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Biomedical subjects

D B Dunger

Publications and source records attributed to D B Dunger.

At least 127 records · Page 7Linked to original sources
PubMed1994

Variations in the management of diabetic ketoacidosis in children.

Cerebral oedema which develops during the treatment of diabetic ketoacidosis is an important cause of mortality and morbidity in children. We examined 25 management protocols from throughout the UK and related variations in fluid, bicarbonate, insulin, and potassium regimens to the incidence of cerebral oedema recalled in each centre. Treatment of shock ranged from 5 to 25 (median 20) ml kg-1 plasma (5 recommended 0.9% saline only) over 10-60 min. Subsequent fluid regimens used 0.9% saline in 24 (0.45% saline in 1); 8 used 0.45% saline if hypernatraemia was present. The rehydration period ranged from 24 h (n = 20) to 48 h (n = 1) and was based on steady (n = 12) or irregular (n = 13) replacement. The quantity of potassium added to fluids was 20-80 (median 30) mmol l-1. Eight centres recalled having seen 1-5 (median 2) cases of cerebral oedema in the past 5 yr, 10 centres recalled none. Compared with the 10 centres without cerebral oedema, protocols from the 8 with cerebral oedema used more plasma to resuscitate (22 +/- 3 (mean +/- SD) vs 18 +/- 4 ml kg-1; p < 0.025), suggested larger maintenance fluid volumes for ages 6-9 yr (81 +/- 2 vs 70 +/- 11 ml kg-1 day-1; p < 0.005) and were more likely to change to 0.18% saline when blood glucose had fallen (8/8 vs 5/10) than 0.45% saline (0/8 vs. 5/10; p < 0.05). Free water overload may contribute to cerebral oedema.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Menstrual irregularities are more common in adolescents with type 1 diabetes: association with poor glycaemic control and weight gain.

Ovarian function in post-menarchal girls with Type 1 diabetes was evaluated. Menstrual histories from 24 adolescents with Type 1 diabetes were compared with those from 24 age and sex matched controls. A fasting blood sample was obtained from subjects with Type 1 diabetes for the measurement of ovarian and adrenal sex hormones, LH and FSH, glucose and insulin, insulin-like growth factor-I (IGF-I), and insulin-like growth factor binding protein-1 (IGFBP-1); and an ovarian ultrasound scan was performed. Menstrual irregularity was more prevalent in patients with Type 1 diabetes than controls (54% vs 21%, p < 0.01) and their mean body mass index (BMI) was greater (22.3 +/- 0.5 (+/- SEM) vs 20.7 +/- 0.6 kg m-2, p < 0.05). Subjects with Type 1 diabetes with irregular menses (when compared with diabetic subjects with a regular cycle) had a significantly higher HbA1 (12.8 +/- 0.4 vs 10.5 +/- 0.5%, p < 0.01) and BMI (23.2 +/- 0.6 vs 21.4 +/- 0.6 kg m-2, p < 0.05) associated with a lower sex hormone binding globulin (SHBG) (37.2 +/- 4.0 vs 52.6 +/- 4.0 nmol l-1, p < 0.025) and IGF-I (1.4 +/- 0.2 vs 2.2 +/- 0.2 mUI-1, p < 0.025) and a higher LH:FSH ratio (2.6 +/- 0.5 vs 1.4 +/- 0.2, p < 0.05). Polycystic ovarian changes were identified in 10/13 (77%) of these patients with an irregular cycle. Menstrual irregularity is common in post-menarchal girls with Type 1 diabetes and is associated with poor glycaemic control and weight gain. The apparent high incidence of polycystic ovarian change requires further investigation.

Adolescent↗
PubMed1994

Growth during childhood and final height in type 1 diabetes.

