First UK survey of paediatric type 2 diabetes and MODY.

AIMS: To estimate the UK prevalence of childhood type 2 diabetes and maturity onset diabetes of the young (MODY), and distinguish them from each other and from type 1 diabetes. METHODS: The British Society for Paediatric Endocrinology and Diabetes Clinical Trials/Audit Group undertook a cross-sectional questionnaire survey of all paediatric diabetes centres during 2000, collecting data on all children with non-type 1 diabetes. RESULTS: Of 112 children reported to the survey, 25 had type 2 diabetes and 20 had MODY. In contrast to type 1, type 2 patients presented later (12.8 v 9.3 years), were usually female, overweight, or obese (92% v 28%), and a greater proportion were of ethnic minority origin (56% v 22%). In contrast to type 2, MODY patients were younger (10.8 years), less likely to be overweight or obese (50% v 92%), and none were from ethnic minority groups. The crude minimum UK prevalence of type 2 diabetes under 16 years is 0.21/100 000, and of MODY is 0.17/100 000. South Asian children have a relative risk of type 2 diabetes of 13.7 compared to white UK children. CONCLUSIONS: UK children still have a low prevalence of type 2 diabetes. Children from ethnic minorities are at significantly higher risk, but in white UK children with non-type 1 diabetes a diagnosis of MODY is as likely as type 2 diabetes. Childhood type 2 diabetes is characterised by insulin resistance, and is distinct from both type 1 and MODY.     

Diabetes, coeliac disease, multiple sclerosis and chronic arthritis in first-degree relatives of patients with juvenile idiopathic arthritis

Aim: To evaluate the occurrence of autoimmune diseases in first‐degree relatives of children with juvenile idiopathic arthritis (JIA) and to compare the figures with published population data. Materials and methods: Families of the 362 children with recently diagnosed JIA admitted to Rheumatism Foundation Hospital, Finland, from 1996 to 2001 were contacted by questionnaires regarding autoimmune diseases in family members. Data were collected on type 1 diabetes, coeliac disease, multiple sclerosis and chronic arthritis, consisting mainly of JIA, rheumatoid arthritis, spondyloarthropathy or psoriatic arthritis. Results: In all, 21.4% of the 355 families with a patient with JIA had members with type 1 diabetes, coeliac disease, multiple sclerosis or chronic arthritis. Thirty‐three mothers and 23 fathers had type 1 diabetes, coeliac disease, multiple sclerosis or chronic arthritis in 15.2% (95% CI 11.6–19.4) of the families, and 23 mothers and 15 fathers had chronic arthritis in 10.7% (95% CI 7.7–14.5) of the families. When compared with available research data, the prevalences of rheumatoid arthritis, spondyloarthropathy, psoriatic arthritis, paediatric type 1 diabetes and JIA (in siblings) were increased in JIA families. Coeliac disease was as prevalent as in the population. Conclusion: Autoimmune diseases cluster in families with a child with JIA.     

Clinical outcome in patients from a single region who were dependent on parenteral nutrition for 28 days or more.

BACKGROUND: The frequency and outcome of intestinal failure (IF) in children are not well defined in the UK. Long-term parenteral nutrition (PN) is an effective intervention, with intestine transplantation offering the possibility of survival should life-threatening complications arise in those with long-term dependency. The ideal model for service provision is a subject of debate. AIMS: We aimed to identify all new cases of IF (defined as PN dependency > or =28 days) in West Yorkshire over a two-year period to determine the rate of serious complications, establish the outcome after two years and clarify the role of specialist referral. METHOD: Pharmacists in all the West Yorkshire paediatric units were contacted to establish the number of children with IF during 2001-2002. Underlying diagnosis, complications and outcome at two years were obtained by case-note review for 93 of the 96 children identified. RESULTS: IF patients were exclusively managed in one or other of the three large teaching hospitals. At the two-year follow-up, six (6.4%) children had died (one while listed for a small bowel transplantation), but 85 (91%) had established full enteral feeding and were well. Two remained PN dependent and were assessed in the supra-regional intestinal transplantation unit (Birmingham); in neither case was small bowel transplantation thought to be appropriate. The most common complications were central venous catheter sepsis (69% of patients) and cholestasis (59%). CONCLUSIONS: This study shows that a favourable outcome for IF can be achieved in a regional centre with appropriate multidisciplinary support. A single UK supra-regional unit undertaking small bowel transplantation is probably adequate for assessment of the most complex patients, although this should remain under review.     

