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Biomedical subjects

C D Byrne

Publications and source records attributed to C D Byrne.

At least 19 recordsLinked to original sources
PubMed2005

Investigating the role of the growth hormone-insulin-like growth factor (GH-IGF) axis as a determinant of male bone mineral density (BMD).

INTRODUCTION: The GH-IGF axis has profound effects on bone metabolism and may be important in the etiology of idiopathic osteoporosis. Serum IGF-I is often low in men with osteoporosis, which may be attributable to GH hypo-secretion or hepatic GH insensitivity. We studied the GH-IGF axis in depth to look for evidence to support these hypotheses. MATERIALS AND METHODS: 28 healthy 60- to 70-year-old men with low, intermediate, or normal BMD were studied. GH secretion was measured by overnight urine collection. GH reserve was assessed by exercise and glucagon stimulation tests. Hepatic IGF-I production was investigated using a GH-IGF-I generation test. Data were analyzed using Pearson's correlation coefficient, linear regression, and analysis of variance. RESULTS: Serum IGF-I was reduced in subjects with low BMD (P = 0.009). There was no difference in GH secretion or reserve between the groups. Overall, GH reserve and IGF-I were positively related but this was attenuated in the low BMD group. However, no statistically significant difference in IGF-I generation capacity between BMD groups was found. CONCLUSIONS: Men with reduced BMD have low IGF-I but normal GH secretion and reserve. Our data suggested, but could not confirm, hepatic resistance to GH as a mechanism for this association.

Aged↗
PubMed2005

Electrical muscle stimulation acutely mimics exercise in neurologically intact individuals but has limited clinical benefits in patients with type 2 diabetes.

BACKGROUND: Electrical muscle stimulation mimics exercise in individuals with neurological injury or disease and improves measures of fitness and glucose metabolism. Physical activity improves features of the metabolic syndrome in patients with type 2 diabetes but many patients find it difficult to exercise. AIMS: To determine whether use of an electrical muscle stimulator mimics exercise in neurologically intact individuals and has metabolic benefits in patients with type 2 diabetes. METHODS: Acute changes in pulse, blood pressure and energy expenditure were measured in 33 healthy volunteers using the muscle stimulator. Acute changes in glucose uptake were measured in five subjects with type 2 diabetes. Body composition, features of the metabolic syndrome and measures of insulin sensitivity were measured before and after 12 weeks daily use of the stimulator in four subjects with type 2 diabetes. RESULTS: The muscle stimulator acutely increased pulse, blood pressure, energy expenditure and glucose uptake. Daily use over 12 weeks improved insulin stimulated nonesterified fatty acid suppression but did not result in changes in body composition or clinical parameters. CONCLUSION: Although the muscle stimulator acutely mimics exercise, limitations in the size of the stimulating current mean that the magnitude of these changes is too small to produce clinical benefit.

Adult↗
PubMed2005

Prognostic value of the Framingham cardiovascular risk equation and the UKPDS risk engine for coronary heart disease in newly diagnosed Type 2 diabetes: results from a United Kingdom study.

AIMS: To determine the prognostic value of the Framingham equation and the United Kingdom Prospective Diabetes Study (UKPDS) risk engine in patients with newly diagnosed Type 2 diabetes. METHODS: A community-based cohort (n=428; aged 30-74 years) free of clinically evident CVD and newly diagnosed with Type 2 diabetes were studied over a median 4.2 (sd+/-0.62) years. Predicted (using baseline variables at diagnosis) and observed proportions of primary CVD and CHD events were compared using the Framingham equations and the UKPDS risk engine (only CHD events). The discrimination (c-statistic) and calibration (HLchi2) of the risk equations were calculated. The sensitivity and specificity of the Framingham equation at a 15%, 10-year CHD risk threshold (NICE guidelines) was compared with that of the ADA lipid threshold (LDLc>or=2.6 mmol/l or triglycerides>or=4.5 mmol/l). RESULTS: The Framingham equations underestimated the overall number of cardiovascular events by 33% and coronary events by 32% and showed modest discrimination and poor calibration for CVD [c=0.673; HLchi2=32.8 (P<0.001)] and CHD risk [c=0.657; HLchi2=19.8 (P=0.011)]. Although the overall underestimate was lower and non-significant with the UKPDS risk engine for CHD (13%), its performance in terms of discrimination and calibration were similar [c=0.670; HLchi2=17.1 (P=0.029)]. The 15%, 10-year CHD risk threshold with both the Framingham and UKPDS risk engines had similar sensitivity for primary CVD as the lipid level threshold [85.7 and 89.8% vs. 93.9% (P=0.21 and 0.34)] and both had greater specificity [33.0 and 30.3% vs. 12.1% (P<0.001 and P<0.001)]. CONCLUSIONS: In people with newly diagnosed Type 2 diabetes, both the Framingham equation and UKPDS risk engine are moderately effective at identifying those at high-risk (discrimination) and are poor at quantifying risk (calibration). Nonetheless, at a population level, a 15% 10-year CHD risk threshold using either risk calculator has similar sensitivity as an approach based on a single lipid risk factor level and may have benefits in terms of cost-effectiveness given the improved specificity.