The growth of 184 children with Type 1 diabetes was analysed using data collected prospectively in the Oxford district between 1969 and 1992. The overall mean height standard deviation score (Ht SDS +/- SD) at diagnosis was 0.35 +/- 1.05 which was significantly greater than the national standard of Tanner (1966). However, there is evidence of a secular trend in the heights of Oxford children over the last 20 years when compared with Tanner. When data from children with diabetes were compared with local controls, it was only the children aged 5-10 years at diagnosis who were taller (Ht SDS +/- SD, 0.58 +/- 1.14, versus 0.31 +/- 0.90, n = 73, p < 0.05). Those diagnosed under the age of 5 years (n = 37) were shorter (Ht SDS 0.12 +/- 0.93) and those diagnosed aged more than 10 years (n = 74) were similar in size (Ht SDS 0.22 +/- 0.98) to controls. These differences could not be explained by social class. Loss of height occurred between diagnosis and puberty, particularly in those diagnosed between the ages of 5 and 10 years. The pubertal growth spurt was blunted in all groups but this abnormality was more profound in the girls (mean peak height velocity SDS -1.09 +/- 1.02, p < 0.0005) than in the boys (mean peak height volocity SDS -0.5 +/- 1.14, p < 0.025). The mean final height SDS was -0.74 +/- 0.96 in those diagnosed < 5 years, 0.00 +/- 1.26 in those diagnosed between the ages of 5 and 10 years and 0.09 +/- 1.10 in those aged more than 10 years at diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Eating habits and attitudes of mothers of children with non-organic failure to thrive.

The eating habits and attitudes concerning body shape and weight among 26 mothers of children with non-organic failure to thrive (the index group) were studied using the eating disorder examination. They were compared with equivalent data on 26 individually matched women who participated in a large community survey. The index mothers' views of their child's weight and shape were also studied. The principal findings were, firstly, that when compared with the comparison group, mothers of children with non-organic failure to thrive had higher levels of dietary restraint. Secondly, despite their child's low weight, 50% of the index mothers were restricting their child's intake of 'sweet' foods, and a further 30% were restricting foods they considered 'fattening' or 'unhealthy'. These results raise the question of whether maternal eating habits and attitudes have a causal role in the genesis of non-organic failure to thrive. They suggest that careful inquiry about the mothers' eating habits and attitudes is needed when assessing children with non-organic failure to thrive.

Adult↗
PubMed1994

The effects of recombinant human insulin-like growth factor-I (IGF-I) administration on the levels of IGF-I, IGF-II and IGF-binding proteins in adolescents with insulin-dependent diabetes mellitus.

Insulin-dependent diabetes mellitus (IDDM) during puberty is associated with a reduction in circulating concentrations of insulin-like growth factor-I (IGF-I) and low IGF bioactivity. Altered levels of the IGF-binding proteins (IGFBPs), including low IGFBP-3 and elevated IGFBP-1, have also been described. These abnormalities have been linked to poor growth and deteriorating blood glucose control. We have therefore examined the effects of recombinant human IGF-I (rhIGF-I) administration on the levels of IGF-I, IGF-II, IGFBP-1, IGFBP-3 and IGF bioactivity in a group of 9 late-pubertal adolescents with IDDM. This was a double-blind placebo controlled study with each individual admitted on two occasions when either rhIGF-I (40 micrograms/kg) or placebo was administered by subcutaneous injection in the thigh at 1800 h. Blood samples were then taken for the subsequent 22 h. The half-life of administered rhIGF-I (12.1-22.2 h) was similar to that previously described in normal subjects. There was a small increase in IGFBP-3 concentrations overnight following rhIGF-I administration when compared to placebo, whereas the levels of IGF-II decreased. Under strict euglycaemic conditions, the relationship between insulin and IGFBP-I did not appear to be affected by rhIGF-I administration although the levels of IGFBP-1 tended to be higher overnight. IGF bioactivity was low during the placebo study, and although within the normal adult range following administration of IGF-I, was still relatively low for adolescents in late puberty.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Anterior pituitary function and computed tomography/magnetic resonance imaging in patients with Langerhans cell histiocytosis and diabetes insipidus.

