An assessment of pancreatic endocrine function and insulin sensitivity in patients with transient neonatal diabetes in remission.

AIMS: To examine derived indices of beta cell function, peripheral insulin sensitivity, and the pancreatic response to intravenous glucose loading in children with a previous history of transient neonatal diabetes currently in remission, repeated after a period of two or more years. METHODS: The standard intravenous glucose tolerance test (IVGTT) was used to measure the first phase insulin response (FPIR) cumulatively at one and three minutes. In addition, fasting insulin and glucose values were used to estimate insulinogenic indices (beta cell function) and QUICKI (insulin sensitivity). PATIENTS: Six patients with known previous transient neonatal diabetes currently in remission with no exogenous insulin requirement were tested. Control data from 15 children of a similar age were available for derived fasting indices of beta cell functional capacity and insulin sensitivity. RESULTS: One child had a subnormal insulin secretory response to intravenous glucose that remained abnormal two and four years later. The other children had relatively normal or entirely normal responses over two years. Measures of beta cell function and insulin sensitivity in the fasting state showed comparable results to those obtained from normal controls. CONCLUSIONS: Most children with transient neonatal diabetes in remission have no evidence of beta cell dysfunction or insulin resistance in the fasting state, although they might have been expected to show subtle defects given the tendency to relapse in adolescence. Measures of insulin response to intravenous glucose loading are often normal but suggest future recurrence if profoundly abnormal.

Poor growth in school entrants as an index of organic disease: the Wessex growth study.

OBJECTIVE: To establish whether poor height or height velocity, assessed during the year of school entry, might identify children with previously undiagnosed organic disease. DESIGN: Observation of a total population and their case controls. SETTING: Community base. SUBJECTS: All 14,346 children in two health districts entering school during two consecutive years were screened for height by school nurses, and those whose height lay below the 3rd centile according to Tanner and Whitehouse standards (n = 180) were identified. After excluding 32 with known organic disease, five from ethnic minorities, and three who refused to take part, the remaining 140 short normal children were matched with 140 age and sex matched controls of average height (10th-90th centile) and their height velocities over 12 months measured. MAIN OUTCOME MEASURES: Height, height velocity, previously diagnosed organic disease, and organic disease diagnosed as a result of blood tests and specialist examination. RESULTS: Twenty five of the 180 short children (14%) were already known to have chronic organic disease which could explain their poor growth. Blood tests and specialist examination revealed a further seven with organic disease, which was acquired rather than congenital in three, and a second cause of short stature in one with known organic disease. These eight conditions had been missed at the school entry medical examination. The shorter the child, the more likely an underlying organic disorder, with seven of the 12 children whose heights were more than 3 standard deviations below the mean having some organic disease. Height velocity measured over 12 months, however, did not distinguish short normal children from those with disease or from their matched controls. CONCLUSIONS: Height, but not height velocity, is a useful index for identifying unrecognised organic disease at school entry. The shorter the stature the greater the prevalence of organic disease. The frequency of newly diagnosed remediable disease in this study (1 in 3-4000) is similar to that of neonatal hypothyroidism, which is routinely screened for. Routine investigation of all very short school entrants is recommended.

Are short normal children at a disadvantage? The Wessex growth study.

