c-peptide and Critical-Illness

β-hydroxy-β-methylbutyrate (HMB) might improve muscle function and maintain its mass in critically ill patients. We aimed to investigate whether the administration of HMB influenced the plasma levels of growth hormone (GH)/insulin-like growth factor-1 (IGF-1), C-peptide, and 25-OH vitamin-D.. Post-hoc analysis of the study HMB-ICU, a randomized, placebo-controlled double-blind trial.. Intensive care unit (ICU) patients depending on mechanical ventilation on day 3 with functional gastrointestinal tract. Patients were randomized to HMB (3 g/day) or placebo (maltodextrin) from day 4 on, for 30 days. Blood samples were collected on days 4 and 15. We determined the GH, C-peptide, 25-OH vitamin-D, and IGF-1. Statistics by ANCOVA.. Blood samples of 26 patients were available on day 4, and 23 on day 15. While age and severity of disease did not differ, diabetes was more frequent in the HMB group (p = 0.041), and obesity was more frequent in the placebo group (p = 0.021). Glucose intake, blood glucose (BG) and amount of insulin to maintain blood glucose between 6 and 8 mM did not differ between groups. There was no difference between groups for C-peptide, GH, IGF-1, and 25-OH vitamin-D. IGF-1 increased significantly from day 4-15 (p = 0.026) in both groups.. Subject to possible insufficient power of the study, we did not reach conclusive results. HMB intervention does not affect significantly the plasma concentrations of insulin, GH/IGF axis activity, C-peptide, and 25-OH vitamin-D.. NCT03628365.

Topics: Blood Glucose; C-Peptide; Cohort Studies; Critical Illness; Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor I; Intensive Care Units; Vitamin D; Vitamins

Intensive insulin therapy (IIT) improved outcome in the adult and pediatric intensive care unit (PICU) compared with conventional insulin therapy (CIT). IIT did not increase the anabolic hormone IGF-I in critically ill adults, but feeding in critically ill children and pediatric hormonal responses may differ. Twenty-five percent of the children with IIT experienced hypoglycemia, which may have evoked counterregulatory responses.. We hypothesized that IIT reactivates the somatotropic axis and anabolism in PICU patients.. This was a preplanned subanalysis of a randomized controlled trial on IIT.. We studied 369 patients who stayed in PICU for at least 3 d (study 1) and 126 patients in a nested case-control study (study 2).. Circulating insulin, C-peptide, GH, IGF-I, bioavailable IGF-I, IGF-binding protein (IGFBP)-1, IGFBP-3, and acid-labile subunit were analyzed upon admission and d 3. In the nested case-control study, the somatotropic axis, cortisol, and glucagon were analyzed before and after hypoglycemia.. On d 3, C-peptide was more than 10-fold lower (P < 0.0001) in the IIT group than in the CIT group. IIT increased circulating GH (P = 0.04) and lowered bioavailable IGF-I (P = 0.002). IIT also decreased IGFBP-3 (P = 0.0005) and acid-labile subunit (P = 0.007), while increasing IGFBP-1 (P = 0.04) and the urea/creatinine ratio, a marker of catabolism (P = 0.03). In the nested case-control study, IGFBP-1 was increased after hypoglycemia, whereas the somatotropic axis and the counterregulatory hormones cortisol and glucagon did not change.. Despite improved PICU outcome, IIT did not counteract the catabolic state of critical illness. Suppression of portal insulin may have resulted in lower bioavailable IGF-I.

Topics: Adolescent; C-Peptide; Case-Control Studies; Child; Child, Preschool; Critical Illness; Female; Glucagon; Human Growth Hormone; Humans; Hydrocortisone; Hypoglycemia; Hypoglycemic Agents; Infant; Infant, Newborn; Insulin; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Intensive Care Units, Pediatric; Male; Prospective Studies

