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D I Phillips

Publications and source records attributed to D I Phillips.

At least 19 recordsLinked to original sources
PubMed2005

Non-esterified fatty acid concentrations are independently associated with hepatic steatosis in obese subjects.

AIMS/HYPOTHESIS: We tested the hypothesis that NEFA concentrations are higher in obese subjects with fatty liver than in obese subjects without fatty liver. MATERIALS AND METHODS: We recruited 22 obese (BMI>30 kg/m(2)) men aged 42-64 years, in whom liver fat was assessed by ultrasound and classified into categories of no, mild to moderate and severe fatty liver by two independent radiologists. Regional and visceral abdominal fat were assessed by dual-energy X-ray absorptiometry and magnetic resonance imaging, and endogenous glucose production, whole-body glucose disposal during an insulin clamp, and NEFA concentrations were measured, along with NEFA suppression (percent (%) suppression and insulin sensitivity index for NEFA during an OGTT). RESULTS: Seven subjects had no evidence of fatty liver, nine had mild or moderate fatty liver and six had severe fatty liver. The amount of visceral fat was not associated with the degree of fatty liver. Whole-body glucose disposal was inversely associated with fatty liver (38.4, 26.5 and 23.9 mumol kg(-1) min(-1) for the groups with no fatty liver, mild to moderate fatty liver and severe fatty liver, respectively, p=0.004). NEFA suppression during the OGTT was decreased (62.5, 50.8 and 41%, p=0.03, for no, mild to moderate, and severe fatty liver, respectively) and the insulin sensitivity index for NEFA was decreased (0.80, 0.40 and 0.34, p<0.0001). Regression modelling suggested that NEFA concentrations were associated with fatty liver independently of whole-body glucose production and disposal measurements. CONCLUSIONS/INTERPRETATION: In obese men, NEFA concentrations during an OGTT are associated with fatty liver independently of classic measures of insulin sensitivity determined by the hyperinsulinaemic clamp. The contribution to this association by factors regulating NEFA concentrations requires further study.

Abdomen↗
PubMed2004

Plasma leptin concentration and change in bone density among elderly men and women: the Hertfordshire Cohort Study.

Several studies have shown an association between circulating leptin concentration and bone mineral density. but most studies are cross-sectional in design and report findings in women only. We per-formed a population-based longitudinal study relating baseline plasma leptin concentration to bone mass at the lumbar spine and femoral neck and to change in bone density at these sites over four years in a cohort of 302 men and women aged 60 75 years born and still resident in Hertfordshire, UK. Baseline plasma leptin concentration was strongly positively correlated with body mass index (men: r = 0.71, P 0.0001; women: r = 0.79, P < 0.0001) and with bone mineral content,bone mineral density, and volumetric bone mineral density at all sites (r = 0.24-0.36, P < 0.001) in both sexes: associations with change in bone density were markedly weaker and inconsistent. Adjustment for adult lifestyle determinants of osteoporosis made little difference to our results, but the associations of leptin with bone mass were no longer significant after adjustment for body mass index. These results suggest that the relationship between plasma leptin and bone mass is similar in men and women and that it is mediated through the strong association of both variables with adiposity, rather than through a direct association of leptin on bone cell function.

Aged↗
PubMed2001

Testing the fetal origins hypothesis in twins: the Birmingham twin study.

AIMS/HYPOTHESIS: To test whether the link between birthsize and raised blood pressure or glucose tolerance is due to genetic or intrauterine factors, we studied whether differences in birthweight between pairs of monozygous and dizygous twins are associated with adult differences in blood pressure and glucose tolerance. METHODS: A sample of 58 monozygous and 140 dizygous twins were identified from a register of births in Birmingham, United Kingdom, between 1950 and 1954. The twins had their blood pressure measured and underwent an oral glucose tolerance test. RESULTS: There were no statistically significant associations between birthweight, length or ponderal index, and either blood pressure or glucose tolerance in the twins. Although there were substantial within-pair differences in birthweight between monozygous and dizygous twin pairs, these differences did not correlate with the adult outcomes. Monozygous correlations, however, for both blood pressure and glucose tolerance were statistically significantly higher than dizygous correlations and a quantitative genetic model suggested statistically significant heritability for these traits. In contrast correlations of birthsize were similar in monozygous and dizygous pairs suggesting only a small genetic component in determining fetal size. CONCLUSION/INTERPRETATION: Our results show that birthsize in twins does not predict adult blood pressure or glucose tolerance. We also suggest that shared genetic determinants for fetal growth and adult outcomes are not likely to be prevalent or powerful.

