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OBJECTIVES: The COVID-19 pandemic affected the mental health of children and adolescents in the general population, yet its impact on those with chronic conditions is relatively unknown. This study aimed to compare the incidences of comorbid mental disorders and substance misuse in children and adolescents with type 1 diabetes before and during the pandemic. METHODS: A total of 42,975 patients aged 6-18 years from the multicentre DPV (Diabetes Prospective Follow-up) registry were included. Multivariable regression models were applied to compare newly diagnosed comorbid mental disorders, adjusted for demographic and clinical variables, among them the number of medical visits, during the pre-pandemic period (09/2017-02/2020) and the COVID-19 pandemic period (03/2020-08/2022). RESULTS: Analysing both sexes together, there were no differences in the incidence rates of overall mental disorders between the pandemic and the pre-pandemic period. However, girls showed an increased incidence rate (odds ratio 1.2, CI 1.1-1.3) during the pandemic. Adolescent girls also displayed higher incidence rates of depression, eating disorders, and self-harm. Substance misuse declined overall during the pandemic (odds ratio 0.8, CI 0.7-0.9). CONCLUSIONS: During the COVID-19 pandemic, we found higher incidence rates of overall mental disorders in girls, but not in boys and not in the total study population of children and adolescents with type 1 diabetes. Adolescent girls displayed increased incidence rates of depression, eating disorders, and self-harm. Substance misuse declined substantially. Clinicians should be aware of the high-risk group of adolescent girls during times of increased strain.
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COVID-19 , Diabetes Mellitus Tipo 1 , Trastornos Mentales , Sistema de Registros , Humanos , Adolescente , COVID-19/epidemiología , COVID-19/psicología , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/psicología , Diabetes Mellitus Tipo 1/complicaciones , Femenino , Masculino , Niño , Trastornos Mentales/epidemiología , Incidencia , Comorbilidad , Estudios Prospectivos , SARS-CoV-2 , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/complicaciones , Pandemias , Estudios de SeguimientoRESUMEN
Aims: To investigate (1) daily, emotional, and physical caregiving burdens in parents of children with type 1 diabetes, (2) the sociodemographic and clinical predictors of three burdens, and (3) support measures that parents wish to receive. Methods: The study was a multicenter cross-sectional survey conducted in nine German pediatric diabetes centers. A questionnaire assessing three types of burdens and wishes for support was distributed to parents with a child with type 1 diabetes visiting one of the pediatric centers for a routine check-up. Results: Data from 1,107 parents (83% mothers) were analyzed. Parents reported significantly higher emotional burdens compared to daily and physical burdens (p < 0.0001). Mothers felt more burdened than fathers did. Parents of younger children reported higher daily and physical burdens compared to the parents of older children, and similarly, parents of technology users reported higher daily and physical burdens compared to the parents of nontechnology users. However, emotional burdens did not differ in both comparisons. Other demographic factors (i.e., parent's age, migration status, and single-parent family status) predicted high levels of daily or physical burdens, but only HbA1c level and the parent's gender (mother) predicted a high emotional burden. Independent of the level of burden, 78% of parents wanted additional diabetes training. Conclusion: Despite parents reporting high emotional burdens in connection with diabetes care, HbA1c and the gender of the reporting parent were the only risk factors. As the child gets older, parents' daily and physical distress decrease but not the emotional burden. Diabetes training including regularly offered booster sessions as well as low-threshold interventions for mental health issues and practical self-care skills is recommended to provide continuous support for parents.
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Diabetes Mellitus Tipo 1 , Femenino , Humanos , Niño , Adolescente , Diabetes Mellitus Tipo 1/terapia , Estudios Transversales , Hemoglobina Glucada , Padres , MadresRESUMEN
OBJECTIVE: To study diabetic cataract in type 1 diabetes in a large pediatric cohort. METHODS: The 92,633 patients aged 0.5-21 years from German/Austrian multicenter diabetes registry (DPV) were analyzed. The 235 patients (0.25%) with diabetic cataract were found, 200 could be categorized: 67 with early cataract (3 months before diabetes onset - 12 months afterwards), 133 with late cataract (>12 months after diabetes onset). Regression models adjusted for age and gender were used to compare clinical parameters at diabetes onset. Regression models for patients with late cataract were implemented for the total documentation period and additionally adjusted for diabetes duration. RESULTS: Rate of cataract development shows a peak at diabetes onset and declines with longer diabetes duration. Patients with cataract showed strong female preponderance. Patients developing early cataract were older at diabetes onset (12.8 years [11.8/13.9] vs. 8.9 [8.9/9.0]; p < 0.001) and showed higher HbA1c than patients without cataract (9.0% [8.55/9.38] vs. 7.6% [7.60/7.61]; p < 0.001). They had lower height-SDS, (-0.22 [-0.48/0.04] vs. 0.25 [0.24/0.26]; p < 0.001), lower weight-SDS (-0.31 [-0.55/-0.08] vs. 0.21 [0.20/0.21]; p < 0.001) and lower BMI-SDS (-0.25 [-0.49/-0.02] vs. 0.12 [0.12/0.13); p = 0.002). Patients with late cataract showed higher HbA1c at diabetes onset (8.35% [8.08/8.62] vs. 8.04% [8.03/8.05]; p = 0.023) and higher mean HbA1c during total documentation period (8.00% [7.62/8.34] vs. 7.62% [7.61/7.63]; p = 0.048). CONCLUSIONS: Our data confirm known demographic and clinical characteristics of patients developing early cataract. Hyperglycemia-induced osmotic damage to lens fibers at diabetes onset might be the main pathomechanism. Long term glycemic control is associated with cataract development.