Hyperglycemia and hyperinsulinemia are common in intensive care unit (ICU) patients and relate to illness severity. Intensive insulin therapy (IIT) to maintain normoglycemia reduces morbidity and mortality. Blood glucose control explains this benefit because a high insulin dose is associated with adverse outcome. Mitogenic insulin effects could theoretically explain this link.. To investigate further the association between insulin dose and adverse outcome, we studied the effect of IIT on circulating insulin levels, markers of insulin sensitivity, and the metabolic and mitogenic insulin signaling molecules in key tissues.. This is a subanalysis of a large randomized, controlled study.. The study was performed in a university hospital surgical ICU.. A total of 339 critically ill patients, treated in ICU for at least a week, were included in this subanalysis.. Strict normoglycemia with IIT compared with conventional insulin therapy was performed.. Severalfold higher insulin doses than with conventional insulin therapy were required to maintain normoglycemia with IIT. However, serum insulin levels were only transiently higher with IIT, despite the much lower blood glucose levels. IIT normalized the elevated serum C-peptide levels and increased circulating adiponectin levels. The metabolic insulin signal was increased by IIT in muscle, but not in liver. The mitogenic insulin signal in either tissue was not affected by IIT.. Normoglycemia can be maintained in ICU patients without a sustained further elevation of insulinemia. Together with the increased adiponectin levels, this finding suggests that IIT may improve insulin sensitivity. Skeletal muscle, but not liver, revealed an increased metabolic insulin signal. The therapy did not impose mitogenic risk in these tissues.

Topics: Adiponectin; Aged; Blood Glucose; C-Peptide; Critical Illness; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 1; Liver; Male; Middle Aged; Muscle, Skeletal; Receptors, Adiponectin; Signal Transduction

To study the effects of growth hormone administration on insulin-like growth factor I concentration, nitrogen balance, and fuel utilization, and to study its safety in critically ill nonseptic patients.. Prospective, randomized, placebo-controlled trial.. Medical intensive care unit of a university hospital.. Eighteen critically ill nonseptic patients were studied for 8 days after admission.. Growth hormone (0.1 mg/kg/day) or placebo was administered as a continuous intravenous infusion on the second, third, and fourth days after admission. The study period was 8 days.. Plasma hormone concentrations were measured every 6 hrs and average daily values were calculated. The 24-hr urinary nitrogen and 3-methylhistidine excretion were measured. Indirect calorimetry was used to calculate fuel utilization. Insulin-like growth factor I concentrations increased in the treatment group from subnormal to normal values and remained increased despite discontinuation of growth hormone treatment (p = .02). Nitrogen balance differed between the groups upon admission: growth hormone group (3.9 +/- 4.1 g/day) vs. controls (13.8 +/- 5.4 g/day), but improved with growth hormone. This finding appeared independent of the imbalance between the groups. The 3-methylhistidine excretion was not different between the groups and did not change during growth hormone administration. Free fatty acids and glycerol concentrations increased during growth hormone treatment, but calculated fuel utilization did not change. During growth hormone treatment, insulin concentrations increased, due to the increased administration of insulin necessary for glycemic control. Side effects other than hyperglycemia were not observed.. Growth hormone administration in a heterogeneous group of critically ill nonseptic patients resulted in normalization of insulin-like growth factor I levels, even after cessation of growth hormone treatment. Nitrogen balance improved, but this change was transient. Hence, growth hormone affects nitrogen balance, probably partly independent of insulin-like growth factor I.

Topics: Blood Glucose; C-Peptide; Critical Illness; Double-Blind Method; Energy Metabolism; Glucagon; Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor I; Lipids; Methylhistidines; Minerals; Nitrogen; Oxygen Consumption; Prospective Studies

