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See detailInsulin delivery by injection in children and adolescents with diabetes
Hanas, R.; De Beaufort, Carine UL; Hoey, H. et al

in Pediatric Diabetes (2011), 12(5), 518-526

Type 1 diabetes is treated with insulin, which has traditionally been delivered by vial and syringe. However, for many patients, dosing inaccuracy, pain, anxiety, inconvenience, and social acceptability ... [more ▼]

Type 1 diabetes is treated with insulin, which has traditionally been delivered by vial and syringe. However, for many patients, dosing inaccuracy, pain, anxiety, inconvenience, and social acceptability present barriers to this method of administration (1-5). This has contributed to the increased popularity of alternative insulin delivery systems, including pen delivery devices (4, 6). Evidence suggests that discreet devices, such as insulin pens, facilitate adherence to intensive insulin therapy regimens, help improve lifestyle flexibility, and reduce injection pain compared with the conventional syringe-based regimens, as shown in studies in adults and adolescents (7). In addition, compared with the vial and syringe method of insulin administration, pens may provide more accurate dosing - which is particularly important in children - thereby improving short-term blood glucose control and potentially improving long-term outcomes (5, 8). Children, in particular, may benefit from insulin pens that are simple to use as adherence issues may be more evident in this patient group (9). Pens for insulin delivery in children with type 1 diabetes have been used for a long time in Europe, and have recently gained in popularity in many other places around the world (4, 10). Furthermore, the conventional vial and syringe method of insulin delivery is beginning to be considered as obsolete (11). Moreover, there is a continued drive to improve insulin pen technology, to refine and enhance the functionality and usability of these pens. However, despite recent advances in pen design and function, the selection of pens available especially for children is limited. © 2011 John Wiley & Sons A/S. [less ▲]

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See detailBirth order and childhood type 1 diabetes risk: A pooled analysis of 31 observational studies
Cardwell, C. R.; Stene, L. C.; Joner, G. et al

in International Journal of Epidemiology (2011), 40(2), 363-374

Background: The incidence rates of childhood onset type 1 diabetes are almost universally increasing across the globe but the aetiology of the disease remains largely unknown. We investigated whether ... [more ▼]

Background: The incidence rates of childhood onset type 1 diabetes are almost universally increasing across the globe but the aetiology of the disease remains largely unknown. We investigated whether birth order is associated with the risk of childhood diabetes by performing a pooled analysis of previous studies. Methods: Relevant studies published before January 2010 were identified from MEDLINE, Web of Science and EMBASE. Authors of studies provided individual patient data or conducted pre-specified analyses. Meta-analysis techniques were used to derive combined odds ratios (ORs), before and after adjustment for confounders, and investigate heterogeneity. Results: Data were available for 6 cohort and 25 case-control studies, including 11 955 cases of type 1 diabetes. Overall, there was no evidence of an association prior to adjustment for confounders. After adjustment for maternal age at birth and other confounders, a reduction in the risk of diabetes in second-or later born children became apparent [fully adjusted OR=0.90 95% confidence interval (CI) 0.83-0.98; P=0.02] but this association varied markedly between studies (I2=67%). An a priori subgroup analysis showed that the association was stronger and more consistent in children <5years of age (n=25 studies, maternal age adjusted OR=0.84 95% CI 0.75, 0.93; I2=23%). Conclusion: Although the association varied between studies, there was some evidence of a lower risk of childhood onset type 1 diabetes with increasing birth order, particularly in children aged <5 years. This finding could reflect increased exposure to infections in early life in later born children. Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2010; all rights reserved. [less ▲]

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See detailManagement of familial hypercholesterolemia in children and young adults: Consensus paper developed by a panel of lipidologists, cardiologists, paediatricians, nutritionists, gastroenterologists, general practitioners and a patient organization
Descamps, O. S.; Tenoutasse, S.; Stephenne, X. et al

in Atherosclerosis (2011), 218(2), 272-280

Since heterozygous familial hypercholesterolemia (HeFH) is a disease that exposes the individual from birth onwards to severe hypercholesterolemia with the development of early cardiovascular disease, a ... [more ▼]

