Efficacy and Safety of Abrilumab in a Randomized, Placebo-Controlled Trial for Moderate-to-Severe Ulcerative Colitis.

BACKGROUND & AIMS: The α4ß7 integrin is a validated target in inflammatory bowel disease. This randomized, phase 2b, placebo-controlled, double-blind study evaluated the efficacy and safety of the anti-α4ß7 antibody abrilumab in patients with moderate-to-severe ulcerative colitis despite treatment with conventional therapies. METHODS: Patients (total Mayo Score 6-12, recto-sigmoidoscopy score ≥2) with inadequate response or intolerance to conventional therapies were randomized to receive subcutaneous abrilumab (7, 21, or 70 mg) on day 1, weeks 2 and 4, and every 4 weeks; abrilumab 210 mg on day 1; or placebo. The primary end point was remission (total Mayo Score ≤2 points, no individual sub-score >1 point) for the 2 highest dosages at week 8. Key secondary end points were response and mucosal healing (centrally read) at week 8. RESULTS: For 354 patients who received ≥1 dose of investigational product (placebo, n = 116; 7 mg, n = 21; 21 mg, n = 40; 70 mg, n = 98; 210 mg, n = 79), non-adjusted remission rates at week 8 were 4.3%, 13.3%, and 12.7% for the placebo and abrilumab 70-mg and 210-mg groups, respectively (P < .05 for 70 and 210 mg vs placebo); odds of achieving remission were significantly greater with abrilumab 70 mg (odds ratio 3.35; 90% CI 1.41-7.95; P = .021) and 210 mg (odds ratio 3.33; 90% confidence interval 1.34-8.26; P = .030) than with placebo. Response and mucosal healing rates with these dosages also were significantly greater than with placebo. Higher baseline α4ß7 levels on naïve CD4+ T cells were a prognostic indicator for overall outcome, but not a predictive biomarker of abrilumab response. There were no cases of progressive multifocal leukoencephalopathy or deaths. CONCLUSIONS: Abrilumab treatment for 8 weeks induced remission, clinical response, and mucosal healing in patients with moderate-to-severe ulcerative colitis. ClinicalTrials.gov, number NCT01694485.

Neurological and Neurosurgical Emergencies in Patients with Hematological Disorders.

PURPOSE OF REVIEW: Hematologic diseases are blood disorders which can affect different organs, including the central and peripheral nervous systems. Some of them are associated with increased risk of permanent disability and death. This review highlights a selected group of primary and acquired hematologic disorders that can present as neurologic or neurosurgical emergencies. RECENT FINDINGS: There is an increasing recognition of the broad neurologic presentations of hematologic disorders. Diagnostic criteria continue to be revised as we learn more about these diseases. Treatment options are varied depending on the hematologic syndrome. Clinical judgment is important on a case by case basis given the complexity of these patients. Early recognition of neurologic manifestations of hematologic disorders is important as emergent treatment may be warranted. Clinical signs, appropriate laboratory testing and progression of disease must be taken into consideration to make a timely and definitive diagnosis which will aid in guiding treatment.

Fatty liver in adolescents on the U.S.-Mexico border.

PURPOSE: To describe the physical and metabolic characteristics of children diagnosed with fatty liver disease in a gastroenterology clinic in El Paso, Texas. DATA SOURCES: A retrospective chart review of 31 patients aged 8-18 diagnosed with fatty liver was conducted. CONCLUSIONS: These children were diagnosed with fatty liver by elevated alanine aminotransferase (ALT) levels (mean ALT levels 126 +/- 08 U/L) and increased hepatic echogenicity measured via ultrasound. The majority of children were adolescents (12-17 years of age) and Mexican American. All subjects were overweight (body mass index [BMI] > or = 95th percentile) based on Centers for Disease Control and Prevention standards. In a subset of children for whom results from laboratory test were available, we found 40% had high triglycerides (> or = 150 mg/dL), 53% had low high-density lipoprotein cholesterol (< or = 35 mg/dL), and 17% had prediabetes (fasting glucose > or = 100 mg/dL). The clinical and laboratory findings in this patient population with fatty liver are consistent with a diagnosis of nonalcoholic fatty liver disease (NAFLD). IMPLICATIONS FOR PRACTICE: Despite the increasing trend in overweight among children and adolescents, data suggest low rates of diagnosis and management of overweight and related comorbidities by healthcare providers. Overweight has been associated with fatty liver disease in the pediatric population and includes other comorbidities such insulin resistance and features of metabolic syndrome. Screening for overweight in children should constitute the first step in identifying children at risk for NAFLD. Nurse practitioners should include in the evaluation of pediatric patients calculation of BMI and waist circumference for age and screening for other overweight-related comorbidities.

