leptin and Critical-Illness

Obesity has become a world-wide pandemic and is considered a major risk factor for various diseases. Despite this, recent intriguing clinical observations have been made suggesting that being overweight has some advantages. Overweight and some obese patients were reported to have significantly lower all-cause mortality, described as the 'obesity paradox'. This phenomenon resulted in increased research aimed at investigating the influence of adipose tissue on outcomes of various clinical states including critical illness. In this review, we summarise research findings on the effect burn injury and trauma-related critical illness have on adipose tissue and discuss potential mechanisms by which adipose tissue influences outcomes in burn and other critically ill patients. Burn injury and critical illness influence adipose tissue functionally and morphologically, with circulating levels of fat derived hormones, adipokines, altered in patients following injury and/or critical illness. As adipokines regulate a variety of processes including inflammation and metabolism, this disruption in the adipokine axis may explain the obesity paradox phenomenon observed in critically ill patients. We conclude that further research on the influence of individual adipokines on prognosis in burn and critically ill patients and the mechanisms involved is required to increase understanding of their therapeutic potential.

Topics: Adipokines; Adiponectin; Adipose Tissue; Burns; Critical Illness; Fibrosis; Ghrelin; Humans; Inflammation; Leptin; Nicotinamide Phosphoribosyltransferase; Obesity; Overweight; Resistin; Skin; Wound Healing

Observational studies report lower mortality in obese than in lean critically ill patients, an association referred to as the "obesity paradox." This may suggest a possible protective role for adipose tissue during severe illness.. Relevant publications were identified based on searches in PubMed and on secondary searches of their bibliographies.. The endocrine functions of adipose tissue might play a role in the adaptation to critical illness. In the acute phase of illness, the anti-inflammatory adiponectin is reduced, whereas proinflammatory cytokine expression in adipose tissue is up-regulated. In the prolonged phase of critical illness, both adiponectin and anti-inflammatory cytokine production are increasing. Studies on the proinflammatory adipokine leptin during critical illness are inconsistent, possibly due to confounders such as gender, body mass index, and feeding. Morphologically, adipose tissue of critically ill patients reveals an increased number of newly differentiated, smaller adipocytes. Accentuated macrophage accumulation showing a phenotypic switch to M2-type suggests an adaptive response to the microenvironment of severe illness. Functionally, adipose tissue of critically ill patients develops an increased ability to store glucose and triglycerides.. Endocrine, metabolic, and morphologic properties of adipose tissue change during critical illness. These alterations may suggest a possible adaptive, protective role in optimizing chances of survival. More research is needed to understand the exact role of adipose tissue in lean vs. obese critically ill patients, in order to understand how illness-associated alterations contribute to the obesity paradox.

Topics: Adaptation, Physiological; Adipocytes; Adiponectin; Adipose Tissue; Body Mass Index; Critical Illness; Cytokines; Endocrine System; Energy Metabolism; Humans; Leptin; Macrophage Activation; Obesity

Our study aim was to assess how the macronutrient intake during total parenteral nutrition (TPN) modulates plasma total free fatty acids (FFAs) levels and individual fatty acids in critically ill patients.. Adult patients aged 18-80, admitted to the intensive care unit (ICU), who were indicated for TPN, with an expected duration of more than three days, were included in the study. Isoenergetic and isonitrogenous TPN solutions were given with a major non-protein energy source, which was glucose (group G) or glucose and lipid emulsions (Smof lipid; group L). Blood samples were collected on days 0, 1, 3, 6, 9, 14, and 28.. A significant decrease (. Decreased plasma FFA in critically ill patients who receive TPN may result from increased insulin sensitivity with a better effect in group G, owing to higher insulin and glucose dosing and no lipid emulsions. It is advisable to include a lipid emulsion at the latest from three weeks of TPN to prevent essential fatty acid deficiency.

Topics: Aged; alpha-Tocopherol; Critical Illness; Emulsions; Fatty Acids, Essential; Fatty Acids, Nonesterified; Female; Glucose; Humans; Insulin Resistance; Intensive Care Units; Leptin; Lipids; Male; Middle Aged; Parenteral Nutrition, Total; Prospective Studies

Previous studies have shown a beneficial effect of curcuminoids supplementation on serum concentrations of adipokines; however, there are no published studies that have examined this effect among critically ill patients. We aimed to assess the effects of supplementation with curcuminoids on serum concentrations of leptin and adiponectin in critically ill patients with traumatic brain injury (TBI). In this trial, 62 critically ill patients with TBI, aged 18-65 years, were randomly allocated to receive either 500 mg/day curcuminoids (co-administered with 5 mg/day piperine) or matched placebo for 7 days. Patients in both intervention groups received routine treatments for TBI as well as enteral nutrition. Serum concentrations of leptin and adiponectin were measured at baseline and at the end of trial. We found a significant reduction in serum levels of leptin in both curcuminoids (47.1%) and placebo (22.8%) groups; though the magnitude of reduction was greater in the former (p < .05). Supplementation with curcumioinds was not found to alter serum concentrations of adiponectin (p > .05). Supplementation with curcumioinds significantly reduced serum levels of leptin but had no significant effect on adiponectin levels in critically ill patients with TBI. Further clinical trials, particularly those with a long-term period, are needed to confirm our findings.