HLA association is different in children and adults with severe acquired aplastic anemia

BACKGROUND: Severe aplastic anemia (SAA) is defined as pancytopenia caused by bone marrow failure. The pathogenesis of SAA is thought to involve autoimmune processes. Increased susceptibility to autoimmunity has been shown to be associated with several different HLA alleles. In SAA, few large studies based on data mainly from adults describe a positive HLA correlation with HLA-DR2 (DRB1*15) and HLA-B14. PROCEDURE: This study explored the HLA constitution of 181 children with SAA who were enrolled in the prospective multi-center study SAA94 between January 1994 and January 2002. The control group consisted of 303 healthy individuals of comparable demographic background. Allelic frequencies between patients and controls are compared using Fisher's exact test. RESULTS: In our pediatric cohort, we describe a positive association with HLA-B14 (P = 0.0039), but no association of HLA-DR2 with SAA. CONCLUSION: HLA associations appear to be different in children and adults with SAA. This might point towards a difference in pathophysiology between at least part of the children and adults.     

Immunoglobulin subclasses and HLA alleles in immunoglobulin A deficiency

Objective : The term “IgA Deficiency (IgAD)” should be reserved for the individuals who do not have detectable disorders known to be associated with low IgA levels. IgG subclass deficiency or a lack of the IgG2 subclass that is specific against polysaccharide antigens, can be seen in many cases.Methods : Forty-five patients (27 males and 18 females; mean age 8.6 years, range 6.3 to 12.8 years) with IgA deficiency who had been admitted to the Department of Pediatric Immunology in Uludag University School of Medicine, Turkey, were included in this study. Serum immunoglobulin (Ig) class and IgG subclass levels, and HLA haplotypes were prospectively determined in patients and healthy controls.Results : Of the 45 patients with IgAD, 1 was found to have a low level of IgG in the serum. Serum Ig levels were also examined in the families of 22 patients. Five patients had low-normal levels of IgM, whilst one had low levels of IgA and IgG. The levels of IgG sublasses were assessed in 23 patients. One patient had a low level of IgG1 ; 2 had low levels of both IgG2 and IgG3, and 11 had low levels of IgG3. IgG subclass concentrations were found to be normal in control groups. HLA alleles were tested in 25 patients. An increased prevelence of HLA-A1, -B8, -B14, -DR1, -DR3, and -DR7 were previously observed in patients with Ig A deficiency. In this study, HLA-A1 allel was found in 3 patients (12 %), HLA-B14 in 3 patients (12%), HLA-DR1 in 10 patients (40 %), HLA-DR7 in 4 patients (16 %) and HLA-DR3 in 1 patient (4 %). HLA-B8 allel was not found in any patient. Twenty-five children with normal IgA levels have chosen as a control group. They had HLA-DR1 (36%), HLA-DR7 (16 %), HLA-B8 (8%), HLA-DR3 (16%). HLA-A1 was not found in any member of our control group.Conclusion : No statistically significant difference in HLA susceptibility alleles was found between patients and healthy controls. Our data suggest that there may be heterogenous HLA distribution patterns in IgA deficiency, or that HLA allel-associated tendency to IgA deficiency may be polygenic.     