Physical activity, cardiorespiratory fitness, and metabolic syndrome in young Mexican and Mexican-American women.

Young adult women have had the greatest increase in prevalence of metabolic syndrome (MetS) over time, and prevalence is highest in Hispanic women, compared with women of other ethnicities. Factors contributing to the high prevalence of MetS in Hispanic women are unknown. This study was conducted to determine if physical activity or fitness were associated with individual features of MetS in young Mexican and Mexican-American women, and if the associations were independent of fat mass. Sixty young Mexican and Mexican-American women participated in the study. MetS was defined according to the Adult Treatment Panel III. A fasting blood sample was drawn for the measurement of glucose, insulin, high-density lipoprotein cholesterol (HDL-c), and triglycerides. Physical activity was assessed by questionnaire and accelerometer. Fitness was assessed by progressive treadmill test to exhaustion and ventilatory threshold. Body composition was assessed with Bod Pod. Multivariate regression was used to establish the independent contributions of physical activity and fitness to the individual features of MetS. After controlling for fat mass and fat-free mass, physical activity was found to be independently related to HDL-c and fitness was found to be independently related to triglycerides (p < 0.05). The independent associations between physical activity, fitness, and features of MetS were mediated by, rather than independent of, fat mass. Fat mass was independently related to triglycerides, systolic blood pressure, and diastolic blood pressure. Although physical activity and fitness were related to features of MetS, these associations were not independent of fat mass.

Frequency of hypoglycaemia during the intravenous glucose tolerance test in overweight children.

The study aimed to assess the frequency of hypoglycaemia during the insulin-modified, frequently sampled intravenous glucose tolerance test (FSIVGTT) in overweight Hispanic children. The study included 210 children, mean age=11+/-1.7 years, BMI percentile=97.2+/-2.9 who where enrolled in a longitudinal study to explore risk factors for type 2 diabetes. Two fasting blood samples were collected to determine basal glucose and insulin concentrations. At time 0, glucose (0.3 g/kg body weight) was administered intravenously. Eleven blood samples were collected until 180 min post glucose injection. Insulin (0.02 U/kg body weight) was injected intravenously at 20 min. Plasma was analyzed for glucose and insulin and used for the determination of insulin sensitivity. Hypoglycaemia, defined as a plasma glucose<50 mg/dl, was observed in one asymptomatic subject (<0.5% subjects). In addition, only 1.9% of subjects (n=4) had plasma glucose<60 mg/dl at any time during the FSIVGTT. The frequency of hypoglycaemia during the insulin modified FSIVGTT is very low in overweight Hispanic youth.

Adiponectin independently predicts metabolic syndrome in overweight Latino youth.