OBJECTIVE: To examine whether short stature through childhood represents a disadvantage at around 12 years. DESIGN: Longitudinal non-intervention study of the physical and psychological development of children recruited from the community in 1986-7 after entry into primary school at age 5-6 years; this is the second psychometric assessment made in 1994-5 after entry into secondary school at age 11-13 years. SETTING: Southampton and Winchester health districts. SUBJECTS: 106 short normal children (< 3rd centile for height when recruited) and 119 controls of average stature (10th-90th centile). MAIN OUTCOME MEASURES: Psychometric measures of cognitive development, self concept development, behaviour, and locus of control. RESULTS: The short children did not differ significantly from the control children on measures of self esteem (19.4 v 20.2), self perception (104.2 v 102.4), parents' perception (46.9 v 47.0), or behaviour (6.8 v 5.3). The short children achieved significantly lower scores on measures of intelligence quotient (IQ) (102.6 v 108.6; P < 0.005), reading attainment (44.3 v 47.9; P < 0.002), and basic number skills (40.2 v 43.5; P < 0.003) and displayed less internalisation of control (16.6 v 14.3; P < 0.001) and less satisfaction with their height (P < 0.0001). More short than control children, however, came from working class homes (P < 0.05). Social class was a better predictor than height of all measures except that of body satisfaction. Attainment scores were predicted by class and IQ together rather than by height. Height accounted for some of the variance in IQ and locus of control scores. CONCLUSIONS: These results provide only limited support for the hypothesis that short children are disadvantaged, at least up until 11-13 years old. Social class seems to have more influence than height on children's psychological development.

Growth potential and skeletal maturity in children with chronic renal insufficiency.

The growth potential of 27 boys with varying degrees of chronic renal insufficiency has been determined from their present height centile for both bone age and chronological age. With increasing age their growth potential diminishes. The delay in bone age is greatest in those children whose disease dates from infancy, but does not correlate with their present state of renal function. Bone age continues to advance in the presence of severe osteodystrophy and growth arrest. Knowledge of the growth potential of children with chronic renal failure is of relevance in interpreting the height increments observed following renal transplantation. Serial determination of bone age is therefore an important aspect of their clinical management.

Growth pattern and dietary intake of children with chronic renal insufficiency.

The growth pattern and dietary intake of 33 children with varying degrees of renal insufficiency has been investigated. The development of impaired renal function in infancy has a more deleterious effect on linear growth than has its onset in later years. A reduction in growth velocity may occur once the glomerular filtration rate falls below 25 ml/min/1.73m(2). There was a significant reduction of the energy, protein, and vitamin D intakes of children with renal insufficiency compared with those recommended for their age, and of energy intake compared with that of normal children of their own height. Reduced growth velocity occurred when energy intake fell below 80% of that recommended. The reduction in the intake of energy and nutrients in these children may in part be responsible for their growth retardation.

Plasma and urine amino acid concentrations in children with chronic renal insufficiency.

Amino acids were determined in plasma and urine from controls and children with chronic renal insufficiency. Significant differences were found in the mean plasma concentration of serine, threonine, glutamic acid, tyrosine, arginine, cystine and glycine in children with severe renal failure. There was a marked increase in clearance of the majority of amino acids when glomerular filtration rate (GFR) fell below 30 ml/min/1.73 m2: the exceptions were the basic amino acids and cystine which did not change. As GFR decreased there was a significant reduction in the percentage tubular reabsorption of individual amino acids. Children with severe renal failure excreted up to 40% of the filtered load of amino acids in the urine. This significant increase in urinary amino acid loss may contribute to the derangement of plasma amino acid conentrations found in uraemia.

Oral desmopressin in neonatal diabetes insipidus.

A neonate with cranial diabetes insipidus was successfully treated with oral desmopressin. The patient had a midline cleft lip and palate and we obtained a more consistent response using the oral route than using the usual nasal route.

Growth and nutrition of uremic piglets.

Piglets aged 6 days were rendered uremic by subtotal nephrectomy and their growth and dietary intakes studied over the next 21 days. Eleven control piglets fed a voluntary intake of a sow's milk substitute (group A), 11 nephrectomized piglets fed a voluntary intake of the same feed (group B), 6 nephrectomized piglets tube fed the same milk (group C), and 11 nephrectomized piglets fed a voluntary intake of a low protein, isocaloric food (group D) were studied. After nephrectomy the piglets had an initial rapid rise in blood urea concentration which had fallen by day 7 and then leveled out around 13 mmol/liter in group B and 8 mmol/liter in group D. After operation control piglets (group A) ate more from day 4 and were larger from day 7 than the nephrectomized piglets (group B). Those piglets tube fed (group C) were of a similar size to the controls but all died between day 7 and day 11 with associated high blood urea concentrations. Piglets fed the low protein, isocaloric feed (group D) were smaller than both the controls and group B. They also ate less food than the controls and those nephrectomized piglets in group B which were on a voluntary intake of the normal feed.

