Target setting in intensive insulin management is associated with metabolic control: the Hvidoere childhood diabetes study group centre differences study 2005.

OBJECTIVE: To evaluate glycaemic targets set by diabetes teams, their perception by adolescents and parents, and their influence on metabolic control. METHODS: Clinical data and questionnaires were completed by adolescents, parents/carers and diabetes teams in 21 international centres. HbA1c was measured centrally. RESULTS: A total of 2062 adolescents completed questionnaires (age 14.4 +/- 2.3 yr; diabetes duration 6.1 +/- 3.5 yr). Mean HbA 1c = 8.2 +/- 1.4% with significant differences between centres (F = 12.3; p < 0.001) range from 7.4 to 9.1%. There was a significant correlation between parent (r = 0.20) and adolescent (r = 0.21) reports of their perceived ideal HbA1c and their actual HbA1c result (p < 0.001), and a stronger association between parents' (r = 0.39) and adolescents' (r = 0.4) reports of the HbA1c they would be happy with and their actual HbA1c result. There were significant differences between centres on parent and adolescent reports of ideal and happy with HbA1c (8.1 < F > 17.4;p < 0.001). A lower target HbA1c and greater consistency between members of teams within centres were associated with lower centre HbA1c (F = 16.0; df = 15; p < 0.001). CONCLUSIONS: Clear and consistent setting of glycaemic targets by diabetes teams is strongly associated with HbA1c outcome in adolescents. Target setting appears to play a significant role in explaining the differences in metabolic outcomes between centres.

Associations between physical activity, sedentary behavior, and glycemic control in a large cohort of adolescents with type 1 diabetes: the Hvidoere Study Group on Childhood Diabetes.

BACKGROUND: The Hvidoere Study Group on Childhood Diabetes has demonstrated persistent differences in metabolic outcomes between pediatric diabetes centers. These differences cannot be accounted for by differences in demographic, medical, or treatment variables. Therefore, we sought to explore whether differences in physical activity or sedentary behavior could explain the variation in metabolic outcomes between centers. METHODS: An observational cross-sectional international study in 21 centers, with demographic and clinical data obtained by questionnaire from participants. Hemoglobin A1c (HbA1c) levels were assayed in one central laboratory. All individuals with diabetes aged 11-18 yr (49.4% female), with duration of diabetes of at least 1 yr, were invited to participate. Individuals completed a self-reported measure of quality of life (Diabetes Quality of Life - Short Form [DQOL-SF]), with well-being and leisure time activity assessed using measures developed by Health Behaviour in School Children WHO Project. RESULTS: Older participants (p < 0.001) and females (p < 0.001) reported less physical activity. Physical activity was associated with positive health perception (p < 0.001) but not with glycemic control, body mass index, frequency of hypoglycemia, or diabetic ketoacidosis. The more time spent on the computer (r = 0.06; p < 0.05) and less time spent doing school homework (r = -0.09; p < 0.001) were associated with higher HbA1c. Between centers, there were significant differences in reported physical activity (p < 0.001) and sedentary behavior (p < 0.001), but these differences did not account for center differences in metabolic control. CONCLUSIONS: Physical activity is strongly associated with psychological well-being but has weak associations with metabolic control. Leisure time activity is associated with individual differences in HbA1c but not with intercenter differences.

Molecular analysis of novel PROP1 mutations associated with combined pituitary hormone deficiency (CPHD).

OBJECTIVE: Homozygous mutations in the gene encoding the pituitary transcription factor PROP1 are associated with combined pituitary hormone deficiency (CPHD) in both mice and humans with a highly variable phenotype with respect to the severity and time of initiation of pituitary hormone deficiency. We have ascertained three pedigrees with PROP1 mutations from a large cohort of patients with variable degrees of CPHD who were screened for mutations in PROP1. RESULTS: Affected individuals from all three pedigrees were found to harbour novel PROP1 mutations. We have identified two siblings in one family who were homozygous for an intronic mutation (c.343-11C > G) that disrupts correct splicing resulting in the loss of exon 3 from the PROP1 transcript. Two siblings from a second, unrelated family are compound heterozygotes for two point mutations in the coding region, a missense mutation (p.R125W) that leads to impaired transcriptional activation, and a deletion of a single nucleotide (c.310delC) resulting in a frameshift and nonfunctional mutant protein. Additionally, we identified a homozygous deletion of the PROP1 locus in two patients born to consanguineous parents. CONCLUSION: Mutations in PROP1 are a frequent cause of familial CPHD. We have described four novel mutations in PROP1 in 3 pedigrees, all resulting in PROP1 deficiency by different mechanisms. The phenotypic variation observed in association with PROP1 mutations both within and between families, together with the evolving nature of hormone deficiencies and sometimes changing pituitary morphology indicates a need for continual monitoring of these patients.

