RESUMEN
AIMS: This article describes the methods, results and limitations of the International Diabetes Federation (IDF) Diabetes Atlas 9th edition estimates of worldwide numbers of cases of type 1 diabetes in children and adolescents. METHODS: Most information in the published literature is in the form of incidence rates derived from registers of newly-diagnosed cases. After systematic review of the published literature and recent conference abstracts, identified studies were quality graded. If no study was available, extrapolation was used to assign a country the rate from an adjacent country with similar characteristics. Estimates of incident cases were obtained by applying incidence rates to United Nations 2019 population estimates. Estimates of prevalent cases were derived from incidence rates after making allowance for higher mortality rates in less-developed countries. RESULTS: Incidence rates were available for 45% of countries (ranging from 6% in the sub-Saharan Africa region to 77% in the European region). Worldwide annual incidence estimates were 98,200 (128,900) new cases in the under 15â¯year (under 20â¯year) age-groups. Corresponding prevalence estimates were 600,900 (1,110,100) existing cases. Compared with estimates in earlier Atlas editions, numbers have increased in most IDF regions, reflecting incidence rate increases, but prevalence estimates have decreased in sub-Saharan Africa because allowance has been made for increased mortality in those with diabetes. CONCLUSIONS: Worldwide estimates of numbers of children and adolescents with type 1 diabetes continue to increase.
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Diabetes Mellitus Tipo 1/epidemiología , Adolescente , Niño , Diabetes Mellitus Tipo 1/mortalidad , Femenino , Salud Global , Humanos , Incidencia , Lactante , Masculino , Prevalencia , Tasa de SupervivenciaRESUMEN
AIMS/HYPOTHESIS: Against a background of a near-universally increasing incidence of childhood type 1 diabetes, recent reports from some countries suggest a slowing in this increase. Occasional reports also describe cyclical variations in incidence, with periodicities of between 4 and 6 years. METHODS: Age/sex-standardised incidence rates for the 0- to 14-year-old age group are reported for 26 European centres (representing 22 countries) that have registered newly diagnosed individuals in geographically defined regions for up to 25 years during the period 1989-2013. Poisson regression was used to estimate rates of increase and test for cyclical patterns. Joinpoint regression software was used to fit segmented log-linear relationships to incidence trends. RESULTS: Significant increases in incidence were noted in all but two small centres, with a maximum rate of increase of 6.6% per annum in a Polish centre. Several centres in high-incidence countries showed reducing rates of increase in more recent years. Despite this, a pooled analysis across all centres revealed a 3.4% (95% CI 2.8%, 3.9%) per annum increase in incidence rate, although there was some suggestion of a reduced rate of increase in the 2004-2008 period. Rates of increase were similar in boys and girls in the 0- to 4-year-old age group (3.7% and 3.7% per annum, respectively) and in the 5- to 9-year-old age group (3.4% and 3.7% per annum, respectively), but were higher in boys than girls in the 10- to 14-year-old age group (3.3% and 2.6% per annum, respectively). Significant 4 year periodicity was detected in four centres, with three centres showing that the most recent peak in fitted rates occurred in 2012. CONCLUSIONS/INTERPRETATION: Despite reductions in the rate of increase in some high-risk countries, the pooled estimate across centres continues to show a 3.4% increase per annum in incidence rate, suggesting a doubling in incidence rate within approximately 20 years in Europe. Although four centres showed support for a cyclical pattern of incidence with a 4 year periodicity, no plausible explanation for this can be given.
