on lipolysis, glucose, and protein metabolism in critically ill medical patients. For our methods, the patients were studied twice. In study 1, blood glucose (BG) concentrations were maintained between 7 and 9 mmol/l with intravenous insulin. After study 1, patients entered one of four protocols for 48 h until study 2: low-insulin high-glucose (LIHG; variable insulin, BG of 7-9 mmol/l), low-insulin low-glucose (LILG; variable insulin of BG 4-6 mmol/l), high-insulin high-glucose [HIHG; insulin (2.0 mU . kg(-1).min(-1) plus insulin requirement from study 1), BG of 7-9 mmol/l], or high-insulin low-glucose [HILG; insulin (2.0 mU.kg(-1).min(-1) plus insulin requirement from study 1), BG of 4-6 mmol/l]. Age-matched healthy control subjects received two-step euglycemic hyperinsulinemic clamps achieving insulin levels similar to the LI and HI groups. In our results, whole body proteolysis was higher in patients in study 1 (P < 0.006) compared with control subjects at comparable insulin concentrations and was reduced with LI (P < 0.01) and HI (P = 0.001) in control subjects but not in patients. Endogenous glucose production rate (R(a)), glucose disposal, and lipolysis were not different in all patients in study 1 compared with control subjects at comparable insulin concentrations. Glucose R(a) and lipolysis did not change in any of the study 2 patient groups. HI increased glucose disposal in the patients (HIHG, P = 0.001; HILG, P = 0.07 vs. study 1), but this was less than in controls receiving HI (P < 0.03). In conclusion, low-dose intravenous insulin administered to maintain BG between 7-9 mmol/l is sufficient to limit lipolysis and endogenous glucose R(a) and increase glucose R(d). Neither hyperinsulinemia nor normoglycemia had any protein-sparing effect.

Current recommended parenteral protein intakes do not support protein synthesis in critically ill septic, insulin-resistant adolescents with tight glucose control

“…All septic patients showed considerable insulin resistance with an about 65% decrease in insulin sensitivity when compared to values of ϳ11 (mg⅐kg -1 ⅐min -1 )/ (microunit⅐mL -1 ) reported in fasting healthy adolescents (51,52), and the degree of insulin resistance is comparable to that observed in critically ill adults (4.6 [mg⅐ kg -1 ⅐min -1 ]/[mU ⅐ mL Ϫ1 ]) (53). Despite significant insulin resistance, when the SAA intake was supplied in the presence of insulin, endogenous glucose production was suppressed, which is in agreement with previous studies in critically ill adults (54)(55)(56)(57).…”

“…Insulin did not decrease lipolysis, and this is consistent with data in critically ill adults (56,60). Furthermore, lipolysis increased at HAA intakes, again raising concern for increased insulin resistance when the HAA intake was provided.…”

Moderate glucose control results in less negative nitrogen balances in medical intensive care unit patients: a randomized, controlled study

“…Acute hyperglycemia enhances proteolysis in the entire body during hyperinsulinemia in normal men [50]. Additionally, Whyte and colleagues demonstrated that the administration of insulin which resulted in supraphysiological concentrations did not attenuate protein breakdown and had no effect on the net protein balance in critically ill patients [51]. …”

Protein Requirements of the Critically Ill Pediatric Patient

“…Insulin is essential for skeletal muscle protein deposition by inhibiting muscle protein degradation, stimulating protein synthesis, and improving energy homeostasis 47 . Several studies have found that insulin stimulates skeletal muscle protein synthesis and inhibits muscle protein degradation during critical illness 48 , 49 but has failed to attenuate whole‐body proteolysis when provided at higher than physiological concentrations, 50 , 51 due to systemic inflammation and circulating cytokines (ie, tumor necrosis factor–α) 52 , 53 . The beneficial effects of insulin on whole‐body protein metabolism are present only with adequate availability of amino acids, 25 , 50 , 53 , 54 related to glucose and energy homeostasis, 42 , 55 and are associated with stimulation of translation signaling pathways with a resultant increase in protein synthesis, 56 modulation of protein degradation, 42 , 50 and intrinsic anti‐inflammatory effects 57 …”