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Biomedical subjects

A M Prentice

Publications and source records attributed to A M Prentice.

At least 37 records · Page 2Linked to original sources

Glucose, insulin and lipid metabolism in rural Gambians exposed to early malnutrition.

AIMS: There is now substantial evidence to suggest that susceptibility to certain non-communicable diseases may be increased by early undernutrition. In rural Gambia, an annual hungry season reduces birth weight by 200-300 g and increases the prevalence of low birth weight (< 2500 g) from 11% to 24%. The aim of this study was to investigate whether fetal nutritional stress (using season of birth as a proxy measure for prenatal growth retardation) or early childhood malnutrition (using historical anthropometric records) had a residual influence on risk factors for cardiovascular disease in a cohort of rural Gambian adults. METHODS: Two hundred and nineteen adults (mean age = 35.8 years; mean body mass index = 21.3 kg/m2; women = 181) for whom month of birth and infant anthropometric records were available participated in this study. Risk factors for cardiovascular disease were measured. RESULTS: No differences were found between season of birth groups (hungry vs. harvest) and fasting measures of glucose, insulin, lipids, fibrinogen or cortisol, or against 30 and 120 min glucose and insulin levels following an oral glucose tolerance test, or blood pressure. Similarly, these risk factors for adult disease were not related to the subjects' weight-for-age as children. CONCLUSIONS: Moderate-to-severe fetal and childhood malnutrition in rural Gambia caused no detectable impairment of the glucose/insulin axis, or of other cardiovascular disease risk factors in adults remaining lean and fit on a low-fat diet.

Adult↗

Beyond body mass index.

Body mass index (BMI) is the cornerstone of the current classification system for obesity and its advantages are widely exploited across disciplines ranging from international surveillance to individual patient assessment. However, like all anthropometric measurements, it is only a surrogate measure of body fatness. Obesity is defined as an excess accumulation of body fat, and it is the amount of this excess fat that correlates with ill-health. We propose therefore that much greater attention should be paid to the development of databases and standards based on the direct measurement of body fat in populations, rather than on surrogate measures. In support of this argument we illustrate a wide range of conditions in which surrogate anthropometric measures (especially BMI) provide misleading information about body fat content. These include: infancy and childhood; ageing; racial differences; athletes; military and civil forces personnel; weight loss with and without exercise; physical training; and special clinical circumstances. We argue that BMI continues to serve well for many purposes, but that the time is now right to initiate a gradual evolution beyond BMI towards standards based on actual measurements of body fat mass.

Adipose Tissue↗

De novo lipogenesis during controlled overfeeding with sucrose or glucose in lean and obese women.

BACKGROUND: The results of previous studies suggest that de novo lipogenesis may play an important role in the etiology of obesity, particularly during overconsumption of different carbohydrates. OBJECTIVE: We hypothesized that de novo lipogenesis would increase during overfeeding, would vary depending on the type of carbohydrate consumed, and would be greater in obese than in lean women. DESIGN: De novo lipogenesis was measured during 96 h of overfeeding by 50% with either sucrose or glucose and during an energy balance treatment (control) in 8 lean and 5 obese women. De novo lipogenesis was determined by measuring the amount of deuterium incorporation into plasma triacylglycerols. Fat and carbohydrate balance were measured simultaneously by continuous whole-body calorimetry. RESULTS: De novo lipogenesis did not differ significantly between lean and obese subjects, except with the control treatment, for which de novo lipogenesis was greater in the obese subjects. De novo lipogenesis was 2- to 3-fold higher after overfeeding by 50% than after the control treatment in all subjects. The type of carbohydrate overfeeding (sucrose or glucose) had no significant effect on de novo lipogenesis in either subject group. Estimated amounts of absolute VLDL production ranged from a minimum of 2 g/d (control) to a maximum of 10 g/d after overfeeding. This compares with a mean fat balance of approximately 275 g after 96 h of overfeeding. Individual subjects showed characteristic amounts of de novo lipogenesis, suggesting constitutive (possibly genetic) differences. CONCLUSION: De novo lipogenesis increases after overfeeding with glucose and sucrose to the same extent in lean and obese women but does not contribute greatly to total fat balance.

Body Composition↗

Immune function in rural Gambian children is not related to season of birth, birth size, or maternal supplementation status.

