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P Betts

Publications and source records attributed to P Betts.

At least 19 recordsLinked to original sources
PubMed2005

Increasing body weight predicts the earlier onset of insulin-dependant diabetes in childhood: testing the 'accelerator hypothesis' (2).

AIMS AND METHODS: It has recently been hypothesized that weight gain in childhood accelerates the onset of Type 1 diabetes, as well as increasing its risk, and that Type 1 diabetes and Type 2 diabetes may be one and the same disorder of insulin resistance. An explanation is needed for the rising incidence of childhood diabetes and, to test the Accelerator Hypothesis, we examined the anthropometric measurements recorded from birth in 168 young people presenting with Type 1 diabetes between 1980 and 2002. Pre-onset as well as peri- and post-onset measurements of height and weight were available, and waist circumference was recorded at various intervals after onset. RESULTS: The mean birth weight of the children and their height, weight and body mass index (BMI) at diagnosis lay close to the population mean. However, pre-onset and post-onset BMI were both well above the population mean, were closely correlated with each other (r = 0.79, P < 0.001) and (inversely) with age at onset (r = -0.30, P < 0.001). A significant correlation was also found between BMI standard deviation scores (sds) and year of diagnosis (r = 0.27, P < 0.001) and, importantly, waist circumference sds in the children with Type 1 diabetes was found to be substantially greater than average for the population [boys: +0.96 (sd 1.04), girls: +1.30 (sd 0.89)]. CONCLUSIONS: The data suggest that children with Type 1 diabetes have become progressively heavier at diagnosis over the past 20 years, and that the heavier child develops it earlier. Waist circumference, a proxy for visceral fat mass and insulin resistance, is substantially greater in children with Type 1 diabetes. Weight centile crossing appears to be an important environmental accelerator which may contribute to or account for the striking increase in both Type 1 diabetes and Type 2 diabetes in childhood. A reduction of body weight and improved lifestyle might reverse this trend in both types of diabetes.

Age of Onset↗
PubMed2004

Congenital hypothyroidism and apparent athyreosis with compound heterozygosity or compensated hypothyroidism with probable hemizygosity for inactivating mutations of the TSH receptor.

OBJECTIVE: We wished to ascertain whether mutations in the TSH receptor (TSHR) gene were present in two siblings with congenital hypothyroidism with no parental consanguinity. DESIGN: The pituitary-thyroid axis and thyroid gland morphology were investigated in both affected siblings and their parents. The TSHR gene was analysed in each subject. MEASUREMENTS: Basal thyroid function together with circulating thyroglobulin levels were measured in each subject. In addition, a TRH stimulation test was undertaken in each parent. All family members underwent thyroid ultrasonography. The TSHR gene was amplified from genomic DNA using the polymerase chain reaction and receptor mutations were identified by sequence analysis. RESULTS: Two siblings were diagnosed with severe congenital hypothyroidism (total T4 19-21 nmol/l, TSH 160-230 mU/l on neonatal screening). Although radioiodine scanning showed no tracer uptake and ultrasound imaging in both individuals failed to demonstrate thyroid tissue, suggesting complete athyreosis, circulating thyroglobulin levels were measurable. The thyroid status of the parents was discordant: in the father, baseline thyroid function (FT4 13 pmol/l, TSH 4 mU/l), the peak TSH level after TRH stimulation (30 mU/l) were normal and he exhibited an appropriate rise in circulating thyroid hormones in response to the elevated TSH; in contrast, in the mother, baseline thyroid function was abnormal (FT4 10 pmol/l, TSH 15 mU/l), the TSH response to TRH was exaggerated (110 mU/l), with no subsequent rise in circulating thyroid hormones. An eutopic, slightly hypoplastic thyroid gland was visualized on ultrasonography in the mother and her thyroid antibody status was negative. Both children were compound heterozygotes for missense (alanine to threonine at codon 553, A553T) and premature stop (tryptophan at codon 546, W546X) mutations in the fourth transmembrane domain of the TSH receptor. The mother and father were heterozygous for W546X and A553T mutations, respectively. Each mutation is known to abolish the function or cellular surface expression of the TSH receptor. CONCLUSIONS: Inactivating mutations in the TSH receptor can be associated with severe TSH resistance presenting as congenital hypothyroidism with apparent athyreosis. Our observations also suggest that heterozygosity for an inactivating TSHR mutation may be associated with compensated hypothyroidism and thyroid hypoplasia.

Congenital Hypothyroidism↗
PubMed2004

Personality functioning: the influence of stature.