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Catarata , Diabetes Mellitus Tipo 1 , Adolescente , Adulto , Austria/epidemiología , Catarata/epidemiología , Catarata/etiología , Niño , Preescolar , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/epidemiología , Femenino , Alemania/epidemiología , Hemoglobina Glucada , Humanos , Lactante , Insulina , Sistema de Registros , Adulto JovenRESUMEN
OBJECTIVE: To investigate the occupational and financial consequences for parents following the onset of type 1 diabetes in their child. RESEARCH DESIGN AND METHODS: A questionnaire assessing occupational and financial situations before and in the first year after the onset of diabetes was distributed to all families with a child ≤14 years of age at diagnosis with a diabetes duration of at least 12 months in nine German pediatric diabetes centers. RESULTS: Data of 1,144 children (mean age at diagnosis 6.7 [3.6] years; 46.5% female) and their families were obtained. Mothers' occupational status reflected in paid working hours was significantly reduced in the first year after their child's diabetes diagnosis (P < 0.001). Overall, 15.1% of mothers stopped working, and 11.5% reduced working hours. Mothers of preschool children were particularly affected. Fathers' working status hardly changed (P = 0.75). Nearly half of the families (46.4%) reported moderate to severe financial losses. Compared with an earlier similar study in 2003, significant negative occupational consequences for mothers and financial burden on families remained unchanged in 2018 (P = 0.59 and 0.31, respectively). CONCLUSIONS: Mothers of young children with newly diagnosed diabetes experienced negative consequences in their occupational situation. This inequality for mothers can have long-term negative consequences for their mental health and future economic situation. There is an urgent need for action to reduce the burden on families and to provide professional, social, and regulatory support, especially for mothers of young children with diabetes.
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Diabetes Mellitus Tipo 1 , Madres , Cuidadores/economía , Cuidadores/psicología , Cuidadores/estadística & datos numéricos , Niño , Preescolar , Costo de Enfermedad , Diabetes Mellitus Tipo 1/economía , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/psicología , Padre/psicología , Padre/estadística & datos numéricos , Femenino , Alemania/epidemiología , Humanos , Masculino , Salud Mental , Madres/psicología , Madres/estadística & datos numéricos , Padres/psicología , Encuestas y CuestionariosRESUMEN
BACKGROUND: Despite increasing use of technology in type 1 diabetes, persistent ethnic and socio-economic disparities have been reported. We analyzed how the use of insulin pump therapy and continuous glucose monitoring (CGM) evolved over the years in Germany depending on demographics and area deprivation. METHOD: We investigated the use of insulin pump and CGM between 2016 and 2019 in 37,798 patients with type 1 diabetes aged < 26 years from the German Prospective Follow-up Registry (DPV). Associations with federal state, area-deprivation quintile (German Index of Multiple Deprivation 2010 on district level), gender, and migration background were investigated over time using multiple logistic regression. RESULTS: Between 2016 and 2019, the regional distribution of insulin pump use did not change substantially and the association with area deprivation remained non-linear and statistically non-significant. The effect of area deprivation on CGM use decreased continuously and disappeared in 2019 (OR [95%-CI] Q1 vs Q5: 1.85 [1.63-2.10] in 2016; 0.97 [0.88-1.08] in 2019). The effect of migration background on the use of either technology decreased over the years but remained significant in 2019. Girls had constantly higher odds of using an insulin pump than boys (OR: 1.25 [1.18-1.31] in 2019), whereas no gender difference was identified for CGM use. CONCLUSIONS: Although disparities decreased in Germany, access to diabetes technology still depends on migration background in 2019, and gender differences in pump use persist. As technological advances are made, further research is needed to understand the reasons for these persistent disparities.