Topics: Adipokines; Adiponectin; Adolescent; Adult; Aged; Alkaloids; Benzodioxoles; Critical Illness; Curcumin; Diarylheptanoids; Dietary Supplements; Double-Blind Method; Female; Humans; Iran; Leptin; Male; Middle Aged; Piperidines; Placebos; Polyunsaturated Alkamides; Young Adult

Both critical illness and fasting induce low circulating thyroid hormone levels in the absence of a rise in TSH, a constellation-labeled nonthyroidal illness syndrome (NTI). The contribution of restricted nutrition during critical illness in the pathophysiology of NTI remains unclear.. The objective of the study was to investigate the impact of nutrient restriction early during critical illness on the NTI, in relation to outcome.. A preplanned subanalysis in a group of intensive care unit (ICU) patients admitted after complicated surgery and for whom enteral nutrition was contraindicated (n = 280) of a randomized controlled trial, which compared tolerating pronounced nutritional deficit for 1 week in the ICU [late parenteral nutrition (PN)] with early initiation of parenteral nutrition (early PN).. Circulating TSH, total T4, T3, rT3, and leptin levels were quantified upon admission and on ICU day 3 or the last day when patients were discharged earlier. After correction for baseline risk factors, the role of these changes from baseline in explaining the outcome benefit of late PN was assessed with the multivariable Cox proportional hazard analysis.. Late PN reduced complications and accelerated recovery. Circulating levels of TSH, total T4, T3, the T3 to rT3 ratio, and leptin levels were all further reduced by late PN. The further lowering of T4 appeared to reduce the outcome benefit of late PN, whereas the further reduction of T3 to rT3 ratio appeared to statistically explain part of the outcome benefit.. Tolerating nutrient restriction early during critical illness, shown to accelerate recovery, further aggravated the NTI. The statistical analyses suggested that the more pronounced peripheral inactivation of the thyroid hormone with nutrient restriction during critical illness could be a beneficial adaptation, whereas the lowering of T4 could be deleterious.

Topics: Aged; Critical Care; Critical Illness; Fasting; Female; Food Deprivation; Humans; Leptin; Male; Middle Aged; Parenteral Nutrition; Proportional Hazards Models; Prospective Studies; Recovery of Function; Risk Factors; Thyroid Gland; Thyrotropin; Thyroxine; Treatment Outcome; Triiodothyronine

Critically ill patients requiring intensive care uniformly develop insulin resistance. This is most pronounced in patients with sepsis. Recently, several hormones secreted by adipose tissue have been identified to be involved in overall insulin sensitivity in metabolic syndrome-related conditions. However, little is known about these adipokines in critical illness.. We studied circulating levels of the adipokines adiponectin, retinol-binding protein 4 (RBP4), and leptin during critical illness, and the impact of intensive insulin therapy, a therapy shown to affect insulin sensitivity, in serum samples from prolonged critically ill patients with a respiratory critical illness (n = 318). For comparison, we studied healthy subjects (n = 22) and acutely stressed patients (n = 22).. During acute critical illness, circulating levels of adiponectin, RBP4, and leptin were low. Patients with sepsis had lower levels of leptin and RBP4 than did nonseptic patients. When critical illness was sustained, adipokine levels returned to normal reference values. Insulin therapy enhanced adiponectin, blunted the rise of RBP4, and did not alter leptin levels.. Acute critical illness is associated with immediate, but transiently low serum adipokine levels. Adiponectin and RBP4 are associated with altered insulin resistance in critical illness.

Topics: Adiponectin; Aged; Aged, 80 and over; Critical Illness; Female; Humans; Leptin; Lung Diseases; Male; Middle Aged; Retinol-Binding Proteins, Plasma