BACKGROUND: The Wessex Growth Study has monitored the psychological development of a large cohort of short normal and average height control participants since school entry. AIMS: To examine the effect of stature on their personality functioning now that they are aged 18-20 years. METHODS: This report contains data from 48 short normal and 66 control participants. Mean height SD score at recruitment was: short normals -2.62 SD, controls -0.22 SD. Final height SD score was: short normals -1.86, controls 0.07. The Adolescent to Adult Personality Functioning Assessment (ADAPFA) measures functioning in six domains: education and employment, love relationships, friendships, coping, social contacts, and negotiations. RESULTS: No significant effect of recruitment height or final height was found on total ADAPFA score or on any of the domain scores. Socioeconomic status significantly affected total score, employment and education, and coping domain scores. Gender had a significant effect on total score, love relationships, coping, and social contacts domain scores. Salient aspects of daily living for this sample were identified from the interviews (prevalence%): consuming alcohol (94%), further education (63%), love relationships (55%), current drug use (29%), experience of violence (28%), parenthood (11%), and unemployment (9%). Stature was not significantly related to behaviour in any of these areas. CONCLUSIONS: Despite previously reported links between short stature and poorer psychosocial adaptation, no evidence was found that stature per se significantly affected the functioning of the participants in these areas as young adults.

Adolescent↗
PubMed2001

Longitudinal study of urinary albumin excretion in young diabetic patients--Wessex Diabetic Nephropathy Project.

AIMS: This study was established to follow changes in albumin/creatinine ratio (ACR) and to determine the prevalence and degree of progression of microalbuminuria (MA) or of clinical proteinuria (CP) in children with Type 1 diabetes. The study has investigated subjects for up to 12 years in establishing the correlation between MA and gender, age, duration of diabetes and glycated haemoglobin (HbA1c). The study has defined clinical cut-offs for MA in daytime clinic urine samples in young diabetic subjects. METHODS: Three hundred and sixty-one patients were involved in the study, with 221 (61.2%) having over six sets of data. Urine samples were collected at routine annual clinic visits and analysed without prior freezing for ACR. Blood samples were taken for HbA1c measurement. Data including sex, age and duration of diabetes were recorded. RESULTS: A random clinic ACR of < 4.5 mg/mmol (males) and 5.2 mg/mmol (females) creatinine was used as the 'clinical cut-off' to define the presence of MA. The presence of MA was independent of HbA1c and duration of diabetes but appeared be associated with the adolescent years (> 10 years). There was little evidence of progression from normoalbuminuria to MA, or from MA to CP. Of patients aged 10-18 years, 30.9% of males and 40.4% of females had one or more episodes of MA. CONCLUSIONS: Persistent MA and random episodes of MA or CP may be associated with the adolescent years but not with duration of diabetes. Further study will reveal if the substantial increases in ACR sometimes seen during adolescence are predictive of diabetic nephropathy. Clinical cut-offs of < 4.5 and < 5.2 mg/mmol creatinine for males and females, respectively, are suggested for the interpretation of changes in ACR in random urine samples in young people with Type 1 diabetes.

Adolescent↗
PubMed2001

A multicentre trial of recombinant growth hormone and low dose oestrogen in Turner syndrome: near final height analysis.

BACKGROUND: Turner syndrome accounts for 15-20% of childhood usage of growth hormone (GH) in the UK but final height benefit remains uncertain. The most effective strategy for oestrogen replacement is also unclear. METHODS: Fifty eight girls who, at start of treatment, were of mean age 9.1 years and projected final height 142.2 cm were randomised to receive in year 1, either low dose ethinyloestradiol 50-75 ng/kg/day, GH 28 IU/m(2) surface area/week as a daily injection, or a combination of ethinyloestradiol and GH. After the first year, the ethinyloestradiol treated girls received combination treatment. After two years, girls aged over 12 years were given escalating ethinyloestradiol to promote pubertal development. RESULTS: Near final height was available for 49 girls at age 16.5 years, 146.8 cm, representing a gain of 4.6 cm, range -7.9 to +11.7 cm. Twelve of the 49 girls gaining 7.5 cm or more were less than 13 years at the start and had received GH for at least four years. Height gain was correlated with greater initial height deficit. Fifteen girls (31%) reached 150 cm or more compared to a predicted 10%. Early supplementation with ethinyloestradiol provided no final height advantage. CONCLUSIONS: Final height gain was modest at 4.6 cm. Younger, shorter girls gained greatest height advantage from GH. Low dosage ethinyloestradiol before planned induction of puberty was not beneficial.

Adolescent↗
PubMed1997

Early infection and subsequent insulin dependent diabetes.