Adult↗
PubMed2005

The metabolic syndrome and type 2 diabetes.

The metabolic syndrome describes the clustering of dyslipidaemia, glucose intolerance and hypertension with central adiposity. The syndrome is increasing in prevalence worldwide as a consequence of increasing obesity prevalence. It will have global effects on the prevalence of cardiovascular disease. This review summarises current knowledge of the syndrome with special emphasis on the aetiology and pathogenesis and examines the clinical consequences of occlusive vascular disease and non alcoholic steatohepatitis. The roles of nutrition, exercise and pharmacological treatments of the syndrome are discussed.

Animals↗
PubMed2004

Schizophrenia, the metabolic syndrome and diabetes.

The prevalence of diabetes is increased in patients with schizophrenia. Although many reasons, including hereditary and lifestyle factors, contribute to this association, recently there has been heightened interest in the subject because of the link between the use of the newer atypical anti-psychotic drugs and the development of diabetes. These drugs cause significant weight gain and this may be one of the mechanisms by which they increase incident diabetes. The increased prevalence of diabetes among people with schizophrenia has implications for the delivery of care by psychiatrists, diabetologists and primary care.

Antipsychotic Agents↗
PubMed2003

Variants in the APOC3 promoter insulin responsive element modulate insulin secretion and lipids in middle-aged men.

Variation in the insulin responsive element (IRE) of the APOC3 promoter has been shown to be associated with insulin and glucose concentrations after an oral glucose tolerance test (OGTT) in young healthy men. We evaluated two variants in the IRE (-455T>C and -482C>T) in the Ely study, a prospective cohort study of middle-aged men (n=223) and women (n=279), to determine if the effect of these variants on glucose homeostasis could be explained by altered nonesterified fatty acid (NEFA) levels and if these effects are modulated by age and gender. Both variants had significant effects on the 30-min insulin incremental response in men alone (-482C>T, P=0.007; -455T>C, P=0.0155), with rare allele homozygotes having a 33.3% and 23.3% lower insulin increment as compared to common allele homozygotes, respectively. Thirty-minute NEFA concentrations were also significantly associated with genotype in men and levels were approximately 10% higher in carriers homozygous for the rare alleles as compared to subjects homozygous for the common alleles (-482C>T, P=0.04; -455T>C, P=0.006). In addition, there was a strong interaction between both variants and cigarette smoking affecting fasting triglyceride levels in both men (interaction: -455T>C, P=0.02; -482C>T, P=0.008) and women (interaction: -455T>C, P=0.007; -482C>T, P=0.013). Taken together, the data shows that men who carry the rare alleles of the IRE variants have disturbed glucose homeostasis and an unfavourable lipid phenotype. The finding of an elevated 30-min NEFA may be an important mechanistic link between triglyceride-rich lipoprotein (TRL) metabolism and glucose homeostasis.

Apolipoprotein C-III↗
PubMed2001

Variation in the promoter of the human hormone sensitive lipase gene shows gender specific effects on insulin and lipid levels: results from the Ely study.

We previously identified a hormone sensitive lipase (HSL) promoter variant, -60C>G, which in vitro exhibits 40% reduced promoter activity. In this study we examined the effect of the -60C>G on glycemic and lipid measures in the population based Ely study of metabolic function and insulin resistance in 218 middle-aged men and 276 middle-aged women. Adipose tissue HSL is the rate-limiting step in triglyceride lipolysis, generating free fatty acids for energy utilization. HSL is also expressed in pancreatic beta-cells where its activity therefore may affect insulin secretion. In the women, carriers of the HSL -60G allele had significantly lower fasting insulin levels (P=0.0005) and a lower total area under the curve for insulin during the oral glucose tolerance test (P=0.005). There was no demonstrable association in men with these measures of insulin sensitivity but carriers of the -60G allele had significantly lower fasting non-esterified fatty acid (NEFA) levels (P=0.025) and higher low density lipoprotein cholesterol levels (P=0.02) than men who were non-carriers. This study provides additional evidence for a role for HSL in the development of insulin resistance, from which carriers of the -60G allele, associated here with markers of insulin sensitivity in women, and with lower NEFA levels in men, might be protected.

Diabetes Mellitus, Type 2↗
PubMed2001

Influence of the unpacked section on the chromatographic performance of duplex strong anion-exchange columns in capillary electrochromatography.