In order to document anterior pituitary dysfunction in patients with biopsy-proven Langerhans cell histiocytosis (LCH) and diabetes insipidus and to correlate this with structural changes on imaging, we performed an insulin tolerance test, enhanced computed tomography (CT), and unenhanced magnetic resonance imaging (MRI) in nine patients. Six of the nine patients had growth hormone deficiency, which in two patients was part of panhypopituitarism and in one was associated with poor cortisol response to insulin hypoglycemia. One patient had an exaggerated growth hormone response and one who had had neck irradiation as an infant, had a high resting thyroid stimulating hormone (TSH) suggesting compensated primary hypothyroidism. All enhanced CTs were abnormal, bony defects being the only abnormality in two patients and opaque mastoids in one. The remaining six patients all had structural changes in the hypothalamic/pituitary region. Unenhanced MRI confirmed the CT findings except in one child who had been treated with radiotherapy in the intervening period, but, in addition, confirmed diabetes insipidus by showing absence of the posterior pituitary bright signal and picked up white matter changes in a child with clinical neurological dysfunction. Our findings indicate that the development of diabetes insipidus in LCH is commonly associated with anterior pituitary dysfunction and is usually associated with structural changes in the hypothalamic/pituitary axis.

Body Height↗
PubMed1993

The effects of recombinant insulin-like growth factor I administration on growth hormone levels and insulin requirements in adolescents with type 1 (insulin-dependent) diabetes mellitus.

Type 1 (insulin-dependent) diabetes mellitus in adolescence is associated with reduced levels of insulin-like growth factor I, elevated growth hormone concentrations and insulin resistance. In order to determine whether restoring insulin-like growth factor I levels to normal might lead to a reduction in growth hormone levels and insulin requirements, we undertook a double-blind placebo controlled study of a single s.c. dose of recombinant insulin-like growth factor I (40 micrograms/kg body weight) in nine late pubertal subjects with Type 1 diabetes. After administration of placebo or insulin-like growth factor I at 18.00 hours, a variable rate insulin infusion was used to maintain euglycaemia overnight. Plasma insulin-like growth factor I, growth hormone, free insulin, and intermediate metabolite concentrations were monitored throughout the study. Recombinant insulin-like growth factor I led to a rise in plasma concentrations which reached a peak at 5.5 h (413.1 +/- 28.2 ng/ml, mean +/- SEM). Mean growth hormone levels between 20.00 and 08.00 hours were significantly reduced after recombinant insulin-like growth factor I (19.4 +/- 4.0 compared with 33.6 +/- 5.8 mU/l; p = 0.01), as were the insulin requirements for euglycaemia (0.25 +/- 0.02 compared with 0.31 +/- 0.04 mU.kg-1.min-1; p = 0.03). Plasma free insulin levels were lower after recombinant insulin-like growth factor I administration (31.9 +/- 2.7 compared with 67.9 +/- 16.0 mU/l; p = 0.001) but no significant differences in ketone or lactate levels were detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

The effects of growth hormone and insulin-like growth factors I and II on glutamine metabolism by skeletal muscle of the rat in vitro.

Soleus muscle preparations of the rat were incubated in the presence of growth hormone, IGF-I or IGF-II. Growth hormone (10 and 100 ng/ml) increased, but IGF-I and IGF-II were without effect on the concentration of glutamine in soleus muscle. Growth hormone was without effect on the rate of release of glutamine from muscle. In contrast, the rate of release of glutamine was decreased in the presence of IGF-I (750 ng/ml) and increased in the presence of IGF-II (250 and 750 ng/ml). Growth hormone and the IGFs may therefore play an important role in the control of glutamine metabolism by skeletal muscle.

Amino Acids↗
PubMed1993

The frequency and amplitude of growth hormone secretory episodes as determined by deconvolution analysis are increased in adolescents with insulin dependent diabetes mellitus and are unaffected by short-term euglycaemia.

