Lp(a)-cholesterol is associated with HDL-cholesterol in overweight and obese African American children and is not an independent risk factor for CVD.

BACKGROUND: The role of lipoprotein (a) cholesterol {Lp(a)-C}as an additional and/or independent risk factor for cardiovascular disease (CVD) is not clear. We evaluated the associations between Lp(a)-C and other CVD risk factors including plasma lipoprotein concentrations and body fatness in overweight and obese African American children. METHODS: A cross-sectional analysis was carried out using data from a sample of 121 African American children aged 9-11 years with body mass index (BMI)'s greater than the 85th percentile. Body height, weight and waist circumference (WC) were measured. Fasting plasma concentrations of Lp(a)-C, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), very low density lipoprotein cholesterol (VLDL-C), intermediate density lipoprotein cholesterol (IDL-C), low density lipoprotein cholesterol (LDL-C), and triacylglycerides (TAG) were analyzed using the vertical auto profile (VAP) cholesterol method. RESULTS: After adjusting for child age, gender, and pubertal status, Lp(a)-C was positively associated with both HDL-C and TC, and negatively associated with VLDL-C and TAG. Including BMIz and WC as additional covariates did not alter the direction of the relationships between Lp(a)-C and the other lipoproteins. Finally, after adjusting for the other plasma lipoproteins, Lp(a)-C remained strongly associated with HDL-C, whereas the associations of Lp(a)-C with the other lipoproteins were not significant when HDL-C was simultaneously included in the regression models. CONCLUSIONS: Lp(a)-C was positively associated with HDL-C and this association is not influenced by other lipoprotein subclasses or by the degree of obesity. We conclude that Lp(a) cholesterol is not an independent risk factor for CVD in African American children.

Identifying metabolic syndrome in African American children using fasting HOMA-IR in place of glucose.

INTRODUCTION: Metabolic syndrome (MetS) is increasing among young people. We compared the use of homeostasis model assessment of insulin resistance (HOMA-IR) with the use of fasting blood glucose to identify MetS in African American children. METHODS: We performed a cross-sectional analysis of data from a sample of 105 children (45 boys, 60 girls) aged 9 to 13 years with body mass indexes at or above the 85th percentile for age and sex. Waist circumference, blood pressure, and fasting levels of blood glucose, insulin, triglycerides, and high-density lipoprotein cholesterol were measured. RESULTS: We found that HOMA-IR is a stronger indicator of MetS in children than blood glucose. Using HOMA-IR as 1 of the 5 components, we found a 38% prevalence of MetS in this sample of African American children and the proportion of false negatives decreased from 94% with blood glucose alone to 13% with HOMA-IR. The prevalence of MetS was higher in obese than overweight children and higher among girls than boys. CONCLUSION: Using HOMA-IR was preferred to fasting blood glucose because insulin resistance was more significantly interrelated with the other 4 MetS components.

Insulin resistance is improved in overweight African American boys but not in girls following a one-year multidisciplinary community intervention program.

AIM: To assess potential for effectiveness, in a non-randomized pilot study, of a community-based lifestyle intervention program to reduce the risk for type 2 diabetes mellitus in overweight African American (AA) children. RESEARCH DESIGN: Sample of 165 9-11 year-old AA children with body mass index (BMI) >85th percentile were recruited from local recreational sites, schools and churches. Participants self-selected to attend one of two study sites, blinded to the specifics of the intervention administered at each site. The intervention group received a programmatically focused 2-week summer camp with once-a-week community-based exercise, nutrition, and behavioral modification sessions, and their families were invited to monthly nutrition educational sessions. Control group participants received a 2-week conventional YMCA summer camp and their families received nutrition and physical activity education material through the mail. Baseline assessment and 1-year follow-up were conducted in collaboration with the YMCA of the East Bay and Children's Hospital Oakland, CA, with 109 participants (66%) having pre/post data. RESULTS: After one-year of intervention, treatment boys showed a drop in homeostasis model assessment of insulin-resistance (HOMA-IR) (-0.58 vs +0.17; p = 0.003), fasting glucose (Gf, mg/dL) (mean change: -2.9 vs +0.4; p = 0.126) and fasting insulin (If, microU/mL) (-2.2 vs +0.7; p = 0.009) compared to control boys, after accounting for baseline differences and pubertal stage of the child. Treatment girls had similar changes to the control girls in HOMA-IR (-0.02 vs -0.17; p = 0.66), Gr (-0.3 vs +1.4; p = 0.29) and If (+0.03 vs +0.17; p = 0.57). CONCLUSION: After one year, this community-based intervention program effectively improved insulin resistance and thus reduced risk for type 2 diabetes mellitus in overweight AA boys but did not change the risk in girls compared to control children.

