Metabolomic Changes in Serum of Children with Different Clinical Diagnoses of Malnutrition.

BACKGROUND: Mortality in children with severe acute malnutrition (SAM) remains high despite standardized rehabilitation protocols. Two forms of SAM are classically distinguished: kwashiorkor and marasmus. Children with kwashiorkor have nutritional edema and metabolic disturbances, including hypoalbuminemia and hepatic steatosis, whereas marasmus is characterized by severe wasting. The metabolic changes underlying these phenotypes have been poorly characterized, and whether homeostasis is achieved during hospital stay is unclear. OBJECTIVES: We aimed to characterize metabolic differences between children with marasmus and kwashiorkor at hospital admission and after clinical stabilization and to compare them with stunted and nonstunted community controls. METHODS: We studied children aged 9-59 mo from Malawi who were hospitalized with SAM (n = 40; 21 with kwashiorkor and 19 with marasmus) or living in the community (n = 157; 78 stunted and 79 nonstunted). Serum from patients with SAM was obtained at hospital admission and 3 d after nutritional stabilization and from community controls. With the use of targeted metabolomics, 141 metabolites, including amino acids, biogenic amines, acylcarnitines, sphingomyelins, and phosphatidylcholines, were measured. RESULTS: At admission, most metabolites (128 of 141; 91%) were lower in children with kwashiorkor than in those with marasmus, with significant differences in several amino acids and biogenic amines, including those of the kynurenine-tryptophan pathway. Several phosphatidylcholines and some acylcarnitines also differed. Patients with SAM had profiles that were profoundly different from those of stunted and nonstunted controls, even after clinical stabilization. Amino acids and biogenic amines generally improved with nutritional rehabilitation, but most sphingomyelins and phosphatidylcholines did not. CONCLUSIONS: Children with kwashiorkor were metabolically distinct from those with marasmus, and were more prone to severe metabolic disruptions. Children with SAM showed metabolic profiles that were profoundly different from stunted and nonstunted controls, even after clinical stabilization. Therefore, metabolic recovery in children with SAM likely extends beyond discharge, which may explain the poor long-term outcomes in these children. This trial was registered at isrctn.org as ISRCTN13916953.

Social, dietary and clinical correlates of oedema in children with severe acute malnutrition: a cross-sectional study.

BACKGROUND: Severe acute malnutrition is a serious public health problem, and a challenge to clinicians. Why some children with malnutrition develop oedema (kwashiorkor) is not well understood. The objective of this study was to investigate socio-demographic, dietary and clinical correlates of oedema, in children hospitalised with severe acute malnutrition. METHODS: We recruited children with severe acute malnutrition admitted to Mulago Hospital, Uganda. Data was collected using questionnaires, clinical examination and measurement of blood haemoglobin, plasma c-reactive protein and α1-acid glycoprotein. Correlates of oedema were identified using multiple logistic regression analysis. RESULTS: Of 120 children included, 77 (64%) presented with oedematous malnutrition. Oedematous children were slightly older (17.7 vs. 15.0 months, p = 0.006). After adjustment for age and sex, oedematous children were less likely to be breastfed (odds ratio (OR): 0.19, 95%-confidence interval (CI): 0.06; 0.59), to be HIV-infected (OR: 0.10, CI: 0.03; 0.41), to report cough (OR: 0.33, CI: 0.13; 0.82) and fever (OR: 0.22, CI: 0.09; 0.51), and to have axillary temperature > 37.5 °C (OR: 0.28 CI: 0.11; 0.68). Household dietary diversity score was lower in children with oedema (OR: 0.58, CI: 0.40; 85). No association was found with plasma levels of acute phase proteins, household food insecurity or birth weight. CONCLUSION: Children with oedematous malnutrition were less likely to be breastfed, less likely to have HIV infection and had fewer symptoms of other infections. Dietary diversity was lower in households of children who presented with oedema. Future research may confirm whether a causal relationship exists between these factors and nutritional oedema.

