RESUMEN
Higher levels of Dickkopf-1, which is an inhibitor of Wnt/ß-catenin bone metabolic pathway, could be indicative of downregulated Wnt system, with possible lower osteoblast activation and higher osteoclast signaling in type 1 diabetes mellitus children and adolescents. Dickkopf-1 could significantly contribute to diabetes osteopathy. INTRODUCTION: Increased fracture risk and elevated Dickkopf-1 levels, which is an inhibitor of Wnt/ß-catenin bone metabolic pathway, have been documented in adult patients with type 2 diabetes mellitus (T2D), while no relevant data exist on childhood type 1 diabetes (T1D). Our aim was to study plasma Dickkopf-1 distribution in children and adolescents with T1D and to correlate Dickkopf-1 with metabolic bone markers and bone mineral density (BMD). METHODS: We evaluated 40 children and adolescents with T1D (mean ± SD age 13.04 ± 3.53 years, T1D duration 5.15 ± 3.33 years) and 40 healthy age-matched and gender-matched controls (age 12.99 ± 3.3 years). Dickkopf-1 and bone metabolic markers were measured, while total body and lumbar spine BMD were evaluated with dual-energy X-ray absorptiometry (DXA). RESULTS: Dickkopf-1 demonstrated a Gaussian distribution, with higher levels in T1D patients (13.56 ± 5.34 vs 11.35 ± 3.76 pmol/L, p = 0.024). Higher values were found in boys and in prepubertal children. Dickkopf-1 correlated positively with osteoprotegerin and fasting glucose in patients, while positive correlation with sclerostin and total soluble receptor activator of nuclear factor-kappaB ligand (s-RANKL) was found in controls. Positive correlations with C-telopeptide cross-links (CTX), osteocalcin, alkaline phosphatase, phosphate, and insulin-like growth factor 1 (IGF1) were documented in both groups. Lumbar spine Z-score was positively associated with Dickkopf-1 in controls, while a negative trend was found in patients. CONCLUSIONS: Higher levels of Dickkopf-1 could indicate a downregulated Wnt/ß-catenin system with possible lower osteoblast activation and higher osteoclast signaling in T1D children and adolescents. Dickkopf-1 could possibly be a significant contributor of T1D osteopathy. Future therapies could focus on Wnt/ß-catenin metabolic pathway.
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Diabetes Mellitus Tipo 1/sangre , Regulación hacia Abajo/fisiología , Péptidos y Proteínas de Señalización Intercelular/sangre , Osteoporosis/sangre , Vía de Señalización Wnt/fisiología , Proteínas Adaptadoras Transductoras de Señales , Adolescente , Biomarcadores/sangre , Glucemia/metabolismo , Densidad Ósea/fisiología , Proteínas Morfogenéticas Óseas/sangre , Estudios de Casos y Controles , Niño , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/fisiopatología , Femenino , Marcadores Genéticos , Humanos , Masculino , Osteoblastos/metabolismo , Osteoporosis/etiología , Osteoporosis/fisiopatología , Pubertad/fisiología , Caracteres SexualesRESUMEN
UNLABELLED: Simultaneous lower bone mineral density, metabolic bone markers, parathyroid hormone (PTH), magnesium, insulin-like growth factor 1 (IGF1), and higher levels of total soluble receptor activator of nuclear factor-kappa B ligand (s-RANKL), osteoprotegerin (OPG), and alkaline phosphatase (ALP) are indicative of lower osteoblast and increased osteoclast signaling in children and adolescents with type 1 diabetes mellitus, predisposing to adult osteopenia and osteoporosis. INTRODUCTION: Type 1 diabetes mellitus (T1DM) is a risk factor for reduced bone mass, disrupting several bone metabolic pathways. We aimed at identifying association patterns between bone metabolic markers, particularly OPG, s-RANKL, and bone mineral density (BMD) in T1DM children and adolescents, in order to study possible underlying pathophysiologic mechanisms of bone loss. METHODS: We evaluated 40 children and adolescents with T1DM (mean ± SD age 13.04 ± 3.53 years, T1DM duration 5.15 ± 3.33 years) and 40 healthy age- and gender-matched controls (aged12.99 ± 3.3 years). OPG, s-RANKL, osteocalcin, C-telopeptide cross-links (CTX), IGF1, electrolytes, PTH, and total 25(OH)D were measured, and total body along with lumbar spine BMD were evaluated with dual energy X-ray absorptiometry (DXA). Multivariate regression and factor analysis were performed after classic inference. RESULTS: Patients had significantly lower BMD, with lower bone turnover markers, PTH, magnesium, and IGF1 than controls, indicating lower osteoblast signaling. Higher levels of total s-RANKL, OPG, and total ALP were observed in patients, with log(s-RANKL) and OPG correlation found only in controls, possibly indicating increased osteoclast signaling in patients. Coupling of bone resorption and formation was observed in both groups. Multivariate regression confirmed simultaneous lower bone turnover, IGF1, magnesium, and higher total s-RANKL, OPG, and ALP in patients, while factor analysis indicated possible activation of RANK/RANKL/OPG system in patients and its association with magnesium and IGF1. Patients with longer disease duration or worse metabolic control had lower BMD. CONCLUSIONS: T1DM children and adolescents have impaired bone metabolism which seems to be multifactorial. Reduced osteoblast and increased osteoclast signaling, resulting from multiple simultaneous disturbances, could lead to reduced peak bone accrual in early adulthood, predisposing to adult osteopenia and osteoporosis.
