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Biomedical subjects

K D Hopkins

Publications and source records attributed to K D Hopkins.

At least 37 records · Page 2Linked to original sources
PubMed1995

A comparison of the effects of IGF-I and insulin on glucose metabolism, fat metabolism and the cardiovascular system in normal human volunteers.

The metabolic and cardiovascular effects of recombinant human IGF-I were compared to insulin in six normal subjects. Subjects were studied twice and intravenously received an infusion of [6,6-2H2]glucose (0-480 min) and in random order either IGF-I 20 micrograms kg-1 h-1 (43.7 pmol kg-1 min-1 or insulin 0.5 mU kg-1 min-1 (3.4 pmol kg-1 min-1) with an euglycaemic clamp. One subject was withdrawn following a serious adverse event. During the IGF-I infusion glucose appearance rate (Ra) decreased from 1.79 +/- 0.13 at baseline (150-180 min) to 0.35 +/- 0.26 mg kg-1 min-1 (P < 0.01) at 360 min, and glucose utilization rate (Rd) increased from 1.79 +/- 0.28 to 4.17 +/- 0.84 mg kg-1 min-1 (P < 0.01). There was no change in free fatty acids (FFA) and an increase (percentage change from pre-infusion mean) in cardiac output +l37.3% +/- 9% (P < 0.01), heart rate +13% +/- 2% (P < 0.01) and stroke volume +21% +/- 7% (P < 0.05). During the insulin infusion glucose Ra decreased from 1.89 +/- 0.13 to 0.34 +/- 0.33 mg kg-1 min-1 (P < 0.01) and FFA from 0.546 mmol l-1 to 0.198 mmol l-1 (P < 0.01), glucose Rd increased from 1.89 +/- 0.18 to 5.41 +/- 1.47 mg kg-1 min-1 (P < 0.01) and there were no significant changes in the cardiovascular variables.

Adult↗
PubMed1994

Time series analysis and control of blood glucose levels in diabetic patients.

This paper describes features of a computer-based decision support system which is being developed to assist in the management of insulin-dependent diabetic patients. The clinical context is the provision of advice on the adjustment of the basic insulin regimen such as occurs at regular visits to the clinician. The integrated system combines data processing and interpretation, generation of qualitative advice and testing the implications of that advice using a glucose/insulin dynamic simulator. The two major features described in this paper are time series analysis of blood glucose data, and their interpretation in relation to the provision of advice for controlling the patient's blood glucose level. It is demonstrated that two approaches may be adopted in such time series analysis: an intuitive approach, manipulating symbolic representations of the data, and formal time series methods which decompose the series into clinically related components.

Blood Glucose↗
PubMed1994

Aortic compliance measured by non-invasive Doppler ultrasound: application of a personal computer based MkII system and its repeatability.

A non-invasive pulse-wave-velocity Doppler ultrasound technique for the assessment of aortic compliance is described. A computational approach for correcting for the effect of non-chronic changes in blood pressure is considered and applied to compliance measurements performed on an age-select cohort of 70 normotensive, normal healthy volunteers. In order to permit the wider availability of the pulse-wave-velocity Doppler ultrasound technique, the authors have developed a MkII system based on a standard 80486/33 MHz IBM compatible WINDOWS based personal computer; real-time spectral analysis being achieved using a relatively inexpensive but fast analogue to digital signal processing card. An overview of the new apparatus is provided and verification work to compare the repeatability of the MkI and MkII systems is described. Medical disorders such as atherosclerosis, diabetes mellitus, familial hypercholesterolaemia, growth hormone deficiency, and Ehlers-Danlos and Marfan's syndromes have all been shown to affect arterial wall compliance. We suggest that the in vivo clinical measurement of blood pressure corrected aortic distensibility using the MkII system may be a useful, reproducible, non-invasive tool for assessing such patients' susceptibility to atheromatous arterial disease as well as for monitoring their response to therapeutic interventions. Measurements in the aorta may be especially pertinent since the natural history of fatty streaks there tends to parallel that in the coronary vasculature thereby potentially affording a convenient surrogate estimate of coronary heart disease.

Aorta↗
PubMed1994

Use of a leucine clamp to demonstrate that IGF-I actively stimulates protein synthesis in normal humans.