How to improve blood-glucose control in type-1 diabetes

Glucose control in UK children with diabetes is below the EU average, as shown in several multicentre studies over the last 10 years. There are many reasons, from social factors (high divorce rate in the UK, more single-parent families, more isolation) to medical causes (undue reliance on twice-daily premixed insulins, reluctant acceptance of poor HbA1c levels by some UK paediatricians and parents). Unfortunately, the long-term effects on shortened life expectancy, cardiovascular disease, blindness and renal failure mean that poor glucose control is no longer acceptable. This review seeks to review the evidence for factors that relate to improved glucose control; it suggests a checklist of points to cover with children in the outpatient clinic, an example of an individualized spreadsheet glucose diary, and an individualized insulin dose schedule. The key message here is that we need to intensify diabetes treatment in the UK to bring it up to the levels of the best European centres. This will be achieved only by the wholehearted acceptance of this approach by paediatric diabetes teams, and willingness of children and families to invest time and energy into learning and implementing more complex insulin-adjustment regimens.     

Is the risk of cancer increased in Asians living in the UK?

The pattern of cancer in white and Asian (Indian, Pakistani, and Bangladeshi) children living in the West Midlands Health Authority Region was investigated using age standardised incidence rates. Two sets of rates were calculated, a 10 year rate (1982-91) using survey based estimates of the ethnic population and a four year rate (1989-92) using the ethnic population counts from the 1991 census. The 10 year rates showed a significantly higher annual incidence of cancer in Asian (159.1/million/year) than in white (130.8) children. The pattern of cancers in Asian children was different, with an excess of lymphomas and germ cell tumours, and a deficit of rhabdomyosarcomas. These findings were confirmed by the four year rates. Although underestimation of the Asian population probably contributes to the apparent excess, there remains cause for concern that UK Asian children may be at higher risk of cancer. Accurate ethnic population figures and confirmatory studies are urgently required.     

Minimizing risks: the ethics of predictive diabetes mellitus screening research in newborns

Type 1 diabetes mellitus is the most common metabolic disease of childhood. Two states offer newborn screening to identify children with a genetic predisposition to it. It is a voluntary test offered in conjunction with the mandatory newborn metabolic screening. There are no preventive treatments, but children discovered to be at increased risk may participate in follow-up studies to determine whether and when the child develops autoantibodies (preclinical disease) or overt diabetes. This study examined the ethics of predictive genetic research in newborns for type 1 diabetes. Prediction research has serious psychosocial implications, and research designs must account for them. The study concluded that, to minimize harm to infants and their families, (1) if the research does not incorporate a prevention strategy, studies should avoid disclosure of results; and (2) if disclosure is necessary, then the research should be restricted to newborns with an affected first-degree relative.     

Is the risk of cancer increased in Asians living in the UK?

The pattern of cancer in white and Asian (Indian, Pakistani, and Bangladeshi) children living in the West Midlands Health Authority Region was investigated using age standardised incidence rates. Two sets of rates were calculated, a 10 year rate (1982-91) using survey based estimates of the ethnic population and a four year rate (1989-92) using the ethnic population counts from the 1991 census. The 10 year rates showed a significantly higher annual incidence of cancer in Asian (159.1/million/year) than in white (130.8) children. The pattern of cancers in Asian children was different, with an excess of lymphomas and germ cell tumours, and a deficit of rhabdomyosarcomas. These findings were confirmed by the four year rates. Although underestimation of the Asian population probably contributes to the apparent excess, there remains cause for concern that UK Asian children may be at higher risk of cancer. Accurate ethnic population figures and confirmatory studies are urgently required.     

