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Biomedical subjects

C V Felton

Publications and source records attributed to C V Felton.

8 recordsLinked to original sources

An apparently anomalous relationship between insulin and C-peptide concentrations in their initial response to intravenous glucose.

Intravenous glucose tolerance tests (IVGTTs) with determination of plasma glucose, insulin, and C-peptide concentrations were performed in 136 men and 154 women. It was found that in 4% of men and 12% of women the plasma concentration of insulin exceeded that of C-peptide during the initial response to glucose. Subjects exhibiting this phenomenon had lower fasting and post-glucose C-peptide concentrations than those who did not; however, there were no statistically significant differences in glucose or insulin concentrations. The phenomenon was age-related, being absent from individuals aged 35 years and under, while in older age groups it appeared to be more prevalent in women than in men, suggesting an additional effect of menopause. However, in three follow-up IVGTTs performed in a subgroup of postmenopausal women over a period of 18 months, the phenomenon failed to recur in any of the individuals who first exhibited it, although it did occur in others. Our observations suggest the existence of an age-related but intermittent decrease in pancreatic insulin secretion, which does not lead to any significant change in plasma insulin concentrations, possibly as a result of reduced hepatic uptake of insulin. One consequence appears to be an excess of insulin over C-peptide during the early part of the IVGTT, which is probably related to the different distributional kinetics of the two peptides.

Adult

Ageing and the response of plasma insulin, glucose and C-peptide concentrations to intravenous glucose in postmenopausal women.

1. Eighty-six apparently healthy postmenopausal women not receiving hormone replacement therapy were given an intravenous glucose tolerance test. Plasma glucose, insulin and C-peptide concentrations were determined in fasting and post-glucose challenge samples. 2. Using a multivariate regression model, with predictor variables of chronological age, menopausal age and body mass index, neither chronological age nor menopausal age correlated with fasting or post-challenge plasma glucose or C-peptide concentrations. In contrast, menopausal age was positively associated with fasting plasma insulin concentration (P = 0.038, model r2 = 0.107), insulin area (P = 0.01, model r2 = 0.236) and incremental insulin area (P = 0.024, model r2 = 0.243). This relationship could not be explained by differences in lifestyle variables of alcohol consumption, physical activity, previous duration of oral contraceptive usage, history of cigarette smoking or body mass index. 3. Our findings suggest that loss of ovarian function is associated with hyperinsulinaemia, possibly via alterations in the clearance of circulating insulin from the plasma. The hyperinsulinaemia observed may contribute to the increased risk of cardiovascular disease seen in postmenopausal women.

Adult

Serum prolactin concentration in normal and small for gestational age fetuses.

OBJECTIVES: To study fetal and maternal serum prolactin concentrations in appropriately-grown (AGA) fetuses and in small for gestational age (SGA) fetuses. DESIGN: A cross-sectional study of 27 AGA and 27 SGA fetuses undergoing cordocentesis for prenatal diagnosis or for determination of fetal karyotype and acid-base balance. Serum prolactin concentration was measured by radioimmunoassay. SETTING: Harris Birthright Research Centre for Fetal Medicine. RESULTS: In the AGA group, both fetal and maternal serum prolactin concentration increased significantly with gestation (P < 0.001 and P < 0.01, respectively). In the SGA group, the fetal concentration of prolactin was significantly higher (P < 0.05), but the maternal serum prolactin concentration was not different from that of the AGA group. CONCLUSIONS: The finding of prolactin in the fetal circulation suggests that the anterior lobe of the pituitary is functioning from at least 12 weeks gestation. The increased serum prolactin concentration in SGA fetuses may be the consequence of hypoglycemic stress on the pituitary or the relative immaturity of the inhibitory hypothalamic-pituitary pathways.

Cross-Sectional Studies

Effect of body mass index and fat distribution on insulin sensitivity, secretion, and clearance in nonobese healthy men.

The effects of variation in body mass index (BMI; kg/m2) and body fat topography on insulin sensitivity, secretion, and clearance were determined in a group of 146 nonobese nondiabetic males. Volunteers underwent an i.v. glucose tolerance test, with determination of plasma glucose, insulin, and C-peptide levels. BMI was taken as a measure of overall adiposity, while skinfold thickness ratios were used to assess the centrality of fat distribution and the localization of central fat within the trunk. Measurements of insulin sensitivity, secretion, and clearance were obtained by mathematical modelling of the i.v. glucose tolerance test concentration profiles. Increasing BMI and centrality of fat distribution had no significant effect on glucose tolerance, but were independently associated with diminished insulin sensitivity and increased insulin secretion. The elevation in secretion occurred almost entirely during the second phase of pancreatic insulin release. These results show that the variations in insulin sensitivity and secretion that have often been reported in obesity are also present in a group within the normal range of BMI. However, the absence of any decrease in hepatic uptake, also reported in the obese, indicates that this might be an additional mechanism recruited to maintain glycemic control at higher levels of adiposity. Localization of central fat in the lower trunk was correlated with elevated first phase insulin secretion, but no concomitant change in insulin sensitivity. There may, therefore, be a direct effect of the distribution of central fat on insulin secretion.