Effects of randomized supplementation of methionine or alanine on cysteine and glutathione production during the early phase of treatment of children with edematous malnutrition.

BACKGROUND: We have shown that a low glutathione concentration and synthesis rate in erythrocytes are associated with a shortage of protein-derived cysteine in children with edematous severe acute malnutrition (SAM). OBJECTIVE: We tested the hypothesis that methionine supplementation may increase protein-derived cysteine and upregulate cysteine synthesis, thereby improving glutathione synthesis during the early treatment of edematous SAM. DESIGN: The cysteine flux, its de novo synthesis and release from protein breakdown, and erythrocyte glutathione synthesis rate were measured in 12 children with edematous SAM in the fed state by using stable isotope tracers at 3 clinical phases as follows: 3 ± 1 d (±SE) [clinical phase 1 (CP1)], 8 ± 1 d [clinical phase 2 (CP2)], and 14 ± 2 d (clinical phase 3) after admission. Subjects were randomly assigned to receive equimolar supplements (0.5 mmol ⋅ kg(-1) ⋅ d(-1)) of methionine or alanine (control) immediately after CP1. RESULTS: In the methionine compared with the alanine group, cysteine flux derived from protein breakdown was faster at CP2 than CP1 (P < 0.05), and the change in plasma cysteine concentration from CP1 to CP2 was greater (P < 0.05). However, there was no evidence of a difference in cysteine de novo synthesis and its total flux or erythrocyte glutathione synthesis rate and concentration between groups. CONCLUSIONS: Methionine supplementation increased cysteine flux from body protein but had no significant effect on glutathione synthesis rates. Although cysteine is made from methionine, increased dietary cysteine may be necessary to partially fulfill its demand in edematous SAM because glutathione synthesis rates and concentrations were less than previous values shown at full recovery. This study was registered at clinicaltrials.gov as NCT00473031.

The effect of serum magnesium levels and serum endothelin-1 levels on bone mineral density in protein energy malnutrition.

An inadequate and imbalanced intake of protein and energy results in protein-energy malnutrition (PEM). It is known that bone mineral density and serum magnesium levels are low in malnourished children. However, the roles of serum magnesium and endothelin-1 (ET-1) levels in the pathophysiology of bone mineralization are obscure. Thus, the relationships between serum magnesium and ET-1 levels and the changes in bone mineral density were investigated in this study. There was a total of 32 subjects, 25 of them had PEM and seven were controls. While mean serum ET-1 levels of the children with kwashiorkor and marasmus showed no statistically significant difference, mean serum ET-1 levels of both groups were significantly higher than that of the control group. Serum magnesium levels were lower than normal value in 9 (36%) of 25 malnourished children. Malnourished children included in this study were divided into two subgroups according to their serum magnesium levels. While mean serum ET-1 levels in the group with low magnesium levels were significantly higher than that of the group with normal magnesium levels (p < 0.05), mean bone mineral density and bone mineral content levels were significantly lower (p < 0.05). In conclusion, many factors play a role in the pathophysiology of changes in bone mineral density in malnutrition. Our study suggested that lower magnesium levels and higher ET-1 levels might be important factors in changes of bone mineral density in malnutrition. We recommend that the malnourished patients, especially with hypomagnesaemia, should be treated with magnesium early.

The effect of serum magnesium levels and serum Endothelin-1 levels on bone mineral density in protein energy malnutrition / Efecto de los niveles séricos de magnesio y los niveles séricos de Endotelina-1 sobre la densidad mineral osea en la malnutrición calórico-proteica

