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Context First-degree relatives of women with polycystic ovary syndrome (PCOS) present hormonal and metabolic alterations compared to girls unrelated to PCOS. It is unknown whether glucose intolerance in the PCOS proband confers a more severe metabolic predisposition on their first-degree relatives. Objective To determine whether glucose tolerance status in women with PCOS is associated with worsened glucose metabolism and sex hormone levels in their peripubertal daughters or sisters. Design Cross-sectional study. Setting Seven academic centers in North America, South America, and Europe. Patients Sixty-four pairs of women with PCOS and their daughters or younger sisters aged between 8 and 14 years were recruited. Twenty-five mothers or older sisters with PCOS were glucose intolerant (GI) and 39 were normal glucose tolerant (NGT). Main Outcome Measures Beta-cell function estimated by the insulin secretion-sensitivity index-2 (ISSI-2) during an oral glucose tolerance test and by the disposition index during a frequently sampled IV glucose tolerance test. Free testosterone and 17-hydroxyprogesterone (17-OHP) levels. Results Being related to a GI PCOS proband was associated with a lower ISSI-2 (P-value = 0.032) after adjusting for ethnicity, body mass index z-score, and pubertal stage. They also had higher free testosterone (P-value = 0.011) and 17-OHP levels compared to girls with an NGT proband, the latter becoming significant after adjusting for confounders (P-value = 0.040). Conclusions Compared to first-degree female relatives of women with PCOS and NGT, first-degree relatives of women with PCOS and GI display lower beta-cell function and hyperandrogenemia, putting them at higher risk of GI and PCOS development.

Objective: To examine the prospective associations between exposure to perfluoroalkyl substances (PFASs) and longitudinal measurements of glucose metabolism in high-risk overweight and obese Hispanic children. Methods: Forty overweight and obese Hispanic children (8–14 years) from urban Los Angeles underwent clinical measures and 2-hour oral glucose tolerance tests (OGTT) at baseline and a follow-up visit (range: 1–3 years after enrollment). Baseline plasma perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonic acid (PFHxS), and the plasma metabolome were measured by liquid-chromatography with high-resolution mass spectrometry. Multiple linear regression models were used to assess the association between baseline PFASs and changes in glucose homeostasis over follow-up. A metabolome-wide association study coupled with pathway enrichment analysis was performed to evaluate metabolic dysregulation associated with plasma PFASs concentrations. We performed a structural integrated analysis aiming to characterize the joint impact of all factors and to identify latent clusters of children with alterations in glucose homeostasis, based on their exposure and metabolomics profile. Results: Each ln (ng/ml) increase in PFOA and PFHxS concentrations was associated with a 30.6 mg/dL (95% CI: 8.8–52.4) and 10.2 mg/dL (95% CI: 2.7–17.7) increase in 2-hour glucose levels, respectively. A ln (ng/ml) increase in PFHxS concentrations was also associated with 17.8 mg/dL increase in the glucose area under the curve (95% CI: 1.5–34.1). Pathway enrichment analysis showed significant alterations of lipids (e.g., glycosphingolipids, linoleic acid, and de novo lipogenesis), and amino acids (e.g., aspartate and asparagine, tyrosine, arginine and proline) in association to PFASs exposure. The integrated analysis identified a cluster of children with increased 2-h glucose levels over follow up, characterized by increased PFAS levels and altered metabolite patterns. Conclusions: This proof-of-concept analysis shows that higher PFAS exposure was associated with dysregulation of several lipid and amino acid pathways and longitudinal alterations in glucose homeostasis in Hispanic youth. Larger studies are needed to confirm these findings and fully elucidate the underlying biological mechanisms. Keywords: Perfluoroalkyl substances, Type 2 diabetes, Glucose metabolism, Metabolomics, Children

