D. I. W. Phillips
Southampton General Hospital
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by D. I. W. Phillips.
Diabetologia | 1996
D. I. W. Phillips
Impaired tissue sensitivity to the action of insulin (insulin resistance) is a major abnormality underlying non-insulin-dependent diabetes mellitus (NIDDM). Insulin resistance is also associated with hypertension and dyslipidaemia, and may be an important and preventable cause of heart disease [1]. Although influenced by ageing, obesity, physical inactivity and certain drugs, current opinion holds that insulin resistance is hereditary in origin. Recent evidence, however, suggests a new hypothesis that insulin resistance may occur as a consequence of the persistence of a fetal response to undernutrition. It is suggested that the undernourished fetus makes metabolic adaptations from which it benefits in the short term by increasing fuel availability but that these adaptations become permanently programmed and persist throughout life.
Diabetologia | 2001
Janis Baird; Clive Osmond; Alex J. MacGregor; Harold Snieder; C. N. Hales; D. I. W. Phillips
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. [Diabetologia (2001) 44: 33–39]
Journal of Clinical Pathology | 2000
Christopher D. Byrne; D. I. W. Phillips
The past 10 years have provided unequivocal evidence that there are associations between birth size measures and future development of adult diseases, such as type 2 diabetes and coronary artery disease. Despite initial concern that bias or residual confounding in the analyses had produced these rather bizarre associations, the findings have now been reproduced in different cohorts by independent investigators from many parts of the world. The challenge for the next decade must be to discover the cellular and molecular mechanisms giving rise to these associations. If this aim is accomplished, it might be possible to devise strategies to reduce the impact of these disabling, chronic, and expensive diseases. The purpose of this review is to describe some of the relevant, important, and more recent epidemiological studies, and also to discuss potential mechanisms underpinning the associations.J Clin Pathol(J Clin Pathol 2000;53:822–828)
Diabetologia | 1995
Doris J. Taylor; C. H. Thompson; Graham J. Kemp; P. R. J. Barnes; Alison L. Sanderson; George K. Radda; D. I. W. Phillips
SummaryThinness at birth is associated with insulin resistance and an increased prevalence of non-insulin-dependent diabetes mellitus in adult life. As muscle is an important site of insulin resistance, and because thin babies have reduced muscle mass, thinness at birth may affect muscle structure and function and impair carbohydrate metabolism. We have therefore used 31P magnetic resonance spectroscopy to investigate the bioenergetics of gastrocnemius and flexor digitorum superficialis muscles in 16 normoglycaemic women who had a low (≤ 23 kg/m3) and 9 women who had a high (>23 kg/m3) ponderal index at birth. In the flexor digitorum superficialis study anaerobic metabolism was stressed with a constant heavy workload. Low ponderal index subjects fatigued more rapidly (3.3 vs 5.8 min); as phosphocreatine decreased, the accompanying drop in muscle pH was less than in the high ponderal index group. In the first minute of exercise phosphocreatine fell and adenosine diphosphate rose more rapidly (p=0.04 and 0.03, respectively). Gastrocnemius showed a similar trend late in exercise (this exercise was more oxidative, becoming more anaerobic with increasing workload). These changes were not explained by differences in body composition, muscle mass or blood flow. The findings are consistent with a decreased lactic acid and glycolytic adenosine triphosphate production in the low ponderal index group and suggest the possibility that the mechanisms which control substrate utilisation and metabolism in adult life be programmed during prenatal life.
Diabetologia | 2004
Elaine M. Dennison; Holly E. Syddall; Avan Aihie Sayer; S. Craighead; D. I. W. Phillips; C Cooper
Aims/hypothesisPrevious studies have suggested that the high bone density often observed in type 2 diabetic patients may be explained by insulin resistance. We explored this hypothesis in the Hertfordshire Cohort Study.MethodsA total of 465 men and 444 women aged 59 to 71 years and with no prior diagnosis of diabetes attended a clinic where a glucose tolerance test was performed and bone density measured at the femoral neck and lumbar spine. Biochemical markers of bone turnover (serum osteocalcin and urinary mean c-terminal cross-linking telopeptide of type II collagen) were measured in 163 men.ResultsAccording to WHO criteria, 83 men and 134 women were diagnosed with impaired glucose tolerance and a further 33 men and 32 women were diagnosed as having type 2 diabetes. Bone density was higher in newly diagnosed diabetic subjects, with relationships stronger in women (p<0.001) than men (p<0.05) and attenuated by adjustment for body mass index. In both sexes, we observed positive correlations between the total femur and femoral neck bone mineral density with measures of insulin resistance (r=0.17–0.22), with stronger results observed in women. These relationships did not apply after adjustment for body mass index. Glucose status did not lead to differences in osteocalcin level or c-terminal cross-linking telopeptide of type II collagen levels.Conclusions/interpretationOur findings suggest that hyperinsulinaemia may affect bone mineral density through indirect effects, e.g. body weight.