An inadequate and imbalanced intake of protein and energy results in protein-energy malnutrition (PEM). It is known that bone mineral density and serum magnesium levels are low in malnourished children. However, the roles of serum magnesium and endothelin-1 (ET-1) levels in the pathophysiology of bone mineralization are obscure. Thus, the relationships between serum magnesium and ET-1 levels and the changes in bone mineral density were investigated in this study. There was a total of 32 subjects, 25 of them had PEM and seven were controls. While mean serum ET-1 levels of the children with kwashiorkor and marasmus showed no statistically significant difference, mean serum ET-1 levels of both groups were significantly higher than that of the control group. Serum magnesium levels were lower than normal value in 9 (36%) of 25 malnourished children. Malnourished children included in this study were divided into two subgroups according to their serum magnesium levels. While mean serum ET-1 levels in the group with low magnesium levels were significantly higher than that of the group with normal magnesium levels (p < 0.05), mean bone mineral density and bone mineral content levels were significantly lower (p < 0.05). In conclusion, many factors play a role in the pathophysiology of changes in bone mineral density in malnutrition. Our study suggested that lower magnesium levels and higher ET-1 levels might be important factors in changes of bone mineral density in malnutrition. We recommend that the malnourished patients, especially with hypomagnesaemia, should be treated with magnesium early.

El consumo inadecuado y desbalanceado de proteínas y calorías energía conduce a la malnutrición calórico-proteica (MCP). Se sabe que la densidad mineral ósea y los niveles séricos de magnesio son bajos en los ninos malnutridos. Sin embargo, no está claro el papel que desempenan los niveles séricos de magnesio y los niveles séricos de endotelina-1 (ET-1) en la patofisiología de la mineralización del hueso. Por consiguiente, las relaciones entre los niveles séricos de magnesio y los niveles séricos de ET-1, y los cambios en la densidad mineral ósea, constituyen el objeto de investigación de este estudio. Hubo un total de 32 sujetos; 25 de ellos tenían DCP y 7 eran considerados. Si bien los niveles séricos promedios de ET-1 de los ninos con kwashiorkor y marasmo no mostraron diferencia estadística significativa, los niveles séricos promedio de ET-1 de ambos grupos fueron significativamente más altos que los del grupo de control. Los niveles séricos de magnesio estuvieron por debajo del valor normal en 9 (36%) de 25 ninos malnutridos. Los ninos malnutridos incluidos en este estudio fueron divididos en dos sub-grupos según sus niveles de magnesio en suero. Mientras que los niveles séricos promedio de ET-1 en el grupo con niveles bajos de magnesio fueron significativamente más altos que los del grupo con niveles normales de magnesio (p < 0.05), la densidad mineral ósea promedio y los niveles promedio del contenido mineral óseo fueron significativamente más bajos (p < 0.05). En conclusión, muchos factores juegan un papel en la patofisiología de los cambios en la densidad mineral ósea por la malnutrición. Nuestro estudio sugirió niveles más bajos de magnesio y niveles más altos de ET-1 podrían ser factores importantes en los cambios de densidad mineral ósea en la malnutrición. Se recomienda que los pacientes malnutridos, especialmente a causa de hipomagnesemia, sean tratados con magnesio lo más pronto posible.

Kwashiorkor and marasmus are both associated with impaired glucose clearance related to pancreatic ß-cell dysfunction.

Severe malnutrition is a major health problem in developing countries and can present as kwashiorkor or marasmus. Kwashiorkor is associated with septicaemia, profound metabolic changes including hepatic steatosis, altered protein metabolism and increased oxidative stress. Limited data suggest that children with kwashiorkor have an impaired glucose tolerance and insulin secretion. Our objective was to determine glucose tolerance in children with kwashiorkor compared to marasmus and its relation to insulin secretion and sensitivity. Six children with kwashiorkor and 8 children with marasmus were studied. We were also able to include 3 healthy children for comparison. They received a primed (13 mg/kg), constant infusion (0.15 mg/kg/min) of [6,6-(2)H(2)]glucose for 4 h with serial blood sampling. In addition, an oral glucose tolerance test (OGTT) was performed with labeled 10 mg/g [U-(13)C]glucose. Glucose clearance was determined using mathematical modeling. Glucose clearance rates during the OGTT were -392 (range 309) mL/kg in children with kwashiorkor, -156 (426) mL/kg in marasmus and 279 (345) mL/kg in the control group. Glucose clearance rates correlated with plasma albumin concentrations (r=0.67, P=.001). Insulin responses were strongly impaired in both kwashiorkor and marasmus. There was no indication of peripheral or hepatic insulin resistance in the malnourished groups. We show that glucose clearance rates are affected in both children with marasmus as well as kwashiorkor, which correlate with plasma albumin concentrations. The disturbed glucose clearance in malnutrition is related to an impairment in insulin availability.