Adult↗
PubMed2001

Plasma antioxidant vitamins and carotenoids and age-related cataract.

OBJECTIVE: To investigate the relationships between plasma concentrations of antioxidant vitamins and carotenoids and nuclear, cortical, and posterior subcapsular cataracts in a group of elderly men and women. DESIGN: Cross-sectional survey. PARTICIPANTS: Three hundred seventy-two men and women, aged 66 to 75 years, born and still living in Sheffield, England. METHODS: The Lens Opacities Classification System (LOCS) III was used to grade nuclear, cortical, and posterior subcapsular lens opacities. Fasting blood samples were taken to assess plasma concentrations of vitamin C, vitamin E, alpha-carotene, beta-carotene, lycopene, lutein, zeaxanthin, and beta-cryptoxanthin. MAIN OUTCOME MEASURES: Logistic regression analyses of the associations between plasma vitamin concentrations and cataract subtype, adjusting for age, gender, and other risk factors. RESULTS: After adjustment for age, gender, and other risk factors, risk of nuclear cataract was lowest in people with the highest plasma concentrations of alpha-carotene (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.3-0.9, P for trend 0.006) or beta-carotene (OR, 0.7; 95% CI, 0.4-1.4, P for trend 0.033). Risk of cortical cataract was lowest in people with the highest plasma concentrations of lycopene (OR, 0.4; 95% CI, 0.2-0.8, P for trend 0.003), and risk of posterior subcapsular cataract was lowest in those with higher concentrations of lutein (OR, 0.5; 95% CI, 0.2-1.0, P for trend 0.012). High plasma concentrations of vitamin C, vitamin E, or the carotenoids zeaxanthin and beta-cryptoxanthin were not associated with decreased risk. CONCLUSIONS: These findings suggest that a diet rich in carotenoids may protect against cataract development, but because they are based on observational data, they need to be confirmed in randomized controlled trials.

Aged↗
PubMed2001

The impact of fetal size and length of gestation on 6-sulphatoxymelatonin excretion in adult life.

Recent studies have shown that intrauterine growth retardation or fetal distress in human infants is associated with a pronounced reduction in melatonin secretion during the first 3 months of life. It is not known whether these associations persist beyond infancy. We have therefore examined the relationship between birthsize and melatonin secretion in 159 men and women aged 20, born in Adelaide, South Australia. Melatonin secretion was estimated by analysing the overnight urinary excretion of 6-sulphatoxymelatonin. The overnight excretion ranged from 1.7 to 128.9 nmoles/subject, was higher in women than in men (46.5 vs 34.1 nmoles, P = 0.003) and was significantly negatively correlated with the body mass index (P = 0.006). Excretion correlated with both birthweight and ponderal index at birth (P = 0.04 and P = 0.01 respectively after adjustment for gestational age) and also fell with increased duration of gestation (P = 0.007). The effects of adult body mass index added to that of low birthweight in predicting 6-sulphatoxymelatonin excretion. These data suggest that urinary 6-sulphatoxymelatonin excretion was impaired in adults who were growth restricted prenatally or were delivered after 40 weeks gestation.

Adult↗
PubMed2001

Intracellular pH, intrauterine growth and the insulin resistance syndrome.