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Enfermedades Óseas Metabólicas/etiología , Diabetes Mellitus Tipo 1/sangre , Osteoclastos/fisiología , Osteoprotegerina/sangre , Ligando RANK/sangre , Absorciometría de Fotón/métodos , Adolescente , Biomarcadores/sangre , Densidad Ósea/fisiología , Enfermedades Óseas Metabólicas/sangre , Enfermedades Óseas Metabólicas/fisiopatología , Remodelación Ósea/fisiología , Estudios de Casos y Controles , Niño , Estudios Transversales , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/fisiopatología , Femenino , Humanos , Vértebras Lumbares/fisiopatología , Masculino , Osteoporosis/sangre , Osteoporosis/etiología , Osteoporosis/fisiopatología , Transducción de Señal/fisiologíaRESUMEN
AIM: To evaluate the predictive value of various clinical and laboratory parameters on the identification of acute extensive and/or multifocal renal involvement in children with febrile urinary tract infections (UTI). METHODS: The medical records of 148 children (median age: 2.4 months, range: 11 days-24 months), who were admitted during a 3-year period with a first episode of febrile UTI, were analysed. Acute dimercaptosuccinic acid scintigraphy (DMSA), clinical and laboratory parameters were evaluated. RESULTS: Seventy six children (51%) had abnormal findings on the acute DMSA. Of them, 20 had DMSA grade 2, while 56 had grade 3 and 4. Patients with a DMSA grade 3 and 4 were more likely to have shivering (OR 3.4), white blood count (WBC) ≥ 18 000/µL (OR 2.4), absolute neutrophil count (ANC) ≥ 9300/µL (OR 4.4), C-reactive protein (CRP) ≥ 50 mg/L (OR 2.7) and procalcitonin (PCT) ≥ 1.64 ng/mL (OR diagnostic). There was a significant difference of WBC (p = 0.004), ANC, CRP and PCT levels (p < 0.001) between children with normal and grade 2 aDMSA versus those with aDMSA grade 3 and 4. CONCLUSIONS: Shivering and elevated inflammatory markers increase the risk of acute extensive and/or multifocal kidney involvement in children with febrile UTI. Procalcitonin seems to be an excellent marker of the severity of acute parenchymal involvement.
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Fiebre/microbiología , Pielonefritis/diagnóstico , Pielonefritis/microbiología , Infecciones Urinarias/diagnóstico , Técnicas de Laboratorio Clínico , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
AIMS: To define the reproducibility of vibration perception thresholds (VPTs) and the possible associated factors, as an early index of peripheral diabetic neuropathy (PDN) in type 1 diabetes mellitus (T1DM) children and adolescents. METHODS: A single examiner studied 118 T1DM subjects (aged 13.5±3.4 years) and 79 controls (aged 12.0±3.07 years). Glycaemic control was assessed with HbA1c levels. VPT was measured twice on upper and lower limbs, using a Biothesiometer. Concordance between the two VPT measurements was evaluated using the Cohen's Weighted Kappa statistic (Kappa=0.41-0.60âmoderate concordance, Kappa=0.61-0.80âsubstantial concordance). RESULTS: T1DM children had significantly higher VPTs than controls at all sites (p=0.001), but with lower Kappa values (0.64-0.70). VPT values increased in parallel with HbA1c (a.<8%, b. 8-9.5%, c.>9.5%) and T1DM duration (a.<5 years, b.5.1-10, c.>10 years). However, Kappa values were lower in the groups with the poorest control (HbA1c>9.5%) (Kappa=0.54-0.76) or the longest T1DM duration (>10 years) (Kappa=0.49-0.71). Although VPTs increased with stature and male gender, no effect on VPT reproducibility was observed. However, obesity was associated with lower VPT values and poorer concordance. CONCLUSIONS: These findings suggest that the reproducibility of VPTs is lower in the high-risk patients for early subclinical PDN development, who need a regular follow-up.
