Altogether 29,000 children and young people have diabetes in the UK today and the incidence is rising at a rate of 3% per year. Despite clear evidence showing that poor glycaemic control increases the risk of long-term complications only 15.8% of children and young people in England and Wales have an HbA1c within target range. Potential complications include growth and endocrine disorders, acute problems such as diabetic ketoacidosis and hypoglycaemia as well as future microvascular and macrovascular disease. This article reviews these complications together with long-term survival associated with childhood diabetes describing how the outlook for these children and young people can be improved both by optimizing glycaemic control and by screening and prompt treatment of complications. Finally, possible future therapeutic options including the “artificial pancreas”, islet cell transplantation and stem cell technology are reviewed.

BACKGROUND:Maturity-onset diabetes of the young (MODY) is uncommon; however, accurate diagnosis facilitates personalized management and informs prognosis in probands and relatives.OBJECTIVE:The objective of the study was to highlight that the appropriate use of genetic and nongenetic investigations leads to the correct classification of diabetes etiology.CASE DISCUSSION:A 30-year-old European female was diagnosed with insulin-treated gestational diabetes. She discontinued insulin after delivery; however, her fasting hyperglycemia persisted. β-Cell antibodies were negative and C-peptide was 0.79 nmol/L. Glucokinase (GCK)-MODY was suspected and confirmed by the identification of a GCK mutation (p.T206M).METHODS:Systematic clinical and biochemical characterization and GCK mutational analysis were implemented to determine the diabetes etiology in five relatives. Functional characterization of GCK mutations was performed.RESULTS:Identification of the p.T206M mutation in the proband's sister confirmed a diagnosis of GCK-MODY. Her daughter was diagnosed at 16 weeks with permanent neonatal diabetes (PNDM). Mutation analysis identified two GCK mutations that were inherited in trans-p. [(R43P);(T206M)], confirming a diagnosis of GCK-PNDM. Both mutations were shown to be kinetically inactivating. The proband's mother, other sister, and daughter all had a clinical diagnosis of type 1 diabetes, confirmed by undetectable C-peptide levels and β-cell antibody positivity. GCK mutations were not detected.CONCLUSIONS:Two previously misclassified family members were shown to have GCK-MODY, whereas another was shown to have GCK-PNDM. A diagnosis of type 1 diabetes was confirmed in three relatives. This family exemplifies the importance of careful phenotyping and systematic evaluation of relatives after discovering monogenic diabetes in an individual.

Using targeted exome sequencing, we identified mutations in NNT, an antioxidant defense gene, in individuals with familial glucocorticoid deficiency. In mice with Nnt loss, higher levels of adrenocortical cell apoptosis and impaired glucocorticoid production were observed. NNT knockdown in a human adrenocortical cell line resulted in impaired redox potential and increased reactive oxygen species (ROS) levels. Our results suggest that NNT may have a role in ROS detoxification in human adrenal glands.

CONTEXT:Maternally inherited 3-kb STX16 deletions cause autosomal dominant pseudohypoparathyroidism type Ib (PHP-Ib) characterized by PTH resistance with loss of methylation restricted to the GNAS exon A/B.OBJECTIVE:The objective of the study was to search for the 3-kb STX16 deletion and to establish haplotypes for the GNAS region for two PHP-Ib patients and their families.SETTING:The study was conducted at a research laboratory and tertiary care hospitals.PATIENTS:The index cases presented at the ages 8 and 9.5 yr, respectively, with hypocalcemia, hyperphosphatemia, and elevated PTH.INTERVENTIONS:There were no interventions.RESULTS:DNA analyses of the index cases revealed an isolated loss of the GNAS exon A/B methylation and the 3-kb STX16 deletion. In the first family, the patient's healthy mother and sister showed no genetic or epigenetic abnormality, yet microsatellite analysis of the GNAS region indicated that both siblings share the same maternal allele, with the exception of an allelic loss for marker 261P9-CA1 (located within STX16), leading to the conclusion that a de novo mutation had occurred on the maternal allele. In the second family, three siblings of the index case are also affected, and an analysis of their DNA revealed the 3-kb STX16 deletion, which was also found in the healthy mother and a maternal uncle. Analysis of the siblings of the deceased maternal grandfather and some of their descendants excluded the 3-kb STX16 deletion, but haplotype analysis of the GNAS region suggested that he had acquired the mutation de novo.CONCLUSIONS:De novo 3-kb STX16 deletions, reported only once previously, are infrequent but should be excluded in all cases of PHP-Ib, even when the family history is negative for an inherited form of this disorder.

Screening for congenital hypothyroidism has been available for more than 30 years. Recent developments have included improvements in lab TSH screening with lower cut-off points usually at 6 mU/litre, earlier commencement of levothyroxine therapy and high dose treatment regimens. Normalization of TSH levels during the first 2 years with frequent thyroid function testing is likely to be beneficial to outcome. Children with agenesis of the thyroid gland or low free T4 at diagnosis still show significantly reduced IQ results at assessment years later.

Prader Willi syndrome is a rare genetic disorder associated with extreme obesity, short stature, and learning disability. There is a characteristic behavioural phenotype. Understanding of the genetic mechanisms has expanded in recent years as new laboratory techniques have been developed. Nowadays the clinical diagnosis is normally made in infancy. Management focuses on improving nutrition in the early months, then restricting calories to limit rapid weight gain. Several endocrine problems are encountered and these are discussed. There is increasing experience of growth-hormone therapy both to increase longitudinal growth but also to improve body composition and possibly improve mobility.

