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Biomedical subjects

D B Dunger

Publications and source records attributed to D B Dunger.

At least 73 records · Page 4Linked to original sources
PubMed2000

Arginine vasopressin secretion in Kenyan children with severe malaria.

Hyponatraemia is common in African children with severe malaria, but the cause is unknown. We measured plasma sodium (p[Na]) and arginine vasopressin concentrations (p[AVP]) in 30 consecutive children with severe malaria (19 had cerebral malaria), on admission, at 48 and 96 h after admission. Hyponatraemia (p[Na] < 130 mmol/l) occurred in 53 per cent of the children and was unrelated to peripheral parasite density, dehydration or abnormal renal function. The highest p[AVP] were seen in patients with cerebral malaria. Overall, p[AVP] declined 96 h after treatment. In children with hyponatraemia (cerebral and non-cerebral), p[AVP] levels were not suppressed and in 67 per cent of cases they were deemed inappropriate. Inappropriate AVP secretion is common in children with severe malaria and may influence fluid therapy after correction of initial dehydration.

Arginine Vasopressin↗
PubMed2000

Increased bone mineral density and serum leptin in non-obese girls with precocious pubarche: relation to low birthweight and hyperinsulinism.

BACKGROUND: Hyperinsulinism and hyperandrogenism have the capacity to increase bone mineral density (BMD) and serum leptin, independently of body fat mass. We therefore assessed lumbar BMD and serum leptin in girls with the sequence of a low birthweight and precocious pubarche (PP) in childhood, in whom hyperinsulinism and hyperandrogenism have been described. METHODS: Fifty-two non-obese PP girls were studied (age range 6.9-14.9 years). Serum leptin was also measured in 42 control girls, matched for age, body mass index and pubertal stage. RESULTS: BMD SDS, measured by dual-energy X-ray absorptiometry, was elevated in PP girls compared to the population reference (0.39 +/- 0.18 SDS; p = 0.03) and bone age, assessed from hand radiographs, was significantly advanced compared to chronological age (1.2 +/- 0.1 years; p < 0.0005). CONCLUSION: Compared to control girls, PP girls had higher leptin levels for degree of body mass index (PP girls: 9.4 +/- 0.6 ng/ml; controls: 7.8 +/- 0.6 ng/ml; p = 0.01). In PP girls, serum leptin was inversely related to birthweight (r = -0.32, p = 0.01) and positively related to free androgen index (FAI) (r = 0.71, p < 0.0005). BMD SDS was also inversely related to birthweight (r = -0.26, p < 0.05) and positively related to serum leptin (r = 0.42, p < 0.05), FAI (r = 0.45, p < 0.05) and mean serum insulin during oral glucose tolerance testing (MSI) (r = 0.59, p < 0.0005). In multiple regression, MSI was the strongest determinant of BMD SDS (beta = 0.50, p = 0.002). In conclusion, elevated BMD and serum leptin in non-obese PP girls were related to degrees of low birthweight, hyperinsulinism and hyperandrogenism. The characteristic hyperinsulinism of PP girls is proposed to be the key variable in this constellation.

Adolescent↗
PubMed2000

Thrifty genotypes and phenotypes in the pathogenesis of type 2 diabetes mellitus.

Dramatically high rates of type 2 diabetes mellitus (DM) have been observed in historically undernourished, recently urbanized populations. A comparable model is the high risk of DM in individuals who were growth restrained in utero and subsequently catch up in size. While it is proposed that undernutrition may somehow adversely program metabolism, both models could also be explained by genotypes that promoted survival during earlier nutritional adversity but later add to the risk of DM. Our recent studies in a contemporary birth cohort have identified two different candidate thrifty genotypes. The insulin gene VNTR III/III genotype promotes fetal growth and historically could thereby have enhanced survival during infancy. In contrast, the maternally inherited 16189 mitochondrial DNA variant is associated with restrained fetal growth and may therefore enhance the likelihood of maternal survival. Both genotypes are associated with an increased risk of adult type 2 DM in historical cohorts. However, the development of DM in individuals from contemporary birth cohorts may prove to be influenced more by genetic and other early determinants of childhood obesity.

Child↗
PubMed2000

Risk of nephropathy can be detected before the onset of microalbuminuria during the early years after diagnosis of type 1 diabetes.