Although beta cell dysfunction has been proved to predict prognosis among humans and animals, its prediction on severity of disease remains unclear among children. The present study was aimed to examine the relationship between beta cell dysfunction and severity of disease among critically ill children.This prospective study included 1146 critically ill children, who were admitted to Pediatric Intensive Care Unit (PICU) of Hunan Children's Hospital from November 2011 to August 2013. Information on characteristics, laboratory tests, and prognostic outcomes was collected. Homeostasis model assessment (HOMA)-β, evaluating beta cell function, was used to divide all participants into 4 groups: HOMA-β = 100% (group I, n = 339), 80% ≤ HOMA-β < 100% (group II, n = 71), 40% ≤ HOMA-β < 80% (group III, n = 293), and HOMA-β < 40% (group IV, n = 443). Severity of disease was assessed using the worst Sequential Organ Failure Assessment (SOFA) score, Pediatric Risk of Mortality (PRISM) III score, incidence of organ damage, septic shock, multiple organ dysfunction syndrome (MODS), mechanical ventilation (MV) and mortality. Logistic regression analysis was used to evaluate the risk of developing poor outcomes among patients in different HOMA-β groups, with group I as the reference group.Among 1146 children, incidence of HOMA-β < 100% was 70.41%. C-peptide and insulin declined with the decrement of HOMA-β (P < 0.01). C-reactive protein and procalcitonin levels, rather than white blood cell, were significantly different among 4 groups (P < 0.01). In addition, the worst SOFA score and the worst PRISMIII score increased with declined HOMA-β. For example, the worst SOFA score in group I, II, III, and IV was 1.55 ± 1.85, 1.71 ± 1.93, 1.92 ± 1.63, and 2.18 ± 1.77, respectively. Furthermore, patients with declined HOMA-β had higher risk of developing septic shock, MODS, MV, and mortality, even after adjusting age, gender, myocardial injury, and lung injury. For instance, compared with group I, the multivariate-adjusted odds ratio (95% confidence interval) for developing septic shock was 2.17 (0.59, 8.02), 2.94 (2.18, 6.46), and 2.76 (1.18, 6.46) among patients in group II, III, and IV, respectively.Beta cell dysfunction reflected the severity of disease among critically ill children. Therefore, assessment of beta cell function is critically important to reduce incidence of adverse events in PICU.

Topics: Adolescent; C-Peptide; C-Reactive Protein; Calcitonin; Child; Child, Preschool; Critical Illness; Female; Homeostasis; Humans; Incidence; Infant; Infant, Newborn; Insulin; Insulin-Secreting Cells; Intensive Care Units, Pediatric; Logistic Models; Male; Multiple Organ Failure; Odds Ratio; Organ Dysfunction Scores; Prognosis; Prolactin; Prospective Studies; Respiration, Artificial; Risk Assessment; Risk Factors; Severity of Illness Index; Shock, Septic

Causes of hyperglycemia in critically ill non-diabetic children may differ from those in adults. The objective of this study was to investigate the pathogenesis of critical illness hyperglycemia (CIH) in terms of insulin resistance and β-cell dysfunction. Critically ill children with blood glucose (BG) levels of >150 mg/dL (8.3 mmol/L) were enrolled in the study. Insulin sensitivity and β-cell function in the hyperglycemic and euglycemic periods were analyzed with BG/insulin and BG/C-peptide ratios, and utilizing homeostasis model assessment (HOMA). A total of 40 patients were enrolled in the study. BG/insulin and BG/C-peptide ratios were significantly higher in the hyperglycemic period. The HOMA-B and S scores for the hyperglycemic period revealed that out of all the patients who survived (n=30), 20 had β-cell dysfunction, while the remaining (n=11) had insulin resistance. β-cell dysfunction was significantly higher in the hyperglycemic period (p<0.001). As in adults, β-cell dysfunction may play a major role in the pathophysiology of CIH in children.

Topics: Adolescent; Blood Glucose; C-Peptide; Child; Child, Preschool; Critical Illness; Female; Humans; Hyperglycemia; Infant; Insulin Resistance; Insulin-Secreting Cells; Male

