C-reactive protein (CRP) in high altitude Bolivian peri-urban adolescents varies by adiposity, current illness, height, socioeconomic status, sex, and menarcheal status: The potential benefits and costs of adipose reserves in arduous environments.

OBJECTIVES: In non-industrialized and low-income populations, adipose stores can serve as a valuable buffer against harsh conditions such as seasonal food scarcity. However, these reserves may incur costs due to adipocytes' production of pro-inflammatory cytokines; inflammation is associated with increased risk for cardiometabolic diseases later in life. Life history theory posits that, especially in populations with high juvenile mortality, higher adiposity may nonetheless be advantageous if its benefits in early life outweigh its later costs. Relatively little is known about adolescents' C-reactive protein concentration (CRP; an inflammation biomarker) in such environments. We investigated CRP and its associations with several hypothesized predictors in adolescents in an economically diverse peri-urban Andean community. METHODS: We measured CRP in dried blood spots and collected data on anthropometrics, illnesses, socioeconomic status (SES), and menarcheal status in 59 female and 40 male adolescents ("Alteños", 11.0-14.9 years old) with normal vital signs in El Alto, Bolivia (~4150 m amsl). We used Cole's LMS method to standardize all anthropometrics for sex and age, and principal components analysis to construct a "fat-factor" variable loading on these standardized z-scores. We used multiple linear regression to assess the influence of fat-factor and other likely predictors on CRP rank. RESULTS: Compared to a national Bolivian growth reference, Alteños were, on average, shorter and leaner; only 6% were classified as overweight and none were obese. Pre-menarche females were on average leaner than post-menarche females. The best-fitting model explained 24% of the variance in CRP rank. Significant predictors were fat-factor, SES, current illness for males and pre-menarche females, and z-height for females. CONCLUSIONS: Our results are consistent with a tradeoff between investments in growth versus immune functioning, as might be expected in an environment with limited resources and high pathogen exposure (e.g., soil-transmitted helminths, poor sanitation). Thinner Alteños appear to maintain a minimum CRP concentration independent of fat-factor, while fatter (or less-thin) Alteños' CRP rises with fat-factor. Female Alteños appear to be trading off investment in immune response for investment in growth and maturation. Alteños' high rate of stunting and absence of obesity suggests chronic, presumably multifactorial, stress. Adipose stores likely buffer against some of these stressors and, in an environment such as this-in which many lack sufficient nutritious foods, potable water, adequate sewage, and health care-may confer a net lifetime benefit.