Are family factors universally related to metabolic outcomes in adolescents with Type 1 diabetes?

AIMS: To assess the importance of family factors in determining metabolic outcomes in adolescents with Type 1 diabetes in 19 countries. METHODS: Adolescents with Type 1 diabetes aged 11-18 years, from 21 paediatric diabetes care centres, in 19 countries, and their parents were invited to participate. Questionnaires were administered recording demographic data, details of insulin regimens, severe hypoglycaemic events and number of episodes of diabetic ketoacidosis. Adolescents completed the parental involvement scale from the Diabetes Quality of Life for Youth--Short Form (DQOLY-SF) and the Diabetes Family Responsibility Questionnaire (DFRQ). Parents completed the DFRQ and a Parental Burden of Diabetes score. Glycated haemoglobin (HbA(1c)) was analysed centrally on capillary blood. RESULTS: A total of 2062 adolescents completed a questionnaire, with 2036 providing a blood sample; 1994 parents also completed a questionnaire. Family demographic factors that were associated with metabolic outcomes included: parents living together (t = 4.1; P < 0.001), paternal employment status (F = 7.2; d.f. = 3; P < 0.001), parents perceived to be over-involved in diabetes care (r = 0.11; P < 0.001) and adolescent-parent disagreement on responsibility for diabetes care practices (F = 8.46; d.f. = 2; P < 0.001). Although these factors differed between centres, they did not account for centre differences in metabolic outcomes, but were stronger predictors of metabolic control than age, gender or insulin treatment regimen. CONCLUSIONS: Family factors, particularly dynamic and communication factors such as parental over-involvement and adolescent-parent concordance on responsibility for diabetes care appear be important determinants of metabolic outcomes in adolescents with diabetes. However, family dynamic factors do not account for the substantial differences in metabolic outcomes between centres.

Diabetes services in the UK: fourth national survey; are we meeting NSF standards and NICE guidelines?

BACKGROUND: Previous surveys of children's diabetes service provision in the UK have shown gradual improvements but continuing deficiencies. AIM: To determine whether further improvements in services have occurred. METHODS: A questionnaire was mailed to all paediatricians in the UK identified as providing care for children and adolescents with diabetes. Responses were compared with results of three previous surveys, and with recommendations in the Diabetes NSF and the NICE type 1 diabetes guidelines. RESULTS: Replies were received from 187 consultant paediatricians in 169 centres looking after children; 89% expressed a special interest in diabetes, 98% saw children in a designated diabetic clinic, and 95% clinics now have more than 40 patients. In 98% of the clinics there was a specialist nurse (82% now children's trained), but 61% clinics had a nurse:patient ratio <1:100; 39% of clinics did not have a paediatric dietician and in 78% there was no access to psychology/psychiatry services in clinics. Glycated haemoglobin was measured routinely at clinics in 86%, annual screening for retinopathy performed in 80%, and microalbuminuria in 83%. All centres now have local protocols for ketoacidosis, but not for children undergoing surgery (90%) or severe hypoglycaemia (74%). Mean clinic HbA1c levels were significantly lower in the clinics run by specialists (8.9%) than generalists (9.4%). There have been incremental improvements over the last 14 years since the surveys began, but only two clinics met all the 10 previously published recommendations on standards of care. CONCLUSIONS: The survey shows continuing improvements in organisational structure of services for children with diabetes but serious deficiencies remain. Publication and dissemination of the results of the previous surveys may have been associated with these improvements and similar recurrent service review may be applicable to services for other chronic childhood conditions.

Extreme hypervascularity and bruit in a treated hypothyroid goitre.

A child in early puberty, who presented with a modestly enlarged thyroid gland and confirmed hypothyroidism, was successfully treated with thyroxine. Subsequently a widespread bruit developed in the neck caused by bilaterally dilated superior thyroid arteries with increased blood flow to the goitre. At thyroidectomy, histopathology showed features of dyshormonogenesis with greatly increased vascularity and widespread diffuse staining for vascular endothelial growth factor (VEGF). It is likely that VEGF in association with other angiogenetic factors was associated with enlargement of the gland and its hypervascularity.

Graves' disease in DiGeorge syndrome: patient report with a review of endocrine autoimmunity associated with 22q11.2 deletion.