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Automonitorización de la Glucosa Sanguínea , Diabetes Mellitus Tipo 1 , Glucemia , Demografía , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/epidemiología , Femenino , Alemania/epidemiología , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Sistemas de Infusión de Insulina , Masculino , Estudios Prospectivos , TecnologíaRESUMEN
BACKGROUND: Systemic juvenile idiopathic arthritis (sJIA) is a complex disease with dysregulation of the innate immune system driven by cytokines. A major role is ascribed to interleukin-1ß (IL-1ß), supporting the autoinflammatory character of the disease and offering an effective blocking mechanism for treatment. Here we present clinical practice data from the German AID-registry for patients treated with IL-1 inhibition (IL-1i). METHODS: In 2009 a clinical and research consortium (AID-Net) was established, including an online AID-registry. Patients with documented sJIA diagnosis were identified. Data for this retrospective IL-1i study were recorded by 17 centers. Response to treatment was evaluated according to Wallace criteria and additionally by an own classifying clinical response system. RESULTS: In 6 years, 202 patients with confirmed sJIA were recorded in the AID-registry. Out of these, 111 children received therapy with Anakinra (ANA) (n = 84, 39 f) and/or Canakinumab (CANA) (n = 27, 15 f) at a median age of 8.7 y (range 0.6-19.1). During the first 12 months 75/111 (ANA 55, CANA 20) patients were evaluated according to Wallace criteria (achievement of inactive disease 28/55 and 17/20, remission over 6 months under medication 13/55 and 7/20 cases). Over the whole period of time, clinical response was preserved in the majority of patients (ANA 54/80, CANA 20/27). Arthritis mostly persisted in polyarticular (PA) courses. During treatment with IL-1i concomitant medication could be tapered in about 15%. IL-1i was discontinued in 59/111 patients. 45 (15) adverse events (AE)s in ANA (CANA) treated patients (19.7 (26.6) AE/100 ANA (CANA) exposure years, 95%CI: 14.4-26.4 (14.9-43.9)) were reported. CONCLUSION: In a large cohort of sJIA patients from Germany, we can confirm an overall favorable clinical response to both available IL-1 blocking agents. IL-1i was well tolerated with acceptable safety and effectiveness in a real-life clinical setting.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Interleucina-1beta/antagonistas & inhibidores , Adolescente , Niño , Preescolar , Alemania , Humanos , Lactante , Sistema de Registros , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: To investigate temporal trends and contemporary use of insulin pump therapy and glucose monitoring in type 1 diabetes. RESEARCH DESIGN AND METHODS: In a population-based study, we analyzed the use of insulin pump therapy, continuous glucose monitoring (CGM), and self-monitoring of blood glucose (SMBG) from 1995 to 2017 in patients with type 1 diabetes identified from the Diabetes Prospective Follow-up (DPV) database in Germany and Austria. Patients were stratified by age, sex, migration background, and country. RESULTS: Among 96,547 patients with type 1 diabetes (median age 17.9 years, 53% males), the percentage using insulin pump therapy increased from 1% in 1995 to 53% in 2017, with the highest rates in the youngest patients (92% in preschoolers, 74% in children, 56% in adolescents aged <15 years, 46% in adolescents aged ≥15 years, 37% in adults). The percentage of patients using CGM increased from 3% in 2006 to 38% in 2017, with the highest rates in the youngest patients (58%, 52%, 45%, 33%, and 15% of respective age-groups). Daily SMBG frequencies increased from 1995 to 2016 and decreased afterward, most prominently in the youngest patients. Between 2015 and 2017, pump therapy was more frequently used in female versus male adolescents and adults (all P < 0.001), while no sex differences were observed for pump use in children <10 years (all P = 1.0) and for CGM use in all age-groups (all P = 1.0). CONCLUSIONS: Since 1995, insulin pump use has continuously increased, and insulin pump therapy is now standard in patients aged <15 years. CGM use sharply rose in recent years, particularly in young children.
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Automonitorización de la Glucosa Sanguínea/tendencias , Diabetes Mellitus Tipo 1/terapia , Hipoglucemiantes/uso terapéutico , Sistemas de Infusión de Insulina/tendencias , Insulinas/uso terapéutico , Adolescente , Adulto , Austria , Glucemia/análisis , Niño , Preescolar , Bases de Datos Factuales , Diabetes Mellitus Tipo 1/sangre , Femenino , Estudios de Seguimiento , Alemania , Humanos , Estudios Longitudinales , Masculino , Estudios Prospectivos , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the association between socioeconomic status (SES) and diabetes outcomes in German children and adolescents. METHODS: A total of 1829 subjects <18 years old with type 1 diabetes mellitus from 13 German diabetes centers were included from June 2013 until June 2014. Data were collected within the multicenter DPV (Diabetes Prospective Follow-up) registry. SES was measured with a composite index. Multivariable regression models were applied to analyze the association of SES and outcomes adjusted for age, sex, diabetes duration, and migration status. RESULTS: Low SES was significantly associated with worse diabetes outcomes: higher hemoglobin A1C (HbA1c) (64.3 mmol/mol), lower proportion of insulin pump therapy (43.6%), fewer daily self-monitored blood glucose (SMBG) measurements (5.7), more inpatient days per patient-year (5.8) compared to patients with medium/high SES (HbA1c: 61.3 mmol/mol, P < 0.001/59.8 mmol/mol, P < 0.0001; proportion of pump therapy: 54.5%, P < 0.01/ 54.9%, P < 0.01; SMBG: 6.0, P < 0.01/ 6.1, P < 0.01; inpatient days: 4.5, P < 0.0001/3.4, P < 0.0001). The inclusion of migration status in the models resulted in only minor changes in the outcomes. CONCLUSION: Despite free health care, low SES is associated with unfavorable diabetes outcomes in Germany. The poorer diabetes outcomes of children with diabetes have been attributed to their migration status and may be partly explained by low SES. Both factors must become part of targeted diabetes care in children and adolescents with type 1 diabetes.