Defects of both sodium-hydrogen exchange (NHE) and sodium-lithium countertransport (SLC) have been described in subjects at increased risk of coronary heart disease (CHD). Sodium transport is linked to the regulation of cell volume, intracellular pH and cell growth, which may explain aspects of this association. However, impaired growth in early life is also linked to adult CHD, and 'programmed' alterations of cell behaviour are postulated to be responsible for this. In this study, therefore, we examined whether NHE or SLC in adults are predicted by anthropometric measures at birth, as well as being associated with insulin resistance syndrome (IRS) variables in adulthood. Red cell SLC was measured in 26 adults, and NHE in dermal fibroblasts from another 15 subjects characterized anthropometrically at birth. SLC activity correlated with LDL cholesterol, triglycerides and urate (r=0.42 - 0.49; 0.05 > P>0.01), but not birth anthropometry. NHE V(max) correlated with plasma insulin (r=0.80; P<0.001), but birth weight was unrelated to V(max), K(m) or Hill coefficient for H(i)(+). However, pH(i) correlated with birth weight (r=0.74; P=0.002), insulin sensitivity (r=0.52; P<0.05), fasting glucose (r=-0.52; P<0.05) 2 h insulin (r=0.51; P<0.05) 2 h glucose (r=-0.54; P<0.05). In conclusion, red cell SLC is related to IRS variables, but not with birth weight measures. In contrast, low intracellular pH(i) is related to both low birth weight and adult insulin resistance, suggesting it might be a 'programmed' cell phenotype, although this is not apparently explained by altered NHE kinetics.

Anthropometry↗
PubMed2001

Fetal growth and programming of the hypothalamic-pituitary-adrenal axis.

1. Epidemiological studies have shown that small size at birth is associated with an increased risk of coronary heart disease and its risk factors, including hypertension and type 2 diabetes. 2. It is suggested that these observed links between low birthweight with disease result from an imbalance between fetal nutrient demand and supply. This imbalance results in metabolic and endocrine adaptations that benefit the fetus in the short term by reducing fetal growth and increasing fuel availability but, in the longer term, are maladaptive, leading to an increased risk of coronary heart disease. 3. Experimental data in animals and recent human observations have suggested that an alteration in the set point of the hypothalamic-pituitary-adrenal axis is an important long-term change that occurs in association with reduced fetal growth. 4. These data raise the possibility that the nature and amplitude of the stress response may be determined by intra-uterine factors.

Animals↗
PubMed2001

Associations of micro-albuminuria with intra-uterine growth retardation.

BACKGROUND/AIM: Micro-albuminuria is associated with insulin resistance and a high blood pressure and predicts an increased risk of cardiovascular disease in both diabetic and non-diabetic populations. Relationships have been described for micro-albuminuria with both low birth weight and short stature in adulthood. We have tested the hypothesis that micro-albuminuria in non-diabetic adults may be associated with markers of intra-uterine growth retardation. METHODS: We measured the urinary albumin excretion rate in 818 men and women from three populations, in whom detailed records of birth weight were available, of whom 354 had records of length at birth to provide an estimate of the ponderal index. RESULTS: The albumin excretion rates were higher in men than in women (5.1 vs. 3.8 microg/min) and were related to age (r = 0.23, p < 0.001) and body mass index (r = 0.08, p = 0.02) as well as fasting plasma glucose and blood pressure. Considered as a continuous variable, the albumin excretion rate was not related to any measure of size at birth or to adult height. Fifty-four subjects (6.6%) were micro-albuminuric (albumin excretion rate > or = 20 microg/min), and these subjects were thinner at birth than normo-albuminuric subjects (12.9 vs. 13.8 oz/in3, p = 0.09). Compared to those subjects whose ponderal index had been in the upper third of the distribution, people whose ponderal index had been in the lower third of the distribution had an odds ratio for micro-albuminuria of 3.1 (p for trend 0.05). CONCLUSION: The association between micro-albuminuria, insulin resistance, and coronary heart disease may be a consequence of growth retardation representing a common antecedent.

Age Factors↗
PubMed2001

Altered control of cortisol secretion in adult men with low birth weight and cardiovascular risk factors.