Protracted critical illness is marked by protein wasting resistant to feeding, by accumulation of fat stores, and by suppressed pulsatile release of GH and TSH. We previously showed that the latter can be reactivated by brief infusion of GH-releasing peptide (GHRP-2) and TRH. Here, we studied combined GHRP-2 and TRH infusion for 5 days, which allowed a limited evaluation of the metabolic effectiveness of this novel trophic endocrine strategy. Fourteen patients (mean +/- SD age, 68 +/- 11 yr), critically ill for 40 +/- 28 days, were compared to a matched group of community-living control subjects at baseline and subsequently received 5 days of placebo and 5 days of GHRP-2 plus TRH (1 + 1 microg/kg x h) infusion in random order. At baseline, impaired anabolism, as indicated by biochemical markers (osteocalcin and leptin), was linked to hyposomatotropism [reduced pulsatile GH secretion, as determined by deconvolution analysis, and low GH-dependent insulin-like growth factor and binding protein (IGFBP) levels]. Biochemical markers of accelerated catabolism (increased protein degradation and bone resorption) were related to tertiary hypothyroidism and the serum concentration of IGFBP-1, but not to hyposomatotropism. Metabolic markers were independent of elevated serum cortisol. After 5 days of GHRP-2 plus TRH infusion, osteocalcin concentrations increased 19% vs. -6% with placebo, and leptin had rose 32% vs. -15% with placebo. These anabolic effects were linked to increased IGF-I and GH-dependent IGFBP, which reached near-normal levels from day 2 onward. In addition, protein degradation was reduced, as indicated by a drop in the urea/creatinine ratio, an effect that was related to the correction of tertiary hypothyroidism, with near-normal thyroid hormone levels reached and maintained from day 2 onward. Concomitantly, a spontaneous tendency of IGFBP-1 to rise and of insulin to decrease was reversed. Cortisol concentrations were not detectably altered. In conclusion, 5-day infusion of GHRP-2 plus TRH in protracted critical illness reactivates blunted GH and TSH secretion, with preserved pulsatility, peripheral responsiveness, and feedback inhibition and without affecting serum cortisol, and induces a shift toward anabolic metabolism. This provides the first evidence of the metabolic effectiveness of short term GHRP-2 plus TRH agonism in this particular wasting condition.

Topics: Adult; Aged; Aged, 80 and over; Bone and Bones; Critical Illness; Cross-Over Studies; Female; Human Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor Binding Proteins; Leptin; Male; Middle Aged; Oligopeptides; Proteins; Thyrotropin; 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

Topics: Adult; Aged; Body Mass Index; Critical Illness; Cross-Over Studies; Female; Growth Hormone-Releasing Hormone; Human Growth Hormone; Humans; Hydrocortisone; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Male; Middle Aged; Oligopeptides; Proteins; Thyroid Hormones; Thyrotropin-Releasing Hormone

Altered levels of some blood markers might be linked with the degree of severity and mortality of patients with SARS-CoV-2 infection. This study aimed to find out if there are correlations between serum leptin levels and classical biomarkers.. We present a single-center observational cohort study on SARS-CoV-2 infected patients. The study was conducted at Infectious Diseases Clinic of Academic Emergency Hospital Sibiu, from May through November 2020. In this study, we retrospectively analyzed 54 patients, all with confirmed SARS-CoV-2 infection.. Our results revealed that there is a negative correlation between serum leptin and Interleukin-6 levels and a positive correlation between serum leptin and blood glucose levels. A positive correlation between ferritin and lactate dehydrogenase levels was also observed. No correlation was found between leptin and other biomarkers such as ferritin, neutrophil/lymphocyte ratio, lactate dehydrogenase, C-reactive protein, fibrinogen, erythrocyte sedimentation rate, or D-dimer.. Further studies need to be conducted to investigate the role of leptin in SARS-CoV-2 infection. The results of this research could contribute to the introduction of the determination of serum leptin levels in the routine evaluation of patients with critical illness.

Topics: Biomarkers; C-Reactive Protein; COVID-19; Critical Illness; Ferritins; Humans; Lactate Dehydrogenases; Leptin; Retrospective Studies; SARS-CoV-2

Leptin, the prototype adipokine, exerts immunomodulatory actions being implicated in inflammatory responses during sepsis. Clinical evidence regarding its role in sepsis has been contradictory, while free leptin has not been studied. The aim of this study was to jointly investigate circulating total leptin, its soluble receptor (sOB-R), and free leptin, as well as their kinetics in critically ill patients with sepsis regarding their diagnostic and prognostic value.. In a prospective study, serum total leptin, sOB-R and free leptin index (FLI) were determined in 102 critically ill patients with sepsis within 48 hours from sepsis onset and one week after enrollment, and in 102 age and gender-matched healthy controls.. Upon enrolment, total leptin, sOB-R and FLI were significantly higher in septic patients compared to controls and they were positively correlated with sepsis severity scores, while they presented a significant decrease during the first week (P<0.001). The decrease in total leptin and sOB-R was significantly higher in patients with sepsis compared to septic shock and in survivors compared to non-survivors at 28 days (P<0.001). Higher serum total leptin was independently associated with survival at 28 days (enrollment: HR 0.86, P=0.03; one week after: HR 0.77, P<0.001). Higher kinetics of total leptin (but not FLI) was independently associated with survival after adjustment (HR: 0.48, P=0.001).. Higher circulating total leptin and its higher kinetics during the first week from sepsis onset independently predict 28-day survival in critically ill patients. Free leptin did not present any additional diagnostic and prognostic value in sepsis.

