Search

LAY SUMMARYThis study compared the baseline physical and mental health of officer candidates attending military college and officer training programs (i.e., non-direct-entry officer or non-DEO stream) with those of officers entering through a direct stream (direct-entry officer or DEO stream). Overall, DEO candidates had better health than non-DEO candidates. Female DEO and non-DEO candidates also reported more physical activity than male DEO and non-DEO candidates, and female non-DEO candidates had more symptoms of mental illness than male non-DEO candidates. A better understanding of these groups may lead to opportunities to customize health screening and supports depending on officer entry stream and sex; however, more research is needed to inform policy.

Adverse childhood experiences (ACEs) have consistently been associated with adult psychopathology and are commonly reported among military populations, with women more likely to report many types of ACEs than men. Limited research has examined the role of gender in the association between ACEs and mental health in military populations. The current study assessed the significance of gender differences in ACEs and mental health and explored the associations among these variables in a sample of Canadian Armed Forces recruits/officer cadets. Analyses with cross-sectional Recruit Health Questionnaire (RHQ) data from 50,603 recruits/officer cadets indicated that women were more likely to report witnessing domestic violence, experiencing sexual abuse, and living with someone with mental health problems or alcohol misuse, odds ratios (ORs) = 1.22-4.35, ps.001. Women were more likely to screen positive for depression, adjusted (aORs) = 1.25-1.49, p.001-p = .002, and anxiety, aORs = 2.00-2.33, ps.001, before basic military training. ACEs were associated with screening positive for probable mental health conditions, aORs = 1.54-6.13, p.001-p = .017. A significant interaction suggested the association between childhood sexual abuse and depression was stronger for men, aOR = 2.49, p.001, than women, aOR = 1.63, p = .002, as was the association between childhood sexual abuse and posttraumatic stress disorder, men: aOR = 6.06, p.001, women: aOR = 3.36, p.001. These results underscore the importance of considering gender and childhood trauma in mental health interventions with military personnel.

Physics-based electrochemical battery models derived from porous electrode theory are a very powerful tool for understanding lithium-ion batteries, as well as for improving their design and management. Different model fidelity, and thus model complexity, is needed for different applications. For example, in battery design we can afford longer computational times and the use of powerful computers, while for real-time battery control (e.g. in electric vehicles) we need to perform very fast calculations using simple devices. For this reason, simplified models that retain most of the features at a lower computational cost are widely used. Even though in the literature we often find these simplified models posed independently, leading to inconsistencies between models, they can actually be derived from more complicated models using a unified and systematic framework. In this review, we showcase this reductive framework, starting from a high-fidelity microscale model and reducing it all the way down to the Single Particle Model (SPM), deriving in the process other common models, such as the Doyle-Fuller-Newman (DFN) model. We also provide a critical discussion on the advantages and shortcomings of each of the models, which can aid model selection for a particular application. Finally, we provide an overview of possible extensions to the models, with a special focus on thermal models. Any of these extensions could be incorporated into the microscale model and the reductive framework re-applied to lead to a new generation of simplified, multi-physics models., 50 pages, 9 figures

Introduction: Transition to civilian life may not only be highly challenging for service members, but also for their spouses, especially following a medical release. Often, the families of ill or injured service members must confront unexpected responsibilities related to caring for the member, while having to adjust to civilian life. This study was conducted to examine military to civilian transition challenges and engagement in caregiving among spouses of newly released Canadian Armed Forces (CAF) Veterans and their associations with spousal well-being. Methods: The Canadian Armed Forces Transition and Well-Being Survey (CAFTWS) was administered to spouses of CAF Veterans released in 2016 ( N = 595). The survey assessed spouses’ experiences with a range of military to civilian transition challenges and engagement in caregiving, as well as various indicators of their well-being (e.g., daily stress and psychological distress). Regression analyses were conducted to assess the associations of transition challenges and caregiving with well-being. Results: Results revealed that challenges related to finding educational opportunities and health care providers, and loss of military identity, as well as more frequent engagement in caregiving, were significantly associated with elevated levels of daily stress and psychological distress among spouses of Veterans. Discussion: This study is among the first to examine transition experiences, caregiving and well-being in a representative sample of Veterans’ spouses. Findings outline key challenges experienced and underline important predictors of well-being. Recommendations on services that could help facilitate or improve the experiences of families during the transition process are discussed.

Recent reported increases in sexually transmitted infections (STIs) among young Canadian Armed Forces (CAF) members prompt a need to better understand risky sexual behaviors. Although CAF members m...

Recent studies showing an association between adverse childhood experiences and the development of alexithymia in military personnel have generated interest regarding the role of alexithymia in the pathway linking childhood trauma exposure to mental health disorders. Accordingly, the current study was conducted to (a) examine the associations among adverse childhood experiences, alexithymia, and symptoms of depression and posttraumatic stress disorder (PTSD) among recently deployed Canadian military personnel and (b) assess the mediating role of alexithymia in these associations. Data collected from 2,927 members of the Canadian Armed Forces at baseline and after their return from an overseas deployment were subjected to a prospective path analysis. The results of the path analysis, R2 = .35, pointed to a significant direct effect of childhood adversity on postdeployment mental health symptoms. Contrary to our expectations, the results also pointed to a negative indirect effect of childhood neglect, suggesting that childhood neglect contributed to lower levels of postdeployment depression and PTSD symptoms through the dimension of alexithymia related to difficulty in describing feelings. These patterns of associations, for the most part, persisted even when accounting for combat exposure during recent deployments, R2 = .42. The present results are discussed in light of study limitations and methodological considerations, and policy and clinical implications are noted.