Accuracy of self-assessed Tanner staging against hormonal assessment of sexual maturation in overweight African-American children.

AIM: To evaluate the accuracy of self-reported Tanner (SRT) staging against a proxy method of physician's assessment of sexual maturation, using pubertal hormones in overweight African-American (AA) children. METHODS: Cross-sectional data from 196 children (113 girls, 83 boys) aged 9-11 years, who were 'overweight' (>85th and <95th percentile for age- and gender-matched BMI; n = 43) or 'obese' (>95th percentile; n = 153) were used. Children assessed their breast or genital and pubic hair development using standardized Tanner drawings representing different stages of sexual maturity. SRT data were compared to pubertal stage assessed by measuring fasting serum concentrations of luteinizing hormone (LH) in boys, and LH and estradiol (E2) in girls, which were used to stage children into pubertal stages 1-5. RESULTS: SRT stages of genital and pubic hair assessments in boys, and breast and pubic hair assessments in girls, yielded 15-20% concordance (kappa statistic = 0.02-0.12) compared to their hormone-derived pubertal stages. CONCLUSIONS: Among overweight AA 9-11 year-old children, self-assessment of Tanner staging did not accurately assess their pubertal development when compared to a hormone-derived pubertal assessment method.

Influence of body dissatisfaction on 1-year change in nutrient intake of overweight and obese inner-city African American children.

This analysis aimed to examine the relationship of baseline body dissatisfaction with 1-year change in nutrient intake of inner-city, overweight and obese, African American children. This is a secondary analysis of 1-year pre-post data available for a convenience sample of 88 children. After adjusting for baseline intake of dietary variables and intervention group status, baseline body dissatisfaction was associated with 1-year increases in intake of energy, and all macronutrients in girls, but not in boys. These relationships were not substantially altered after adjusting for baseline BMIz and global self-worth. After including all adjustment factors, increasing baseline body dissatisfaction in girls was associated with 1-year increased intake of total energy, total sugars, total fat, discretionary fat, and total carbohydrates. This analysis suggests that, in girls but not necessarily in boys, body dissatisfaction might need to be targeted during interventions that aim to improve nutrient intake.

Diet induced obesity increases the risk of colonic tumorigenesis in mice.

A large body of epidemiological data indicates that obesity increases the risk of colon cancer in humans. There are limited studies using rodent models where the relationship between obesity and colon cancer has been studied. In this study, wild-type diet-induced obese (DIO) mice and lean wild-type controls were used to investigate the influence of obesity on the risk of colon cancer. We hypothesized that the obese phenotype would exhibit increased colonic tumorigenesis. Colon cancer was chemically induced by injecting the mice with azoxymethane (AOM) at levels that we experimentally determined to result in equivalent AOM concentrations in circulating blood. Risk of colon cancer was assessed via microscopic examination of entire colons for aberrant crypts, aberrant crypt foci and proliferation levels. The DIO mice were found to have significantly more aberrant crypts and aberrant crypt foci as well as increased proliferation of colonocytes per mouse compared to wild-type control mice, supporting the epidemiological data that obesity increases the risk of colonic tumorigenesis.

Risk of colonic cancer is not higher in the obese Lep(ob) mouse model compared to lean littermates.