Topics: Critical Illness; Humans; Leptin; Prospective Studies; Receptors, Leptin; Sepsis

Ghrelin is a hormone mainly produced by cells of the gastric mucosa, which has been shown to possess anti-inflammatory and immunomodulatory properties. The objective of the study was to investigate ghrelin levels during sepsis, as well as in an experimental sepsis model.. All consecutive admissions to the ICU of a tertiary hospital in Athens, Greece were screened for eligibility during the study. Thirty four non-septic patients upon ICU admission who subsequently developed sepsis were enrolled. Clinical data and scores were recorded, and blood samples were obtained at baseline (upon ICU admission), and at sepsis development. Total and active ghrelin, leptin, and cytokines were measured. Moreover, lipopolysaccharide (LPS) was administered to mice in order to induce endotoxemia and at specified time points, blood and tissue samples were collected.. In patients, serum total and active ghrelin concentrations were significantly elevated in sepsis compared to baseline (553.8 ± 213.4 vs 193.5 ± 123.2, p < 0.001; 254.3 ± 70.6 vs 56.49 ± 16.3, p < 0.001). Active ghrelin levels at the sepsis stage were inversely correlated with SOFA score and length of stay in the ICU (p = 0.023 and p = 0.027 respectively). In the mouse endotoxemia model ghrelin levels were elevated following LPS treatment, and the same trend was observed for leptin, TNFα and IL-6. Ghrelin administration managed to reduce IL-6 levels in mouse serum and in BALF. Pulmonary expression of ghrelin and its receptor GHSR1a was found decreased in LPS-treated mice.. In a well-defined cohort of ICU patients, we have demonstrated that active and total ghrelin increase in sepsis. The same is true for the experimental sepsis model used in the study. The inverse correlation of active ghrelin levels with SOFA score and length of ICU stay among septic patients is indicative of a potential protective role of active ghrelin during the septic process.

Topics: Animals; Critical Illness; Cytokines; Endotoxemia; Enzyme-Linked Immunosorbent Assay; Female; Ghrelin; Humans; Intensive Care Units; Leptin; Lipopolysaccharides; Male; Mice, Inbred C57BL; Middle Aged; Sepsis

Adipokines play an important role in the regulation of metabolism. In critical illness, they alter serum levels and are suspected to worsen clinical outcomes. But the effect of the route of nutrition on adipokines is not known. The purpose of this study was to evaluate the association between the route of nutrition and adipokine levels in critically ill patients.. This prospective study was performed in an intensive care unit (ICU). Patients admitted to the ICU for least 72 h and receiving either enteral nutrition (EN) via tube feeding or parenteral nutrition (PN) were enrolled. Serum was obtained at baseline, 24 h, and 72 h for concentrations of leptin, adiponectin, resistin, glucagon–like peptide 1 (GLP–1), insulin–like growth factors 1 (IGF–1), and ghrelin.. A total of 26 patients were included in the study. Thirteen patients received EN and 13 patients received PN. In the PN group, leptin level significantly increased (P = 0.037), adiponectin and ghrelin significantly decreased during follow up (P = 0.037, P = 0.008, respectively). There was no significant change between all adipokines in the EN group and resistin, IGF–1 and GLP–1 in the PN group during follow up. Resistin levels were markedly lower in the EN group at both 24 h (P = 0.015) and 72 h (P = 0.006) while GLP–1 levels were higher in the EN group at baseline, 24 h, and 72 h (P = 0.018, P = 0.005, and P = 0.003, respectively). There were no differences in leptin, adiponectin, IGF–1, and ghrelin levels over time.. The delivery of EN in critical illness was associated with decreased resistin levels and increased GLP–1 levels. Thus, the route of nutrition may impact the clinical outcome in critical illness due to adipokines.

Topics: Adipokines; Adult; Aged; Biomarkers; Critical Illness; Female; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin-Like Growth Factor I; Leptin; Male; Middle Aged; Nutritional Support; Pilot Projects; Prospective Studies; Resistin

The objective of this study was to evaluate leptin, ghrelin, and leptin/ghrelin ratio in critically ill patients and association of leptin/ghrelin ratio with outcomes. This is a sub-study of the PermiT trial (ISRCTN68144998). A subset of 72 patients who were expected to stay >14 days in the Intensive care unit were enrolled. Blood samples were collected on days 1, 3, 5, 7, and 14. Samples were analyzed for leptin and active ghrelin in addition to other hormones. Baseline leptin/ghrelin ratio was calculated, and patients were stratified into low and high leptin/ghrelin ratio based on the median value of 236. There was a considerable variation in baseline leptin level: Median 5.22 ng/mL (Q1, Q3: 1.26, 17.60). Ghrelin level was generally low: 10.61 pg/mL (Q1, Q3: 8.62, 25.36). Patients with high leptin/ghrelin ratio compared to patients with low leptin/ghrelin ratio were older, had higher body mass index and more likely to be diabetic. There were no differences in leptin/ghrelin ratio between patients who received permissive underfeeding and standard feeding. Multivariable logistic regression analysis showed that age and body mass index were significant independent predictors of high leptin-ghrelin ratio. Leptin-ghrelin ratio was not associated with 90-day mortality or other outcomes. Age and body mass index are predictors of high leptin/ghrelin ratio. Leptin/ghrelin ratio is not affected by permissive underfeeding and is not associated with mortality.

