Gender differences in the responses of serum insulin-like growth factor-1 and transthyretin (prealbumin) to trauma.

OBJECTIVE: To determine whether factors such as age, gender, and severity of injury should be considered when evaluating serum insulin-like growth factor (IGF)-1 and transthyretin concentrations as markers of nutritional status after trauma. A large, diverse group of patients was studied before the confounding effects of acute nutrient deprivation. DESIGN: Prospective, randomized, descriptive study. SETTING: Emergency room of a university hospital. PATIENTS: One hundred eight trauma patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In this heterogeneous group of patients, Injury Severity Score ranged from 1 to 45 (11.5 +/- 10.3 [SD]), age ranged from 18 to 77 yrs (35 +/- 15.3 [SD]), and 68% were male and 32% were female. A venous blood sample was collected on admission and analyzed for serum IGF-1, transthyretin, albumin, and C-reactive protein concentrations. Relationships among variables were tested with multiple regression, Pearson's correlation coefficients, and analysis of variance. Gender, age, and severity of injury demonstrated strong and interactive effects on serum IGF-1 concentrations. IGF-1 concentrations were predicted with the following equations in women and men, respectively: y = 414 - 10.87(age) + 1.19(Injury Severity Score) + .09(age2); y = 454 - 10.87(age) - 2.57(Injury Severity Score) + .09(age2); (R2 = .35, p < .0001). The relationship between age and IGF-1 was curvilinear in both men and women. IGF-1 concentrations increased with age until approximately 57 yrs, and then decreased with increasing age. In women, IGF-1 concentrations increased with increasing severity of injury. In men, IGF-1 concentrations decreased with increasing Injury Severity Scores. This dissimilar response to injury between men and women was also seen in the significant interaction between gender and Injury Severity Score in predicting transthyretin concentrations (R2 = .32, p < .05). In men, transthyretin concentrations decreased significantly with severe injury; in women, transthyretin concentrations remained stable with severe injury. Albumin concentrations were predicted by injury severity and serum osmolality, but not gender. C-reactive protein, and time postinjury did not significantly influence the serum proteins (serum IGF-1, transthyretin, or albumin). Without consideration of age or severity of injury, mean concentrations of IGF-1, transthyretin, albumin, and C-reactive protein were not different between men and women, and were within normal expected ranges. CONCLUSIONS: Serum IGF-1 and transthyretin concentrations, measured without the confounding effects of acute nutrient deprivation, were influenced by the severity of the injury in patients suffering traumatic injury. Age was an important determinant of serum IGF-1 in men and women even in severe trauma. The present study indicated that men and women demonstrate different physiologic responses to trauma. Women responded to increasing severity of injury with increased serum IGF-1 and little change in transthyretin concentrations. In men, both IGF-1 and transthyretin concentrations decreased with severe injury. Interpretation of serum concentrations of IGF-1 and transthyretin as markers of nutritional status after trauma should include consideration of age, gender, and severity of injury.

Serum insulin-like growth factor binding protein-3 responds differently to trauma in men and women.