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Diabetes Mellitus Tipo 1/terapia , Adolescente , Niño , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/epidemiología , Manejo de la Enfermedad , Femenino , Alemania/epidemiología , Humanos , Masculino , Sistema de Registros , Clase SocialRESUMEN
OBJECTIVE: Continuous subcutaneous insulin infusion (CSII) is on the rise among pediatric patients with type 1 diabetes mellitus. Metabolic effects alone cannot explain this rising popularity. From the patient's perspective, the main benefits of CSII may be found in subjective psychosocial health outcomes (patient-reported outcomes [PRO]). SUBJECTS AND METHODS: In a multicenter open randomized controlled trial, children and adolescents aged 6 to16 years currently treated with multiple daily injections (MDI) were randomized 1:1, stratified by center, to either starting with CSII immediately after the baseline interview or to continuing MDI while waiting 6 months for transmission to CSII. The primary outcomes were patient-reported diabetes-specific health-related quality of life (DHRQOL) and diabetes burden of the main caregiver. Secondary outcomes were caregiver stress, fear of hypoglycemia, satisfaction with treatment, and HbA1c. RESULTS: Two-hundred and eleven patients were randomized between February 2011 and October 2014, and 186 caregivers and 170 patients were analyzed using the intention-to-treat principle for primary outcomes. Children 8 to 11 years in the CSII group reported improved DHRQOL at follow-up compared to MDI (median difference [MD] 9.5, 95% confidence interval [CI] 3.6-16.7, P = 0.004). There were no treatment differences in the adolescent age-group 12 to 16 years (MD 2.7; 95% CI -3.2-9.5; P = 0.353). The main caregivers of the CSII group reported a significant decline of overall diabetes burden at follow-up compared to the MDI group (MD 0; 95% CI -1-0; P = 0.029). Secondary PROs also were in favor of CSII. CONCLUSIONS: CSII has substantial psychosocial benefits. PROs demonstrate these benefits. Registered as NCT01338922 at clinicaltrials.gov.
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Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/psicología , Familia/psicología , Sistemas de Infusión de Insulina , Insulina/administración & dosificación , Calidad de Vida/psicología , Adolescente , Niño , Costo de Enfermedad , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/epidemiología , Femenino , Alemania/epidemiología , Humanos , Sistemas de Infusión de Insulina/psicología , Masculino , Medición de Resultados Informados por el Paciente , Satisfacción del Paciente/estadística & datos numéricos , Psicología del Adolescente , Resultado del TratamientoRESUMEN
BACKGROUND: To assess the change in rates of pediatric real-time or intermittent scanning continuous glucose monitoring (CGM) use over the past 5 years, and how it impacts glycemic control, data from two registries were compared: the US-based type 1 diabetes Exchange Registry (T1DX) and the German/Austrian DPV (Prospective Diabetes Follow-Up Registry). METHODS: Registry participants aged <18 years with T1D duration ≥1 year encompassed 29 007 individuals in 2011 and 29 150 participants in 2016. Demographic data, CGM use and hemoglobin A1c (HbA1c) were obtained from medical records. RESULTS: CGM use increased from 2011 to 2016 in both registries across all age groups, regardless of gender, ethnic minority status or insulin delivery method. The increase in CGM use was most pronounced in the youngest patients, and usage rates remain lowest for adolescent patients in 2016. For both registries in 2016, mean HbA1c was lower among CGM users regardless of insulin delivery method compared to pump only (P < 0.001) and injection only (P < 0.001), and CGM users were more likely to achieve glycemic target of HbA1c <7.5% (56% vs 43% for DPV and 30% vs 15% for T1DX, P < 0.001). T1DX participants had a higher mean HbA1c compared with DPV despite whether they were CGM users or non-users; however, the difference was less pronounced in CGM users (P < 0.001). CONCLUSIONS: Pediatric CGM use increased in both registries and was associated with lower mean HbA1c regardless of insulin delivery modality.
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Automonitorización de la Glucosa Sanguínea/estadística & datos numéricos , Glucemia/análisis , Diabetes Mellitus Tipo 1/sangre , Sistema de Registros , Dispositivos Electrónicos Vestibles/estadística & datos numéricos , Adolescente , Niño , Preescolar , Femenino , Humanos , MasculinoRESUMEN
OBJECTIVE: To investigate differences in cardiovascular risk factors and metabolic control in girls with type 1 diabetes with or without use of oral contraceptives (OC) from the multicenter "diabetes prospective follow-up" (DPV) registry. METHODS: Twenty-four thousand eleven adolescent girls (13 to < 18 years of age) from Germany, Austria or Luxembourg with type 1 diabetes from the DPV registry were included in this cross-sectional study. Multivariable regression models were applied to compare clinical characteristics (hemoglobin A1c [HbA1C ], blood pressure, serum lipids, body mass index) and lifestyle factors (smoking, physical inactivity, alcohol consumption) between girls with or without OC use. Confounders: age, diabetes duration and migration background. STATISTICAL ANALYSIS: SAS 9.4. RESULTS: In girls with type 1 diabetes and OC use, clinical characteristics and lifestyle factors were less favorable compared to non-users. Differences were most pronounced for the prevalence of dyslipidemia (OC-users: 40.0% vs non-users: 29.4; P < .0001) and the number of smokers (OC-users: 25.9% vs non-users: 12.5%; P < .0001). OC use, sociodemographic characteristics and lifestyle factors explained between 1 and 7% of the population variance in serum lipids and blood pressure. The use of OC explained a small additional proportion in all variables considered (<1%). CONCLUSIONS: OC use in adolescent girls with type 1 diabetes was associated with a poorer cardiovascular risk profile. Biological risk factors were partly explained by a clustering of sociodemographic and lifestyle factors with a small additional contribution of OC use. Prescription of OC should therefore be combined with a screening for cardiovascular risk factors and targeted education.