Context Studies in rodents and humans suggest that high-fructose corn syrup (HFCS)–sweetened diets promote greater metabolic dysfunction than sucrose-sweetened diets. Objective To compare the effects of consuming sucrose-sweetened beverage (SB), HFCS-SB, or a control beverage sweetened with aspartame on metabolic outcomes in humans. Methods A parallel, double-blinded, NIH-funded study. Experimental procedures were conducted during 3.5 days of inpatient residence with controlled feeding at a research clinic before (baseline) and after a 12-day outpatient intervention period. Seventy-five adults (18-40 years) were assigned to beverage groups matched for sex, body mass index (18-35 kg/m2), and fasting triglyceride, lipoprotein and insulin concentrations. The intervention was 3 servings/day of sucrose- or HFCS-SB providing 25% of energy requirement or aspartame-SB, consumed for 16 days. Main outcome measures were %hepatic lipid, Matsuda insulin sensitivity index (ISI), and Predicted M ISI. Results Sucrose-SB increased %hepatic lipid (absolute change: 0.6 ± 0.2%) compared with aspartame-SB (-0.2 ± 0.2%, P Conclusion Consumption of both sucrose- and HFCS-SB induced detrimental changes in hepatic lipid, insulin sensitivity, and circulating lipids, lipoproteins and uric acid in 2 weeks.

Objective The aim of this study was to determine whether human milk oligosaccharides (HMOs) at 1 month predicted infant weight gain at 6 months and whether associations varied by HMO secretor status. Methods Participants were 157 Hispanic mother-infant pairs. Human milk samples were collected at 1 month. Nineteen individual HMOs were analyzed using high-performance liquid chromatography, and secretor status was determined by the presence of 2'-fucosyllactose or lacto-N-fucopentaose (LNFP) I. Infant weight was measured at 1 and 6 months. Path analysis was used to test effects of HMO composition on infant weight gain, adjusting for maternal age, prepregnancy BMI, and infant age, sex, and birth weight. Results In the total sample, higher LNFPII predicted lower infant weight gain (g1 = -4.1, P = 0.004); this was observed in both nonsecretor (g1 = -3.0, P = 0.006) and secretor groups (g1 = -4.7, P = 0.014). In the nonsecretor group, higher lacto-N-neotetraose (g1 = 7.6, P = 0.011) and disialyllacto-N-tetraose (g1 = 14.3, P = 0.002) predicted higher infant weight gain. There were no other associations in the secretor group. Conclusions Our data suggest that higher LNFPII in human milk may decrease obesity risk across all infants, whereas higher lacto-N-neotetraose and disialyllacto-N-tetraose may increase obesity risk in infants of nonsecretors only.

Objective T-lymphocytes are potential initiators and regulators of adipose tissue (AT) inflammation, but there is limited human data on omental AT. The aim of this study was to assess the relationship between T cells, particularly Foxp3+ regulatory T (Treg) cells, in human subcutaneous (subQ) and omental AT and type 2 diabetes risk. Methods SubQ and deep subQ (DsubQ) abdominal and omental AT biopsies were collected from 44 patients (body mass index, BMI ≥25) undergoing elective abdominal surgery. Flow cytometry was used to quantify CD4+ T cell (T effector and Treg) and macrophages (M1 and M2), and systemic inflammation was measured in fasting blood. Results Tregs were significantly lower in omental versus subQ and DsubQ AT, and M1 cell counts were significantly higher in the omental and DsubQ depot relative to the subQ. Only omental AT Tregs were negatively associated with fasting glucose and MCP-1 and positively associated with homeostasis model assessment (HOMA)-β. M1 and M2 cell counts across multiple depots had significant relationships with HOMA-insulin resistance, tumor necrosis factor-α, insulin, and HOMA-β. All relationships were consistent across ethnicities. Conclusions Tregs were significantly lower in omental versus both subQ adipose depots. Fewer omental Tregs may have metabolic implications based on depot-specific relationships with higher fasting glucose and lower β-cell function.

