Associations of Apolipoprotein A, High-Sensitivity C-Reactive Protein and Fasting Plasma Insulin in Obese Children With and Without Family History of Cardiovascular Disease.

BACKGROUND: The worldwide prevalence of childhood obesity has increased from 4.2% to 6.7% during the last two decades. Pediatric obesity is a major health problem, which is dramatically increasing in Greece. A variety of inflammatory variables have been also found to associate with cardiometabolic (CV) risk in obese children. The purpose of this study was to identify and examine the effects of possible CV risk factors in obese and non-obese children with and without family history (FH) of cardiovascular disease (CVD). METHODS: Sixty-eight (68) healthy children and adolescents aged 7 - 13 years participated in the study. Anthropometrical and biochemical indexes were obtained from all children as well as FH of CVD. RESULTS: Systolic blood pressure (SBP), total cholesterol (TC), triglyceride (TG), high-sensitivity C-reactive protein (hsCRP), fasting plasma insulin (FPI) and homeostasis model assessment of insulin resistance (HOMA-IR) levels were found statistically significantly higher in the obese group compared to the non-obese one. High-density lipoprotein (HDL) levels were observed to be statistically significantly lower in the obese children compared to their normal peers. CONCLUSIONS: Apolipoprotein A, hsCRP and FPI levels were significantly higher in the obese children with FH of CVD compared to the ones without FH of CVD. TC and SBP were found to be independently associated with obesity (odds ratio (OR): 1.965, 95% confidence interval (CI): 1.935 - 2.97, P < 0.031 and OR: 1.045, 95% CI: 1.016 - 1.074, P < 0.002, respectively).

Clitoromegaly as first presentation of a neurocutaneous syndrome in a 3-year-old girl.

A rare cause of clitoral hypertrophy in a child is neurofibromatosis type 1 (NF1). Although evaluation, including karyotype and hormonal studies, is necessary to exclude ambiguous genitalia, the diagnosis of neurofibromatosis as a possible cause of clitoromegaly may help avoid lengthy and sometimes invasive interventions.

Neurophysiologic evaluation of infants with congenital hypothyroidism before and after treatment.

We performed a systematic neurophysiological evaluation of newborns-infants newly diagnosed with congenital hypothyroidism and started on replacement therapy, in order to document the maturation of visual, auditory and somesthetic pathways and to evaluate the influence of treatment. Twenty-one patients (9 boys, 12 girls) were studied. They underwent neurophysiological evaluation consisting of visual, auditory, and somatosensory evoked potentials at diagnosis, as well as 6 and 12 months after initiation of treatment. At the time of diagnosis, 47.61 % of the patients had abnormal evoked potentials, with visual evoked potentials being most commonly abnormal. Twelve months after the onset of treatment, abnormal evoked potentials were detected in 33.3 % of the patients. In newly diagnosed infants with congenital hypothyroidism there is a high relevance of abnormal evoked potentials (47.61 %) at the time of diagnosis, declining with time and not correlating with the severity of the disease at diagnosis, the time of diagnosis or the initial dose of thyroxine.

Children and adolescents with type 1 diabetes mellitus have a sixfold greater risk for prolonged QTc interval.

BACKGROUND: QT-wave abnormalities have been detected in type 1 diabetes mellitus (T1DM). Prolongation of the heart rate corrected QT interval (QTc) has been associated with cardiovascular mortality. We evaluated how often QT/QTc abnormalities are present in youth with T1DM and if they are associated with disease parameters. METHODS: Sixty-two T1DM youngsters and equal age- and gender-matched controls were studied. Demographic, anthropometric, and laboratory data were determined. QT was measured on a 12-lead resting electrocardiogram. QTc was calculated using Bazett's formula. RESULTS: T1DM patients had significantly longer QT/QTc than controls, but significance disappeared after adjustment for confounders. Abnormally prolonged QTc≥440 ms was observed six times more frequently in those with T1DM. QT was correlated with age, age at disease onset, but not with glycated hemoglobin or diabetes duration; QTc was only correlated with pubertal stage. CONCLUSIONS: T1DM youths have a sixfold increased risk for QT/QTc prolongation and should have regular follow-up for cardiac autonomic dysfunction.

