Associations of infant nutrition with insulin resistance measures in early adulthood: evidence from the Barry-Caerphilly Growth (BCG) study

Background

Previous studies suggest that over-nutrition in early infancy may programme long-term susceptibility to insulin resistance.

Objective

To assess the association of breast milk and quantity of infant formula and cows'' milk intake during infancy with insulin resistance measures in early adulthood.

Design

Long-term follow-up of the Barry Caerphilly Growth cohort, into which mothers and their offspring had originally been randomly assigned, between 1972–1974, to receive milk supplementation or not. Participants were the offspring, aged 23–27 years at follow-up (n = 679). Breastfeeding and formula/cows'' milk intake was recorded prospectively by nurses. The main outcomes were insulin sensitivity (ISI₀) and insulin secretion (CIR₃₀).

Results

573 (84%) individuals had valid glucose and insulin results and complete covariate information. There was little evidence of associations of breastfeeding versus any formula/cows'' milk feeding or of increasing quartiles of formula/cows'' milk consumption during infancy (<3 months) with any outcome measure in young adulthood. In fully adjusted models, the differences in outcomes between breastfeeding versus formula/cows'' milk feeding at 3 months were: fasting glucose (−0.07 mmol/l; 95% CI: −0.19, 0.05); fasting insulin (8.0%; −8.7, 27.6); ISI₀ (−6.1%; −11.3, 12.1) and CIR₃₀ (3.8%; −19.0, 32.8). There was also little evidence that increasing intakes of formula/cows'' milk at 3 months were associated with fasting glucose (increase per quartile of formula/cows'' milk intake = 0.00 mmol/l; −0.03, 0.03); fasting insulin (0.8%; −3.2, 5.1); ISI ₀ (−0.9%; −5.1, 3.5) and CIR₃₀ (−2.6%; −8.4, 3.6).

Conclusions

We found no evidence that increasing consumption of formula/cows'' milk in early infancy was associated with insulin resistance in young adulthood.     

The effect of changing living standards on iron status in pregnancy in Calabar urban.

Reduced meat intake is often associated with iron deficiency anaemia. Reduced meat intake that arose from the frugality associated with a prolonged period of national economic reorientation policy, known as the "structural adjustment programme" (SAP), may have placed iron-stress on pregnancy in particular. Iron status of pre-SAP and SAP pregnancies were established from measurement of the haematological values of subjects. Indices such as haemoglobin (Hb), packed cell volume, serum Fe were lower in pregnancy especially during SAP. However, SAP pregnancy serum ferritin did not respond significantly to iron depletion. Unlike PCV, Total Iron Binding Capacity (TIBC) and serum transferrin values showed a reverse behaviour. The level of these values, however, portends a toll exerted on body iron status in pregnancy associated with reduced haem iron intake. The changes in these values did not, however, lead to any over symptoms of iron deficiency probably because increased sea food (molluscs) consumption ameliorates the iron-toll from low absorbed non-haem iron. For lower income rural women in non-coastal areas, the absence of seafood in their diets exacerbates the low iron status in Pregnancy.     

Cows' milk protein intolerance: a possible association with gastroenteritis,lactose intolerance,and IgA deficiency.

Twenty-five children with cows'' milk protein intolerance were studied. Twenty had presented with an illness clinically indistinguishable from infantile gastroenteritis; an enteropathogenic Escherichia coli was isolated from the stools in two children, and in six another member of the family simultaneously developed acute diarrhoea and vomiting. Twenty-three children had lactose intolerance secondary to cows'' milk protein intolerance. Eight out of 20 children were found to be partially IgA deficient. An acute attack of gastroenteritis, in damaging the small mucosa, may act as a triggering mechanism in cows'' milk protein intolerance, and a deficiency in IgA may be a predisposing factor in so far as it allows the patient to become sensitised to foreign protein.     

Case-control study of risk of dehydrating diarrhoea in infants in vulnerable period after full weaning.

