Vinicius J. B. Martins

Long-Lasting Effects of Undernutrition

Undernutrition is one of the most important public health problems, affecting more than 900 million individuals around the World. It is responsible for the highest mortality rate in children and has long-lasting physiologic effects, including an increased susceptibility to fat accumulation mostly in the central region of the body, lower fat oxidation, lower resting and postprandial energy expenditure, insulin resistance in adulthood, hypertension, dyslipidaemia and a reduced capacity for manual work, among other impairments. Marked changes in the function of the autonomic nervous system have been described in undernourished experimental animals. Some of these effects seem to be epigenetic, passing on to the next generation. Undernutrition in children has been linked to poor mental development and school achievement as well as behavioural abnormalities. However, there is still a debate in the literature regarding whether some of these effects are permanent or reversible. Stunted children who had experienced catch-up growth had verbal vocabulary and quantitative test scores that did not differ from children who were not stunted. Children treated before 6 years of age in day-hospitals and who recovered in weight and height have normal body compositions, bone mineral densities and insulin production and sensitivity.

A baixa estatura leve está associada a índices mais elevados de gordura corporal: estudo de uma população de baixa renda

OBJECTIVE: To determine the impact of transferring a pediatric population to mechanical ventilator dependency units (MVDUs) or to home mechanical ventilation (HMV) on bed availability in the pediatric intensive care unit (ICU). METHODS: This is a longitudinal, retrospective study of hospitalized children who required prolonged mechanical ventilation at the MVDU located at the Hospital Auxiliar de Suzano, a secondary public hospital in Sao Paulo, Brazil. We calculated the number of days patients spent at MVDU and on HMV, and analyzed their survival rates with Kaplan-Meier estimator. RESULTS: Forty-one patients were admitted to the MVDU in 7.3 years. Median length of stay in this unit was 239 days (interquartile range = 102-479). Of these patients, 22 came from the ICU, where their transfer made available 8,643 bed-days (a mean of 14 new patients per month). HMV of eight patients made 4,022 bed-days available in the hospital in 4 years (a mean of 12 new patients per month in the ICU). Survival rates of patients at home were not significantly different from those observed in hospitalized patients. CONCLUSION: A hospital unit for mechanical ventilator-dependent patients and HMV can improve bed availability in ICUs. Survival rates of patients who receive HMV are not significantly different from those of patients who remain hospitalized.

Adolescents with Mild Stunting Show Alterations in Glucose and Insulin Metabolism

Purpose. To evaluate glucose and insulin profiles in adolescents with mild stunting and overweight in order to assess the possibility of increased predisposition to diabetes. Subjects and Methods. The study population consisted of 66 pubertal adolescents classified as mildly stunted (height-for-age z scores ≥−2 and <−1) or of normal stature, as well as overweight (body mass index ≥85th percentile) or normal weight. Beta-cell function and insulin resistance were evaluated according to the homeostasis model assessment (HOMA). Results. In the group with mild stunting, glucose, insulin, and HOMA-IR levels were significantly higher in overweight adolescents compared with those of normal weight, whereas HOMA-B levels were significantly lower. Adolescents with mild stunting showed significantly higher accumulations of body and abdominal fat than their normal stature counterparts. Conclusions. The presence of mild stunting was associated with higher levels of glucose and insulin, diminished function of beta cells, and increased insulin resistance. These results reinforce the need for intervention in adolescents with mild stunting.

Children recovered from malnutrition exhibit normal insulin production and sensitivity.

Protein-energy malnutrition promotes adaptive hormonal changes that result in stunting. A previous study showed that stunted children had increased insulin sensitivity and diminished pancreatic beta-cell function. The objectives of the present study were to analyse the glucose, insulin, homeostasis model assessment of insulin sensitivity (HOMA-S) and homeostasis model assessment of pancreatic beta-cell function (HOMA-B) levels after nutritional recovery. The recovered group (n 62) consisted of malnourished children after treatment at a nutrition rehabilitation centre. At the beginning of treatment their age was 2.41 (sd 1.28) and 2.31 (sd 1.08) years, weight-for-age Z score - 2.09 (sd 0.94) and - 2.05 (sd 0.55) and height-for-age Z score - 1.85 (sd 1.11) and - 1.56 (sd 0.90), for boys and girls respectively. The control group consisted of well-nourished children without treatment (n 26). After treatment, boys of the recovered group gained 1.29 (sd 1.06) Z scores of height-for-age and 1.14 (sd 0.99) Z scores of weight-for-age, and girls, 1.12 (sd 0.91) and 1.21 (sd 0.74) Z scores respectively. No differences were found between control and recovered groups in insulin levels for boys (P = 0.704) and girls (P = 0.408), HOMA-B for boys (P = 0.451) and girls (P = 0.330), and HOMA-S (P = 0.765) for boys and girls (P = 0.456) respectively. The present study shows that the changes observed previously in glucose metabolism and insulin were reverted in children who received adequate treatment at nutritional rehabilitation centres and showed linear catch-up.