Investigation of anthropometric, biochemical and dietary parameters of obese children with and without non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) in children has been recognized as a major health burden. The high prevalence of NAFLD is probably due to the contemporary epidemics of obesity, unhealthy dietary pattern, and sedentary lifestyle. The purpose of this study was to investigate anthropometric, biochemical and dietary intake parameters of obese Greek children with and without NAFLD. Eighty two obese children aged 8-15 (45 boys/37 girls) participated in the study. Ultrasonography (US) was used to diagnose NAFLD in all participated subjects. Liver indexes were measured in all children. A 3-day dietary was recorded for all subjects. Data for continuous variables is expressed as mean values±standard deviation. Thirty-five out of eighty two subjects (42.6%) had NAFLD. Body Mass Index levels (P<0.001) and Waist Circumference (P<0.046) levels were statistically higher in the children with severe NAFLD (37.2kg/m(2)±6.2 and 102.9cm±14) compared to children with mild NAFLD (26.6kg/m(2)±3.3 and 86.1cm±9.9) and absent of fatty liver (25.3kg/m(2)±3.6 and 85.2cm±11.2), respectively. Total carbohydrates intakes were significantly higher in subjects with NAFLD (288.8g±70.6) compared to children without NAFLD (244.5g±67.5), (P<0.001). Saturated fatty acids (SFAs) intake was proportionally increased to the degree of hepatic steatosis, while n-3 fatty acids (n-3 FA) consumption was inversely related with NAFLD. In multiple regression analysis of factors associated with NAFLD, HOMA-IR (OR: 1.260, 95%CI: 1.110-1.470, P<0.001) and n-3FA (OR:1.921, 95%CI:1.132-2.187, P<0.001) were the most significant ones. Our results showed that IR, high dietary intakes of CHO and SFA and a low dietary consumption of fiber and n-3 FA were positively associated with the pathogenesis of NAFLD.

Are dietary cholesterol intake and serum cholesterol levels related to nonalcoholic Fatty liver disease in obese children?

Background. Nonalcoholic fatty liver disease (NAFLD) in children has been recognized as a major health burden. Serum lipids as well as dietary cholesterol (DC) intake may positively relate to development of NAFLD. The purpose of this study was to investigate anthropometric, biochemical, and dietary intake parameters of obese Greek children with and without NAFLD. Materials and Methods. Eighty-five obese children aged 8-15 (45 boys/40 girls) participated in the study. NAFLD was diagnosed by ultrasonography (US) in all subjects. Liver indexes were measured in all children. A 3-day dietary was recorded for all subjects. Results. 38 out of 85 children (44.7%) were found to have fatty liver. Obese children with increased levels of TC (95% CI: 1.721-3.191), low density lipoprotein (LDL) (95% CI: 1.829-3.058), and increased dietary cholesterol intakes (95% CI: 1.511-2.719) were 2.541, 2.612, and 2.041 times more likely to develop NAFLD compared with the children without NAFLD. Conclusion. The present study showed that TC, LDL, and DC were the strongest risk factors of development of NAFLD. Reducing body weight and dietary cholesterol intakes as well as decreasing serum TC and LDL levels are urgently necessary in order to prevent NAFLD and possible other health implications later in life.

Risk factors for childhood obesity in a Greek paediatric population.

OBJECTIVE: Obesity in children is a serious public health issue in Greece. The purpose of the current study was to identify risk factors such as birth weight, breast-feeding, dietary patterns, family history of obesity and sedentary behaviours that are possibly associated with paediatric obesity. DESIGN: Two hundred and five overweight and obese children (OW/OB; group 1) aged 7-15 years from eight primary and secondary schools and a control group (group 2) of normal-weight children were matched for age and sex. Overweight and obesity were calculated based on the International Obesity Taskforce criteria. Lifestyle parameters as well as anthropometric data were collected in all children. Conditional logistic regression analysis was used to identify risk factors for obesity. RESULTS: Breast-feeding (> or =3 months) and leisure-time physical activity proved to be protector factors against obesity (OR = 0.21, 95 % CI 0.11, 0.79, P < 0.001 and OR = 0.87, 95 % CI 0.85, 0.89, P < 0.001 respectively). On the other hand, family history of obesity (OR = 3.79, 95 % CI 2.61, 4.18, P < 0.001), sugar-sweetened beverage consumption (OR = 1.77, 95 % CI 1.03, 2.76, P < 0.001) and watching television (OR = 1.99, 95 % CI 1.54, 2.76, P = 0.04) were found to be positively associated with a higher obesity risk. CONCLUSIONS: The current findings support the literature according to which duration of breast-feeding (<3 months), a family history of obesity, watching television, sedentary lifestyle and consumption of sugar-sweetened beverages are important risk factors for childhood obesity. More studies are needed to elucidate the relationship of paediatric obesity and possible predictor factors in order to avoid health consequences in these children later on in life.