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Enfermedades Cardiovasculares/etiología , Anticonceptivos Orales , Diabetes Mellitus Tipo 1/complicaciones , Sistema de Registros , Adolescente , Estudios Transversales , Femenino , Conductas de Riesgo para la Salud , Humanos , Estilo de VidaRESUMEN
OBJECTIVE: Research on ß-cell autoimmunity in cystic fibrosis (CF)-related diabetes (CFRD) is still rare. We aimed to analyze the frequency of ß-cell autoimmunity and the influence on age at diabetes onset, insulin requirement, type of insulin therapy, and hypoglycemic or ketoacidotic events in patients with CFRD compared with antibody-negative patients with CFRD in the Diabetes Patienten Verlaufsdokumentation (DPV) registry. RESEARCH DESIGN AND METHODS: We analyzed data of 837 patients with CFRD in the German/Austrian DPV database by multivariable mixed-regression modeling. RESULTS: In our cohort, 8.5% of patients with CFRD (n = 72) were found to be ß-cell antibody positive. There was a female preponderance in this patient group: 65.3 vs. 57.6%. Diabetes onset (median [interquartile range]) was earlier (14.00 [10.15-15.90] vs. 16.10 [13.50-21.20] years; P < 0.005), and insulin dose/kg body weight was higher (0.95 [0.61-1.15] vs. 0.67 [0.33-1.04] IU/kg; P < 0.05). There were also differences in the type of insulin treatment. Insulin pump therapy was used significantly more often in patients with CFRD with ß-cell autoimmunity (18.2 vs. 6.4%; P < 0.05). The differences for multiple daily injections (ICT) and conventional therapy (CT) were not significant (ICT: 67.7 vs. 79.0%; CT: 15.2 vs. 14.6). Oral antidiabetic agents were rarely used in both groups. Rate of severe hypoglycemia with coma and rate of ketoacidosis were higher in antibody-positive patients (hypoglycemia with coma: 8.0 vs. 1.4, P < 0.05; ketoacidosis: 9.3 vs. 0.9, P < 0.05). CONCLUSIONS: Presence of ß-cell autoantibodies in our cohort of patients with CFRD (8.5%) appeared to be greater than in the general population and was associated with female sex, earlier onset of diabetes, and higher insulin requirement. Insulin pump therapy was used significantly more often in patients with ß-cell antibodies. Severe hypoglycemia and ketoacidosis were significantly more frequent in CFRD with ß-cell autoimmunity compared with ß-cell antibody-negative patients with CFRD.
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Autoinmunidad/inmunología , Fibrosis Quística/inmunología , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 2/inmunología , Células Secretoras de Insulina/inmunología , Adolescente , Adulto , Austria , Autoanticuerpos/sangre , Índice de Masa Corporal , Peso Corporal , Niño , Estudios de Cohortes , Fibrosis Quística/complicaciones , Fibrosis Quística/diagnóstico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/etiología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/etiología , Relación Dosis-Respuesta a Droga , Femenino , Alemania , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemia/tratamiento farmacológico , Hipoglucemia/etiología , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Insulina/administración & dosificación , Insulina/efectos adversos , Sistemas de Infusión de Insulina , Cetosis/tratamiento farmacológico , Cetosis/etiología , Masculino , Análisis Multivariante , Estudios Prospectivos , Sistema de Registros , Población Blanca , Adulto JovenRESUMEN
BACKGROUND: Diabetes mellitus is rare in young infants and neonates. Continuous subcutaneous insulin infusion (CSII) is used most frequently for insulin treatment in this age group. However, the individual doctor's experience is scarce because of the low prevalence of diabetes in this age. For this study patients treated with CSII with an age below 1 year were selected from the German/Austrian DPV (Diabetes-Patienten-Verlaufsdokumentation) database, and basal rate and bolus calculation were described. MATERIALS AND METHODS: For all patients less than 1 year of age, basal rate and mealtime boluses were compared among infants with type 1 diabetes mellitus (T1DM), infants with neonatal diabetes mellitus (NDM), and infants with antibody status unknown diabetes mellitus (AUDM). RESULTS: Fifty-eight patients with T1DM, 67 neonates with NDM, and 43 infants with early diabetes development after 6 months and negative ß-cell antibodies (AUDM) could be analyzed. T1DM patients at onset required a median total insulin amount of 0.83 IU/kg of body weight, whereas NDM patients required 0.74 IU/kg of body weight (P = 0.63). Basal insulin requirement however, was different between the two groups (0.56 IU/kg of body weight in NDM vs. 0.43 IU/kg in T1DM) (P = 0.036). The percentage basal profile of NDM and T1DM patients was quite similar to children at the age of 1-5 years. The proportion of prandial insulin at onset was significantly different (32% in NDM vs. 53% in T1DM) (P < 0.00001). AUDM patients showed almost similar data to T1DM patients. The pattern of mealtime bolus insulin was not different among the groups. CONCLUSIONS: The presented data can be used as an initial guide value to start CSII treatment in neonates and infants. To be on the safe side we recommend the lower quartile for the dosage as the starting value in nonketotic patients.
Asunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Cálculo de Dosificación de Drogas , Femenino , Estudios de Seguimiento , Alemania , Humanos , Hipoglucemiantes/uso terapéutico , Lactante , Recién Nacido , Infusiones Subcutáneas , Insulina/uso terapéutico , Sistemas de Infusión de Insulina , Masculino , Comidas , Guías de Práctica Clínica como Asunto , Sistema de RegistrosRESUMEN
High circulating levels of asymmetric dimethylarginine (ADMA) and low circulating levels of homoarginine (hArg) are known cardiovascular risk factors in adults. While in adults with type 1 diabetes mellitus (T1DM) circulating ADMA is significantly elevated, in children and adolescents the reported ADMA data are contradictory. In 102 children with T1DM and 95 healthy controls (HC) serving as controls, we investigated the L-arginine (Arg)/nitric oxide (NO) pathway. Children with T1DM were divided into two groups, i.e., in children with newly diagnosed diabetes mellitus [T1DM-ND; n = 10; age, 8.8 (4.4-11.2) years; HbA1c, 13 (8.9-13.9) %] and in those with long-term treatment [T1DM-T; n = 92; age, 12.5 (10.5-15.4) years; HbA1c, 8.0 (7.2-8.6) %]. The age of the HC was 11.3 (8-13.3) years. Amino acids and NO metabolites of the Arg/NO pathway, creatinine and the oxidative stress biomarker malondialdehyde (MDA) were measured by GC-MS or GC-MS/MS. Plasma hArg, ADMA and the hArg/ADMA molar ratio did not differ between the T1DM and HC groups. There was a significant difference between T1DM-T and HC with regard to plasma nitrite [0.53 (0.48-0.61) vs 2.05 (0.86-2.36) µM, P < 0.0001] as well as to urinary nitrite [0.09 (0.06-0.17) vs 0.22 (0.13-0.37) µmol/mmol creatinine, P < 0.0001]. Plasma, but not urinary nitrite, differed between T1DM-ND and HC [0.55 (0.50-0.66) vs 2.05 (0.86-2.36) µM, P < 0.0001]. Plasma MDA did not differ between the groups. The urinary nitrate-to-nitrite molar ratio (UNOXR), a measure of nitrite-dependent renal carbonic anhydrase (CA) activity, was higher in T1DM-T [1173 (738-1481), P < 0.0001] and T1DM-ND [1341 (1117-1615), P = 0.0007] compared to HC [540 (324-962)], but did not differ between T1DM-T and T1DM-ND (P = 0.272). The lower nitrite excretion in the children with T1DM may indicate enhanced renal CA-dependent nitrite reabsorption compared with healthy children. Yet, lower plasma nitrite concentration in the T1DM patients may have also contributed to the higher UNOXR. Patients' age correlated positively with plasma hArg and hArg/ADMA and urinary DMA/ADMA. Plasma ADMA and urinary ADMA, DMA, nitrite and nitrate correlated negatively with age of the T1DM-T children. Significant correlations were found between plasma hArg and plasma Arg (r = 0.468, P < 0.0001), and urinary DMA (r = -0.426, P = 0.0001), ADMA (r = -0.266, P = 0.021) and nitrate (r = -0.234, P = 0.043). Plasma hArg correlated positively with age at diagnosis (r = +0.337, P = 0.002). ADMA, but not hArg, correlated with HbA1c in T1DM-T (r = -0.418, P < 0.0001) and T1DM-ND (r = +0.879, P = 0.0016). The greatest differences between T1DM-T and T1DM-ND were observed for urinary ADMA, DMA/ADMA ratio, nitrite and nitrate. The Arg/NO pathway is altered in T1DM in childhood and adolescence, yet the role and the importance of hArg and ADMA in T1DM remain to be elucidated. In young T1DM patients, oxidative stress (lipid peroxidation) is not elevated.