The aim of this study was threefold: (a) to assess the factor structure of the Kessler Psychological Distress Scale (K10) to determine whether interpreting the scale as a single dimensional measure...

Aim To assess cholesterol screening of children with Type 1 diabetes by diabetes professionals using a survey of current practice, given that National Institute of Health and Care Excellence guidelines on childhood Type 1 diabetes do not recommend cholesterol screening, yet the National Paediatric Diabetes Audit has an annual cholesterol measure (> 12 years) as a key outcome indicator. Methods An online survey was sent to 280 members of the Association of Children's Diabetes Clinicians to assess cholesterol screening practice in children. Results A total of 87 diabetes professionals (31%) responded. The results showed that 94% of respondents measured cholesterol, 33% did this annually on all children, and 7% measured fasting cholesterol. A total of 63% used no guidelines to decide treatment or further investigation. The definition of ‘high’ cholesterol varied from > 4.5 to > 8 mmol/l, with 40% giving no response or specific level. Only 14% of clinicians had started statin therapy in their diabetes clinic in the previous 5 years. Conclusion Whilst the majority of diabetes professionals measured cholesterol in children with Type 1 diabetes, there was marked variability in sampling, in children screened and in action taken if levels were considered abnormal. It is debatable whether cholesterol measures should be undertaken, certainly more than once, and whether cholesterol level should feature as a key outcome in the national audit in future., What's new? Annual measurement of cholesterol in children aged > 12 years with Type 1 diabetes is one of the seven core care processes outlined in the National Paediatric Diabetes Audit (NPDA).The National Institute for Health and Care Excellence (NICE) guidelines (NG18) for management of children and young people with diabetes 2015, do not include cholesterol screening for children with Type 1 diabetes.There is much variation in cholesterol measurement, evaluation and treatment among clinicians looking after children with Type 1 diabetes.We suggest further evidence is needed on the utility of cholesterol screening in the paediatric population, and consistency is needed between NICE guidance and NPDA standards.

Aims To determine the efficacy and patient perception of various transfer procedures from paediatric to adult diabetes services. Methods Comparison between four districts in the Oxford Region employing different transfer methods, by retrospective study of case records and interviews of patients recently transferred from paediatric diabetes clinics. The main outcome measures were age at transfer, clinic attendance rates, HbA1c measurements and questionnaire responses. Results Two hundred and twenty-nine subjects (57% males) > 18 years old in 1998 and diagnosed with Type 1 diabetes

We have investigated the relation between nocturnal insulin requirements and nocturnal growth hormone (GH) release in 26 diabetic adolescents at various puberty stages and have examined the effect of nocturnal GH suppression on pre-breakfast insulin requirement. In all the studies, euglycaemia was maintained overnight using a computer-calculated variable-rate insulin infusion, and 15-min blood samples were collected for GH assay. During initial clamp studies, insulin infusion rates were greater from 0500-0800 h (15.22 +/- 0.95 mU/kg/h, mean +/- SEM) than from 0100-0400 h (12.42 +/- 0.84 mU/kg/h, P less than 0.001). The increase in insulin infusion rate correlated with mean overnight GH concentration (r = 0.68, P less than 0.001), and was maximal at puberty stage 3 in both sexes. In seven of the subjects, a second identical clamp was performed following administration of 100 mg oral pirenzepine. During these studies, mean overnight GH levels were reduced by 11-85%, from 17.6 +/- 1.6 to 7.5 +/- 2.2 mU/l; P less than 0.01. Insulin requirements were not significantly different between the periods 0100-0400 and 0500-0800 h during these studies, and the reduction in pre-breakfast (0500-0800 h) insulin requirement when compared with the baseline studies correlated with the fall in GH secretion (rs = 0.82, P less than 0.01). The dawn increase in insulin requirement in adolescents with IDDM is related to the overnight GH secretion during puberty, and pre-breakfast insulin requirement can be reduced by suppressing nocturnal GH release.

Following a standard mixed meal, plasma concentrations of growth hormone releasing hormone (GHRH), somatostatin (SMS) and growth hormone (GH) were measured every 30 min for 300 min in six young adults with type I insulin-dependent diabetes mellitus (IDDM) and five normal controls. Mean blood glucose concentrations were higher and mean free insulin levels lower in the diabetics compared with controls both in fasting specimens and at all times following the mixed meal. Basal concentrations (mean +/- SEM) of GHRH were similar in diabetic (12.7 +/- 1.8 pg/ml) and control subjects (11.8 +/- 1.1 pg/ml). Following ingestion of the mixed meal, a rise in GHRH was observed in the control subjects maximal between 30 and 240 min (P less than 0.025) but the response was blunted in the diabetics. Mean GHRH concentrations were greater in the controls than in the diabetic subjects at all stages during the test, the maximum difference being noted at 120 mins (P less than 0.04). Basal SMS concentrations and those observed after the mixed meal were similar in diabetic and control subjects. These results indicate that glucose and insulin may play a role in the regulation of GHRH release following a mixed meal but circulating levels of GHRH and SMS are unlikely to be relevant to the abnormal regulation of GH in IDDM.

