March 1, 2021

expert reaction to study looking at birthweight, circulating levels of insulin-like growth factor-1 (IGF-1) in adulthood and type 2 diabetes

A study published in the BMJ Open Diabetes Research & Care looks at birthweight, adulthood levels of insulin-like growth factor-1 (IGF-1), and type 2 diabetes.

Prof Andrew Whitelaw, Emeritus Professor of Neonatal Medicine, University of Bristol, said:

“The press release is misleading in stating that “a birthweight of 2.5 kg or more is strongly linked to the risk of developing type 2 diabetes in adulthood”.  There has been consistent and worldwide evidence for the last 20 -30 years that a birthweight below 2.5 kg is associated with increased risk of ischaemic heart disease and type 2 diabetes decades later.  This study relied on self-reported birthweight and was unable to distinguish whether low birth weight was due to being born early (preterm) or being intrauterine growth restricted at or near term.  The difference is important as there is evidence that calorie deprivation in fetal life can set up long term metabolic programming by which the body conserves calories (fat) even when food becomes plentiful in childhood and adult life thus leading to obesity.

“This study by Geng does not show evidence that low birth weight protected against type 2 diabetes.

“What the present study showed was that, in adults with birthweight above 2.5 kg, a low (adult) blood level of Insulin-like Growth Factor-1 (IGF-1) was associated with increased risk of type 2 diabetes.  This was even when they allowed for the acknowledged links with: Age, body mass index, Townsend Deprivation Index, smoking status, alcohol consumption, sleep duration, physical inactivity, maternal smoking, menopause status and hormone-replacement therapy (women only), family history of diabetes, and history of hypertension.

“In individuals with birth weight below 2.5 kg, they did not find an association between adult IGF-1 in blood taken decades after birth and risk of type 2 diabetes.

“I cannot see that this study has new information which is relevant to the general public or those worried about type 2 diabetes.”

Prof Tom Sanders, Professor Emeritus of Nutrition and Dietetics, King’s College London, said:

“This study suggests that increasing birth weight modifies risk to developing type 2 diabetes in men but not women.  This conclusion is based on a retrospective observational study in men and women (age 37-73 years) recruited into the UK Biobank study.  It shows that low insulin-like growth factor (IGF-1) levels were associated with almost a doubling of risk of type 2 diabetes.  In further analysis, it was shown that risk of diabetes decreased with higher IGF-1 levels in men with a self-reported birth weight greater than 2.5 kg but not below 2.5 kg.  However, the confidence intervals were large for the comparison of IGF levels and risk in infants below 2.5 kg and this might reflect different causes of low birth weight such as preterm birth and intrauterine growth retardation.

“IGF-1 is a hormone produced in the liver that has properties in common with insulin in helping remove glucose from blood into tissues.  The production of IGF-1 is stimulated by growth hormone and its main role is to promote growth.  IGF-1 levels are high during childhood and decline steeply with age (a 60% fall from the age of 18 to 50 years).  Consequently, the levels of IGF-1 observed in these adults may not reflect the levels in infancy but there is evidence that the decline in IGF-1 with age tracks according to the original percentile.

“The headline message in the press release is confusing because it might be interpreted as suggesting that babies with birthweight greater than 2.5 kg are at increased risk of developing diabetes, whereas the opposite is the case.  Normal birthweight is 3.5 kg with a range from 2.5 kg to 4 kg (boys on average are 0.12 kg heavier than girls).  Low birthweight is associated with increased perinatal mortality and has significant long-term effects on adult health.  Previous research based on prospective observational studies following children from birth finds low birth weight to be associated with an increased risk of developing metabolic syndrome, type 2 diabetes, and death from cardiovascular disease in adult life.  IGF-1 levels are lower in low-birth weight infants with inter-uterine growth retardation.  It is also known that low birth weight babies who show accelerated growth in the first year of life are more likely to develop type 2 diabetes as adults.  It is not surprising that fetuses who grow well have higher IGF-levels and are at lower risk of developing type 2 diabetes as adults.  However, babies over 4 kg are known to be at greater risk of developing type 2 diabetes.  This large study adds some interesting data to support the theory that early growth in utero is important in programming IGF-1 levels in adult life.  This observation also has implications for an increased risk colorectal and prostate cancers which are associated with higher IGF-1 levels.”

‘Birth weight modifies the relation between adulthood levels of insulin-like growth factor-1 and type 2 diabetes: a prospective cohort study’ by Tingting Geng et al. was published in BMJ Open Diabetes Research & Care at 23:30 UK time on Monday 1 March 2021.

DOI: 10.1136/bmjdrc-2020-001885

Declared interests

Prof Andrew Whitelaw: “I have no conflict of interest.”

Prof Tom Sanders: “I chaired the British Nutrition Foundation Task Force Report on Nutrition and Development: Wiley-Blackwell, Chichester, 2013: https://www.nutrition.org.uk/bnf-publications/task-force-reports/development.html.”