Diabetic Medicine | 2009
Richard I. G. Holt; D. I. W. Phillips; K Jameson; C Cooper; Elaine M. Dennison; Robert Peveler
Aims To assess the relationship between depression scores and diabetes, glucose and insulin in a cross‐sectional population‐based study.
Clinical Endocrinology | 1985
D. I. W. Phillips; D. J. P. Barker; B. Rees Smith; Suzanne Didcote; Dilys Morgan
In a prospective study of the incidence of thyrotoxicosis sera from 216 thyrotoxic patients in seven English towns were assayed for TSH‐receptor antibodies. The incidence of antibody negative thyrotoxicosis correlated closely with the previous prevalence of endemic goitre in the towns (r= 0·9) indicating a high current incidence of toxic nodular goitre in previously goitrous towns. Antibody positive thyrotoxicosis, an indicator of Graves’ disease, showed no correlation with goitre although there was statistically significant geographical variation in incidence. The percentage of all thyrotoxic patients who were antibody positive varied between towns, from 35% to 92%.
Calcified Tissue International | 2004
Elaine M. Dennison; Holly E. Syddall; Caroline H.D. Fall; M K Javaid; N K Arden; D. I. W. Phillips; C Cooper
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 performed 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 < 0.000l; 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.
The Lancet | 1995
D. J. P. Barker; P D Winter; Clive Osmond; D. I. W. Phillips; H.Y. Sultan
The geographic association between ovarian cancer and tall stature suggests a link with rapid growth in early childhood. Among 5585 women born in Hertfordshire, UK, 41 who died from ovarian cancer had had a high rate of weight gain in infancy. Whereas their mean birthweight was the same as that of the other women, their mean weight at 1 year was higher (22.3 pounds [10.1 kg] vs 21.4 pounds [9.7 kg], p = 0.01). These observations are consistent with the hypothesis that ovarian cancer is linked to altered patterns of gonadotropin release established in utero when the fetal hypothalamus is imprinted.
Journal of Human Hypertension | 2007
Kimmo Feldt; Katri Räikkönen; Johan G. Eriksson; Sture Andersson; Clive Osmond; D. J. P. Barker; D. I. W. Phillips; Eero Kajantie
The relationships of body size and gestational age at birth with adult blood pressure (BP) are relatively modest compared to their stronger associations with cardiovascular disease. BP reactivity is a strong predictor of cardiovascular morbidity, and it is possible that reactivity, rather than resting level, is determined in utero. We investigated whether body size and gestational age at birth predict BP reactivity during experimentally induced psychosocial stress in late adulthood. A total of 73 men and 80 women born after 36 weeks’ gestation in Helsinki, Finland, during 1934–1944 underwent the Trier Social Stress Test (TSST); a standardized psychosocial stress test consisting of a public speech and an arithmetic task. Changes in BP were monitored continuously by a non-invasive finger photoplethysmography (Finometer, FMS, Amsterdam, The Netherlands). The results showed that the most robust early determinant of BP reactivity was gestational age; however, with opposite relationships between the sexes (P for interaction <0.001). A 1-week increase in gestational age was associated with a 3.1 mm Hg (95% confidence interval (CI), 0.2 to 6.0) and 1.2 mm Hg (95% CI, −0.1 to 2.6) decreases in systolic and diastolic BP reactivity in women, but with 5.2 mm Hg (95% CI, 1.9 to 8.4) and 2.3 mm Hg (95% CI, 0.9 to 3.8) increases in men. In conclusion, normal variation in gestational age at birth predicts cardiovascular stress reactivity in later adulthood. Given that hypothalamic–pituitary–adrenal axis contributes to the regulation of autonomic nervous system function and the timing of parturition, and shows well-established sex differences, we speculate a role for early programming of this axis in explaining the findings.