To analyze the variation of serum insulin levels in critically ill children and investigate the underlying mechanism and clinical significance to provide the basis for treatment.. Totally 332 critically ill children admitted in pediatric intensive care unit (PICU) of Hunan Children's Hospital from Nov., 2011 to April, 2012 were studied. The high insulin group (n = 332) was defined as insulin levels within 24 h > 11.1 mU/L and was divided into 2 groups: mildly elevated group (n = 194): 11.10 - 33.30 mU/L, increased three times group (n = 138): > 33.3 mU/L. Insulin, C-peptide and blood glucose were measured within 24 hours after admission, on day 3 and 7. Other results of inflammatory markers, lactate, cardiac enzymes, amylase, pancreatic ultrasound, hepatic and renal function as well as indicators related to severity and prognosis were recorded after admission.. The peak of insulin level was seen on day 1, then presented a downward trend and reached the normal level on day 7. The peaks of blood glucose and C-peptide level were seen on day 1 then declined, the levels on day 7 were still slightly higher than normal level. The insulin level on admission (41.47 ± 30.85) mU/L were positively correlated with lactic acid (2.29 ± 1.81) mmol/L and procalcitonin level (5.08 ± 6.70) ng/ml (r = 0.370, P = 0.000; r = 0.168, P = 0.002) (P < 0.01). The insulin level on admission in children with 1 organ failure (41.24 ± 22.60) mU/L or 2 or multiple organ failure (48.98 ± 22.17) mU/L was higher than that in children with non-organ failure (34.11 ± 29.84) mU/L (U = 1621.001, P = 0.000;U = 1300.000, P = 0.000) (P < 0.01). The insulin level on admission in death group (52.99 ± 32.34) mU/L was higher than that in survival group (32.85 ± 24.10) mU/L (U = 1585.000, P = 0.000) (P < 0.01). Ten cases in death group were complicated with pancreatic damage and the average insulin level on admission was (65.29 ± 50.53) mU/L.. The high insulin level was correlated with the degree of inflammatory response, ischemia and hypoxia. The high insulin level in critically ill children was relevant to the pancreatic damage, the severity of the disease, organ dysfunction, and evaluation of prognosis.

Topics: Adolescent; Blood Glucose; C-Peptide; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Critical Illness; Female; Humans; Infant; Infant, Newborn; Insulin; Intensive Care Units, Pediatric; Male; Multiple Organ Failure; Pancreas; Prognosis; Protein Precursors; Survival

To observe the relationship between inflammatory response and the constituents of islet β cell secretion during stress hyperglycemia (SHG) in critically ill patients, in order to study the impact of inflammatory response on insulin resistance and the secretion function of islet β cells.. According to the state of inflammatory response, 45 critical patients with SHG were divided into two groups: stress and the convalescence period. Twenty five healthy individuals were enrolled as control group. The blood levels of tumour necrosis factor β (TNF-β), blood glucose (BG), and insulin components including proinsulin (PI), immunoreactive insulin (IRI), true insulin (TI), C-peptide (C-P) were measured respectively. The levels of BG, TNF-β, insulin components, insulin resistance index (HOMA-IR) and the secretion index (HOMA-β) were compared among groups. The relationship between TNF-β and BG, insulin components, HOMA-IR, HOMA-β were analyzed.. (1)There was no difference in concentrations of TI among stress period, convalescence stage and control group [3.68 (1.57, 7.70), 3.42 (2.41, 7.40), 1.46 (0.35, 4.90) mU/L, all P >0.05], whereas the concentration of BG [(10.04 ± 2.43) mmol/L], TNF-β [13.70 (11.77, 20.00) ng/L], PI [6.20 (3.22, 9.27) pmol/L], IRI [13.45 (9.88, 19.88) mU/L] and C-P [3.01 (2.37, 4.00) μg/L]in stress period were significantly higher than those in the convalescence stage[BG: (6.09 ± 0.84) mmol/L, TNF-β: 11.58 (8.80, 13.22) ng/L,PI: 1.54 (0.36, 11.82) pmol/L, IRI: 10.80 (5.35, 12.60) mU/L, C-P: 2.42 (1.17, 3.56) μg/L] and control group [BG: (4.87 ± 0.56) mmol/L,TNF-β: 9.27 (7.48, 12.16) ng/L, PI: 2.20 (1.88, 4.54) pmol/L, IRI: 5.50 (4.00, 8.00) mU/L, C-P: 1.15 (0.87, 1.76) μg/L, P <0.05 or P <0.01]. (2)The HOMA-IR [5.17 (3.41, 11.51)] in stress period was significantly higher than that in the convalescence[3.24 (1.51, 6.95)] and control group [1.14 (0.81, 1.79), P <0.05 and P<0.01]. The HOMA-β [10.80 (3.72, 31.40)] of isletβ cell in stress period was significantly lower than that in the convalescence [28.42 (6.46, 125.01)] and control group [21.94 (7.77, 62.01), P <0.01 and P <0.05]. (3)There were positive correlations between the concentration of TNF-β and PI, IRI, C-P and HOMA-IR ( r 1=0.292, r 2=0.344, r 3=0.397, r 4=0.324, P <0.05 or P <0.01). There were negative correlation between concentration of TNF-β and HOMA-β ( r =-0.235 , P <0.05) .. The severer the inflammatory response, the higher PI, IRI and C-P, while the secretion of TI is relatively deficient.Inflammatory response could affect insulin resistance and the secretion function of islet βcell during SHG in critically ill patients.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Case-Control Studies; Critical Illness; Female; Humans; Hyperglycemia; Inflammation; Insulin; Insulin Resistance; Islets of Langerhans; Lymphotoxin-alpha; Male; Middle Aged; Young Adult

