Interactions between peroxisome proliferator-activated receptor gene polymorphism and birth length influence risk for type 2 diabetes.
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Aged↗
Biomedical subjects
Clive Osmond
Publications and source records attributed to Clive Osmond.
Size at birth, gestational age and cortisol secretion in adult life: foetal programming of both hyper- and hypocortisolism?
OBJECTIVE: Recent studies have suggested that lifelong programming of the hypothalamic-pituitary-adrenal (HPA) axis in utero is an important mechanism in explaining the link between small size at birth and adult cardiovascular disease. However, direct evidence from human birth cohorts has so far been contradictory. We set out to study reasons for this discrepancy by examining the relationship between adult HPA axis function and birthweight and body proportions at birth in a group of elderly subjects with detailed birth records. DESIGN: Birth cohort study. SUBJECTS: Four hundred and twenty-one men and women (mean age 69.5 years, range 65.1-75.8 years) born at term in Helsinki, Finland, during 1924-33, with body size and gestational age at birth recorded. MEASUREMENTS: Fasting serum cortisol and cortisol-binding globulin concentrations. The concentration of free cortisol was estimated by their ratio. RESULTS: There was no significant correlation between fasting cortisol concentrations and birthweight in either men or women. However, there was a weak inverse association between fasting cortisol and length at birth in women but not in men. There was also a significant positive association between cortisol and ponderal index in both genders. We found that the association between foetal growth on fasting total and free cortisol concentrations differed in subjects born at different gestational ages. In subjects born before 39 weeks of gestation, both total and free cortisol showed inverse correlations with birthweight (P = 0.02 and P = 0.09, respectively) and length at birth (P = 0.001 and P = 0.02), whereas in subjects born after 40 weeks of gestation there were positive correlations with birthweight (P = 0.06 and P = 0.002) and ponderal index at birth (P = 0.003 and P = 0.003). The interactions between birthweight and gestational age were statistically significant (P = 0.01 for total and P = 0.003 for free cortisol). CONCLUSIONS: These data suggest that the relationship between size at birth and cortisol concentrations in adult life is different in subjects born at different gestational ages: both hyper- and hypocortisolism may arise as a consequence of foetal programming of the hypothalamic-pituitary-adrenal axis during intrauterine life.
Adult↗
Is birthweight associated with thyroid autoimmunity? A study in twins.
Although extensive studies have suggested that an individual's predisposition to develop autoantibodies to thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) has a genetic component, a recent report has suggested that growth restriction during fetal life may also contribute. We have therefore measured TPOAb and TgAb in a population-based study of twins (44 monozygous and 91 dizygous) born between 1950 and 1955 who were identified through a registry of birth records in Birmingham, United Kingdom. TPOAb and TgAb were measured by a highly sensitive immunoprecipitation assay in which 0.01 U/mL and 0.1 U/mL, respectively, were detectable. TPOAb were found in 49 of 156 (31%) of women and 7 of 116 (6%) of men with similar values for TgAb (31% and 9%, respectively). Of 28 monozygous pairs, 10 were concordant for TgAb and 7 discordant giving a probandwise concordance rate of 74%. Concordance rates for TPOAb were similar (64%) and were higher than concordance rates in dizygous twins. Monozygous twins had a higher prevalence of TgAb than dizygous twins (30% vs. 17%, p = 0.01). In addition, we found that where there was discordance in birth size within monozygous twin pairs, the smaller twin had a higher prevalence of TPOAb (p = 0.01). Our results suggest that both heritable and early environmental components contribute to the susceptibility to thyroid autoimmunity.
Adult↗
Growth and living conditions in childhood and hypertension in adult life: a longitudinal study.
OBJECTIVES: To examine the interplay between childhood growth and living conditions in the development of hypertension. DESIGN: A longitudinal study of people whose growth between birth and 12 years, and social circumstances during childhood and adult life, were recorded. SETTING: Helsinki, Finland. PARTICIPANTS: Eight thousand seven hundred and sixty men and women born in Helsinki University Central Hospital during 1934-44, who attended child welfare clinics in the city and were still resident in Finland in 1971. MAIN OUTCOME MEASURES: Incidence of hypertension defined by prescription of medication. RESULTS: The 1404 children who later developed hypertension grew differently to other children. Low birthweight and shortness or thinness at birth were followed by rapid compensatory growth in weight and height, and an above-average body mass index (BMI, kg/m(2)) from the age of 8 years onwards. Some 25% of children with low birthweight but high BMI at 12 years subsequently developed hypertension, compared to 9% of those with high birthweight but low BMI. Growth had large effects on the risk of later hypertension in children living in poor social conditions, but only small effects in children in good living conditions. Living conditions in adult life did not affect the risk of hypertension. CONCLUSIONS: Hypertension originates in slow fetal growth followed by rapid compensatory growth in childhood. This path of growth has a greater effect on the risk of disease among children who live in poor social conditions. Living conditions in adult life do not seem to be important.
Birth Weight↗
The effects of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 gene on insulin sensitivity and insulin metabolism interact with size at birth.
Type 2 diabetes is known to be associated with a small body size at birth. Body size at birth is an indicator of the intrauterine environment. There is also a well-established association between the peroxisome proliferator-activated receptor (PPAR)-gamma2 gene and type 2 diabetes. We therefore assessed whether the effects of the Pro12Ala polymorphism of the PPAR-gamma2 gene on insulin sensitivity and insulin concentrations in adult life are modified by size at birth. We found that the effects of the Pro12Pro and Pro12Ala polymorphisms of the PPAR-gamma2 gene in elderly people depended on their body size at birth. The well-known association between small body size at birth and insulin resistance was seen only in individuals with the high-risk Pro12Pro allele. In those who had low birth weight, the Pro12Pro polymorphism of the PPAR-gamma2 gene was associated with increased insulin resistance (P < 0.002) and elevated insulin concentrations (P < 0.003). These interactions between the effects of the Pro12Ala polymorphisms of the PPAR-gamma2 gene on adult traits and the effects of birth weight link two previously unknown associations together within the context of type 2 diabetes. We suggest that these findings reflect gene-environment interaction.
Alanine↗