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Diabetes Mellitus Tipo 1/epidemiología , Adolescente , Niño , Preescolar , Europa (Continente)/epidemiología , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Estudios Prospectivos , Sistema de RegistrosRESUMEN
This paper describes the methodology, results and limitations of the 2013 International Diabetes Federation (IDF) Atlas (6th edition) estimates of the worldwide numbers of prevalent cases of type 1 diabetes in children (<15 years). The majority of relevant information in the published literature is in the form of incidence rates derived from registers of newly diagnosed cases. Studies were graded on quality criteria and, if no information was available in the published literature, extrapolation was used to assign a country the rate from an adjacent country with similar characteristics. Prevalence rates were then derived from these incidence rates and applied to United Nations 2012 Revision population estimates for 2013 for each country to obtain estimates of the number of prevalent cases. Data availability was highest for the countries in Europe (76%) and lowest for the countries in sub-Saharan Africa (8%). The prevalence estimates indicate that there are almost 500,000 children aged under 15 years with type 1 diabetes worldwide, the largest numbers being in Europe (129,000) and North America (108,700). Countries with the highest estimated numbers of new cases annually were the United States (13,000), India (10,900) and Brazil (5000). Compared with the prevalence estimates made in previous editions of the IDF Diabetes Atlas, the numbers have increased in most of the IDF Regions, often reflecting the incidence rate increases that have been well-documented in many countries. Monogenic diabetes is increasingly being recognised among those with clinical features of type 1 or type 2 diabetes as genetic studies become available, but population-based data on incidence and prevalence show wide variation due to lack of standardisation in the studies. Similarly, studies on type 2 diabetes in childhood suggest increased incidence and prevalence in many countries, especially in Indigenous peoples and ethnic minorities, but detailed population-based studies remain limited.
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Diabetes Mellitus Tipo 1/epidemiología , Salud Global/estadística & datos numéricos , Adolescente , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , PrevalenciaRESUMEN
INTRODUCTION: Disturbances in carbohydrate metabolism during pregnancy may result in harmful fetal and neonatal consequences. OBJECTIVES: To assess the fetal and neonatal complications of pregnancy in mothers with gestational and pregestational diabetes during a 10-year period in a county hospital in Hungary. METHODS: Retrospective analysis of infants of diabetic mothers admitted to the neonatal unit between 2001 and 2010. RESULTS: 32% of the infants were transferred to the neonatal unit. Neonatal macrosomia (birth weight >90 centile) was observed in one quarter of the infants. 39% of the infants developed hypoglycemia (blood glucose <2.6 mmol/l), in the majority of the cases within the first 8 hours. Hypoglycaemia was symptomatic in 55% of the infants. Hypocalcemia was observed in 17%, hyperviscosity in 23%, hyperbilirubinaemia in 32%, respiratory distress syndrome and/or transient tachypnoe in 22% and cardiac complications in 13% of the infants. 10% of the inafnts were affected with birth injuries. Congenital anomalies were seen in 17% of the cases, and severe malformations were present in 4% of the infants. CONCLUSIONS: Despite modern diabetes management, there is still a higher incidence of fetal macrosomia, adverse neonatal outcomes and a higher rate of severe congenital malformations in neonates of diabetic mothers.
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Anomalías Congénitas/epidemiología , Diabetes Gestacional , Enfermedades Fetales/epidemiología , Enfermedades del Recién Nacido/epidemiología , Embarazo en Diabéticas , Adulto , Asfixia Neonatal/epidemiología , Glucemia/metabolismo , Cardiomegalia/epidemiología , Anomalías Congénitas/etiología , Diabetes Gestacional/sangre , Femenino , Enfermedades Fetales/etiología , Edad Gestacional , Humanos , Hungría/epidemiología , Hiperbilirrubinemia/epidemiología , Hipocalcemia/epidemiología , Hipoglucemia/epidemiología , Recién Nacido , Enfermedades del Recién Nacido/etiología , Infecciones/epidemiología , Masculino , Policitemia/epidemiología , Embarazo , Embarazo en Diabéticas/sangre , Síndrome de Dificultad Respiratoria del Recién Nacido/epidemiología , Estudios RetrospectivosRESUMEN
Short interbirth interval has been associated with maternal complications and childhood autism and leukemia, possibly due to deficiencies in maternal micronutrients at conception or increased exposure to sibling infections. A possible association between interbirth interval and subsequent risk of childhood type 1 diabetes has not been investigated. A secondary analysis of 14 published observational studies of perinatal risk factors for type 1 diabetes was conducted. Risk estimates of diabetes by category of interbirth interval were calculated for each study. Random effects models were used to calculate pooled odds ratios (ORs) and investigate heterogeneity between studies. Overall, 2,787 children with type 1 diabetes were included. There was a reduction in the risk of childhood type 1 diabetes in children born to mothers after interbirth intervals <3 years compared with longer interbirth intervals (OR 0.82 [95% CI 0.72-0.93]). Adjustments for various potential confounders little altered this estimate. In conclusion, there was evidence of a 20% reduction in the risk of childhood diabetes in children born to mothers after interbirth intervals <3 years.