Objective Circulating cytokines are frequently cited as contributors to insulin resistance in children with obesity. This study examined whether circulating adipocytokines, independent of adiposity, predicted pubertal changes in insulin sensitivity (SI), insulin secretion (AIR), and β-cell function in high-risk adolescents. Methods 158 Hispanic adolescents with overweight or obesity were followed for a median of 4 years. Adipocytokines were measured using Luminex technology. SI, AIR, and the disposition index were derived from an intravenous glucose tolerance test and minimal modeling. Total fat mass was measured by DXA and visceral adipose tissue (VAT) by MRI. Results Surprisingly, mean IL-8, IL-1β, IL-6, and TNF-α decreased between 5% and 6.5% per year from baseline (P

Summary Objective The objective of this study was to examine the relationship between diet and inflammation, and adiposity in minority youth. Design and Methods The study was designed as a cross-sectional analysis of 142 overweight (≥85th body mass index percentile) Hispanic and African–American adolescents (14–18 years) with the following measures: anthropometrics, adiposity via magnetic resonance imaging, dietary intake via 24-h dietary recalls, and inflammation markers from fasting blood draws utilizing a multiplex panel. Partial correlations were estimated and analysis of covariance (ancova) models fit to examine the relationship among dietary variables, inflammation markers and adiposity measures with the following a priori covariates: Tanner stage, ethnicity, sex, total energy intake, total body fat and total lean mass. Results Inference based on ancova models showed that the highest tertile of fibre intake (mean intake of 21.3 ± 6.1 g d−1) vs. the lowest tertile of fibre intake (mean intake of 7.4 ± 1.8 g d−1) was associated with 36% lower plasminogen activator inhibitor-1 (P = 0.02) and 43% lower resistin (P = 0.02), independent of covariates. Similar results were seen for insoluble fibre. No other dietary variables included in this study were associated with inflammation markers. Conclusions These results suggest that increases in dietary fibre could play an important role in lowering inflammation and therefore metabolic disease risk in high-risk minority youth.

Author(s): Alderete, Tanya L; Sattler, Fred R; Richey, Joyce M; Allayee, Hooman; Mittelman, Steven D; Sheng, Xia; Tucci, Jonathan; Gyllenhammer, Lauren E; Grant, Edward G; Goran, Michael I | Abstract: ObjectiveSalsalate treatment has well-known effects on improving glycemia, and the objective of this study was to examine whether the mechanism of this effect was related to changes in adipose tissue.MethodsA randomized double-blind and placebo-controlled trial in obese Hispanics (18-35 years) was conducted. The intervention consisted of 4 g day(-1) of salsalate (n = 11) versus placebo (n = 13) for 4 weeks. Outcome measures included glycemia, adiposity, ectopic fat, and adipose tissue gene expression and inflammation.ResultsIn those receiving salsalate, plasma fasting glucose decreased by 3.4% (P l 0.01), free fatty acids decreased by 42.5% (P = 0.06), and adiponectin increased by 27.7% (P l 0.01). Salsalate increased insulin AUC by 38% (P = 0.01) and HOMA-B by 47.2% (P l 0.01) while estimates of insulin sensitivity/resistance were unaffected. These metabolic improvements occurred without changes in total, abdominal, visceral, or liver fat. Plasma markers of inflammation/immune activation were unchanged following salsalate. Salsalate had no effects on adipose tissue including adipocyte size, presence of crown-like structures, or gene expression of adipokines, immune cell markers, or cytokines downstream of NF-κB with the exception of downregulation of IL-1β (P l 0.01).ConclusionsFindings suggest that metabolic improvements in response to salsalate occurred without alterations in adiposity, ectopic fat, or adipose tissue gene expression and inflammation.

Objective One hour (1-hr) glucose during an oral glucose tolerance test (OGTT) is an emerging biomarker for type 2 diabetes. We compared the predictive power of 1-hr glucose to traditional glycemic markers for prospectively identifying prediabetes in youth. Research design and methods Obese normoglycemic Latino youth (N = 116) were assessed at baseline for glycated hemoglobin (HbA1c), fasting, 1-hr, and 2-hr glucose during an OGTT and were followed for up to 8 yr for the development of prediabetes. Receiver operating characteristic (ROC) curves were used and a multivariable prediction model was developed. Results The area under the 1-hr glucose ROC curve was the most powerful predictor of prediabetes over time [0.73, 95% confidence interval (CI) = 0.64–0.83]. However, combining all indicators into a single model was superior to individual marker models (0.77, 95% CI = 0.690.86). Conclusions These results further support the utility of 1-hr glucose during an OGTT as a prospective marker of diabetes risk in youth.

