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.

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.

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.

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.

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.

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.

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.

Unique effect of visceral fat on insulin sensitivity in obese Hispanic children with a family history of type 2 diabetes.

OBJECTIVE: This study aimed to establish whether total fat or central fat was related to measures of insulin in obese Hispanic children with a family history of type 2 diabetes. RESEARCH DESIGN AND METHODS: Subjects were 32 children aged 8-13 years. Visceral fat and subcutaneous abdominal fat were determined by magnetic resonance imaging at the umbilicus and total body fat was determined by dual-energy X-ray absorptiometry. Insulin sensitivity (S(i)) and acute insulin response (AIR) were determined by frequently sampled intravenous tolerance test with minimal modeling. RESULTS: Mean fasting glucose and insulin, S(i), and AIR (+/- SD) were 5.3 +/- 0.3 mmol/l, 206 +/- 105 pmol/l, 11.8 +/- 5.7 [x 10(-4) min(-1)/(pmol/l)], and 17,175 +/- 9,695 (pmol/l x 10 min), respectively. In multivariate regression analysis, total fat mass was independently and positively related to fasting insulin (P < 0.01) and negatively related to S(i) (P < 0.05) but was not related to AIR. Visceral fat was independently and positively related to fasting insulin (P < 0.05) and AIR (P < 0.01) and negatively related to S(i) (P < 0.001). CONCLUSIONS: -These findings support the hypothesis that specific accumulation of visceral fat in addition to overall adiposity in Hispanic children increases the risk of type 2 diabetes.

Insulin resistance and associated compensatory responses in african-american and Hispanic children.

OBJECTIVE: The objective of this study was to compare insulin resistance relative to body fat and the associated compensatory responses in 57 healthy children living in Los Angeles, California (14 Caucasians, 15 African-Americans, and 28 Hispanics). RESEARCH DESIGN AND METHODS: Insulin sensitivity and acute insulin response were determined by intravenous glucose tolerance test. Insulin secretion, hepatic insulin extraction, and insulin clearance were estimated by C-peptide and insulin modeling. RESULTS: Insulin sensitivity was significantly lower in Hispanics and African-Americans compared with Caucasian children, and acute insulin response was significantly higher in African-American children. No ethnic differences were noted in the first-phase secretion, but second-phase insulin secretion was significantly higher in Hispanic children than in African-American children (200 +/- 53 vs. 289 +/- 41 nmol/min; P = 0.03). The greater acute insulin response in African-Americans, despite lower secretion, was explained by a lower hepatic insulin extraction in African-Americans compared with Hispanics (36.6 +/- 2.9 vs. 47.3 +/- 2.2%; P = 0.0006). CONCLUSIONS: In conclusion, Hispanic and African-American children are more insulin resistant than Caucasian children, but the associated compensatory responses are different across ethnic groups.

Association between insulin sensitivity and post-glucose challenge plasma insulin values in overweight Latino youth.

OBJECTIVE: To determine associations between directly measured insulin sensitivity (SI) and oral glucose tolerance test (OGTT)-derived plasma insulin values, or calculated SI indices, in overweight peripubertal Latino children at risk for type 2 diabetes. RESEARCH DESIGN AND METHODS: Thirty overweight Latino children with a family history of type 2 diabetes, aged 8-13 years, Tanner stages 1-2, underwent an OGTT. Fasting and 2-h plasma insulin values and OGTT-derived SI indices were compared with SI derived from a frequently sampled intravenous glucose tolerance test (FSIGTT) with minimal model analysis, before and after adjustment for total body fat and lean tissue mass, or BMI. RESULTS: FSIGTT-derived SI for all subjects was 1.62 +/- 0.78 x 10(-4) min (-1) x (microU/ml), with no sex differences. SI correlated (all P values < 0.001) with fasting (r = -0.57) and 2-h (r = -0.58) plasma insulin and all SI indices (r = -0.57 to 0.67). After adjusting for total body fat and lean tissue mass, or BMI, the associations between SI and either fasting insulin or fasting SI indices were no longer significant. However, the 2-h insulin and post-glucose challenge SI indices maintained significant independent associations with SI, even after adjustment for body composition. CONCLUSIONS: In overweight, peripubertal Latino children at risk for type 2 diabetes, the 2-h plasma insulin value and postchallenge SI indices are better independent correlates of SI than fasting values, after accounting for body composition. The 2-h insulin may therefore be superior to fasting insulin as a single blood sample value for clinical or epidemiological estimates of SI, especially when combined with assessment of body composition.