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Diabetes Mellitus Tipo 1/etiología , Adulto , Orden de Nacimiento , Peso al Nacer , Niño , Femenino , Humanos , Embarazo , Factores de Riesgo , Factores de TiempoRESUMEN
UNLABELLED: There are no population-based data on the autoimmune morbidity and vascular complications of young adults with childhood-onset type 1 diabetes in Hungary. AIMS: To assess the prevalence of these morbidities after 20 years of diabetes duration. METHOD: Postal questionnaire. RESULTS: 6.2% of the patients had celiac disease. Diabetes was diagnosed at a significantly earlier age in patients with diabetes and celiac disease as compared to those without celiac diasease. Thyroid autoimmunity was reported in 7.6% of cases. They were significantly older with longer duration of diabetes. Every fifth patients reported retinopathy, one sixth of patients was treated for hypertension. Neuropathy was found in 3.4% and kidney disease in 4.8% of the cases. CONCLUSIONS: Apart from retinopathy and hypertension, the prevalence of microvascular complications was relatively low. Considering the limitations of questionnaire studies, laboratory screening is warranted to assess the true prevalence of comorbidities and complications.
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Autoinmunidad , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/epidemiología , Angiopatías Diabéticas/epidemiología , Adolescente , Adulto , Edad de Inicio , Enfermedad Celíaca/epidemiología , Enfermedad Celíaca/inmunología , Niño , Preescolar , Comorbilidad , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/inmunología , Neuropatías Diabéticas/epidemiología , Neuropatías Diabéticas/inmunología , Retinopatía Diabética/epidemiología , Retinopatía Diabética/inmunología , Femenino , Humanos , Hungría/epidemiología , Hipertensión/epidemiología , Hipertensión/inmunología , Masculino , Microcirculación , Prevalencia , Encuestas y Cuestionarios , Tiroiditis Autoinmune/epidemiología , Factores de Tiempo , Adulto JovenRESUMEN
The aim of this study was to examine secular trends in the incidence of type 1 diabetes in children aged 0-14 yr in Hungary over the period 1989-2009. Newly diagnosed children with type 1 diabetes aged 0-14 yr in Hungary were prospectively registered from 1989 to 2009. Primary ascertainment of cases was by prospective registration using hospital notifications. Case ascertainment was over 96% complete using the capture-recapture method. Standardized incidence rates were calculated and secular trends estimated using Poisson regression analysis. In Hungary during 1989-2009 a total number of 3432 children were identified, giving a standardized incidence rate of 12.5 [95% confidence interval (CI) 12.1-12.9] per 100,000 person yr. The overall incidence rate has doubled from 7.7 (95% CI 6.4-9.15) per 100,000 per yr in 1989 to 18.2 (95% CI 15.7-20.9) per 100,000 per yr in 2009. A significant linear trend in incidence (p < 0.001) has been observed over time, with a mean annual increase of 4.4%. The increase in incidence was present in both genders and in all age groups, with the largest relative increase in the youngest age group (6.2%; p < 0.001). The incidence of type 1 diabetes in Hungarian children continues to increase, with the highest rate in the very young. Although it seems that transient periods of stabilization followed by increases in incidence are apparent, the long-term trend continues to be steadily upward. Incidence of childhood type 1 diabetes is a dynamic process, probably reflecting the changes of the environmental exposures and continued registration is necessary to recognize these trends.
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Diabetes Mellitus Tipo 1/epidemiología , Adolescente , Edad de Inicio , Niño , Preescolar , Femenino , Predicción , Humanos , Hungría/epidemiología , Incidencia , Lactante , Recién Nacido , Funciones de Verosimilitud , Masculino , Estudios Prospectivos , Factores Sexuales , Factores de TiempoRESUMEN
UNLABELLED: Aim of this study was to examine secular trends in the incidence of type 1 diabetes in children aged 0-14 years in Hungary over the period 1989-2009. METHODS: Newly diagnosed children with type 1 diabetes aged 0-14 years in Hungary were prospectively registered from 1989 to 2009. Standardized incidence rates were calculated and secular trends were estimated using Poisson regression analysis. RESULTS: Between 1989 and 2009 a total number of 3432 children were identified, giving a standardized incidence rate of 12.5 (95%CI 12.1-12.9) per 100 000 person/year. The overall incidence rate has doubled from 7.7 (95%CI 6.4-9.15) per 100 000 per year in 1989 to 18.2 (95%CI 15.7-20.9) per 100 000 per year in 2009. A significant linear trend in incidence (p<0.001) has been observed over time, with a mean annual increase of 4.4%. The increase in incidence was present in both genders and in all age groups, with the largest relative increase in the youngest age group (6.2%; p<0.001). CONCLUSION: The incidence of type 1 diabetes in Hungarian children continues to increase, with the highest rate in the very young.