DiGeorge syndrome, which falls within a wider phenotypic spectrum associated with deletions of 22q11.2, is associated with a number of endocrine disorders. These include hypoparathyroidism, hypothyroidism and growth hormone deficiency. We report an unusual case of autoimmune hyperthyroidism (Graves' disease) presenting in a 3 year-old male with DiGeorge syndrome. The development of endocrine specific autoimmune disease in a syndrome associated with immune deficiency and the spectrum of endocrine autoimmunity associated with deletions of 22q11.2 are described. Paediatricians and patients with 22q11.2 deletions should be particularly aware of the risks of developing disorders of thyroid function.

Acute pancreatitis and its association with diabetes mellitus in children.

Acute pancreatitis is more common in childhood than has been appreciated previously. During acute attacks of pancreatitis, hyperglycaemia and glycosuria are not uncommon but permanent diabetes mellitus is rare. Acute pancreatitis can also be associated with diabetic ketoacidosis and the association between these two is of a two-way cause and effect relationship. Early imaging of the pancreas is recommended in children with severe prolonged abdominal pain.

Suppression of TSH in congenital hypothyroidism is significantly related to serum levels and dosage of thyroxine.

AIM: To assess thyrotropin (thyroid-stimulating hormone; TSH) suppression and serum thyroxine (T(4)) concentrations in infants with congenital hypothyroidism in relation to T(4) dose and pretreatment parameters. METHOD: A retrospective study of all cases treated in a single centre since neonatal screening began was performed. RESULTS: In 54 infants treated with a mean daily T(4) dose of 9.8 microg/kg, the TSH concentration was suppressed (<6 mU/l) in 65% of the cases by 6 months with the serum T(4) level at the upper end of the infant reference range. Infants who suppressed their TSH later did not differ in pretreatment serum TSH or T(4) concentration. T(4) dose and serum T(4) level were lower in infants whose TSH was not suppressed. CONCLUSIONS: TSH suppression in congenital hypothyroidism is significantly related to serum levels and dosage of T(4). We suggest that a delay in TSH suppression is mainly due to undertreatment.

Diabetes services in the UK: third national survey confirms continuing deficiencies.

AIMS: To determine the current level of diabetes services and to compare the results with previous national surveys. METHODS: A questionnaire was mailed to all paediatricians in the UK identified as providing care for children with diabetes aged under 16 years. Information was sought on staffing, personnel, clinic size, facilities, and patterns of care. Responses were compared with results of two previous national surveys. RESULTS: Replies were received from 244 consultant paediatricians caring for an estimated 17 192 children. A further 2234 children were identified as being cared for by other consultants who did not contribute to the survey. Of 244 consultants, 78% expressed a special interest in diabetes and 91% saw children in a designated diabetic clinic. In 93% of the clinics there was a specialist nurse (44% were not trained to care for children; 47% had nurse:patient ratio >1:100), 65% a paediatric dietitian, and in 25% some form of specialist psychology or counselling available. Glycated haemoglobin was measured routinely at clinics in 88%, retinopathy screening was performed in 87%, and microalbuminuria measured in 66%. Only 34% consultants used a computer database. There were significant differences between the services provided by paediatricians expressing a special interest in diabetes compared with "non-specialists", the latter describing less frequent clinic attendance of dietitians or psychologists, less usage of glycated haemoglobin measurements, and less screening for vascular complications. Non-specialist clinics met significantly fewer of the recommendations of good practice described by Diabetes UK. CONCLUSIONS: The survey shows improvements in services provided for children with diabetes, but serious deficiencies remain. There is a shortage of diabetes specialist nurses trained to care for children and paediatric dietitians, and a major shortfall in the provision of psychology/counselling services. The services described confirm the need for more consultant paediatricians to receive specialist training and to develop expertise and experience in childhood diabetes.

Prolonged hypothermia following respiratory syncytial viral infection in infancy.

Following proven respiratory syncytial viral infection, a previously healthy 2 year old boy displayed notable persistent hypothermia-the lowest temperature being 34.2 degrees C. No obvious ill effects were observed.

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.

Diabetes unmasked by electric shock.

Following an accidental electric shock, a boy with no previous symptoms developed hyperglycaemia, rapidly evolving into diabetes. He was aglycosuric for 24 hours after the shock. Islet cell antibodies were shown shortly after the accident. Although destined to develop diabetes, it seems likely that the electric shock unmasked impaired glucose tolerance. Glucose homoeostasis should be monitored in children following significant electric shocks.