There are limited data on the influence of vegetable consumption on adiposity and metabolic health, specifically nonstarchy vegetables and vegetables that are dark green and deep orange/yellow (also known as nutrient-rich vegetables). Our study examines the relationship between vegetable intake and adiposity, liver fat, and insulin dynamics in overweight Latino youth. This cross-sectional study of 175 overweight (body mass index ≥85th percentile) Latino youth (aged 8 to 18 years), with data collected during 2006-2011, included the following: dietary intake via multiple 24-hour recalls, total body fat via dual-energy x-ray absorptiometry, adipose tissue distribution and liver fat via magnetic resonance imaging, and insulin dynamics via frequently sampled intravenous glucose tolerance test. Linear regression and analysis of covariance were used for analysis, with the following a priori covariates: age, sex, energy intake, and total body fat. Participants who consumed the most nonstarchy vegetables (mean intake=1.7±1.0 servings/day) compared with the least (mean intake=0.1±0.1 servings/day) had 44% less liver fat (10.0%±8.5% vs 5.6%±8.7%; P =0.01). Nutrient-rich vegetable intake was positively correlated with insulin sensitivity ( r =0.19; P =0.03). Consumers of nutrient-rich vegetables (mean intake=0.3±0.4 servings/day [n=107]), compared with nonconsumers (n=68), had 31% increased insulin sensitivity (1.6±1.6 vs 2.1±1.3×10 –4 /min/μU/mL; P =0.03) and 17% less visceral adipose tissue (2.3±0.9 vs 1.9±0.7 L; P =0.01). Consumption of specific vegetable types by overweight Latino youth is associated with positive metabolic outcomes, including reduced visceral and liver fat and risk factors for type 2 diabetes, even when consumed in small quantities. These may be relevant targets for interventions.

Excessive consumption of added sugars negatively impacts metabolic systems; however, effects on cognitive function are poorly understood. Also unknown is whether negative outcomes associated with consumption of different sugars are exacerbated during critical periods of development (e.g., adolescence). Here we examined the effects of sucrose and high fructose corn syrup-55 (HFCS-55) intake during adolescence or adulthood on cognitive and metabolic outcomes. Adolescent or adult male rats were given 30-day access to chow, water, and either (1) 11% sucrose solution, (2) 11% HFCS-55 solution, or (3) an extra bottle of water (control). In adolescent rats, HFCS-55 intake impaired hippocampal-dependent spatial learning and memory in a Barne's maze, with moderate learning impairment also observed for the sucrose group. The learning and memory impairment is unlikely based on nonspecific behavioral effects as adolescent HFCS-55 consumption did not impact anxiety in the zero maze or performance in a non-spatial response learning task using the same mildly aversive stimuli as the Barne's maze. Protein expression of pro-inflammatory cytokines (interleukin 6, interleukin 1β) was increased in the dorsal hippocampus for the adolescent HFCS-55 group relative to controls with no significant effect in the sucrose group, whereas liver interleukin 1β and plasma insulin levels were elevated for both adolescent-exposed sugar groups. In contrast, intake of HFCS-55 or sucrose in adults did not impact spatial learning, glucose tolerance, anxiety, or neuroinflammatory markers. These data show that consumption of added sugars, particularly HFCS-55, negatively impacts hippocampal function, metabolic outcomes, and neuroinflammation when consumed in excess during the adolescent period of development.