In a study of 58 children under the age of 16 with insulin dependent diabetes (IDDM) and 172 matched non-diabetic controls, infection during the first year of life was associated with a reduction in diabetes risk (odds ratio 0.81, 95% confidence interval 0.67 to 0.98, per infective episode). Decreased exposure to common infections during infancy may be linked with subsequent IDDM.

Adolescent↗
PubMed1992

Autoantibodies to endogenous growth hormone in short children (the Wessex Growth Study).

Small stature is associated with low growth hormone secretion, but in most cases the reason is unknown. The commonest cause of hormone insufficiency is autoimmunity, and autoantibodies to hormones are often found where there is autoimmune disease of the corresponding gland. Displaceable growth hormone binding by the sera of 125 short (< 3rd centile) but otherwise normal school entrants was significantly higher (P < 0.05) than by the sera of 100 age-matched children of normal height (10th-90th centile), and binding in 21 (17%) of the small children exceeded the upper limit of 95% of the normal population. Furthermore, urinary growth hormone excretion was significantly lower in the small children (total overnight output 0.6-1.7 ng) compared with controls (1.5-3.7 ng) (P < 0.05) even when corrected for body surface area. Thus, growth hormone binding and growth hormone excretion discriminated between two groups of children selected only on the basis of height. The assay used for growth hormone binding was specific for IgG, suggesting that the binding factor was antibody. Autoimmunity merits further investigation as a basis for poor growth.

Autoantibodies↗
PubMed1989

The Wessex Growth Study: first report.

The Wessex Growth Study is a community-based longitudinal survey of short children recruited from two Health Districts in Wessex during 1985-86 (cohort I) and 1986-87 (cohort II). Screening of new school entrants during 1985-86 identified only 1.3% who were at or below the 3rd centile for height as defined by Tanner and Whitehouse, suggesting a strong secular trend and an urgent need for updated height charts. After exclusion of the small number of children with underlying organic pathology and those from ethnic minorities, there were 84 children in cohort I on whom this report is based. These apparently normal, short children were sex- and age-matched with normal controls (10th-90th centile) from the same school class. Forty-two per cent of cohort I had a delayed bone age, and 34% lay above the 3rd centile after correction for parental height. Forty-four per cent were of low birth weight. The correlation between two successive height velocities measured at 6 and 12 months was only -0.14 for cohort I and -0.15 for their controls. Twelve-month mean height velocity SD scores (SDS) were -0.45 and +0.25, respectively, corresponding to the 33rd and 60th centiles, and rather higher than the 25th and 50th centiles expected in view of the heights of these children. Thirty-eight per cent of cohort I had a 12-month height velocity below the 25th centile, and in 16% height velocity was below the 10th centile. As a group, the children in cohort I grew more slowly than their controls, but the height velocity in 88% of cases lay within the control range.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Determination by Skeleton↗
PubMed1989

A bloodspot androstenedione assay suitable for home-monitoring of steroid replacement therapy in congenital adrenal hyperplasia.

A bloodspot assay has been developed using an antiserum raised against androstenedione-3-carboxymethyloxime-bovine serum albumin (AD-3CMO-BSA) conjugate and 125I-AD-3CMO-histamine tracer. The method has a detection limit of 0.6 nmol/L blood and a working range from 0.6 to 40 nmol/L blood. The between-batch precision ranged from 8.4% to 23.3%. Bloodspot androstenedione (AD) concentrations were measured in 50 neonates (26 male, 24 female) and in 95 children (54 male, 41 female) aged 6 months to 18 years. No sex difference in concentrations was found in neonates, in pre-pubertal children up to 8 years of age, in pubertal children (males 8-16 years, females 8-14 years) or post-puberty. Bloodspot AD concentrations ranged from less than 0.6 to 2.7 nmol/L in neonates, less than 0.6 nmol/L in pre-pubertal children, 0.6-2.1 nmol/L in pubertal children and less than 0.6-4.6 nmol/L post-puberty. Daytime bloodspot profiles in 10 children on replacement therapy for congenital adrenal hyperplasia generally showed good correlation between 17 alpha-hydroxyprogesterone and AD concentrations (r = 0.928, P less than 0.001). Bloodspot AD profiles have advantages over 17 alpha-hydroxyprogesterone profiles for the assessment of the adequacy of glucocorticoid replacement therapy.

17-alpha-Hydroxyprogesterone↗
PubMed1988

On the relationship between islet cell antibodies and insulin autoantibodies in patients at risk from insulin dependent diabetes.