Possible Health Implications and Low Vitamin D Status during Childhood and Adolescence: An Updated Mini Review.

Vitamin D deficiency is common in the developing countries and exists in both childhood and adult life. The great importance of Vitamin D is the moderation of calcium (Ca) and phosphorus (P) homeostasis as well as the absorption of Ca. While insufficiency of vitamin D is a significant contributing factor to risk of rickets in childhood, it is possible that a more marginal deficiency of vitamin D during life span contribute to osteoporosis as well as potentially to the development and various other chronic diseases such as cardiovascular disease, cancer and diabetes. This paper reviews the metabolism, epidemiology, and treatment of vitamin D and calcium insufficiency as well as its relation to various diseases during childhood and adolescence.

Is there any association between high-density lipoprotein, insulin resistance and non-alcoholic fatty liver disease in obese children?

Non-alcoholic fatty liver disease (NAFLD) is estimated to occur in about 50% of obese children. The purpose of this study is to examine the association of anthropometric, biochemical and liver indexes in obese children with and without NAFLD and its relation with insulin resistance (IR). Forty-three obese children participated in the study. NAFLD was diagnosed by ultrasonography. Liver indices (SGOT, SGPT), lipid profile, glucose and insulin levels were performed in all patients. IR was measured by means of the homeostasis model assessment and oral glucose insulin sensitivity. Among the 43 obese patients, 18/43 (41.8%) had NAFLD based on ultrasonography. Fifty percent of them had mild steatosis and 50% had moderate/severe steatosis. In logistic regression analysis of factors associated with NAFLD, homeostasis model assessment IR (ExpB, 1.607; 95% confidence interval, 1.058-2.440; P <0.02) and high-density lipoprotein (0.952; 95% confidence interval, 0.814-1.075; P <0.03) were the most significant. IR, as has already been proved, is associated with NAFLD. Furthermore, high-density lipoprotein levels seem to play an additional role in predicting NAFLD in obese children.

Are saturated fatty acids and insulin resistance associated with fatty liver in obese children?

BACKGROUND: Fatty liver (FL) is a common cause of liver disease in children. Obesity and insulin resistance (IR) play an important role in pathogenesis of FL. Diet has been reported to affect IR and possibly FL. The purpose of this study was to investigate certain parameters (anthropometric, biochemical, dietary intake) of obese Greek children with and without FL. METHODS: Forty-three obese children aged 9-14 (25 boys/18 girls) participated in the study. FL was diagnosed by ultrasonography (US). Liver indexes (ALT, AST, gamma-GT) were measured in all children. A 3-day dietary was recorded for all subjects. None of the subjects were positive for viral hepatitis or had a history of consuming alcohol. RESULTS: Eighteen out of 43 subjects (41.8%) had FL based on US. Intakes of carbohydrates and simple refined carbohydrates were significantly higher in subjects with FL compared to children without FL, while saturated fatty acids (SFA) were proportionally increased to the degree of hepatic steatosis. In multiple regression analysis of factors associated with FL, only HOMA-IR [Beta: 0.160, 95%CI (0.122-1.340), P<0.001] and SFA [Beta: 0.455, 95%CI (0.129-2.129), P<0.001] were the most significant one. CONCLUSIONS: Our results suggest that high intake of carbohydrates and simple refined carbohydrates as well as low intake of fiber may be correlated with the pathogenesis of FL. Moreover, IR and high intake of SFA are independently associated with FL in obese children.

Holoprosencephaly and diabetes insipidus in a 3-month-old infant.