Impaired glucose absorption in children with severe malnutrition.

OBJECTIVE: To quantify intestinal glucose absorption in children with two types of severe malnutrition, kwashiorkor and marasmus, compared with healthy children. STUDY DESIGN: Children with kwashiorkor (n = 6) and marasmus (n = 9) and control subjects (n = 3) received a primed (13 mg/kg), constant infusion (0.15 mg/kg/min) of [6,6H2]glucose for 4.5 hours. Two hours after start of the infusion an oral bolus of glucose 1.75 g/kg labeled with [U-13C]glucose 10 mg/g was given and was followed by periodic blood sampling. Mathematical modeling was applied to determine oral glucose absorption. RESULTS: Median total glucose absorption was 5.9 mmol/kg, interquartile range (IQR) 4.5-6.7 mmol/kg and 4.4 (IQR 2.9-5.9) mmol/kg in children with kwashiorkor and marasmus compared with 7.7 (IQR 5.8-9.0) mmol/kg in control subjects; P = .03 compared with marasmus). Children with the lowest glucose absorption were found specifically in the kwashiorkor group and marasmic children with hypoalbuminemia. Severe impairment in absorption correlated with urinary 8-hydroxydeoxyguanosine secretion (r = -0.62, P = .01). CONCLUSIONS: Severe malnutrition is associated with an impaired glucose absorption and decreased glucose absorption correlates with oxidative stress in these children.

Concentracion sérica de cobre ®libre¼ y ceruloplasmina en niños con desnutricion aguda grave antes de iniciar la terapia nutricional y al momento de recuperar el apetito en turbo, antioquia, colombia / Serum concentrations of free copper and ceruloplasmin in children with severe acute malnutrition before nutritional therapy and after children have recovered the apetite in turbo, antioquia, colombia

Introduction: copper supplementation therapy has been used in children with acute and severe malnutrition. Scientific evidence has shown that malnourished children with edema have free copper in plasma which could produce oxidative stress. Objective: To compared plasma concentrations of free copper between children with acute and severe malnutrition and a control group. Methodology: Cross sectional study where 66 normal and malnourished children were studied. A longitudinal study (before and after type) design was used including 40 children with severe and acute malnutrition; free copper was merasured by high-resolution capillary electrophoresis; ceruloplasmin and PCR by nephelometry. Results: In the cross sectional study children with marasmus had higher free copper serum concentrations than children with oedematous malnutrition, but the difference was not significant. In the control group this metal was not found. Children with oedema showed significant lower ceruloplasmin concentrations than children with marasmus (p=0.00) while the difference in PCR was also no significant for both groups. When the relationship between free copper serum concentrations and the presence of infection was analyzed no significant differences were obtained. However, serum albumin concentration was significantly lower for children with oedematous malnutrition than the marasmic group (p=0.016). After children recovered the appetite in the longitudinal study, serum free copper concentration decreased for both groups and ceruloplasmin concentration increased but no significant differences were observed. Conclusion: Copper supplementation could be considered as nutritional therapy for undernourished children since the beginning of the nutritional treatment, as it is recommended by WHO.