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.

Obesity and risk of type 2 diabetes and cardiovascular disease in children and adolescents.

Overweight/obesity continues to increase in children and adolescents, and annual obesity-related hospital costs in 6-17 yr olds have reached 127 million dollars per year. Overweight children and adolescents are now being diagnosed with impaired glucose tolerance and type 2 diabetes, and they show early signs of the insulin resistance syndrome and cardiovascular risk. Several risk factors have been identified as contributors to the development of type 2 diabetes and cardiovascular risk in youth. These factors include increased body fat and abdominal fat, insulin resistance, ethnicity (with greater risk in African-American, Hispanic, and Native American children), and onset of puberty. There is no clear explanation of how these factors increase risk, but they appear to act in an additive fashion. We hypothesize that the constellation of these risk factors may be especially problematic during the critical period of adolescent development, especially in individuals who may have compromised beta-cell function and an inability to compensate for severe insulin resistance. Therefore, the purpose of this paper is to review the pathophysiology of type 2 diabetes and cardiovascular risk in obese children and adolescents.

Influence of family history of type 2 diabetes on insulin sensitivity in prepubertal children.

The objective of this study was to examine the influence of positive family history (FH) of type 2 diabetes (T2D) on aspects of insulin resistance in prepubertal children. Twenty-one children (Tanner stage I or II) with a positive FH were compared with children with no FH. FH was defined by presence of T2D in a parent or grandparent as assessed by interview. The two groups of children were matched for age, gender, Tanner stage, ethnicity, geographical location, and body fat mass using a pair-matched design. These 21 pairs of children included Caucasian, African American, and Hispanic children who were studied either in Birmingham, Alabama, or Los Angeles, California, using similar techniques. Insulin sensitivity (S(I)) and the acute insulin response to glucose (AIR) were determined by an iv glucose tolerance test and minimal modeling, and body composition was determined by dual-energy x-ray absorptiometry. There were no significant differences in fasting glucose or insulin, S(I), AIR, the disposition index (product of S(I) and AIR), or body composition between children with a FH vs. those without a FH of T2D, and there were no significant differences in these parameters when the data were analyzed separately in each ethnic group. In conclusion, a positive FH for T2D does not seem to have any significant effect on insulin sensitivity, as assessed by the minimal model and associated risk factors for T2D in young children.

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.

Impaired glucose tolerance and reduced beta-cell function in overweight Latino children with a positive family history for type 2 diabetes.

The objective of this study was to examine relationships between impaired glucose tolerance (IGT) and body composition and insulin-related phenotypes in 150 overweight Latino children with a family history of type 2 diabetes. Glucose tolerance was assessed by an oral glucose challenge. Body composition was assessed by dual energy x-ray absorptiometry and magnetic resonance imaging. Insulin sensitivity, the acute insulin response, and the disposition index (DI), as an index of beta-cell function, were determined by an iv glucose tolerance test and compared between normal glucose-tolerant and IGT children. IGT was present in 28% of children, and was similar across obesity groups, but higher in children exposed to gestational diabetes mellitus (41% IGT). There were no significant differences in body composition, fat distribution, insulin sensitivity, or acute insulin response, but DI was significantly lower in IGT children by 16% (P < 0.02), and DI was inversely related to age. In conclusion, IGT is present in 28% of overweight Latino children with a family history of type 2 diabetes, is not influenced by obesity, is more prevalent in children exposed to gestational diabetes mellitus, and is related to poor beta-cell function, which shows signs of deterioration with age in this population.

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.

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.

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.