Since heterozygous familial hypercholesterolemia (HeFH) is a disease that exposes the individual from birth onwards to severe hypercholesterolemia with the development of early cardiovascular disease, a clear consensus on the management of this disease in young patients is necessary. In Belgium, a panel of paediatricians, specialists in (adult) lipid management, general practitioners and representatives of the FH patient organization agreed on the following common recommendations.1.Screening for HeFH should be performed only in children older than 2 years when HeFH has been identified or is suspected (based on a genetic test or clinical criteria) in one parent.2.The diagnostic procedure includes, as a first step, the establishment of a clear diagnosis of HeFH in one of the parents. If this precondition is satisfied, a low-density-lipoprotein cholesterol (LDL-C) level above 3.5mmol/L (135mg/dL) in the suspected child is predictive for differentiating affected from non-affected children.3.A low saturated fat and low cholesterol diet should be started after 2 years, under the supervision of a dietician or nutritionist.4.The pharmacological treatment, using statins as first line drugs, should usually be started after 10 years if LDL-C levels remain above 5mmol/L (190mg/dL), or above 4mmol/L (160mg/dL) in the presence of a causative mutation, a family history of early cardiovascular disease or severe risk factors. The objective is to reduce LDL-C by at least 30% between 10 and 14 years and, thereafter, to reach LDL-C levels of less than 3.4mmol/L (130mg/dL).Conclusion: The aim of this consensus statement is to achieve more consistent management in the identification and treatment of children with HeFH in Belgium. © 2011 Elsevier Ireland Ltd. [less ▲]

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See detailMultinational study in children and adolescents with newly diagnosed type 1 diabetes: Association of age, ketoacidosis, HLA status, and autoantibodies on residual beta-cell function and glycemic control 12 months after diagnosis
Mortensen, H. B.; Swift, P. G.; Holl, R. W. et al

in Pediatric Diabetes (2010), 11(4), 218-226

Objective: To identify predictors of residual beta-cell function and glycemic control during the first 12 months after the diagnosis of type 1 diabetes (T1D).Subjects and Methods: Clinical information and ... [more ▼]

Objective: To identify predictors of residual beta-cell function and glycemic control during the first 12 months after the diagnosis of type 1 diabetes (T1D).Subjects and Methods: Clinical information and blood samples were collected from 275 children. HbA1c, antibodies, HLA typing and mixed meal-stimulated C-peptide levels 1, 6, and 12 months after diagnosis were analyzed centrally.Results: Mean age at diagnosis was 9.1 yr. DKA with standard bicarbonate <15 mmol/L was associated with significantly poorer residual beta-cell function 1 (p = 0.004) and 12 months (p = 0.0003) after diagnosis. At 12 months, the decline in stimulated C-peptide levels compared with the levels at 1 month was 69% in the youngest age group and 50% in patients 10 yr and above (p < 0.001). Stimulated C-peptide at 12 months was predicted by younger age (p < 0.02) and bicarbonate levels at diagnosis (p = 0.005), and by stimulated C-peptide (p < 0.0001), postmeal blood glucose (p = 0.0004), insulin antibodies (IA; p = 0.02) and glutamic acid decarboxylase antibodies (GADA; p = 0.0004) at 1 month. HbA1c at 12 months was predicted by HbA1c at diagnosis (p < 0.0001), GADA at 1 month (p = 0.01), and non-white Caucasian ethnicity (p = 0.002).Conclusions: Younger age, ketoacidosis at diagnosis, and IA and GADA 1 month after diagnosis were the strongest explanatory factors for residual beta-cell function at 12 months. Glycemic control at 12 months was influenced predominantly by ethnicity, HbA1c at diagnosis, and GADA at 1 month. © 2009 John Wiley & Sons A/S. [less ▲]

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See detailTransition from pediatric to adult diabetes care: Smooth or slippery?
De Beaufort, Carine UL; Jarosz-Chobot, P.; Frank, M. et al

in Pediatric Diabetes (2010), 11(1), 24-27

de Beaufort C, Jarosz-Chobot P, Frank M, Frank M, de Bart J, Deja G. Transition from pediatric to adult diabetes care: smooth or slippery?Objectives: The purpose of this study is to evaluate the practices ... [more ▼]

de Beaufort C, Jarosz-Chobot P, Frank M, Frank M, de Bart J, Deja G. Transition from pediatric to adult diabetes care: smooth or slippery?Objectives: The purpose of this study is to evaluate the practices of diabetes health care providers concerning the transition from pediatric to adult diabetes care. The information presented here may help increase awareness of the organization of transitional care for young people with diabetes and prevent the loss of follow-up during this vulnerable period in their lives.Methods: A questionnaire with an explanatory letter was sent to all members (n = 578) of the International Society for Pediatric and Adolescent Diabetes (ISPAD). A follow-up mailing was sent 4 months later.Results: In total, 92 questionnaires (16%) from members representing 36 countries were included in the analysis. In 76% of the centers, youth are seen until the age of 18 yr; 36% of the pediatric centers see adults > 25 yr; 30% report children under the age of 16 receive follow up from adult diabetologists or internists. About half of the programs already have a structured transition process usually targeting youth 16-25 yr of age. The majority of responders propose that preparation for transition starts at least 1 yr prior to leaving the pediatric center.Conclusion: Youth with type 1 diabetes often struggle to keep diabetes management a priority and find it challenging to maintain optimal metabolic control. When they graduate from pediatric care, some of these young people opt out of care altogether, only to resurface in the medical system when they develop complications which may have been prevented. Our survey of diabetes health care professionals in 36 countries worldwide shows that the actual transition practices in many places are far from optimal and require improvement. Transitional care should start early and strategies should promote uninterrupted, comprehensive, and accessible adult care. © 2009 John Wiley & Sons A/S. [less ▲]

