Wallace, J.M., Milne, JS., Aitken, RP., Horgan, G.W. and Adam, C.
||Low birthweight is a risk factor for later adverse health. Here the impact of placentally-mediated prenatal growth-restriction followed by postnatal nutrient abundance on growth, glucose metabolism and body composition was assessed in both sexes at key stages from birth to mid-adult life. Singleton-bearing adolescent dams were fed control or high nutrient intakes to induce normal or growth-restricted pregnancies, respectively. Restricted lambs had ~40% reduced birthweight. Fractional growth rates were higher in restricted lambs of both sexes predominantly during suckling/juvenile phases. Thereafter, rates and patterns of growth differed by sex. Absolute catch-up was not achieved and restricted offspring had modestly reduced weight and stature at mid-adulthood necropsy (~109 weeks, both sexes). Dual energy X-ray absorptiometry revealed lower bone mineral density in restricted versus normal lambs at 11, 41, 64 and 107 weeks, with males>females from 41 weeks onwards. Body fat percentage was higher in females versus males throughout, and in restricted versus normal lambs at weaning (both sexes), and in restricted-females at mid-adulthood. Insulin secretion after glucose-challenge was greater in restricted versus normal of both sexes at 7 weeks, and in restricted-males at 32 weeks. In both sexes fasting glucose concentrations were greater in restricted offspring across the life-course, while glucose area-under-the-curve after challenge was higher in restricted offspring at 32, 60, 85 and 106 weeks, indicative of persistent glucose intolerance.
At 7, 32 and 60 weeks, fasting insulin/glucose concentrations, and insulin secretion after glucose-challenge were greater in restricted versus normal, but by 106 weeks sex-effects dominated (M>F for insulin, M