Epidemiological data suggest that obesity increases the risk of colorectal cancer in humans. Given that diet-induced obesity mouse models verified the epidemiological data, the present study aimed to determine whether obese C57BL/6J-Lep(ob) male mice (a different obesity in vivo model) were at greater risk of colonic cancer than their lean male littermates. Risk of colonic tumorigenesis was assessed by numbers of aberrant crypts, aberrant crypt foci and colonic tumors. Proliferation of the colonic epithelia was assessed histochemically following administration of BrdU. Availability of the procarcinogen, azoxymethane (AOM) to target tissues was assessed by quantifying via HPLC plasma AOM concentrations during the 60 min period following AOM injection. When obese and lean mice were injected with azoxymethane (AOM) at doses calculated to provide equivalent AOM levels per kg lean body mass, obese animals had significantly fewer aberrant crypts/colon and fewer aberrant crypt foci/colon than the lean animals. Tumors were identified in the colonic mucosa of lean (4 tumors in 14 mice) but not obese (0 tumors in 15 mice) mice. Colonic cell proliferation was not significantly different for obese and lean mice. Because these results were unexpected, plasma AOM concentrations were measured and were found to be lower in the obese than lean mice. When plasma AOM levels were comparable for the lean and obese mice, the Lep(ob) mice continued to have significantly fewer aberrant crypt foci/colon than the lean mice, but differences were not statistically different for aberrant crypts/colon. Interestingly, obese Lep(ob) mice did not exhibit increased risk of colonic cancer as expected. Instead, Lep(ob) mice exhibited equivalent or lower risk of colon cancer when compared to the lean group. These results taken together with in vivo results from diet-induced obesity studies, imply that leptin may be responsible for the increased risk of colon cancer associated with obesity.

Use of HbA(1C) testing to diagnose pre-diabetes in high risk African American children: a comparison with fasting glucose and HOMA-IR.

OBJECTIVE: This study aimed to compare the discriminating power of HbA(1C) with other pre-diabetes diagnostic tests specifically in high-risk African American children. RESEARCH DESIGN AND METHODS: A cross-sectional analysis was performed on a sample of 172 children (70 boys and 102 girls) aged 9-11 years with BMI's above the 85th percentile. Fasting glucose, insulin and HbA(1C) were analyzed from the plasma samples. RESULTS: Of the 172 participants included in this analysis, 21 (12.2%) had HbA(1C) concentrations above the cutoff of 5.7 used to identify pre-diabetes. None (0%) of these 21 participants, however, were observed to have a glucose concentration above the pre-diabetes cutoff of 110 mg/dl, and only 13 of 21 participants had HOMA-IR above the pre-diabetes cutoff of 2.5. When compared to the previously identified glucose cutoff of 110 mg/dl and HOMA-IR cutoff of 2.5 for pre-diabetes, HbA(1C) showed high specificity (88 and 93%, respectively) but very low sensitivity (0 and 21%, respectively). Glucose, insulin and HOMA-IR were significantly interrelated, but HbA(1C) was not significantly correlated with these biochemical prediabetes assessment variables, nor with anthropometric (BMIz, WC) risk factors. CONCLUSION: Our results suggest that HbA(1C) had poor discrimination power to identify prediabetes in overweight and obese 9- to 11-year-old African American children. Future studies are recommended to compare the feasibility, sensitivity and predictive power of different screening tests currently recommended to avoid inadequacy when screening for prediabetes and diabetes.

One-year change in energy and macronutrient intakes of overweight and obese inner-city African American children: effect of community-based Taking Action Together type 2 diabetes prevention program.

Taking Action Together (TAT) was a controlled community-based intervention protocol developed to reduce risk of T2DM among low-income, high BMI, 9-10 year old African American children. A secondary hypothesis of this study was that there would be greater improvements in the treatment group in dietary intakes and physical activity. To evaluate the primary study objectives, multiple linear regression models were employed, with 1 year change in dietary variables as dependent variables. Intervention group status was the independent variable of interest and BMIz was included as a covariate in all analyses to adjust for group differences in baseline obesity status of the children. The findings from this analysis suggest that 1 year change in dietary intakes in boys was associated with group intervention status, with boys in the treatment group reducing their intakes of energy and fat to a significantly greater extent than boys in the control group. Differences in energy intakes were not significant, however, for girls. Based on the differences in gender response to our comprehensive TAT intervention, we conclude that interventions designed for and delivered only to African American girls might be more successful than those delivered in mixed gender settings.

Dietary intakes of urban, high body mass index, African American children: family and child dietary attributes predict child intakes.