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See detailL'éducation thérapeutique: Une solution pour vaincre l'inertie clinique et le défaut d'observance
Scheen, A. J.; Bourguignon, J. P.; Guillaume, M. et al

in Revue Medicale de Liege (2010), 65(5-6), 250-255

Therapeutic education (TPE) aims to enable the patient suffering from a chronic diseases to manage his/her illness and treatment, and prevent avoidable complications, while keeping or improving his/her ... [more ▼]

Therapeutic education (TPE) aims to enable the patient suffering from a chronic diseases to manage his/her illness and treatment, and prevent avoidable complications, while keeping or improving his/her quality of life. it comprises a set de practical tools aiming the patient to acquire skills to manage himself/herself the disease, its care and supervision, in partnership with healthcare providers. TPE may contribute to improve therapeutic compliance and to reduce clinical inertia, two drawbacks frequently encountered in the management of patients with chronic diseases. As an illustration, we briefly present edudora2 («Education thérapeutique et préventive face au diabète et à l'obésité à risque chez l'adulte et l'adolescent» = "Preventive and therapeutic education for diabetes and at risk obesity in adults and adolescents"), an ongoing original project in three frontier regions (Wallonia - Grand-duchy of Luxembourg - Lorraine). [less ▲]

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See detailTarget setting in intensive insulin management is associated with metabolic control: The Hvidoere Childhood Diabetes Study Group Centre Differences Study 2005
Swift, P. G. F.; Skinner, T. C.; De Beaufort, Carine UL et al

in Pediatric Diabetes (2010), 11(4), 271-278

Objective: To evaluate glycaemic targets set by diabetes teams, their perception by adolescents and parents, and their influence on metabolic control.Methods: Clinical data and questionnaires were ... [more ▼]

Objective: To evaluate glycaemic targets set by diabetes teams, their perception by adolescents and parents, and their influence on metabolic control.Methods: Clinical data and questionnaires were completed by adolescents, parents/carers and diabetes teams in 21 international centres. HbA1c was measured centrally.Results: A total of 2062 adolescents completed questionnaires (age 14.4 ± 2.3 yr; diabetes duration 6.1 ± 3.5 yr). Mean HbA 1c = 8.2 ± 1.4% with significant differences between centres (F = 12.3; p < 0.001) range from 7.4 to 9.1%. There was a significant correlation between parent (r = 0.20) and adolescent (r = 0.21) reports of their perceived ideal HbA1c and their actual HbA1c result (p < 0.001), and a stronger association between parents' (r = 0.39) and adolescents' (r = 0.4) reports of the HbA1c they would be happy with and their actual HbA1c result. There were significant differences between centres on parent and adolescent reports of ideal and happy with HbA1c (8.1 < F > 17.4;p < 0.001). A lower target HbA1c and greater consistency between members of teams within centres were associated with lower centre HbA1c (F = 16.0; df = 15; p < 0.001).Conclusions: Clear and consistent setting of glycaemic targets by diabetes teams is strongly associated with HbA1c outcome in adolescents. Target setting appears to play a significant role in explaining the differences in metabolic outcomes between centres. © 2009 John Wiley & Sons A/S. [less ▲]

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See detailDisease progression and search for monogenic diabetes among children with new onset type 1 diabetes negative for ICA, GAD- and IA-2 Antibodies
Pörksen, S.; Laborie, L. B.; Nielsen, L. et al

in BMC Endocrine Disorders (2010), 10

Background: To investigate disease progression the first 12 months after diagnosis in children with type 1 diabetes negative (AAB negative) for pancreatic autoantibodies [islet cell autoantibodies(ICA ... [more ▼]