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Diabetes Mellitus Tipo 1/epidemiología , Adolescente , Distribución por Edad , Niño , Preescolar , Femenino , Humanos , Hungría/epidemiología , Incidencia , Lactante , Masculino , Distribución por SexoRESUMEN
Autoimmune diseases are initiated by interaction between genetic and environmental factors and caused by the loss of immunologic tolerance to self-antigens. They cluster within families and individuals, but the aggregation in a triad is quite rare. We report a case of a young girl affected by three organ-specific autoimmune disorders, from which type 1 diabetes developed first, then Hashimoto's thyroiditis and juvenile rheumatoid arthritis were diagnosed. Hitherto unreported detailed genetic studies included genotyping of HLA class II, CTLA4, and PTPN22 gene regions. These genes have been associated with autoimmunity in general and some of their variants confer increased risk to all three diseases. Our results - with the limitation of reporting only on a single patient - contribute to the complex genetic background of these clustering organ-specific autoimmune diseases and the analysis of further similar cases might help to reveal how the major and minor genetic factors determine the individual clinical phenotype.
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Artritis Juvenil/complicaciones , Enfermedades Autoinmunes/complicaciones , Diabetes Mellitus Tipo 1/complicaciones , Enfermedad de Hashimoto/complicaciones , Adolescente , Antígenos CD/genética , Artritis Juvenil/genética , Enfermedades Autoinmunes/genética , Antígeno CTLA-4 , Niño , Preescolar , Diabetes Mellitus Tipo 1/genética , Femenino , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Enfermedad de Hashimoto/genética , Humanos , Proteína Tirosina Fosfatasa no Receptora Tipo 22/genéticaRESUMEN
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.
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Protección a la Infancia/tendencias , Diabetes Mellitus Tipo 1/epidemiología , Sistema de Registros , Adolescente , Distribución por Edad , Niño , Preescolar , Costo de Enfermedad , Diabetes Mellitus Tipo 1/complicaciones , Europa (Continente)/epidemiología , Femenino , Predicción , Planificación en Salud , Necesidades y Demandas de Servicios de Salud , Humanos , Incidencia , Lactante , Funciones de Verosimilitud , Modelos Lineales , Masculino , Vigilancia de la Población , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Distribución por SexoAsunto(s)
Diabetes Mellitus Tipo 1/epidemiología , Salud Global , Adolescente , Distribución por Edad , Edad de Inicio , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Masculino , Sistema de Registros , Distribución por SexoRESUMEN
Type 1 diabetes is often accompanied with acute hypoinsulinemia that may theoretically inhibit the conversion of essential fatty acids to their longer-chain metabolites. Previously, we found significant reduction in plasma arachidonic (C20:4n-6) and docosahexaenoic (C22:6n-3) acid values in a group of diabetic children during diabetic ketoacidosis. Here we report data on the changes of fatty acids in plasma phospholipids in a diabetic teenager during and after nine subsequent episodes of diabetic ketoacidosis (DKA). Plasma phospholipid linoleic acid (C18:2n-6) values significantly decreased [23.05 (1.05) versus 19.22 (3.22), % w/w, median (IQR), p < 0.01], while values of dihomo-gamma-linolenic acid (C20:3n-6) and docosatetraenoic acid (C22:4n-6) significantly increased [1.72 (0.44) versus 1.80 (0.63) and 0.40 (0.01) versus 0.45 (0.07), respectively, p < 0.05]. Values of alpha-linolenic acid (C18:3n-3) did not change, while values of docosahexaenoic acid were significantly higher after than during the ketoacidosis [1.57 (0.67) versus 1.87 (0.32), p < 0.05). These data obtained in the same patient during repeated episodes of diabetic ketoacidosis support the concept that hypoinsulinemia plays an important role in disturbances of essential fatty acid metabolism in diabetes.