Topics: Adult; Aged; Biomarkers; Critical Illness; Female; Ghrelin; Humans; Leptin; Logistic Models; Male; Middle Aged; Multivariate Analysis; Young Adult

To determine if selected serum biomarkers are superior to the acute patient physiologic and laboratory evaluation (APPLE) complete score in predicting 30-day mortality in a non-homogeneous disease population of critically ill dogs.. Prospective cohort study comparing the serum biomarkers adiponectin, leptin, C-reactive protein, and S100A12 concentrations between surviving and nonsurviving critically ill dogs.. University small animal teaching hospital.. Seventy critically ill dogs were prospectively recruited, and an APPLE complete score was calculated within 24 hours of being admitted to the intensive care unit. Logistic regression models were fit to estimate the association between biomarkers and 30-day survival. Results were interpreted at the 5% level of significance.. Leptin was the only biomarker that was significantly correlated with the APPLE complete score (P < 0.001). Only the APPLE complete score (P = 0.003) and illness duration of < 1 day (P = 0.043) were significantly associated with outcome.. Based on the results of this study, there appears to be no benefit in using biomarkers over the APPLE score for disease severity stratification. Serum leptin concentration was significantly correlated with disease severity as determined by APPLE scoring. Longer duration of illness prior to admission was associated with a higher risk of death. APPLE scores were highest in dogs with infectious and immune-mediated diseases and bite wounds.

Topics: Adiponectin; Animals; Biomarkers; C-Reactive Protein; Cohort Studies; Critical Illness; Dog Diseases; Dogs; Female; Hospitals, Animal; Intensive Care Units; Leptin; Male; Prospective Studies; S100A12 Protein; Severity of Illness Index; South Africa

Physiologically, leptin concentration is controlled by circadian rhythm. However, in critically ill patients, circadian rhythm is disrupted. Thus we hypothesized that circadian leptin concentration changes are not preserved in critically ill patients. Ten consecutive critically ill heart failure patients with the clinical indication for mechanical ventilation and sedation were included into our study. Plasma leptin concentration was measured every 4 h during the first day (0-24 h) and during the third day (48-72 h) after admission. During the first day, there were significant leptin concentration changes (ANOVA, p<0.05), characterized by an increase in concentration by 44 % (16-58 %); p=0.02 around noon (10 am-2 pm) and then a decrease in concentration by 7 % (1-27 %); p=0.04 in the morning (2 am-6 am). In contrast, there was no significant change in leptin concentration during the third day after admission (ANOVA, p=0.79). Based on our preliminary results, we concluded that in critically ill heart failure patients, the circadian rhythm of plasma leptin concentration seems to be preserved during the first but not during the third day after admission.

Topics: Aged; Circadian Rhythm; Critical Illness; Female; Heart Failure; Humans; Leptin; Male; Middle Aged

The pathophysiology of delirium remains poorly understood. Low leptin level has been associated with features leading to delirium such as dysregulated immune functions and loss of neuroprotective effects. The purpose of the present study was to investigate the relationship between plasma leptin level at intensive care unit (ICU) entry and subsequent occurrence of delirium in critically ill patients. This single-center prospective cohort study in China allocated 336 critically ill patients admitted to ICU between 05/2015 and 05/2016 into a delirium group (n=102) and non-delirium group (n=234) based on whether delirium occurred during their stay at the ICU. Patients were examined at least twice daily and delirium was diagnosed using the Confusion Assessment Method for the ICU (CAM-ICU). Blood samples were obtained after ICU entry. Plasma leptin concentrations were measured by ELISA. Delirium occurred in 30.4% (102/336) of patients. Patients who developed delirium showed significantly lower leptin level at ICU entry than those who did not (6.1±3.2 vs. 9.2±5.9ng/mL; P<0.001). Low plasma leptin level at ICU entry was independently associated with subsequent occurrence of delirium (OR, 0.865; 95%CI, 0.802-0.934; P<0.001). Other independent risk factors for delirium included increasing age (OR, 1.050; 95%CI, 1.020-1.080; P=0.001) and Acute Physiology and Chronic Health Evaluation-II (APACHE-II) score (OR, 1.148; 95%CI, 1.092-1.208; P<0.001). Patients who developed delirium had a prolonged duration of ICU stay and higher mortality. Low plasma leptin level at ICU entry was associated with the occurrence of delirium in critically ill patients.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; China; Cohort Studies; Critical Illness; Delirium; Female; Humans; Incidence; Intensive Care Units; Length of Stay; Leptin; Male; Middle Aged; Prospective Studies; Risk Factors