Type 2 diabetes mellitus: incidence,management and prognosis

Type 2 diabetes mellitus in childhood emerged in the UK in about 2000, and now affects about 250 children or 1% of all childhood diabetes in the UK. It characteristically presents in an obese child, around the time of puberty, with osmotic symptoms of thirst and polyuria. Some children are identified co-incidentally, and a small proportion may present with decompensation and diabetic ketoacidosis. Acanthosis nigricans is a common feature. There is a significant female preponderance, with children from ethnic minorities disproportionately represented, and usually a history of type 2 diabetes mellitus in first-degree relatives. In contrast to type 1 diabetes, children with type 2 may have already have microvascular complications by the time they are diagnosed. The differential diagnosis clearly includes type 1 diabetes, usually distinguished by the presence of autoantibodies GAD65, ICA and IAA; but also diabetes secondary to monogenic causes, transplant and immunosuppression, and rarer syndromes. Management includes confirming the diagnosis of diabetes according to World Health Organisation criteria; screening for both microvascular complications and complications of metabolic syndrome; and initiating lifestyle, dietary and exercise advice to decrease calorie intake and increase energy expenditure. Children with osmotic symptoms or HbA1c greater than 8.5% should be commenced on insulin therapy then weaned off over 1–3 months. Metformin should also be instituted from diagnosis provided there is no ketoacidosis, and the dose increased to the maximum tolerated. Insulin is currently the only second line treatment licensed for use in the UK. A pragmatic approach is to offer once a day long acting insulin; and add in mealtime short acting insulin if insufficient response. The glycated haemoglobin target for optimal glycaemic control is less than 7.0%. Future treatments under investigation for paediatric use include the GLP-1 antagonists and DPPV4 inhibitors. It is hoped that the current batch of phase III studies will lead to an evidence base for better treatments in future.     

Children with type 1 diabetes in COVID-19 pandemic: Difficulties and solutions

Children/adolescents with type 1 diabetes (T1D) require holistic approach and continuous care. However, the coronavirus disease 2019 (COVID-19) pandemic has made challenges for the T1D children and their caregivers, professionals, and the healthcare system. This minireview aims to consolidate and discuss the difficulties and solutions of children with type 1 diabetes in the COVID-19 pandemic. T1D has been the most common type of diabetes in children and adolescents and the last decades has seen a rapid increase in the prevalence of T1D in youths worldwide, which deserves a public concern particularly in the COVID-19 pandemic. As reported in previous studies, T1D is a risk factor related to severe cases, while the virus may induce new-onset diabetes and serious complications. Moreover, restriction strategies influence medical availability and lifestyle, impact glycemic control and compilation management, and thus pose stress on families and health providers of youths with T1D, especially on those with certain fragile conditions. Therefore, special treatment plans are required for children provided by caregivers and the local health system. Latest health tools such as improved medical devices and telemedicine service, as well as a combined support may benefit in this period. This minireview emphasises that continued medical access and support are required to prevent deteriorated condition of children and adolescents with diabetes throughout this pandemic. Therefore, strategies are supposed to be formulated to mitigate the difficulties and stress among this group, particularly in the most at-risk population. Proposed solutions in this minireview may help individuals and the health system to overcome these problems and help youths with T1D in better diabetes management during such emergency situations.     

Screening for preclinical type 1 diabetes in a discrete population with an apparent increased disease incidence

Environmental agents are proposed to play a role in triggering or exacerbating pancreatic islet autoimmunity in people genetically predisposed to type 1 diabetes. However, with few exceptions, these agents remain enigmatic. Clues to environmental agents may be found by investigating population/geographic clusters or 'hotspots' of high disease incidence. We were alerted to a small community where the incidence of type 1 diabetes appeared to be five-fold higher than expected. Because type 1 diabetes is now recognized to have a subclinical phase during which anti-islet antibodies can be detected, we aimed to identify and characterize a reservoir of children with subclinical disease in this community. Venous blood samples were collected from 1906/2347 (81%) local school children during one week. Islet cell antibodies (ICAs) were detected in 122 (6.4%) children, 18 (0.9%) being high titer (> or = 20 Juvenile Diabetes Foundation units (JDFu)). On retest, 15 months later, the majority of low titer ICAs were undetectable, whereas high-titer ICAs persisted. The latter were found in two distinct age-related, ethnically similar groups. The younger group, aged 6-9 yr, had antibodies to insulin (IAAs), glutamic acid decarboxylase (GAD) and tyrosine phosphatase IA2 in addition to ICA, human leukocyte antigen (HLA) genes associated with susceptibility to type 1 diabetes, and lower first-phase insulin responses (FPIRs) to intravenous glucose. The older group, aged 13-16 yr, the age cohort of the index clinical cases, had few antibodies other than ICA, non-susceptibility HLA genes and normal FPIRs. During follow-up, three children, all from the younger group with multiple antibodies and FPIRs less than the first percentile, developed diabetes 4, 6 and 7 yr after screening. The finding of two age groups of subclinical disease suggests that if environmental agents triggered islet autoimmunity they did not act constantly on the community. Furthermore, the absence of multiple autoantibodies and/or HLA susceptibility genes in the older group, the source of index clinical cases, implies they are a residual subgroup with slow or absent progressive beta-cell destruction. This study illustrates that the natural history of type 1 diabetes may be elucidated by analyzing age-related subclinical disease in the general population.     