Mild stunting is associated with higher body fat: study of a low-income population

OBJECTIVE To test if individuals having height-for-age z scores between -2 and -1 present higher body fat percentage and, therefore, should not be categorized as having normal nutritional status. METHODS The study involved 96 individuals (52 boys and 44 girls); 57% of whom had already attained puberty. Body composition was analyzed by dual energy X-ray absorptiometry. RESULTS The percentage of abdominal body fat in pre-pubertal stunted girls was higher (27.4%; p = 0.01) in comparison with their non-stunted counterparts (20.6%). Similar differences in abdominal fat content (%) were observed for pubertal stunted and non-stunted girls and boys (37.6 and 29.8%, respectively, p = 0.01; 24.6 and 15.7%, p = 0.01, respectively). The percentages of total body fat percent in pre-pubertal stunted girls and pubertal stunted boys (29.9 and 24.5%, p = 0.03; 26.3 and 18.1%, p = 0.01, respectively) were higher than those of their non-stunted counterparts. Non-stunted groups showed lower waist circumferences. CONCLUSION Adolescents with mild stunting exhibit alterations in body composition indicating increased risk of metabolic diseases.

Mild stunting is associated with higher blood pressure in overweight adolescents

BACKGROUND Studies have shown that pre/postnatal undernutrition leads to higher risk of non communicable diseases such as diabetes, hypertension and obesity in adulthood. OBJECTIVE To determine whether overweight adolescents with mild stunting [height-for-age Z scores (HAZ) in the range <-1 to ≥ -2] have higher blood pressure than overweight individuals with normal stature (HAZ ≥ -1). METHODS Participants were classified as mildly stunted or of normal stature, and further stratified according to body mass index-for-age percentiles as overweight, normal or underweight. Systolic (SBP) and diastolic (DPB) blood pressures were determined according to guidelines, and abdominal fat was analyzed by dual energy X-ray absorptiometry. RESULTS Mild stunted overweight individuals showed higher DBP values (p=0.001) than their underweight counterparts (69.75 ± 12.03 and 54.46 ± 11.24 mmHg, respectively), but similar to those of normal BMI. No differences were found in DBP values of normal, overweight and underweight individuals among the normal stature groups. An increase in SBP (p=0.01) among mild stunted individuals was found when those with overweight were compared to their underweight and normal BMI counterparts (114.70 ± 15.46, 97.38 ± 10.87 and 104.72 ± 12.24 mmHg, respectively). Although no differences were observed in the means of SBP between mild stunting and normal stature groups, a significant intercept was found (p=0.01), revealing higher SBP among stunted individuals. There was a correlation between SBP and abdominal fat (r=0.42, ρ=0.02) in the stunted group. CONCLUSION Stunted individuals with overweight showed higher SBP than those of normal stature and overweight. These findings confirm that mild stunting increase the risk of future hypertension and alterations are evident at early age.BACKGROUND: Studies have shown that pre/postnatal undernutrition leads to higher risk of non communicable diseases such as diabetes, hypertension and obesity in adulthood. OBJECTIVE: To determine whether overweight adolescents with mild stunting [height-for-age Z scores (HAZ) in the range -2] have higher blood pressure than overweight individuals with normal stature (HAZ >-1). MEHTODS: Participants were classified as mildly stunted or of normal stature, and further stratified according to body mass index-for-age percentiles as overweight, normal or underweight. Systolic (SBP) and diastolic (DPB) blood pressures were determined according to guidelines, and abdominal fat was analyzed by dual energy X-ray absorptiometry. RESULTS: Mild stunted overweight individuals showed higher DBP values (p=0.001) than their underweight counterparts (69.75 ± 12.03 and 54.46±11.24 mmHg, respectively), but similar to those of normal BMI. No differences were found in DBP values of normal, overweight and underweight individuals among the normal stature groups. An increase in SBP (p=0.01) among mild stunted individuals was found when those with overweight were compared to their underweight and normal BMI counterparts (114.70 ± 15.46, 97.38 ± 10.87 and 104.72 ± 12.24 mmHg, respectively). Although no differences were observed in the means of SBP between mild stunting and normal stature groups, a significant intercept was found (p=0.01), revealing higher SBP among stunted individuals. There was a correlation between SBP and abdominal fat (r=0.42, ρ=0.02) in the stunted group. CONCLUSION: Stunted individuals with overweight showed higher SBP than those of normal stature and overweight. These findings confirm that mild stunting increase the risk of future hypertension and alterations are evident at early age.