Asunto(s)
Anhidrasas Carbónicas/metabolismo , Diabetes Mellitus Tipo 1/sangre , Homoarginina/sangre , Riñón/enzimología , Óxido Nítrico/sangre , Adolescente , Adulto , Niño , Preescolar , Estudios Transversales , Diabetes Mellitus Tipo 1/patología , Femenino , Humanos , Riñón/patología , Peroxidación de Lípido , Masculino , Estrés Oxidativo , Estudios ProspectivosRESUMEN
Adult subjects with growth hormone (GH) deficiency (GHD) are known to have reduced life expectancy due to increased cardiovascular and cerebrovascular events. In adults, these events are associated with elevated circulating concentrations of asymmetric dimethylarginine (ADMA) which is an endogenous inhibitor of L-arginine (Arg)-derived nitric oxide (NO). Low circulating concentrations of homoarginine (hArg) emerged as a cardiovascular risk factor. In adults, hArg seems to antagonize ADMA. In the present work, we tested the hypothesis that children with short stature without or with GHD have altered Arg/NO pathway as compared to children with normal growth. We studied 66 short stature children (38 boys, 28 girls) aged 3.5-17.3 years, who underwent the routine L-Arginine Test to diagnose presence of GHD. GHD was confirmed in 47 children (GHD group; 30 boys, 17 girls) and was absent in the remaining 19 children (non-GHD group; 8 boys, 11 girls). In addition, we investigated 24 healthy age- and gender-matched children (10 boys, 14 girls) with normal growth. In EDTA plasma samples of all children, we determined by mass spectrometry-based methods the concentrations of Arg, hArg and ADMA, and calculated the Arg/ADMA and hArg/ADMA molar ratios. With respect to these biochemical parameters, we did not find statistically significant differences between the GHD and non-GHD groups. Comparing short with normal stature children, we found small differences regarding plasma hArg concentrations [mean ± SD; median (25th-75th percentile)]: 2.06 ± 0.52 µM; 2.12 (1.74-2.36) µM vs. 1.7 ± 0.5 µM; 1.6 (1.4-1.8) µM, P < 0.001. Compared to normal stature children, short stature children had considerably higher plasma concentrations of ADMA [0.77 ± 0.15 µM; 0.77 (0.66-0.85) µM vs. 0.57 ± 0.09 µM; 0.58 (0.50-0.63) µM, P < 0.001], but not of Arg [83.3 ± 19.2 µM; 82.2 (71.9-90.3) µM vs. 86.5 ± 17.8 µM; 84.8 (77.2-94.8) µM, P = 0.336], or the hArg/ADMA ratio [2.74 ± 0.76; 2.7 (2.2-3.1) vs. 3.1 ± 1.2; 2.85 (2.42-3.66), P = 0.161. hArg in the GHD group (r = 0.41, P = 0.004) and the hArg/ADMA ratio in both groups (r = 0.44, P = 0.002 in GHD; r = 0.55, P = 0.01 in non-GHD)], but not ADMA were positively correlated with insulin-like growth factor-1 (IGF-1). hArg and hArg/ADMA differed between girls and boys in the GHD and non-GHD groups but in the normal growth group. The hArg/ADMA ratio increased with age in all groups. Our study suggests that hArg and ADMA are involved in growth in the childhood, presumably in an antagonistic manner, with ADMA slowing and hArg accelerating growth.
Asunto(s)
Arginina/análogos & derivados , Trastornos del Crecimiento/sangre , Homoarginina/sangre , Hormona de Crecimiento Humana/deficiencia , Adolescente , Adulto , Arginina/sangre , Niño , Femenino , Trastornos del Crecimiento/diagnóstico , Trastornos del Crecimiento/fisiopatología , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , MasculinoRESUMEN
OBJECTIVE: To analyze the prevalence of juvenile idiopathic arthritis (JIA) and diabetes end points in pediatric patients with type 1 diabetes. STUDY DESIGN: Patients with type 1 diabetes, recorded from 1995 up to September 2013 in the Diabetes Patienten Verlaufsdokumentation database (n = 54,911, <16 years of age, 47% girls), were analyzed. The patients' height, weight, and body mass index SDS, glycosylated hemoglobin A1c (HbA1c); insulin dose; hypertension and dyslipidemia prevalence; rate of hypoglycemic events; and ketoacidosis were compared between patients with and without JIA. To adjust for age, sex, diabetes duration, and migration background, data were analyzed in hierarchic multivariable regression models. RESULTS: The prevalence of JIA in type 1 diabetes was 106 of 54,911 patients; 66% were girls. Diabetes onset was earlier in children with JIA (7.2 years vs 8.3 years, P = .04). Children with JIA were smaller (SDS: -0.22 vs 0.09, P = .004). Correspondingly, weight SDS was lower in patients with JIA (-0.02 vs 0.22, P = .01). Body mass index SDS did not differ. HbA1c was marginally lower in children with JIA (63 mmol/mol [8.0%] vs 67 mmol/mol [8.3%], P = .06). Insulin requirement was greater in patients with JIA (1.03 vs 0.93 insulin units/weight/day, P = .003). Hypertension and dyslipidemia were comparable in both groups. CONCLUSIONS: The JIA-prevalence in patients with type 1 diabetes (0.19%) was considerably greater than in the general population (0.05%). Growth is influenced negatively by JIA. Surprisingly, HbA1c was somewhat lower in children with JIA, possibly because of a more intensive treatment or a latent hemolysis caused by the inflammation.