Asunto(s)
Diabetes Mellitus Tipo 1/complicaciones , Neuropatías Diabéticas/diagnóstico , Examen Neurológico/métodos , Umbral Sensorial , Percepción del Tacto , Vibración , Adolescente , Factores de Edad , Biomarcadores/sangre , Estudios de Casos y Controles , Niño , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Neuropatías Diabéticas/etiología , Neuropatías Diabéticas/fisiopatología , Diagnóstico Precoz , Femenino , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes/uso terapéutico , Masculino , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Factores de Riesgo , Adulto JovenRESUMEN
Diabetic neuropathy (DN) is a major complication of type 1 diabetes mellitus (T1DM) with significant morbidity and mortality in adulthood. Clinical neuropathy is rarely seen in paediatric populations, whereas subclinical neuropathy is commonly seen, especially in adolescents. Peripheral DN involves impairment of the large and/or small nerve fibres, and can be diagnosed by various methods. Nerve conduction studies (NCS) are the gold-standard method for the detection of subclinical DN; however, it is invasive, difficult to perform and selectively detects large-fibre abnormalities. Vibration sensation thresholds (VSTs) and thermal discrimination thresholds (TDTs) are quicker and easier and, therefore, more suitable as screening tools. Poor glycaemic control is the most important risk factor for the development of DN. Maintaining near-normoglycaemia is the only way to prevent or reverse neural impairment, as the currently available treatments can only relieve the symptoms of DN. Early detection of children and adolescents with nervous system abnormalities is crucial to allow all appropriate measures to be taken to prevent the development of DN.
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Diabetes Mellitus Tipo 1/fisiopatología , Neuropatías Diabéticas/fisiopatología , Técnicas de Diagnóstico Neurológico , Potenciales Evocados Somatosensoriales , Piel/irrigación sanguínea , Adolescente , Niño , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/epidemiología , Neuropatías Diabéticas/epidemiología , Neuropatías Diabéticas/etiología , Técnicas de Diagnóstico Neurológico/instrumentación , Femenino , Calor , Humanos , Masculino , Conducción Nerviosa , Examen Neurológico , Umbral Sensorial , Piel/inervación , Estados Unidos/epidemiología , VibraciónRESUMEN
BACKGROUND/AIMS: Type 1 diabetes (T1DM) is associated with gastric autoimmunity, which is characterized by the presence of parietal cell antibodies (APCA). We investigated gastric autoimmunity prevalence in T1DM children, its manifestations, determinants and association with thyroid gland (anti-Tg, anti-TPO) and pancreatic ß-cell autoimmunity (anti-GAD) at baseline and 4 years later. METHODS: The initial cohort (D1) included 97 children with T1DM. At follow-up after 4 years (D2), 84.5% of participants were evaluated. We assessed APCA, anti-Tg, anti-TPO, and anti-GAD presence, as well as symptoms of gastritis. APCA-positive patients were evaluated with gastrin, B12, ferritin levels and were submitted to gastroscopy. RESULTS: Thyroid antibody positivity was increased among the APCA-positive patients. Four years later, among initially APCA-positive patients, 2/6 became APCA negative, while 4/6 developed high titers of APCA. On gastroscopy, 2 patients had chronic hypertrophic gastritis and one Helicobacter pylori gastritis. CONCLUSIONS: Gastric autoimmunity was associated with thyroid autoimmunity and anti-GAD persistence. After 4 years, the majority of APCA-positive patients developed high titers of APCA and mild symptoms of gastritis. Thus, patients with T1DM, and in particular those with thyroid and/or pancreatic autoimmunity, should have periodic autoantibody screening for the early diagnosis and follow-up of gastric autoimmunity.
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Autoinmunidad , Diabetes Mellitus Tipo 1/inmunología , Células Parietales Gástricas/inmunología , Adolescente , Autoanticuerpos/análisis , Niño , Estudios de Cohortes , Estudios Transversales , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/complicaciones , Femenino , Estudios de Seguimiento , Gastritis/complicaciones , Glutamato Descarboxilasa/antagonistas & inhibidores , Grecia , Hospitales Universitarios , Humanos , Células Secretoras de Insulina/inmunología , Masculino , Servicio Ambulatorio en Hospital , Estudios Prospectivos , Glándula Tiroides/inmunologíaRESUMEN
Adolescents with diabetes are at increased risk of developing psychiatric (10-20%) or eating disorders (8-30%), as well as substance abuse (25-50%), leading to non-compliance with treatment and deterioration of diabetic control. At high risk are female adolescents with family problems and other comorbid disorders. Impaired cognitive function has also been reported among children with diabetes, mainly in boys, and especially in those with early diabetes diagnosis (< 5 years), or with episodes of severe hypoglycaemia or prolonged hyperglycaemia. Type 1 diabetes mellitus contributes to the development of problems in parent-child relationships and employment difficulties, and negatively affects the quality of life. However, insulin pumps appear to improve patients' metabolic control and lifestyle. The contributions of family and friends to the quality of metabolic control and emotional support are also crucial. In addition, the role of the primary-care provider is important in identifying patients at high risk of developing psychosocial disorders and referring them on to health specialists. At high risk are patients in mid-adolescence with comorbid disorders, low socioeconomic status or parental health problems. Multisystem therapy, involving the medical team, school personnel, family and peer group, is also essential. The present review focuses on the prevalence of nutritional and psychosocial problems among adolescents with diabetes, and the risk factors for its development, and emphasizes specific goals in their management and prevention.