OBJECTIVE: The early detection of a rise in albumin excretion within the normal range could permit early intervention to prevent the development of microalbuminuria (MA) in genetically susceptible subjects with type 1 diabetes. In the Oxford Regional Prospective Study we prospectively examined urine albumin excretion during the first years after diagnosis of childhood type 1 diabetes. RESEARCH DESIGN AND METHODS: Between 1986 and 1995, 511 subjects aged < 16 years were recruited at diagnosis and followed for a median of 6 years (range 1-14). In 78 subjects (designated cases), an annual assessment of the albumin-to-creatinine ratio (ACR) in three morning first-void urine samples detected MA (males: ACR > or =3.5 mg/mmol, females: ACR > or =4.0 mg/mmol in two of three urine samples). In 63 of these subjects and 396 normoalbuminuric diabetic control subjects, rates of change of the ACR were calculated as the slope of the ACR over diabetes duration. RESULTS: The baseline ACR (median [interquartile (IQ) range]), as measured at 1-2.5 years' duration of diabetes, was higher in microalbuminuric subjects than in the normoalbuminuric subjects (1.0 mg/mmol [0.6-2.1], n = 52, vs. 0.8 mg/mmol [0.6-1.2], n = 303; P = 0.02). The rate of increase of the ACR in the years before the onset of MA was higher in the microalbuminuric subjects than in the normoalbuminuric subjects (70% per year [37-149], n = 63, vs. 1% per year [-9 to 13], n = 396; P < 0.001). The mean HbA1c level after the onset of puberty was weakly correlated with the rate of change of the ACR (r = 0.11, P = 0.024, n = 418). CONCLUSIONS: Higher levels of ACR within the first 2 years after diagnosis and a significantly higher rate of increase of the ACR within the first 5 years from diagnosis can be detected in subjects who subsequently develop MA. HbA1c is a determinant of risk for MA, but pubertal factors have a greater effect on rates of progression of urine albumin excretion during adolescence in this cohort.

Adolescent↗
PubMed1999

Human leucocyte antigen and insulin gene regions and nephropathy in type I diabetes.

AIMS/HYPOTHESIS: Diabetic nephropathy seems to have a strong genetic component. Genes involved in the genetic susceptibility to Type I (insulin-dependent) diabetes have been suggested to have a role in the development of diabetic nephropathy. This study aimed to examine the role of human leucocyte antigen and insulin genes in susceptibility to nephropathy in patients with Type I diabetes. METHODS: We carried out a genetic association study examining insulin gene polymorphisms using three large cohorts of patients with Type I diabetes: nephropathy (n = 258), long duration non-nephropathy (n = 153) and a recently diagnosed (sporadic) diabetic cohort (n = 264). Human leucocyte antigen typing results were obtained in a smaller number due to assay failures (n = 182, 126 and 200 respectively). RESULTS: No significant difference was seen in the distribution of human leucocyte antigen A, B, C, DR, DQA1 and DQB1 haplotypes and alleles between the three diabetic cohorts. No significant difference was seen in insulin '+' and '-' genotypes and alleles between the three diabetic cohorts. CONCLUSIONS/INTERPRETATION: Human leucocyte antigen and insulin gene loci are unlikely to have a major role in the susceptibility to nephropathy in Caucasian patients with Type I diabetes in the United Kingdom.

Adult↗
PubMed1999

The relationship between insulin, IGF-I and weight gain in cystic fibrosis.