Type 2 diabetes risk and its relationship to free fatty acid (FFA) exposure and visceral fat by prediabetes status in minority adolescents have yet to be explored. Therefore, the objective of this study was to examine the association of circulating FFA under varying conditions with prediabetes in Latino adolescents and to determine the relative relationships of FFA and visceral adiposity to insulin sensitivity, secretion, and β-cell function. Overweight or obese, but otherwise healthy Latino adolescent males and females (n = 164, 14.2 ± 2.5 years), were recruited for assessment of prediabetes, abdominal fat, and FFA levels taken at a fasting state (FFAF), during an OGTT (FFAOGTT), and overnight (FFANOCTURNAL). Prediabetic adolescents had a higher FFAF than those with normal glucose tolerance when controlling for age, sex, pubertal status, total percent body fat, and visceral fat. FFAOGTT and FFANOCTURNAL did not differ between participants with prediabetes and those with normal glucose tolerance after adjusting for covariates. Visceral fat was independently related to insulin sensitivity and secretion in pubertal adolescents; however, in post-pubertal adolescents, FFAF and visceral fat were both independent and negatively related to β-cell function. These results support a plausible progression of the lipotoxicity theory of diabetes development during the pubertal transition.

Objective: Obesity in childhood is associated with an inllammatory state in adipose tissue and liver, which elevates risk lor diabetes and liver disease. No prior study has examined associations between pathologies occurring in adipose tissue and liver to identily elements of tissue damage associated with type 2 diabetes risk, This study sought to determine whether inllammation and librosis in abdominal sub­ cutaneous adipose tissue (SAl) in obese/overweight children (BMI-z 2.3:': 0.76) was related to the extent of observed liver disease or type 2 diabetes risk, Methods: Biopsy samples 01 abdominal (SAl) and liver were simultaneously collected Irom 33 Italian children (mean BMI 28.1 :': 5.1 kg/m 2 and mean age 11.6:': 2.2 years) with confirmed NAFLD. Histology and immunohistochemistry were conducted on biopsies to assess inllammation and flbrosls in adipose tissue and fibrosis and inflammation in liver. Results: Presence vs. absence 01 crown-like structures (CLS) in SAT was signilicantly related to liver librosis scores (1.7:': 0.7 vs. 1.2:': 0.7, P ~ 0.04) independent 01 BMI. SAT librosis was significantly corre­ lated with a lower disposition index (r = -0.48, P = 0.006). No other adipose measures were associated with liver disease parameters. Conclusion: Markers of subcutaneous white adipose tissue inllammation are associated with greater extent 01 liver librosis independent of obesity and SAT fibrosis may contribute to diabetes risk through reduced insulin secretion.

Exposure to man-made combustion products, including secondhand tobacco smoke, maternal smoking during pregnancy, and near-roadway air pollution (NRAP), have been associated with increased body mass index and obesity in children and have been shown to result in excess weight gain in animal models. Potential mechanisms include pro-inflammatory central nervous system effects of airborne particles on appetite control, resulting in increased caloric intake, or changes in basal metabolism due to effects on mitochondria and brown adipose tissue. Combustion-derived polyaromatic hydrocarbons have also been linked to altered lipid metabolism, epigenetic effects on PPARγ expression, particle-induced estrogenic effects, and alterations in the distribution of visceral fat. Emerging evidence that a broad spectrum of environmental chemicals have “obesogenic” properties and alter the metabolic profile of adipose tissue challenges the prevailing model that the childhood obesity epidemic is explained solely by increased caloric density of food and decreased physical activity. Research on environmental obesogens could identify novel targets for intervention and yield public health benefits, since NRAP and SHS exposure are both common in populations most at-risk for development of obesity.

Results: Comparing HC with NF, SI was inversely associated with activation in the anterior cingulate (r 2 = 0.65; P < 0.05), the insula (r 2 = 0.69; P < 0.05), the orbitofrontal cortex (r 2 = 0.74; P < 0.05), and the frontal and rolandic operculum (r 2 = 0.76; P < 0.001). Associations remained significant after adjustment for body mass index. Association of fasting insulin and cerebral activation disappeared after adjustment for waist circumference. Conclusion: In addition to weight loss, insulin sensitivity may pose an important target to regulate neural responses to food cues in the prevention of excessive weight gain.