BACKGROUND: We previously showed that mortality from infectious diseases among young adults in rural Gambia is strongly correlated with the season of their birth. This suggests that early life insults that involve fetal malnutrition, exposure to natural toxins, or highly seasonal infections affecting the infant or pregnant mother cause permanent damage to the immune system. Excess mortality begins after puberty and has a maximal odds ratio of >10 for deaths between ages 25 and 50 y. OBJECTIVE: We investigated the immune function of children according to birth weight, season of birth, and exposure to maternal dietary supplementation during pregnancy. DESIGN: Immune function was measured in 472 prepubertal children aged 6.5-9.5 y from 28 villages in rural Gambia. The mothers of these children had been randomly assigned to a high-energy prenatal supplementation program, which significantly increased birth weight. This permitted supplementation status, birth weight, and season of birth to be investigated as exposure variables. The outcome variables tested were naive responses to rabies and pneumococcus vaccines, delayed-type hypersensitivity skin reactions, and mucosal defense (secretory immunoglobulin A and dual-sugar permeability). RESULTS: Immune responses were strongly related to current age and sex, suggesting a high level of sensitivity, but were not consistently related to birth weight, season of birth, or maternal supplementation (control compared with intervention). CONCLUSION: Events in early life did not predict a measurable defect in immune response within this cohort of rural Gambian children. It is possible that the early programming of immune function may be mediated through a defect in immunologic memory or early senescence rather than through impairment of early responses.

Adult↗

Obesity and its potential mechanistic basis.

Obesity plays a central role in the development of the thrifty phenotype. The metabolic disturbances of the cardiovascular metabolic syndrome, frequently ascribed to the thrifty phenotype, are rare in the absence of obesity and their expression is generally proportional to the size of the excess fat mass. Thus obesity interacts with early-life programming in the establishment of disease. Surprisingly, the evidence that fetal or infant diet leads to programming of obesity itself is rather weak, though this may be explained by the fact that life-style influences obscure the linkage between metabolic predisposition and maturity-onset obesity. This paper summarises the possible metabolic basis of obesity with special reference to those processes for which there are plausible mechanisms by which long-term programming may operate. It is concluded that the newly-emerging molecular discoveries in body weight regulatory systems point to the need for detailed studies of gene-environment interactions and life-course influences before we will fully understand the aetiology of complex phenotypes such as the metabolic syndrome.

Disease Susceptibility↗

Evaluation of the novel Tanita body-fat analyser to measure body composition by comparison with a four-compartment model.

The Tanita body-fat analyser is a novel device to estimate body fat, based on the principles of bioelectrical impedance. It differs from other impedance systems which use surface electrodes in that the subjects stand bare-footed on a metal sole-plate which incorporates the electrodes, hence impedance is measured through the legs and lower trunk. In 104 men and 101 women (16-78 years and BMI 16-41 kg/m2) the mean bias in body-fat mass measured using the Tanita body-fat analyser was 0.8 (2SD 7.9) kg relative to a four-compartment model. This is comparable to the other prediction techniques tested (conventional tetrapolar impedance -1.3 (2SD 6.9) kg, skinfold thicknesses 0.3 (2SD 7.4) kg, and BMI-based formulas -0.2 (2SD 9.0) kg and -0.6 (2SD 8.5) kg), but the agreement was poorer than for 'reference' methods to measure body fat (density 0.2 (2SD 3.7) kg, total body water -0.9 (2SD 3.4) kg and dual-energy X-ray absorptiometry 0.1 (2SD 5.0) kg). The present paper also describes the derivation of a new prediction equation for the calculation of body composition from the Tanita body-fat analyser. The equation incorporates sex, age, and a log-transformation of height, weight and the measured impedance to predict body fat measured by a four-compartment model. This approach is recommended in the derivation of other prediction equations in body composition analysis. Using this novel prediction equation the residual standard deviations were 4.8% for men and 3.3% for women. A similar analysis using data collected with a conventional tetrapolar system yielded residual standard deviations of 4.3% for men and 3.1% for women. This demonstrates that the practical simplicity of the novel Tanita method is not associated with a clinically significant decrement in performance relative to a traditional impedance device.