Introducción: La recuperación de los niños con desnutrición aguda grave incluye suplementación con cobre desde el inicio de la terapia; existen evidencias que niños edematosos pueden tener cobre libre en plasma el cual podría generar estrés oxidativo. Objetivo: Comparar concentraciones séricas de cobre libre y ceruloplasmina en un grupo de desnutridos agudos graves y un grupo control Metodología: estudio transversal al ingreso entre niños con y sin desnutrición en una muestra de 66 sujetos y longitudinal de tipo antes y después en 40 niños desnutridos. Se determinó cobre libre por electroforesis capilar de alta resolución; ceruloplasmina y PCR por nefelometría, además de variables clínicas Resultados: En el transversal, los marasmáticos presentaron niveles de cobre libre mayores que los edematosos sin diferencia significativa; en el grupo control este metal no se detectó. En los edematosos la concentración de ceruloplasmina fue significativamente menor con relación a los marasmáticos (p=0.00) y la PCR no presentó diferencia significativa entre ellos. No se encontraron diferencias significativas entre los niveles de cobre libre y presencia o no de infección. La albúmina se encontró más baja en los edematosos con diferencia significativa respecto a los marasmáticos (p=0.016). En el longitudinal, al recuperar el apetito el cobre libre disminuyó y la ceruloplasmina aumentó en los dos grupos sin diferencia significativa Conclusión: el suplemento de cobre como componente de la terapia nutricional puede ser suministrado a los desnutridos desde el inicio como lo propone el protocolo de la OMS.

Prevalence of aflatoxins in blood and urine of Egyptian infants with protein-energy malnutrition.

The aim of the present work was to study the presence of aflatoxins in blood and urine of infants with protein-energy malnutrition (PEM). The study was conducted on 60 infants, 30 with kwashiorkor and 30 with marasmus, with 10 age-matched healthy infants studied as a control group. Complete blood count, liver function tests, and determination of the level of aflatoxins (B1, B2, G1, G2, M1, M2, G2a, B3, GM1, P, and aflatoxicol R0) in blood and urine were carried out in all studied infants. Serum aflatoxins were detected in more infants with kwashiorkor (80%) than in those with marasmus (46.7%). The mean serum levels of total aflatoxins, AFB1, AFG1, and AFB2a, were significantly higher in infants with kwashiorkor (p <.001). Aflatoxin B1 (AFB1) was the most commonly detected type. The prevalence of aflatoxin excretion in the urine of infants with kwashiorkor was 80%, a higher value than that in infants with marasmus (46.7%). The mean urinary concentration of total aflatoxins followed the same pattern of distribution (p < .052). There were no significant differences between groups in the mean urinary concentrations of AFB1, AFG1, AFB2a, AFM1, and AFG2a. Aflatoxins were not detected in any of the serum or urine samples of the control group. Aflatoxins are highly prevalent in this study population and show a high degree of correlation with severe PEM.

Hepatic proteins and nutrition assessment.

Serum hepatic protein (albumin, transferrin, and prealbumin) levels have historically been linked in clinical practice to nutritional status. This paradigm can be traced to two conventional categories of malnutrition: kwashiorkor and marasmus. Explanations for both of these conditions evolved before knowledge of the inflammatory processes of acute and chronic illness were known. Substantial literature on the inflammatory process and its effects on hepatic protein metabolism has replaced previous reports suggesting that nutritional status and protein intake are the significant correlates with serum hepatic protein levels. Compelling evidence suggests that serum hepatic protein levels correlate with morbidity and mortality. Thus, serum hepatic protein levels are useful indicators of severity of illness. They help identify those who are the most likely to develop malnutrition, even if well nourished prior to trauma or the onset of illness. Furthermore, hepatic protein levels do not accurately measure nutritional repletion. Low serum levels indicate that a patient is very ill and probably requires aggressive and closely monitored medical nutrition therapy.

The evaluation of serum leptin level and other hormonal parameters in children with severe malnutrition.