OBJECTIVE: In cystic fibrosis, reduced body mass is related to low levels of IGF-I and changes in the IGF binding proteins. Our aim was to determine whether these abnormalities are linked to pancreatic endocrine dysfunction. PATIENTS AND DESIGN: We measured serum levels of insulin, IGF-I, IGFBP-I, IGFBP-3 and IGF bioactivity in 77 fasting subjects (43 male) mean age 9.6 years (range 2.99-17.98 years). Data were analysed with respect of body mass, puberty and stature and compared with control data established in the same laboratory. RESULTS: The mean height standard deviation score (SDS (SD)) was -0.54 (0.97) and the body mass index SDS -0.24 (1.09). Both body mass index SDS (r = -0.40, P = 0.0003) and IGF-I SDS (r = - 0.32, P = 0.009) declined with age. Insulin levels were also low and correlated with IGF-I and IGFBP-3 (r = 0.42, P = 0.0004, and r = 0.45, P = 0.0002, respectively) whereas levels of IGFBP-I were inversely related to those of IGF-I and insulin (r = - 0.43, P = 0. 0004, r = - 0.52, P < 0.0001). IGF bioactivity was reduced and inversely related to IGFBP-I (r = - 0.31, P = 0.009). In multiple regression analysis, body mass index SDS was negatively related to age (P < 0.0001) and positively related to insulin and IGF-I (P = 0. 04, P = 0.03, respectively). Height SDS was correlated with IGF bioactivity (P = 0.003) and negatively with IGFBP-I (P = 0.01). CONCLUSIONS: We conclude that progressive insulin deficiency may result in reduced IGF-I levels and IGF-bioactivity and may determine weight gain and statural growth in cystic fibrosis.

Adolescent↗
PubMed1999

Polycystic ovaries and associated clinical and biochemical features in young women.

OBJECTIVE: To determine the prevalence of polycystic ovaries as identified by ultrasound in a group of young, postmenarcheal women in the normal population, and to investigate how polycystic ovaries are related to the spectrum of clinical and biochemical symptoms associated with the polycystic ovary syndrome (PCOS). DESIGN: Cross-sectional observational study. SUBJECTS AND METHODS: Volunteers were recruited from two universities and two general practice surgeries in Oxford. 230 women aged 18-25 years participated. Information collected and measurements performed included: a menstrual history, anthropometric measurements, clinical observation of acne and hirsutism, transabdominal pelvic ultrasound, and biochemical analysis of a fasting blood sample. MAIN OUTCOME MEASURES: Prevalence of polycystic ovaries and their association with symptoms of the polycystic ovary syndrome. RESULTS: Polycystic ovarian morphology was identified in 74 (33%, 95% CI = 27-39%) of the 224 women who attended for an ultrasound scan. In the non-users of hormonal contraception, irregular menstrual cycles were 20% more common in women with polycystic ovaries than in women with normal ovaries (P = 0.07). There were no significant differences in acne, hirsutism, body mass index or body fat percentage between women with polycystic and normal ovaries. Analysis of biochemical data showed that women with polycystic ovaries had higher total serum testosterone concentrations (P = 0.03). The prevalence of PCOS in this age group was as low as 8% or as high as 26% depending on which criteria were applied to define the syndrome. Sub-group analyses of women according to ovarian morphology and features of PCOS revealed greater mean BMI in women with PCOS, and also indicated lower fasting insulin concentrations and greater insulin sensitivity in polycystic ovary and PCOS groups when compared to women with normal ovaries. CONCLUSIONS: Polycystic ovaries are very common in this age group but are not necessarily associated with other symptomatology. The prevalence of polycystic ovary syndrome varies widely according to the definition applied. Sub-group analysis of women with polycystic ovaries according to the presence or absence of features of polycystic ovary syndrome does not reveal an increasing trend for progression of endocrine abnormalities usually associated with polycystic ovary syndrome.

Adult↗
PubMed1999

Glycaemic control and familial factors determine hyperlipidaemia in early childhood diabetes. Oxford Regional Prospective Study of Childhood Diabetes.

AIMS: To determine whether abnormal lipid levels in children with Type 1 diabetes mellitus are the result of poor metabolic control or may in part be determined by genetic factors. METHODS: Non-fasting lipid levels were measured in 141 children with Type 1 diabetes (age range 7.7-19 years) 3 years after diagnosis, and in 192 of their parents. Glycosylated haemoglobin and the urinary albumin-creatinine ratio (three urine samples) were estimated in each child annually. RESULTS: The children had a mean total cholesterol of 4.46 +/- 1.25 mmol/l (+/- SD) and a median triacylglycerol of 1.18 mmol/l (range 0.32-4.7). A total of 15.3% of the population had a total cholesterol > 5.2 mmol/l and 17.9% had a triacylglycerol > 1.7 mmol/l; in 5.6% both total cholesterol and triacylglycerol were greater than these cut-off points. Total cholesterol, triacylglycerol and very low density lipoprotein-cholesterol were significantly correlated to glycaemic control. However, total cholesterol was also significantly related to parental total cholesterol either as analysed separately or as mean parental total cholesterol (r = 0.37, P = 0.0001). In stepwise multiple regression analysis both mean parental total cholesterol (P = 0.001) and HbA1c (P = 0.015) were significant determinants of the child's total cholesterol. The children studied were being followed prospectively for the development of microalbuminuria and there was a weak association across tertiles of total cholesterol, linking higher levels to the development of microalbuminuria (P < 0.05). CONCLUSIONS: We conclude that both glycaemic control and familial factors may be important determinants of lipid levels in young people with diabetes. Both may contribute to the subsequent risk of cardiovascular disease and possibly the development of incipient diabetic nephropathy.