Objective To investigate the impact of eating frequency on dietary intake, physical activity (PA), metabolic, and adiposity measures in minority youth. Methods This analysis included 185 overweight (≥85th BMI percentile) Hispanic and African-American youth (8-18 years) with the following cross-sectional measures: height, weight, BMI, dietary intake, body composition, metabolic parameters, PA, visceral adipose tissue (VAT), and subcutaneous adipose tissue. Each eating occasion (EO) was defined as ≥50 calories and ≥15 minutes from any previous EO. Participants were dichotomized based on EOs per 24-h into meal skippers

OBJECTIVE Little attention has been paid to possible intrinsic biological mechanisms for the decline in physical activity that occurs during puberty. This longitudinal observational study examined the association between baseline insulin sensitivity (SI) and declines in physical activity and increases in sedentary behavior in peripubertal minority females over a year. RESEARCH DESIGN AND METHODS Participants were Hispanic and African American girls (n = 55; 76% Hispanic; mean age 9.4 years; 36% obese). SI and other insulin indices were measured at baseline using the frequently sampled intravenous glucose tolerance test. Physical activity was measured on a quarterly basis by accelerometry and self-report. RESULTS Physical activity declined by 25% and time spent in sedentary behaviors increased by ∼13% over 1 year. Lower baseline SI predicted the decline in physical activity measured by accelerometry, whereas higher baseline acute insulin response to glucose predicted the decline in physical activity measured by self-report. Time spent in sedentary behavior increased by ~13% over 1 year, and this was predicted by lower baseline SI. All models controlled for adiposity, age, pubertal stage, and ethnicity. CONCLUSIONS When evaluated using a longitudinal design with strong outcome measures, this study suggests that lower baseline SI predicts a greater decline in physical activity in peripubertal minority females.

Objective Cortisol has been associated with preferential visceral adipose tissue (VAT) deposition; however, findings in humans are mixed, which may be clarified when diet is considered. Design and Methods Participants included 165 African-American and Latino, overweight adolescents (BMI% 97.2±3.2%, ages 13-18, 67% Latino, 66% female). Body composition was determined by dual energy X-ray absorptiometry, abdominal fat depots [VAT, subcutaneous (SAT)] by multiple-slice MRI, time-controlled serum sample to measure cortisol, and 2-day multi-pass 24-hour dietary recall. Linear regression analysis examined the cross-sectional relationship between cortisol, and the interaction of diet and cortisol on adiposity measures. Sex, race, age, and total body fat were a priori covariates. Results There was a significant interaction between cortisol and sugar (total and added) in the prediction of VAT (Pinteraction ≤ 0.05). Amongst participants with high total or added-sugar intake, cortisol was significantly associated with VAT (s = 0.031 P

Blunted diurnal cortisol variation has been associated with overt cardiovascular disease in adults. The relationship between the diurnal cortisol variation and subclinical atherosclerosis in youth has yet to be investigated. The objectives of this study were to (1) determine the relationship between overnight cortisol measures and CIMT in overweight and obese, African-American and Latino children; (2) assess ethnic differences in these relationships; and (3) explore whether overnight cortisol and CIMT relationships were independent of inflammatory markers, C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-∝ (TNF-∝).One hundred fifty-six overweight and obese African-American and Latino children (ages 8-17, 86 M/70 F, 55 African-American/101 Latino) underwent measures of CIMT by B-mode ultrasound, nocturnal cortisol rise (NCR = salivary cortisol rise from 2200 h to awakening at 0530 h), cortisol awakening response (CAR = salivary cortisol from time of awakening to 30 min later), fasting serum cortisol and overnight urinary free cortisol.Using linear regression, salivary cortisol(0530 h) and NCR were negatively associated with CIMT (β(standardized) = -0.215 and -0.220, p0.01) independent of age, height, percent body fat, ethnicity and systolic blood pressure. Nocturnal salivary cortisol(2200 h), morning serum cortisol, and overnight urinary free cortisol were not associated with CIMT. Using ANCOVA, participants with LOW NCR (NCR0.44 μg/dL, n = 52) had significantly greater CIMT than those with HIGH NCR (NCR ≥ 0.91 μg/dL, n = 52; 0.632 ± 0.008 vs. 0.603 ± 0.008 mm, p=0.01) after controlling for covariates. Ethnicity was independently associated with CIMT, whereby African-American children had greater CIMT than Latino children (-0.028 ± 0.009, p=0.006). The relationships between cortisol measures and CIMT did not differ between the two ethnic groups (all p(interaction) = 0.28-0.97). CRP, IL-6 and TNF-∝ were not associated with CIMT (p0.05). IL-6 was inversely related to NCR (r = -0.186, p = 0.03), but it did not explain the relationship between NCR and CIMT.Salivary cortisol(0530 h) and NCR, but not CAR, nocturnal salivary cortisol(2200 h), morning serum cortisol or overnight urinary free cortisol were associated with CIMT, independent of relevant covariates, including inflammatory factors. A low awakening salivary cortisol or a blunted NCR may be related to increased atherosclerosis risk in overweight and obese minority youth. These findings support adult studies suggesting flattened daytime diurnal cortisol variation impacts cardiovascular disease risk.

