Cardiometabolic phenotype in children with obesity.

OBJECTIVES: To investigate the anthropometric and metabolic correlates of different patterns of left ventricular (LV) geometry in a cohort of outpatient children with high prevalence of obesity. STUDY DESIGN: Anthropometric measures, lipid profile, blood pressure (BP), fasting plasma glucose (FPG), and echocardiographic variables were evaluated in 281 white children (6-16 years), of whom 105 were obese and 105 were morbidly obese. Patterns of LV geometry were defined as follows: normal geometry, eccentric LV hypertrophy (LVH), concentric LV remodeling, and concentric LVH. RESULTS: One hundred forty-eight children exhibited normal LV geometry, 53 eccentric LVH, 36 concentric LV remodeling, and 44 concentric LVH. The 4 groups differed in body mass index, waist circumference, waist-to-height ratio, triglycerides/high-density lipoprotein cholesterol ratio (Tg/HDL-C), and BP (P < .05-.0001). A statistically significant impairment of diastolic function (expressed as greater E/E', P < .002) was observed across patterns of LV geometry. Among anthropometric measures, waist-to-height ratio showed better performance in relation to LVH, with an optimal cut-point of 0.58, compared with body mass index and waist circumference. Children with concentric LVH exhibited the worst metabolic risk profile, with greater prevalence of visceral obesity, high Tg/HDL-C, high BP, and high-normal FPG, than children with normal LV geometry. CONCLUSIONS: In children with high levels of obesity, an unfavorable "cardiometabolic phenotype" can be identified, which includes concentric LVH, visceral obesity, high BP, high Tg/HDL-C, and high-normal FPG.

Primary herpes virus infection and ischemic stroke in childhood: a new association?

We describe, to our knowledge, the first case of arterial ischemic stroke after primary herpes simplex virus type 1 (HSV1) infection in a previously healthy child, without signs of encephalitis. A 10-year-old previously healthy girl was admitted to our hospital with acute left-sided hemiparesis which involved the lower half of her face. Submandibular lymphadenitis and oral vesicular lesions were present. MRI confirmed the suspicion of an acute ischemic stroke. Immunoglobulin M antibodies to HSV1 were detected. Cerebrospinal fluid polymerase chain reaction for herpes virus was negative. She was treated with aspirin (3mg/kg) and intravenous acyclovir (10mg/kg every 8 hours) for 21 days. Immunoglobulin G antibodies to HSV1 appeared 16 days after admission. Twelve months after her hospitalization the patient's examination was normal. Stroke should be considered a possible complication of HSV1 primary infection. Guidelines for the management of acute stroke in children are needed.

Glomerular filtration rate and cardiometabolic risk in an outpatient pediatric population with high prevalence of obesity.

OBJECTIVE: To evaluate the relationship between estimated glomerular filtration rate (eGFR) and cardiometabolic risk factors (CMRF) in an outpatient pediatric population with high prevalence of obesity. DESIGN AND METHODS: eGFR was evaluated in 901 children unselected for chronic kidney disease of whom 694 were overweight/obese (6-16 years) and 207 were age- and sex-matched normal weight (NW). We generated three categories of eGFR: mild-low eGFR (< 20th percentile), high eGFR (>80th percentile) and intermediate eGFR (20-80th percentile), considered as the reference category RESULTS: Children with either mild-low or high eGFR category showed a 2-4 fold higher Odds ratio of high blood pressure, left ventricular hypertrophy, and microalbuminuria compared with children of the intermediate eGFR category. In addition, children with mild-low eGFR levels showed a 1.5-2 fold higher Odds ratio of impaired fasting glucose and high white blood cell count compared with children with intermediate eGFR levels. CONCLUSIONS: In outpatient children with high prevalence of obesity, children with either mildly reduced or high eGFR have an increased burden of CMRF. Children with eGFR < 97 mL/min/1.73 m² show a worse CMR profile. This finding supports the usefulness to assess eGFR to identify children with unfavorable CMR profile.

Usefulness of the high triglyceride-to-HDL cholesterol ratio to identify cardiometabolic risk factors and preclinical signs of organ damage in outpatient children.