Adolescent↗
PubMed1999

The role of leptin in human growth and puberty.

Experimental animal studies demonstrate the effects of leptin on appetite, weight gain and metabolism. The biological effects of leptin in human adults are still to be determined, but recent reports show that congenital leptin deficiency leads to hyperphagia and excessive weight gain from early infancy as well as failure of pubertal onset in adolescence. Our recently reported data from two longitudinal cohorts suggest a role for leptin in the normal regulation of childhood weight gain, maturation and the development of secondary sexual features and body composition. Low leptin levels in cord blood closely reflected decreased adiposity at birth and strongly predicted high rates of weight gain in infancy and catch-up growth. In adolescents, leptin levels rose gradually with age prior to puberty, suggesting that a threshold effect may trigger puberty. In girls, low leptin levels at the start of puberty predicted large gains in the percentage of fat mass, perhaps suggesting a role in the preparation for childbearing.

Adipose Tissue↗
PubMed1999

A decade of growth hormone treatment in girls with Turner syndrome in the UK. UK KIGS Executive Group.

Fifteen per cent of children treated with growth hormone (GH) are receiving treatment for Turner syndrome, but few results are available on final height in the UK. In this study, data were obtained from the UK KIGS database for 485 girls with Turner syndrome who were treated from 1986, allowing an audit of practice and outcome over 10 years. Over the decade, the mean age of starting growth hormone treatment fell from 10.4 to 8.5 years and the starting dose increased from 0.55 to 0.95 IU/kg/week. The frequency of injections increased from three to six or seven/week. Some girls received suboptimal doses, which also differed depending on whether they were based on weight or surface area. To assess what height gain might be expected at final height, all 52 girls who were prepubertal at the start of treatment, which continued for four years or more, and who had reached final height or had a growth velocity < 2 cm/year were selected. Their mean gain in final height was 5.2 cm and the GH dose was 0.78 IU/kg/week over 5.8 years. Final height gain correlated significantly with duration of treatment, total dose received, and first year response, which itself related to starting dose. This audit shows a changing pattern of treatment over the past decade, which in many instances has been inadequate. When treatment starts before puberty and continues through to final height, with a dose of 30 IU/m2/week in six or seven injections, a mean increase in final height of 5 cm or more would be expected.

Adolescent↗
PubMed1999

Cognitive function and mood after profound nocturnal hypoglycaemia in prepubertal children with conventional insulin treatment for diabetes.

OBJECTIVES: To examine the frequency of nocturnal hypoglycaemia, and the effects on cognitive function and mood, in children with insulin dependent diabetes mellitus (IDDM). DESIGN: Two overnight glucose profiles, in the home environment, and assessments of cognitive function and mood the following day. Twenty nine prepubertal patients with IDDM (median age, 9.4 years; range, 5.3-12.9) and 15 healthy controls (single overnight profile), median age 9.5 (range, 5.6-12.1) years were studied. RESULTS: Asymptomatic hypoglycaemia (glucose < 3.5 mmol/l) was observed in 13 of 29 patients studied on night 1: four of these and seven others were hypoglycaemic on night 2. The median glucose nadir was 1.9 (range, 1.1-3.3) mmol/l and the median duration of hypoglycaemia was 270 (range, 30-630) minutes. Hypoglycaemia was related to insulin dose, but not glycosylated haemoglobin (HbA1c) values, and was partially predicted by a midnight glucose of < 7.2 mmol/l. Cognitive performance was not altered after hypoglycaemia but a lowering of mood was observed. CONCLUSIONS: Young children on conventional insulin regimens are at high risk for profound, asymptomatic nocturnal hypoglycaemia, which is difficult to predict. There was no short term effect on cognitive function but mood change was detected.