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Diabetes Mellitus Tipo 1/sangre , Cetoacidosis Diabética/sangre , Cetoacidosis Diabética/tratamiento farmacológico , Ácidos Grasos Insaturados/sangre , Adolescente , Glucemia/metabolismo , Índice de Masa Corporal , Diabetes Mellitus Tipo 1/fisiopatología , Cetoacidosis Diabética/fisiopatología , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Sistemas de Infusión de Insulina , RecurrenciaRESUMEN
It has been reported that urinary interleukin-6 (IL-6) and IL-8 levels are decreased in adult diabetic women with asymptomatic bacteriuria (ASB) when compared with non-diabetic women with ASB. Such impaired cytokine excretion might play a role in the higher prevalence of ASB among diabetic subjects. The aim of this study was to examine the urinary IL profile in children and young adults with type 1 diabetes mellitus (T1DM) with and without ASB. Midstream clean voiding urine samples were collected and cultured from 133 patients with T1DM (age: 15.6 +/- 5.7 yr) and 178 controls (14.1 +/- 4.7 yr) for two consecutive days. ASB was diagnosed in the case of >or=10(5) bacteria/mL. The urinary IL-6 and IL-8 concentrations were determined, and the presence of leukocyturia was also recorded. The prevalence of ASB was 16.5% in diabetic subjects and 2.8% in controls (p = 0.001). There was no difference between the diabetic and the control groups in the prevalence of 'IL-6-uria' (21.9 vs. 18.0%; p = 0.41), but IL-8 was more frequently detectable in the diabetic group (47.4 vs. 27.5%; p = 0.001). In individuals with ASB, the IL-8 level was similar in the diabetic (median: 70.0 pg/mg creatinine) and control group (42.3 pg/mg creatinine; p = 0.8). Indeed, the IL-8 levels were higher in diabetic subjects with ASB as compared with those without it (70.0 vs. <3.1 pg/mg creatinine; p = 0.001), and there was a significant association between the urinary IL-8 concentration and the bacterial count (p = 0.001). Diabetic patients with leukocyturia had higher IL-8 concentration than those without it (20.9 vs. <3.1 pg/mg creatinine; p = 0.003). Weak significant correlation was found between urinary IL-8 and hemoglobin A1c (HbA1c) (r = 0.4; p = 0.002). The sensitivity and specificity of leukocyturia were 50 and 89.9% in the whole population and those of IL-8 were 74.1 and 67.5%, respectively. In diabetic patients, 36.4% of the bacteriuria were gram-negative and 63.6% gram-positive. Our results suggest that diabetic children with ASB mount an IL-8 response to pathogens, which is comparable to non-diabetic children with bacteriuria. Thus, early in the natural history of diabetes, there are no significant changes in the IL response of children with ASB, as previously reported in adults.
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Bacteriuria/complicaciones , Diabetes Mellitus Tipo 1/inmunología , Interleucina-6/orina , Interleucina-8/orina , Adolescente , Adulto , Bacteriuria/inmunología , Estudios de Casos y Controles , Niño , Preescolar , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/orina , Femenino , Hemoglobina Glucada/análisis , Bacterias Gramnegativas/aislamiento & purificación , Bacterias Grampositivas/aislamiento & purificación , Humanos , Leucocitosis/orina , Masculino , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: The overlap between genetic susceptibility to celiac disease (CD) and to type 1 diabetes is incomplete; therefore, some genetic polymorphisms may significantly modify the risk of CD in subjects with type 1 diabetes. This study aimed to investigate whether the susceptibility to CD in diabetic children is modified by positivity for HLA-DQB1*02-DQA1*05 and DQB1*0302-DQA1*03 and by alleles of single nucleotide polymorphisms within the genes encoding CTLA4, transforming growth factor (TGF)-beta, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1, IL-2, IL-6, and IL-10. RESEARCH DESIGN AND METHODS: Genotypic data were compared between 130 case subjects (children with type 1 diabetes and CD diagnosed using endomysium antibodies) and 245 control subjects (children with type 1 diabetes only, optimally two per case, matched for center, age at type 1 diabetes onset, and type 1 diabetes duration). The subjects were recruited from 10 major European pediatric diabetes centers performing regular screening for CD. The polymorphisms were determined using PCR with sequence-specific primers, and the risk was assessed by building a step-up conditional logistic regression model using variables that were significantly associated with CD in the univariate analysis. RESULTS: The best-fitted model showed that risk of CD is increased by presence of HLA-DQB1*02-DQA1*05 (odds ratio 4.5 [95% CI 1.8-11], for homozygosity, and 2.0 [1.1-3.7], for a single dose) and also independently by TNF -308A (1.9 [1.1-3.2], for phenotypic positivity), whereas IL1-alpha -889T showed a weak negative association (0.6 [0.4-0.9]). CONCLUSIONS: The results indicate that the risk of CD in children with type 1 diabetes is significantly modified both by the presence of HLA-DQB1*02-DQA1*05 and by a variant of another gene within the major histocompatibility complex, the TNF -308A.
