Programming of hormonal axes contributing to the link between fetal growth, diabetes and cardiovascular disease

Flanagan, Daniel Edward Henry (1999) Programming of hormonal axes contributing to the link between fetal growth, diabetes and cardiovascular disease. University of Southampton, Doctoral Thesis.

Abstract

Type 2 diabetes is though to be the result of a combined defect in the ability of the body to respond to insulin (insulin resistance) and an inability to compensate for this by increasing insulin secretion.

Previous work has suggested that babies that are born small are more insulin resistant as adults in middle age and later life. Previous studies have also indicated that alterations in other hormonal axes may be contributing to the insulin resistant state. Possible mechanisms include increased sympatho-adrenal activity or alterations in the hypothalamic pituitary adrenal axis leading to insulin resistance.

I have studied a cohort of 20 year old men and women in whom detailed information on birthsize was available. Using an established measure of insulin sensitivity, the intravenous glucose tolerance test, I have examined the relationship between size at birth, insulin sensitivity and insulin secretion in young adults where the confounding influences of obesity and physical inactivity are minimised. Male babies born small were less insulin sensitive but showed no defect in insulin secretion. The same trends were not seen in women.

Using spectral analysis of heart rate variability I have shown a relationship between the autonomic control of heart rate and insulin sensitivity. Men with increased cardiac sympathetic activity were more insulin resistant but this did not show relationships with birthsize. Again these trends were not seen in women. I have also studied the relationship between size at birth and plasma cortisol levels. Again men who were small at birth show higher 9.00 cortisol levels but there was no relationship with features of the insulin resistance syndrome. Subjects were small at birth show lower levels of overnight growth hormone hormone and melatonin production suggesting that fetal programming is occurring at the hypothalamic/pituitary level.

In conclusion size at birth predicts insulin resistance, an established cardiovascular risk, in young adult life. A number of other hormonal axes may be contributing to this risk.

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