Improved diabetic control in adolescents using the Penject syringe for multiple insulin injections.

Eleven adolescent diabetics, aged 15.1 +/- 1.3 years (mean +/- 1SD) in poor glycaemic control (HbA1 12.0 +/- 1.5% at entry) were commenced on a four times daily insulin injection regimen using the Penject fountain-pen syringe with Initard (50:50 mixture of porcine soluble and isophane) insulin on a sliding scale. Diabetic control improved over a 3-month period, assessed by a reduction in both the mean preprandial blood glucose concentrations (10.9 +/- 3.3 mmol/l to 7.7 +/- 2.3 mmol/l) and mean glycosylated haemoglobin concentrations (12.0 +/- 1.5% to 9.5 +/- 0.9%). Further improvement was again seen in 5 patients who remained on four daily injections for an additional 3 months (mean HbA1: 9.6 +/- 0.9% to 8.4 +/- 1.0%), whereas diabetic control in 6 patients who returned to twice daily injections deteriorated (mean HbA1 rose from 9.5 +/- 1.0% to 10.6 +/- 1.6%). Multiple insulin injections using an injection pen are acceptable to adolescent diabetics and improve their control.

Role of dietary energy supplementation in growth of children with chronic renal insufficiency.

The effect of dietary energy supplements in children with varying degrees of chronic renal insufficiency was investigated. Despite an increased energy intake of 8-4% there was no increase growth velocity, although some patients reported improved wellbeing and activity. The proportion of dietary energy supplied by protein fell significantly during supplementation. The evidence suggests that the reduced energy intake of children with chronic renal insufficiency is a related but not causal factor in their growth retardation.

Short stature at school entry--an index of social deprivation? (The Wessex Growth Study).

This study was carried out to examine the biological and environmental variables associated with non-organic short stature. We observed an unselected population of very short normal children (SN) and their age- and sex-matched controls (C) within the community. All 14,346 children in two health districts entering school during 2 consecutive years were screened for short stature, and those whose height lay below the 3rd centile, according to Tanner and Whitehouse standards (n = 180) were identified. Excluding 32 with pathology, five from ethnic minorities and three who refused to take part, the remaining SN children (mean height SDS-2.26) were matched with 140 age- and sex-matched controls (C) of average height (mean height SDs 0.14). Birth weight, target height and predicted adult height (based on parental height and bone age respectively), medical and social background (obtained from parental interviews), and school performance (assessed by class teachers) were the main outcome measures. Mean birth weight of the SN children was significantly lower than C (SN = 2845 g, C = 3337 g, P < 0.001). Mean mid-parental target height was also very different (SN = 162.0 cm, C = 170.9 cm, P < 0.001). Thirty-five per cent of SN children (C = 6%) had height SD scores below parental target range, though only 10% had predicted heights below target range (mean delay in bone age 0.68 years). There was a significant difference between SN children and C in the number of children in the household (SN = 2.8, C = 2.4 (P = 0.007) and in socio-economic status (P < 0.002). Many more SN children were in social classes IV and V (SN = 31%, C = 13%, P < 0.002), and had an unemployed father (SN = 22%, C = 10%, P < 0.010), highlighting the importance of environmental influences on growth. One in four SN children was judged to have serious psychosocial problems. However, the lower the socio-economic class, the less likely the SN children were to be inappropriately short for parents. Significantly more SN children were reported to have asthma (SN = 18%, C = 7%, P < 0.007) and eczema (SN = 19%, C = 5%, P < 0.001), though only the latter was significantly associated with stature below target height for both SN and C groups. Biological variables are often insufficient to explain short stature. No child, whatever the parental height, should be dismissed as normal without careful evaluation, as poor growth in the early years may be an important pointer to an adverse but potentially remediable environment.