To determine the extent to which spontaneous plasma GH concentrations are abnormal in adolescents with insulin-dependent diabetes mellitus we performed 12-h overnight plasma GH profiles in 21 diabetic adolescents (11 males and 10 females; aged 9.8-16.5 yr; median, 13.6 yr) and 34 healthy adolescent controls (17 males and 17 females; aged 9.1-20.9 yr; median, 13.1 yr). Data were analyzed using the pulse detection program Pulsar and time series analysis, and are presented with respect to age and puberty stage. Mean and maximum GH concentrations, sum of the peak amplitudes, and mean calculated baseline concentrations in the normal children were higher during puberty; highest levels were seen in girls at puberty stages 2-3, and in boys at stages 4-5. A similar pattern was observed in the diabetic adolescents, but all measures of pulse height and mean calculated baseline concentrations were significantly greater than those in the normal subjects (multivariate analysis, P less than 0.001). Pulse frequency did not change during puberty in the normal or diabetic subjects, and the dominant pulse periodicity in both groups was about 180 min. We conclude that the predominant change in GH release during puberty is in pulse amplitude, and that this is increased in diabetes, whereas pulse frequency remains constant in both normal and diabetic adolescents.

With increasing numbers of children being diagnosed with type 1 diabetes at younger ages, and intensification of insulin regimens, many more children require support with their diabetes at primary school. I report here our own experience of setting up a structure for support in schools based on trained volunteers who can supervise or administer insulin with pens or pumps, and who do so based on intensive management including carbohydrate counting and correction doses. There is a clear legal framework to support families asking for help in schools but still no compulsion on schools to provide a member of staff to carry out care, which has to rely on volunteers. We have, however, negotiated a system with our primary care trust and local authority whereby diabetes specialist nurses (DSNs) train up volunteers identified by the school, and, together with the parents, draw up a comprehensive medical management plan. The volunteers are then trained by the DSN, and the parent agrees to go into the school to supervise until both the volunteer and parent are happy that they are competent, when the DSN then goes back into school to certify competence. This has taken several years to complete, but all schools in Oxfordshire but one have agreed to work according to this guidance so that over 130 children now receive appropriate care in school. Copyright © 2012 John Wiley & Sons.

Applying Cognitive Appraisal Theory (Lazarus & Folkman, 1984), this study sought to determine the mediating effect of cognitive appraisal on combat exposure and psychological distress. A total of 3...

Aim To assess the provision of UK paediatric and adolescent diabetes services and examine changes in service delivery since 2002. Method Questionnaires were sent to the lead paediatric consultant from all paediatric and adolescent diabetes services (n=205). Questions were based on National Institute for Health and Clinical Excellence and Scottish Intercollegiate Guidelines recommendations for diabetes care in childhood. Results were analysed using parametric and non-parametric tests. Results 129 Services (63%) returned questionnaires involving 220 clinics. Staffing has improved and 98% of consultants have a special interest in diabetes (89%, 2002). In 88% of services, the diabetes specialist nurse worked solely in paediatric diabetes (53%, 2002). Only 21% of clinics have a psychological professional integrated within the diabetes team (20%, 2002). Over 94% of services offered support with intensive insulin regimens causing problems at school for 36% of services. Almost all services offer annual microvascular screening (98–100%) but transitional care was variable; only 76% of services have specific local protocols for transition and 21% organise transfer by letter only. Conclusion Paediatric and adolescent diabetes services are rising to the challenge of providing high-quality care despite rising prevalence and increasingly complex insulin regimes. Services have improved in a number of key areas but serious deficiencies remain.

Diabet. Med. 27, 1284–1288 (2010) Abstract Introduction There is some evidence of long-term tracking of HbA1c levels within diabetes centres, but little evidence of individual tracking. Methods HbA1c levels of children in the clinic over a period of 15 years were retrieved from the clinical chemistry laboratory information system. We measured the correlation of HbA1c between years (Spearman and Pearson rank correlation), as well as the relationship of HbA1c with age and the change over time in the clinic. Results Data were collected from 362 children and young people [158 female (44%)], aged 0–18 years (median 10.4 years), with 0–13.6 years of follow-up (median 4.7 years). Mean HbA1c levels fell from 9.3 ± 1.5% (78 ± 16 mmol/mol) in 2001 to 8.1 ± 1.3% (65 ± 14 mmol/mol) in 2009 in those at least 6 months after diagnosis (P

Diabetes mellitus is one of the most common long-term conditions in childhood. The management of children and young people is predominantly carried out by general paediatricians with a special interest in diabetes, together with paediatric diabetes specialist nurses and dieticians. Various guidelines and recommendations have been published with the aim of improving standards and quality of care; however, surveys conducted in the United Kingdom at periodic intervals have regularly shown deficiencies in the provision of care for these children and young people. With intensification of insulin regimens, education of the child and family is the cornerstone of management with a view to enabling self-care. Targets of each service should be to improve glycaemic control and thereby to prevent complications. Psychological support, social services, counselling, ophthalmology, and podiatry should be available. To ensure that care is of the highest standard, the team should have access to good clinic and hospital facilities and adequate manpower. Services should be commissioned accordingly to meet the demands of the local population. Regional networks form an important forum to discuss case load, sharing of resources, training for consistency in the region, and collection of outcome data with contribution to national audit.