OBJETIVOS: En poblaciones no industrializadas y de bajos ingresos, las reservas adiposas pueden servir como un valioso amortiguador frente a condiciones duras como la escasez estacional de alimentos. Sin embargo, estas reservas pueden tener un coste debido a la producción de citoquinas proinflamatorias por parte de los adipocitos; la inflamación se asocia a un mayor riesgo de enfermedades cardiometabólicas en etapas posteriores de la vida. La teoría de la historia vital postula que, especialmente en poblaciones con una elevada mortalidad juvenil, una mayor adiposidad puede ser ventajosa si sus beneficios en los primeros años de vida compensan sus costes posteriores. Se sabe relativamente poco sobre la concentración de proteína C reactiva (PCR; un biomarcador de inflamación) de los adolescentes. Investigamos la PCR y sus asociaciones con varios predictores hipotéticos en adolescentes de una comunidad andina periurbana económicamente diversa. MÉTODOS: Se midió la PCR en muestras de sangre seca y se recogieron datos sobre antropometría, enfermedades, nivel socioeconómico (NSE) y menarquia en 59 mujeres y 40 varones adolescentes («alteños¼, 11,0­14,9 años de edad) con signos vitales normales en El Alto, Bolivia (~4150m amsl). Usamos el método LMS de Cole para estandarizar todos los parámetros antropométricos para sexo y edad, y análisis de componentes principales para construir una variable «factor de grasa¼ cargada en estos puntajes z­estandarizados. Se utilizó la regresión lineal múltiple para evaluar la influencia del factor grasa y otros posibles predictores en el rango de la PCR. RESULTADOS: En comparación con una referencia nacional boliviana de crecimiento, los alteños eran, en promedio, más bajos y más delgados; sólo el 6% estaban clasificados con sobrepeso y ninguno era obeso. Las chicas premenárquicos eran, en promedio, más delgados que las chicas postmenárquicos. El modelo de regresión que mejor se ajustaba explicaba el 24% de la varianza en el rango de PCR. Observamos una nueva asociación entre la adiposidad y la PCR. Cuando el factor adiposidad es >0, el rango de la PCR aumenta linealmente con el factor adiposidad. Cuando el factor adiposidad es <0, la PCR no varía con el factor adiposidad. Estos patrones sugieren que los Alteños más delgados mantienen una concentración mínima de PCR independiente del factor adiposidad, mientras que la PCR de los Alteños más gordos (menos delgados) aumenta con el factor adiposidad. Además, existe una mayor variación en el rango de la PCR en los adolescentes más delgados que en los más gordos. El autoinforme de una enfermedad actual en niños y niñas premenárquicas se asoció con una PCR significativamente más alta. La ausencia de una asociación significativa entre la enfermedad actual y la PCR en las chicas postmenárquicas puede reflejar confusión por cambios en la PCR durante el ciclo menstrual. Manteniendo constantes todos los demás factores predictivos, la PCR aumentó con el incremento del nivel socioeconómico. En las niñas, el aumento de la estatura se asoció a una disminución de la PCR, lo que sugiere que las niñas favorecen la inversión en crecimiento y maduración frente a la inversión en respuestas inmunitarias inflamatorias a corto plazo. En los chicos, no se observó una relación significativa entre la estatura y la PCR. La baja estatura y la delgadez de estos adolescentes sugieren que pueden estar invirtiendo en defensas humorales a más largo plazo (por ejemplo, anticuerpos contra helmintos), pero esta hipótesis requiere más estudios. CONCLUSIONES: La alta tasa de retraso en el crecimiento y la ausencia de obesidad de los alteños sugieren un estrés crónico, presumiblemente multifactorial. Muchas familias carecen de alimentos nutritivos suficientes, agua potable, alcantarillado adecuado y atención sanitaria. Es probable que las reservas adiposas amortigüen algunos de estos factores de estrés y confieran un beneficio neto a lo largo de la vida (la reducción de la mortalidad juvenil puede compensar cualquier aumento del riesgo de enfermedades cardiometabólicas en etapas posteriores de la vida). Sin embargo, estas compensaciones tienen un coste para los individuos y las sociedades. Reducir los riesgos de patógenos y mejorar la capacidad de los habitantes del altiplano para acceder sistemáticamente a agua limpia y a alimentos sanos suficientes y asequibles probablemente reportaría beneficios para la salud a lo largo de toda la vida.

Socioeconomic impacts on Andean adolescents' growth: Variation between households, between communities and over time.

Background/Objectives: We evaluated potential socioeconomic contributors to variation in Andean adolescents' growth between households within a peri-urban community undergoing rapid demographic and economic change, between different community types (rural, peri-urban, urban) and over time. Because growth monitoring is widely used for assessing community needs and progress, we compared the prevalences of stunting, underweight, and overweight estimated by three different growth references. Methods: Anthropometrics of 101 El Alto, Bolivia, adolescents (Alteños), 11.0-14.9 years old in 2003, were compared between households (economic status assessed by parental occupations); to one urban and two rural samples collected in 1983/1998/1977, respectively; and to the WHO growth reference, a representative sample of Bolivian children (MESA), and a region-wide sample of high-altitude Peruvian children (Puno). Results: Female Alteños' growth was positively associated with household and maternal income indices. Alteños' height averaged ∼0.8SD/∼0.6SD/∼2SDs greater than adolescents' height in urban and rural communities measured in 1983/1998/1977, respectively. Overweight prevalence was comparable to the WHO, and lower than MESA and Puno, references. Stunting was 8.5/2.5/0.5 times WHO/MESA/Puno samples, respectively. Conclusions/Implications: Both peri-urban conditions and temporal trends contributed to gains in Alteños' growth. Rural out-migration can alleviate migrants' poverty, partly because of more diverse economic options in urbanized communities, especially for women. Nonetheless, Alteños averaged below WHO and MESA height and weight medians. Evolved biological adaptations to environmental challenges, and the consequent variability in growth trajectories, favor using multiple growth references. Growth monitoring should be informed by community- and household-level studies to detect and understand local factors causing or alleviating health disparities.

Seasonal and circadian variation in salivary testosterone in rural Bolivian men.