Comparative incidence of Type I diabetes in children aged under 15 years from South Asian and White or Other ethnic backgrounds in Leicestershire, UK, 1989 to 1998.

AIMS/HYPOTHESIS: Estimates of incidence of Type I (insulin-dependent) diabetes mellitus in childhood populations vary around the world. This study aimed to estimate and compare the incidence of Type I diabetes in Leicestershire of children of South Asian and White or Other ethnic backgrounds. METHODS: All new cases of childhood-onset Type I diabetes diagnosed before 15 years of age in Leicestershire during the period 1989-98 were studied. Population data for Leicestershire from the 1991 census was used. Ethnicity was assigned to all children in the study according to their surnames. Incidence rates (95%-Confidence limits) for the South Asian and white or other ethnic group were estimated and compared. RESULTS: Over the 10-year period, 46 South Asian children and 263 children who were white or from another ethnic group fulfilled the criteria for inclusion in the study. Crude incidence rates per 100,000 person-years were 19.2 (12.0, 29.1) girls and 20.3 (13.0, 30.3) boys for South Asians and 17.7 (14.8, 21.1) girls and 17.7 (14.8, 20.9) boys for whites/others. Age and sex-specific rates were higher for South Asians over 5 years of age but differences were not statistically significant. CONCLUSION/INTERPRETATION: Type I diabetes incidence rates for South Asian children in Leicestershire were very similar to those for children who were in the white/other ethnic group, in contrast to very low rates reported from Asia. The convergence of rates for South Asians with other ethnic groups in Leicestershire suggests that environmental factors are more important than genetic predisposition in causing Type I diabetes in people of South Asian ethnic background.

Persistent differences among centers over 3 years in glycemic control and hypoglycemia in a study of 3,805 children and adolescents with type 1 diabetes from the Hvidøre Study Group.

OBJECTIVE: Twenty-one international pediatric diabetes centers from 17 countries investigated the effect of simple feedback about the grand mean HbA(1c) level of all centers and the average value of each center on changes in metabolic control, rate of severe hypoglycemia, and insulin therapy over a 3-year period. RESEARCH DESIGN AND METHODS: Clinical data collection and determination of HbA(1c) levels were conducted at a central location in 1995 (n = 2,780, age 0-18 years) and 1998 (n = 2,101, age 11-18 years). RESULTS: Striking differences in average HbA(1c) concentrations were found among centers; these differences remained after adjustment for the significant confounders of sex, age, and diabetes duration. They were apparent even in patients with short diabetes duration and remained stable 3 years later (mean adjusted HbA(1c) level: 8.62 +/- 0.03 vs. 8.67 +/- 0.04 [1995 vs. 1998, respectively]). Three centers had improved significantly, four centers had deteriorated significantly in their overall adjusted HbA(1c) levels, and 14 centers had not changed in glycemic control. During the observation period, there were increases in the adjusted insulin dose by 0.076 U/kg, the adjusted number of injections by 0.23 injections per day, and the adjusted BMI by 0.95 kg/m(2). The 1995 versus 1998 difference in glycemic control for the seven centers could not be explained by prevailing insulin regimens or rates of hypoglycemia. CONCLUSIONS: This study reveals significant outcome differences among large international pediatric diabetes centers. Feedback and comparison of HbA(1c) levels led to an intensification of insulin therapy in most centers, but improved glycemic control in only a few.

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.

Partial remission phase of diabetes in children younger than age 10 years.

There is renewed interest in the phase of partial remission in recently diagnosed diabetes because of the potential for pharmacological and immune intervention to preserve beta cell function. 95 children younger than 10 years were investigated to assess the influence of age, sex, diabetic ketoacidosis (DKA), admission at diagnosis, and ethnicity on the frequency of remission and insulin requirements during the first two years after diagnosis. Partial remission was defined as a requirement of insulin < 0.5 U/kg body weight/day. There was partial remission in 41 patients, with no differences for children aged 2-4 years and those aged 5-9 years. None of the five children aged < 2 years remitted. Forty five of 95 children were admitted to hospital at diagnosis, of whom 26 of 45 had DKA (blood pH < 7.25). In this number of children we were unable to show a statistical difference in the rate of remission with respect to DKA, admission to hospital at diagnosis, sex, or South Asian ethnic background. There were no differences in insulin requirements between the different groups by the end of two years and at that time seven of the children required insulin < 0.5 U/kg/day. The results suggest that even in preschool children there is potential for attempting to preserve beta cell function.