CONTEXT: Adiponectin may be important in the pathogenesis of insulin resistance and the metabolic syndrome in youth. OBJECTIVE: The objective of the study was to determine the unique effect of adiponectin on the metabolic syndrome in overweight Latino youth. PARTICIPANTS: Participants included 175 overweight children (aged 11.1 +/- 1.7 yr, body mass index percentile 97.3 +/- 2.9) with a family history of type 2 diabetes. METHODS: Metabolic syndrome was defined according to a pediatric adaptation of the Adult Treatment Panel III report and included dyslipidemia, abdominal obesity, elevated blood pressure, and prediabetes (impaired fasting glucose or impaired glucose tolerance from a 2-h oral glucose tolerance test). Body composition was estimated via dual-energy x-ray absorptiometry, insulin sensitivity was quantified by the frequently sampled iv glucose tolerance test, visceral fat was measured using magnetic resonance imaging, and adiponectin was determined in fasting serum. RESULTS: In simple linear regression, adiponectin was significantly and inversely related to systolic blood pressure (P < 0.05), waist circumference (P < 0.001), triglycerides (P < 0.001), and 2-h glucose levels (P < 0.05) and positively related to high-density lipoprotein-cholesterol (P < 0.001). In multiple linear regression, adiponectin was significantly related to triglycerides (P < 0.01) and high-density lipoprotein-cholesterol (P < 0.01) independent of age, gender, Tanner stage, body composition, and insulin sensitivity. Analyses of covariance established that adiponectin levels were approximately 25% higher in healthy overweight youth, compared with those with the metabolic syndrome (12.5 +/- 3.5 vs. 9.4 +/- 2.8 microg/ml; P < 0.05). In multiple logistic regression, adiponectin was a significant independent predictor of the metabolic syndrome, even after adjustment for confounders including insulin sensitivity and visceral fat. CONCLUSIONS: Hypoadiponectinemia is an independent biomarker of the metabolic syndrome, and thus, adiponectin may play a role in the pathophysiology of the disorder in overweight youth.

Effects of resistance training on insulin sensitivity in overweight Latino adolescent males.

PURPOSE: Insulin resistance is thought to be a core defect in the pathophysiology of obesity-related comorbidities in children, such as type 2 diabetes. Exercise training is known to improve insulin resistance and reduce the risk of type 2 diabetes in adults. However, very little is known regarding the effects of exercise on insulin resistance in youth. Therefore, we examined the effects of a 16-wk resistance training exercise intervention on insulin sensitivity in youth at high risk for developing type 2 diabetes. METHODS: Twenty-two overweight Latino adolescent males were randomly assigned to either a twice-per-week resistance training group (RT=11) or a nonexercising control group (C=11) for 16 wk. Strength was assessed by one-repetition maximum, body composition was quantified by dual-energy x-ray absorptiometry, and insulin sensitivity was determined by the frequently sampled intravenous glucose tolerance test with minimal modeling. RESULTS: Significant increases in upper- and lower-body strength were observed in the RT compared with the C group. The RT group significantly increased insulin sensitivity compared with the C group (P<0.05), and this increase remained significant after adjustment for changes in total fat mass and total lean tissue mass (P<0.05). Compared with baseline values, insulin sensitivity increased 45.1+/-7.3% in the RT group versus -0.9+/-12.9% in controls (P<0.01). CONCLUSION: A twice-per-week 16-wk resistance training program can significantly increase insulin sensitivity in overweight Latino adolescent males independent of changes in body composition.

Longitudinal changes in insulin sensitivity, insulin secretion, and beta-cell function during puberty.

OBJECTIVE: To determine longitudinal changes in insulin sensitivity (SI), insulin secretion, and beta-cell function during puberty in white and black youth. STUDY DESIGN: The tolbutamide-modified frequently sampled intravenous glucose tolerance test and minimal modeling were used to measure SI, the acute insulin response to glucose (AIRg), and beta-cell function (disposition index, DI) in white (n = 46) and black (n = 46) children (mean [+/-SD] age at baseline = 10.2 +/- 1.7 years). Growth curve models (including 272 observations) with SI, AIRg, and DI regressed on Tanner stage were run after adjusting for covariates. RESULTS: After adjusting for covariates, growth curve models revealed that SI decreased and subsequently recovered by the end of puberty in whites and blacks (both p < .05), AIRg decreased linearly across Tanner stages in both races (both p < .001), and DI decreased across puberty in blacks (p = .001) but not in whites (p = .2). CONCLUSIONS: White and black youth exhibited transient insulin resistance and diminished AIRg during puberty. The progressive decline in DI among blacks versus whites may reflect a unique effect of puberty on beta-cell compensation in blacks. Future studies are needed to identify whether this difference contributes to the increased risk of type II diabetes in young blacks.