Absorptiometry, Photon↗

Randomized controlled trial of changes in dietary carbohydrate/fat ratio and simple vs complex carbohydrates on body weight and blood lipids: the CARMEN study. The Carbohydrate Ratio Management in European National diets.

OBJECTIVE: To investigate the long-term effects of changes in dietary carbohydrate/fat ratio and simple vs complex carbohydrates. DESIGN: Randomized controlled multicentre trial (CARMEN), in which subjects were allocated for 6 months either to a seasonal control group (no intervention) or to one of three experimental groups: a control diet group (dietary intervention typical of the average national intake); a low-fat high simple carbohydrate group; or a low-fat high complex carbohydrate group. SUBJECTS: Three hundred and ninety eight moderately obese adults. MEASUREMENTS: The change in body weight was the primary outcome; changes in body composition and blood lipids were secondary outcomes. RESULTS: Body weight loss in the low-fat high simple carbohydrate and low-fat high complex carbohydrate groups was 0.9 kg (P < 0.05) and 1.8 kg (P < 0.001), while the control diet and seasonal control groups gained weight (0.8 and 0.1 kg, NS). Fat mass changed by -1.3kg (P< 0.01), -1.8kg (P< 0.001) and +0.6kg (NS) in the low-fat high simple carbohydrate, low-fat high complex carbohydrate and control diet groups, respectively. Changes in blood lipids did not differ significantly between the dietary treatment groups. CONCLUSION: Our findings suggest that reduction of fat intake results in a modest but significant reduction in body weight and body fatness. The concomitant increase in either simple or complex carbohydrates did not indicate significant differences in weight change. No adverse effects on blood lipids were observed. These findings underline the importance of this dietary change and its potential impact on the public health implications of obesity.

Adult↗

Energy adaptations in human pregnancy: limits and long-term consequences.

The very slow rate of human fetal growth generates a lower incremental energy stress than in any other mammalian species. This creates a situation in which adaptive changes in metabolic rate and in the amount of additional maternal fat stored during gestation can make a profound difference to the overall energy needs of pregnancy. Comparisons of women in affluent and poor countries have recorded mean population energy needs ranging from as high as 520 MJ to as low as -30 MJ per pregnancy. These energy costs are closely correlated with maternal energy status when analyzed both between and within populations, suggesting that they represent functional adaptations that have been selected for their role in protecting fetal growth. Although this metabolic plasticity represents a powerful mechanism for sustaining pregnancy under very marginal nutritional conditions, it must not be construed as a perfect mechanism that obviates the need for optimal nutritional care of pregnant women. The fact that fetal weight represents up to 60% of total pregnancy weight gain in many pregnancies in poor societies (compared with a well-nourished norm of 25%) indicates that the fetus is developing under suboptimal nutritional and physiologic conditions. It has long been recognized that this has immediate consequences for the offspring in terms of increased perinatal mortality. The more recent appreciation that impaired fetal growth may also precipitate longer-term defects in terms of adult susceptibility to noncommunicable and infectious diseases reinforces the view that pregnancy may be the most sensitive period of the life cycle in which nutritional intervention may reap the greatest benefits.

Adaptation, Physiological↗

Macronutrient disposal during controlled overfeeding with glucose, fructose, sucrose, or fat in lean and obese women.

BACKGROUND: Previous short-term studies (< or =6 h) showed differences in energy expenditure (EE) and macronutrient oxidation in response to overfeeding with different types of dietary carbohydrate. This finding could have implications for obesity. OBJECTIVE: We used 96-h continuous whole-body calorimetry in 8 lean and 5 obese women to assess metabolic disposal (energy dissipation and glycogen or fat storage) of a controlled excess of dietary energy supplied as different carbohydrate sources or as fat. DESIGN: Five dietary treatments were applied in random order: energy balance (control) and overfeeding by 50% of energy requirements with fat (O(fat)) or predominantly with glucose, fructose, or sucrose (O(cho)). Macronutrient oxidation rates were assessed from nonprotein gaseous exchanges. Net macronutrient balances were calculated as cumulative differences between intake and oxidation. RESULTS: Increased EE in response to overfeeding dissipated 7.9% of the energy excess with a variation in EE of <1.7% across overfeeding treatments (NS). EE during the O(fat) treatment significantly exceeded that during the control treatment in the lean but not in the obese women. There were no significant differences between lean and obese women in macronutrient oxidation or balances, so data were pooled. O(cho) induced glycogen storage on day 1 ( approximately 100 g) but thereafter progressively stimulated carbohydrate oxidation so that balance was reached on days 3 and 4. Fat oxidation was proportionately suppressed. Of the excess carbohydrate, 74% was oxidized; there were no significant differences between the various O(cho) treatments. O(fat) stimulated fat oxidation by 18% and suppressed carbohydrate oxidation. On average, 12% of the excess energy was stored as glycogen and 88% as fat; there was no significant difference between overfeeding treatments. CONCLUSION: There was no significant difference in fat balance during controlled overfeeding with fat, fructose, glucose, or sucrose.