Aims Carbohydrate (CHO) quantification is used to adjust pre-meal insulin in intensive insulin regimens. However, the precision in CHO quantification required to maintain postprandial glycaemic control is unknown. We determined the effect of a ±10-g variation in CHO amount, with an individually calculated insulin dose for 60 g CHO, on postprandial glycaemic control. Methods Thirty-one children and adolescents (age range 9.5–16.8 years), 17 using continuous subcutaneous insulin infusion (CSII) and 14 using multiple daily injections (MDI), participated. Each subject consumed test lunches of equal macronutrient content, differing only in carbohydrate quantity (50, 60, 70 g CHO), in random order on three consecutive days. For each participant, the insulin dose was the same for each meal, based on their usual insulin : CHO ratio for 60 g CHO. Activity was standardized. Continuous glucose monitoring was used. Results The CSII and MDI subjects demonstrated no difference in postprandial blood glucose levels (BGLs) for comparable carbohydrate loads (P > 0.05). The 10-g variations in CHO quantity resulted in no differences in BGLs or area under the glucose curves for 2.5 h (P > 0.05). Hypoglycaemic episodes were not significantly different (P = 0.32). The 70-g meal produced higher glucose excursions after 2.5 h, with a maximum difference of 1.9 mmol/l at 3 h (P = 0.01), but the BGLs remained within international postprandial targets. Conclusions In patients using intensive insulin therapy, an individually calculated insulin dose for 60 g of carbohydrate maintains postprandial BGLs for meals containing between 50 and 70 g of carbohydrate. A single mealtime insulin dose will cover a range in carbohydrate amounts without deterioration in postprandial control.

Objective: Type 1 diabetes mellitus (T1DM) is a chronic condition whose management affects the whole family, and siblings of children with chronic conditions have been shown to be at higher risk of emotional and behavioural problems. The aims of this study were to investigate sibling adjustment to T1DM using a cross-sectional questionnaire survey design. Methods: Forty-one families (48% of those eligible) were recruited from a children’s diabetes clinic. From each family, one parent and one sibling of the child with T1DM participated. Parents completed questionnaires measuring sibling adjustment and measures of major life events, social support and parenting stress. Demographic and disease information was obtained from medical records. Siblings completed questionnaires assessing cognitive appraisals and coping strategies. A semi-structured interview was also administered to siblings. Results: Siblings were found to be better adjusted than normative data (p

The term ‘diabetic coma' is outdated, confusing and should probably no longer be used. Traditionally, it has been an alternative term for diabetic ketoacidosis (DKA), even when the child is not technically in coma. Although DKA remains the most common and important cause of coma in a child with diabetes, there can be other causes which must be borne in mind. This review will focus on the various causes of coma in children with diabetes, the underlying pathophysiology, clinical presentation and current thoughts on their management in an attempt to guide the paediatrician when faced with a comatose diabetic patient.

BACKGROUNDCerebral oedema is a major cause of morbidity and mortality in children with insulin dependent diabetes.AIMSTo determine the risk and outcome of cerebral oedema complicating diabetic ketoacidosis (DKA).METHODSAll cases of cerebral oedema in England, Scotland, and Wales were reported through the British Paediatric Surveillance Unit between October 1995 and September 1998. All episodes of DKA were reported by 225 paediatricians identified as involved in the care of children with diabetes through a separate reporting system between March 1996 and February 1998. Further information about presentation, management, and outcome was requested about the cases of cerebral oedema. The risk of cerebral oedema was investigated in relation to age, sex, seasonality, and whether diabetes was newly or previously diagnosed.RESULTSA total of 34 cases of cerebral oedema and 2940 episodes of DKA were identified. The calculated risk of developing cerebral oedema was 6.8 per 1000 episodes of DKA. This was higher in new (11.9 per 1000 episodes) as opposed to established (3.8 per 1000) diabetes. There was no sex or age difference. Cerebral oedema was associated with a significant mortality (24%) and morbidity (35% of survivors).CONCLUSIONSThis first large population based study of cerebral oedema complicating DKA has produced risk estimates which are more reliable and less susceptible to bias than those from previous studies. Our study indicates that cerebral oedema remains an important complication of DKA during childhood and is associated with significant morbidity and mortality. Little is known of the aetiology of cerebral oedema in this condition and we are currently undertaking a case control study to address this issue.

Cerebral oedema remains the leading cause of death and morbidity in children with Type 1 diabetes mellitus. Around seven per thousand episodes of diabetic ketoacidosis (DKA) are complicated by cerebral oedema, and one-quarter of those children will die from it. The cause or causes of cerebral oedema are still very poorly understood, but lawyers are already keen to implicate various aspects of the management of DKA. There have been many theories as to the pathophysiology of cerebral oedema, and possible contributing factors may be excessive rate of rehydration, falling plasma osmolality (particularly that due to a reduction in plasma sodium concentration), hypoxia and insulin dosage. There is some supportive evidence for all of these factors in some cases, but there have been no sizeable case-control studies, in part because of the rarity of the condition. Furthermore, cerebral oedema can still occur even when the management of DKA follows current 'best practice' guidelines. As the mechanisms of cell volume regulation within the brain are increasingly understood, different questions may provide greater insights. For example, what is it about children that makes them so much more susceptible to cerebral oedema than adults? And why does one child treated in a certain way develop cerebral oedema whereas another does not? The anxiety over causing cerebral oedema has driven most of the changes in the management of DKA over recent decades, yet there is no evidence that the incidence has reduced. Until the causes are understood, we cannot be dogmatic about treatment recommendations.