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Enfermedad Celíaca/genética , Diabetes Mellitus Tipo 1/genética , Antígenos HLA-DQ/genética , Factor de Necrosis Tumoral alfa/genética , Adolescente , Estudios de Casos y Controles , Enfermedad Celíaca/complicaciones , Enfermedad Celíaca/inmunología , Niño , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/inmunología , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Cadenas alfa de HLA-DQ , Cadenas beta de HLA-DQ , Humanos , Masculino , Fenotipo , Análisis de Regresión , Factores de RiesgoRESUMEN
BACKGROUND AND AIM: Previously we reported significantly higher plasma values of the essential fatty acids but significantly lower values of their longer-chain metabolites in diabetic children than in healthy controls. Here, we report data on the acute effect of diabetic ketoacidosis (DKA) on the fatty acid composition of plasma lipids. METHODS: Diabetic children (n=9; age: 16.1 [3.3] y; duration of diabetes: 5.0 [5.3.] y; daily insulin dose: 0.87 [0.66] unit/kg body weight/d; glycated haemoglobin: 13.4 [2.8] %; median [IQR]) were investigated at admission for DKA (during DKA) and at the end of the treatment of DKA (after DKA). Fatty acid composition of plasma lipid classes was determined by high-resolution capillary gas-liquid chromatography. RESULTS: Blood glucose (27.0 [8.5] vs 6.5 [1.6] mmol/l), pH (7.28 [0.35] vs 7.36 [0.06]) and base excess (-8.9 [15.1] vs -2.2 [6.3] mmol/l) were grossly abnormal during but not after DKA. Values of linoleic acid were significantly lower after than during DKA (non-esterifed fatty acids (NEFA): 15.55 [1.47] vs 12.27 [5.74] % wt/wt; triacylglycerols (TG): 20.84 [9.23] vs 17.40 [5.78]; p<0.05). In contrast, values of gamma-linolenic acid (NEFA: 0.87 [0.54] vs 2.34 [1.85]; p<0.05) and arachidonic acid (TG: 1.37 [0.71] vs 1.74 [0.57]; p<0.05) were significantly lower during than after DKA. The product/substrate ratios for delta-6 desaturation were significantly lower during than after DKA. CONCLUSION: Successful treatment of diabetic ketoacidosis is associated with a significant increase of long-chain polyunsaturated fatty acid values in blood plasma in diabetic children. This observation suggests that disturbances of essential fatty acid metabolism in diabetic children are related not only to diet but to hypoinsulinaemia as well.
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Cetoacidosis Diabética/sangre , Ácidos Grasos Insaturados/sangre , Adolescente , Femenino , Humanos , Ácido Linoleico/sangre , Masculino , Fosfolípidos/químicaRESUMEN
OBJECTIVE: To investigate clinical and metabolic characteristics of diabetic children with screening detected celiac disease in a multicenter case-control study. CASES: 98 diabetic patients were diagnosed as having silent celiac disease by screening with endomysial antibodies and subsequent biopsy. CONTROLS: two controls in the same center were chosen, (stratified by age and age-at-diabetes onset) who were negative for endomysial antibodies (n = 195). Height, weight, HbA1c, insulin dosage and acute complications were documented for at least 1 year of follow up. RESULTS: Mean age of diabetes manifestation was 6.5 +/- 4.1 years and diagnosis of celiac disease was made at 10.0 +/- 5.4 years. Biopsy showed total or subtotal mucosal atrophy in 74 patients. The mean observation period after the diagnosis of celiac disease was 3.3 +/- 1.9 years. Mean HbA1c levels were similar between cases and controls (8.63% +/- 1.45% versus 8.50% +/- 1.39%; P = 0.35). There was also no difference in the frequency of severe hypoglycemia, ketoacidosis and the applied insulin dosage (P = 0.45). Body mass index-standard deviation score at celiac disease diagnosis (0.57 +/- 1.24 versus 0.52 +/- 1.07) and height-standard deviation score (0.14 +/- 1.13 versus 0.30 +/- 0.95) did not differ between cases and controls. After diagnosis of celiac disease, weight gain was diminished in boys with celiac disease compared with their controls (P < 0.05). Female cases also had a lower body mass index than female controls (P = 0.067). CONCLUSION: In a cohort of diabetic children, silent celiac disease had no obvious effect on metabolic control but negatively influenced weight gain.