OBJECTIVES: To investigate risk factors for dehydrating diarrhoea in infants, with special interest in the weaning period. DESIGN: Case-control study. SETTING: Metropolitan area of Porto Alegre, Brazil. SUBJECTS: Cases were 192 children aged 0-23 months hospitalised with acute diarrhoea and moderate to severe dehydration. Controls were 192 children matched for age and neighbourhood who did not have diarrhoea in the previous week. MAIN OUTCOME MEASURES: Associations between dehydrating diarrhoea and child''s age, type of milk consumed, time since breast feeding stopped, and breast feeding status. RESULTS: In infants aged < 12 months the risk of dehydrating diarrhoea was significantly higher in the first 9 months of life (P < 0.001), and in those aged 12-23 months the risk was again greater in younger children (12-17 months) (P = 0.03). The type of milk consumed before start of diarrhoea episode was strongly associated with dehydration independent of socioeconomic, environmental, maternal reproductive, demographic, and health services factors. Compared with infants exclusively breast fed, bottle fed infants were at higher risk (odds ratio (95% confidence interval) for cow''s milk 6.0 (1.8 to 19.8), for formula milk 6.9 (1.4 to 33.3)). Compared with those still breast feeding, children who stopped in the previous two months were more likely to develop dehydrating diarrhoea (odds ratio 8.4 (2.4 to 29.6)). This risk decreased with time since breast feeding stopped. CONCLUSION: These results confirm the protective effect of breast feeding and suggest there is a vulnerable period soon after breast feeding is stopped, which may be of relevance for developing preventive strategies.     

Latent anaphylactic sensitisation of infants of low birth weight to cows' milk proteins.

Latent systemic anaphylactic sensitisation to cows'' milk was assessed in 61 preterm infants who were randomly assigned to receive either a special formula for preterm infants based on cows'' milk or banked breast milk or one or other of these as a supplement to maternal milk. A single sample of venous blood was taken near to the time of discharge from the neonatal intensive care unit, and the histamine release by blood basophils in response to in vitro challenge with cows'' milk and anti-IgE was measured. Compared with the blood from infants fed on human milk, that from infants fed on preterm formula showed a significant increase in histamine release to challenge with cows'' milk, the response being greater in blood from infants of lower birth weight and gestational age. A smaller but significant increase in blood histamine release with anti-IgE challenge was observed in the group fed on preterm formula. Infants of low birth weight fed on preterm formula based on cows'' milk may develop latent systemic sensitisation more rapidly than infants born at term. The clinical importance of this requires further investigation.     

Effect of antigen load on development of milk antibodies in infants allergic to milk.

The phenomenon that large amounts of antigen, such as are absorbed during the neonatal period, suppress the IgE response while low-dose exposure enhances it was investigated by analysing the antibody responses of infants allergic to milk according to their degree of exposure to cows''-milk protein. IgG, IgA, and IgM milk-specific antibodies in these infants and in age-matched controls were measured by enzyme-linked immunosorbent assay. Milk-specific IgE and total IgE were also measured. Children allergic to milk who were breast fed and had had minimal exposure to cows'' milk had decreased titres of IgG, IgA, and IgM milk antibodies compared with infants allergic to milk who, before diagnosis, had been fed substantial volumes of cows'' milk. Conversely, the infants with minimal exposure to cows'' milk showed vastly increased total and milk-specific IgE antibodies compared with the milk-fed infants. These results support recent experimental evidence that appreciable amounts of allergen suppress rather than stimulate IgE production. These data may have important implications for dietary regimens in at-risk infants. The results also lend support for the role of IgE in immediate-type allergic reactions and suggest that various non-IgE immune mechanisms play a part in the aetiology of intolerance to cows''-milk protein in some children.     

