IGF-I has a critical role in growth and metabolism. A microsatellite polymorphism 1 kb upstream to the IGF-I gene has recently been associated with several adult phenotypes. In a large Dutch cohort, the absence of the commonest allele (Z) was associated with reduced serum IGF-I levels, reduced height, and an increased risk of type 2 diabetes and myocardial infarction. This result has not been replicated, and the role of this polymorphism in these traits in U.K. subjects is not known. We sought further evidence for the involvement of this variant in type 2 diabetes using a case-control study and IGF-I and diabetes-related traits in a population cohort of 640 U.K. individuals aged 25 years. Absence of the common allele was not associated with type 2 diabetes (odds ratio 0.70, 95% CI 0.47-1.04 for X/X versus Z/Z genotype, 2 test for trend across genotypes, P ‫؍‬ 0.018). In the population cohort, the common allele (Z) was associated with decreased IGF-I levels (P ‫؍‬ 0.01), contrary to the Dutch study, but not with adult height (P ‫؍‬ 0.23), glucose tolerance (P ‫؍‬ 0.84), oral glucose tolerance test-derived values of ␤-cell function (P ‫؍‬ 0.90), or insulin resistance (P ‫؍‬ 0.66). There was no association with measures of fetal growth, including birth weight (P ‫؍‬ 0.17). Our results do not support the previous associations and suggest that the promoter microsatellite is unlikely to be functionally important.

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The findings suggest that endothelial dysfunction is a consequence of foetal malnutrition, consistent with contributing to the clinical features of the 'Small Baby Syndrome' in later adult life.

Abstract-There is a consistent inverse association between birth weight and systolic blood pressure; however, few studies have been able to examine the immediate postnatal period. We have examined whether accelerated postnatal growth predicts adult systolic and diastolic blood pressure. We followed up participants from the Barry Caerphilly Growth Study. Blood pressure data were obtained on 679 of the original 951 subjects (73%) aged Ϸ25 years. Both multivariable linear regression and spline models were used to examine the association among weight, length, and growth velocities with systolic blood pressure and diastolic blood pressure. Both statistical approaches showed that birth weight was inversely associated with systolic blood pressure. Only the spline models found that immediate (0 to 5 months) weight gain (␤ coefficient: 1.29 mm Hg; 95% CI: 0.36 to 2.23; Pϭ0.007) and weight gain between 1 year and 9 months to 5 years (␤ coefficient: 1.44 mm Hg; 95% CI: 0.31 to 2.57; Pϭ0.01) were independently associated with systolic blood pressure, whereas only immediate weight gain (␤ coefficient: 0.74 mm Hg; 95% CI: 0.08 to 1.41; Pϭ0.03) was associated with diastolic blood pressure. This is the first study to demonstrate that only immediate postnatal growth predicts diastolic blood pressure in term births, whereas it adds further evidence that both birth weight and postnatal growth are associated with systolic blood pressure in support of both the fetal origins and growth acceleration hypotheses. (Hypertension. 2008;52:638-644.)Key Words: blood pressure Ⅲ birth weight Ⅲ cohort study Ⅲ growth and development Ⅲ public health

At this time the patient's serum lactate, pyruvate, folate, red blood cell folate serum B12, zinc, copper, cholesterol, and the lipoprotein values were all normal. Activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and y-glutamyltransferase were raised.After supplementation with vitamin E for 6 months the nystagmus had resolved. After 18 months of treatment the ataxia had lessened, hand coordination was improved, and Romberg's sign was negative. She was still areflexic. DiscussionA neurological syndrome secondary to vitamin E deficiency which has responded to vitamin E supple-, ments has been reported in adults with cystic fibrosis.4 5 Our patient resembled these previous reports but presented much earlier. This was presumably because of impaired bile salt solubility of the vitamin in addition to pancreatic insufficiency. Luminal bile salt concentrations were likely to have been reduced in our patient. Firstly she had multiple resections of the ileum, the site of the active reabsorption of bile salts; secondly, the situation would be exacerbated by stasis in the dilated jejunum producing a 'blind loop' effect; and finally biliary fibrosis would result in impaired biliary excretion.Although this neurological complication seems to be relatively uncommon in cystic fibrosis, it is important to be aware of it. A careful neurological examination of these patients for evidence of cerebellar, posterior column, and peripheral nerve dysfunction is emphasised. Monitoring of serum vitamin E concentrations in all patients would be ideal and is recommended if possible, yet limited laboratory facilities for measurement make this impractical for many paediatricians. In patients with cystic fibrosis, 50 to 400 mg daily of a water miscible product has generally resulted in normal plasma and tissue levels of ct-tocopherol.' 3 6 In the absence of laboratory facilities regular vitamin E supplementation of a water miscible preparation of vitamin E is recommended in a dosage of 100 to 200 mg daily.

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Objective: Insulin-like growth factors (IGF) are increasingly recognized as important determinants of adult health, in particular risk of certain cancers. However, little is known about the determinants of adult IGFs and to what degree they may be programmed by early life influences. Design: Randomized controlled trial of prenatal and postnatal milk supplementation among 951 subjects born in 1972 to 1974 in South Wales. Main outcome measure: Measures of IGF-I, IGF binding protein 3, and the molar ratio. Results: Data on adult IGFs were available from 663 subjects at a mean age of 25 years. Subjects in the intervention arm had lower IGF-I (À8.5 ng/mL; 95% confidence interval, À15.1 to À1.8, P = 0.01) and ratio (À1.20; 95% confidence interval, À2.33 to À0.04, P = 0.04). These differences could not be explained by follow-up bias or confounding factors. Conclusions: These results provide experimental data on the role of early life programming either in the intrauterine or postnatal period that may have long-term influences on the IGF axis, with potential implications for disease risk.