Kyriaki Karavanaki

Cardiovascular disease in childhood: the role of obesity

In recent years, childhood obesity is becoming an epidemic health problem. It is now evident from many studies that childhood obesity is correlated with adult excess weight status and the development of risk factors for cardiovascular diseases in adulthood, including hypertension, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome. The exposure to obesity and to the above risk factors during childhood subsequently lead to atherosclerotic development, such as altered vascular structure and function, although the mechanisms are still unclear. Several non-invasive, and thus easy-to-obtain measures of arterial structure and function, have been shown to be clinically useful in providing information about vasculature early in the course of atherosclerosis, including measurement of endothelial function, carotid intima media thickness, and arterial stiffness. The early detection of cardiovascular abnormalities is essential because the control of the atherogenic process is more effective during its early stages. The present review focuses on the cardiovascular consequences of obesity, on the mechanisms and the methods of measurement of endothelial dysfunction in obese children and adolescents, and on the ways of intervention for the improvement of vascular health.

Screening for Associated Autoimmunity in Children and Adolescents with Type 1 Diabetes Mellitus (T1DM)

Background/Aims: Type 1 diabetes (T1DM) is associated with autoimmune thyroid, celiac, autoimmune gastric and Addison’s disease. Our aim was to investigate the prevalence of associated autoantibodies in relation to the demographic and β-cell autoantibody status (anti-GAD). Methods: Antibodies against thyroid peroxidase (anti-TPO), thyroglobulin (anti-Tg), tissue transglutaminase (anti-tTG IgA), parietal cells (APCA) and adrenal tissue (AAA) were measured in 144 children with T1DM with a mean ± SD age of 12.3 ± 4.6 years and a diabetes duration of 4.6 ± 3.8 years. Results: The prevalence of antibody positivity among our patients was: anti-GAD 53.2%, anti-thyroid (anti-TPO 17.4%, anti-Tg 11.1%); anti-tTG IgA 7.6%, APCA 4.0%, and AAA 0%. Among the children with positive anti-thyroid antibodies, 60% developed autoimmune thyroiditis, while among those anti-tTG IgA positive, 62.5% developed biopsy-confirmed celiac disease. Female gender was more frequent among anti-tTG IgA-positive patients (OR 4.47, p = 0.068), while increasing age was associated with anti-Tg positivity (OR 22.9, p = 0.041). The presence of anti-thyroid antibodies was associated with the presence of anti-GAD (OR 1.45, p = 0.01) and parietal cell antibodies (OR 4.98, p = 0.09). Conclusion: Among T1DM patients, the prevalence rates of anti-thyroid and parietal cell antibodies increased with age and diabetes duration. As the presence of anti-GAD was associated with gastric and thyroid autoimmunity, it could serve as marker for the development of additional autoimmunity in adolescents with diabetes.

Breast-Feeding and Childhood-Onset Type 1 Diabetes: A pooled analysis of individual participant data from 43 observational studies

OBJECTIVE To investigate if there is a reduced risk of type 1 diabetes in children breastfed or exclusively breastfed by performing a pooled analysis with adjustment for recognized confounders. RESEARCH DESIGN AND METHODS Relevant studies were identified from literature searches using MEDLINE, Web of Science, and EMBASE. Authors of relevant studies were asked to provide individual participant data or conduct prespecified analyses. Meta-analysis techniques were used to combine odds ratios (ORs) and investigate heterogeneity between studies. RESULTS Data were available from 43 studies including 9,874 patients with type 1 diabetes. Overall, there was a reduction in the risk of diabetes after exclusive breast-feeding for >2 weeks (20 studies; OR = 0.75, 95% CI 0.64–0.88), the association after exclusive breast-feeding for >3 months was weaker (30 studies; OR = 0.87, 95% CI 0.75–1.00), and no association was observed after (nonexclusive) breast-feeding for >2 weeks (28 studies; OR = 0.93, 95% CI 0.81–1.07) or >3 months (29 studies; OR = 0.88, 95% CI 0.78–1.00). These associations were all subject to marked heterogeneity (I2 = 58, 76, 54, and 68%, respectively). In studies with lower risk of bias, the reduced risk after exclusive breast-feeding for >2 weeks remained (12 studies; OR = 0.86, 95% CI 0.75–0.99), and heterogeneity was reduced (I2 = 0%). Adjustments for potential confounders altered these estimates very little. CONCLUSIONS The pooled analysis suggests weak protective associations between exclusive breast-feeding and type 1 diabetes risk. However, these findings are difficult to interpret because of the marked variation in effect and possible biases (particularly recall bias) inherent in the included studies.

Procalcitonin is a Predictor for High-Grade Vesicoureteral Reflux in Children: Meta-Analysis of Individual Patient Data

OBJECTIVE To assess the predictive value of procalcitonin, a serum inflammatory marker, in the identification of children with first urinary tract infection (UTI) who might have high-grade (≥3) vesicoureteral reflux (VUR). STUDY DESIGN We conducted a meta-analysis of individual data, including all series of children aged 1 month to 4 years with a first UTI, a procalcitonin (PCT) level measurement, cystograms, and an early dimercaptosuccinic acid scan. RESULTS Of the 152 relevant identified articles, 12 studies representing 526 patients (10% with VUR ≥3) were included. PCT level was associated with VUR ≥3 as a continuous (P = .001), and as a binary variable, with a 0.5 ng/mL preferred threshold (adjusted OR, 2.5; 95% CI, 1.1 to 5.4). The sensitivity of PCT ≥0.5 ng/mL was 83% (95% CI, 71 to 91) with 43% specificity rate (95% CI, 38 to 47). In the subgroup of children with a positive results on dimercaptosuccinic acid scan, PCT ≥0.5 ng/mL was also associated with high-grade VUR (adjusted OR, 4.8; 95% CI, 1.3 to 17.6). CONCLUSIONS We confirmed that PCT is a sensitive and validated predictor strongly associated with VUR ≥3, regardless of the presence of early renal parenchymal involvement in children with a first UTI.