OBJECTIVE: High overnight plasma growth hormone (GH) levels in insulin-dependent diabetes mellitus (IDDM) are reflected in both an increase in the GH pulse amplitude and elevated baseline GH concentrations. To determine whether these are a result of an increase in GH secretory episodes, we undertook deconvolution analysis of overnight GH profiles using previously determined half-life data. DESIGN: Deconvolution of overnight GH profiles (2000-0800 h) was undertaken from normal and diabetic adolescents (either on their usual insulin regime (n = 15), during overnight euglycaemic clamp using a variable rate insulin infusion (n = 29), or during clamp plus 100 mg pirenzepine to suppress endogenous GH (n = 7)). PATIENTS: Thirty-five normal and 29 diabetic adolescents of both sexes at all stages of puberty. MEASUREMENTS: GH secretory rates were calculated from deconvolution analysis, and Fourier transformation was increased mean overnight GH secretion when analysed by sex and by puberty stage compared to normal subjects; overnight GH secretion median (range) of diabetic group 1.88 (0.56-3.81) mU/min; control group 0.62 (0.32-1.92) mU/min (P < 0.001). Fourier transform analysis of these secretory episodes showed greater pulse frequency in the diabetics with dominant pulse periodicity of 90 minutes compared with 135 minutes in normal subjects. During overnight euglycaemia, mean +/- SEM overnight GH secretory rates were comparable to subjects' usual regime night (1.82 +/- 0.33 vs 1.91 +/- 0.37 mU/min) and there was no change in the dominant pulse periodicity of 90 minutes. Pirenzepine administration in diabetic subjects significantly reduced overnight GH secretion from 1.57 +/- 0.19 to 0.71 +/- 0.80 mU/min (P < 0.001) showing a median (range) reduction of 63 (9.3-82.8)% when compared to the subjects' clamp night. However, dominant pulse periodicity was not altered by pirenzepine administration, and remained at 90 minutes. CONCLUSION: In patients with insulin-dependent diabetes mellitus there is an increase in both the amplitude and frequency of pulsatile GH secretion compared to normal subjects, which is not affected by maintenance of overnight normoglycaemia. The anticholinergic drug pirenzepine appears to suppress the amplitude of GH pulse secretion but has no effect on frequency.

Adolescent↗
PubMed1993

Urinary excretion and clearance of insulin in diabetic and normal children and adolescents.

Seventy-two diabetic (38 males) and 86 normal (41 males) children provided timed overnight urine collections. Fourteen of the diabetic and 33 of the normal children had concurrent overnight plasma insulin profiles. Urinary insulin clearance in the diabetic subjects was compared with excretion of albumin, growth hormone, retinol-binding protein, and N-acetyl-beta-D-glucosaminidase. In the normal subjects, urinary insulin excretion correlated with mean overnight plasma levels in the boys (r = 0.82, p < 0.001) but not in the girls (r = 0.32), and varied with puberty stage in the boys. Insulin clearance was greater in boys than girls during puberty, and fell in both sexes with advancing puberty. Insulin excretion was greater in diabetic than normal children in both sexes at all puberty stages. Insulin clearance was also greater in diabetic than normal subjects (1.05 +/- 0.1 ml min-1 1.73 m-2 vs 0.48 +/- 0.05 ml min-1 1.73 m-2, p < 0.001). Insulin excretion as a percentage of the filtered load was also greater in diabetic than normal subjects (1.9 +/- 0.27% vs 0.85 +/- 0.09%, p < 0.01). In the diabetic children, there was a correlation between urinary insulin and growth hormone excretion (r = 0.52, p < 0.02), and retinol-binding protein in those (n = 10) with higher retinol binding protein excretion (r = 0.76, p = 0.01). The value of urinary insulin excretion as a measure of free plasma insulin levels in normal and diabetic children may be limited by sex differences in renal insulin clearance, and by proximal renal tubular dysfunction in children with diabetes.

Acetylglucosaminidase↗
PubMed1993

Evaluation of a district growth screening programme: the Oxford Growth Study.