The frequencies of islet cell antibodies (ICA) and insulin autoantibodies (IAA) were studied in three clinically well defined groups, using an aprotinin sensitised indirect immunofluorescence assay for ICA and a direct binding solid ELISA for IAA, and the association of these two serological markers for insulin dependent diabetes analysed. Frequency of ICA was 10.7% in siblings of diabetics, 15.5% in discordant identical twins and 65.9% in newly diagnosed diabetic patients. Frequency of IAA was 7.1% in siblings, 46.7% in discordant twins and 38.6% in newly diagnosed diabetic patients. No correlation was demonstrated between the two autoantibodies in the siblings. In the newly diagnosed diabetic patients there were sera positive or negative for both, but 22 (50%) of the sera showed dissociation between the two antibodies. The studies of twins showed that IAA and ICA fluctuated independently with time, and demonstrate the inappropriateness of seeking such an association in cross-sectional surveys. An association could not be demonstrated in this group even if data from multiple samples taken at different points in time were pooled, scoring an individual as positive if at any time their sera had been positive for the corresponding antibody. Thus our data showed no correlation between ICA and IAA in any of the groups studied.

Adolescent↗
PubMed1986

The interpretation of bloodspot 17 alpha-hydroxyprogesterone levels in term and pre-term neonates.

Bloodspot 17 alpha-hydroxyprogesterone, plasma cortisol, plasma sodium and urinary 17 alpha-hydroxyprogesterone, cortisol, sodium and creatinine levels were determined in 24 term and 32 pre-term infants on the third, eighth and fourteenth days of life. Pre-term infants, whether 'well' or 'sick', had significantly raised bloodspot 17 alpha-hydroxyprogesterone levels (up to 158 nmol/L) compared with those found in term infants (up to 18.8 nmol/L). Urinary 17 alpha-hydroxyprogesterone creatinine ratios were also higher in pre-term infants. Plasma cortisol results showed similar ranges for term and pre-term infants, and bloodspot 17 alpha-hydroxyprogesterone/plasma cortisol ratios for day 3 specimens correlated with the degree of prematurity. These results may be due either to immature enzyme systems in the pre-term baby or to an excess of related steroids cross-reacting in the 17 alpha-hydroxyprogesterone assay. We propose the use of two distinct upper limits of normal of 20 nmol/L (term infants) and 200 nmol/L (pre-term infants), for the interpretation of bloodspot 17 alpha-hydroxyprogesterone levels at the end of the first week of life.

17-alpha-Hydroxyprogesterone↗
PubMed1984

Effect of glycaemic control and duration of disease on overnight albumin excretion in diabetic children.

Urine albumin excretion rates were measured in overnight timed samples from diabetic and non-diabetic schoolchildren. The excretion rates in the diabetics were significantly higher than those in the controls and were positively correlated with age, duration of diabetes, and glycaemic control. Diabetic children aged 12 years and older had significantly higher albumin excretion rates than younger diabetic children matched for duration of disease. Among the non-diabetic controls there was no correlation between albumin excretion rate and age and the girls excreted significantly more albumin than the boys. Measurement of the overnight albumin excretion rate may provide a useful early indicator of the progression to clinical proteinuria in diabetes and is free from random variations such as that due to exercise.

Adolescent↗
PubMed1984

Bloodspot 17 alpha-hydroxyprogesterone radioimmunoassay for diagnosis of congenital adrenal hyperplasia and home monitoring of corticosteroid replacement therapy.

A convenient and inexpensive radioimmunoassay for bloodspot 17 alpha-hydroxyprogesterone (17-OHP) has been evaluated in the screening of newborn infants for congenital adrenal hyperplasia (CAH) and for home monitoring of CAH patients on steroid replacement therapy. In the screening study, analysis of 491 bloodspots taken for routine screening programmes for phenylketonuria and hypothyroidism established the upper limit of normal for infants aged 5-10 days as 64 nmol 17-OHP/l blood (99.9 centile). Home monitoring of patients by examination of fingerprick bloodspot 17-OHP profiles taken by parents over Saturday and Sunday on consecutive weekends showed that changes in control occurred as a result of transition from inpatient to outpatient treatment or following adjustment of steroid replacement regimens. The method was found to be valuable in the diagnosis and management of children with CAH.

17-alpha-Hydroxyprogesterone↗
PubMed1984

Production of human chorionic gonadotrophin by a hepatoblastoma resulting in precocious puberty.

A two year old boy presented with precocious puberty associated with hepatoblastoma. Serum concentrations of beta human chorionic gonadotrophin and alpha-fetoprotein were raised. An aggressive chemotherapeutic regimen resulted in useful palliation and interesting changes in the beta human chorionic gonadotrophin and alpha-fetoprotein concentrations. In contrast to a previous report, the ultrastructure of the tumour showed frequent Golgi apparatus but no other electron dense membrane bound vesicles.

Carcinoma, Hepatocellular↗