Holoprosencephaly is a developmental defect caused by incomplete cleavage of the embryonic forebrain structures during early embryogenesis. We describe a 3-month-old boy with median cleft palate, surgically reconstructed cleft lip, hypotelorism with a flat nose, cryptorchidism, clubfoot, and microcephaly. During the laboratory investigation, his blood sodium level was 154 mmol/L and urine specific gravity was 1.007. Serum osmolarity was 317 mOsm/kg and urine osmolarity was 268 mOsm/kg. Given these findings and the clinical response to vasopressin, diagnosis of central diabetes insipidus was made. Magnetic resonance imaging revealed semilobar holoprosencephaly. The patient responded very well to vasopressin treatment with restoration of serum electrolytes, which remained within normal limits on follow-up. In case of midline facial defects accompanied by hypotelorism with or without developmental delay, the brain should be imaged to confirm its morphology and investigations should be directed by a high index of suspicion of associated endocrinologic dysfunctions.

Ghrelin and leptin levels in obese adolescents. Relationship with body fat and insulin resistance.

OBJECTIVE: Ghrelin and leptin levels are influenced by body fat (BF%), pubertal stage and possibly insulin resistance (IR). The aim of our study was: 1) To compare fasting ghrelin and leptin levels between obese and non-obese, adolescents, 2) to investigate possible correlations of these hormones with BF %, as well as IR. DESIGN: Twenty obese insulin resistant (IR) adolescents, twenty obese non IR (NIR) and fifteen healthy non-obese, age-matched adolescents were studied. In all participants, height, weight, body mass index (BMI) and BF % were measured. Fasting glucose, insulin, ghrelin and leptin levels were determined. IR was assessed using HOMA-IR index. RESULTS: BMI, BF %, insulin and HOMA-IR values were positively correlated with leptin and negatively with ghrelin levels. A negative correlation between circulating leptin and ghrelin levels was found. A suggestive positive correlation between leptin levels and BF %, independent of BMI, was also observed (P=0.075). Ghrelin levels were significantly correlated with insulin levels and HOMA-IR, independent of BMI (P=0.077). CONCLUSIONS: Obesity and IR may play an important role in the release of ghrelin as well as in the negative correlation between ghrelin and leptin.

Ghrelin serum levels during oral glucose tolerance test in prepubertal obese children with insulin resistance.

BACKGROUND: An involvement of ghrelin in glucose metabolism has been suggested; nevertheless, the relationship between ghrelin and insulin resistance (IR) remains unclear. AIMS: 1. To investigate the effect of glucose loading on ghrelin in prepubertal obese children with IR. 2. To assess possible correlations between IR and changes in circulating ghrelin. PATIENTS AND METHODS: Twenty prepubertal obese, insulin-resistant and 18 age- and sex-matched lean children were studied. Fasting glucose, insulin and ghrelin levels were measured. In the obese group, measurements were repeated during an OGTT. RESULTS: Ghrelin levels were decreased at 60 min, but thereafter increased to baseline values. The fall in circulating ghrelin was negatively correlated with IR and the respective rise in insulin levels. CONCLUSIONS: In prepubertal, insulin-resistant obese children, ghrelin is significantly suppressed shortly after glucose intake. It is possible that the above effect is attenuated by IR and the resultant increase in insulin levels.

Update on non-alcoholic fatty liver disease in children.

Non-alcoholic fatty liver disease (NAFLD) is probably the most common cause of liver disease in the pediatric community. It is closely associated with obesity and insulin resistance. NAFLD may lead to non-alcoholic steatohepatitis (NASH). Although NASH is a prerequisite for the definition of NAFLD in adults and children, distinct differences are often apparent in the extent or location of fat, inflammation and fibrosis. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies; however, staging the disease requires a liver biopsy. Current treatment relies on weight loss and exercise, although various insulin-sensitizing agents, antioxidants and medications appear promising. The aim of this review is to summarize what is known about pediatric NAFLD in terms of prevalence, pathogenesis, diagnosis, histology and treatment.

Bone mineral density in survivors of childhood acute lymphoblastic leukemia.

