Kajantie, Eero, Fall, Caroline H., Seppala, Markku, Koistinen, Riita, Dunkel, Leo, Yliharsila, Hilkka, Osmond, Clive, Andersson, Sture, Barker, David J.P., Forsen, Tom, Holt, Richard I.G., Phillips, David I.W. and Eriksson, Johan
Serum insulin-like growth factor (IGF)-I and IGF-binding protein-1 in elderly people: relationships with cardiovascular risk factors, body composition, size at birth, and childhood growth
Journal of Clinical Endocrinology and Metabolism, 88, (3), . (doi:10.1210/jc.2002-021380).
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The IGF system is important in regulation of fetal and childhood growth. In later life, IGF-I and IGF-binding protein-1 (IGFBP-1) have been implicated in the pathogenesis of arteriosclerosis. They are, thus, potential candidates in explaining the link between early growth and adult cardiovascular disease. We measured fasting serum IGF-I and IGFBP-1 concentrations in 394 men and women from a cohort of 7086 individuals, born between 1924 and 1933 in Helsinki, Finland, whose weight and height were recorded at birth and from 7 to 15 yr of age. They also underwent clinical examination, including measurement of body fat using bioimpedance, blood pressure, glucose tolerance, and plasma insulin and fibrinogen concentrations. Serum IGF-I was positively correlated with fasting glucose (r = 0.10, P = 0.06) and fibrinogen (r = 0.19, P = 0.0001) concentrations and blood pressure (systolic and diastolic r = 0.10, P 0.05) and inversely with percentage body fat (r = -0.13, P = 0.01) and waist circumference (r = -0.11, P = 0.03). IGFBP-1 was inversely correlated with adult body mass index (BMI) (r = -0.46, P < 0.0001), fasting glucose and insulin concentrations, and blood pressure.
There were correlations between the adult level of IGFBP-1 and birth weight (r = 0.11, P = 0.03) and ponderal index (weight/length3) at birth (r = 0.13, P = 0.01), but IGF-I was not related to birth measurements. There were interactive effects between childhood height or BMI and adult BMI on IGF-I and IGFBP-1 in adulthood. Tall height and high BMI at 7 yr were associated with low IGF-I (P = 0.03 for height and P = 0.003 for BMI) and high IGFBP-1 (P = 0.02 and P = 0.06) in adulthood but only in those subjects whose current BMI was below median. On further analysis these interactive effects were particularly strong for height in childhood and adult lean BMI (lean body mass/height2). Among men and women of below-average lean BMI, tall height at 7 yr was associated with low adult IGF-I (P = 0.007) and high IGFBP-1 (P = 0.0004) concentrations [interaction (7-yr height x adult lean BMI); P = 0.008 for IGF-I and 0.001 for IGFBP-1].
There is no evidence that reduced fetal growth programs IGF-I concentrations in old age. An association between small size at birth and low IGFBP-1 concentrations may in part reflect fetal programming effects on insulin resistance. Given the anabolic effects of the GH-IGF-I axis, subjects with tall height in childhood but low adult lean body mass may be at risk of late-life GH-IGF-I axis dysfunction. Prospective studies should address whether this group is susceptible to type 2 diabetes, coronary heart disease, and osteoporosis.
This work was supported by grants from Academy of Finland, British Heart Foundation, Cancer Society of Finland, Finska Läkaresällskapet, Helsinki University Central Hospital Research Fund, The Foundation for Pediatric Research, Sigrid Jusélius Foundation, Sydäntutkimussäätiö, and National Institute of Child Development Grant 1-R01-HD41107-01 (to D.I.W.P.).
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