It has been suggested that increased activity of the hypothalamic-pituitary-adrenal axis may link low birth weight with subsequent development of cardiovascular risk factors and disease. Two hundred and five men, aged 66-77 yr, who were born and still live in East Hertfordshire underwent an overnight very low dose (0.25 mg) dexamethasone suppression test followed by a low dose 1-microgram ACTH-(1-24) stimulation test. A 24-h urine sample was collected for analysis of cortisol metabolites by gas chromatography/electron impact mass spectrometry. Men with lower birth weight had enhanced responses of plasma cortisol to ACTH-(1-24) (P = 0.03), increased total urinary cortisol metabolite excretion (after adjustment for confounding effects of increased obesity and lean body mass in high birth weight men; P = 0.04), but no difference in plasma cortisol after dexamethasone. Features of the metabolic syndrome were independently associated with enhanced adrenal responsiveness to ACTH-(1-24) (raised blood pressure, P = 0.02; glucose intolerance, P = 0.09; hypertriglyceridemia, P = 0.02), with trends to increased urinary cortisol metabolite excretion, but not with differences in plasma cortisol after dexamethasone. Men with low birth weight and/or the metabolic syndrome have increased activity of the hypothalamic-pituitary-adrenal axis. This may be an important mechanism underpinning the effects of events in early life on later cardiovascular disease.

Aged↗
PubMed2001

Elevated plasma cortisol in glucose-intolerant men: differences in responses to glucose and habituation to venepuncture.

Recent evidence suggests that variations in cortisol activity within the physiological range contribute to associations between multiple cardiovascular risk factors. Plasma cortisol measurements during a glucose tolerance test differ in men with hypertension, insulin resistance, and glucose intolerance, but it is unclear whether this reflects altered responses of cortisol to glucose, altered circadian rhythm, or altered habituation to multiple sampling. We performed a single-blind randomized cross-over study comparing 75 g oral glucose with placebo in 39 fasted men (22 glucose intolerant and 17 controls) aged 68-77 yr. In all subjects, plasma cortisol fell during the glucose tolerance test. Subjects with glucose intolerance had significantly higher plasma cortisol following placebo (P = 0.001), suggesting an altered circadian rhythm. Treatment with an oral glucose load blunted the circadian fall in plasma cortisol (P = 0.002), but this response was no different in controls or glucose intolerant subjects. In addition, 0900 h plasma cortisol was higher in the first study phase in controls (P = 0.01) but not in glucose-intolerant subjects (P = 0.18), who showed a lack of habituation to repeated plasma measurements. These data support the hypothesis that alterations in central regulation of the hypothalamic-pituitary-adrenal axis may be important in glucose intolerance.

Aged↗
PubMed2001

Regulation of glucocorticoid receptor alpha and beta isoforms and type I 11beta-hydroxysteroid dehydrogenase expression in human skeletal muscle cells: a key role in the pathogenesis of insulin resistance?