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Diabetes Mellitus Tipo 1/complicaciones , Trastornos Mentales/complicaciones , Adolescente , Diabetes Mellitus Tipo 1/psicología , Diabetes Mellitus Tipo 1/terapia , Trastornos de Alimentación y de la Ingestión de Alimentos/complicaciones , Trastornos de Alimentación y de la Ingestión de Alimentos/epidemiología , Femenino , Humanos , Masculino , Trastornos Mentales/prevención & control , Calidad de Vida/psicología , Trastornos Relacionados con Sustancias/complicaciones , Trastornos Relacionados con Sustancias/epidemiologíaRESUMEN
UNLABELLED: Diabetes mellitus Type 1 (T1D) is an autoimmune disorder attributed to both genetic and environmental factors. The aim of this study was to identify certain stressful conditions potentially associated with the pathogenesis and/or expression of T1D. The study group included 107 children with diabetes (CD) and 153 controls of comparable age and gender distribution at diagnosis of T1D (10.73+/-3.62 yr vs 9.59 +/-3.42 yr, respectively). The parents of both groups completed a questionnaire on socioeconomic status and stressful life events or adverse situations at home and school. RESULTS: Lower social class was more prevalent among the mothers of CD (p=0.002) in comparison with the controls. Stressful life events (parental death, divorce, parental job loss), problems at home (parental abuse, parental dispute) and at school (poor performance) were more frequently observed in the CD group than in the controls (parental death: p=0.05, job loss: p=0.05, parental abuse: p=0.002, quarrels between parents: p=0.05, and among siblings p=0.002, poor school performance: p=0.037). A stepwise logistic regression analysis indicated that lower maternal social class [odds ratio (OR): 3.86, 95% confidence interval (CI): 1.37,10.9], parental dispute or divorce (OR: 2.78, 95%CI: 0.97,7.95), body mass index (OR: 0.87, 95%CI: 0.78,0.97), increasing age (OR: 1.14, 95%CI: 1.02,1.27) were the factors potentially influencing the occurrence of T1D, while the 2-yr period prior to diabetes occurrence emerged as the most important one (OR: 2.49, 95%CI: 1.14,5.42). CONCLUSION: Children with diabetes seem to experience certain stressful conditions with significantly increased frequency compared to controls, especially during the 2 yr preceding the diagnosis of T1D, with a higher clustering in those of lower social class. The resultant stress possibly contributes to the development of T1D in genetically susceptible individuals.
Asunto(s)
Diabetes Mellitus Tipo 1/etiología , Estrés Psicológico/complicaciones , Adolescente , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Humanos , Lactante , Acontecimientos que Cambian la Vida , Masculino , Clase SocialRESUMEN
Diabetic cardiomyopathy is a well-defined complication of diabetes that occurs in the absence of ischemic heart disease or hypertension. Moreover impaired circadian blood pressure (BP) variation has been associated with autonomic dysfunction. The aim of our study was to evaluate diurnal BP fluctuations and autonomic function and their association with left ventricular function in adolescents with Type 1 diabetes mellitus (T1DM). In 48 normotensive, normoalbuminuric diabetic adolescents, with a mean (+/-SD) age of 17.3 (+/-4.1) yr and a mean (+/-SD) diabetes duration of 8.5 (+/-3.3) yr, 24-h ambulatory BP was recorded. Moreover 24-h heart rate (HR) monitoring was performed. Myocardial structural parameters were studied by echocardiogram. Left ventricular end-diastolic (EDDLV) and end-systolic diameters (ESDLV) were estimated and left ventricular mass index (LVMI) was calculated using the Devereux formula. The patients were divided into 2 groups according to the absence of decrease (non-dippers) or the decrease (dippers) of nocturnal diastolic BP (DBP). The non-dippers showed, in comparison with the dippers, reduced mean 24-h HR (79.6 vs 84.0 beats/min, p=0.05) and reduced mean day-time HR (81.3 vs 86.0 beats/min, p=0.05). The nondippers also presented greater ESDLV (28.7 vs 25.9 mm, p=0.001) and EDDLV (47.8 vs 45.1 mm, p=0.040), and LVMI (90.2 vs 78.3 g/m2, p=0.044), in comparison with the dippers. During stepwise multiple regression, the most important variables affecting LVMI were mean HR (day): (b=-0.40, p=0.001), high frequency domain variable of HR variability (b=0.38, p=0.016) and glycosylated hemoglobin (b=0.67, p=0.001). In conclusion, we found that a group of normotensive diabetic adolescents with impaired nocturnal BP reduction, also had autonomic dysfunction, together with impaired left ventricular function. These findings suggest that there is a close relationship between autonomic function and left ventricular remodeling in patients with T1DM, which may be attributed to altered diurnal BP profile, autonomic neuropathy and poor glycemic control.