OBJECTIVES: Protein-energy malnutrition (PEM) is a clinical problem caused by inadequate intake of one or more nutritional elements, and remains as one of the most important health problems in developing countries. The aim of this study is to determine the relationship among leptin concentrations, body weight and concentrations of some serum hormones, e.g., basal GH, IGF-1, basal cortisol and IGF-BP3, in severe malnourished children, and to determine the effects of leptin in malnourished children. DESIGN AND METHODS: The study group consisted of 36 children diagnosed with PEM. Thirty healthy children were enrolled as the control group. After an overnight fast and before initiation of feedings, fasting venous blood samples were obtained from a forearm vein with needle technique for routine tests, and leptin, IGF-1, IGF-BP3, basal GH and cortisol levels were measured. Tests were carried out in the laboratories of the Department of Biochemistry by commercial kits. RESULTS: Serum leptin levels of infants with marasmus and kwashiorkor were significantly lower than that of the controls (2.09 +/- 0.93 and 2.27 +/- 1.01, 6.82 +/- 2.28 ng/ml, respectively, P < 0.001). However, there was no significant difference between serum leptin levels in children with marasmus and those with kwashiorkor (P > 0.05). Serum IGF-1 and IGF-BP3 levels were significantly lower in malnourished children (P < 0.001, both). Also, basal GH and cortisol levels were significantly higher in malnourished children (P < 0.001, both). There was a positive correlation among serum leptin levels and IGF-1 and IGF-BP3 levels and also a negative correlation among serum leptin levels and basal GH and cortisol levels in children diagnosed with marasmus or kwashiorkor and the control group. CONCLUSIONS: The decrease of energy intake and adipose tissue and serum IGF-1 levels in children with PEM may result in decrease of leptin secretion. Decrease in serum leptin levels may initiate food intake by increasing appetite and stimulating the secretion of cortisol and GH that might increase energy expenditure through an autocrine mechanism. Moreover, serum leptin level may be an important signal to reflect the metabolism of children with PEM.

Selenium serum concentrations in malnourished Ecuadorian children: a case-control study.

Little is known about the selenium status of children living in the Andean regions of South America, which commonly have volcanic soil with low selenium content. Human selenium deficiency has been hypothesized to have a negative impact on immune function and to increase the risk of infection. The objective of this study was to evaluate the serum selenium concentrations of severely malnourished children living in urban and rural Andean Ecuador, and to compare them to a control group of normally nourished children from the same communities. Forty-three children, aged six to 36 months, with marasmus or kwashiorkor and 30 control children were enrolled from July to November 1993 in Quito, Ecuador. Serum selenium concentrations were lower in the children with marasmus (0.91 +/- 0.28 microM/L, n = 21) and kwashiorkor (0.37 +/- 0.15 microM/L, n = 22) than in those who were normally nourished (1.77 +/- 0.75 microM/L, n = 30, p < 0.001 for each difference). The serum selenium concentrations in children with kwashiorkor were significantly lower than those in children with marasmus (p < 0.001). All 22 of the children with kwashiorkor, 15 of the 21 children with marasmus, and five of the 30 normal children had serum levels < 1.08 microM/L (8.5 micrograms/dL) (chi 2 = 38.4, p < 0.00000001). In the Andean regions of Ecuador, selenium deficiency is prevalent in children with protein and caloric deficiency. Furthermore, 17% of Ecuadorian children with normal weight-for age-Z score are selenium-deficient.

Cysteine supplementation improves the erythrocyte glutathione synthesis rate in children with severe edematous malnutrition.