Deterioration of insulin sensitivity and beta-cell function in overweight Hispanic children during pubertal transition: a longitudinal assessment.

PURPOSE: To examine 1-year changes in insulin dynamics in overweight Hispanic children at high-risk of type 2 diabetes as a function of body composition and pubertal transition. EXPERIMENTAL DESIGN: Longitudinal changes in insulin dynamics, body composition and maturation were determined in 132 Hispanic children (70 boys/62 girls; aged 10.9 +/- 1.8 years). METHODS: Body composition was determined by dual energy x-ray absorptiometry and Tanner stage by physical examination. Insulin sensitivity (SI), the acute insulin response to glucose (AIR) and the disposition index (DI; an index of beta-cell function) were determined using an insulin modified intravenous glucose tolerance test. These measures were conducted at baseline and 1-year later. RESULTS: Fat mass increased by 13% (3.0 kg) and SI declined by 24%. In repeated measures analysis of variance, the fall in insulin sensitivity over 1 year remained highly significant even after adjusting for baseline fat mass, age, gender and change in fat mass. The fall in SI was not significantly influenced by Tanner stage. However, subjects in earlier maturation showed a compensatory increase in AIR (i.e. appropriate beta-cell compensation), whereas subjects in the latter stages of maturation did not (i.e. poor compensation). CONCLUSIONS: These results indicate that failure to increase AIR in response to the fall in SI may be one factor in the pathogenesis of the progression of pediatric type 2 diabetes in this at risk population.

Predicting abdominal adipose tissue in overweight Latino youth.

OBJECTIVES: 1) Examine associations between visceral adipose tissue (VAT), subcutaneous abdominal adipose tissue (SAAT), and anthropometric and demographic variables; 2) generate and cross-validate prediction equations for estimating VAT and SAAT in overweight Latino children. STUDY DESIGN: Cross-sectional. PARTICIPANTS: 196 overweight 8-13-year-old Latino youth. Two-thirds (n = 131) were randomly assigned to a development group to generate prediction equations for VAT and SAAT; one-third (n = 65) was used as a cross-validation group. METHODS AND PROCEDURES: Anthropometric measurements (height, weight, skinfold thicknesses, and circumferences) were performed. VAT and SAAT were measured using magnetic resonance imaging (MRI). RESULTS: The strongest univariate correlate for VAT was waist circumference (WC) (r = 0.65, p < 0.01) while the strongest correlate for SAAT was hip circumference (r = 0.88, p < 0.001). Regression analyses showed approximately 50% of the variance in VAT was explained by WC (43.8%), Tanner stage (4.2%) and calf skinfold (1.7%). Variance in the SAAT model was explained by WC (77.8%), triceps skinfold (4.2%) and gender (2.3%). Residual analyses showed no bias in either equation. Though mean differences between measured and predicted VAT and SAAT were small, there was a large degree of variability at the individual level especially for VAT. CONCLUSIONS: Both VAT and SAAT prediction equations performed well at the group level, but the relatively high degree of variability suggests limited clinical utility of the VAT equation. MRI is currently required to derive an accurate measure of VAT at the individual level.

Acculturation is Associated With Higher VO2max in Overweight Hispanic Children.

Acculturation has been implicated to be associated with physical activity (PA) behaviors in adults; little is known, however, with respect to the pediatric population. The purpose of this study was to determine whether cardiorespiratory fitness (VO2max) and/or PA were associated with acculturation status in overweight Hispanic children. In a sample of 144 children 8-13 years old, acculturation status was determined by place of birth: foreign born (n = 17), 1st generation (n = 101), or 2nd/3rd generation (n = 26), and by questionnaire: less assimilated (n = 76) or more assimilated (n = 34). VO2max was measured using a treadmill protocol, PA was assessed by questionnaire, and body composition by DEXA. ANOVA and ANCOVA were used to determine unadjusted and adjusted group differences, respectively. After adjusting for covariates, the 2nd/3rd generation group had significantly higher VO2max compared with the 1st generation group: 2.26 ± 0.20 L/min vs. 2.15 ± 0.19 L/min, p = .03. No differences were noted for PA, however. Acculturation to the U.S. is associated with higher VO2max in overweight Hispanic children. Longitudinal analyses are needed to determine whether these fitness differences confer protective health effects in this at-risk population.