OBJECTIVE: To evaluate whether the high triglyceride-to-HDL cholesterol (TG-to-HDL-C) ratio is associated with cardiometabolic risk (CMR) factors and preclinical signs of organ damage in an outpatient population of white children and adolescents. RESEARCH DESIGN AND METHODS: The study population included 884 subjects (aged 6-16 years), of whom 206 (23%) were normal weight, 135 (15%) were overweight, and 543 (61%) were obese. Biochemical variables were analyzed in the whole sample, whereas homocysteine and left ventricular (LV) geometry and function were evaluated in 536 and 258 children, respectively. RESULTS: The percentage of pubertal children (P < 0.001), as well as measurements of BMI, waist circumference, homeostasis model assessment of insulin resistance, white blood cell count, alanine aminotransferase (ALT), systolic blood pressure (P < 0.0001, for all), creatinine (P < 0.001), and diastolic blood pressure (P < 0.02), increased from the lowest to the highest tertile of the TG-to-HDL-C ratio. Age, sex, homocysteine, and glomerular filtration rate did not change. Moreover, interventricular septum thickness, relative wall thickness, and LV mass index (P = 0.01 to P < 0.0001) increased across tertiles of the TG-to-HDL-C ratio. Children with a TG-to-HDL-C ratio ≥2.0 showed a two- to threefold higher risk of elevated ALT levels and concentric LV hypertrophy than those with a TG-to-HDL-C ratio <2.0, independent of confounding factors. CONCLUSIONS: The high TG-to-HDL-C ratio is associated with several CMR factors and preclinical signs of liver and cardiac abnormalities in the outpatient, white pediatric population. Thus, a TG-to-HDL-C ratio ≥2.0 may be useful in clinical practice to detect children with a worsened CMR profile who need monitoring to prevent cardiovascular disease in adulthood.

Fasting plasma glucose and clustering of cardiometabolic risk factors in normoglycemic outpatient children and adolescents.

OBJECTIVE: To evaluate whether fasting plasma glucose (FPG) within a normoglycemic range is associated with cardiometabolic risk factors (CMRF) among children and adolescents in an outpatient setting. RESEARCH DESIGN AND METHODS: Subjects (780; age 6-16 years) with FPG <100 mg/dL were divided into tertiles of FPG. RESULTS: BMI, waist circumference, homeostasis model assessment-insulin resistance, systolic blood pressure, and white blood cell (WBC) count (P < 0.0001) increased across tertiles of FPG. Subjects with high-normal FPG (89-99 mg/dL) showed a higher risk of insulin resistance, hypertension, and high WBC count compared with subjects with low-normal FPG, independent of BMI z score. CONCLUSIONS: In outpatient children and adolescents, higher FPG within the normal range is associated with several CMRF, independent of obesity. Thus the simple measurement of FPG may help identify subjects who warrant some monitoring in relation to cardiovascular risk.

Preclinical manifestations of organ damage associated with the metabolic syndrome and its factors in outpatient children.

BACKGROUND: To evaluate whether the pediatric metabolic syndrome (MetS) or its factors are useful to detect subclinical abnormalities of cardiac, liver, and glomerular damage in an outpatient population. METHODS: The population study included 799 children (age 10 ± 3 years, mean ± SD), 24% of whom were normalweight, 25% overweight, and 51% obese. Alanine-aminotransferase (ALT) levels, estimated glomerular filtration rate (eGFR) and HOMA-IR were analyzed in all children. Microalbuminuria (MA) and left ventricular (LV) geometry and function were evaluated in 501 and 247 children, respectively. MetS was defined using Cook's criteria. RESULTS: MetS was diagnosed in 131 children (16%). Children with MetS+ and MetS- were similar for age, gender and Tanner stage distribution. Children with MetS+ showed higher ALT levels (31 ± 19 vs 21 ± 11 IU/L, p<0.0001), LV mass (39 ± 10 vs 34 ± 10 g/h(2.7), p<0.001) and relative wall thickness (0.37 ± 0.06 vs 0.35 ± 0.05, p<0.01) than MetS-. The two groups were similar for MA and eGFR. At multiple logistic regression analysis, children MetS+ showed a higher risk (OR, 95% Cl) adjusted for confounding factors, of high ALT levels (1.71, 1.12-2.59, p=0.012) and concentric LV hypertrophy (2.17, 1.01-4.66, p=0.047) than children MetS-. The risk of preclinical liver and cardiac damage associated with the MetS phenotype was not higher than predicted by its single components. CONCLUSIONS: Children with MetS show a 2-fold greater risk of having high ALT levels and concentric LV hypertrophy. However, the risk of subclinical manifestations of liver and cardiac damage can be predicted equally well by the single components of the syndrome.