The aim of our study was to evaluate bone metabolism with measurement of bone mineral density (BMD) after management (chemo-, radiotherapy) for childhood acute lymphoblastic leukemia (ALL). Bone mineral density (g/cm2) of lumbar spine was measured by dual energy X-ray absorptiometry (Norland bone densitometer) in 18 children with ALL and a median of 34 months' post-diagnosis with no history of relapse, secondary malignancy, or transplantation. In addition, patients' BMDs were correlated with particular attention to age, sex and time (years) from completion of chemotherapy. The results were compared with healthy age- and sex-matched controls of the same population and expressed as standard deviation scores (SDS). Mean age of children was 9.8 +/- 3.7 years. Of 18 children (10 boys and 8 girls), 13 were grouped as standard and 5 as high-risk, respectively. Based on z-score values, 9 were classified as normal (z-score <1 SD), 7 as osteopenic (z-score 1-2.5 SD) and 2 as osteoporotic (z-score >2.5 SD). Children with ALL had reduced lumbar BMDs (z score -0.99) in comparison to healthy controls (z score -0.14) (p=0.011), which is indicative of relative osteopenia. Moreover, the reduced BMD was associated with patient age (z score -0.14 and -1.52 for ages <10 and >10 years, respectively, p=0.016). Reduced BMD was not correlated with time from completion of chemotherapy (p=0.33), risk group (p=0.9) and sex (p=0.3). We conclude that children's BMDs are reduced after completion of chemotherapy for ALL. The causes are multifactorial and mainly related to antineoplastic treatments, such as corticosteroids and methotrexate, physical inactivity and cranial irradiation. We suggest that further studies are needed to evaluate the long-term effect on BMD in these children and to prevent pathological fractures later in life.

Total serum homocysteine, folate and vitamin B12 in a Greek school age population.

BACKGROUND & AIMS: Moderate hyperhomocysteinemia is an independent risk factor for cardiovascular disease (CVD) even among children. The purpose of this study is to investigate for the first time the distribution and determinants of total serum homocysteine (tHcy) levels in healthy Greek children. METHODS: tHcy, folate, B12 were measured in 524 children (275 boys and 249 girls) aged 6-15 years old from different socioeconomic status in Northern Greece. RESULTS: The geometric mean tHcy level for boys and girls was 7.8 (3.4-24.2) and 7.5 (3.9-29.0) micromol/L, respectively. Eighty one (15.4%) children had homocysteine levels above the upper reference limits (>10 micromol/L). The geometric mean serum tHcy level was significantly (P<0.001) increasing with age; 6.4 (3.4-11.2) micromol/L was found in the age group of 6-9 yr (group1), 7.2(4.1-22.1) micromol/L in the one of 10-12 yr (group 2) and 8.5 (3.9-29.0) micromol/L in the one of 13-15 yr (group 3). Serum folate levels were found to be statistically significant (P<0.001) between age group 1 and age group 3 [11.8 (4.66-20.00) vs. 7.5 (0.99-20.00)ng/mL) and between age group 2 and 3 [10.0 (1.82-20.0) vs. 7.5 (0.99-20.00)ng/mL]. Vitamin B12 levels were significantly (P<0.001) different in the three age groups [1048 (117-2000), 805 (296-2000), 700 (214-2000)pg/mL] respectively. Age, BMI, waist circumference (WC), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were positively correlated with tHcy, whereas serum folate and vitamin B12 were negatively correlated. No association was found between tHcy levels and parental education status. In multiple linear regression analysis only age (Beta: 0.248, 95%, CI: (0.159-0.361), P<0.05) and folate (Beta: 0.347, 95%, CI: [(-0.206)-(-0.118)], P<0.05) were found significantly and independently associated with tHcy. CONCLUSIONS: tHcy levels were increasing with age and boys were found to have slightly higher levels than girls. Age and folate levels were the most significantly and independently determinants associated with tHcy. Children with tHcy levels above the upper reference limits (>10 micromol/L) were found to be correlated with BMI, WC, SBP, serum folate and vitamin B12 levels. These children should be encouraged to include high folate food items in their diet and where necessary folate supplements should be recommended. In addition, more prospective studies are necessary in order to evaluate the relationship of tHcy and CVD risk factors in children of our region.

Metabolic syndrome in children and adolescents with acute lymphoblastic leukemia after the completion of chemotherapy.