Impact of nutritional recovery with linear growth on the concentrations of adipokines in undernourished children living in Brazilian slums

Undernutrition in early life has been reported to be closely associated with the development of non-communicable diseases in adulthood. Adequate treatment is important for reversing these effects. In the present study, we investigated the effects of undernutrition and anthropometric recovery on the weights and heights of children in relation to the concentrations of leptin, adiponectin and plasminogen activator inhibitor-1 (PAI-1). A total of 119 children (aged 6-16 years) from the slums of São Paulo were selected according to their nutritional status and divided into three groups as follows: control (healthy without intervention, n 38) with a height-for-age Z score (HAZ) and a BMI-for-age Z score (BAZ) > -1·6; undernourished (HAZ and/or BAZ < -1·6, n 54); recovered from undernutrition (after treatment in a rehabilitation centre; HAZ and BAZ > -1·6, n 27). Blood samples were collected to determine insulin, glucose, leptin, adiponectin and PAI-1 concentrations. Leptin concentrations in the undernourished group were lower than those in the control and recovered groups (mean 0·92 (95% CI 0·67, 1·25), 2·03 (95% CI 1·46, 2·82) and 1·66 (95% CI 1·15, 2·44) ng/ml, P=0·003), which had similar leptin concentrations. There were no differences in adiponectin and PAI-1 concentrations among the groups. A positive correlation between waist circumference and leptin concentrations was observed in all the girls and boys of the control group (control: r 0·729, P<0·01; undernourished: r 0·490, P<0·05; and recovered: r 0·829, P<0·01; r 0·673, P<0·05). Stronger correlations between leptin and insulin concentrations were observed in the recovered group. The results of the present study indicate that normal leptin concentrations are found when normal height and weight are achieved.

A 15-year study on the treatment of undernourished children at a nutrition rehabilitation centre (CREN), Brazil.

OBJECTIVE To build a life table and determine the factors related to the time of treatment of undernourished children at a nutrition rehabilitation centre (CREN), São Paulo, Brazil. DESIGN Nutritional status was assessed from weight-for-age, height-for-age and BMI-for-age Z-scores, while neuropsychomotor development was classified according to the milestones of childhood development. Life tables, Kaplan-Meier survival curves and Cox multiple regression models were employed in data analysis. SETTING CREN (Centre of Nutritional Recovery and Education), São Paulo, Brazil. SUBJECTS Undernourished children (n 228) from the southern slums of São Paulo who had received treatment at CREN under a day-hospital regime between the years 1994 and 2009. RESULTS The Kaplan-Meier curves of survival analysis showed statistically significant differences in the periods of treatment at CREN between children presenting different degrees of neuropsychomotor development (log-rank = 6·621; P = 0·037). Estimates based on the multivariate Cox model revealed that children aged ≥24 months at the time of admission exhibited a lower probability of nutritional rehabilitation (hazard ratio (HR) = 0·49; P = 0·046) at the end of the period compared with infants aged up 12 months. Children presenting slow development were better rehabilitated in comparison with those exhibiting adequate evolution (HR = 4·48; P = 0·023). No significant effects of sex, degree of undernutrition or birth weight on the probability of nutritional rehabilitation were found. CONCLUSIONS Age and neuropsychomotor developmental status at the time of admission to CREN are critical factors in determining the duration of treatment.