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Enfermedad Celíaca/diagnóstico , Diabetes Mellitus Tipo 1/complicaciones , Autoanticuerpos/sangre , Estudios de Casos y Controles , Enfermedad Celíaca/epidemiología , Enfermedad Celíaca/patología , Niño , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/análisis , Humanos , Masculino , Tamizaje Masivo , Prevalencia , Factores Sexuales , Aumento de PesoRESUMEN
We aimed to assess the possible contribution of the PAX4 transcription factor gene to the genetic background of type 1 diabetes. We analyzed four coding polymorphisms of the PAX4 gene in 498 cases with type 1 diabetes and 825 control subjects from Finland and Hungary. All patients were diagnosed under the age of 15 years according to the World Health Organization criteria. All four PAX4 variants (three in exon 9 and one in exon 3) were genotyped using DNA sequencing. In addition, all Finnish subjects were typed for HLA DR-DQ, insulin gene (-23) HphI, and CTLA4 CT60 polymorphisms. The +1,168 C/A coding variant of PAX4 was found to be polymorphic in both populations (P321H, rs712701). No difference was observed in the genotype frequencies between cases and control subjects, nor was any disease association detected when patients were stratified according to age at diagnosis, sex, HLA, insulin gene, or CTLA4 genotypes. Our data indicate that the +1,168 C/A variant of PAX4 gene does not play any essential role in genetic type 1 diabetes susceptibility. The strong coherence between the datasets of the two ethnic groups studied with highly contrasting disease incidence, socioeconomic characteristics, and profoundly diverse environment emphasizes the impact of this finding.
Asunto(s)
Diabetes Mellitus Tipo 1/genética , Proteínas de Homeodominio/genética , Factores de Transcripción Paired Box/genética , Adolescente , Niño , Preescolar , Clima , Femenino , Finlandia , Predisposición Genética a la Enfermedad , Humanos , Hungría , Lactante , Recién Nacido , Masculino , Factores SocioeconómicosRESUMEN
Decreased first-phase secretion of insulin may play a role in the development of insulin resistance. In the development of type 2 diabetes an abnormal function of the beta-cells and insulin resistance of liver, fat cells and muscle play the main role. An early sign of beta-cell damage can be the loss of first-phase insulin response. This is supposed to precede the development of insulin resistance. Decrease of first-phase secretion of insulin can induce early postprandial hyperglycaemia and hypertriglyceridaemia damaging endothelium of precapillary arterioles of the nutritive capillaries. Insulin-induced endothelium-dependent dilation of these arterioles is inhibited by high glucose and triglyceride levels preventing metabolic effect of insulin on the parenchymal cells surrounded by nutritive capillaries and leading this way to insulin resistance. Second-phase hyperinsulinaemia develops in the impaired glucose tolerance. With the progression of the disease into the type 2 diabetes, insulin secretion decreases in the second-phase, as well. Because of decrease of first-phase insulin secretion in type 2 diabetic patients, early insulin therapy could be a choice of treatment in type 2 diabetes. Results of the UKPDS suggest that insulin-treated type 2 diabetic patients are longer in the near-euglycaemic state compared to those treated by oral hypoglycaemic agents. Recent data support that early insulin therapy of type 2 diabetic patients retains their own insulin secretion capacity and results in lower haemoglobin A1c. A comparison of before-meal rapid-acting insulin analogue and bedtime NPH insulin regimens verified that rapid-acting insulin analogue decreased haemoglobin A1c compared to NPH insulin treatment in type 2 diabetes. On the basis of these data arises the possibility of the change of the attitude "Oh no, not insulin in type 2 diabetes" to the "early rapid-acting insulin analogue treatment" of these patients.