Background: To investigate disease progression the first 12 months after diagnosis in children with type 1 diabetes negative (AAB negative) for pancreatic autoantibodies [islet cell autoantibodies(ICA), glutamic acid decarboxylase antibodies (GADA) and insulinoma-associated antigen-2 antibodies (IA-2A)]. Furthermore the study aimed at determining whether mutations in KCNJ11, ABCC8, HNF1A, HNF4A or INS are common in AAB negative diabetes.Materials and methods: In 261 newly diagnosed children with type 1 diabetes, we measured residual β-cell function, ICA, GADA, and IA-2A at 1, 6 and 12 months after diagnosis. The genes KCNJ11, ABCC8, HNF1A, HNF4A and INS were sequenced in subjects AAB negative at diagnosis. We expressed recombinant K-ATP channels in Xenopus oocytes to analyse the functional effects of an ABCC8 mutation.Results: Twenty-four patients (9.1%) tested AAB negative after one month. Patients, who were AAB-negative throughout the 12-month period, had higher residual β-cell function (P = 0.002), lower blood glucose (P = 0.004), received less insulin (P = 0.05) and had lower HbA1c(P = 0.02) 12 months after diagnosis. One patient had a heterozygous mutation leading to the substitution of arginine at residue 1530 of SUR1 (ABCC8) by cysteine. Functional analyses of recombinant K-ATP channels showed that R1530C markedly reduced the sensitivity of the K-ATP channel to inhibition by MgATP. Morover, the channel was highly sensitive to sulphonylureas. However, there was no effect of sulfonylurea treatment after four weeks on 1.0-1.2 mg/kg/24 h glibenclamide.Conclusion: GAD, IA-2A, and ICA negative children with new onset type 1 diabetes have slower disease progression as assessed by residual beta-cell function and improved glycemic control 12 months after diagnosis. One out of 24 had a mutation in ABCC8, suggesting that screening of ABCC8 should be considered in patients with AAB negative type 1 diabetes. © 2010 Pörksen et al; licensee BioMed Central Ltd. [less ▲]

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See detailPaediatric primary care in Europe: Variation between countries
Van Esso, D.; Del Torso, S.; Hadjipanayis, A. et al

in Archives of Disease in Childhood (2010), 95(10), 791-795

Background: Although it is known that differences in paediatric primary care (PPC) are found throughout Europe, little information exists as to where, how and who delivers this care. The aim of this study ... [more ▼]

Background: Although it is known that differences in paediatric primary care (PPC) are found throughout Europe, little information exists as to where, how and who delivers this care. The aim of this study was to collect information on the current existing situation of PPC in Europe. Methods: A survey, in the form of a questionnaire, was distributed to the primary or secondary care delegates of 31 European countries asking for information concerning their primary paediatric care system, demographic data, professionals involved in primary care and details of their training. All of them were active paediatricians with a broad knowledge on how PPC is organised in their countries. Results: Responses were received from 29 countries. Twelve countries (41%) have a family doctor/general practitioner (GP/FD) system, seven (24%) a paediatrician-based system and 10 (35%) a combined system. The total number of paediatricians in the 29 countries is 82 078 with 33 195 (40.4%) working in primary care. In only 15 countries (51.7%), paediatric age at the primary care level is defined as 0-18 years. Training in paediatrics is 5 years or more in 20 of the 29 countries. In nine countries, training is less than 5 years. The median training time of GPs/FDs in paediatrics is 4 months (IQR 3-6), with some countries having no formal paediatric training at all. The care of adolescents and involvement in school health programmes is undertaken by different health professionals (school doctors, GPs/FDs, nurses and paediatricians) depending on the country. Conclusions: Systems and organisations of PPC in Europe are heterogeneous. The same is true for paediatric training, school healthcare involvement and adolescent care. More research is needed to study specific healthcare indicators in order to evaluate the efficacy of different systems of PPC. [less ▲]

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See detailNew definition for the partial remission period in children and adolescents with type 1 diabetes
Mortensen, H. B.; Hougaard, P.; Swift, P. et al

in Diabetes Care (2009), 32(8), 1384-1390

OBJECTIVE - To find a simple definition of partial remission in type 1 diabetes that reflects both residual β-cell function and efficacy of insulin treatment. RESEARCH DESIGN AND METHODS - A total of 275 ... [more ▼]

