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 a...
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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.
Reduced fetal growth is associated with insulin resistance and a high prevalence of glucose intolerance in adult life. Because babies who are growth retarded have elevated levels of triglyceride and non-esterified fat...
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Reduced fetal growth is associated with insulin resistance and a high prevalence of glucose intolerance in adult life. Because babies who are growth retarded have elevated levels of triglyceride and non-esterified fatty acids (NEFA), and because similar abnormalities are observed in subjects with the insulin resistance syndrome, impaired regulation of lipid metabolism could be one of the mechanisms explaining the link between reduced fetal growth and insulin resistance, We have, therefore, measured fasting plasma triglyceride and NEFA, and the insulin-mediated suppression of NEFA during an oral glucose tolerance test in 93 men and women aged 50, born in Preston, whose birthweight and body size at birth had been recorded. Elevated fasting plasma triglycerides and reduced NEFA suppression during the oral glucose tolerance test were associated with the male sex, glucose intolerance, central obesity as indicated by a high waist to hip ratio and insulin resistance as measured by a short insulin tolerance test. However there were no statistically significant relationships between the birth measurements and the circulating lipid levels. Moreover in regression analyses the relationships between thinness at birth and insulin resistance or glucose intolerance in adult life were unaffected by the addition of triglyceride or NEFA in the models. These results suggest that the link between reduced fetal growth and insulin resistance in the adult is not mediated by an abnormal regulation of lipid metabolism.
Recent studies show reduced fetal growth is associated with insulin resistance and a raised prevalence of glucose intolerance in adult life. Because early growth retardation in animal models leads to permanent changes...
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Recent studies show reduced fetal growth is associated with insulin resistance and a raised prevalence of glucose intolerance in adult life. Because early growth retardation in animal models leads to permanent changes in body composition and a reduction in the mass of muscle, a major insulin sensitive tissue, reduced adult muscle mass could explain the link between impaired fetal growth and glucose intolerance. To investigate this hypothesis, muscle mass has been determined in a group of men and women aged around 50 who were born in Preston, Lancashire and compared with their birthweight or body size at birth and their current insulin resistance and glucose tolerance. Subjects who had lower birthweights were shorter and lighter but their weight adjusted for height (BMI) was similar to that of other subjects. Much of the difference in weight was accounted for by a reduction in muscle mass. Muscle mass as estimated by the urinary creatinine excretion rose from 18.8 % of body weight in women who had birthweights of 2.5 kg or less to 24.7% of bodyweight in those with birthweights of 3.4 kg or more. Trends in men were similar. Regression analysis showed that adult muscle mass was predicted by low birthweight (p = 0.004), low placental weight (p= 0.02), and small head circumference (p = 0.02) but not, however, by thinness at birth, the birth measurement most predictive of insulin resistance. In addition there were no significant relationships between muscle mass and insulin resistance or glucose tolerance in either men or women. These results may be explained by the existence of two populations of babies both characterized by low birthweight. Babies who are symmetrically small at birth have reduced muscle mass in adult life. They do not, however, have increased insulin resistance or a tendency to develop glucose intolerance. Thin babies have a normal adult muscle mass;their tendency to develop insulin resistance or glucose intolerance is not explained by alterations in mu
The extent to which the oral glucose tolerance test can be used to estimate insulin secretion and insulin resistance has been evaluated by comparing glucose and insulin concentrations during an oral glucose tolerance ...
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The extent to which the oral glucose tolerance test can be used to estimate insulin secretion and insulin resistance has been evaluated by comparing glucose and insulin concentrations during an oral glucose tolerance test with specific measurements of insulin secretion and insulin resistance in 85 normoglycaemic subjects and 23 subjects with impaired glucose tolerance (IGT). Insulin secretion was measured by the first phase insulin response to intravenous glucose and insulin resistance by the insulin tolerance test which measures the decline of plasma glucose after the injection of a bolus of insulin. The best measure of insulin secretion was the ratio of the 30 min increment in insulin concentration to the 30 min increment in glucose concentration following oral glucose loading. This correlated with the first phase insulin release following intravenous glucose (r = 0.61, p < 0.001) but not insulin resistance (r = -0.05, p > 0.05). Insulin resistance could be estimated by the fasting insulin, proinsulin, or split proinsulin concentrations. However, fasting split proinsulin appeared to discriminate best between insulin resistance (r = -0.53, p < 0.001) and insulin secretion (r = 0.07, p > 0.05). Relative insulin resistance estimated by homeostasis model assessment (HOMA), also correlated well with insulin resistance (r = -0.57, p < 0.001) but not insulin secretion (r = 0.01, p > 0.05). We conclude that the oral glucose tolerance test can be used to derive estimates of the relative roles of insulin secretion and insulin resistance in population studies of glucose tolerance.
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