Both starvation and critical illness are hallmarked by changes in circulating thyroid hormone parameters with typically low T(3) concentrations in the absence of elevated TSH. This constellation is labeled nonthyroidal illness (NTI). Because critical illness is often accompanied by anorexia and a failing gastrointestinal tract, the NTI of critical illness may be confounded by nutrient deficiency. In an experimental study performed in a rabbit model, we investigated the impact of nutritional deficit on the NTI of sustained critical illness. Critically ill rabbits were randomly allocated to parenteral nutrition (moderate dose 270 kcal/d) initiated on the day after injury and continued until d 7 of illness or to infusing a similar volume of dextrose 1.4% (14 kcal/d). With early parenteral nutrition during illness, the decrease in serum T(3) observed with fasting was reversed, whereas the fall in T(4) was not significantly affected. The rise in T(3) with parenteral nutrition paralleled an increase of liver and kidney type-1 and a decrease of liver and kidney type-3 deiodinase activity and an increase in circulating and central leptin. Nuclear staining of constitutive androstane receptor and its downstream expression of sulfotransferases were reduced in fasting ill animals. TRH expression in the hypothalamus was not different in fasted and fed ill rabbits, although circulating TSH levels were higher with feeding. In conclusion, in this rabbit model of sustained critical illness, reduced circulating T(3), but not T(4), levels could be prevented by parenteral nutrition, which may be mediated by leptin and its actions on tissue deiodinase activity.

Topics: Animals; Constitutive Androstane Receptor; Critical Illness; Disease Models, Animal; Dithiothreitol; Euthyroid Sick Syndromes; Gene Expression Regulation; Hypothalamo-Hypophyseal System; Iodide Peroxidase; Leptin; Male; Nutrition Disorders; Parenteral Nutrition Solutions; Rabbits; Random Allocation; Receptors, Cytoplasmic and Nuclear; Thyroid Gland; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine

Severe infection and sepsis are common causes of morbidity and mortality. Early diagnosis in critically ill patients is important to reduce these complications. The present study was conducted to determine the role of serum leptin at early diagnosis and differentiation between patients with manifestations of systemic inflammatory response syndrome (SIRS) and those with sepsis in patients suffering from a broad range of diseases in the intensive care unit (ICU) and its correlation with other biomarkers, such as C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha).. One hundred and six adult ICU patients were observed. CRP, leptin, IL-6 and TNF-alpha were compared among the following groups: sepsis group (n = 40), SIRS group (n = 34) and non-SIRS group (n = 32). Patients were classified into these groups at the time of blood analysis for these biomarkers.. Non-significant differences were observed among patients in different groups regarding biomarkers on the day of ICU admission. On the second day of ICU admission, significant elevation of leptin, IL-6 and TNF-alpha occurred in the SIRS and sepsis groups. Delayed elevation of CRP started on the fourth day of ICU admission in patients with sepsis. At the end of the first week, only CRP level was elevated in septic patients.. Serum leptin correlates well with serum level of IL-6 and TNF-alpha. Leptin helps to differentiate SIRS from non-SIRS patients. CRP is a classic marker of sepsis but is of late onset.

Topics: Adult; Biomarkers; C-Reactive Protein; Critical Illness; Diagnosis, Differential; Early Diagnosis; Egypt; Female; Humans; Intensive Care Units; Interleukin-6; Leptin; Male; Middle Aged; Monitoring, Physiologic; Observation; Predictive Value of Tests; Prospective Studies; Sepsis; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha

The value of monitoring serum leptin in critically ill patients is important for early diagnosis and differentiation between sepsis and non-infectious systemic inflammatory response syndrome (SIRS). The early diagnosis of sepsis, the identification of its origin, and an adequate therapeutic management are crucial to overcome sepsis-associated mortality. Cytokine levels are an obvious choice as sepsis markers, since cytokines are key mediators of the inflammatory response to sepsis. Leptin, a hormone mainly generated by adipocytes, acts centrally in the hypothalamus to regulate body weight and energy expenditure. There is, however, strong evidence that leptin is also involved in cell-mediated immunity and cytokine crosstalk. The finding that a serum leptin threshold of 38 microg/l can distinguish between sepsis and non-infectious SIRS (sensitivity 91.2%, specificity 85%) is the major finding in the article by Yousef and colleagues (in this issue). Much remains to be learned about the precise mechanisms by which leptin signaling participates in sepsis and non-infectious SIRS. This knowledge will potentially contribute to new therapeutic approaches.

Topics: Biomarkers; Critical Illness; Humans; Leptin; Sepsis

The adipocyte-derived cytokine leptin was implicated to link inflammation and metabolic alterations. We investigated the potential role of leptin components in critically ill patients, because systemic inflammation, insulin resistance, and hyperglycemia are common features of critical illness. Upon admission to Medical Intensive Care Unit (ICU), free leptin and soluble leptin-receptor serum concentrations were determined in 137 critically ill patients (95 with sepsis, 42 without sepsis) and 26 healthy controls. Serum leptin or leptin-receptor did not differ between patients or controls and were independent of sepsis. However, serum leptin was closely associated with obesity and diabetes and clearly correlated with markers of metabolism and liver function. Leptin-receptor was an unfavourable prognostic indicator, associated with mortality during three years follow-up. Our study indicates a functional role of leptin in the pathogenesis of severe illness and emphasizes the impact of complex metabolic alterations on the clinical outcome of critically ill patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Critical Illness; Diabetes Mellitus; Diagnosis, Differential; Female; Glucose; Humans; Inflammation; Intensive Care Units; Kaplan-Meier Estimate; Leptin; Lipid Metabolism; Male; Middle Aged; Obesity; Prognosis; Receptors, Leptin; Sepsis; Young Adult