The relation of sugar intake to beta cell function in overweight Latino children.

BACKGROUND: Few studies have investigated the association between sugar intake and insulin dynamics in children, and none have examined this association in overweight Latino youth. OBJECTIVE: We aimed to examine the relation between dietary components, especially sugar intake, and insulin dynamics in overweight Latino youth. DESIGN: We examined 63 overweight Latino children aged 9-13 y. Dietary intake was determined by 3-d records, and body composition was measured with dual-energy X-ray absorptiometry. Insulin sensitivity (S(I)), acute insulin response (AIR), and disposition index (an index of beta cell function) were measured by using a frequently sampled intravenous-glucose-tolerance test and minimal modeling. Hierarchical regression analysis ascertained the potential independent relation between insulin dynamics and dietary components. RESULTS: The relation between macronutrient intake and any variable related to insulin dynamics was not significant. However, higher total sugar intake, although not related to S(I), was significantly associated with lower AIR (beta = -0.296, P = 0.045) and lower beta cell function (beta = -0.421, P = 0.043), independent of the covariates age, sex, body composition, Tanner stage, and energy intake. Sugar-sweetened beverage intakes trended toward inverse association with lower AIR (beta = -0.219, P = 0.072) and beta cell function (beta = -0.298, P = 0.077). CONCLUSIONS: In overweight Latino children, higher intakes of sugar and sugar-sweetened beverages were associated with lower AIR and disposition index, which suggested that these children already have early signs of poor beta cell function. These results emphasize the need for early nutritional interventions to reduce daily sugar intake in overweight Latino children and potentially reduce their risk for type 2 diabetes.

Dietary fat intake and insulin resistance in black and white children.

OBJECTIVE: The purpose of this study was to determine whether dietary fat intake above current Acceptable Macronutrient Distribution Range (AMDR) guidelines was associated with greater insulin resistance in black and white children. RESEARCH METHODS AND PROCEDURES: We studied 142 healthy children (n = 81 whites, n = 61 blacks), 6.5 to 14 years old. Dietary composition was determined by repeated 24-hour dietary recall, body composition by DXA, visceral fat by computed tomography, and insulin sensitivity (SI) and acute insulin response to glucose (AIRg) by frequently sampled intravenous glucose tolerance test. Subjects were categorized by ethnicity (white/black) and dietary fat intake (above-AMDR/within-AMDR guidelines), and differences were analyzed by 2 x 2 analysis of covariance, adjusting for covariates. RESULTS: After adjusting for total body fat, gender, and Tanner stage, subjects consuming dietary fat above AMDR intake guidelines had lower SI and higher AIRg. This effect was specific to black children (32% lower SI and 62% higher AIRg in above-AMDR compared with within-AMDR blacks) and was not seen in whites. DISCUSSION: In black, but not white, children, those with dietary fat intake above current AMDR guidelines had lower SI and higher AIRg than those who met AMDR guidelines. These findings support current AMDR guidelines for dietary fat in black children and adolescents. The mechanism(s) underlying the ethnic differences in the relationship between dietary fat intake and SI in children require further investigation.

Decreased beta-cell function in overweight Latino children with impaired fasting glucose.