This work describes initial investigations of strong anion-exchange (SAX) packing materials for capillary electrochromatography (CEC). The use of SAX phases in CEC is theoretically appealing for the analysis of negatively charged species. The reversed direction of the electroosmotic flow (EOF) generated by SAX phases (in comparison to reversed phases and strong cation-exchange phases) means that negative species can migrate with the EOF, not against it, hence the analysis times, of such species should be decreased and efficiencies improved. Duplex CEC columns (the standard for instruments using UV detection) consist of a packed and an unpacked section. Using common reversed-phase packing materials the direction of the EOF in both sections is co-linear, however when normal fused-silica capillaries are packed with SAX material the direction of the EOF in the two sections oppose one another. It has been shown, using conventional duplex CEC columns and fully packed CEC-MS columns that the opposing direction of EOF causes a massive degradation in column performance. Consequentially, it is demonstrated that if the EOF in the open section of the duplex SAX column can be controlled via pH or capillary derivatisation then good, reproducible CEC can be performed on anionic species using SAX packed CEC columns.

Anion Exchange Resins↗
PubMed2001

Suppressing thrombin generation is compatible with the development of atherosclerosis in mice.

Thrombin has been proposed to play a key role in the development of atherosclerosis, both by promoting fibrin deposition into the atherosclerotic vessel wall and also by signalling through thrombin receptors. Unfortunately, mice homozygous for a deletion of the prothrombin gene (FII) die in utero, making a direct assessment of the role of thrombin during atherogenesis difficult. We have assessed the contribution of thrombin-dependent processes to vascular lipid lesion formation in the atherosclerosis-prone apolipoprotein E (ApoE)-deficient mice by inhibiting thrombin generation with warfarin. ApoE-/- mice were treated with warfarin at a dose that increased the prothrombin time (PT) more than 10-fold (250-375 microg/kg body weight/day) for 12 weeks from the age of 12 weeks onwards. The extent and composition of the vascular lipid lesions that developed were assessed using oil red O to measure neutral lipid in the vessel wall and quantitative immunofluoresence to measure fibrin(ogen) levels as well as macrophage and smooth muscle cell numbers. Mice treated with warfarin developed lesions both in the aortic sinus and the descending aorta to the same degree as mice receiving no treatment (28,351+/-350 microm2/mouse treated with warfarin versus 27,952+/-750 micro2/control mouse; P = .86). However, the amount of fibrin(ogen) deposited in the vessel wall was decreased by more than 60% (34+/-11 arbitrary units in warfarin treated mice versus 92+/-11 arbitrary units in control mice; P < .01). Staining of macrophage and for smooth muscle cell markers was unaltered by treatment with warfarin. We conclude that suppressing thrombin generation does not alter the development of vascular lipid lesions in mice with a severe disorder of lipid metabolism, despite a marked reduction in fibrin(ogen) deposition.

Animals↗
PubMed2001

Effects of maternal iron restriction in the rat on hypoxia-induced gene expression and fetal metabolite levels.

The mechanism by which maternal Fe deficiency in the rat causes fetal growth retardation has not been clearly established. This study compared the effects on the fetuses from dams fed a control diet with two groups of dams fed Fe-restricted diets. One Fe-restricted group was fed the Fe-restricted diet for 1 week prior to mating and throughout gestation and the second Fe-restricted group was fed the Fe-restricted diet for 2 weeks prior to mating and throughout gestation. On day 21 of gestation Fe-restricted dams, and their fetuses, were anaemic. Fetal weight was reduced in both Fe-restricted groups compared with controls. Expression of hypoxia-inducible factor (HIF)-1alpha and vascular endothelial growth factor (VEGF) are induced by hypoxia. The levels of HIF-1alpha mRNA were highest in placenta, then in kidney, heart and liver but were not different between the groups. Levels of plasma VEGF were not different between the groups. Maternal plasma triacylglycerol was decreased in the 1-week Fe-restricted dams compared with controls. Maternal plasma cholesterol and free fatty acid levels were not different between the groups. In fetal plasma, levels of triacylglycerol and cholesterol were decreased in both Fe-restricted groups. In maternal plasma, levels of a number of amino acids were elevated in both Fe-restricted groups. In contrast, levels of a number of amino acids in fetal plasma were lower in both Fe-restricted groups. Fetal plasma lactate was increased in Fe-restricted fetuses but fetal plasma glucose and beta-hydroxybutyrate were not affected. These changes in fetal metabolism may contribute to fetal growth retardation in this model. This study does not support the hypothesis that the Fe-restricted fetus is hypoxic.

Amino Acids↗
PubMed2001

Programming other hormones that affect insulin.