OBJECTIVE - To find a simple definition of partial remission in type 1 diabetes that reflects both residual β-cell function and efficacy of insulin treatment. RESEARCH DESIGN AND METHODS - A total of 275 patients aged <16 years were followed from onset of type 1 diabetes. After 1, 6, and 12 months, stimulated C-peptide during a challenge was used as a measure of residual β-cell function. RESULTS - By multiple regression analysis, a negative association between stimulated C-peptide and A1C (regression coefficient -0.21, P < 0.001) and insulin dose (-0.94, P < 0.001) was shown. These results suggested the definition of an insulin dose-adjusted A1C (IDAA1C) as A1C (percent) + [4 × insulin dose (units per kilogram per 24 h)]. A calculated IDAA1C ≤9 corresponding to a predicted stimulated C-peptide >300 pmol/l was used to define partial remission. The IDAA1C ≤9 had a significantly higher agreement (P < 0.001) with residual β-cell function than use of a definition of A1C ≤7.5%. Between 6 and 12 months after diagnosis, for IDAA1C ≤9 only 1 patient entered partial remission and 61 patients ended partial remission, for A1C ≤7.5% 15 patients entered partial remission and 53 ended, for a definition of insulin dose ≤0.5 units · kg-1 · 24 h-1 5 patients entered partial remission and 66 ended, and for stimulated C-peptide (>300 pmol/l) 9 patients entered partial remission and 49 ended. IDAA1C at 6 months has good predictive power for stimulated C-peptide concentrations after both 6 and 12 months. CONCLUSIONS - A new definition of partial remission is proposed, including both glycemic control and insulin dose. It reflects residual β-cell function and has better stability compared with the conventional definitions. © 2009 by the American Diabetes Association. [less ▲]

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See detailIncidence trends for childhood type 1 diabetes in Europe during 1989-2003 and predicted new cases 2005-20: a multicentre prospective registration study Lancet
Patterson, C.C.; Dahlquist, G.G.; Gyürüs, E. et al

in Lancet (2009), 373(9680), 2027-2033

Background The incidence of type 1 diabetes in children younger than 15 years is increasing. Prediction of future incidence of this disease will enable adequate fund allocation for delivery of care to be ... [more ▼]

Background The incidence of type 1 diabetes in children younger than 15 years is increasing. Prediction of future incidence of this disease will enable adequate fund allocation for delivery of care to be planned. We aimed to establish 15-year incidence trends for childhood type 1 diabetes in European centres, and thereby predict the future burden of childhood diabetes in Europe. Methods 20 population-based EURODIAB registers in 17 countries registered 29 311 new cases of type 1 diabetes, diagnosed in children before their 15th birthday during a 15-year period, 1989–2003. Age-specific log linear rates of increase were estimated in five geographical regions, and used in conjunction with published incidence rates and population projections to predict numbers of new cases throughout Europe in 2005, 2010, 2015, and 2020. Findings Ascertainment was better than 90% in most registers. All but two registers showed significant yearly increases in incidence, ranging from 0·6% to 9·3%. The overall annual increase was 3·9% (95% CI 3·6–4·2), and the increases in the age groups 0–4 years, 5–9 years, and 10–14 years were 5·4% (4·8–6·1), 4·3% (3·8–4·8), and 2·9% (2·5–3·3), respectively. The number of new cases in Europe in 2005 is estimated as 15 000, divided between the 0–4 year, 5–9 year, and 10–14 year age-groups in the ratio 24%, 35%, and 41%, respectively. In 2020, the predicted number of new cases is 24 400, with a doubling in numbers in children younger than 5 years and a more even distribution across age-groups than at present (29%, 37%, and 34%, respectively). Prevalence under age 15 years is predicted to rise from 94 000 in 2005, to 160 000 in 2020. Interpretation If present trends continue, doubling of new cases of type 1 diabetes in European children younger than 5 years is predicted between 2005 and 2020, and prevalent cases younger than 15 years will rise by 70%. Adequate health-care resources to meet these children's needs should be made available. Funding European Community Concerted Action Program. [less ▲]

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See detailAssociations between physical activity, sedentary behavior, and glycemic control in a large cohort of adolescents with type 1 diabetes: The Hvidoere Study Group on Childhood Diabetes
Åman, J.; Skinner, T. C.; De Beaufort, Carine UL et al

in Pediatric Diabetes (2009), 10(4), 234-239

Background: The Hvidoere Study Group on Childhood Diabetes has demonstrated persistent differences in metabolic outcomes between pediatric diabetes centers. These differences cannot be accounted for by ... [more ▼]