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Presión Sanguínea/fisiología , Ritmo Circadiano/fisiología , Diabetes Mellitus Tipo 1/fisiopatología , Frecuencia Cardíaca/fisiología , Disfunción Ventricular Izquierda/fisiopatología , Adolescente , Adulto , Factores de Edad , Niño , Diabetes Mellitus Tipo 1/complicaciones , Femenino , Estudios de Seguimiento , Humanos , Masculino , Disfunción Ventricular Izquierda/complicaciones , Disfunción Ventricular Izquierda/diagnósticoRESUMEN
AIMS: The aim of our study was to assess diurnal blood pressure (BP) and heart rate variability and their possible relationship to the duration of the QT interval in adolescents with Type 1 diabetes. METHODS: In 48 normotensive, normoalbuminuric diabetic adolescents, with a mean (+/- sd) age of 17.3 (+/- 4.1) years and a mean (+/- sd) diabetes duration of 8.5 (+/- 3.3) years, 24-h ambulatory BP was recorded. In addition, 24-h heart rate (HR) monitoring was performed and QT and corrected QT (QTc) intervals were estimated as indices of autonomic function. The patients were divided into two groups according to the absence of a decrease (non-dippers) or the presence of a decrease (dippers) in nocturnal diastolic BP (DBP). RESULTS: In comparison with the dippers, the non-dippers showed reduced mean 24-h HR (79.6 vs. 84.0 beats/min, P = 0.05) and reduced mean daytime HR (81.3 vs. 86.0 beats/min, P = 0.05). The QT interval was prolonged in the non-dippers (366.3 vs. 347.5 ms, P = 0.015), and end systolic (28.7 vs. 25.9 mm, P = 0.004) and end diastolic left ventricular diameters (47.8 vs. 45.5 mm, P = 0.037) were greater. In stepwise multiple regression, HR variables were the most important factors affecting DBP ratio or the duration of the QT interval. CONCLUSIONS: In conclusion, normotensive diabetic adolescents with impaired nocturnal BP reduction also have impaired autonomic function tests, in association with prolonged QT interval and increased left ventricular diameters. These findings suggest that diabetic adolescents who have the 'non-dipper' phenomenon may need close follow-up for the possible development of vascular complications, such as cardiac arrhythmias and left-ventricular hypertrophy.
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Ritmo Circadiano , Diabetes Mellitus Tipo 1/etiología , Angiopatías Diabéticas/etiología , Síndrome de QT Prolongado/etiología , Disfunción Ventricular Izquierda/etiología , Adolescente , Monitoreo Ambulatorio de la Presión Arterial/métodos , Diabetes Mellitus Tipo 1/fisiopatología , Angiopatías Diabéticas/fisiopatología , Electrocardiografía/métodos , Femenino , Humanos , Síndrome de QT Prolongado/fisiopatología , Masculino , Albúmina Sérica/análisis , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
One hundred and twenty-nine (87%) out of a county population of 150 eligible children with type 1 diabetes mellitus (DM) and 144 age- and sex-matched control children participated in a longitudinal, epidemiological study of the evolution of diabetic microvascular disease. The mean (SD) age of the children with DM was 12.4 (+/- 3.4) years with a mean DM duration of 4.5 (+/- 3.2) years and a mean HbA1c of 11.1 (+/- 2.2)%. Two sets of measurements were made over a period of 18 months. Pupillary adaptation in darkness (PD), as an index of sympathetic dysfunction, was assessed using a portable Polaroid pupillometer. Urinary albumin excretion, as an index of incipient nephropathy, was assessed in children with DM from a fraction of all voidings during two separate 48-h periods and was expressed as urinary albumin/creatinine ratio (A/C). Heart rate variation (HRV), as an index of cardiovascular autonomic dysfunction, was assessed using a heart rate monitor and computer. Blood pressure (BP) was measured using a random zero sphygmomanometer. Reduced PD was found in 14/129 (13.8%) children with DM and in 5.8% of the controls. The diabetic children with reduced PD had longer DM duration, higher HbA1c, raised diastolic BP and higher urinary A/C than those with normal PD. Fifty percent of these children also had increased A/C and impaired HRV, in addition to impaired PD. Another group of 25/129 (19.4%) children with DM presented intermittently raised mean urinary A/C, while five children presented persistently raised A/C in both 48-h urine collections. The characteristics which differentiated the microalbuminuric group from the normoalbuminuric one were older age, longer DM duration, poorer glycemic control, reduced PD, impaired HRV and raised diastolic BP. It seems that diabetic nephropathy (DN) and autonomic neuropathy (DAN) exist in concert in childhood DM. Diabetic children with impaired indices of DN and DAN are older, pubertal and have longer DM duration and higher HbA1c values than the rest of the diabetic population.