Objective Genetic variation in six genes has been associated with elevated liver fat and nonalcoholic fatty liver disease in adults. The influence of these genes on liver fat and whether a genetic risk score (GRS) would improve upon the ability of common clinical risk factors to predict elevated liver fat content (ELF) in Hispanic children was determined. Design and Methods 223 obese Hispanic children were genotyped for six SNPs. MRI was used to measure liver fat. A GRS was tested for association with ELF using multivariate linear regression. Predictors were assessed via ROC curves and pair-wise analysis was used to determine significance alone and combined with clinical markers. Results Only variants in PNPLA3 and APOC3 genes were associated with liver fat (P

Summary Purpose: Insulin responses to oral and intravenous glucose markedly differ by ethnicity. This study examined whether ethnic differences in pancreatic insulin secretion, hepatic insulin extraction and clearance explain these disparate findings in 35 obese African–American and 41 Latina girls (Tanner Stages: IV–V; ages: 14–18; body mass index percentile: 85.9–99.8%). Methods: Pancreatic insulin secretion, hepatic insulin extraction and clearance were estimated by C-peptide and insulin modeling during an oral glucose tolerance test. Insulin sensitivity (SI), acute insulin response to glucose (AIRG) and disposition index were derived from a frequently sampled intravenous glucose tolerance test. Results: Compared to Latinas, obese African–American adolescents had lower pancreatic insulin secretion (21.3%; P 0.05). Conclusions: Compensatory mechanisms to insulin resistance do not appear to explain the ethnic differences in insulin responses to oral and intravenous glucose in obese African–American and Latina girls.

Obesogens are compounds that disrupt the function and development of adipose tissue or the normal metabolism of lipids, leading to an increased risk of obesity and associated diseases. Evidence for the adverse effects of industrial and agricultural obesogens, such as tributyltin, bisphenol A and other organic pollutants is well-established. Current evidence suggests that high maternal consumption of fat promotes obesity and increased metabolic risk in offspring, but less is known about the effects of other potential nutrient obesogens. Widespread increase in dietary fructose consumption over the past 30 years is associated with chronic metabolic and endocrine disorders and alterations in feeding behaviour that promote obesity. In this Perspectives, we examine the evidence linking high intakes of fructose with altered metabolism and early obesity. We review the evidence suggesting that high fructose exposure during critical periods of development of the fetus, neonate and infant can act as an obesogen by affecting lifelong neuroendocrine function, appetite control, feeding behaviour, adipogenesis, fat distribution and metabolic systems. These changes ultimately favour the long-term development of obesity and associated metabolic risk.

OBJECTIVE In adults, 1-h glucose during an oral glucose tolerance test (OGTT) predicts the development of type 2 diabetes independent of fasting and 2-h glucose concentrations. The purpose of the current investigation was to examine the utility of elevated 1-h glucose levels to prospectively predict deterioration in β-cell function and the development of prediabetes in high-risk youth. RESEARCH DESIGN AND METHODS Obese Latino youth with a family history of type 2 diabetes (133 male and 100 female; age 11.1 ± 1.7 years) completed a baseline OGTT and were divided into two groups based upon a 1-h glucose threshold of 155 mg/dL ( RESULTS Over time, the ≥155 mg/dL group exhibited a significantly greater decline in β-cell function compared with youth with a 1-h glucose CONCLUSIONS These data suggest that a 1-h glucose ≥155 mg/dL during an OGTT is an independent predictor of β-cell deterioration and progression to prediabetes among obese Latino youth.