Background: The Hvidoere Study Group on Childhood Diabetes has demonstrated persistent differences in metabolic outcomes between pediatric diabetes centers. These differences cannot be accounted for by differences in demographic, medical, or treatment variables. Therefore, we sought to explore whether differences in physical activity or sedentary behavior could explain the variation in metabolic outcomes between centers. Methods: An observational cross-sectional international study in 21 centers, with demographic and clinical data obtained by questionnaire from participants. Hemoglobin A1c (HbA1c) levels were assayed in one central laboratory. All individuals with diabetes aged 11-18 yr (49.4% female), with duration of diabetes of at least 1 yr, were invited to participate. Individuals completed a self-reported measure of quality of life (Diabetes Quality of Life - Short Form [DQOL-SF]), with well-being and leisure time activity assessed using measures developed by Health Behaviour in School Children WHO Project. Results: Older participants (p < 0.001) and females (p < 0.001) reported less physical activity. Physical activity was associated with positive health perception (p < 0.001) but not with glycemic control, body mass index, frequency of hypoglycemia, or diabetic ketoacidosis. The more time spent on the computer (r = 0.06; p < 0.05) and less time spent doing school homework (r = -0.09; p < 0.001) were associated with higher HbA1c. Between centers, there were significant differences in reported physical activity (p < 0.001) and sedentary behavior (p < 0.001), but these differences did not account for center differences in metabolic control. Conclusions: Physical activityis strongly associated with psychological well-being but has weak associations with metabolic control. Leisure time activity is associated with individual differences in HbA1c but not with intercenter differences. © 2009 John Wiley & Sons A/S. [less ▲]

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See detailOvaries and female phenotype in a girl with 46,XY karyotype and mutations in the CBX2 gene.
Biason-Lauber, Anna; Konrad, Daniel; Meyer, Monika et al

in American journal of human genetics (2009), 84(5), 658-663

A girl with a prenatal 46,XY karyotype was born with a completely normal female phenotype, including uterus and histologically normal ovaries. In mice with a similar phenotype, the ablation of M33, an ... [more ▼]

A girl with a prenatal 46,XY karyotype was born with a completely normal female phenotype, including uterus and histologically normal ovaries. In mice with a similar phenotype, the ablation of M33, an ortholog of Drosophila Polycomb, causes male-to-female sex reversal. The analysis of the human homolog of M33, Chromobox homolog 2 (CBX2), in this girl revealed loss-of-function mutations that allowed us, by placing CBX2 upstream of SRY, to add an additional component to the still incomplete cascade of human sex development. [less ▲]

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See detailRelation of circulating concentrations of chemokine receptor CCR5 ligands to C-peptide, proinsulin and HbA1c and disease progression in type 1 diabetes
Pfleger, C.; Kaas, A.; Hansen, L. et al

in Clinical Immunology (2008), 128(1), 57-65

Th1 related chemokines CCL3 and CCL5 and Th2 related CCL4 as ligands of the receptor CCR5 contribute to disease development in animal models of type 1 diabetes. In humans, no data are available addressing ... [more ▼]

Th1 related chemokines CCL3 and CCL5 and Th2 related CCL4 as ligands of the receptor CCR5 contribute to disease development in animal models of type 1 diabetes. In humans, no data are available addressing the role of these chemokines regarding disease progression and remission. We investigated longitudinally circulating concentrations of CCR5 ligands of 256 newly diagnosed patients with type 1 diabetes. CCR5 ligands were differentially associated with beta-cell function and clinical remission. CCL5 was decreased in remitters and positively associated with HbA1c suggestive of a Th1 associated progression of the disease. Likewise, CCL3 was negatively related to C-peptide and positively associated with the beta-cell stress marker proinsulin but increased in remitters. CCL4 associated with decreased beta-cell stress shown by negative association with proinsulin. Blockage of chemokines or antagonism of CCR5 by therapeutic agents such as maraviroc may provide a new therapeutic target to ameliorate disease progression in type 1 diabetes. [less ▲]

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See detailAssociation of IL-1ra and adiponectin with C-peptide and remission in patients with type 1 diabetes
Pfleger, C.; Mortensen, H.B.; Hansen, L. et al

in Diabetes (2008), 57(4), 929-937

OBJECTIVE: We investigated the association of anti-inflammatory cytokine interleukin (IL)-1 receptor antagonist (IL-1ra), adiponectin, proinflammatory cytokines IL-1 beta, IL-6, and CCL2, and tumor ... [more ▼]