The metabolic syndrome is associated with a marked increase in risk of type 2 diabetes and atherosclerotic vascular disease (AVD). The mechanism responsible for the metabolic syndrome is uncertain, but recent evidence suggests that a combination of low birth weight and adult obesity is associated with a markedly increased prevalence. Insulin resistance is the cardinal feature of the metabolic syndrome. Several hormones, have modes of action that either potentiate or reduce the biological actions of insulin and, therefore, attenuate or induce insulin resistance. Since insulin action may be modified, these hormones potentially contribute to the pathogenesis of the metabolic syndrome. The purpose of this review is to discuss programming of hormones that modulate insulin action. The review focuses on two major endocrine pathways: (i) glucocorticoid hormone action; and (ii) the growth hormone (GH)-insulin-like growth factor (IGF-1) axis, and discusses mechanisms linking abnormal activity of these pathways with reduced early growth, adult obesity and the metabolic syndrome.

Diabetes Mellitus, Type 2↗
PubMed2001

Do different dimensions of the metabolic syndrome change together over time? Evidence supporting obesity as the central feature.

OBJECTIVE: The metabolic syndrome is a loosely defined cluster of cardiovascular risk factors including low HDL cholesterol, hypertriglyceridemia, glucose intolerance, and hypertension. Evidence for inclusion of these features in the syndrome has mostly come from cross-sectional studies, and a few studies have examined how the various factors change together over time. RESEARCH DESIGN AND METHODS: We conducted a prospective population-based cohort study of 937 individuals aged 40-65 years who underwent oral glucose tolerance testing on two occasions at 4.5-year intervals. Changes in the components of the metabolic syndrome were analyzed by principal component analysis in the entire population and in a subgroup of 471 individuals who did not receive pharmaceutical therapy for hypertension and dyslipidemia. RESULTS: Principal component analysis identified three independent factors in men: a blood pressure factor (systolic and diastolic blood pressure and BMI), a glucose factor (fasting and 120-min postload glucose, BMI, waist-to-hip ratio [WHR], and fasting insulin level), and a lipid factor (triglycerides and HDL cholesterol, BMI, WHR, and fasting insulin level). In women, an additional factor was identified, which included BMI, WHR, fasting insulin, and triglycerides. Analysis of the contribution of these variables to the different subdimensions indicated that BMI was the central feature of the syndrome in both sexes. CONCLUSIONS: This analysis of change in the features of the metabolic syndrome over time provides evidence of the fundamental importance of obesity in the origin of this disorder.

Adult↗
PubMed2000

A common apolipoprotein B signal peptide polymorphism modifies the relation between plasma non-esterified fatty acids and triglyceride concentration in men.

Insulin and non-esterified fatty acids (NEFA) are important regulators of triglyceride metabolism. The relations between these compounds and the effect of a common 3 amino acid deletion in the apolipoprotein B (ApoB) signal peptide (SP) following an oral glucose challenge have been investigated. The frequency of the shorter SP-24 allele was 32% (95% C.I. 29.5-36.5) in 725 subjects undergoing an oral glucose tolerance test (OGTT). Fasting plasma triglyceride concentration was positively correlated with fasting plasma insulin concentration and negatively with the degree of plasma NEFA suppression following the glucose challenge. Linear regression analysis showed the relation between triglyceride concentration and NEFA suppression, but not the relation between triglyceride concentration and fasting insulin, to be altered by the SP polymorphism in men but not in women. The strength of the association was dependent on the number of SP-24 alleles, with SP-24 homozygotes showing the greatest dependence (men P=0.031, women P=0. 914). It was proposed that the complex regulation of very low density lipoprotein (VLDL) output by NEFA and by insulin may explain, at least in part, the conflicting reports concerning the presence of the ApoB SP polymorphism, fasting serum lipids and ischaemic heart disease (IHD).

Adult↗
PubMed2000

Hypertension and its treatment influence changes in fasting nonesterified fatty acid concentrations: a link between the sympathetic nervous system and the metabolic syndrome?

In previous studies, a cross-sectional association has been described between blood pressure (BP) and nonesterified fatty acid (NEFA) concentrations. The direction of causality, and thus, the mechanism explaining this relationship, remains uncertain. Therefore, we analyzed a prospective population-based cohort of 937 subjects who underwent an oral glucose tolerance test (OGTT) on two occasions separated by 4.5 years. In cross-sectional analysis, NEFA measures were correlated with systolic and diastolic BP, both at baseline and at follow-up study. In longitudinal analysis, baseline systolic and diastolic BP predicted changes in fasting NEFA levels (both P < .01). However, baseline NEFA levels did not predict change in BR In multivariate analysis, the relationship between baseline BP and change in fasting NEFA was independent of age and sex. Obesity and its interaction with BP did not explain this association. Absolute changes in NEFA concentrations were greater among subjects who were hypertensive at baseline compared with the normotensive individuals. This change was greater in subjects treated with diuretics compared with those treated with beta-adrenergic antagonists (P < .01), an observation that provides support for a role of sympathetic nervous system (SNS) activity in explaining the relationship between BP and NEFA concentration.

Adrenergic beta-Antagonists↗