OBJECTIVE: To identify family and child nutrition and dietary attributes related to children's dietary intakes. DESIGN: African American children (ages 8-11 years, n = 156), body mass index > 85th percentile, from urban, low-income neighborhoods. Baseline, cross-sectional data collected as part of an ongoing diabetes prevention intervention. Dietary intakes were collected by 3-day food diary to assess total energy, percent fat, discretionary fat, added sugar, whole grains, vegetables, fruit, meat, and dairy. Questionnaires on nutrition and dietary attributes administered to children and parents were used to develop 5 diet-related indices: child knowledge, child preferences, child snack habits, child beverage habits, and family food habits. RESULTS: A higher child nutrition knowledge score was significantly related to a lower starchy vegetable intake. Higher scores on the child snack habits index were significantly related to higher intakes of fruit, total fruits and vegetables, total fruits and nonstarchy vegetables, and to lower intakes of added sugars. A higher score on the family food habits index was significantly related to lower intakes of total energy and discretionary fat. CONCLUSIONS AND IMPLICATIONS: Targeting both child and family food and nutrition attributes may be used to promote more healthful eating among urban, low-income, overweight African American children.

Insulin resistance and self-perceived scholastic competence in inner-city, overweight and obese, African American children.

PURPOSE: scholastic competence is a predictor of future achievement, yet there is little research about health factors that influence the development of self-perceived scholastic competence (SPSC). This study examined the relationship of insulin resistance and body fatness with SPSC in low-income, overweight and obese, African American children. METHODS: data were analyzed from a convenience sample of 9-10years old African American children (89 boys and 113 girls) enrolled in a type 2 diabetes prevention study. Health variables analyzed for their influence on SPSC (Harter scale) included insulin resistance (Homeostatic model-derived insulin sensitivity, HOMA-IR) and body fatness (% body fat). Adjustments were made for self-esteem (Global Self Worth). RESULTS: there was a significant gender by insulin resistance interaction effect on the child's SPSC, so separate regression models were developed for each gender. In boys, neither insulin resistance nor body fatness was related to SPSC. In girls, however, insulin resistance was negatively related to SPSC scores, and the significance of the relationship increased further after adjusting for body fatness. Body fatness alone was not significantly related to SPSC in girls, but after adjusting for insulin resistance, body fatness was positively related to SPSC. Thus, insulin resistance and body fatness mutually suppressed SPSC in girls. CONCLUSION: high SPSC was associated with lower insulin resistance and, with insulin resistance held constant, with higher body fatness in girls but not in boys. These relationships were not influenced by self-esteem in these children.

Accelerometer response to physical activity intensity in normal-weight versus overweight African American children.

BACKGROUND: Different movement efficiency in overweight children may affect accelerometer output data. The purpose was to investigate the ability of accelerometers to assess physical activity intensity and number of steps in normal-weight compared with overweight children. METHODS: Eleven normal-weight and 14 overweight African American children walked at 2, 4, 5, and 6 km/h on a treadmill wearing Lifecorder, ActiGraph, RT3, and Biotrainer. Oxygen uptake was measured and steps manually counted. Fat free mass (FFM) was assessed from bioelectrical impedance analysis. Accelerometer counts and the individual linear regression lines of accelerometer counts versus VO(2)/FFM were evaluated, together with steps recorded by Lifecorder and Actigraph. RESULTS: Correlations between accelerometer counts and VO(2)/FFM for all monitors were r ≥ .95 (P < .01). The accelerometer counts and their relationship to VO(2)/FFM did not generally differ significantly by body weight status. Lifecorder and Actigraph underestimated steps at 4, 5, and 6 km/h by less than 9%, but the error was up to -95% at 2 km/h. CONCLUSIONS: All 4 accelerometers show high ability to assess physical activity intensity, and can be used to compare physical activity between normal-weight and overweight children. The Lifecorder and the ActiGraph showed high accuracy in assessing steps, providing speed of movement exceeded 2 km/h.

Relationship of insulin resistance to psychobehavioral characteristics of overweight and obese African American children.