Calorimetry↗

Fat and energy needs of children in developing countries.

The fat requirements of children can be judged according to 4 criteria: 1) the possible obligate needs of fat as a metabolic fuel, 2) the provision of a sufficiently energy-dense diet to meet energy needs, 3) the adequate supply of essential fatty acids, and 4) the supply of sufficient fat to allow adequate absorption of fat-soluble vitamins. In these respects the fat requirements of children in developing countries are probably similar to those of children in affluent nations except for the additional needs imposed by environmental stresses, particularly recurrent infections. In many developing countries, the low energy density of weaning foods appears to be a major contributor to growth faltering and ultimate malnutrition. Evidence from doubly labeled water studies suggests that these diets are adequate when children are healthy but fail to support rapid catch-up growth after diarrhea and other infections. The issues in determining and meeting the fat needs of children in developing countries are illustrated with use of detailed comparative dietary data from a rural community in The Gambia and from Cambridge, United Kingdom. The outstanding feature of the Gambian data is the great importance of breast milk as a source of fat and essential fatty acids up until the end of the second year of life. Weaning foods and adult foods contain low amounts of fat, which causes a sharp transition from adequate fat intakes to probable inadequate fat intakes when children are weaned from the breast. The effects of such low fat intakes, particularly in terms of immune function, require investigation.

Adolescent↗

Report of the IDECG Working Group on the modulating effect of stressors on the upper and lower limits of lipid and carbohydrate intake. International Dietary Energy Consultative Group.

The recommended caloric intake should be increased by 2870kJ (670Kcal)/d in the exclusively breast-feeding woman. Of this increase, 10% should be ingested as protein, up to 50% as lipid and no less than 40% as carbohydrate. If weight loss is desired lipid intake can be reduced but carbohydrate intake should be maintained. Of the total energy increment 3% should be supplied by essential fatty acids (linoleic and alpha-linolenic acids) and 0.5% by n-3 fatty acids. The issue of dietary supplementation with long-chain polyunsaturated fatty acids remains for future research.

Dietary Carbohydrates↗

Effects of inactivity and diet composition on human energy balance.

OBJECTIVES: To investigate the influences of inactivity and dietary macronutrient composition on energy and fat balance and to look for interactions between them. DESIGN: Two-day measurements of energy expenditure and substrate oxidation on five occasions; ad libitum food intake from diets of 35% and 60% energy as fat, with and without imposed activity, and a fixed overfeeding at 35% fat with free activity. SUBJECTS: Eight normal-weight male volunteers. MEASUREMENTS: Energy expenditure and substrate oxidation by indirect whole-body calorimetry, and macronutrient intakes from food consumption on ad libitum regimens. RESULTS: Subjects consumed the same energy, mean 11.6 MJ/d, regardless of activity level, on the 35% diet. Subjects consumed more energy on the 60% than the 35% diet, mean 14 vs. 11.6 MJ/d. Inactivity induced a strong positive energy balance: 5.1 (60% diet), and 2.6 MJ/d (35% diet). Energy balance with activity was not significantly different between diets, nor significantly different from zero: 1.1 MJ/d (60% diet), and -0.2 MJ/d (35% diet). When intentionally overfed, subjects failed to compensate by raising voluntary activity. CONCLUSION: Energy intake was not regulated over a 2-day period in response to either imposition of inactivity or a high-fat diet. Activity proved essential to the avoidance of significant positive energy balance.

Adult↗

Prenatal or early postnatal events predict infectious deaths in young adulthood in rural Africa.