OBJECTIVES: Insulin-like growth factor-1 (IGF-1) has been studied as a marker of nutrition in critical illness, but there is little research on IGF-binding protein-3, which regulates the bioactivity of IGF-1. The objectives of the present study were to measure serum IGF-binding protein-3 concentrations in trauma patients and to determine whether factors such as age, gender, and severity of injury should be considered when evaluating serum IGF-binding protein-3 concentrations as a marker of nutritional or clinical status. DESIGN: Prospective, randomized, descriptive study. SETTING: Emergency room of a university hospital. PATIENTS: One hundred eight trauma patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In this diverse group of patients, Injury Severity Score ranged from 1 to 45 (11.5 +/- 10.3 [SD]), age ranged from 18 to 77 yrs (35 +/- 15.3), and 68% were male. A venous blood sample was collected at the time of admission into the study and was analyzed for serum IGF-binding protein-3 concentration (by radioimmunoassay), serum osmolality, IGF-1 concentration, and C-reactive protein concentration. Relationships between variables were tested using Pearson's correlation coefficients and multiple regression analysis. Age, Injury Severity Score, serum osmolality, time since injury, and gender were not significant predictors of serum IGF-binding protein-3 concentrations when all patients were analyzed together. However, when men and women were analyzed separately, notable gender differences were observed. In women, serum IGF-binding protein-3 concentrations were increased with increasing severity of injury (beta = 0.52, R2 = .33, p < .01). In men, the opposite relationship was observed (beta = -0.29, R2 = .17, p < .01). Other predictors in the model (age, serum osmolality, and time since injury) were not significant. Variability in IGF-binding protein-3 concentration could not be explained by differences in body mass index or acute-phase response (serum C-reactive protein). Serum IGF-1 concentrations changed coordinately with IGF-binding protein-3 concentrations in females and males (r = .62, p < .001 and r = .54, p < .001, respectively). IGF-binding protein-3 concentration at the time of admission into the study could not predict mortality, but this value was correlated with length of hospitalization in women (r = .37, p < .05). CONCLUSIONS: Determination of the specificity and sensitivity of IGF-binding protein-3 as an index of nutrition or anabolism requires knowledge of its relationship to nonnutritional factors. These factors are most discernible before the confounding effects of treatments, absence of feeding, and complications. The present study demonstrated that gender and severity of injury must be considered when interpreting serum IGF-binding protein-3 concentrations in trauma patients. In a much wider context, the present findings suggest that the study of the metabolic response to stress requires separate analyses, based on gender.

Influence of zinc on growth, somatomedin, and glycosaminoglycan metabolism in rats.

Weanling male rats were fed control ad libitum, zinc-deficient (ZD, 1 ppm zinc) or pair-fed (PF) control diets for 13 days. Rats subsequently were refed control diets for up to 8 days and serially killed. ZD and PF diets significantly decreased growth rate, feed intake, and feed efficiency compared to controls. Body weight and feed efficiency, but not feed intake, were significantly less in ZD compared to PF. Bone zinc was 315, 286, and 109 micrograms/g (p less than 0.0001) for control, PF, and ZD at the end of depletion. 35SO4 uptake by glycosaminoglycans (GAG) was significantly less in ZD compared to either control ad libitum or PF rats. Xylosyltransferase activity was decreased significantly below PF and control by ZD, suggesting depressed enzyme activity and/or decreased GAG acceptor sites. Bioassayable somatomedin (Sm) activity was 0.81, 0.42 and 0.33 +/- 0.09 relative activity for control, PF and ZD at the end of depletion. Sm was statistically less in ZD compared to PF at day 2 and 5 of refeeding, but not at the end of depletion. Sm activity and GAG metabolism returned to normal after refeeding for 2-5 days in PF and for 5-8 days in ZD rats. Serum insulin but not glucose was significantly depressed by ZD and PF diets. Thus, zinc deficiency depressed growth and cartilage metabolism and was associated with decreased Sm activity and insulin levels. Some of these changes could be attributed to decreased feed intake as a result of ZD.

Effect of dietary fiber in insulin-dependent diabetics: insulin requirements and serum lipids.

Four young adult (18 to 26 years old), nonobese human subjects (two men and two women) with insulin-dependent diabetes mellitus volunteered to consume a series of three diets: baseline (normal daily intake), wheat bran (normal daily intake + 78 gm wheat bran per day), and cellulose (normal daily intake + 30 gm cellulose per day). Wheat bran and cellulose diets both contained 60 gm dietary fiber, with 50% of the dietary fiber from wheat bran or cellulose, respectively. Each patient served as his or her own control. Randomized diets were of 6 weeks' duration, separated by a 4-week "recovery" period. At the conclusion of each diet, subjects were hospitalized and underwent 12 hours of computer-controlled, insulin-glucose infusions. Significant decreases were seen in fasting cholesterol (p less than .05), but the decreases seemed to result largely from the significant reductions in high-density lipoprotein cholesterol. A large reduction in triglycerides was noted with cellulose feeding but not with wheat bran. The mean daily insulin dose decreased (p less than .05) in response to fiber addition (8% and 10% decrease for wheat bran and cellulose feeding, respectively). Mean biostator insulin requirements decreased 11% with wheat bran (p less than .05) but not with cellulose. During biostator monitoring, subjects experienced delayed postprandial blood glucose and insulin-infusion rate peaks with both wheat bran and cellulose feeding. The wheat bran diet reduced peak blood glucose concentration and peak insulin infusion rate in comparison with baseline and cellulose diets. The data suggest that high levels of cellulose or wheat bran are of marginal benefit to insulin-dependent diabetic subjects.