OBJECTIVE: We investigated the association of anti-inflammatory cytokine interleukin (IL)-1 receptor antagonist (IL-1ra), adiponectin, proinflammatory cytokines IL-1 beta, IL-6, and CCL2, and tumor necrosis factor-alpha with beta-cell function, metabolic status, and clinical remission in patients with recent-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: Serum was obtained from 256 newly diagnosed patients (122 males and 134 females, median age 9.6 years). Stimulated C-peptide, blood glucose, and A1C were determined in addition to circulating concentration of cytokines at 1, 6, and 12 months after diagnosis. Analyses were adjusted for sex, age, and BMI percentile. RESULTS: Anti-inflammatory IL-1ra was positively associated with C-peptide after 6 (P = 0.0009) and 12 (P = 0.009) months. The beneficial association of IL-1ra on beta-cell function was complemented by the negative association of IL-1 beta with C-peptide after 1 month (P = 0.009). In contrast, anti-inflammatory adiponectin was elevated in patients with poor metabolic control after 6 and 12 months (P < 0.05) and positively correlated with A1C after 1 month (P = 0.0004). Proinflammatory IL-6 was elevated in patients with good metabolic control after 1 month (P = 0.009) and showed a positive association with blood glucose disposal after 12 months (P = 0.047). CONCLUSIONS: IL-1ra is associated with preserved beta-cell capacity in type 1 diabetes. This novel finding indicates that administration of IL-1ra, successfully improving beta-cell function in type 2 diabetes, may also be a new therapeutic approach in type 1 diabetes. The relation of adiponectin and IL-6 with remission and metabolic status transfers observations from in vitro and animal models into the human situation in vivo. [less ▲]

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See detailCaesarean section is associated with an increased risk of childhood-onset type 1 diabetes mellitus: a meta-analysis of observational studies.
Cardwell, C. R.; Stene, L. C.; Joner, G. et al

in Diabetologia (2008), 51(5), 726-35

AIMS/HYPOTHESIS: The aim of this study was to investigate the evidence of an increased risk of childhood-onset type 1 diabetes in children born by Caesarean section by systematically reviewing the ... [more ▼]

AIMS/HYPOTHESIS: The aim of this study was to investigate the evidence of an increased risk of childhood-onset type 1 diabetes in children born by Caesarean section by systematically reviewing the published literature and performing a meta-analysis with adjustment for recognised confounders. METHODS: After MEDLINE, Web of Science and EMBASE searches, crude ORs and 95% CIs for type 1 diabetes in children born by Caesarean section were calculated from the data reported in each study. Authors were contacted to facilitate adjustments for potential confounders, either by supplying raw data or calculating adjusted estimates. Meta-analysis techniques were then used to derive combined ORs and to investigate heterogeneity between studies. RESULTS: Twenty studies were identified. Overall, there was a significant increase in the risk of type 1 diabetes in children born by Caesarean section (OR 1.23, 95% CI 1.15-1.32, p < 0.001). There was little evidence of heterogeneity between studies (p = 0.54). Seventeen authors provided raw data or adjusted estimates to facilitate adjustments for potential confounders. In these studies, there was evidence of an increase in diabetes risk with greater birthweight, shorter gestation and greater maternal age. The increased risk of type 1 diabetes after Caesarean section was little altered after adjustment for gestational age, birth weight, maternal age, birth order, breast-feeding and maternal diabetes (adjusted OR 1.19, 95% CI 1.04-1.36, p = 0.01). CONCLUSIONS/INTERPRETATION: This analysis demonstrates a 20% increase in the risk of childhood-onset type 1 diabetes after Caesarean section delivery that cannot be explained by known confounders. [less ▲]

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See detailConcerns, expectations and perception regarding stature, physical appearance and psychosocial functioning before and during high-dose growth hormone treatment of short pre-pubertal children born small for gestational age
Lagrou, K.; Froidecoeur, C.; Thomas, M. et al

in Hormone Research (2008), 69(6), 334-342

Background/Aims: Few data are available about parental concerns and psychosocial functioning of young children born small for gestational age (SGA) treated with growth hormone (GH). The present study ... [more ▼]

Background/Aims: Few data are available about parental concerns and psychosocial functioning of young children born small for gestational age (SGA) treated with growth hormone (GH). The present study focused on the perception of short stature and the concerns and expectations of the parents regarding GH treatment. Methods: Forty prepubertal short SGA children, randomized into a GH-treated and a GH-untreated group, and their parents were evaluated by a questionnaire and a semi-structured interview at start and after 2 years of follow-up. Results: Before start, 85% of the parents were concerned about short stature, 76% expected an increase in adult height of ≥10 cm and 81% expected a positive impact on well-being. Half of the parents expressed fears regarding GH treatment. After 2 years, more parents of treated children reported obvious growth and physical changes, and fewer parents reported teasing because of short stature. An improvement of well-being was reported by half of the parents of treated and untreated children. Fears about GH treatment disappeared almost completely. Conclusion: The perspective of GH treatment induced major adult height expectations. In treated children, the physical effects of GH treatment became obvious, teasing because of short stature decreased and initial concerns about short stature and GH therapy decreased. Copyright © 2008 S. Karger AG. [less ▲]