Induction of haem oxygenase-1 causes cortical non-haem iron increase in experimental pneumococcal meningitis: evidence that concomitant ferritin up-regulation prevents iron-induced oxidative damage

Desferrioxamine inhibits cortical necrosis in neonatal rats with experimental pneumococcal meningitis, suggesting that iron-induced oxidative damage might be responsible for neuronal damage. We therefore examined the spatial and temporal profile of changes in cortical iron and iron homeostatic proteins during pneumococcal meningitis. Infection was associated with a steady and global increase of non-haem iron in the cortex, particularly in neuronal cell bodies of layer II and V, and in capillary endothelial cells. The non-haem iron increase was associated with induction of haem oxygenase (HO)-1 in neurones, microglia and capillary endothelial cells, whereas HO-2 levels remained unchanged, suggesting that the non-haem iron increase might be the result of HO-1-mediated haem degradation. Indeed, treatment with the haem oxygenase inhibitor tin protoporphyrin (which completely blocked the accumulation of bilirubin detected in HO-1-positive cells) completely prevented the infection-associated non-haem iron increase. The same cells also displayed markedly increased ferritin staining, the increase of which occurred independently of HO activity. At the same time, no increase in DNA/RNA oxidation was observed in infected animals (as assessed by in situ detection of 8-hydroxy[deoxy]guanosine), strongly suggesting that ferritin up-regulation protected the brain from iron-induced oxidative damage. Thus, although pneumococcal meningitis leads to an increase of cortical non-haem iron, protective mechanisms up-regulated in parallel prevent iron-induced oxidative damage. Cortical damage does not appear to be a direct consequence of increased iron, therefore.     

Strontium-89 and Strontium-90 Levels in Breast Milk and in Mineral-Supplement Preparations

Strontium-90, strontium-89 and S.U. values were determined in human milk before and after the resumption of atmospheric nuclear testings in 1961, and the levels were compared to cows'' milk values reported during the same time. S.U.⁹⁰ levels in human milk were approximately one-fifth of those found in cows'' milk. Assuming an average dietary intake of 11-13 S.U.⁹⁰ during the period tested, the mean strontium/calcium ratio of 1.78 found in human milk represents an Observed Ratio milk-diet of approximately 0.14-0.16. Although strontium-89 was present in cows'' milk already in September 1961, it did not appear in human milk until November 1961. It seems, therefore, that there was a two-month lag period between the appearance of fresh fallout in cows'' milk and human milk. Calcium-supplement mineral preparations used by pregnant and lactating women were tested to find their strontium-89, strontium-90 and S.U. levels, because strontium isotopes, if present in these products, will be transferred to the fetus and to breast-fed infants. The compounds tested had S.U.⁹⁰ levels of 0.13-2.62; in none of the preparations was Sr⁸⁹ present.     

A study of the relationship between placental non-haem iron and iron transfer in the guinea pig: the maturation of the transfer process

The relationship between placental non-haem iron and placental iron transfer has been studied in the guinea pig. From day 25 to day 50, non-haem iron and iron transfer increase. Expressed on placental wet weight or per g of placental DNA, iron transfer and non-haem iron were inversely related; an increase of transfer was accompanied by a decrease of the non-haem iron content. The results are discussed in terms of the hypothesis, that accumulation of non-haem iron in early pregnancy is caused by an imbalance between iron uptake and iron transfer. The steady increase of total non-haem iron till term which has been demonstrated in this study is in contradiction with this hypothesis. The paper describes an alternative hypothesis in which placental non-haem iron, most likely ferritin iron, is assumed to play an active role in the regulation of placental iron transfer.     

Riboflavin-binding protein. Concentration and fractional saturation in chicken eggs as a function of dietary riboflavin.

In female rats with porphyria induced by hexachlorobenzene, the amounts of non-haem iron and porphyrins in liver mitochondrial fractions were increased almost 3-fold and greater than 500-fold respectively compared with that of untreated animals. A considerable fraction of both iron and porphyrins in this fraction was shown to be located in lysosomes. Thus mitochondrial preparations, which were further depleted of lysosomes by Percoll-density-gradient centrifugation, contained 2.78 +/- 0.75 and 2.99 +/- 0.49 nmol of non-haem iron/mg of protein when isolated from the liver of control rats and hexachlorobenzene-treated rats respectively. Mitochondria isolated from the liver of hexachlorobenzene-treated animals contained a pool of iron (about 1 nmol/mg of protein) that was available for haem synthesis in vitro. This pool is similar to that previously reported for mitochondria isolated from the liver of rats with normal haem synthesis. Hexachlorobenzene treatment, therefore, does not affect the iron status of the mitochondria.     