Lead intoxication in children in Birmingham.

Of 38 children investigated between 1966 and 1971 who had a blood lead concentration greater than 37 mug/100 ml eight had encephalopathy and one died; all these eight had a blood lead concentration of 99 mug/100 ml or above. Blood lead levels are related to haemoglobin concentrations and anaemia is common in children with blood lead concentrations of 37-60 mug/100 ml, levels previously accepted as harmless.Children with blood lead concentrations greater than 60 mug/100 ml show radiological evidence of lead intoxication, and treatment for this should be considered when blood lead concentration exceeds 37 mug/100 ml. Children presenting with unexplained encephalopathy should be radiographed for evidence of lead intoxication.

Hormones and handedness.

BACKGROUND: The Wessex Growth Study has monitored the growth and psychological development of short normal (SN) and average height control subjects since they entered school in 1985/1986. During psychometric testing, we found that 25% SN compared to 9% control subjects wrote with their left hand. The short group also attained significantly lower scores on measures of IQ and attainment and displayed less internalisation of control. Laterality, however, is thought to be influenced by the intrauterine environment and has been associated with pubertal delay. At recruitment, short children had a relatively low birth weight, delayed bone age and were more likely than controls to be short for family. OBJECTIVES: To determine if birth conditions were associated with lateral preference and whether laterality could account for the differences found during the psychometric assessment or predict pubertal timing of SN children. METHODS: Subjects were classified as right- (RH) or left-handed (LH) according to the writing hand and the data were investigated examining the effect of handedness and stature. RESULTS: RH and LH SN children were no more likely to suffer birth complications than those of average height. Psychometric testing did not reveal any significant differences between RH and LH SN children and their patterns of growth appeared to be similar. However, both RH and LH SN children scored less well on tests of cognitive ability and analyses of covariance revealed significant gender/handedness effects for both the timing of puberty and final height. CONCLUSIONS: The increase in left-handedness among SN children did not appear to be related to adverse birth conditions, but it may be that the hormones responsible for growth and development also play some part in brain laterality and cognitive development.

Serum cortisol concentrations in children with chronic renal insufficiency.

Children with chronic renal insufficiency have a normal diurnal rhythm and normal nocturnal values for serum cortisol when determined by competitive protein binding. Falsely raised values were obtained when a fluorimetric technique was used for the cortisol determination in these patients.

Bicarbonate excretion in kwashiorkor.

Children with kwashiorkor have an impairment of bicarbonate excretion which may result in the inappropriate production of acid urine in the presence of systemic alkalosis. This defect has resolved after 2 weeks of treatment.

Diabetes care in childhood and adolescence.

The presentation of diabetes in young people has changed significantly over recent years. Not only has there been a rising incidence of Type 1 diabetes, especially in young children, but also there is an increasing recognition of Type 2 diabetes. Young people are also increasingly being diagnosed with genetic defects of B-cell function and with diabetes in association with cystic fibrosis and other chronic diseases. There have also been significant changes in the pattern of paediatric diabetes care. This is increasingly being provided by a specialized paediatric multidisciplinary team in each health district working to agreed national standards. Despite improvements, diabetes control is still suboptimal with a high incidence of complications being reported in young adults. The challenge over the next few years is the provision of a uniform, equitable and first class paediatric service throughout the UK together with the introduction of new approaches to care, aiming to improve individual diabetic control and reduce long-term complications. Increased collaboration with adult colleagues is needed to enable the transition of care in adolescence to a service that young adults perceive to meet their needs, encourage their attendance and improve their diabetes control and quality of life. A national paediatric diabetes register together with regular audit will encourage these objectives.