BACKGROUND: Research over the past decade has suggested that prenatal and early postnatal nutrition influence the risk of developing chronic degenerative diseases up to 60 years later. We now present evidence that risk of death from infectious diseases in young adulthood is similarly programmed by early life events. METHODS: In three rural Gambian villages, affected by a marked annual seasonality in diet and disease, we have kept detailed demographic, anthropometric and health records since 1949. Fate was known with certainty for 3,162 individuals (2,059 alive/1,103 dead, most dying in childhood). For this case-control analysis of antecedent predictors of premature mortality, all adult deaths (n = 61) were paired with two randomly selected controls matched for sex and year of birth. RESULTS: Mean age at death was 25 (SD: 8) years. Adult death was associated with a profound bias in month of birth with 49 cases born in the nutritionally-debilitating hungry season (Jul-Dec) versus 12 in the harvest season (Jan-Jun). Relative to harvest season the hazard ratio for early death in hungry-season births rose from 3.7 (for deaths >14.5 years, P = 0.000013) to 10.3 (for deaths >25 years, P = 0.00002). Anthropometric and haematological status at 18 months of age was identical in cases and controls, indicating an earlier origin to the defect. Most deaths for which cause was known had a definite or possible infectious aetiology; none were from degenerative diseases of affluence. CONCLUSIONS: Early life exposures, correlated with season of birth, strongly influence susceptibility to fatal infections in young adulthood. The evidence suggests that nutritionally-mediated intrauterine growth retardation may permanently impair the development of immune function.

Adolescent↗

A quantitative analysis of the relationship between habitual energy expenditure, fitness and the metabolic cardiovascular syndrome.

Previous epidemiological studies have suggested an association between low levels of physical activity, fitness and the metabolic cardiovascular syndrome. However, many studies have used subjective non-quantitative questionnaire-based methods for assessing physical activity which do not distinguish between the different dimensions of this complex exposure, and in which measurement error in the exposure has not been estimated. These deficiencies in the measurement of this exposure complicate the interpretation of the results of epidemiological studies, and consequently make it difficult to design appropriate interventions and to estimate the expected benefit which would result from intervention. In particular, it is unclear whether public health advice should be to increase total energy expenditure, or to attempt to raise fitness by recommending periods of vigorous activity. To separate the effects of fitness and total energy expenditure in the aetiology of the metabolic cardiovascular syndrome, we measured the physical activity level (PAL), defined as total energy expenditure: BMR, and fitness (maximum O2 consumption (VO2max per kg), measured in a sub-maximal test) in a cross-sectional population-based study of 162 adults aged 30-40 years. Heart-rate monitoring with individual calibration was used to measure total energy expenditure using the HRFlex method (Ceesay et al. 1989) which has been validated previously against doubly-labelled water and whole-body calorimetry. The relationship between a single measure of PAL, VO2max per kg and the usual or habitual level for each exposure was measured in a sub-study of twenty-two subjects who undertook four repeated measures over the course of 1 year. This study design allows the reliability coefficient to be computed, which is used to adjust the observed associations for measurement error in the exposure. Twelve men (16.4%) and sixteen women (18.0%) were defined as having one or more features of the metabolic cardiovascular syndrome. The univariate odds ratio for each increasing quartile for PAL was 0.64 (95% CI 0.43-0.94) and was 0.49 (95% CI 0.32-0.74) for VO2max per kg, suggesting that the association with the metabolic cardiovascular syndrome was stronger for fitness than for PAL. However, after adjustment for obesity and sex, and correction for exposure measurement error, the odds ratio per quartile for PAL was 0.32 (95% CI 0.13-0.83) and 0.44 (95% CI 0.24-0.78) for VO2max per kg. Thus, although univariate analysis would suggest that fitness has a stronger association with the metabolic cardiovascular syndrome than PAL, this conclusion is reversed once confounding and the differences in measurement error are considered. We conclude from the present study that the metabolic cardiovascular syndrome is strongly associated with reduced habitual energy expenditure. The method employed to assess the exposure in the present study demonstrates the utility of assessing a known dimension of physical activity using a physiologically-based and objective measure with repeated estimation to adjust for measurement error. Such quantitative epidemiological data provide the basis for planning and evaluating the expected benefit of population-level interventions.

Adult↗