Insulin-like growth factor I (IGF-I) is thought to mediate the anabolic action of growth hormone. A glucose and amino acid clamp technique was used to investigate the effects of a 3-h intravenous infusion of either 43.7 pmol.kg-1.min-1 (20 micrograms.kg-1.h-1) IGF-I or 3.4 pmol.kg-1.min-1 (0.5 mU.kg-1.min-1) insulin on whole body leucine turnover in five normal human volunteers. During the IGF-I infusion, IGF-I levels increased (P < 0.01; 26.6 +/- 2.8 to 88.9 +/- 14.2 nmol/l) and insulin levels fell (P < 0.05; 0.096 +/- 0.018 to 0.043 +/- 0.009 nmol/l). During the insulin infusion, insulin levels increased (P < 0.01; 0.057 +/- 0.013 to 0.340 +/- 0.099 nmol/l), and there was no change in IGF-I. There was no significant change in leucine production rate (Ra; a measure of protein degradation) during the IGF-I infusion (2.23 +/- 0.17 to 2.13 +/- 0.2 mumol.kg-1.min-1), but there was an increase (P < 0.03) in nonoxidative leucine disposal rate (Rd; a measure of protein synthesis; 1.83 +/- 0.15 to 2.05 +/- 0.21 mumol.kg-1.min-1). In contrast, insulin reduced (P < 0.02) leucine Ra (1.81 +/- 0.24 to 1.47 +/- 0.24 mumol.kg-1.min-1) and had no effect on nonoxidative leucine Rd (1.44 +/- 0.25 to 1.41 +/- 0.22 mumol.kg-1.min-1). We conclude that IGF-I, under conditions of adequate substrate supply, directly increases protein synthesis in contrast to insulin, which exerts its anabolic action by reducing proteolysis.

Adult↗
PubMed1994

Aortic distensibility in post-menopausal women receiving Tibolone.

Both oestrogen and androgens have been shown to affect the structural composition and biophysical properties of the arterial wall in vitro. A non-invasive Doppler ultrasound technique, based on the measurement of pulse wave velocity along the thoraco-abdominal aortic pathway, was used to assess aortic compliance C in vivo in 49 normotensive, normal, healthy post-menopausal female subjects. 23 of the women had been receiving Tibolone, a synthetic steroid structurally related to norethisterone, for at least 3 years. Since C varies with non-chronic changes in blood pressure, an index of intrinsic aortic distensibility, Cp, normally independent of blood pressure, was also calculated. No significant difference was found between the control group and those subjects receiving Tibolone for age, body mass index, systolic blood pressure, diastolic blood pressure, C or Cp. As one would expect the control group Cp values did not show a significant relationship with blood pressure (r = -0.1, not significant). However, in the Tibolone group some dependence of Cp values on pressure still remained (r = -0.58, p < 0.004), suggesting that oral administration of Tibolone had altered the dynamic relationship between structural and functional biophysical properties of the aortic wall in vivo.

Anabolic Agents↗
PubMed1994

Insulin-like growth factor-binding protein-1 is correlated with low density lipoprotein cholesterol in normal subjects.

Insulin-like growth factor-I (IGF-I) has been inversely associated with low-density lipoprotein (LDL) cholesterol in normal women with slightly elevated cholesterol levels and hypothyroid women. More than 95% of IGF-I circulates bound to binding proteins (IGFBPs); of these IGFBP-1 is of particular interest as it is inversely regulated by insulin and is thought to inhibit the action of IGF-I and IGF-II. We examined the relationship between IGFBP-1 and LDL cholesterol in 41 healthy adult subjects. LDL cholesterol correlated with the body mass index (r = 0.40, P < 0.01), sex (r = 0.51, P < 0.001) and IGFBP-1 levels (r = 0.36, P < 0.02). LDL cholesterol did not correlate with age (r = 0.25, P = not significant) or IGF-I (r = 0.06, P = not significant). Upon multivariate regression analysis, sex, body mass index and IGFBP-1 were all independent predictors of LDL cholesterol (all P < 0.05). Elevated IGFBP-1 levels have been associated with an inhibition of serum IGF-I bioactivity in children with insulin-dependent diabetes. IGFBP-1 also appears to inhibit IGF-I hexose-stimulated uptake. IGFBP-1 may also be inhibiting the effect of IGFs on the cellular metabolism of LDL cholesterol.

Adult↗
PubMed1993

Validation and reproducibility of pressure-corrected aortic distensibility measurements using pulse-wave-velocity Doppler ultrasound.

A non-invasive Doppler ultrasound technique is described for the assessment of aortic compliance based on the in vivo measurement of pulse wave velocity along the thoraco-abdominal aortic pathway. A structured protocol, which has been developed to improve the reproducibility of the technique, is validated. A method of correcting for the effect of non-chronic changes in blood pressure on arterial elasticity is considered and applied to compliance measurements performed on 66 normal, healthy volunteers. The results of a study to ascertain the overall reproducibility of the method are provided and problems associated with the technique are discussed. Medical disorders such as atherosclerosis, diabetes mellitus, familial hypercholesterolaemia and growth hormone deficiency have all been shown to affect arterial wall compliance. It is suggested that the in vivo measurement of pressure-corrected aortic distensibility may be a useful, non-invasive tool for assessing such patients' susceptibility to atheromatous arterial disease and for monitoring their response to therapy. Measurements in the aorta may be especially pertinent since the natural history of fatty streaks there tends to parallel that in coronary arteries thereby potentially affording a convenient surrogate estimate of coronary heart disease.