Asunto(s)
Artritis Juvenil/epidemiología , Diabetes Mellitus Tipo 1/epidemiología , Adolescente , Artritis Juvenil/sangre , Índice de Masa Corporal , Niño , Preescolar , Comorbilidad/tendencias , Diabetes Mellitus Tipo 1/sangre , Femenino , Alemania/epidemiología , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Prevalencia , Estudios RetrospectivosRESUMEN
BACKGROUND: In type 1 diabetes (T1D), the use of continuous subcutaneous insulin infusion (CSII) has increased steadily in the last years. Compared with conventional insulin injection regimes, major advantages might be a nearly physiological insulin secretion, lower rates of hypoglycemia, higher flexibility in daily life, and increased quality of life. Data on CSII in cystic fibrosis-related diabetes (CFRD) are scarce. OBJECTIVE: To analyze current use of insulin pumps in CFRD and compare demographics of pump-treated patients between CFRD and T1D. METHODS: Data from the prospective German/Austrian diabetes patient registry on insulin-treated patients with either CFRD (n = 515) or T1D (n = 43 165) aged >10 yr at manifestation of diabetes were analyzed. RESULTS: A total of 4.1% (n = 21) of CFRD and 17.7% (n = 7647) of T1D patients received insulin pump treatment within the recent year of care (p < 0.001). Pump-treated patients with CFRD had a significantly shorter duration of diabetes [median (Q1 ; Q3 ): 5.8 (2.9; 9.5) vs. 7.8 (4.3; 20.4) yr, p = 0.026] and tended to be younger [22.0 (18.2; 30.1) vs. 24.9 (17.3; 45.9) yr] than pump-treated T1D patients. Age at initiation of CSII seemed to be lower in CFRD [19.2 (16.5; 29.2) vs. 23.3 (14.8; 43.5) yr]. Insulin pump therapy was used slightly more often in male CFRD patients than females (4.7 vs. 3.6%), whereas in T1D the opposite was observed (14.9 vs. 21.2%, p < 0.001). Discontinuation rate of CSII was higher in CFRD than T1D (30.0 vs. 12.7%, p = 0.005). CONCLUSIONS: Despite potential advantages, insulin pump therapy was rarely used among adolescent and young adult CFRD patients.
Asunto(s)
Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/epidemiología , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/epidemiología , Sistemas de Infusión de Insulina/estadística & datos numéricos , Insulina/administración & dosificación , Adolescente , Adulto , Fibrosis Quística/complicaciones , Diabetes Mellitus Tipo 1/etiología , Femenino , Alemania/epidemiología , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: In Germany/Austria, data on medical care for cystic fibrosis-related diabetes (CFRD) is limited. METHODS: Anonymized data from 659 CFRD patients were analyzed and compared to the latest ADA/CFF guidelines. RESULTS: Specialized diabetes clinics were attended less frequently than recommended (3.1 vs. 4.0 times yearly). 7.9% of patients had a complete profile of examinations: diabetes education (44.9%), HbA1c (88.8%), blood pressure (79.5%), BMI (86.5%), lipid status (37.5%), retinopathy (29.9%), microalbuminuria (33.2%), and self-monitoring of blood glucose (71.6%). HbA1c and blood pressure were measured less frequently than recommended (2.3 and 2.0 vs. 4.0 times yearly). Overall, guidelines were followed more frequently in children than adults. Contrary to recommendations, not all patients were treated with insulin (77.2 vs. 100.0%). Insulin therapy was initiated earlier in children than adults, but there was still a substantial delay (0.9 vs. 2.7years after diagnosis, p<0.001). CONCLUSION: In CFRD patients studied, adherence to care guidelines was suboptimal.
Asunto(s)
Fibrosis Quística/complicaciones , Fibrosis Quística/terapia , Complicaciones de la Diabetes/terapia , Adhesión a Directriz , Adolescente , Adulto , Austria , Niño , Complicaciones de la Diabetes/etiología , Femenino , Alemania , Hemoglobina Glucada , Humanos , Hipoglucemiantes/uso terapéutico , Masculino , Evaluación Nutricional , Guías de Práctica Clínica como Asunto , Sistema de Registros , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: The prevalence of cystic fibrosis-related diabetes (CFRD) has increased with improved life expectancy of patients. Clinical and care characteristics were compared with type 1 diabetes mellitus (T1DM) in a multicenter analysis of pediatric data. RESEARCH DESIGN AND METHODS: Auxological and treatment data from 47,227 patients aged younger than 21 years with CFRD or T1DM in the German/Austrian Diabetes Prospective Documentation Initiative registry were analyzed by multivariable mixed regression modeling. RESULTS: Diabetes onset (mean [interquartile range]) occurred later in individuals with CFRD (14.5 [11.8-16.3] years) than in individuals with T1DM (8.5 [4.9-11.8] years), with female preponderance in CFRD (59.1% vs. 47.5%; P < 0.01). CFRD patients had lower BMI standard deviation scores (-0.85 [-1.59 to -0.12] vs. +0.52 [-0.10 to +1.16]; P < 0.01) and lower HbA(1c) (6.87% vs. 7.97%; P < 0.01). Self-monitoring of blood glucose was more frequent in patients with T1DM (4.5 vs. 3.5; P < 0.01); 72% of CFRD patients received insulin. In insulin-treated patients, insulin dosage adjusted for age, sex, and diabetes duration differed significantly (T1DM: 0.79 IE per kilogram of body weight; CFRD: 0.83 IE per kilogram of body weight). Use of short-acting and long-acting insulin analogs was significantly more frequent in T1DM (47% vs. 39% and 37% vs. 28%; both P < 0.05). Metabolic control in CFRD patients without insulin was better compared with CFRD on insulin (HbA(1c): 6.00 vs. 7.12; P < 0.01), but duration of disease was significantly shorter (0.8 years [0.1-2.4] compared with 2.4 years [0.6-4.6]). There was no significant difference for BMI standard deviations scores between CFRD patients with or without insulin treatment. CONCLUSIONS: Pediatric patients with CFRD show clear auxological and metabolic differences from those with T1DM, with different treatment choices.