Testosterone (T) plays a key role in the increase and maintenance of muscle mass and bone density in adult men. Life history theory predicts that environmental stress may prompt a reallocation of such investments to those functions critical to survival. We tested this hypothesis in two studies of rural Bolivian adult men by comparing free T levels and circadian rhythms during late winter, which is especially severe, to those in less arduous seasons. For each pair of salivary T(AM)/T(PM) samples (collected in a approximately 12-h period), circadian rhythm was considered classic (C(CLASSIC)) if T(AM) > 110%T(PM), reverse (C(REVERSE)) if T(PM) > 110%T(AM), and flat (C(FLAT)) otherwise. We tested the hypotheses that mean T(AM) > mean T(PM) and that mean T(LW) < mean T(OTHER) (LW = late winter, OTHER = other seasons). In Study A, of 115 T(PM)-T(AM) pairs, 51% = C(CLASSIC), 39% = C(REVERSE), 10% = C(FLAT); in Study B, of 184 T(AM)-T(PM) pairs, 55% = C(CLASSIC), 33% = C(REVERSE), 12% = C(FLAT). Based on fitting linear mixed models, in both studies T(OTHER-AM) > T(OTHER-PM) (A: P = 0.035, B: P = 0.0005) and T(OTHER-AM) > T(LW-AM) (A: P = 0.054, B: P = 0.007); T(PM) did not vary seasonally, and T diurnality was not significant during late winter. T diurnality varied substantially between days within an individual, between individuals and between seasons, but neither T levels nor diurnality varied with age. These patterns may reflect the seasonally varying but unscheduled, life-long, strenuous physical labor that typifies many non-industrialized economies. These results also suggest that single morning samples may substantially underestimate peak circulating T for an individual and, most importantly, that exogenous signals may moderate diurnality and the trajectory of age-related change in the male gonadal axis.

Effect of developmental and ancestral high altitude exposure on chest morphology and pulmonary function in Andean and European/North American natives.

Chest depth, chest width, forced vital capacity (FVC), and forced expiratory volume (FEV1) were measured in 170 adult males differing by ancestral (genetic) and developmental exposure to high altitude (HA). A complete migrant study design was used to study HA natives (Aymara/Quechua ancestry, n = 88) and low altitude (LA) natives (European/North American ancestry, n = 82) at both altitude (La Paz, Bolivia, 3,600 m) and near sea level (Santa Cruz, Bolivia, 420 m). HAN and LAN migrant groups were classified as: N(th) generation migrants, born and raised in a non-native environment; child migrants who migrated during the period of growth and maturation (0-18 yrs); and adult migrants who migrated after 18 years of age. Chest depth, FVC, and FEV1 measures were larger with increasing developmental exposure in both HAN migrants at LA and LAN migrants at HA. Developmental responses were similar between HAN and LAN groups. FVC and FEV1 measures were larger in HANs vs LANs born and raised at HA to suggest a genetic effect, but were similar in HANs and LANs born and raised at LA. The similarity of HAN and LAN groups at LA suggests that the genetic potential for larger lung volumes at HA depends upon developmental exposure to HA. Additional data for females (HANs at HA, n = 20, and LAN adult migrants to HA, n = 17) show similar differences as those shown between male HAN and LAN groups. Am. J. Hum. Biol. 11:383-395, 1999. Copyright 1999 Wiley-Liss, Inc.

Effect of high altitude on protein metabolism in Bolivian children.

In Bolivia, malnutrition in children is a major health problem that may be caused by inadequate protein, energy, and micronutrient intake; exposure to bacterial and parasitic infections; and life in a multistress environment (high altitude, cold, cosmic radiation, low ambient humidity). However, no data on protein absorption and utilization at high altitude were available. Therefore, we evaluated the effect of altitude on protein metabolism in Bolivian children. We measured protein utilization using leucine labeled with a stable isotope ((13)C) in two groups of healthy prepubertal children matched for age. Group 1 (n = 10) was examined at high altitude (HA) in La Paz (3600 m), and group 2 (n = 10) at low altitude (LA) in Santa Cruz (420 m). The nutritional status did not differ between groups but, as was to be expected, the HA group had higher hemoglobin concentration than the LA group. The children consumed casein that was intrinsically labeled with L-(1-(13)C) leucine and expired (13)CO(2) was analyzed. Samples of expired air were measured by isotope ratio mass spectrometer in Clermont-Ferrand. It was found that cumulative leucine oxidation ((13)CO(2)) at 300 min after ingestion was 19.7 +/- 4.9% at HA and 25.2 +/- 3.2% at LA. These results showed that protein absorption and/or utilization is significantly affected by altitude.

Effect of menstrual cycle phase on exercise performance of high-altitude native women at 3600 m.