Adolescent↗
PubMed1993

Aortic compliance measurements using Doppler ultrasound: in vivo biochemical correlates.

A noninvasive Doppler ultrasound technique for the assessment of aortic compliance based on the in vivo measurement of pulse wave velocity along the thoraco-abdominal aortic pathway is described. An approach for correcting for the effect of blood pressure on aortic distensibility is considered. The derivation of an index of intrinsic distensibility, Cp, which is independent of blood pressure, is provided and applied to data collected from normal, healthy volunteers. Overviews are provided of studies utilising the technique to determine aortic compliance in medical disorders, which are known to predispose to premature cardiovascular disease, such as diabetes mellitus, familial hypercholesterolaemia and growth hormone deficiency. The significance of correlations between in vivo aortic compliance measurements and plasma concentrations of total cholesterol, low-density-lipoprotein cholesterol, high-density-lipoprotein cholesterol and insulin-like growth factor-I are discussed. It is proposed that the measurement of aortic compliance in normal, healthy individuals may potentially be a useful in vivo research tool for investigating the effects of biochemical factors on the biophysical properties of the aortic wall. Furthermore, we believe that the routine measurement of blood pressure-corrected aortic distensibility may prove a useful, noninvasive clinical tool for assessing patients' susceptibility to atherosclerosis, as well as for monitoring their response to therapeutic interventions.

Adolescent↗
PubMed1993

Biochemical correlates of aortic distensibility in vivo in normal subjects.

1. Non-invasive aortic compliance measurements have been used previously to assess the distensibility of the aorta in several pathological conditions associated with increased cardiovascular risk. In adult patients with familial hypercholesterolaemia and those with growth hormone deficiency, aortic compliance has been found to correlate inversely with plasma cholesterol levels and age. We set out to establish if a relationship existed between the biophysical measurement of aortic compliance and biochemical variables in normal healthy adult subjects. 2. Blood pressure-corrected aortic distensibility, fasting insulin, insulin-like growth factor-I, total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and triacylglycerol were measured in 38 (18 males, 20 females) normotensive healthy adults. 3. Blood pressure-corrected aortic distensibility was found to correlate inversely with age (r = -0.67, P < 0.001), low-density lipoprotein-cholesterol (r = -0.37, P < 0.02) and the low-density lipoprotein-/high density lipoprotein-cholesterol ratio (r = -0.33, P < 0.05) and positively with insulin-like growth factor-I (r = 0.47, P < 0.01). On separate analysis by sex, significant inverse correlations were observed in females between aortic distensibility and total cholesterol (r = -0.50, P < 0.02), low-density lipoprotein-cholesterol (r = -0.55, P < 0.01) and age (r = -0.74, P < 0.001). A positive correlation was found between aortic distensibility and insulin-like growth factor-I (r = 0.48, P < 0.05). On forced stepwise regression analysis, however, only age (P < 0.02) was found to be significant. In males, an inverse correlation was found between aortic distensibility and age (r = -0.57, P < 0.01), low-density lipoprotein-cholesterol (r = -0.51, P < 0.05), and the low-density lipoprotein-/high-density lipoprotein-cholesterol ratio (r = -0.63, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Insulin secretion and insulin-like growth factor-I levels in active and controlled acromegaly.

OBJECTIVE: We examined the contributions of growth hormone (GH) and insulin-like growth factor-I (IGF-I) to insulin sensitivity and beta-cell function in acromegaly. DESIGN: A cross-sectional study was used with continuous infusion of glucose with model assessment to determine insulin sensitivity and beta-cell function. PATIENTS: Ten patients with active acromegaly, seven with controlled disease and 22 normal individuals were studied. MEASUREMENTS: Glucose and insulin levels were measured fasting and at the end of the one-hour glucose infusion to calculate insulin sensitivity and beta-cell function. Random GH and IGF-I were recorded. Most patients had values of GH taken after a 100-g oral glucose tolerance test and K values from intravenous glucose tolerance tests. RESULTS Patients with active acromegaly had significantly decreased insulin sensitivity compared to the normal population (P less than 0.001), while those with controlled disease did not. There was a significant negative correlation between IGF-I and insulin sensitivity in those with active disease (P less than 0.05). Beta-cell function in both active and controlled patient groups was elevated compared to the normal population (P less than 0.05, P less than 0.01 respectively) and this was significantly related to IGF-I in the active group (P less than 0.05). GH levels did not correlate with fasting insulin, glucose, insulin sensitivity or beta-cell function in either group. CONCLUSIONS: Patients with active acromegaly have decreased insulin sensitivity and increased beta-cell function that are significantly related to IGF-I but not GH levels. When the disease is controlled, beta-cell function remains elevated but insulin sensitivity improves.

Acromegaly↗