Association Between Zinc, Copper, and Iron Concentrations in Breast Milk and Growth of Healthy Infants in Tabriz, Iran

The aims of this study were to determine the effect of breast milk zinc, copper, and iron concentrations on infants’ growth and their possible correlations with maternal dietary intake. Milk samples and information on food intake were collected from 182 lactating women. Concentrations of zinc, copper, and iron in milk were analyzed using atomic absorption spectrophotometry. The infant’s weight for age Z-score (WAZ) and height for age Z-score (HAZ) were calculated. The mean milk zinc, copper, and iron concentrations were 1.85?±?0.5, 0.53?±?0.3, and 0.85?±?0.2 mg/l, respectively. Only zinc mean level was lower than the recommended range. Association between zinc, copper, and iron concentrations of milk and WAZ or HAZ of infants were not significant. However, the WAZ of infants whose mothers' milk zinc was more than 2 mg/l was significantly (P?<?0.039) higher than for others. The mean dietary zinc (5.31?±?2.3 mg/day) and copper (1.16?±?0.7 mg/day) intake of mothers was significantly less than the required daily intake (RDA) recommendations (P?<?0.05). The mean dietary iron intake (11.8?±?8.2 mg/day) was significantly higher than RDA recommendation (P?<?0.001). No significant association was found between maternal mean dietary zinc, copper, and iron intakes with their concentrations in milk. Dietary consultation or/and zinc supplementation is suggested for lactating women and infants.     

The effect of cobalt on the uptake of plasma iron by the liver.

1. After an intraperitoneal injection of 59Fe the recovery of radioactivity in the liver, but not in other tissues, was increased in cobalt-pretreated rats. There was no proportional increase in the radioactivity recovered from liver haem. 2. Rats were injected intravenously with serum containing protein-bound 59Fe and 125I-labelled albumin as a marker. At various times after injection the specific radioactivities of iron in plasma and of non-haem iron in liver were determined; corrections were applied for the content of plasma in samples of liver. In cobalt-pretreated rats there was a more rapid loss of 59Fe radioactivity from the plasma and a corresponding increase in the uptake of 59Fe into liver non-haem iron. 3. The results are discussed in relation to the possible sites of action of cobalt, and the possibility is considered that only a fraction of the liver non-haem iron may be involved.     

Continuous Intragastric Milk Feeds in Infants of Low Birth Weight

In a feeding trial 66 infants of low birth weight received continuous intragastric milk feeds from the fourth hour of life, starting with 60 ml/kg/24 hr and reaching a maximum of 300 ml/kg/24 hr on the ninth day. Each infant received only full-strength milk, which was either expressed human breast milk or SMA-S26 (a proprietary low-protein adapted cows'' milk) or half-cream Regal milk (partly-skimmed evaporated cows'' milk). For various reasons 10 babies had to be withdrawn, and the final assessment was made on the 56 who completed the trial successfully.Persistent vomiting was a problem in only four infants. In two of them the trial was continued after gastric lavage and in the other two vomiting stopped when the volume was reduced. Despite a careful search no evidence was found of aspiration of feeds in any infant. Continuous intragastric milk infusion was shown to be a safe method of feeding infants of low birth weight and SMA-S26 was almost as well tolerated as human milk. Because of the high-protein content of half-cream cows'' milk preparations and the resultant high plasma amino-acid levels when they are given in these large volumes they should be avoided for this type of feeding although they produce better weight gains in the first week of life.     