Summary Although DKA and hypoglycaemia are the main causes of coma in diabetes, a full critical assessment should include the possibility of other causes. The importance of regular neurological observations and careful monitoring of fluid balance in particular in these children is crucial to their management on the ICU.Fig. 1Flow diagram for management of hypoglycaemia in the unconscious or semi-conscious child with diabetes.

Type 1 diabetes in childhood is one of the commoner long term conditions of childhood. It is treated by specialist teams in secondary care using increasingly intensive insulin regimens, but the onset is generally diagnosed by primary care physicians, sometimes later than is ideal. #### Case scenario A 7 year old boy with acute abdominal pain and vomiting is brought to see his general practitioner by his mother. He was being bullied at school, and because his mother attributed his recent onset of bed wetting to stress she did not mention this symptom to the GP. The GP considers appendicitis a possibility but first decides to rule out a urinary tract infection. A urine dipstick test is positive for glucose and ketones. She refers the child at once to the paediatric team for immediate management of his diabetic ketoacidosis. #### How common is it? About 30% of children with newly diagnosed diabetes have had at least one related medical visit before the diagnosis, suggesting that medical practitioners are missing the diagnosis.5 Drinking a lot and …

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 μM), reaching a peak at 0200 (103 ± 16 μM, 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.

Diabet. Med. 27, 348–353 (2010) Abstract Aims Carbohydrate (CHO) counting allows children with Type 1 diabetes to adjust mealtime insulin dose to carbohydrate intake. Little is known about the ability of children to count CHO and whether a particular method for assessing CHO quantity is better than others. We investigated how accurately children and their caregivers estimate carbohydrate, and whether counting in gram increments improves accuracy compared with CHO portions or exchanges. Methods One hundred and two children and adolescents (age range 8.3–18.1 years) on intensive insulin therapy and 110 caregivers independently estimated the CHO content of 17 standardized meals (containing 8–90 g CHO), using whichever method of carbohydrate quantification they had been taught (gram increments, 10-g portions or 15-g exchanges). Results Seventy-three per cent (n = 2530) of all estimates were within 10–15 g of actual CHO content. There was no relationship between the mean percentage error and method of carbohydrate counting or glycated haemoglobin (HbA1c) (P > 0.05). Mean gram error and meal size were negatively correlated (r = −0.70, P

aDivision of Endocrinology, Children’s Hospital Boston, MA, USA; bSchool of Women’s and Children’s Health, University of New South Wales, Sydney, Australia; cUniversity of Toronto, The Hospital for Sick Children, Toronto, Canada; dDepartment of Paediatrics, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK; eDepartment of Paediatrics, John Radcliffe Hospital, Oxford, UK; fEndocrinology Service Department of Paediatric Medicine, KK Children’s Hospital, Singapore; gDivision of Endocrinology, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA; hDepartment of Pediatric Endocrinology, Children’s Hospital, University of Pittsburgh, PA, USA; iDepartment of Pediatrics, Uddevalla Hospital, Uddevalla, Sweden

Diabetes control is poor in children in the UK compared with most European countries; only 17% of children achieve HbA1c levels below the target value of 7.5%.1 Historically, we have tended to use insulin regimens requiring twice-daily injections (before breakfast and before the evening meal), meaning that children did not generally require an insulin injection or blood glucose check during the school day. However, the majority of large centres in this country and most in Europe are now using multiple injection therapy (MIT) and continuous subcutaneous insulin infusions (insulin pumps) which are more physiological and have the potential of improving glycaemic control when used intensively. Both require much greater input throughout the day as insulin is required at every meal-time, and, in order to improve control further, the dose of insulin must be related to the carbohydrate content of the meal and to the prevailing blood glucose level. Diabetes management during the day has thus become far more complex. Parents have learned the new skills well, particularly when these regimens are started from diagnosis, but there are often huge obstacles to setting appropriate support in place in schools. For children over the age of about 10–11 years, who are largely able to carry out their own injections reliably, schools will still have minimal input in most cases. The greater problem comes when doctors and parents wish to use these regimens in children who are too young to perform their own injections and blood glucose testing, even under supervision. So how should we move forward? Do children have the right to help in school or should we adjust the daily regimens so that insulin injections are not required at school? The landmark Diabetes Control and Complications Trial showed beyond doubt that intensive insulin regimens (and this trial was carried out …