Diabetes remains a major contributor to both perinatal mortality and morbidity. The complex problems associated with both gestational and pre-gestational (types 1 and 2) diabetes in pregnancy are diverse and are not always managed optimally. Improvement of obstetric and newborn care in these patients has undoubtedly resulted in a significant reduction in neonatal mortality and morbidity over the last few decades. However, there is still significant room for improvement, and progress has been slow in some areas of clinical management. Evidence has now emerged that type 2 diabetes during pregnancy has a similar outcome for infants as type 1 diabetes. This has obvious implications for the future as the incidence of type 2 diabetes is rising worldwide. The key to success remains pre-pregnancy planning and tight glycaemic control throughout pregnancy/labour, as well as the early recognition and intensive care treatment of newborn complications. A thorough knowledge of potential problems in diabetic pregnancies and the infants of diabetic mothers is mandatory for professionals involved in their care.

Cycling is a healthy activity for children, but accidents do occur and can result in death or disability. In the UK, around 28 children per year die from cycle injuries and most of these are directly attributable to head injury, and figures for permanent brain injury are around 1,000 children a year. What are the potential benefits of legislation on helmet usage and reduction in injury?Early studies from 1996 showed that helmets reduced the risk of severe brain injury by 74%. Subsequent studies in other countries have confirmed these initial findings, and a meta-analysis using 16 studies by Attewell in 2001 showed clear benefits of helmets in reducing injury including when there has been a motor vehicle impac; a situation that is more likely to lead to serious injury than a fall from a bike. Furthermore, upper and mid facial injuries are reduced by helmet usage and Thompson et al. have demonstrated a protective effect of 65%.Legislation for compulsory wearing of cycle helmets has been introduced in many countries including over one-third of States in USA, with significant reductions in head injury rates and deaths. Initial concerns about a reduction of cycling activity have not been confirmed. There is a good case for continued introduction of legislation to maximise helmet wearing by young cyclists.

Reports a study investigating teenage attitudes towards bicycle helmets. A questionnaire was administered to a sample of 1,093 11‐16‐year‐olds to assess their helmet ownership and use and their attitudes towards bicycle helmets. More 11‐13‐year‐olds owned cycle helmets than 14‐16‐year‐olds, with similar wearing rates across age. Girls placed more importance on whether helmet wearing was compulsory at school and comfort of helmets, while boys placed more importance on whether helmet wearing was compulsory by law. Those who owned helmets were more likely to place importance on whether wearing a helmet was law and whether it was a school rule than were those who did not own helmets. The 11‐13‐year‐olds placed more importance on whether helmet wearing was compulsory at school and by law, while 14‐16‐year‐olds placed more importance on comfort, appearance, cost, and their friends’ opinions as reasons.

Objectives—To evaluate the effect of a bicycle helmet promotion campaign on helmet wearing among cyclists less than 16 years of age from 1992–98. Setting—Reading, West Berkshire, UK. Methods—A hospital led bicycle helmet promotion campaign targeted at 5–15 year olds. The campaign focused on education with active involvement of the children, parents, schools, and safety organisations. Local media and children's celebrities raised the profile of the campaign and a low cost helmet purchase scheme was also set up. A self administered questionnaire survey of 3000, 11–15 year olds was carried out over the period of the campaign. A control group of 3000 teenagers was obtained from a neighbouring area without a helmet campaign. Accident and emergency (A&E) figures were obtained from the local hospital within the campaign area on all children aged under 16 years, attending with bicycle injuries. Unfortunately, no figures were available from the A&E department in the control area. Results—Self reported helmet use among 11–15 years olds living in the campaign area increased from 11% at the start of the campaign to 31% after five years (p<0.001), with no change in the control group. Hospital casualty figures in the campaign area for cycle related head injuries in the under 16 years age group, fell from 112.5/100 000 to 60.8/100 000 (from 21.6% of all cycle injuries to 11.7%; p<0.005). Conclusions—This hospital led community bicycle helmet promotion campaign directed at young people showed an increase in the number of children reporting that they “always” wore their helmet while cycling. There was a significantly higher rate of helmet wearing than in the control area, and a significant reduction in head injuries.

It has been clear for many years that there has been a very variable standard of higher medical training in all specialities in this country. Some jobs have been excellent with a large training component, whilst other posts have had all service commitment with no time for research, audit or supervised teaching. Furthermore in 1992 there were concerns expressed by The European Committee of the EEC about UK training of doctors. Dr Kenneth Calman, The Chief Medical Officer chaired a committee looking into training of doctors for consultant posts in 1992/3 and the recommendations of the committee were that specialist training should be shorter, better structured and more intensive. Furthermore regular assessment and appraisal should also be incorporated into these posts to monitor standards. The overall aims of the exercise are summarised in Table 1.

A male infant aged 2 ½ years born to a Malaysian mother presented with a 3-week history of pain and swelling of his right foot. The skin over the swelling was hot and tender. He was started on iv flucloxacillin.Investigations:Hb 10.2 × 109/1WBC 6.2 × 10911Platelets 323 × 109/1CRP 12.SmgtI (normal < 8)Blood culture - no growth after 48hrStaphylococcal antigen tests negativeASO titre < 40 U/ml (normal < 320)

The discovery of insulin in 1921 in Canada led to Leonard Thompson aged 14 years, receiving regular insulin therapy for his diabetes mellitus the following year — the improvement in his health and well-being was remarkable. Very quickly during the next year or so insulin extracted from animal pancreases became available throughout the developed world, resulting in a revolution in treatment of children and adults with diabetes. Prior to this time life expectancy in juvenile deabetes was 18 months, and quality of life was poor due to treatment with starvation diets. Currently the aims of treatment with insulin include prevention of short term symptoms, maintenance of adequate growth, and emontional adjustment but also reduction of long term vascular complications.