OBJECTIVE: To determine whether overweight Latino children with impaired fasting glucose (IFG) (> or = 100 mg/dl) have increased insulin resistance or decreased beta-cell function compared with those with normal fasting glucose (NFG). RESEARCH DESIGN AND METHODS: We studied 207 healthy overweight Latino children, aged 8-13 years, with a family history of type 2 diabetes. Fasting and 2-h glucose and insulin were assessed by oral glucose tolerance test. Insulin sensitivity (S(i)), the acute insulin response to glucose (AIRg), and the disposition index (DI; an index of beta-cell function) were determined using the insulin-modified intravenous glucose tolerance test and minimal modeling. Body composition was determined by dual-energy X-ray absorptiometry. RESULTS: There were no differences in body composition between NFG (n = 182) and IFG (n = 25) children. Compared with children with NFG, children with IFG had higher fasting and 2-h glucose values and higher fasting insulin. After adjusting for covariates, children with IFG had no difference in S(i) but 15% lower DI than NFG children (2,224 +/- 210 vs. 2,613 +/- 76, P < 0.05). Multivariate linear regression showed that AIRg and DI, but not S(i), were significant predictors of fasting blood glucose. CONCLUSIONS: In overweight Latino adolescents with a family history of type 2 diabetes, IFG is associated with impaired beta-cell function and therefore may identify children likely to be at risk for progression to type 2 diabetes. The actual risk of progression of IFG to type 2 diabetes remains to be determined by prospective longitudinal studies.

Cardiovascular fitness and the metabolic syndrome in overweight latino youths.

PURPOSE: To determine whether cardiovascular fitness (.)VO(2max) is associated with the metabolic syndrome and its individual features in overweight Latino youths. METHODS: A total of 163 overweight Latino boys and girls (body mass index (BMI) percentile = 97.0 +/- 3.1; age = 11.2 +/- 1.7 yr) with a family history of Type 2 diabetes participated in this investigation. The metabolic syndrome was defined as having three or more of the following risk factors: abdominal obesity, high blood pressure, low HDL-cholesterol, high triglycerides, and impaired glucose tolerance. (.)VO(2max) was determined by a progressive treadmill test to exhaustion, and body composition was assessed using dual energy x-ray absorptiometry. RESULTS: (.)VO(2max) was not correlated with any individual risk factor of the metabolic syndrome after adjusting for gender, age, and body composition in partial analysis. Furthermore, ANCOVA revealed that children with zero, one, two, or three or more risk factors did not differ in regards to fitness levels. CONCLUSION: (.)VO(2max) is not independently associated with the metabolic syndrome or any individual feature in overweight youths of Latino ethnicity after controlling for differences in confounding variables.

Impaired glucose tolerance and bone mineral content in overweight latino children with a family history of type 2 diabetes.

OBJECTIVE: Research on the skeletal status of pre-diabetic (type 2 diabetic) children is warranted. We examined the hypothesis that bone mineral content (BMC) and bone mineral density (BMD) will be lower in children with impaired glucose tolerance (IGT) versus normal glucose tolerance (NGT). RESEARCH DESIGN AND METHODS: Total body BMC and BMD of 184 overweight Latino children (106 boys, 78 girls, 11.9 +/- 1.7 years) with a family history of type 2 diabetes were measured using dual-energy X-ray absorptiometry. Glucose tolerance was assessed by 2-h glucose after an oral glucose tolerance test. Area under the insulin curve (AUC) assessed the cumulative insulin response to oral glucose. Acute insulin response to glucose (AIR) was determined by an intravenous glucose tolerance test. RESULTS: Partial correlations revealed an inverse relationship between BMC and AIR (r = -0.29, P = 0.00), AUC (r = -0.28, P = 0.00), fasting insulin (r = -0.16, P = 0.04), and 2-h insulin (r = -0.16, P = 0.04). There was no significant difference in BMC or BMD between children with IGT (n = 46) or NGT (n = 138). Stepwise multiple linear regression revealed that 89% of the variance in BMC is attributed to lean mass (87%), age (1%), and AIR (1%). BMD was explained by lean mass (69%), Tanner stage (3%), and AUC (2%). CONCLUSIONS: The findings of this study suggest that in overweight children, lean mass is the primary predictor of BMC and BMD, whereas age, Tanner stage, and the acute and cumulative insulin responses to oral glucose make subtle independent contributions to the total variances. In addition, poor glycemic control does not seem to be detrimental to bone mass of pre-diabetic children.