OBJECTIVES: The objective of this study was to evaluate the relationships of insulin resistance to positive as well as negative dimensions of the child's emotions, behavior and personality (hereafter referred to as "psychobehavioral characteristics") in a convenience sample of inner-city, overweight and obese, African American children. METHODS: A secondary analysis was performed on a sample of 127 children ages 9-12 yr old who were participating in a community-based, Type 2 diabetes prevention program. Psychobehavioral characteristics of children were assessed using both child and parent ratings derived from the Behavioral Assessment for Children, 2nd edition (BASC-2). Body fatness was evaluated using anthropometric techniques, and insulin resistance (HOMA-IR) was calculated from fasting glucose and insulin concentrations. Hierarchical multiple linear regression models were employed with BASC scales as dependent variables and HOMA-IR as the independent variable of interest. RESULTS: After adjusting for child age, pubertal stage, gender, family socioeconomic index, and intervention group assignment, child HOMA-IR was related at p<0.05 to less favorable scores for parent-report of behavioral symptoms and externalizing problems composites, and to content scales for bullying and negative emotionality. Additionally, child HOMA-IR was related at p<0.01 to less favorable scores for child-report inattention/hyperactivity composite. Body fatness suppressed the unfavorable relationship between HOMA-IR and these and other psychobehavioral characteristics as the degree of significance was higher following adjustment for body fatness in this cohort. CONCLUSION: More than one psychobehavioral characteristic were associated with body fatness and insulin resistance in the overweight children of this study. Whether the associations are due to several, or only one, of these psychobehavioral characteristics could not be determined. A much larger and future study will be needed to determine which, if any, of these psychobehavioral characteristics are independently associated with insulin resistance in overweight children.

Accuracy of multisensor activity monitors in normal versus high BMI African American children.

BACKGROUND: Overweight children show different movement patterns during walking than normal-weight children, suggesting the accuracy of multisensory activity monitors may differ in these groups. METHODS: Eleven normal and 15 high BMI African American children walked at 2, 4, 5, and 6 km/h on a treadmill wearing the Intelligent Device for Energy Expenditure and Activity (IDEEA) and SenseWear (SW). Accuracy was determined using indirect calorimetry and manually counted steps as references. RESULTS: For IDEEA, no significant differences in accuracy were observed between BMI groups for energy expenditure (EE), but differences were significant by speed (+15% at 2 km/h to -10% at 6 km/h). For SW, EE accuracy was significantly different for high (+21%) versus normal BMI girls (-13%) at 2 km/h. For high BMI girls, EE was overestimated at low speed and underestimated at higher speeds. Underestimations in steps did not differ by BMI group at 4 to 6 km/h, but were significantly larger at 2 km/h than at the other speeds for all groups with IDEEA, and for normal BMI children with SW. CONCLUSIONS: Similar accuracies during walking may be expected in normal and overweight children using IDEEA and SW. Both monitors showed small errors for steps provided speed exceeded 2 km/h.

Carbohydrate intake and cardiometabolic risk factors in high BMI African American children.

The aim of this study was to evaluate the relationship between intakes of subgroups of energy-providing carbohydrate, and markers of cardiometabolic risk factors in high BMI African American (AA) children.A cross sectional analysis was performed on data from a sample of 9-11 year old children (n = 95) with BMI greater than the 85th percentile. Fasting hematological and biochemical values for selected markers of cardiometabolic risk factors were related to intakes of carbohydrates and sugars.After adjusting for gender, pubertal stage and waist circumference, multivariate regression analysis showed that higher intakes of carbohydrate (with fat and protein held constant) were associated with higher plasma concentrations of triglycerides (TG), VLDL-C, IDL-C, and worse insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR). After dividing carbohydrate into non-sugar versus sugar fractions, sugars were significantly related to higher TG, VLDL-C, IDL-C, lower adipocyte fatty acid insulin sensitivity (ISI-FFA), and was closely associated with increased HOMA-IR. Similar trends were observed for sugars classified as added sugars, and for sugars included in beverages. Further dividing sugar according to the food group from which it was consumed showed that consuming more sugar from the candy/soda food group was highly significantly associated with increased TG, VLDL-C, IDL-C and closely associated with increased HOMA-IR. Sugars consumed in all fruit-containing foods were significantly associated with lower ISI-FFA. Sugars consumed as fruit beverages was significantly associated with VLDL-C, IDL-C and ISI-FFA whereas sugars consumed as fresh, dried and preserved fruits did not show significant associations with these markers.Sugars consumed from in all dairy foods were significantly associated with higher TG, VLDL-C and IDL-C, and with significantly lower HDL-C and ISI-FFA. These effects were associated with sugars consumed in sweetened dairy products, but not with sugars consumed in unsweetened dairy products. This analysis suggests that increases in carbohydrate energy, especially in the form of sugar, may be detrimental to cardiometabolic health in high BMI children.