Body Mass Index↗
PubMed1999

Causes of death in children with insulin dependent diabetes 1990-96.

BACKGROUND: Mortality rates in children with insulin dependent diabetes (IDDM) in the UK are unknown and the causes of death not well documented. AIM: To determine the mortality rate and causes of death in children with IDDM. METHODS: The Office of National Statistics (England and Wales) and the General Register Office (Scotland) notified all deaths under 20 years of age from 1990 to 1996 with diabetes on the certificate. Further details were provided by coroners, pathologists, and clinicians. RESULTS: 116 deaths were notified and 83 were caused by diabetes. The standardised mortality ratio was 2.3 (95% confidence interval (CI), 1.9 to 2.9), being highest in the age group 1-4 years, at 9.2 (95% CI, 5.4 to 14.7). Of the 83 diabetic deaths, hyperglycaemia/diabetic ketoacidosis (DKA) was implicated in 69 and hypoglycaemia in 7. Cerebral oedema was the most common cause of death in young children (25 of 36 diabetes related deaths in children under 12 years of age). 34 young people (10-19 years; 24 male) were either found dead at home (n = 26) or moribund on arrival at hospital (n = 8). In 24 of these, it appeared that DKA was the cause of death, in four hypoglycaemia was likely. Nine of these were found "dead in bed". CONCLUSIONS: Children with IDDM have a higher mortality than the general population. Cerebral oedema accounts for most hospital deaths in young children. There are a large number of young men dying at home from neglected IDDM. Early diagnosis of IDDM in children and closer supervision of young people might prevent some of these deaths.

Adolescent↗
PubMed1999

Longitudinal study of leptin concentrations during puberty: sex differences and relationship to changes in body composition.

Leptin may have a role in the initiation of puberty and the regulation of subsequent weight gain, but this hypothesis has not been tested by longitudinal study. We report data from 40 normal children (20 boys and 20 girls) followed from 8-16 yr of age with hormone measurements and auxology every 6 months. Before the onset of puberty, leptin levels were similar in boys and girls: G1, mean (95% confidence interval), 2.63 (2.17-3.20) ng/mL; B1, 2.47 (2.08-2.94) ng/mL (P = 0.64) and increased with age in both sexes (B, 0.107 +/- 0.042; P = 0.02). With the onset of puberty, leptin levels increased in girls (B2-B5, P < 0.0005), but decreased in boys (G2-G5, P < 0.0005). Similar positive independent relationships were seen between leptin and fat mass in girls (B, 0.106 +/- 0.022; P < 0.0005) and boys (B, 0.121 +/- 0.020; P < 0.0005), and negative relationships were found with fat-free mass [girls: B, -1.104 +/- 0.381 (P < 0.005); boys: B, -1.288 +/- 0.217 (P < 0.0005)]. Girls gained more fat mass than boys, whereas boys gained more fat-free mass, and this explained the sex difference in leptin levels. Leptin levels correlated significantly with a large number of other hormones, but none was independent of changes in body composition. In girls, but not in boys, low leptin levels during prepuberty (B1) predicted subsequent gains in the percent body fat during puberty (r = -0.75; P = 0.005). The sexual dimorphism in leptin levels during puberty reflects differential changes in body composition. Prepubertal leptin levels in girls also predict gains in the percent body fat.

Adipose Tissue↗
PubMed1999

Cord blood leptin is associated with size at birth and predicts infancy weight gain in humans. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood.

Recent discoveries of human genetic leptin deficiency have demonstrated its importance in regulating weight gain in early childhood. To investigate whether normal variation in leptin and insulin levels in cord blood could influence infancy growth, we assayed samples from 197 infants from a representative birth cohort, who were measured at birth, 4, 8, 12 and 24 months. Cord leptin levels correlated most closely with weight and ponderal index (kg/m3) at birth, but also with length and head circumference (all p<0.0005). Independent of birth size, females had higher leptin levels than males (p<0.0005). Cord levels of leptin, but not insulin, were negatively related to weight gain (p<0.005) from birth to 4 months, and accounted for 9.4% of the variance in weight gain, compared with breast/bottle feeding (3.5%) and early/late introduction of solids (1%). The effect of leptin levels on weight gain was independent of birthweight, and was still evident at 24 months. The wide variation in infancy growth ('catch-up' or 'catch-down') may be partly determined by leptin levels preset in utero. Our data support a role for leptin in the regulation of infancy weight gain, and suggest a mechanism whereby infants may 'catch-up' in growth postnatally following an adverse intrauterine environment.