To observe related factors in the stress hyperglycemia (SHG) of critical illness and to investigate possible pathogenesis of insulin-resistance (IR).. Blood glucose (BG), insulin (INS), C-peptide (C-P), cortisol (Cor), somatostatin (SS), glucagon (Gluc), tumor necrosis factor-alpha (TNF-alpha),soluble tumor necrosis factor receptor I (sTNFRI) and sTNFRII were determined respectively by radioimmunoassay (RIA) or enzyme linked immunoadsorbent assay (ELISA) in 47 SHG patients with critical illness and 15 healthy volunteers serving as normal controls. Their insulin sensitivity index (ISI) was calculated.. (1)Eleven of 47 patients died, while 36 cases survived. Mean acute pathology and chronic health evaluation II (APACHEII) was (13.89+/-6.29) scores within 24 hours after admission to intensive care unit (ICU), mean days of stay in ICU was (5.5+/-6.3) days,and mean duration of mechanical ventilation (MV) was (51.49+/-66.01) hours. (2)The concentrations of INS, ISI, C-P, Cor, Gluc, TNF-alpha, sTNFRI and sTNFRII in 47 SHG patients with critical illness were significantly higher than those in normal controls, except for SS, the differences among groups were significant (P<0.05 or P<0.01). (3)The results of analysis of severity of SHG showed that the more severe SHG was, the higher C-P and INS were, and the less prominent ISI was. (4)Analysis of scores of APACHEII in 47 cases of SHG showed that BG was not increased, but duration of MV, Cor, Gluc, SS, TNF-alpha, sTNFRI and sTNFRII were significantly increased with higher scores of APACHEII. (5)The effect of SHG was significant on MV (F=10.438,P<0.01), but not significant for outcome and days of stay in ICU. (6)The main correlative factors of BG were respectively concentrations of INS (r=0.674, P<0.01), C-P(r=0.552,P<0.01), ISI (r=-0.787, P<0.01), APACHE II(r=0.267,P<0.05) and sTNFRI(r=0.465, P<0.01).. These results show that main reason of SHG in critical illness is IR. There is no strong significant correlation between acute stress hormones and the level of SHG. sTNFRI has an influence on SHG. However, the over release of TNF-alpha and sTNFRII could be the results of seriousness of the critical illness. There is closely correlation between BG and MV, but not with the age, outcome and days of stay in ICU. The strategy of control and therapy of SHG should be alleviation of stress and improve the utilization of BG in the tissue, and increase sensitivity of INS in the tissue.

Topics: Adult; Aged; C-Peptide; Critical Illness; Female; Glucagon; Humans; Hydrocortisone; Hyperglycemia; Insulin; Insulin Resistance; Intensive Care Units; Male; Middle Aged; Stress, Physiological; Tumor Necrosis Factor-alpha; Young Adult