Influence of selected amino acid deficiencies on somatomedin, growth and glycosaminoglycan metabolism in weanling rats.

The effects of lysine-, methionine- or histidine-deficient diets compared to a control diet fed ad libitum or 15, 10 or 5 g/d were studied in weanling rats. Feed intake was 5-7 g/d for the amino acid-deficient animals. After 3 wk, all amino acid-deficient rats had lost more weight (P less than 0.01) than the controls fed at comparable energy levels. Serum somatomedin (Sm) activity was significantly decreased in lysine- (0.55 U/ml), methionine- (0.32 U/ml) and histidine-deficient (0.38 U/ml) rats compared to rats fed the control diet ad libitum (1.6 U/ml). Differences between amino acid-deficient and calorie-restricted animals were not significant. A similar response was observed in 35SO4 uptake by cartilage glycosaminoglycans (GAG). Caloric restriction and amino acid deficiency each resulted in lower 35SO4 uptake by cartilage GAG than occurred with ad libitum feeding, but there were no significant differences between the rats fed amino acid-deficient diets and those fed 5 or 10 g of the control diet. Compared to rats fed the control diet ad libitum, plasma growth hormone (GH) concentrations were lower in the rats fed 5 or 10 g of control diet per day and in those fed amino acid-deficient diets (P less than 0.05), but GH concentrations were not consistent with the growth retardation observed. The results confirm that Sm and GAG activities are reduced in protein-energy restriction independent of GH. However, changes could not be attributed to specific deficiencies of lysine, methionine and/or histidine.

Influence of manganese on growth, somatomedin and glycosaminoglycan metabolism.

Day-old chicks were fed control or manganese (Mn deficient diets ad libitum for 25 d. The chicks subsequently were refed control diet for up to 5 d. Mn deficiency significantly decreased growth rate and feed intake compared to controls. After 25 d of depletion, bone Mn concentration was 2% that of controls and 88% of the deficient chicks exhibited signs of perosis. Sulfate (35SO4) uptake into uronic acid was significantly depressed in cartilage from the Mn-depleted chicks and increased rapidly with refeeding, which may indicate increased glycosaminoglycan (GAG) biosynthesis or increased sulfation of the GAG molecule. In vitro activity of glycosyltransferases suggest that GAG synthesis may be interrupted by Mn deficiency. Somatomedin activity, serum insulin and glucose levels were not influenced significantly by Mn deficiency. Thus, while Mn deficiency decreased growth and GAG synthesis these effects were not mediated by somatomedin.

Taste acuity, plasma zinc levels, and weight loss during radiotherapy: a study of relationships.

Thirty-five patients who were to undergo radiotherapy and 13 normal subjects were evaluated with taste questionnaires, taste acuity tests, and plasma zinc analyses. The studies were repeated on the patients in the fifth week of radiotherapy. The mean taste thresholds for NaCl (salt), sucrose (sweet), HCl (sour), and urea (bitter) were elevated and the plasma zinc levels were lower (77.2 +/- 11.8 vs. 94.6 +/- 30.1 g/100 ml, p = 0.055) for the patients than for the controls. However, there was not a significant correlation between the taste thresholds and plasma zinc levels at any time. The mean weight loss experienced by the 14 patients who reported subjective taste alteration in the fifth week was 3.1 kg versus 0.1 kg (p = 0.005) for those who did not report taste alteration. The data suggest that alterations in taste acuity, but not plasma zinc levels, are associated with weight loss during radiotherapy.