92608
document
Leptin levels in protracted critical illness : effects of growth hormone-secretagogues and thyrotropin-releasing hormone . Prolonged critical illness is characterized by feeding-resistant wasting of protein , whereas reesterification , instead of oxidation of fatty acids , allows fat stores to accrue and associate with a low-activity status of the somatotropic and thyrotropic axis , which seems to be partly of hypothalamic origin . To further unravel this paradoxical metabolic condition , and in search of potential therapeutic strategies , we measured serum concentrations of leptin ; studied the relationship with body mass index , insulin , cortisol , thyroid hormones , and somatomedins ; and documented the effects of hypothalamic releasing factors , in particular , GH-secretagogues and TRH . Twenty adults , critically ill for several weeks and supported with normocaloric , continuously administered parenteral and/or enteral feeding , were studied for 45 h. They had been randomized to receive one of three combinations of peptide infusions , in random order : TRH ( one day ) and placebo ( other day ) ; TRH + GH-releasing peptide ( GHRP ) -2 and GHRP-2 ; TRH + GHRH + GHRP-2 and GHRH + GHRP-2 . Peptide infusions were started after a 1-microgram/kg bolus at 0900 h and infused ( 1 microgram/kg.h ) until 0600 h the next morning . Serum concentrations of leptin , insulin , cortisol , T4 , T3 , insulin-like growth factor ( IGF ) -I , IGF-binding protein-3 and the acid-labile subunit ( ALS ) were measured at 0900 h , 2100 h , and 0600 h on each of the 2 study days . Baseline leptin levels ( mean +/- SEM : 12.4 +/- 2.1 micrograms/L ) were independent of body mass index ( 25 +/- 1 kg/m2 ) , insulin ( 18.6 +/- 2.9 microIU/mL ) , cortisol ( 504 +/- 43 mmol/L ) , and thyroid hormones ( T4 : 63 +/- 5 nmol/L , T3 : 0.72 +/- 0.08 nmol/L ) but correlated positively with circulating levels of IGF-I [ 86 +/- 6 micrograms/L , determination coefficient ( R2 ) = 0.25 ] and ALS ( 7.2 +/- 0.6 mg/L , R2 = 0.32 ) . Infusion of placebo or TRH had no effect on leptin . In contrast , GH-secretagogues elevated leptin levels within 12 h. Infusion of GHRP-2 alone induced a maximal leptin increase of +87 % after 24 h , whereas GHRH + GHRP-2 elevated leptin by up to +157 % after 24 h. The increase in leptin within 12 h was related ( R2 = 0.58 ) to the substantial rise in insulin . After 45 h , and having reached a plateau , leptin was related to the increased IGF-I ( R2 = 0.37 ) . In conclusion , circulating leptin levels during protracted critical illness were linked to the activity state of the GH/IGF-I axis . Stimulating the GH/IGF-I axis with GH-secretagogues increased leptin levels within 12 h. Because leptin may stimulate oxidation of fatty acids , and because GH , IGF-I , and insulin have a protein-sparing effect , GH-secretagogue administration may be expected to result in increased utilization of fat as preferential substrate and to restore protein content in vital tissues and , consequently , has potential as a strategy to reverse the paradoxical metabolic condition of protracted critical illness .
92609
Intervention_Pharmacological
growth hormone-secretagogues
92610
Intervention_Pharmacological
thyrotropin-releasing hormone .
92611
Intervention_Pharmacological
TRH
92612
Intervention_Educational
( one day )
92613
Intervention_Control
placebo
92614
Intervention_Control
placebo
92615
Intervention_Pharmacological
TRH
92616
Intervention_Pharmacological
GH-secretagogue
92617
Outcome_Physical
Serum concentrations of leptin
92618
Outcome_Physical
insulin
92619
Outcome_Physical
cortisol
92620
Outcome_Physical
T4
92621
Outcome_Physical
T3
92622
Outcome_Physical
insulin-like growth factor ( IGF ) -I
92623
Outcome_Physical
IGF-binding protein-3
92624
Outcome_Physical
acid-labile subunit ( ALS )
92625
Outcome_Physical
Baseline leptin levels
92626
Outcome_Physical
leptin
92627
Outcome_Physical
leptin levels
92628
Outcome_Physical
maximal leptin increase
92629
Outcome_Physical
leptin
92630
Outcome_Physical
leptin within 12
92631
Outcome_Physical
leptin
92632
Outcome_Physical
increased IGF-I
92633
Outcome_Physical
circulating leptin levels
92634
Outcome_Physical
leptin levels