Lipid peroxide formation in microsomes. The role of non-haem iron

1. Metal ion-chelating agents such as EDTA, o-phenanthroline or desferrioxamine inhibit lipid peroxide formation when rat liver microsomes prepared from homogenates made in pure sucrose are incubated with ascorbate or NADPH. 2. Microsomes treated with metal ion-chelating agents do not form peroxide on incubation unless inorganic iron (Fe²⁺ or Fe³⁺) in a low concentration is added subsequently. No other metal ion can replace inorganic iron adequately. 3. Microsomes prepared from sucrose homogenates containing EDTA (1mm) do not form lipid peroxide on incubation with ascorbate or NADPH unless Fe²⁺ is added. Washing the microsomes with sucrose after preparation restores most of the capacity to form lipid peroxide. 4. Lipid peroxide formation in microsomes prepared from sucrose is stimulated to a small extent by inorganic iron but to a greater extent if adenine nucleotides, containing iron compounds as a contaminant, are added. 5. The iron contained in normal microsome preparations exists in haem and in non-haem forms. One non-haem component in which the iron may be linked to phosphate is considered to be essential for both the ascorbate system and NADPH system that catalyse lipid peroxidation in microsomes.     

Disparity between dietary iron intake and iron status of children aged 10-12 years

Iron status was assessed in a representative sample of 188 adolescents living in a medium-sized city in Poland. Dietary intakes were evaluated using records of diet over a period of seven consecutive days. Subjects were considered to be iron deficient when two or more of the following parameters were abnormal: serum ferritin, transferrin saturation or mean corpuscular haemoglobin concentration. Based on this definition, the prevalence of iron deficiency in the investigated sample of children aged from ten to twelve years was 12.7%. Iron deficiency anaemia was defined using the following criteria: haemoglobin values less than 12.0 g. dl (-1) in girls or less than 12.2 g. dl(-1) in boys, combined with an iron deficiency. With such a definition, the prevalence of iron deficiency anaemia in all subjects was 6.3%. Four boys (3.9%) and six girls (6.8%) were diagnosed as anaemic. The values for Hb in the anaemic boys ranged from 10.9 to 12.2 g. dl (-1) and in anaemic girls from 8.7 to 12.0 g. (-1). It was found that the majority of the individuals studied had a dietary haem-iron intake lower than that recommended. No relationship was found between the level of serum ferritin and total iron and vitamin C dietary intake, but there was positive correlation between serum ferritin and intake of haem iron. A seven-day dietary history questionnaire correctly identified children at risk of iron deficiency anaemia.     

Comparison of minerals in milk of four species

• 1.1. Milk samples of 4 ml or more were obtained from guinea pigs (Cavia porcellus), dairy cattle (Bos taurus), horses (Equus caballus) and humans (Homo sapiens). The milks were analysed for minerals including calcium (Ca), phosphorus (P), magnesium (Mg), potassium (K) and sodium (Na) by Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES).
• 2.2. Calcium was approximately twice as concentrated in guinea pig milk as in cows' milk, which was twice as much as the level in mares' milk, and this, in turn, was twice as concentrated as human milk.
• 3.3. The ratio of Ca to P in guinea pig milk was 1.66:1, while it was 1.24:1 in cows' milk, 1.56:1 in mares' milk and 2.07:1 in human milk.
• 4.4. Potassium was the most abundant mineral in the milks of cows, mares and humans, but not in guinea pig milk, and was much higher in cows' milk than in others.
• 5.5. Sodium was highest in guinea pig milk with cows' milk being a close second.
• 6.6. Magnesium was one-tenth as concentrated as Ca.

     

某军医大学学生2013年营养及体能状况调查

目的:探讨某军医大学学生2013年某一时段营养及体能情况,以提高军校医学生身体素质。方法:选取2013年1月~2013年2月某军医大学在学校餐厅集体就餐的学员682人,采用称重法调查膳食,测定学员体重、身高,计算体重指数(BMI),对学员的体能状况进行测试。结果:调查学生蛋类、食用油摄入过多,而禽肉、豆类、蔬菜、牛奶、水果等均低于军标;Vit A、Vit C以及钙元素每日摄入量明显不足;学生每日获得热能的分配比例较好,均已达到军标;调查学生中男生体能状况优于女生(x2=22.035,P0.001),女生的超重人数明显多于男生(x2=20.142,P0.001)。结论:建议该校对餐厅炊事人员增加供应学生的食物品种,特别是水产、牛奶等富含优质蛋白的食品;强化学生体育锻炼的监督和指导工作,帮助他们增强自身体质,为国防现代化服务。     

Effect of maternal dietary exclusion on breast fed infants with eczema: two controlled studies.