The catabolic state is a major contributor to morbidity and mortality of critical illness and may be related to endocrine changes. We studied whether protein and lipid turnover correlate with insulin and growth and thyroid hormone plasma levels in critically ill infants.. Prospective clinical study.. Pediatric intensive care unit.. Twelve critically ill children and ten age-matched controls.. We measured lipolysis and protein turnover by infusing albumin-bound uniformly 13C palmitic acid and 2H3-leucine for 3 hrs and 2H5-glycerol for 5 hrs to critically ill infants. Simultaneously, we measured serum growth hormones, insulin, C-peptide, thyroid-stimulating hormone, T4, T3, albumin, retinol binding protein (RBP), and prealbumin. Hormone and serum protein levels were also measured in six children when recovered from critical illness. Ten healthy age-matched children served as controls for hormone serum levels comparison.. Palmitic acid and glycerol turnover were 5.6 +/- 2.2 micromol/kg/min and 12.2 +/- 7.3 micromol/kg/min, respectively, whereas alpha-ketoisocaproic turnover was 4.9 +/- 2.8 micromol/kg/min. Alpha-ketoisocaproic turnover positively correlated (R = 0.7, p = .03) with duration of pediatric intensive care unit admission and with prealbumin and RBP serum levels (R = 0.9, p = .001). Insulin-like growth factor binding protein (IGFBP)-2 was significantly higher and IGFBP-3 was significantly lower in critically ill children (p = .03 and p = .04 vs. recovery phase, respectively). No other hormonal differences were found. Serum albumin was significantly lower in sick children. We found a significant correlation between prealbumin and RBP and IGFBP-3 (R = 0.6, p = 0.03 and R = 0.6, p = .04, respectively). Alpha-ketoisocaproic turnover positively correlated with IGFBP-1 (R = 0.79, p = .01) and did not correlate with insulin-like growth factor I (R = -0.5, p = .15 [not significant]) No other correlations were found. Lipid turnover measurements did not correlate with any endogenous hormone levels or with duration of critical illness.. Protein turnover but not lipolysis correlated with a persisting critically ill condition, serum prealbumin, RBP, and plasma IGFBP-1.

Topics: C-Peptide; Carbon Radioisotopes; Child, Preschool; Critical Illness; Glycerol; Growth Hormone; Humans; Infant; Infant, Newborn; Insulin; Insulin Secretion; Insulin-Like Growth Factor Binding Proteins; Keto Acids; Leucine; Lipolysis; Palmitic Acid; Proteins; Retinol-Binding Proteins; Retinol-Binding Proteins, Plasma; Thyrotropin; Thyroxine; Triiodothyronine

Evidence exists indicating that growth hormone (GH) resistance in some disease states such as hypercatabolic conditions may limit the metabolic benefit associated with recombinant human growth hormone (rhGH) administration. It was the purpose of this study to compare the systemic and splanchnic effects of rhGH in patients with sepsis exhibiting systemic inflammatory response syndrome (SIRS) with the response observed in normal volunteers. Because insulin-like growth factor I (IGF-I) is believed to be the dominant factor responsible for the anabolic effects of rhGH, particular attention was given to this secondary effector.. The systemic and splanchnic effects of rhGH (0.15 mg/kg/day) were studied in normal volunteers (n = 5), critically ill patients with sepsis exhibiting SIRS (n = 6), and patients with sepsis exhibiting SIRS while receiving total parenteral nutrition (n = 6). Basal and end study IGF-I, urinary urea excretion, hepatic blood flow, hepatic venous oxygen content, and splanchnic oxygen exchange were measured after a 48-hour course of rhGH.. Fasting basal IGF-I concentrations were reduced by 75% to 83% in patients with sepsis/SIRS relative to normal control subjects. After 48 hours of rhGH, peak IGF-I concentrations were 74% and 76% lower in patients in the Sepsis/SIRS and Sepsis/SIRS + Nutrition groups, respectively, compared with normal control subjects. Despite the attenuated IGF-I rise in patients, urea excretion declined by a similar magnitude in all three groups. Hepatic blood flow remained unaffected, but rhGH administration increased splanchnic oxygen consumption in all groups (control, +57%*; Sepsis/SIRS, +13%; Sepsis/SIRS + Nutr +42%*; *p < 0.05 relative to corresponding basal) resulting in a decline of basal to end therapy hepatic venous oxygen saturation (control, 67 +/- 4% to 62 +/- 11%; Sepsis/SIRS, 51% +/- 14% to 43% +/- 14%*; Sepsis/SIRS + Nutr, 62% +/- 11% to 55% +/- 16%; *p < 0.05 relative to corresponding control value), suggesting that rhGH may induce centrilobular hepatic hypoxia, which may contribute to the diminished IGF-I response.. Although critically ill patients exhibit an IGF-I increase in response to exogenous rhGH, the rise is markedly attenuated compared with healthy volunteers, indicating the presence of GH resistance. Unexpectedly, the changes in the anabolic hormone IGF-I did not appear to be related to the reduction in urea excretion. This may provide some additional evidence for IGF-I resistance. Finally, rhGH is associated with an augmented splanchnic oxygen consumption but no corresponding increase in regional blood flow. As a result, regional tissue hypoxia may arise and contribute to the impaired or suboptimal IGF-I response pattern.