Aims To determine the prevalence of abnormal lipid levels in a large group of children and adolescents with Type 1 diabetes and to examine the changes longitudinally. In addition, to study the relationships of any lipid abnormalities to glycaemic control, age and duration of diabetes. Methods Non-fasting blood samples were taken annually from all the patients in the Oxford Children's diabetes clinic and total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, triglycerides (TG) and glycated haemoglobin (HbA1c) measured over a period of 8 years. Low-density lipoprotein (LDL) cholesterol and non-HDL were calculated from these values and compared. Tests performed less than 4 months after diagnosis were excluded. Results A total of 229 children had complete data from more than 1 year and 798 sets of data were examined. TC was lower in males and increased with duration of diabetes and with increasing HbA1c. HDL cholesterol fell with increasing age, but independently increased with duration, and was not related to HbA1c. LDL cholesterol and non-HDL cholesterol were highly correlated (r = 0.9). Both were lower in males and increased with duration of diabetes. Non-HDL cholesterol increased with HbA1c. A total of 23.7% had HDL cholesterol 5.2 mmol/l. Thirty-eight per cent had LDL cholesterol > 2.6 mmol/l and 10.8% > 3.4 mmol/l, the thresholds for lifestyle and drug intervention respectively. Conclusions Abnormalities in plasma lipid levels are common in this age group and the prevalence increases with poor glycaemic control and with duration of diabetes. Around 10% of adolescents would fit criteria for lipid-lowering medication in adults, but further study is needed to examine the risks and benefits in this age group.

This study investigated the prevalence of mothers' anxiety, depression, and posttraumatic stress disorder (PTSD) symptoms triggered by their child's type 1 diabetes and identified individual diabetes-related traumatic stressors. Sixty mothers of children who had been diagnosed with diabetes within the past 5 years were interviewed using the Structured Clinical Interview (SCID) DSM-IV-PTSD module, and completed the Posttraumatic Stress Diagnostic Scale (PDS) and the Hospital Anxiety and Depression Scale (HADS). Fifteen percent of participants met criteria for partial and 10% for full PTSD. Fifty-five percent of participants identified hearing about their child's diagnosis as the traumatic stressor. Forty percent of participants reported moderate to severe symptoms of state-anxiety and 17% moderate to severe symptoms of depression. This study highlights the significant emotional impact this diagnosis in children can have on mothers, and identifies a population with clinical needs.

Aims To determine whether higher than average albumin excretion during early puberty identifies subjects who will subsequently develop microalbuminuria (MA) and clinical proteinuria. Methods Longitudinal data from the Oxford Regional Prospective Study of Childhood Diabetes (ORPS; n = 554, median duration of follow-up 10 years; range 3.0–16.7) with assessment of albumin/creatinine ratios in three early morning urine samples collected annually. An albumin excretion phenotype was derived from longitudinal data, for each individual, defining deviation from the mean of regression models, including covariates gender, age, duration of diabetes and age at assessment. Tracking of the phenotypes was confirmed in a second independent cohort from Perth, Australia. Results The albumin excretion phenotype showed reasonable correlation between age 11–15 years and age 16–18 years in both cohorts, indicative of good ‘tracking’. In the ORPS cohort, tertiles of the albumin excretion phenotype at aged 11–15 years were predictive of subsequent risk for the development of MA. All of the subjects developing clinical proteinuria had an albumin excretion phenotype in the upper tertile or an HbA1c > 9% at aged 11–15 years. Conclusions Identification of adolescents at risk of diabetic nephropathy using an albumin excretion phenotype is feasible. When combined with elevated HbA1c, it may identify subjects for trial of early intervention with angiotensin-converting enzyme inhibitors/angiotensin-II receptor antagonists and statins to improve long-term prognosis in these subjects where sustained improvement in glycaemic control may be difficult to achieve.

BACKGROUND: A single family has been described in which obesity results from a mutation in the leptin-receptor gene (LEPR), but the prevalence of such mutations in severe, early-onset obesity has not been systematically examined. METHODS: We sequenced LEPR in 300 subjects with hyperphagia and severe early-onset obesity, including 90 probands from consanguineous families, and investigated the extent to which mutations cosegregated with obesity and affected receptor function. We evaluated metabolic, endocrine, and immune function in probands and affected relatives. RESULTS: Of the 300 subjects, 8 (3%) had nonsense or missense LEPR mutations -- 7 were homozygotes, and 1 was a compound heterozygote. All missense mutations resulted in impaired receptor signaling. Affected subjects were characterized by hyperphagia, severe obesity, alterations in immune function, and delayed puberty due to hypogonadotropic hypogonadism. Serum leptin levels were within the range predicted by the elevated fat mass in these subjects. Their clinical features were less severe than those of subjects with congenital leptin deficiency. CONCLUSIONS: The prevalence of pathogenic LEPR mutations in a cohort of subjects with severe, early-onset obesity was 3%. Circulating levels of leptin were not disproportionately elevated, suggesting that serum leptin cannot be used as a marker for leptin-receptor deficiency. Congenital leptin-receptor deficiency should be considered in the differential diagnosis in any child with hyperphagia and severe obesity in the absence of developmental delay or dysmorphism