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See detailAre family factors universally related to metabolic outcomes in adolescents with type 1 diabetes?
Cameron, F. J.; Skinner, T. C.; De Beaufort, Carine UL et al

in Diabetic Medicine: A Journal of the British Diabetic Association (2008), 25(4), 463-468

Aims: To assess the importance of family factors in determining metabolic outcomes in adolescents with Type 1 diabetes in 19 countries. Methods: Adolescents with Type 1 diabetes aged 11-18 years, from 21 ... [more ▼]

Aims: To assess the importance of family factors in determining metabolic outcomes in adolescents with Type 1 diabetes in 19 countries. Methods: Adolescents with Type 1 diabetes aged 11-18 years, from 21 paediatric diabetes care centres, in 19 countries, and their parents were invited to participate. Questionnaires were administered recording demographic data, details of insulin regimens, severe hypoglycaemic events and number of episodes of diabetic ketoacidosis. Adolescents completed the parental involvement scale from the Diabetes Quality of Life for Youth - Short Form (DQOLY-SF) and the Diabetes Family Responsibility Questionnaire (DFRQ). Parents completed the DFRQ and a Parental Burden of Diabetes score. Glycated haemoglobin (HbA1c) was analysed centrally on capillary blood. Results: A total of 2062 adolescents completed a questionnaire, with 2036 providing a blood sample; 1994 parents also completed a questionnaire. Family demographic factors that were associated with metabolic outcomes included: parents living together (t = 4.1; P < 0.001), paternal employment status (F = 7.2; d.f. = 3; P < 0.001), parents perceived to be over-involved in diabetes care (r = 0.11; P < 0.001) and adolescent-parent disagreement on responsibility for diabetes care practices (F = 8.46; d.f. = 2; P < 0.001). Although these factors differed between centres, they did not account for centre differences in metabolic outcomes, but were stronger predictors of metabolic control than age, gender or insulin treatment regimen. Conclusions: Family factors, particularly dynamic and communication factors such as parental over-involvement and adolescent-parent concordance on responsibility for diabetes care appear be important determinants of metabolic outcomes in adolescents with diabetes. However, family dynamic factors do not account for the substantial differences in metabolic outcomes between centres. © 2008 The Authors. [less ▲]

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See detailCo-localisation of the Kir6.2/SUR1 channel complex with glucagon-like peptide-1 and glucose-dependent insulinotrophic polypeptide expression in human ileal cells and implications for glycaemic control in new onset type 1 diabetes
Nielsen, L. B.; Ploug, K. B.; Swift, P. et al

in European Journal of Endocrinology (2007), 156(6), 663-671

Objective: The ATP-dependent K+-channel (KATP) is critical for glucose sensing and normal glucagon and insulin secretion from pancreatic endocrine α- and β-cells. Gastrointestinal endocrine L- and K-cells ... [more ▼]

Objective: The ATP-dependent K+-channel (KATP) is critical for glucose sensing and normal glucagon and insulin secretion from pancreatic endocrine α- and β-cells. Gastrointestinal endocrine L- and K-cells are also glucose-sensing cells secreting glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotrophic polypeptide (GIP) respectively. The aims of this study were to 1) investigate the expression and co-localisation of the KATP channel subunits, Kir6.2 and SUR1, in human L- and K-cells and 2) investigate if a common hyperactive variant of the Kir6.2 subunit, Glu2Lys, exerts a functional impact on glucose-sensing tissues in vivo that may affect the overall glycaemic control in children with new-onset type 1 diabetes. Design and methods: Western blot and immunohistochemical analyses were performed for expression and co-localisation studies. Meal-stimulated C-peptide test was carried out in 257 children at 1, 6 and 12 months after diagnosis. Genotyping for the Glu23Lys variant was by PCR-restriction fragment length polymorphism. Results: Kir6.2 and SUR1 co-localise with GLP-1 in L-cells and with GIP in K-cells in human ileum tissue. Children with type 1 diabetes carrying the hyperactive Glu23Lys variant had higher HbA1c at diagnosis (coefficient= 0.61%, P= 0.02) and 1 month after initial insulin therapy (coefficient= 0.30%, P=0.05), but later disappeared. However, when adjusting HbA1c for the given dose of exogenous insulin, the dose-adjusted HbA1c remained higher throughout the 12 month study period (coefficient= 0.42%, P=0.03). Conclusions: Kir6.2 and SUR1 co-localise in the gastrointestinal endocrine L- and K-cells. The hyperactive Glu2Lys variant of the KATP channel subunit Kir6.2 may cause defective glucose sensing in several tissues and impaired glycaemic control in children with type 1 diabetes. © 2007 Society of the European Journal of Endocrinology. [less ▲]

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