BACKGROUND: Children with severe edematous malnutrition have higher than normal oxidant damage and lower concentrations of the antioxidant reduced glutathione (GSH), which are associated with slower synthesis of GSH and with low extra- and intracellular concentrations of the precursor amino acid cysteine. OBJECTIVE: We tested whether early dietary supplementation with cysteine could restore a normal GSH concentration and synthesis rate in these children. DESIGN: Erythrocyte cysteine and GSH concentrations and the fractional and absolute synthesis rates of GSH were measured in 2 groups of 16 edematous malnourished children, 10 boys and 6 girls aged 6-18 mo, at 3 times after hospital admission: at approximately 2 d (period 1), when they were malnourished and infected; at approximately 11 d (period 2), when they were malnourished but cleared of infection; and at approximately 50 d (period 3), when they had recovered. Supplementation with either 0.5 mmol. kg(-1). d(-1) N-acetylcysteine (NAC group) or alanine (control group) started immediately after period 1 and continued until recovery. RESULTS: From period 1 to period 2 the concentration and the absolute synthesis rate of GSH increased significantly (P < 0.05) in the NAC group but not in the control group. The increases in the GSH concentration and synthesis rate were approximately 150% and 510% greater, respectively, in the NAC group than in the control group. The increases in the NAC group were associated with a significant effect of supplement (P < 0.03) on erythrocyte cysteine concentration. CONCLUSION: These results suggest that the GSH synthesis rate and concentration can be restored during the early phase of treatment if patients are supplemented with cysteine.

Prostaglandin E2 is raised in kwashiorkor.

OBJECTIVE: Infection is a common occurrence in children with kwashiorkor. It has been suggested that infection in kwashiorkor results from immune depression, and that the immune depression of kwashiorkor is caused by a diet-associated elevation of prostaglandin E2 (PGE2). The purpose of this study was to determine whether levels of PGE2 are abnormal in children with kwashiorkor. SETTING AND SUBJECTS: Plasma PGE2 and plasma proteins were measured in children admitted with oedematous kwashiorkor, and compared with PGE2 in children with cerebral palsy. RESULTS: Plasma PGE2 was higher in children with kwashiorkor than in control children (7.25 +/- 3.5 v. 3.51 +/- 1.59, P < 0.01). Within the kwashiorkor study group there was a significant negative correlation between log-transformed serum PGE2 and total plasma protein (r = -0.59, P < 0.001), plasma albumin (r = -0.63, P < 0.001), weight-for-age (r = -0.37, P < 0.05), and height-for-age (r = -0.37, P < 0.05). The difference in mean values of PGE2 in children with kwashiorkor who recovered from the illness and those who died was not significant (7.1 +/- 2.6 v. 9.1 +/- 4.8, P = 0.36). CONCLUSION: Significantly higher PGE2 levels in children with kwashiorkor provide adequate reason for the depression of immune function known to occur in these children. Elevated PGE2 levels may also be implicated in other components of the illness.

Serum concentrations of sex hormone binding globulin are elevated in kwashiorkor and anorexia nervosa but not in marasmus.

BACKGROUND: Customary blood protein markers for malnutrition are of limited value in the diagnosis of protein-energy malnutrition or anorexia nervosa in children and in the follow-up to refeeding in such children. OBJECTIVES: For these diseases, we compared the diagnostic value of sex hormone binding globulin (SHBG) with that of albumin, transferrin, transthyretin, and retinal binding protein and determined the relations between concentrations of insulin, insulin-like growth factor I, and SHBG. DESIGN: SHBG was assayed in children with protein-energy malnutrition (29 children with kwashiorkor and 28 with marasmus), in 29 anorectic girls (before and after refeeding), and in age- and sex-matched control subjects. RESULTS: Mean (+/-SE) serum SHBG concentrations were higher in the children with kwashiorkor (0.18 +/- 0.07 micromol/L) than in the children with marasmus (0.11 +/- 0.05 micromol/L, P < 0.0001) or the control subjects (0.11 +/- 0.03 micromol/L, P < 0.0005). In the children with anorexia nervosa before weight gain, serum SHBG concentrations were significantly higher (0.10 +/- 0.04 micromol/L) than in the age-matched control subjects (0.06 +/- 0.03 micromol/L, P < 0.001) and decreased significantly after 30 d of refeeding (0.04 +/- 0.01 micromol/L, P < 0.0001). This decrease was negatively correlated with insulin-like growth factor I but not with insulin. Mean serum SHBG concentrations were influenced neither by inflammation, as indicated when C-reactive protein was used as a marker (0.27 +/- 0.27, 0.34 +/- 0.42, and <0.04 micromol/L in the children with marasmus, kwashiorkor, and anorexia nervosa, respectively), nor by glomerular filtration, as indicated when cystatin-C was used as a marker (68.46 +/- 23.08, 66.90 +/- 43.08, and 49.23 +/- 7.69 micromol/L, respectively). CONCLUSIONS: The high SHBG concentration observed in anorexia nervosa and kwashiorkor seems to be of multifactorial origin. For these 2 diseases, SHBG is a reliable marker of nutritional status, is unrelated to either C-reactive protein or cystatin-C, and may be helpful in distinguishing kwashiorkor from marasmus and as a follow-up marker after refeeding.

