Fetal growth and insulin secretion in adult life

Abstract

Summary Recent studies suggest that NIDDMislinked with reduced fetal and infant growth. Observations on malnourished infants and studies of experimental animals exposed to protein energy or protein deficiency in fetal or early neonatal life suggest that the basis of this link could lie in the detrimental effects of poor early nutrition on the development of the beta cells of the islets of Langerhans. To test this hypothesis we have measured insulin secretion following an IVGTT in a sample of 82 normoglycaemic and 23 glucose intolerant subjects who were born in Preston, England, and whose birthweight and body size had been recorded at birth. The subjects with impaired glucose tolerance had lower first phase insulin secretion than the normoglycaemic subjects (mean plasma insulin concentrations 3 min after intravenous glucose 416 vs 564 pmol/1, p = 0.04). Insulin secretion was higher in men than women (601 vs 457 pmol/1,p = 0.02) and correlated with fasting insulin level (p = 0.04). However, there was no relationship between insulin secretion and the measurements of prenatal growth in either the normoglycaemic or glucose intolerant subjects. These results argue against a major role for defective insulin secretion as a cause of glucose intolerance in adults who were growth retarded in prenatal life. [Diabetologia (1994) 37: 592-596] Key words NIDDM, insulin secretion, fetal growth, programming.Recent research has suggested that NIDDM may originate through impaired development in fetal life and early infancy. Among 370 men aged 64 years living in Hertfordshire, England, the percentage who had either NIDDM or impaired glucose tolerance was highest in those who had lowest birthweights or weights at age i year [1]. This finding was confirmed by a subsequent study of men and women aged 46 to 54 years who were born in Preston, England, where the association was shown to be due to babies who were small regardless of their gestational age rather than babies who were born

Reduced final height and indications for insulin resistance in 20 year olds born small for gestational age: regional cohort study

“…People who are small for gestational age may therefore have only insulin resistance, with no defects in insulin secretion. This hypothesis is supported by the results of the insulin response to the intravenous glucose tolerance test, which did not correlate with birth weight or ponderal index at birth 29 30 31…”

“…More recently a study of 1333 men aged 50-60 who were born and living in Uppsala confirmed that reduced fetal growth is associated with insulin resistance and non-insulin dependent diabetes mellitus and suggested a specific association with thinness at birth 29. This relation seems to be mediated through insulin resistance rather than through ß cell dysfunction 29 30 31…”

Exposure of the Pregnant Rat to Low Protein Diet Causes Impaired Glucose Homeostasis in the Young Adult Offspring by Different Mechanisms in Males and Females

“…Conversely, if the restricted diet continues into adulthood, no metabolic changes are observed and pathologies associated with chronic diseases are prevented (40). Similarly in humans, fetal growth restriction has been shown to impact insulin action in adulthood (41). Data obtained from epidemiological studies have shown that subjects who had low birth weight or were thin at birth have a higher prevalence of developing insulin resistance syndrome or syndrome X in adulthood, accompanied by the co-existence of glucose intolerance, hypertension and hypertriglyceridemia (35,36,38,42,43).…”

Relation of size at birth to non-insulin dependent diabetes and insulin concentrations in men aged 50-60 years

“…To explain the association between reduced fetal growth and glucose intolerance the Cambridge-Southampton group initially suggested that inadequate fetal nutrition might impair the development of the endocrine pancreas 1 2 3. This is not consistent with the lack of association between birth weight and acute insulin response to intravenous glucose challenge in Uppsala and in an earlier study of men and women born in Preston 4. In the Preston study insulin resistance was inversely related to ponderal index but not to birth weight5; this led the investigators to suggest that the association between reduced fetal growth and glucose intolerance is mediated through insulin resistance.…”

“…Initially it was suggested that the relation between reduced fetal growth and glucose intolerance was mediated through impairment of β cell function 1 3. More recent work has led the same investigators to suggest instead that the association is mediated through insulin resistance 4 5. The objective of our study was to distinguish between these two possible mechanisms.…”