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Diabetes Mellitus Tipo 1 , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/fisiopatología , Neuropatías Diabéticas/complicaciones , Neuropatías Diabéticas/fisiopatología , Adolescente , Albuminuria , Presión Sanguínea , Estudios de Casos y Controles , Niño , Preescolar , Estudios de Cohortes , Creatinina/orina , Diástole , Femenino , Hemoglobina Glucada , Frecuencia Cardíaca , Humanos , Estudios Longitudinales , Masculino , Trastornos de la PupilaRESUMEN
The growth data of 156 children (100 boys, 56 girls) with growth hormone deficiency (GHD), treated with human growth hormone (GH) for 5.7+/-3.7 years, from 1970-1997, were retrospectively analyzed to assess the efficacy of GH treatment and the factors involved. 62.2% of the studied population had idiopathic GHD (IGHD) and 35.2% had organic GHD (OGHD). At initiation of treatment, chronological age (CA) was 10.1+/-4.0 years in children with IGHD and 9.7+/-4.0 years in those with OGHD, while bone age (BA) was 7.0+/-3.7 and 7.7+/-3.2 years, respectively. The SDS of the growth velocity during the first year of therapy (GV1) was negatively related to CA at start of therapy (r = -0.53, p = 0.01). 109 children have reached final height (FH): 67 boys (FH = 165.3+/-6.3 cm) and 42 girls (FH = 153.9+/-5.4 cm). FH SDS was not significantly different from target height (TH) SDS. In the total group, FH SDS was positively related to height SDS for CA and BA at start of therapy (p = 0.01, p = 0.001, respectively), to TH SDS (r = 0.40, p = 0.001), and to GV1 (r = 0.33, p = 0.001). TH SDS was not different between the IGHD and OGHD groups (-1.02+/-0.8 vs. -0.94+/-6.9). The height gain at puberty did not differ between the groups with induced or spontaneous puberty in boys (23.7+/-8.6 vs. 25.4+/-6.9, not significant), while in girls it was higher in the group with spontaneous puberty (12.7+/-7.3 vs. 20.0+/-9.0, p = 0.008). The age and height at start of puberty was higher in girls and boys with induced puberty. In the total group, the FH SDS of children with induced puberty was higher in comparison with those with spontaneous puberty (-1.0+/-0.8 vs. -1.7+/-0.9, p = 0.001) and it was positively related to the height at start of puberty. When the two sexes were analyzed separately, the difference reached significance only in boys. In conclusion, children with GHD on GH treatment achieved a final height which was comparable to their genetic potential. The FH of children with OGHD was not different from those with IGHD. The age and height at start of puberty were the most significant determining factors for FH. Hence, a better FH might be expected by delaying or arresting puberty.
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Estatura , Crecimiento , Hormona de Crecimiento Humana/deficiencia , Hormona de Crecimiento Humana/uso terapéutico , Pubertad/fisiología , Adolescente , Factores de Edad , Estatura/genética , Niño , Femenino , Grecia , Hormona de Crecimiento Humana/administración & dosificación , Humanos , Masculino , Resultado del TratamientoRESUMEN
One hundred and twenty-nine (87%) of a total county population of 150 eligible diabetic children together with 144 age- and sex-matched control children participated in a longitudinal, epidemiological study of the evolution of diabetic microvascular disease. At enrollment the median (range) age of the diabetic children was 12.5 (3.7-16.8) years with a median diabetes duration of 2.9 (0.1-13.4) years and a median HbAl of 11.1 (6.8-17.9)%. Two sets of measurements were made over a period of 18 months for all indices of microvascular disease, while autonomic function was studied on one occasion. Urinary albumin excretion in diabetic children was assessed from all voidings during two timed 48-h urine collections and was expressed as urinary albumin/creatinine ratios (ACR). Blood pressure (BP) was measured using a random zero sphygmomanometer. Autonomic function was assessed by pupillary adaptation in darkness, using a portable Polaroid pupillometer, and by heart rate (HR) variation recorded by dedicated computer. Vibration sensation thresholds (VST) (as indices of peripheral neuropathy) were recorded using a Biothesiometer. Limited joint mobility (LJM) was assessed by the "prayer sign". Five (3.9%) diabetic children presented raised mean ACR in more than two of four 24-h urine collections. Fourteen (10.8%) diabetic children were identified as having persistently raised BP during both study periods. Impaired HR response in one HR test was observed in 20 (15.5%) diabetic children, while ten (7.7%) diabetic children demonstrated abnormalities in two or more HR tests. Reduced pupillary adaptation in darkness was found in eight (7.9%) diabetic children. Persistent vibration sensation impairment (VST) in lower limbs was detected in eight (6.2%) diabetic children, while LJM was present in 12 (9.3%) diabetic children. Eight of the 129 diabetic children (6.2%) were found to have abnormality in two and one in three indices of microvascular and autonomic function. Six of nine children had coexistence of impaired autonomic neuropathy and nephropathy. These nine children were diagnosed at a younger age than the rest of the diabetic population (5.1 vs 8.0 yr, p=0.002). Four of nine were aged >11 yr and five of nine had had diabetes for >5 yr. Thus, a constellation of microvascular and neurological abnormalities were demonstrable in a small proportion of diabetic children, who were younger than the rest of the population at the time of onset of their disease. Longitudinal study of this population will demonstrate the clinical significance of these findings.