Taking Action Together: a YMCA-based protocol to prevent type-2 diabetes in high-BMI inner-city African American children.

BACKGROUND: Associated with a tripling in obesity since 1970, type 2 diabetes mellitus (T2DM) in children has risen 9-10 fold. There is a critical need of protocols for trials to prevent T2DM in children. METHODS/DESIGN: This protocol includes the theory, development, evaluation components and lessons learned from a novel YMCA-based T2DM prevention intervention designed specifically for high-BMI African American children from disadvantaged, inner-city neighborhoods of Oakland, California. The intervention was developed on the basis of: review of epidemiological and intervention studies of pediatric T2DM; a conceptual theory (social cognitive); a comprehensive examination of health promotion curricula designed for children; consultation with research, clinical experts and practitioners and; input from community partners. The intervention, Taking Action Together, included culturally sensitive and age-appropriate programming on: healthy eating; increasing physical activity and, improving self esteem. DISCUSSION: Evaluations completed to date suggest that Taking Action Together may be an effective intervention, and results warrant an expanded evaluation effort. This protocol could be used in other community settings to reduce the risk of children developing T2DM and related health consequences. TRIAL REGISTRATION: ClinicalTrials.gov NCT01039116.

Macronutrient intakes and cardio metabolic risk factors in high BMI African American children.

BACKGROUND: The aim of this study was to evaluate the relationship between intakes of energy-providing macronutrients, and markers of cardio metabolic risk factors in high BMI African American (AA) children. METHODS: A cross sectional analysis of a sample of 9-11 year old children (n = 80) with BMI greater then the 85th percentile. Fasting hematological and biochemical measurements, and blood pressure were measured as selected markers of cardio metabolic risk factors and their relationships to dietary intakes determined. RESULTS: After adjusting for gender, pubertal stage and waist circumference (WC), multivariate regression analysis showed that higher total energy intakes (when unadjusted for source of energy) were associated with higher plasma concentrations of intermediate density lipoprotein cholesterol (IDL-C) and very low density lipoprotein cholesterol (VLDL-C). Higher intakes of carbohydrate energy (fat and protein held constant) were associated with higher IDL-C, VLDL-C, triglycerides (TG) and homeostasis model assessment of insulin resistance (HOMA-IR). Higher intakes of fat (carbohydrate and protein held constant), however, were associated with lower IDL-C; and higher protein intakes (fat and carbohydrate held constant) were associated with lower HOMA-IR. CONCLUSION: The specific macronutrients that contribute energy are significantly associated with a wide range of cardio metabolic risk factors in high BMI AA children. Increases in carbohydrate energy were associated with undesirable effects including increases in several classes of plasma lipids and HOMA-IR. Increases in protein energy were associated with the desirable effect of reduced HOMA-IR, and fat energy intakes were associated with the desirable effect of reduced IDL-C. This analysis suggests that the effect of increased energy on risk of developing cardio metabolic risk factors is influenced by the source of that energy.

Baseline correlates of insulin resistance in inner city high-BMI African-American children.