Prehypertension in outpatient obese children.

BACKGROUND: The aim of the study was to analyze the prevalence of prehypertension (PH) in obese (OB) children and its relation with estimated glomerular filtration rate (eGFR) and left ventricular (LV) function. METHODS: The study included 447 OB and 131 normal-weight children. PH was defined according to the criteria proposed by the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. Insulin sensitivity was evaluated by HOMA(IR), and eGFR was calculated by Schwartz's formula. LV function was analyzed by echocardiography in 165 OB children. RESULTS: PH was observed in 79 OB children (17.7%) and in 2 (1.5%) controls. Among OB children, those with PH had greater percentage of males (P < 0.05), higher level of body mass index (BMI) (P < 0.001), waist circumference (WC) (P < 0.005), and HOMA(IR) (P < 0.001), compared to PH- children. The two groups did not differ for eGFR and LV function. At logistic regression analysis, PH was independently associated with male gender (P < 0.025) and HOMA(IR) (P < 0.002). Gender analysis showed that boys with PH presented higher levels of BMI (P < 0.005), WC (P < 0.01), HOMA(IR) (P < 0.001), and triglycerides (P < 0.005) compared to PH- boys. Females with PH were older and in more advanced postpubertal stage, had higher BMI, WC (P < 0.05, for all), and HOMA(IR) (P < 0.025), compared to PH- girls. CONCLUSIONS: In a population of outpatient OB children, the prevalence of PH was 17.7% and boys were more likely than girls to have PH. This condition is characterized by insulin resistance in both sexes but no impairment in glomerular and LV function.

Association of elevated serum alanine aminotransferase with metabolic factors in obese children: sex-related analysis.

Alanine aminotransferase (ALT) elevations are considered a surrogate marker of nonalcoholic liver disease and predict later development of diabetes and metabolic syndrome in adults. The aim of the present study is to evaluate the prevalence of high ALT levels in obese children using updated and sex-related cutoff ALT value (ALT >30 IU/L for boys and >19 IU/L for girls). We also analyzed the association between ALT levels and metabolic factors in the 2 sexes. Three-hundred fifty-eight obese children (168 boys and 190 girls; age range, 6-16 years) were studied. Inclusion criteria were as follows: obesity, defined by an individual body mass index (BMI) greater than or equal to the 95th percentile for age and sex; negativity of markers for viral hepatitis; and no alcohol consumption. Two hundred six nonobese children (92 boys and 114 girls; age range, 6-16 years) served as a control group for ALT levels. The percentage of obese children with elevated ALT was 36% in boys and 55% in girls. Obese boys with ALT greater than 30 IU/L showed higher mother's BMI (P < .025), BMI, waist circumference, insulin resistance evaluated with homeostasis model assessment (HOMA-IR) index (P < .0001, for all), and systolic and diastolic blood pressure (P < .025, for both) compared with those with ALT not exceeding 30 IU/L. The ALT levels correlated positively with mother's BMI, BMI, waist circumference, HOMA-IR, triglycerides, and blood pressure. In linear regression analysis, waist circumference was the only independent factor associated with ALT level (beta = 0.370, t = 3,905, P < .0001). Obese girls with ALT greater than 19 IU/L exhibited lower age (P < .025) and higher triglycerides (P < .0001) than girls with ALT not exceeding 19 IU/L. The ALT levels correlated positively with triglycerides and HOMA-IR and negatively with age and Tanner stage. In linear regression analysis, ALT levels were independently associated only with triglycerides (beta = 0.330, t = 4.588, P < .0001). Our study shows that a high proportion of obese children present elevated ALT levels. This abnormality is associated in boys, more than in girls, with preclinical traits of the metabolic syndrome. The adoption of sex-related cutoff of ALT levels is desirable also for the pediatric population.