Asunto(s)
Diabetes Mellitus Tipo 1/epidemiología , Angiopatías Diabéticas/epidemiología , Neuropatías Diabéticas/epidemiología , Adaptación Ocular/fisiología , Adolescente , Albuminuria/orina , Enfermedades del Sistema Nervioso Autónomo/epidemiología , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Presión Sanguínea/fisiología , Niño , Preescolar , Creatinina/orina , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/fisiopatología , Angiopatías Diabéticas/fisiopatología , Neuropatías Diabéticas/fisiopatología , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Articulaciones/fisiopatología , Estudios Longitudinales , Masculino , Microcirculación/fisiopatología , Umbral Sensorial/fisiología , Reino Unido/epidemiologíaRESUMEN
Repeat measurements on pupillary adaptation to darkness were performed in a cohort of 66 children and adolescents with insulin-dependent diabetes mellitus (IDDM) (initial age 6.9-17.0 years) after a mean interval of 3.5 years, using a portable pupillometer. While there was a close correlation between the results of the two studies (r = 0.94, p < 0.001), the pupillary dilatation, the ratio of the pupil diameter to the iris diameter % (PD%), had decreased significantly (61.5% vs 62.9%, p < 0.001) over these 3.5 years in children with diabetes. The same measurements were performed on 89 healthy control children in the first study and 66 in the reassessment period and PD% was not significantly different in the two control groups. Five children with diabetes identified as having abnormal pupillary dilatation in the first study were outside the normal range 3.5 years later. In addition 4 children in whom initial testing had been normal, showed abnormality at the time of the second study. None of these children had symptoms of autonomic neuropathy. These findings suggest that abnormality in pupillary adaptation in diabetic children is consistent and increases with time and may serve as an early marker of tissue damage associated with diabetes.
Asunto(s)
Diabetes Mellitus Tipo 1/fisiopatología , Retinopatía Diabética/fisiopatología , Pupila/fisiología , Reflejo Pupilar/fisiología , Adolescente , Niño , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/análisis , Humanos , Masculino , Valores de Referencia , Análisis de Regresión , Factores de TiempoRESUMEN
129 diabetic children in Avon County participated in a longitudinal study of the evolution of microvascular disease together with 129 age- and sex-matched controls. Diabetic children had mean (+/- SD) age 12.7 (+/- 3.4) years (range: 3.7-16.8), mean (+/- SD) diabetes duration 3.9 (+/- 3.2) years (range: 0.1-13.4) and mean (+/- SD) HbA1 11.1% (+/- 2.2) (range: 6.5-18.2). Cardiovascular autonomic function was studied by four heart rate (HR) tests using a computerized system of HR monitoring. As a group, diabetic children had higher mean HR (p = 0.0004) and reduced max/min HR ratio while standing (p = 0.001), compared with the control children. HR ratio while standing was the only variable related to diabetes duration (r = -0.20, p = 0.018), while no correlation of HR variables with glycaemic control was found. Twenty diabetic children (15.5%) had one abnormal HR test. Ten diabetic children (7.7%) demonstrated abnormality in two or more HR tests. When compared with the other diabetic children in the cohort, these ten children were found to be younger in age (mean age: 9.4 vs 12.0 yr, p = 0.05), but did not otherwise differ in terms of diabetes duration or glycaemic control. No pubertal or sex effect in the development of diabetic autonomic neuropathy was detected. These findings suggest that autonomic function may be impaired early in childhood diabetes, independent of the duration of the disease or the quality of glycaemic control.