The development of an innovative education curriculum for 11-16 yr old children with type 1 diabetes mellitus (T1DM)

BACKGROUND: Evidence-based, structured education is recommended for all people with diabetes; tailored to meet their personal needs and learning styles. Adult courses exist in the UK but are of limited value for children. The aim of this study was to adapt the adult Dose Adjustment For Normal Eating (DAFNE) course to design a skills training course, for children aged 11-16 yr, focusing on self-management skills within an intensive insulin regime. To ensure that the course format meets the developmental, intellectual and social needs of children and adolescents and is delivered using educationally sound techniques. METHODS: Relevant professionals and potential users of the course were involved in curriculum design and content in the following ways: (i) The views of 95 pediatric diabetes specialist nurses were sought through a postal survey; (ii) Focus group discussions were conducted with children with type 1 diabetes mellitus (T1DM) and their families to contribute to content and design; and (iii) Secondary school teachers worked with experienced pediatric diabetes staff advising on educational content and teaching format. RESULTS: The developed curriculum uses a progressive modular-based structure to improve self-management in a variety of medical and social situations. It has clear learning objectives and is based on the format of UK schools curricula. Additional support is provided through dedicated parent sessions, involvement of friends and the provision of a school resource pack. CONCLUSION: Collaborative working between health professionals, school teachers and families has resulted in an age-appropriate curriculum, which employs validated educational techniques. This will be refined following pilot courses before formal evaluation in a multicentre randomized controlled trial.     

The prevention of type I diabetes mellitus.

Now that prediction of type I diabetes mellitus has markedly improved, worldwide attempts to prevent the disease are under way (e.g., DPT-1, ENDIT, and TRIGR). Subjects are being recruited and families of children or parents with diabetes should be informed about the availability of such studies and given the option to participate. The creation of a network of study sites or cooperative groups will allow for the implementation of new protocols aimed at preventing the disease. The greatest barrier to the prevention of diabetes is the lack of proven effective interventional agents. The journey toward prevention of type I diabetes mellitus has only just begun.     

Änderung der Berufstätigkeit der Eltern nach Manifestation eines Diabetes mellitus Typ 1 beim Kind

We wondered about the consequences on the professional activity of parents after manifestation of type 1 diabetes in a child. A questionnaire was answered in writing by 103 families of diabetic children cared for in our center. At diabetes manifestation, 43 children were less than 4 years, 30 were 5–7 years, 24 were 8–11 years, and 6 were over 12 years old. After the onset of diabetes in a child, 19 of 53 (35.8%) fully or partially working mothers, but only 1 of 98 (1.0%) fathers, gave up their job completely. Significantly more mothers of preschool children than of schoolchildren stopped working. Incisive changes in planning or timing of work was necessary in many cases. Parents of young children reported more stress and relevant financial loss. For these reasons, psychological support for families with diabetic children is important and may prove to be a good long-term investment.     

Underweight problems in Asian children and adolescents

Most reviews on weight status have focused on obesity, and little information on underweight children is available. This review aimed to examine the prevalence and trends of underweight status among Asian children and adolescent populations in the last two decades. A systematic review of publications between the years 1990 and 2010 was conducted. Underweight in children and adolescents was relatively more prevalent in the South and West Asian countries than in the East Asian countries. In general, underweight was more prevalent in boys within the South and West Asian countries, while it was more prevalent in girls within the East Asian countries. Increasing trends of prevalence of underweight were common among children and adolescents in South and West Asia. Specific public health policies should be formulated to combat the underweight problems in less-developed countries.     