Leptin and interleukin-6 (IL-6) are inversely correlated and associated with decreased survival in critically ill patients. We investigated changes in leptin, IL-6, and troponin in children undergoing open-heart surgery, hypothesizing that IL-6 and troponin will increase after cardiopulmonary bypass (CPB) and will be negatively correlated with leptin.. Serial blood samples were collected from 21 patients 24 hours before and up to 48 hours after surgery.. Leptin levels decreased by 50% during CPB (P < .001), then gradually increased, reaching baseline levels 12 hours after surgery. The IL-6 levels increased (P < .001) during CPB, peaking 2 hours after surgery and remaining slightly elevated at 24 hours after surgery (P < .001). Leptin and IL-6 were negatively correlated (R = -0.448, P < .001). Troponin levels increased during CPB (P < .001). Postoperative leptin and troponin were inversely correlated (r = -0.535, P < .001). Patients with modest elevations in troponin levels (<20 microg/L) had a shorter aortic clamp and CPB time (P < .01), lower IL-6 peak levels (P = .03), and shorter duration of ventilation and inotropic support compared with patients with peak troponin levels greater than 20 microg/L.. Lower leptin and higher IL-6 levels correlated with troponin, a marker of myocardial injury. Because leptin may have cardioprotective effects, the postoperative drop in its levels may further contribute to myocardial dysfunction.

Topics: Biomarkers; Cardiopulmonary Bypass; Critical Illness; Female; Heart Defects, Congenital; Hospital Mortality; Humans; Infant; Inflammation; Interleukin-6; Leptin; Male; Myocardial Ischemia; Postoperative Complications; Prognosis; Survival Analysis; Time Factors; Troponin

Topics: Animals; Arcuate Nucleus of Hypothalamus; Critical Illness; Disease Models, Animal; Euthyroid Sick Syndromes; Fasting; Gene Expression; Homeostasis; Humans; Hypothalamus; Intensive Care Units; Leptin; Mice; Rabbits; Rats; Syndrome; Thyroid Hormones

Topics: Animals; Critical Illness; Humans; Immunity; Leptin; Lung; Malnutrition; Mice; Pneumonia, Pneumococcal; Streptococcus pneumoniae

The relationship between circulation leptin concentrations, mediators of the systemic inflammatory response and illness severity in critically ill patients remains unclear. The aim of the present study was to examine these relationships in critically ill surgical patients admitted to the intensive therapy unit (ITU).. Patients (n = 38) who had undergone surgery and subsequently admitted to ITU were prospectively entered into a cross-sectional study. Circulating concentrations of leptin, cortisol, growth hormone, interleukin-6, C-reactive protein and albumin were measured. Sex and age matched controls (n = 14) were also studied.. On day 1, the critically ill group had lower BMI and leptin concentrations and a pronounced systemic inflammatory response compared with controls. There was a weak positive correlation between leptin concentrations and BMI in the critically ill patients (r = 0.42, P<0.10). In contrast, leptin was inversely correlated with C-reactive protein (r = -0.59, P<0.05) but not with cortisol, growth hormone, interleukin-6, APACHE II or predicted mortality. Leptin concentrations did not alter with the day of admission to ITU.. On ITU admission, leptin concentrations appeared to be low for BMI, related to the magnitude of the systemic inflammatory response but did not appear to be regulated by proposed mediators in critically ill surgical patients.

Topics: Adult; Aged; Body Mass Index; Critical Illness; Female; Humans; Inflammation; Intensive Care Units; Leptin; Male; Middle Aged; Postoperative Care; Respiration, Artificial; Severity of Illness Index

Leptin production is increased in rodents by administration of endotoxin or cytokines. To investigate whether circulating leptin is related to cytokine release and survival in human sepsis, plasma concentrations of leptin, interleukin (IL)-6, IL-1beta, tumor necrosis factor (TNF)-alpha, soluble TNF receptor type I, IL-1 receptor antagonist (IL-1ra), and the inflammatory modulator IL-10 were measured as soon as severe sepsis (n=28) or septic shock (n=14) developed and every 6 h for 24 h. Patients with sepsis or septic shock had leptin concentrations 2.3- and 4.2-fold greater, respectively, than the control group. There was an independent association for leptin with IL-1ra and IL-10 in both patient groups. By discriminant analysis, leptin and IL-6 were independent predictors of death. These findings suggest that increases in leptin levels may be a host defense mechanism during sepsis.