Asunto(s)
Sistema Nervioso Autónomo/fisiología , Diabetes Mellitus Tipo 1/complicaciones , Neuropatías Diabéticas/fisiopatología , Frecuencia Cardíaca/fisiología , Adolescente , Niño , Preescolar , Estudios de Cohortes , Diabetes Mellitus Tipo 1/fisiopatología , Neuropatías Diabéticas/epidemiología , Femenino , Hemoglobina Glucada/análisis , Humanos , Lactante , Estudios Longitudinales , Masculino , Prevalencia , Valores de Referencia , Maniobra de ValsalvaRESUMEN
The progression of early measures of microvascular disease and autonomic neuropathy were studied in a group of 81 children with insulin dependent diabetes mellitus over a mean interval of 4.2 years. Repeated measurements were made of blood pressure, albumin excretion, joint mobility, and pupillary dilatation in darkness. Over the years between the first and the second study, systolic and diastolic blood pressure showed positive tracking correlations (r = 0.38 and r = 0.32) with a small but significant deviation from normality; albumin/creatinine ratio was significantly increased (0.79 v 0.55); a greater number of children were identified in the second study as having limitation of mobility of the fifth metacarpophalangeal joint; and pupillary dilatation in darkness significantly decreased (61.5% v 62.9%); 62% of the children with one or more abnormal measurements in the first study were found to have measurements outside the normal ranges in the second study, indicating a consistency in observations over time. It remains to be seen with what accuracy these measurements predict adult onset clinical disease.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Diabetes Mellitus Tipo 1/fisiopatología , Angiopatías Diabéticas/fisiopatología , Neuropatías Diabéticas/fisiopatología , Adolescente , Albuminuria/etiología , Presión Sanguínea , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Humanos , Artropatías/etiología , Estudios Longitudinales , Masculino , Trastornos de la Pupila/etiologíaRESUMEN
In 1990, 81 children and adolescents with insulin dependent diabetes were studied for early signs of diabetic nephropathy. Nine patients were identified as having microalbuminuria (incipient nephropathy). These subjects were re-examined three years later. In five of these cases, the second examination revealed normal albumin excretion; in three of the four cases in whom microalbuminuria persisted, the rate of albumin excretion had decreased. The general improvement in albumin excretion rates in the initially microalbuminuric group could not be explained by improved glycaemic control nor interventional drug treatment. The lack of progression in this microalbuminuric group from the original prevalence study suggests that this method of identifying early nephropathy in childhood may not be valid or that the progression of incipient nephropathy in childhood is more irregular or slower than in later life.
Asunto(s)
Albuminuria/etiología , Diabetes Mellitus Tipo 1/complicaciones , Adolescente , Niño , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/orina , Nefropatías Diabéticas/orina , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Estudios ProspectivosRESUMEN
OBJECTIVE: To detect the incidence, geographic distribution, and seasonal variation of insulin-dependent diabetes mellitus (IDDM) in all of Greece. RESEARCH DESIGN AND METHODS: One hundred and thirty-seven children (75 boys and 62 girls) up to 14.9 years of age were diagnosed with IDDM in Greece in 1992. RESULTS: The age-adjusted incidence of IDDM in Greece in 1992 was 6.25/100,000 population (boys: 6.17/100,000;: girls: 6.28/100,000). There was a significant pubertal peak. The incidence of IDDM was significantly higher in metropolitan (10.0/100,000) than in rural (4.21/100,000), semirural (7.48/100,000), or urban areas (5.36/100,000) of Athens. There was a marginal difference between rural and semirural areas. No significant seasonal variation in the incidence of IDDM was observed. CONCLUSIONS: We conclude that the incidence of IDDM in Greece is among the five lowest in Europe. An impressive clustering of cases was observed in the Athens metropolitan area compared with the rural and semirural areas, an observation that possibly underlines the importance of environmental factors (stressful situations, infections, dietary habits, and others) in the expression of IDDM.
Asunto(s)
Diabetes Mellitus Tipo 1/epidemiología , Adolescente , Distribución por Edad , Niño , Preescolar , Demografía , Femenino , Grecia/epidemiología , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Análisis de Regresión , Estudios Retrospectivos , Estaciones del Año , Distribución por SexoRESUMEN
Sympathetic function was studied in 101 diabetic children and 102 age and sex matched control children, as part of a longitudinal study of the evolution of microvascular disease in the population of diabetic children and adolescents in Avon County. The median (range) age of the diabetic population was 13.5 (6.0-17.2) years, the duration of diabetes was 4.0 (0.4-13.9) years, and glycated haemoglobin (HbA1) was 10.9 (7.0-18.1)%. Pupillary adaptation in darkness, as an index of sympathetic neuropathy, was measured using a Polaroid portable pupillometer. Diabetic children had a significantly smaller median pupillary diameter, measured as the pupil/iris ratio and expressed as a percentage, than control children (median (range) 62.9 (50.3-72.1) v 65.9 (52.2-73.8)). Pupillary diameter was significantly related to diabetes duration (r = -0.22), HbA1 (r = -0.34), systolic blood pressure (r = -0.25), diastolic blood pressure (r = -0.49), and mean albumin/creatinine ratio on random urine samples (r = -0.26). Pupillary diameter was not related to age (r = -0.1). Eight (7.9%) diabetic and four (3.9%) control children were identified as having abnormal pupillary dilation in darkness. In comparison with the rest of the diabetic population, these diabetic children had longer diabetes duration and poorer glycaemic control. Polaroid pupillometry has demonstrated subclinical autonomic neuropathy in a population of diabetic children and adolescents. These abnormalities were related to poor metabolic control, long diabetes duration, and also to other indices of microvascular disease.