At sea level normally menstruating women show increased ventilation (VE) and hemodynamic changes due to increased progesterone (P) and estrogen (E2) levels during the mid-luteal (L) compared to the mid-follicular (F) phase of the ovarian cycle. Such changes may affect maximal exercise performance. This repeated-measures, randomized study, conducted at 3600 m, tests the hypothesis that a P-mediated increase in VE increases maximal oxygen consumption (V(O(2)max)) during the L phase relative to the F phase in Bolivian women, either born and raised at high altitude (HA), or resident at HA since early childhood. Subjects (N=30) enrolled in the study were aged 27.7 +/- 0.7 years (mean +/- S.E.M.) and non-pregnant, non-lactating, relatively sedentary residents of La Paz, Bolivia, who were not using hormonal contraceptives. Mean salivary P levels at the time of the exercise tests were 63.3 pg ml(-1) and 22.9 pg ml(-1) for the L and F phases, respectively. Subset analyses of submaximal (N=23) and maximal (N=13) exercise responses were conducted only with women showing increased P levels from F to L and, in the latter case, with those also achieving true (V(O(2)max)). Submaximal exercise VE and ventilatory equivalents were higher in the L phase (P<0.001). P levels were significantly correlated to the submaximal exercise VE (r=0.487, P=0.006). Maximal work output (W) was higher (approximately 5 %) during the L phase (P=0.044), but (V(O(2)max)) (l min(-1)) was unchanged (P=0.063). Post-hoc analyses revealed no significant relationship between changes in P levels and changes in (V(O(2)max))) from F to L (P=0.072). In sum, the menstrual cycle phase has relatively modest effects on ventilation, but no effect on (V(O(2)max)) of HA native women.

Salivary progesterone levels and rate of ovulation are significantly lower in poorer than in better-off urban-dwelling Bolivian women.

BACKGROUND: Agriculturalists in less-developed countries (LDC) have lower progesterone levels than urban industrialized populations. However, it is unknown if urban LDC populations are also relatively lower. We tested whether urban Bolivia samples-poorer (Bol-p) and better-off (Bol-b)-have lower progesterone than a Chicago (USA) sample, and whether progesterone and rate of ovulation are lower in Bol-p than in Bol-b. METHODS: Serial salivary samples collected from Bolivians, screened according to strict exclusion criteria during two complete menstrual cycles, were radioimmunoassayed for progesterone; anthropometrics were collected at mid-follicular and mid-luteal phases. RESULTS: Progesterone levels are lower in the Bolivia samples, and higher in the Bol-b than Bol-p; ovulation rate is greater in Bol-b than Bol-p. For only ovulatory cycles, mean-follicular-P (pmol/l), mean-luteal-P (pmol/l), and mean-peak-P (pmol/l) are respectively 65, 142 and 208 in Bol-p; 76, 167 and 232 in Bol-b; and 96, 240 and 330 in Chicago. Principal components representing body-size and progesterone level are positively correlated (r = 0.404, P = 0.005). CONCLUSIONS: Progesterone levels appear to be influenced by chronic and acute ecological conditions, evidenced by the association with body-size and the probability of ovulation respectively. These findings have implications for understanding cancer aetiology, developing population-appropriate hormonal contraceptives, and modelling the evolution and functioning of the reproductive system.

Estudio comparativo de la funcion respiratoria en Niños bolivianos de la altura y el tropico; influencia del estado nutricional y antropometrico / Comparative study of respiratory function of Bolivian children and the influence of the nutritional and anthropometric status

Nuestro proposito tiene una doble finalidad, en primer lugar hacer un analisis de los factores que contribuyen en la funcion respiratoria de niños expuestos a diferentes ambientes ecologicos, altura y tropico y de diferente estado nutricional; en segundo lugar un estudio comparativo que permite ratificar los valores de referencia establecidos con el fin de efectuar una evaluacion funcional en patologia respiratoria infantil. Se comparan los volumenes pulmonares de cuatro grupos de niños en edad prepuberal habitantes de altura (LA PAz 3700 m sobre el nivel del mar, presion barometrica: 495 mmHg y de tierras bajas (Santa Cruz, 420 msnm, presion barometrica: 760 mmHg). El grupo de la altura GA (N=67) fue estudiado en el Instituto Boliviano de Altura (I.B.B.A), y dividido en dos subgrupos GA1 que corresponde a niños de nivel socioeconomico de nivel alto (N=23) y GA2 de nivel socioeconomico bajo (N=44). El grupo de tierras bajas GB (N=71) fue estudiado en CENETROP, y dividido en dos subgrupos GB1 formados por niños de nivel socioeconomicos altos (N=43) y GB2 de nivel socioeconomico bajo (N=28).