Long-term metabolic effects of a high birth weight

The intrauterine environment influences foetal growth as well as future response to risk factors for disease. This occurs partly through epigenetic mechanisms. Thus, birth weight is a possible risk marker of adult disease. Low birth weight is a well-known risk factor for adult disease, particularly when associated with obesity and a U-shaped relationship between birth weight and several metabolic diseases has been suggested. In this thesis we investigated associations between a high birth weight and risk of adult disease, e.g. obesity, cardiovascular disease, type 2 diabetes and gestational diabetes. By analyses of national register data on 759 999 subjects up to the age of 37 years, we could demonstrate an increased risk of type 2 diabetes in males, but not in females, with a high birth weight (>2 SDS). The increase was particularly pronounced in males with a birth weight >3 SDS. There was an association between high birth weight and obesity in males and females, but no such relation was seen for hypertension or serum lipid abnormalities. In a clinical study, 27 cases with a birth weight ≥4 500 grams were compared with 27 controls with normal birth weight, regarding risk factors for cardiovascular disease and diabetes. The cases had a greater radial artery intima thickness and intima:media ratio compared with the controls indicating early atherosclerotic changes. Body mass index, body composition, insulin sensitivity, lipid profiles, blood pressure, resting energy expenditure and respiratory quotient did not differ between cases and controls, but females with a high birth weight had a more disadvantageous distribution of body fat. In order to investigate associations between birth weight and pregnancy outcomes, register data on 305 893 females was analysed. The results demonstrated an association between the female´s own birth weight and offspring birth weight. A high maternal birth weight was associated with increased risk of obesity. The risk of gestational diabetes was increased in females with a low, but not a high birth weight. In conclusion, subjects with a moderately high birth weight did not differ substantially from those with a normal birth weight regarding risk factors for cardiovascular disease. However, differences in arterial wall dimensions were demonstrated in a clinical investigation, and there were differences in BMI and risk of type 2 diabetes on a population level. Since risks are most pronounced in subjects with a birth weight >3 SDS, this group is in particular need of follow up and disease preventive measures