Thirty seven breast fed infants with eczema were studied to see whether changes in their mothers'' diets affected their skin condition. Nineteen mothers and babies took part in a double blind crossover trial of exclusion of egg and cows'' milk, and 18 took part in open exclusion of 11 foods followed by double blind challenge to those mothers whose infants seemed to respond. Babies were examined at the beginning and end of each dietary period, and the extent and severity of the rash were given a numerical score. The eczema improved in six infants when their mothers avoided egg and cows'' milk and worsened again when these were reintroduced. Two infants suffered gastrointestinal reactions after maternal ingestion of egg and cows'' milk, one developing colitis. Maternal dietary exclusion seems to benefit some breast fed babies with eczema.     

Does early nutrition in infants born before term programme later blood pressure?

OBJECTIVES--To test whether nutrition early in infants'' development programmes later blood pressure and whether the reported relation between low birth weight and later high blood pressure is due to poor nutrition or growth before full term. DESIGN--Prospective randomisation of preterm infants to early diets differing greatly in nutrient content in four parallel multicentre trials, with blinded follow up 7.5-8 years later. SETTING--Neonatal units at Cambridge, Ipswich, King''s Lynn, Norwich, and Sheffield. SUBJECTS--758 children weighing under 1850 g at birth. MAIN OUTCOME MEASURE--Blood pressure at age of 7.5-8 years. RESULTS--There were major differences in nutrient intake from randomised diets (preterm formula v standard formula and preterm formula v donor breast milk; in each case with or without mother''s milk), but follow up showed no differences in later blood pressure. Individual subjects showed large variation in protein and energy intakes and in growth performance, including degrees of growth failure seldom seen in utero, but these factors were also unrelated to later blood pressure. CONCLUSION--Extremes of nutritional intake and growth performance in preterm infants do not programme later blood pressure at 7.5-8 years of age. These findings do not support the hypothesis that high blood pressure has early nutritional origins. We suggest that the long term rise in blood pressure reported in individuals who had low birthweight (at full term) is not, as previously speculated, due to poor fetal nutrition or growth as such.     

Liver iron depletion and toxicity of the iron chelator Deferiprone (L, CP20) in the guinea pig

The use of the iron chelator deferiprone (L, CP20, 1,2-dimethyl-3-hydroxypyrid-4-one) for the treatment of diseases of iron overload and other disorders is problematic and requires further evaluation. In this study the efficacy, toxicity and mechanism of action of orally administered L were investigated in the guinea pig using the carbonyl iron model of iron overload. In an acute trial, depletion of liver non-heme iron in drug-treated guinea pigs (normal iron status) was maximal (approximately 50% of control) after a single oral dose of L1 of 200 mg kg, suggesting a limited chelatable pool in normal tissue. There was no apparent toxicity up to 600 mg kg. In each of two sub-acute trials, normal and iron-loaded animals were fed L (300 mg kg day) or placebo for six days. Final mortalities were 12/20 (L) and 0/20 (placebo). Symptoms included weakness, weight loss and eye discharge. Iron-loaded as well as normal guinea pigs were affected, indicating that at this drug level iron loading was not protective. In a chronic trial guinea pigs received L (50 mg kg day) or placebo for six days per week over eight months. Liver non-heme iron was reduced in animals iron-loaded prior to the trial. The increase in a wave latency (electroretinogram), the foci of hepatic, myocardial and musculo-skeletal necrosis, and the decrease in white blood cells in the drug-treated/normal diet group even at the low dose of 50 mg kg day suggests that L may be unsuitable for the treatment of diseases which do not involve Fe overload. However, the low level of pathology in animals treated with iron prior to the trial suggests that even a small degree of iron overload (two-fold after eight months) is protective at this drug level. We conclude that the relationship between drug dose and iron status is critical in avoiding toxicity and must be monitored rigorously as cellular iron is depleted.