The Oxford district growth screening programme was established in 1988 as a community based survey of the heights of children at 3 and 4.5 years of age in a district of 550,000 people. The current birthrate is 7500 births/year and over the first three years of the study 20,338 children were screened in the community; the ascertainment ranged from 61-73.9% of the total expected. Mean height SD scores were significantly greater than the British standards; mean SD scores for boys and girls were 0.33 and 0.35 respectively at age 3, and 0.20 and 0.26 at 4.5 years. Altogether 260 (1.3%) of the total cohort were found to have heights < or = -2SD scores. The mean growth velocity of 2742 children measured at 3 and 4.5 years of age was similar to that of the national standards, 7.14 cm/year in boys and 7.21 cm/year in girls. Follow up data was available from 149 children whose heights were confirmed to be < or = -2SD scores. Of these 69 were already under the care of paediatricians. Thus far diagnoses in the 149 have included growth hormone deficiency (n = 2), Turner's syndrome (n = 2), Noonan's syndrome (n = 4), and emotional deprivation (n = 1). Ways in which ascertainment and detection of treatable causes of short stature could be improved are discussed and it is concluded that community growth screening is a useful part of the child health surveillance programme.

Body Height↗
PubMed1993

Can islet cell antibodies predict IDDM in the general population?

OBJECTIVE: To evaluate the likely prognostic significance of ICAs in children with no family history of IDDM. RESEARCH DESIGN AND METHODS: We examined the prevalence of ICAs in 2925 English schoolchildren aged 9-13 yr and in 274 age-matched siblings of children with diabetes from the same region, and we compared the estimated risk of progression to diabetes within 10 yr in the two groups. RESULTS: ICAs were present at levels > or = 4 JDF U in 2.8% of schoolchildren and 6.6% of siblings and at > or = 20 JDF U in 0.8% of schoolchildren and 2.2% of siblings. Although ICAs are only 2-3 times more prevalent in siblings than schoolchildren, the estimated cumulative risk that siblings will progress to diabetes by age 21 is 13 times greater (2.8 vs. 0.21%). CONCLUSIONS: ICAs are unexpectedly prevalent in English schoolchildren, but only a small minority, with this evidence of immune activation directed against islet cells, will progress to diabetes. Although ICAs alone have limited predictive value in the general population, combining two or more predictive tests in series could achieve a level of prediction equivalent to that now obtained in first-degree relatives.

Adolescent↗
PubMed1993

Evidence for a role for insulin and growth hormone in overnight regulation of 3-hydroxybutyrate in normal and diabetic adolescents.

OBJECTIVE: To determine the relative effects of growth hormone and insulin on ketogenesis during puberty. RESEARCH DESIGN AND METHODS: We studied overnight changes in plasma ketones--3-hydroxybutyrate and acetoacetate--in 35 normal and 26 IDDM adolescents at different stages of puberty. The diabetic adolescents either were on their normal insulin regimen or were studied during an overnight euglycemic clamp with or without suppression of endogenous growth hormone release. RESULTS: Total ketone body and 3-hydroxybutyrate concentrations in the normal adolescents rose significantly from 2000 (29 +/- 5 microM), reaching a peak at 0200 (103 +/- 16 microM, P < 0.001 vs. 2000). After a brief fall, a further rise occurred before breakfast. Fasting 3-hydroxybutyrate concentrations showed a negative correlation with fasting insulin levels (r = -0.46, P = 0.005) and decreased with advancing puberty, while insulin concentrations increased. In the diabetic patients on their usual insulin regimen, free insulin levels waned overnight, and an exaggerated rise in ketones was observed before breakfast. During the euglycemic clamp studies, ketone levels were higher than normal throughout the night. Mean overnight growth hormone and free insulin levels also were higher than in the normal control subjects. The addition of the anticholinergic drug pirenzepine reduced growth hormone secretion and obliterated the early-night peak of 3-hydroxybutyrate. CONCLUSIONS: We conclude that the early-night peak of ketone concentrations is related to growth hormone release, whereas the fasting levels are largely determined by insulin concentration. Inadequate insulin delivery in the presence of the high growth hormone concentrations characteristic of diabetic adolescents could lead to rapid decompensation and ketoacidosis.