Birth Weight↗
PubMed1999

Lispro or regular insulin for multiple injection therapy in adolescence. Differences in free insulin and glucose levels overnight.

OBJECTIVE: Regular insulin given with the evening meal could contribute to the risk of nocturnal hypoglycemia in adolescents with type 1 diabetes using a multiple injection regimen. To test this hypothesis, we compared glucodynamics and free insulin levels on two separate study nights. RESEARCH DESIGN AND METHODS: A total of 14 adolescents were recruited. On both nights, identical doses of regular insulin or insulin lispro were administered 30 min or 10 min, respectively, before the evening meal, using a double-blind randomized crossover study design. Doses of NPH insulin and carbohydrate content of the evening meal and snack were kept identical. Blood samples were taken every 15 min for blood glucose and every 60 min for free insulin and ketones. RESULTS: After insulin lispro administration, glucose levels were significantly lower between the evening meal and the bedtime snack (analysis of variance [ANOVA] P = 0.02), and four hypoglycemic episodes were recorded. This corresponded to a higher (458 +/- 48 vs. 305 +/- 33 pmol/l, P = 0.02), earlier (64 +/- 4.6 vs. 103 +/- 12 min, P = 0.01), and shorter-lasting (245 +/- 21 vs. 365 +/- 39 min, P = 0.01) insulin peak in contrast to regular insulin. After the bedtime snack, glucose levels increased dramatically during the lispro night and stayed higher, up to 0300 in the morning (ANOVA P = 0.01), corresponding to lower mean insulin levels (146 +/- 20 vs. 184 +/- 27 pmol/l, P = 0.04). No differences were seen in glucose and insulin levels between 0300 and 0800. Four episodes of nocturnal hypoglycemia were documented after the bedtime snack during the regular insulin night, in contrast to one episode after insulin lispro. No differences in ketone levels were observed. CONCLUSIONS: The replacement of regular insulin with insulin lispro may reduce the risk of late hypoglycemia, but redistribution of the evening carbohydrate may be needed to ensure good metabolic control and prevent early postprandial hypoglycemia.

Activity Cycles↗
PubMed1999

Eating habits, body weight, and insulin misuse. A longitudinal study of teenagers and young adults with type 1 diabetes.

OBJECTIVE: To examine disordered eating, insulin misuse, weight change, and their relationships with glycemic control and diabetic complications in adolescents with type 1 diabetes followed up over eight years. RESEARCH DESIGN AND METHODS: Of 76 adolescents (43 male, 33 female) with type 1 diabetes aged 11-18 years at the first assessment, 65 were interviewed as young adults (aged 20-28 years). Eating habits were assessed using a standardized Eating Disorder Examination. Height and weight were determined and BMI calculated. Three consecutive urine specimens were collected for measurement of albumin/creatinine ratio and other significant diabetic complications were recorded. Glycemic control was assessed by glycated hemoglobin. RESULTS: Weight and BMI increased from adolescence to young adulthood. Females were overweight as adolescents and both sexes were overweight as young adults. Concern over weight and shape increased significantly for both sexes from adolescence to young adulthood. This increase in concern was reflected in increased levels of dietary restraint. Features of disordered eating were apparent in females at both assessments, but no patients met the criteria for anorexia nervosa or bulimia nervosa at either assessment. A total of 10 (30%) females, but none of the males admitted underusing insulin to control weight. Five (45%) females with microvascular complications had intentionally misused insulin to prevent weight gain. CONCLUSIONS: An increase in BMI from adolescence to adulthood was associated with higher levels of concern over shape and weight and more intense dietary restraint, especially among females. Overt eating disorders were no more prevalent in these patients than in the general population, but milder forms of disordered eating were common and had implications for diabetes management. Insulin omission for weight control was frequent among females and may contribute to poor glycemic control and to risk of complications.

Adolescent↗