Objective: To ascertain whether initial depression of conscious level in children with diabetic ketoacidosis (DKA) is related to hyperosmolality, acidosis or other factors. Objective: Methods: In 225 episodes of DKA without evidence of cerebral edema, we examined the relationship between conscious level and initial biochemical variables. We contrasted these findings with those in 42 children who later developed cerebral oedema. Results: On admission, 42/225 (19%) had mild (pH 7.26–7.35); 96 (44%) moderate (pH 7.11–7.25); and 80 (37%) severe DKA (pH ≤ 7.10). Conscious level: alert and oriented (group 1, n = 123), drowsy but oriented when woken (group 2, n = 62), semiconscious or confused/agitated (group 3, n = 9), comatose (group 4, n = 4). Glasgow Coma Score (GCS) was available in 65. pH varied significantly with conscious level; group 1, 7.20 ± 0.11(mean ± SD); group 2, 7.10 ± 0.16; group 3, 6.96 ± 0.11; group 4, 6.88 ± 0.09 (anova, p

Aims/hypothesis Cerebral oedema complicating diabetic ketoacidosis (DKA) remains the major cause of morbidity and mortality in children with type 1 diabetes, but its aetiology remains unknown. Our objective was to determine the impact of baseline biochemical factors and of treatment-related variables on risk of the development of cerebral oedema in children with DKA. Materials and methods This was a national UK case– control study. Through the British Paediatric Surveillance Unit we identified 43 cases of cerebral oedema. Through a parallel reporting system, we also identified 2,940 episodes of DKA and selected 169 control subjects on the basis of comparable age, sex, numbers of new or known cases of diabetes and date of admission. Baseline biochemical data and treatment-related variables were extracted from the clinical notes of cases and control subjects. Results Allowing for differences in age, sex and new or known diabetes, cases were more acidotic at diagnosis of DKA (odds ratio [OR] for events in the least acidotic compared with the most acidotic tertile=0.02 [95% CI: 0.002–0.15], p

Meckel's diverticula (MD) with areas of gastric heterotopia (metaplasia) are more likely to become symptomatic than those that contain mucosa of purely an intestinal type. Helicobacter pylori has been associated with the pathogenesis of various diseases. The aim of the study was to evaluate whether H. pylori could be identified within metaplastic gastric mucosa in MD. A retrospective evaluation of the histopathological features and the clinical presentation of patients with MD was undertaken. The study group included 32 cases (20 paediatric and 12 adults). The commonest modes of presentation were acute pain (25%), obstruction (19%), bleeding (12.5%) and hernias (9%). On histological examination, heterotopic gastric mucosa was noted to be present in 12 cases. Of these, 3 specimens were noted to have H. pylori organisms present using a specific immunostaining technique. Two patients had concurrent gastric biopsies; one stained positively for H. pylori but the second (1 mm biopsy) was rapid urease-test positive only. In conclusion, the study provides strong evidence that H. pylori may colonise heterotopic gastric mucosa in a minority of MD. H. pylori is apparently not involved in the pathogenesis of most cases of complicated MD. Nonetheless, all 3 patients who had evidence of H. pylori were symptomatic.

Aims The long duration of action of soluble insulin given in the evening could contribute to the high prevalence of nocturnal hypoglycaemia seen in young children with Type 1 diabetes mellitus (T1DM). We examined whether replacing soluble insulin with insulin lispro reduced this risk in children on a three times daily insulin regimen. Methods Open crossover study comparing insulin lispro vs. soluble insulin in 23 (16 boys) prepubertal children (age 7–11 years) with T1DM on three injections/day; long-acting isophane insulin remained identical. At the end of each 4-month treatment arm, an overnight 15-min venous sampled blood glucose profile was performed. Results Despite similar blood glucose levels pre-evening meal (lispro vs. soluble: mean ± se 6.5 ± 1.0 vs. 7.1 ± 1.1 mmol/l, P = 0.5), post-meal (18.00–22.00 h) blood glucose levels were lower on insulin lispro (area under curve 138 ± 12 vs. 170 ± 13 mmol min−1 l−1, P = 0.03). In contrast, in the early night (22.00–04.00 h) the prevalence of low blood glucose levels (

Aims/hypothesis. We measured insulin clearance rates in children and young adults with Type I (insulin-dependent) diabetes mellitus to establish their relation with insulin sensitivity and with factors such as growth hormone secretion and body mass index.¶Methods. We studied 46 subjects [mean (range) age 14.4 (9.8–24.6) years), body mass index 21.1 (15.8–29.6)Kgm2] using an overnight (1800–0800 hours) variable rate insulin infusion euglycaemic clamp protocol (5 mmol/l). Plasma free insulin concentrations during steady-state euglycaemia were used as an index of insulin sensitivity and insulin clearance determined as a ratio of insulin infusion rate to plasma free insulin.¶Results. During steady-state euglycaemia (0500–0730 hours), insulin sensitivity [mean (SEM) plasma insulin 0.020 (0.002) mU/l] and insulin clearance rates [19.1 (1.8) ml · kg–1· min] varied with age non-linearly and in a reciprocal fashion to each other (cubic regression F = 4.09, p = 0.01; F = 3.55, p = 0.02, respectively). Insulin sensitivity was negatively related to BMI (r = –0.37, p = 0.011) and mean overnight growth hormone concentrations (r = –0.40, p = 0.007). Insulin clearance was only related to growth hormone concentrations (r = –0.37, p = 0.014). These relations were still evident after stepwise multiple regression analysis (potential determinants: C peptide, sex, age, puberty stage, HbA1 c, duration of diabetes): insulin sensitivity r = 0.55, p < 0.001; insulin clearance r = 0.37, p < 0.02.¶Conclusions/interpretation. Insulin clearance rates vary with age in young subjects with Type I diabetes and are highest during mid-adolescence when insulin sensitivity is at its lowest. Both insulin sensitivity and insulin clearance are related to circulating growth hormone concentrations. [Diabetologia (2000) 43: 61–68]