Pro-inflammatory cytokines in Turkish children with protein-energy malnutrition.

BACKGROUND: Protein-energy malnutrition (PEM) results from food insufficiency as well as from poor social and economic conditions. Development of PEM is due to insufficient nutrition. Children with PEM lose their resistance to infections because of a disordered immune system. It has been reported that the changes occurring in mediators referred to as cytokines in the immune system may be indicators of the disorders associated with PEM. AIMS: To determine the concentrations of pro-inflammatory cytokines in children with PEM, and to find out whether there was an association with the clinical presentation of PEM. METHODS: The levels of serum total protein, albumin, tumour necrosis factor-alpha, and interleukin-6 were measured in 25 patients with PEM and in 18 healthy children as a control group. PEM was divided into two groups as kwashiorkor and marasmus. The kwashiorkor group consisted of 15 children and the marasmus group consisted of 10 children. RESULTS: Levels of serum total protein and albumin of the kwashiorkor group were significantly lower than both the marasmus group and controls (p < 0.05). In view of tumour necrosis factor-alpha levels, there was no difference between groups (p > 0.05). While levels of interleukin-6 in both the marasmus group and the kwashiorkor group were significantly higher compared with controls (p < 0.05), there was no significant difference between the groups of marasmus and kwashiorkor (p > 0.05). CONCLUSIONS: It was observed that the inflammatory response had increased in children with malnutrition.

Selenium status, kwashiorkor and congestive heart failure.

UNLABELLED: Selenium deficiency is associated with congestive heart failure (CHF) in geographic areas where dietary selenium intake is low and in individuals receiving total parenteral nutrition. Among 66 children with kwashiorkor (including marasmic-kwashiorkor), those who developed CHF had lower serum selenium concentrations than those who did not (32.9 +/- 8.3 vs 41.1 +/- 11.9 microg/L, mean +/- SD, p = 0.03). This association was independent of serum albumin and selenium status was not associated with severity of symptoms, anthropometric indices or HIV infection. CONCLUSION: This association raises the possibility that selenium may contribute to CHF in washiorkor.

[Effects of vitamin A supplementation on nutritional markers on the follow-up of malnutrition in children]. / Effets de la supplémentation en vitamine A sur les marqueurs de la nutrition dans la prise en charge de la malnutrition de l'enfant.

Prospectively assessment of vitamin A supplemented during a follow-up of a protein-energy malnutrition rehabilitation included serum retinol, Retinol Binding Protein (RBP) and prealbumin (PA) determination. This study was conducted during one month on a group of 36 vitamin A (200,000 IU) supplemented malnourished children and 32 age-and sex-matched malnourished children receiving only a nutritional regimen. Determinations were carried out at days 0, 15 and 30. Protein marker concentrations increased steadily in supplemented children as compared to those in the untreated group (p < 0.05, Student's t test). On the other hand, serum concentrations of the two proteins progressively regained normal values in the vitamin A supplemented group. Data also showed that retinol supplementation in conjunction with an appropriate nutritional diet is effective in raising serum concentrations of vitamin A and its binding proteins to normal levels. Therefore, we concluded that the results of this study demonstrates the importance of vitamin A supplementation in the management of these deficiency states.