Leptin levels in protracted critical illness: Effects of growth hormone-secretagogues and thyrotropin-releasing hormone

被引:31
作者
Van den Berghe, G [1 ]
Wouters, P
Carlsson, L
Baxter, RC
Bouillon, R
Bowers, CY
机构
[1] Catholic Univ Louvain, Hosp Gasthuisberg, Dept Intens Care Med, B-3000 Louvain, Belgium
[2] Catholic Univ Louvain, Hosp Gasthuisberg, Dept Med, Div Endocrinol, B-3000 Louvain, Belgium
[3] Sahlgrens Univ Hosp, Dept Internal Med, Res Ctr Endocrinol & Metab, S-41345 Gothenburg, Sweden
[4] Univ Sydney, Kolling Inst, St Leonards, NSW SW2065, Australia
[5] Tulane Univ, Med Ctr, Div Endocrinol, New Orleans, LA 70112 USA
关键词
D O I
10.1210/jc.83.9.3062
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 tone 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-mu g/kg bolus at 0900 h and infused (1 mu g/kg.h) until 0600 h the next morning. Serum concentrations of leptin, insulin, cortisol, T-4, T-3, 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 mu g/L) were independent of body mass index (25 +/- 1 kg/m(2)), insulin (18.6 +/- 2.9 mu IU/mL), cortisol (504 +/- 43 mmol/L), and thyroid hormones (T-4: 63 +/- 5 nmol/L, T-3: 0.72 +/- 0;08 nmol/L) but correlated positively with circulating levels of IGF-I [86 +/- 6 mu g/L, determination coefficient (R-2) = 0.25] and ALS (7.2 +/- 0.6 mg/L, R-2 = 0.32). Infusion of placebo or TRH had no effect on leptin. In contrast, GH-secretagoues 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 36 h. The increase in leptin within 12 h was related (R-2 = 0.58) to the substantial rise in insulin. After 45 h, and having reached a plateau, leptin was related to the increased IGF-I (R-2 = 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.
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收藏
页码:3062 / 3070
页数:9
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