HLA antigens, jejunal morphology and associated diseases in children with dermatitis herpetiformis

Forty-five Hungarian and Finnish children from 1.5 to 15 years with dermatitis herpetiformis were studied for HLA antigens, jejunal morphology on gluten-containing diet and associated diseases in the patients and their relatives. A strong association with HLA-B8 was found in patients of both nationalities, the relative risks were 12.8 and 9.6, respectively. The Hungarian patients were also typed for HLA-DR locus, and an association with DR3 but not with DR7 was observed. Patients with subtotal villous atrophy had slightly more often HLA-B8 and DR3 than those with milder intestinal lesions. Atopic eczema occurred in 20% of the patients and family history of atopy seemed to have an inverse correlation with HLA-B8 and DR3.     

Pediatric diabetes care in Sri Lanka and Bangladesh: Reaching the community

Diabetes is a major non‐communicable disease with long‐term complications. Over one million children and adolescents are affected with type 1 diabetes in the world. The number of children and adolescents with type 2 diabetes is also on the rise due to the increase incidence of childhood diabetes. South East Asian (SEA) contributes 184 100 children and adolescents with type 1 diabetes under the age of 20 years for this global health issue as at 2019. Countries of SEA region share same socio demographic, cultural, and economic challenges when it comes to holistic care of affected children. It is timely to discuss common concerns of these countries to give the best possible care for children affected with diabetes to minimize the burden of diabetes related complications, which would potentially affect the socioeconomic development of the respective countries.     

HLA Antigens, Jejunal Morphology and Associated Diseases in Children with Dermatitis Herpetiformis

ABSTRACT. Forty-five Hungarian and Finnish children from 1.5 to 15 years with dermatitis herpetiformis were studied for HLA antigens, jejunal morphology on gluten-containing diet and associated diseases in the patients and their relatives. A strong association with HLA-B8 was found in patients of both nationalities, the relative risks were 12.8 and 9.6, respectively. The Hungarian patients were also typed for HLA-DR locus, and an association with DR3 but not with DR7 was observed. Patients with subtotal villous atrophy had slightly more often HLA-B8 and DR3 than those with milder intestinal lesions. Atopic eczema occurred in 20 % of the patients and family history of atopy seemed to have an inverse correlation with HLA-B8 and DR3.     

Type 2 and other forms of diabetes in 0-30 year olds: a hospital based study in Leeds, UK.

BACKGROUND AND AIMS: Following recent reports of increased numbers of adolescents being diagnosed with the adult or type 2 form of diabetes we aimed to describe the prevalence of both type 2 and other forms of diabetes in an urban population of children and young people in northern England. METHODS: A hospital based cross sectional study was performed in patients aged < or =30 years attending diabetic clinics in Leeds during the year 2000. RESULTS: A total of 677 subjects were identified, of whom 621 (92%) and 37 (5%) had type 1 and type 2 diabetes respectively. Four patients had confirmed maturity onset diabetes of the young, while the cause was uncertain for four. Median age of all patients was 22 years, with 396 (58%) aged 20-30; 32/37 patients with type 2 diabetes were aged 20-30. The prevalence of type 2 diabetes was 0.13 per 1000 overall, compared to 2.2 per 1000 for patients with type 1 diabetes. Of all type 2 diabetes patients, 24% were south Asian compared to 5% of the background population; 87% were categorised into the two least affluent tertiles of the Townsend score. This link with deprivation was not explained by the proportion of Asian patients across tertiles (approximately 25%). CONCLUSIONS: This study shows extremely low prevalence of type 2 diabetes in 10-19 year olds, but will provide a baseline for future comparisons. Overall, type 2 diabetes is seen more commonly in south Asians, and an association with deprivation is suggested.