Normal cortisol response to cold pressor test, but lower free thyroxine, after recovery from undernutrition

Undernutrition is a stressor with long-term consequences, and the effect of nutritional recovery on cortisol and thyroid hormone status is unknown. To investigate basal thyroid hormones and the cortisol response to a cold pressor test in children recovered from undernutrition, a cross-sectional study was undertaken on children (6-16 years) separated into four groups: control (n 41), stunted (n 31), underweight (n 27) and recovered (n 31). Salivary cortisol was collected over the course of 10 h: upon awakening, before and after an unpleasant and a pleasant stimulus. Cortisol upon awakening was highest in the stunted and lowest in the underweight groups: control=5·05 (95% CI 3·71, 6·89) nmol/l, stunted=6·62 (95% CI 3·97, 11·02) nmol/l, underweight=2·51 (95% CI 1·75, 3·63) nmol/l and recovered=3·46 (95% CI 2·46, 4·90) nmol/l (P=0·005). Girls had higher cortisol concentrations upon awakening compared with boys (P=0·021). The undernourished groups showed an elevated cortisol response both to the unpleasant stimulus and at the last measurement (16.00 hours) compared with that of the recovered group: AUC, control=2·07 (95% CI 1·69, 2·45) nmol/l×30 min, stunted=2·48 (95% CI 1·91, 3·06) nmol/l×30 min, underweight=2·52 (95% CI 2·07, 2·97) nmol/l×30 min, recovered=1·68 (95% CI 1·26, 2·11) nmol/l×30 min (P=0·042); and control=2·03 (95% CI 1·75, 2·39) nmol/l×30 min, stunted=2·51 (95% CI 1·97, 3·19) nmol/l×30 min, underweight=2·61 (95% CI 2·16, 3·16) nmol/l×30 min, recovered=1·70 (95% CI 1·42, 2·03) nmol/l×30 min (P=0·009). Lower free thyroxine (T4) was found in the recovered and stunted groups: control=1·28 (95% CI 1·18, 1·39) pmol/l, stunted=0·98 (95% CI 0·87, 1·10) pmol/l, underweight=1·10 (95% CI 1·01, 1·21) pmol/l and recovered=0·90 (95% CI 0·83, 0·99) pmol/l (P<0·001). Multivariate analysis showed a lower cortisol concentration along 10 h (06.00-16.00 hours) in the recovered compared with the other groups (P=0·017), and similar concentrations between the recovered and control group. In conclusion, the children with recovery in weight and height had a cortisol stress response similar to control but a lower basal free T4. Longitudinal studies are warranted to determine the extent of these endocrine changes after recovery of undernutrition and in adulthood.

Lower waist circumference in mildly-stunted adolescents is associated with elevated insulin concentration

OBJECTIVE Augmented waist circumference (WC) is associated with non-communicable diseases and could represent a valuable marker in screening for metabolic dysfunctions in subjects with insufficient linear growth. The objective of the present study was to determine whether biochemical and hemodynamic parameters and waist circumference vary between mildly-stunted and non-stunted adolescents from impoverished communities of São Paulo, Brazil. METHODS The cross-sectional study involved 206 subjects, aged between 9 and 19 years and living in impoverished areas of São Paulo, Brazil. The sample population was divided according to height-for-age Z-score (HAZ) into stunted (-1 > HAZ ≥ -2) and non-stunted (HAZ ≥ -1) groups, and was sub-divided according to gender. Logistic regression analysis was employed to compare individuals with elevated (> 75th percentile) insulin concentrations. The receiver operating characteristic curves were constructed to determine WC cut-off points that could be used to identify stunted and non-stunted individuals with elevated insulin concentrations. RESULTS WC cut-off points of 58.25cm and 67.2cm allowed for correct classification of 90.7% of stunted and 88.7% of non-stunted individuals in the studied population. While the sensitivity of the model was high for stunted and non-stunted subjects (98.8% and 97.2%, respectively), the specificity was modest (57.1% and 41.2%, respectively). CONCLUSION The results presented herein suggest that an increase in plasma insulin is one of the primary metabolic modifications in stunted individuals, and that this alteration could be identified at a lower WC cut-off point than in non-stunted counterparts.