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. Key messages Children and young people with insulin dependent diabetes still have an increased mortality compared with the general population Diabetic ketoacidosis is the leading cause of death, particularly if it is complicated by cerebral oedema Hypoglycaemia is a rare cause of death even in those dying unexpectedly at home

Diabetic ketoacidosis remains a life-threatening condition. Management is usually straightforward, but there is still a significant mortality and morbidity, largely arising from the unpredictable complication of cerebral oedema. The pathophysiology of this devastating condition is still unknown. Good supervision from senior members of staff is essential, and there should be early concern if progress is not as predicted. Rapid intervention with mannitol and hyperventilation is necessary if signs of cerebral oedema develop.

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 I−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 ± 4ml 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. These data strengthen the case for a nationally agreed protocol and a prospective study of the antecedents to the development of cerebral oedema.

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.

Summary. objective The aim was to investigate the relationship between the nocturnal pulsatile secretory patterns of immunoreactive and bioactive luteinizing hormone In normal children at various stages of puberty. design Blood samples were taken at 15-minute Intervals from 2000 hours to 0800 hours. Pubertal stage was assessed by the method of Tanner (1962). patients Thirty-four healthy siblings (17 males, 17 females) of diabetic children were recruited (median age 13.1, range 9.1–20.9 years). They were of normal height, non-obese, and covered the range of puberty. measurements Follicle stimulating and luteinizing hormone levels were measured by radioimmunoassay in all 34 subjects; bioactive LH (B-LH) was assayed In a sub-group of 13 subjects selected to encompass the range of normal puberty. Oestradiol (girls) and testosterone (boys) were also measured at hourly intervals. results Immunoreactive luteinizing and follicle stimulating hormone concentrations showed a progressive rise during puberty in both sexes. FSH concentrations were significantly higher in females than in males at all stages of puberty. Overnight mean bioactive lutelnizing hormone concentrations were higher than immunoreactive luteinlzing hormone levels in all the girls studied (n= 7). Although the number of bioactive luteinizing hormone pulses (31) was greater than Immunoreactive pulses (27), the profiles were generally very similar. In the early pubertal girls an increase In the bloactive:immunoreactive ratio was observed during the middle of the night with the onset of pulsatility. Oestrogen was detected in the girls in breast stage 4–5 but not in two of the early pubertal girls, despite pulses of immunoreactive and bioactive luteinizing hormone. The boys had higher mean bloactive than immunoreactive luteinizing hormone levels and overall bloactive and immunoreactive luteinizing hormone and testosterone concentrations Increased with puberty stage. Concordance between bioactive and immunoreactive hormone pulses was good although more immunoreactive pulses (16) were seen than bioactive pulses (14). As in the girls, an Increase in the bioactlve:lmmunoreactive ratio was observed In the middle of the night with the onset of pulsatility at genital stage 2 but, in contrast to the oestrogen data In the girls, testosterone secretion always followed lutelnizing hormone pulsatility overnight. conclusion We conclude that mean overnight immunoreactive luteinizing and follicle stimulating hormone concentrations increase during puberty in both sexes. Bioactive luteinizing hormone levels are two to three times higher than Immunoreactive luteinizing hormone in both sexes, but there Is very little discordance between Immunoreactive and bioactive luteinizing hormone pulse-Silty. The bioactive:immunoreactive ratio increases with the occurrence of pulsatility overnight In early pubertal children. The relationship between these changes in bioactive and immunoreactive luteinizing hormone and sex steroids is clearest in boys where the nocturnal testosterone rise always follows pulsatile LH secretion.

The excretion of urinary growth hormone was measured by a highly sensitive direct immunoradiometric assay in a cross-sectional study during puberty in 70 children with Type 1 (insulin-dependent) diabetes mellitus and 94 normal children. In normal children (n = 24) and diabetic children (n = 17) overnight urinary growth hormone excretion correlated significantly with the mean overnight plasma concentration (r = 0.70, p less than 0.001, and r = 0.70, p less than 0.001), indicating that urinary GH excretion reflects the circulating endogenous GH level. Overnight urinary growth hormone excretion increased during puberty. In normal and in diabetic children there was a peak in boys at genital stage 4 (both p less than 0.01), and in girls at breast stage 2 (both p less than 0.02). The diabetic children excreted more urinary growth hormone than the normal children at every pubertal stage. Excretion of albumin, retinol binding protein and N-acetyl-beta-D-glucosaminidase was measured in urine from 38 diabetic children. Urinary growth hormone correlated weakly with urinary albumin (r = 0.49, p less than 0.01), retinol binding protein (r = 0.42, p less than 0.01), and N-acetyl-beta-D-glucosaminidase (r = 0.43, p less than 0.01). Urinary GH excretion was not related to blood glucose control (HbA1) in boys (n = 31) or girls (n = 39). The measurement of urinary growth hormone provides an assessment of endogenous growth hormone during puberty in normal and diabetic children. However, caution must be exercised in interpreting urinary growth hormone data from diabetic patients with increased excretion of albumin and retinol binding protein.