Fetal Growth and Insulin Resistance in Adult Life: Relationship Between Glycogen Synthase Activity in Adult Skeletal Muscle and Birthweight

Growth retardation during fetal life is associated with insulin insensitivity and an increased prevalence of impaired glucose tolerance in adult life. Because insulin-mediated stimulation of glycogen synthase may be an important rate-limiting step for insulin action at the cellular level, we have sought to determine whether impaired activation of muscle glycogen synthase is linked with early growth retardation. Postprandial glycogen synthase activity was therefore measured in muscle biopsies from a group of 27 women with normal glucose tolerance aged around 50 who were born in Preston, Lancashire, whose birthweight and body size at birth were recorded. Glycogen synthase activity measured at 0.1 mmol 1(-1) glucose-6-phosphate correlated with insulin sensitivity as measured by a short insulin tolerance test (r = 0.42, p < 0.05) and the waist to hip ratio (r = -0.48, p < 0.01), but not body mass index, body fat percentage or age. Within the group of women with normal glucose tolerance there was no relationship between intra-uterine growth as evidenced by birthweight or body size at birth and the response to insulin of skeletal muscle glycogen synthase in adult life. Thus we found no evidence for a direct link between fetal growth and insulin sensitivity in this pathway.