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Elevated plasma cortisol concentrations: a link between low birth weight and the insulin resistance syndrome?
D I Phillips1, D J Barker, C H Fall
1Medical Research Council Environmental Epidemiology Unit, University of Southampton, United Kingdom. diwp@mrc.soton.ac.uk
Insights
Low birth weight in men is linked to higher cortisol levels and increased risk of insulin resistance syndrome. This suggests fetal programming of the hypothalamic-pituitary-adrenal axis (HPAA) may explain the association.
Area of Science:
- Endocrinology
- Metabolic Syndrome
- Developmental Biology
Background:
- Reduced fetal growth is increasingly linked to adult insulin resistance syndrome.
- The underlying mechanisms remain unclear, but hypothalamic-pituitary-adrenal axis (HPAA) activity is a potential factor.
Purpose of the Study:
- To investigate the relationship between birth size, plasma cortisol levels, and components of the insulin resistance syndrome in healthy adult men.
- To explore the role of intrauterine programming of the HPAA in the association between low birth weight and adult metabolic health.
Main Methods:
- Measured 0900 h fasting plasma cortisol and corticosteroid-binding globulin in 370 men born between 1920-1930 with recorded birth weights.
- Assessed relationships between plasma cortisol concentrations and systolic blood pressure, glucose tolerance, triglyceride levels, and insulin resistance.
- Examined trends in plasma cortisol levels across different birth weight categories.
Main Results:
- Plasma cortisol concentrations were significantly associated with systolic blood pressure, fasting and 2-h plasma glucose, triglyceride levels, and insulin resistance.
- Cortisol levels progressively decreased with increasing birth weight, independent of age and BMI.
- Men with lower birth weights (<2.50 kg) had higher mean cortisol levels compared to those with higher birth weights (>4.31 kg).
Conclusions:
- Plasma cortisol concentrations within the normal range may significantly influence adult blood pressure and glucose tolerance.
- This study provides the first evidence that intrauterine programming of the HPAA may mediate the link between low birth weight and the insulin resistance syndrome.
- Findings highlight the long-term metabolic consequences of fetal growth and the importance of the HPAA in developmental programming.
Abstract:
Recent studies have shown that reduced fetal growth is associated with the development of the insulin resistance syndrome in adult life. The mechanisms are not known. However increased activity of the hypothalamic-pituitary-adrenal axis (HPAA) may underlie this association; the axis is known to be reset by fetal growth retardation in animals, and there is evidence in humans of an association between raised HPAA activity and the insulin resistance syndrome. We have, therefore, examined the relations among size at birth, plasma cortisol concentrations, and components of the insulin resistance syndrome in a sample of healthy men. We measured 0900 h fasting plasma cortisol and corticosteroid-binding globulin levels in 370 men who were born in Hertfordshire, UK, between 1920-1930 and whose birth weights were recorded. Fasting plasma cortisol concentrations varied from 112-702 nmol/L and were related to systolic blood pressure (P = 0.02), fasting and 2-h plasma glucose concentrations after an oral glucose tolerance test (P = 0.0002 and P = 0.04), plasma triglyceride levels (P = 0.009), and insulin resistance (P = 0.006). Plasma cortisol concentrations fell progressively (P = 0.007) from 408 nmol/L in men whose birth weights were 5.5 lb (2.50 kg) or less to 309 nmol/L among those who weighed 9.5 lb (4.31 kg) or more at birth, a trend independent of age and body mass index. These findings suggest that plasma concentrations of cortisol within the normal range could have an important effect on blood pressure and glucose tolerance. Moreover, this study provides the first evidence that intrauterine programming of the HPAA may be a mechanism underlying the association between low birth weight and the insulin resistance syndrome in adult life.