To characterize the influence of diet-, physical activity-, and self-esteem-related factors on insulin resistance in 8- 10-year-old African-American (AA) children with BMI greater than the 85th percentile who were screened to participate in a community-based type 2 diabetes mellitus (T2DM) prevention trial. In 165 subjects, fasting glucose- and insulin-derived values for homeostasis model assessment of insulin resistance (HOMA-IR) assessed insulin resistance. Body fatness was calculated following bioelectrical impedance analysis, and fitness was measured using laps from a 20-m shuttle run. Child questionnaires assessed physical activity, dietary habits, and self-esteem. Pubertal staging was assessed using serum levels of sex hormones. Parent questionnaires assessed family demographics, family health, and family food and physical activity habits. Girls had significantly higher percent body fat but similar anthropometric measures compared with boys, whereas boys spent more time in high-intensity activities than girls. Scores for self-perceived behavior were higher for girls than for boys; and girls desired a more slender body. Girls had significantly higher insulin resistance (HOMA-IR), compared with boys (P < 0.01). Adjusting for age, sex, pubertal stage, socioeconomic index (SE index), and family history of diabetes, multivariate regression analysis showed that children with higher waist circumference (WC) (P < 0.001) and lower Harter's scholastic competence (SC) scale (P = 0.044) had higher insulin resistance. WC and selected self-esteem parameters predicted insulin resistance in high-BMI AA children. The risk of T2DM may be reduced in these children by targeting these factors.

Acetate and butyrate are the major substrates for de novo lipogenesis in rat colonic epithelial cells.

The objective of these experiments was to investigate the source of substrates used for lipid synthesis and the pathways of substrate incorporation into lipids by epithelial cells of the colon. Within replicates, cells were exposed to all treatments evaluated in that experiment. By comparing the relative incorporation rates of several 14C-labeled substrates into lipids, acetate made a significantly larger carbon contribution to lipids than propionate, butyrate, glucose or glutamine under the in vitro conditions utilized in this study. Other major carbon contributors were butyrate and 3-hydroxybutyrate. Glucose, glutamine and propionate made only minor contributions. (-)-Hydroxycitrate did not affect the incorporation of acetate or butyrate carbon into lipids, even though it inhibited colonic ATP-citrate lyase. These data suggest that SCFA carbon used in the synthesis of lipids by colonocytes is not likely transported to the cytosol as citrate. Competition experiments suggest that ketone bodies and butyrate contribute to a single precursor pool for lipogenesis. Ketone bodies did not significantly suppress acetate incorporation into lipid, however. Incorporation of 3H2O and 14C-acetate was significantly greater into phospholipids than into free fatty acids and triacylglycerides, suggesting that the major role of lipogenesis is for membrane synthesis. In conclusion, colonocytes appear to synthesize lipids using a pathway distinct from the liver by incorporating mainly SCFA and ketone bodies into lipids, and by using citrate to a limited extent, if at all, to transport acetyl units from the mitochondria to the cytosol.

Acetylation of histones associated with the p21WAF1/CIP1 gene by butyrate is not sufficient for p21WAF1/CIP1 gene transcription in human colorectal adenocarcinoma cells.

Butyric acid is well recognized as a histone deacetylase (HDAC) inhibitor, and changes in histone acetylation are thought to alter gene expression. The mechanism by which sodium butyrate (NaB) induces p21WAF1/CIP1, a critical gene involved in the antiproliferative effect of NaB, was studied at the chromatin level. Using chromatin immunoprecipitation (ChIP) assay, acetylation of histone H3 was observed at the proximal region of the promoter within 30 min of NaB exposure and this extended to the distal region within 2 hr. By contrast, histone H4 was acetylated both at the proximal and the distal regions of the promoter within 30 min. NaB did not influence other histone modifications. NaB stimulated recruitment of the transcription factors ZBP89 and Sp1 as well as GCN5, but did not influence recruitment of Sp3, HDAC1, p300, or CBP. As recruitment of HDAC1 to the promoter appeared not to account for NaB-induced changes in histone acetylation, we aimed to influence HDAC activity by altering its phosphorylation status. The kinase inhibitor, H7, suppressed p21WAF1/CIP1 mRNA in both the absence and the presence of NaB without influencing the butyrate-induced hyperacetylation of H3 and H4 associated with the p21WAF1/CIP1 promoter. These results suggest that acetylation of histones at the p21WAF1/CIP1 promoter is not sufficient for NaB to exert antiproliferative effects via transcription of the p21WAF1/CIP1 gene. Induction of p21WAF1/CIP1 transcription by the phosphatase inhibitor, okadaic acid, in the absence of changes in association of acetylated histones with the p21WAF1/CIP1 promoter provides further evidence of the importance of phosphorylation to p21WAF1/CIP1 transcription.