3-Hydroxybutyric Acid↗
PubMed1993

Comparison of cartridge insulin Penmix 50:50/Isophane with soluble/Isophane in type I diabetic adolescents using a multiple injection regimen.

This study investigated the effect on blood sugar control and weight gain of a multiple injection therapy (MIT) regimen in 22 established adolescent diabetics using a pre-prandial 50:50 mixture of Isophane/soluble insulin with night-time Isophane. This regimen was compared in a cross-over study with MIT using pre-prandial soluble insulin and night-time Isophane. After 4 wk for stabilization, there were 2 periods of 16 wk on each regimen. Throughout the study, blood sugar control was monitored by regular HbA1 and fructosamine measurements. The total daily dose of insulin was unchanged throughout the study, 1.0 +/- 0.3 iu/kg/day for Penmix/Isophane and 1.1 +/- 0.3 iu/kg/day for soluble/Isophane. The mean HbA1 and fructosamine did not alter significantly on either regimen. There was no significant weight gain during the Penmix therapy, despite the increased proportion of longer-acting despite the increased proportion of longer-acting insulin. Lean body mass (LBM) measured by skinfold thickness and electrical impedance only changed marginally on either regimen; the correlation between the 2 measuring techniques for LBM was good. Patient acceptance of the 50:50 Penmix insulin was high, 13 of 19 children preferring it to the conventional regimen.

Adipose Tissue↗
PubMed1992

The effect of insulin-like growth factor II on glucose uptake and metabolism in rat skeletal muscle in vitro.

The effect of insulin-like growth factor II (IGF II) on the rates of lactate formation, glycogen synthesis and glucose transport in the presence of a range of concentrations of insulin were investigated using an isolated preparation of rat skeletal muscle. IGF II, at a concentration of 65 ng/ml, caused a small but significant increase in the rates of these processes at a basal physiological insulin concentration (10 muunits/ml), but was without effect in the presence of 1, 100, 1000 or 10,000 muunits of insulin/ml. Hence IGF II increased the insulin sensitivity of this tissue. This effect was removed if the incubation medium was supplemented with an equimolar concentration of IGF binding protein 1 (BP1). It is suggested that changes in the concentration of IGF II and/or BP1 may regulate glucose uptake and metabolism in skeletal muscle and have physiological significance in the control of blood glucose level.

Animals↗
PubMed1992

Contrasting metabolic effects of continuous and pulsatile growth hormone administration in young adults with type 1 (insulin-dependent) diabetes mellitus.

Plasma growth hormone profiles in adolescents with Type 1 (insulin-dependent) diabetes mellitus are characterized by both increases in pulse amplitude and higher baseline concentrations. To determine which of these abnormalities adversely affect metabolic control, we studied six young adults overnight on three occasions. On each night somatostatin (50-100 micrograms.m2-1.h-1) and glucagon (1 ng.kg-1.min-1) were infused continuously and 18 mU/kg of growth hormone was given as either: three discrete pulses of 6 mU.kg-1.h-1 at 180-min intervals or a 12-h infusion (1.5 mU.kg-1.h-1) or buffer solution only on a control night. Euglycaemia was maintained by an insulin-varying clamp. Blood samples were taken every 15 min for glucose and growth hormone and every hour for intermediate metabolites and non-esterified fatty acids. Comparable normoglycaemic conditions were achieved on all three nights. Growth hormone levels achieved (mean +/- SEM) on study nights were: 32.8 +/- 2.2 mU/l (peak level during growth hormone pulses); 9.8 +/- 0.8 mU/l (continuous growth hormone) and 1.1 +/- 0.3 mU/l (control level). Pulsatile growth hormone administration led to an increase in insulin requirements (mean +/- SEM: 0.17 +/- 0.03 vs control 0.09 +/- 0.01 mU.kg-1.min-1, p less than 0.05) whereas insulin requirements following continuous growth hormone administration were unchanged. Cross-correlation confirmed an increase in insulin requirements occurring 135 min after a growth hormone pulse (r = 0.21, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