Adipose Tissue

Maturation of the secretion of thyroid hormone and thyroid-stimulating hormone in the fetus.

BACKGROUND: Data on human fetal thyroid function have largely been derived from histologic studies or studies of cord-blood samples obtained at hysterotomy or delivery. These data may not represent true normal values. Cordocentesis (ultrasound-guided blood sampling from the umbilical cord) is a technique that allows investigation of physiologic processes in fetuses not under stress. METHODS: We measured serum thyroid-stimulating hormone, total and free thyroxine (T4), total and free triiodothyronine (T3), and thyroxine-binding globulin in blood samples from 62 fetuses. The samples were obtained by cordocentesis (n = 58) or cardiocentesis (n = 4) at 12 to 37 weeks of gestation. Maternal serum samples were obtained immediately before fetal blood sampling. RESULTS: Fetal serum thyroid-stimulating hormone, thyroxine-binding globulin, and total and free T4 and T3 concentrations increased significantly with the length of gestation (P less than 0.001). The only significant association among these variables, independent of the length of gestation, was between thyroid-stimulating hormone and free T4 (P less than 0.0001). Maternal serum concentrations of these variables did not change during gestation, and there was no significant relation between fetal and maternal values. Most fetal serum concentrations of thyroid-stimulating hormone were higher, whereas most serum total and free T3 concentrations were lower than the respective values for normal adults. The fetal serum total T4, free T4, and thyroxine-binding globulin values reached the level of the mean adult values at approximately 36 weeks of gestation. CONCLUSIONS: The increases in fetal serum concentrations of thyroid-stimulating hormone, thyroxine-binding globulin, and total and free T4 and T3 during gestation reflect increasing maturation of the pituitary, thyroid, and liver. The finding of increasing fetal serum concentrations of thyroid-stimulating hormone in the presence of increasing thyroid hormone concentrations suggests that the sensitivity of the fetal pituitary gland to negative feedback is limited or is counterbalanced by increasing stimulation by thyrotropin-releasing hormone from the hypothalamus.

Female

Relations between the fetal circulation and pituitary-thyroid function.

OBJECTIVE: To study the relation between changes in the fetal thyroid hormone and thyroid stimulating hormone (TSH) concentrations and alterations in the fetal circulation as assessed by Doppler ultrasound. DESIGN: A cross-sectional study of small for gestational age (SGA) and red-cell isoimmunized fetuses undergoing cordocentesis and Doppler studies for the assessment and determination of fetal karyotype, acid-base balance and haemoglobin concentration. SETTING: Harris Birthright Research Centre for Fetal Medicine, King's College, London. SUBJECTS: 38 growth retarded and 38 red-cell isoimmunised fetuses. INTERVENTIONS: Cordocentesis. MAIN OUTCOME MEASURES: Serum TSH total and free thyroxine (T4, FT4) and total and free triiodothyronine (T3, FT3) concentrations; middle cerebral artery (MCAVm) and descending thoracic aorta (AoVm) mean blood velocities; fetal Po2 and haemoglobin concentration (Hb). RESULTS: Delta values (delta) calculated as the number of SDs from the respective normal mean for gestation were used to compare the results with those from a previous study of normal fetuses. Mean AoVm was increased in the isoimmunized fetuses (P less than 0.001) but decreased in the SGA fetuses (P less than 0.001). Mean MCAVm was increased in both groups (P less than 0.01; P less than 0.001). There were significant associations between the gestational age adjusted values for TSH and MCAVm (r = 0.23, P less than 0.05) and between T4, FT4 or FT3 and AoVm (r = 0.41, P less than 0.01; r = 0.50, P less than 0.01; r = 0.36, P less than 0.01 respectively). In addition, T4 and FT4 were associated with delta Po2 and delta Hb. CONCLUSION: In the hypoxaemic hypoxia of growth retardation and the anaemic hypoxia of rhesus disease there are significant associations between changes in fetal thyroid hormone concentrations and changes in fetal blood flow as assessed by Doppler. Irrespective of whether altered blood flow is the cause or effect of changes in thyroid hormone concentrations, the observed changes could have beneficial effects for fetal survival, in the presence of a hostile intrauterine environment.

Blood Circulation

Thyroid function in small for gestational age fetuses.

Thyroid function was studied in fetal blood samples obtained by funipuncture from 49 small for gestational age (SGA) fetuses at 21-38 weeks' gestation. Levels of TSH, thyroxine-binding globulin, thyroxine (T4), free T4, triiodothyronine (T3), and free T3 were compared with those from 62 appropriate for gestational age (AGA) fetuses. Levels of TSH were significantly higher and T4 and free T4 significantly lower in the SGA than in AGA fetuses. Furthermore, there were significant associations between the increase in TSH and decrease in free T4 and the degrees of fetal hypoxemia and acidemia, respectively.

Female

Thyroid function in anemic fetuses.

Thyroid function was studied in 75 fetal blood samples obtained by cordocentesis from red cell isoimmunized pregnancies at 18-37 weeks of gestation. Thyroid-stimulating hormone (TSH), and free and total thyroxine and triiodothyronine were significantly higher than in normal controls. Furthermore, there was a significant association between the increase in TSH and the degree of fetal anemia.

Anemia