Glucocorticoid excess frequently results in obesity, insulin resistance, glucose intolerance, and hypertension and may be the product of altered glucocorticoid hormone action. Tissue sensitivity to glucocorticoid is regulated by the expression of glucocorticoid receptor isoforms (GRalpha and GRbeta) and 11beta-hydroxysteroid dehydrogenase type I (11betaHSD1)-mediated intracellular synthesis of active cortisol from inactive cortisone. We have analyzed the expression of GRalpha, GRbeta, and 11betaHSD1 and their hormonal regulation in skeletal myoblasts from men (n = 14) with contrasting levels of adiposity and insulin resistance. Immunohistochemical, Northern blot, and Western blot analysis indicated abundant expression of GRalpha and 11betaHSD1 under basal conditions. The apparent K(m) and maximum velocity for the conversion of cortisone to cortisol were 440 +/- 14 nmol/L and 75 +/- 7 pmol/mg protein.h and 437 +/- 16 nmol/L and 33 +/- 6 pmol/mg protein.h (mean +/- SEM; n = 4) in the presence and absence of 20% serum. Incubation of myoblasts with increasing concentrations of glucocorticoid (50-1000 nmol/L) resulted in a dose-dependent decline in GRalpha expression and a dose-dependent increase in GRbeta expression. 11betaHSD1 activity was sensitively up-regulated by increasing concentrations of glucocorticoid (50-1000 nmol/L: P < 0.05). Abolition of these effects by the GR antagonist, RU38486, indicates that regulation of GRalpha, GRbeta, and 11betaHSD1 expression is mediated exclusively by the GRalpha ligand-binding variant. In contrast, 11betaHSD1 was down-regulated by insulin (20-100 mU/mL: P < 0.01) in the presence of 20% serum, whereas incubation with insulin under serum-free conditions resulted in a dose-dependent increase in 11betaHSD1 activity (P < 0.05). Incubation with insulin-like growth factor I resulted in a similar pattern of 11betaHSD1 activity. Although neither testosterone nor androstenedione (5-200 nmol/L) affected 11betaHSD1 activity, incubation of myoblasts with dehydroepiandrosterone (500 nmol/L) resulted in a decline in 11betaHSD1 activity (P < 0.05). These data suggest that glucocorticoid hormone action in skeletal muscle is determined principally by autoregulation of GRalpha, GRbeta, and 11betaHSD1 expression by the ligand-binding GRalpha isoform. Additionally, insulin and insulin-like growth factor I regulation of 11betaHSD1 may represent a novel mechanism that maintains insulin sensitivity in skeletal muscle tissue by diminishing glucocorticoid antagonism of insulin action.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2001

Fetal growth and the fetal origins hypothesis in twins--problems and perspectives.

Although there is substantial evidence from studies of singletons that small size at birth is linked with long-term adverse health effects, until recently little was known as to whether these associations extend to twins. A review of published studies suggests that at present there is little consistent evidence that birthsize in twins is associated with increased morbidity or morality. While, these findings may reflect methodological limitations, it is also argued that they arise as a consequence of the substantially different biology of fetal growth in twins.

Birth Weight↗
PubMed2001

Relation between size at birth and age-related cataract.

PURPOSE: To determine whether poor fetal growth, as determined by size at birth, is associated with an increased risk of age-related cataract. METHODS: A total of 741 men and women born in Sheffield, England between 1922 and 1930 and whose size at birth was available were traced and invited to take part in the study. Of these, 392 (53%) attended for ophthalmic examination. Lens opacity in these volunteers was graded using the Lens Opacities Classification System (LOCS) III. RESULTS: After adjusting for age, gender, gestational age, and risk factors for cataract there were no consistent associations between size at birth and age-related cataract. However, the odds ratio for nuclear cataract (opalescence) among subjects whose birth weight was more than 8 lb was 2.4 (95% CI 1.2 to 5.0) compared with those who weighed under 6 lb 12 oz at birth. Risk of cortical cataract by contrast fell with increasing birth weight, but the trend was not significant and became weak after adjusting for gestational age and other risk factors for cataract. No relation was evident between risk of posterior subcapsular cataract and size at birth. CONCLUSIONS: There is no consistent association between size at birth and age-related cataract. The higher risk of nuclear cataract with increased birth weight was contrary to the expected trend. The apparent difference in direction of the relation between birth weight and different subtypes of cataract may be a chance finding but warrants further exploration.

Aged↗
PubMed2000

Birth weight, climate at birth and the risk of obesity in adult life.

OBJECTIVE: To determine whether obesity in adults is related to seasonal or climatic conditions around the time of birth. SUBJECTS: 1750 men and women born in Hertfordshire between 1920 and 1930. MEASUREMENTS: Height and weight measured in the home by trained fieldworkers. RESULTS: Body mass index (BMI) rose with increasing birth weight in men and women. In men, BMI and the prevalence of obesity (BMI > or = 30 kg/m2) varied as a function of month of birth and was greater among those born in January-June than among those born in July-December. The relationship between birth weight and adult obesity was also stronger in those born in the first 6 months of the year or following cold winters than in those born in the last 6 months of the year or following mild winters. CONCLUSIONS: These findings suggest that adult obesity is linked both to high birth weight and to early cold exposure. Consequently, exposures in early life may contribute to individual variation in susceptibility to obesity in adults.

Adult↗