Topics: Analysis of Variance; Bacteremia; Biomarkers; Confidence Intervals; Critical Illness; Cytokines; Discriminant Analysis; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-10; Interleukin-6; Leptin; Predictive Value of Tests; Prognosis; Proteins; Receptors, Interleukin-1; Receptors, Leptin; Receptors, Tumor Necrosis Factor; Shock, Septic; Sialoglycoproteins; Survival Rate; Survivors

Recent animal and human studies have suggested that leptin secretion is closely linked to the functions of the hypothalamic-pituitary-adrenal (HPA) axis and the immune system, both of which are crucial in influencing the course and outcome of critical illness. Therefore, we measured basal plasma leptin levels and examined the circadian secretion of leptin, in parallel with the hormones of the HPA axis and a key cytokine, interleukin-6, in critically ill patients with acute sepsis. Sixteen critically ill patients from the University of Leipzig Intensive Care Unit were recruited for this study. All of these patients fulfilled the standard diagnostic criteria for sepsis. Plasma leptin levels were measured in all patients and controls at 09:00. In addition, in a subgroup of eight critically ill patients and all of the nine controls plasma leptin, cortisol, ACTH and interleukin-6 concentrations were measured every 4 hours for 24 hours. Mean plasma leptin levels were three-fold higher (18.9 +/- 4.5 ng/ml) in critically ill patients than controls (3.8 +/- 1.0 ng/ml, p < 0.05). Similarly, ACTH levels were lower (7.8 +/- 3.4 pmol/l) in patients than in controls (17.1 +/- 1.5 pmol/l, p < .001), while plasma cortisol levels were increased (947.6 +/- 144 nmol/l) in patients compared to controls (361.1 +/- 29, p < 0.001). Morning plasma interleukin-6 levels were markedly elevated in all patients with sepsis (1238.0 +/- 543.1 pg/ml) versus controls (6.4 +/- 1.7, p < 0.001). The controls exhibited a nyctohemeral fluctuation in plasma leptin levels with peak levels at 23:00; in contrast, septic patients, had no nocturnal rise of leptin. In healthy controls, plasma leptin and cortisol had reciprocal circadian rhythms with high nocturnal leptin levels and low nocturnal cortisol concentrations; in critically ill patients, this relation was abolished. Mean leptin levels were three-fold higher in patients who survived the septic episode (25.5 +/- 6.2, n = 10) than in non-survivors (8.0 +/- 3.7, n = 6, p < 0.01). We conclude that in addition to its function as an anti-obesity factor, leptin may play a role in a severe stress state such as acute sepsis.

Topics: Biomarkers; Circadian Rhythm; Critical Illness; Follow-Up Studies; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Leptin; Pituitary-Adrenal System; Proteins; Reference Values; Survivors; Systemic Inflammatory Response Syndrome

Both leptin and interleukin-6 (IL-6) are hypersecreted in acute critical illness, such as sepsis. Leptin is produced by adipocytes, it inhibits appetite and stimulates the sympathetic nervous system, thereby reducing adipose mass. IL-6 is produced by immune cells and adipocytes, it reduces the production of other inflammatory cytokines and stimulates release of acute phase proteins by the liver, participating in the control of inflammation. Leptin inhibits, whereas IL-6 stimulates, the hypothalamic-pituitary-adrenal axis. While high IL-6 levels are associated with poor outcome in critically ill patients, the role of leptin in critical illness and its importance for survival are not known. To examine the relation between IL-6, leptin and cortisol in critical illness, we performed frequent 4 h plasma sampling in eight patients on day 1 of intensive care unit admission for acute sepsis. Sampling was repeated on days 3 and 5 in the five survivors. The levels of all three hormones were markedly elevated; there was a lack of the normal diurnal rhythmicity of leptin and IL-6 and a blunted diurnal rhythmicity of cortisol secretion. A strong negative correlation between mean 24 h plasma IL-6 and leptin was revealed. Although such a relationship could possibly be explained by the negative and positive effects of cortisol hypersecretion on each hormone respectively, a negative correlation between leptin and cortisol was detected, whereas there was no significant correlation between IL-6 and cortisol. Mean IL-6 values were higher (1389.5+/-644.9 vs. 658.8+/-250.5) and leptin levels were lower (2.73+/-1.1 vs. 26.5+/-11.6) in the non-survivors than in the survivors. These findings suggest that IL-6 is not the principal stimulus of leptin hypersecretion in critically ill patients with sepsis. The negative relation between IL-6 and leptin is of potential importance, as high IL-6 levels have been associated with poor outcome in critically ill patients, and relatively low leptin levels may impair sympathetic system and immune functions.

Topics: Circadian Rhythm; Critical Illness; Female; Humans; Hydrocortisone; Interleukin-6; Leptin; Male; Prospective Studies; Proteins; Sepsis

Topics: Adrenocorticotropic Hormone; Circadian Rhythm; Critical Illness; Female; Heat-Shock Proteins; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Leptin; Male; Pituitary-Adrenal System; Proteins; Stress, Physiological