Topics: APACHE; C-Peptide; C-Reactive Protein; Critical Illness; Energy Intake; Hemodynamics; Human Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor I; Liver Circulation; Middle Aged; Nitrogen; Oxygen; Parenteral Nutrition, Total; Recombinant Proteins; Reference Values; Sepsis; Splanchnic Circulation; Systemic Inflammatory Response Syndrome; Urea

This study investigates the regulation of the insulin-like growth factors (IGFs) and their regulatory proteins in 14 critically ill patients during the 30-day period following admission to an intensive care unit (ICU). Levels of IGF-I, IGF-II, IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS) were low on admission, and in the 8 patients whose serum IGF-I levels failed to increase over 30 days, levels of the other proteins also remained low, while IGFBP-3 proteolytic activity increased. Of these proteins, ALS correlated best with serum levels of nutritional indicators, particularly prealbumin. IGFBP-2 and IGFBP-6 levels tended to be high in critically ill patients, but showed little change over the 30-day period. In contrast, IGFBP-1 levels were high on admission, correlated with early changes in nitrogen balance, and fell rapidly during the first week. By demonstrating that the IGF-I response in ICU patients is related to changes in the IGF regulatory proteins, this study may be of value in planning therapeutic intervention using growth hormone or IGF-I.

Topics: Adult; Aged; C-Peptide; Critical Illness; Female; Human Growth Hormone; Humans; Hydrocortisone; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Intensive Care Units; Male; Middle Aged; Regression Analysis; Thyrotropin; Thyroxine; Time Factors

To determine the magnitude and time course of adrenergic effects on metabolism in volunteers and possible implications for the use of sympathomimetics in the critically ill.. Descriptive laboratory investigation.. 7 volunteers.. Primed continuous infusions of stable isotope tracers ([15N2]-urea, [6,6-D2]-glucose, [methyl-D3]-L-leucine, [15N]-L-alanine) were used. After isotopic steady state had been reached an infusion of adrenaline (0.1 microgram/kg/min) was administered (4 h). Isotopic enrichment was measured using gas chromatography-mass spectrometry and the corresponding rates of appearance were calculated.. Glucose production increased from 14.1 +/- 1.2 to 21.5 +/- 2.0 mumol/kg/min (p < 0.05) after 80 min of adrenergic stimulation and then decreased again to 17.9 +/- 1.2 mumol/kg/min after 240 min. Leucine and ketoisocaproate (KIC) fluxes were 2.3 +/- 0.2 and 2.6 +/- 0.2 mumol/kg/min, respectively, at baseline and gradually decreased to 1.8 +/- 0.2 and 2.2 +/- 0.1 mumol/kg/min, respectively, after 240 min of adrenaline infusion (both p < 0.05). Alanine flux increased from 3.7 +/- 0.5 to 6.9 +/- 0.9 mumol/kg/min (p < 0.05) after 80 min of adrenergic stimulation. Urea production slightly decreased from 4.8 +/- 0.9 to 4.3 +/- 0.8 mumol/kg/min during adrenaline (p < 0.05).. Adrenaline induced an increase in glucose production lasting for longer than 240 min. The decrease in leucine and KIC flux suggests a reduction in proteolysis, which was supported by the decrease in urea production. The increase in alanine flux is therefore most likely due to an increase in de-novo synthesis. The ammonia donor for alanine synthesis in peripheral tissues and the target for ammonia after alanine deamination in the liver remain to be investigated. These results indicate that adrenaline infusion most probably will not promote already enhanced proteolysis in critically ill patients. Gluconeogenesis is an energy consuming process and an increase may deteriorate hepatic oxygen balance in patients.

Topics: Adult; Alanine; Amino Acids; Blood Glucose; C-Peptide; Caproates; Critical Illness; Epinephrine; Gas Chromatography-Mass Spectrometry; Glucagon; Gluconeogenesis; Humans; Infusions, Intravenous; Insulin; Keto Acids; Leucine; Liver; Male; Metabolic Clearance Rate; Oxygen Consumption; Proteins; Time Factors; Urea