The metabolic syndrome is a cluster of potent risk factors for cardiovascular diseases. To provide information on the late complications of chemotherapy for acute lymphoblastic leukemia (ALL), the authors prospectively studied the frequency of overweight, obesity, and metabolic syndrome in survivors of ALL in the initial years after the completion of therapy. Children and adolescents were classified as having the metabolic syndrome if they met three or more of the following criteria: hypertriglyceridemia, low levels of high-density lipoprotein (HDL), high fasting glucose, obesity, and hypertension. Obesity was defined on the basis of Body Mass Index (BMI) (kg/m2) standard deviation scores or z-scores. Cutoff points for triglycerides and HDL were taken from equivalent pediatric percentiles with the cutoff points proposed by the Adult Treatment Panel III (ATPIII). Hyperglycemia was defined using the ATPIII cutoff points. Elevated systolic or diastolic blood pressure was defined as a value greater than the 95th percentile for age, gender, and height. Fifty-two subjects (29 male and 23 female) with a median age of 15.2 years (range 6.1-22.6 years) were evaluated. Median interval since completion of therapy was 37 months (range 13-121 months). All of them had been treated according to the ALL-BFM 90 chemotherapy protocol and none had received cranial radiotherapy. Of the 52 subjects, 25 (48%) were overweight (BMI z-score >1.5) and 3 (5.76%) were obese (BMI z-score >2); among them, 1 was severely obese (BMI z-score >2.5). Three criteria for the metabolic syndrome (high triglyceride levels, glucose intolerance, and obesity) were fulfilled by three subjects (5.76%). Twenty-nine subjects (55.7%) had at least one risk factor for metabolic syndrome. Hyperglycemia and hypertension were infrequent. Prompt recognition of the risk factors for metabolic syndrome and intervention seem mandatory to ensure early prevention of cardiovascular disease in survivors of ALL.

Evaluation of bone metabolism in children with acute lymphoblastic leukemia after induction chemotherapy treatment.

Osteopenia and osteoporosis are currently receiving particular attention as late effects of therapy in survivors of childhood acute lymphoblastic leukemia (ALL). The aim of this study was to evaluate abnormalities in bone mass and mineral homeostasis in children with ALL after induction therapy (during consolidation treatment). Lumbar spine (L2-L4) bone mineral density (BMD, g/cm(2)) was measured by dual energy X-ray absorptiometry in 20 children with ALL, a median of 25.9 months postdiagnosis and results were expressed as z-scores relative to healthy Caucasian children (controls). Serum levels of intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), calcium, phosphate, and magnesium were also analyzed. In addition, the body mass indexes (kg/cm(2)) of patients and controls were calculated. Results were compared with those of 40 healthy controls. Among the 20 children with ALL (12 boys and 8 girls), 12 presented z-scores < 1 SD (normal) and 8 were osteopenic (z-score between 1 and 2.5 SD). In addition, children with ALL had reduced lumbar BMDs (z-score -0.817) in comparison to healthy controls (z-score -0.353) (p = .04). Moreover, alkaline phosphatase and intact parathyroid hormone values were significantly increased compared to controls values. The data demonstrate that bone metabolism in children with ALL during consolidation therapy is disturbed, resulting in a reduced BMD and z-score with respect to healthy controls. Since a reduced BMD predisposes to osteopenia and osteoporosis, specific attention and therapeutic interventions should be considered.

Description and molecular analysis of SRY and AR genes in a patient with 46,XY pure gonadal dysgenesis (Swyer syndrome).

46,XY pure gonadal dysgenesis, first described in 1955 by Swyer, results from testicular tissue loss during the first 8 weeks of fetal life, a critical period for male differentiation. We describe a case of an 18 years old patient presented to us with a chief complain of primary amenorrhea. Chromosomal analysis revealed a 46,XY karyotype. A molecular investigation was undertaken in an attempt to determine mutations in SRY and AR genes through DNA sequencing. Mutations were shown to be absent. The molecular basis of Swyer syndrome is still unknown, although the presence of mutations in testicular organizing genes downstream of SRY is still to rule out. The patient, who is considered as female, was placed on estrogen replacement therapy, while bilateral prophylactic laparoscopic gonadectomy was programmed due to the high prevalence of gonadal tumors in this syndrome. No signs of malignance were detected in the gonadal tissue, which predicts that an intact SRY gene is usually, but not always, not related to the formation of malignancies like dysgeminomas or gonadoblastomas.