Fetal origins hypothesis in twin children : a metabolic evaluation

Abstract

This thesis explores whether low birth weight affects glucose homeostasis and other aspects of the metabolic syndrome in twin children. The key parameter studied is insulin resistance, and whether insulin resistance is also associated with abnormalities in blood pressure or other aspects of the metabolic syndrome. This thesis is a comparison of twins to singletons, rather than being a study of these traits within twin pairs. The fetal origins hypothesis suggests that low birth weight ultimately is associated with adult onset diseases namely coronary heart disease, glucose intolerance and hypertension. All twins to a degree are born prematurely and with low birth weight. It is unclear whether their metabolism in later life reflects this, or alternatively reflects their uniqueness as twins irrespective of birth weight. This thesis reviews how adaptation for their unique fetal life has affected in particular, glucose homeostasis in twins. Insulin resistance has been consistently identified prior to the onset of both type 2 diabetes mellitus and hypertension and is also the primary metabolic abnormality persisting from programming of the undernourished fetus. Both small-for-gestational-age and prematurely born infants are insulin resistant when examined in mid-childhood. It has been postulated that this represents an attempt of the fetus to salvage itself from a state of inadequate nutrition. Twins when examined in this thesis are also shown to be insulin resistant, or to have a reduction in insulin sensitivity. This insulin resistance was independent of low birth weight and prematurity, and reflected a unique twin effect. Examing blood pressure precisely revealed that twins had increased night-time blood pressure, a feature also seen in a variety of pre-hypertensive states. However, there was no association between low birth weight and any 24 hour blood pressure monitoring parameter in twins. Twins also had elevated leptin levels but reduced TNF-alpha levels in twins irrespective of birth weight or prematurity. Twins have unique metabolic profiles which are not correlated with low birth weight, and twins should be considered an exception to the fetal origins hypothesis.