Relation between acanthosis nigricans and insulin sensitivity in overweight Hispanic children at risk for type 2 diabetes.

OBJECTIVE: To investigate in a population of Hispanic children if 1) the presence of acanthosis nigricans (AN) is related to insulin sensitivity (S(i)) independent of adiposity and 2) scale scoring AN severity adds to the clinical estimation of insulin sensitivity, above and beyond the presence or absence AN alone. RESEARCH DESIGN AND METHODS: The study population, 131 Hispanic overweight children (mean BMI percentile 97.0 +/- 3.1, 72 boys, 59 girls, ages 8-13 years, mean Tanner stage 2.4 +/- 1.5) with a family history of type 2 diabetes, underwent a physical examination of the neck to determine AN absence or presence (0-1), AN extent score (0-4 scale), AN texture score (0-3 scale), and an AN combined score (extent + texture; 0-7 scale). S(i) was measured by the frequently sampled intravenous glucose tolerance test and minimal modeling. Multivariate linear regression analysis was used to determine the role of BMI and AN in predicting S(i). RESULTS: BMI was the main predictor of S(i), explaining approximately 41% of the variance. The presence of AN explained an additional 4% of the variability in S(i); scale scoring of AN extent or texture did not significantly improve the prediction. CONCLUSIONS: Although AN is an independent risk factor for insulin resistance in overweight Hispanic children at risk for type 2 diabetes, body adiposity is the primary determinant of insulin sensitivity. In addition, scale scoring AN seems of minimal usefulness in clinically estimating the severity of insulin resistance over and above assessing the presence or absence of AN and calculating BMI.

The metabolic syndrome in children and adolescents.

The metabolic syndrome was recently defined by the Adult Treatment Panel III. Despite a lack of uniform definition of the syndrome in pediatrics, recent studies have shown that the syndrome develops during childhood and is highly prevalent among overweight children and adolescents. The hypothesized central role of insulin resistance and obesity as a common underlying feature of the metabolic syndrome also appears to be already manifested in childhood. In view of the current obesity epidemic in children and adolescents, there is a vital need to provide adequate guidelines for the definition of the metabolic syndrome in pediatrics and for the development of screening and treatment strategies. This article focuses on the above issues, as well as on the impact of the syndrome on two major disease outcomes, type 2 diabetes and cardiovascular disease.

The metabolic syndrome in overweight Hispanic youth and the role of insulin sensitivity.

The prevalence of the metabolic syndrome is highest among Hispanic adults. However, studies exploring the metabolic syndrome in overweight Hispanic youth are lacking. Subjects were 126 overweight children (8-13 yr of age) with a family history for type 2 diabetes. The metabolic syndrome was defined as having at least three of the following: abdominal obesity, low high-density lipoprotein (HDL) cholesterol, hypertriglyceridemia, hypertension, and/or impaired glucose tolerance. Insulin sensitivity was determined by the frequently sampled iv glucose tolerance test and minimal modeling. The prevalence of abdominal obesity, low HDL cholesterol, hypertriglyceridemia, systolic and diastolic hypertension, and impaired glucose tolerance was 62, 67, 26, 22, 4, and 27%, respectively. The presence of zero, one, two, or three or more features of the metabolic syndrome was 9, 22, 38, and 30%, respectively. After controlling for body composition, insulin sensitivity was positively related to HDL cholesterol (P < 0.01) and negatively related to triglycerides (P < 0.001) and systolic (P < 0.01) and diastolic blood pressure (P < 0.05). Insulin sensitivity significantly decreased (P < 0.001) as the number of features of the metabolic syndrome increased. In conclusion, overweight Hispanic youth with a family history for type 2 diabetes are at increased risk for cardiovascular disease and type 2 diabetes, and this appears to be due to decreased insulin sensitivity. Improving insulin resistance may be crucial for the prevention of chronic disease in this at-risk population.