Factors for thyroid autoimmunity in children and adolescents with type 1 diabetes mellitus.

Abstract Introduction. Type 1 diabetes mellitus (T1DM) is associated with an autoimmune reaction to thyroid antigens including thyroid peroxidase (anti-TPO) and thyroglobulin (anti-Tg). Aims. We determined in children with T1DM the relationship of positive anti-thyroid antibodies to potential risk factors, including, age, gender, duration of diabetes, and glutamic acid decarboxylase antibodies (anti-GAD). Materials and methods. We studied 144 children and adolescents with T1DM. Their age was 12.3 ± 4.6 (mean ± SD) years, and duration of diabetes was 4.6 ± 3.8 years. Anti-thyroid antibodies were determined using a luminescence method and anti-GAD using an enzyme-linked immunosorbent assay. Results. The prevalence rates of anti-thyroid antibodies among the children with T1DM in our study were: anti-TPO (17.4%), anti-Tg (11.1%), and of both anti-thyroid antibodies (10.4%). The presence of serum anti-thyroid antibodies was positively associated with age (16.6 years in those with positive tests versus 12.0 years in those with negative tests, P = 0.027), duration of diabetes (7.4 versus 4.3 years, P = 0.031), and serum TSH (Thyroid-stimulating hormone) levels (4.8 versus 2.3 μIU/mL, P = 0.002). The presence of both anti-thyroid antibodies was associated with female sex (boys: 4/75 (5.3%), girls: 11/69 (15.9%), chi-square = 6.44, P = 0.04). Subclinical autoimmune thyroiditis (SAIT) was present in 55.5% of the patients with thyroid antibody-positivity and was positively associated with age (16.6 versus 12.0 years, P = 0.001) and diabetes duration (7.6 versus 4.2 years, P = 0.001). Multiple logistic regression analysis revealed that the development of anti-thyroid antibodies was predicted by: 1) the presence of anti-GAD (odds ratio (OR) 1.45, 95% confidence interval (CI) 1.09–1.92), 2) the presence of a second anti-thyroid antibody (OR 134.4, 95% CI 7.7–2350.3), and 3) older age (OR 22.9, 95% CI 1.13–463.2). Conclusions. Thyroid autoimmunity was associated with female gender, increasing age, long diabetes duration, the persistence of anti-GAD, and with TSH elevation, indicating subclinical hypothyroidism.

Psychological stress as a factor potentially contributing to the pathogenesis of Type 1 diabetes mellitus

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.

Associated autoimmune diseases in children and adolescents with type 1 diabetes mellitus (T1DM).

Type 1 diabetes (T1DM) is an autoimmune disease with aberrant immune responses to specific β-cell autoantigens, resulting in insulin deficiency. Children and adolescents with T1DM may also develop organ-specific multiple autoimmunity in the context of APS (autoimmune polyendocrine syndrome) type 1, 2 or 3. The most frequently encountered associated autoimmune disorders in T1DM are autoimmune thyroid, followed by celiac, autoimmune gastric disease and other rare autoimmune conditions. There are limited previous studies on the prevalence of associated autoimmunity, especially multiple, in children with T1DM. The present review reports on the classification of autoimmune diabetes, and on the prevalence, pathogenesis, predictive factors and clinical presentation of pancreatic autoimmunity and of all associated autoimmune disorders in children with T1DM. The impact of associated autoimmunity on diabetes control and general health is also discussed, along with suggestions regarding screening strategies and follow-up for early detection and management of the autoimmunity.

Early signs of left ventricular dysfunction in adolescents with Type 1 diabetes mellitus : The importance of impaired circadian modulation of blood pressure and heart rate

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 (T1 DM). 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.

Transient and chronic neutropenias detected in children with different viral and bacterial infections

AIM The aim of the study was to identify the relationship of acquired neutropenias with infections in childhood and to assess their course, complications, short and long-term outcome. METHOD During a two-year period, all children admitted to the pediatric ward with neutropenia were investigated for underlying infections with indices of infection, cultures of body fluids and serological tests. RESULTS Sixty-seven previously healthy children, aged (median, 25-75%) 0.7 years (0.2-1.5), were identified with neutropenia (frequency: 2.0%). An infectious agent was identified in 34/67 cases (50.7%) (viral infection: n=24, bacterial: n=10). In 50/67 (74.6%) children, neutropenia recovered within 2 months (transient neutropenia, TN), while in 17/67 (25.4%) of them it persisted for more than two months. Two years after diagnosis 50/67 children (74.6%) accepted to be reassessed. Of these children, 8/50 (16%) remained neutropenic (neutropenic children, NC), while 42/50 had recovered completely. CONCLUSION Neutropenia during childhood is usually transient, often following viral and common bacterial infections, does not present serious complications and in the majority, it resolves spontaneously. However, in a significant percentage of patients, neutropenia is discovered during the course of an infection, on a ground of a preceding chronic neutropenic status.

National data on the epidemiology of IDDM in Greece : cases diagnosed in 1992

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.