Evidence suggests that ambient air pollution (AAP) exposure may contribute to the development of obesity and type 2 diabetes. The objective of this study was to determine whether exposure to elevated concentrations of nitrogen dioxide (NO2) and particulate matter with aerodynamic diameter

The 2011 Pennington Biomedical Research Center's Scientific Symposium focused on adiposity in children and adolescents. The symposium was attended by 15 speakers and other invited experts. The specific objectives of the symposium were to (i) integrate the latest published and unpublished findings on the laboratory and clinical assessment of depot-specific adiposity in children and adolescents, (ii) understand the variation in depot-specific adiposity and related health outcomes associated with age, sex, maturation, ethnicity and other factors and (iii) identify opportunities for incorporating new markers of abdominal obesity into clinical practice guidelines for obesity in children and adolescents. This symposium provided an overview of important new advances in the field and identified directions for future research. The long-term goal of the symposium is to aid in the early identification of children and adolescents who are at increased health risk because of obesity and obesity-related conditions.

Summary Objective: We performed this study to examine the metabolic differences arising from higher liver fat accumulation in obese Hispanic adolescents, with a particular focus on circulating levels of adipocytokines and insulin resistance. Methods: Forty-one obese Hispanic adolescents (15.3 1.0 years, body mass index percentile: 97.0 3.9) were assessed for: visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and hepatic fat fraction (HFF) by magnetic resonance imaging; fasting measures of serum glucose, insulin and adipocytokines; homeostasis model assessment of insulin resistance (HOMA-IR); and insulin sensitivity (SI) and the acute insulin response to glucose (AIR) by intravenous glucose tolerance test. Subjects with normal levels of HFF (below 5%; n = 25) were compared to those with HFF > 5% (n = 16). Results: The two groups differing in HFF were similar for total body fat, VAT and SAT. The group with HFF > 5% had significantly (P < 0.05) higher interleukin-8 (IL-8) (6.1 1.6 vs. 3.2 0.4 pg mL -1 ), NGF (30.2 9.9 vs. 13.9 1.6 pg mL -1 ), HOMA-IR (8.8 1.1 vs. 5.5 0.5), AIR (1869 206 vs. 1092 165) and a tendency for lower SI (1.2 0.4 vs. 2.1 0.3; P = 0.06), with no significant differences in any of other factors measured. Conclusions: These data suggest that elevated liver fat is most closely associated with elevated serum IL-8 and NGF levels as well as increased AIR and HOMA-IR. These elevated factors may play significant roles in the metabolic abnormalities associated with elevated liver fat in obese Hispanics.

OBJECTIVE To examine in obese young adults the influence of ethnicity and subcutaneous adipose tissue (SAT) inflammation on hepatic fat fraction (HFF), visceral adipose tissue (VAT) deposition, insulin sensitivity (SI), β-cell function, and SAT gene expression. RESEARCH DESIGN AND METHODS SAT biopsies were obtained from 36 obese young adults (20 Hispanics, 16 African Americans) to measure crown-like structures (CLS), reflecting SAT inflammation. SAT, VAT, and HFF were measured by magnetic resonance imaging, and SI and β-cell function (disposition index [DI]) were measured by intravenous glucose tolerance test. SAT gene expression was assessed using Illumina microarrays. RESULTS Participants with CLS in SAT (n = 16) were similar to those without CLS in terms of ethnicity, sex, and total body fat. Individuals with CLS had greater VAT (3.7 ± 1.3 vs. 2.6 ± 1.6 L; P = 0.04), HFF (9.9 ± 7.3 vs. 5.8 ± 4.4%; P = 0.03), tumor necrosis factor-α (20.8 ± 4.8 vs. 16.2 ± 5.8 pg/mL; P = 0.01), fasting insulin (20.9 ± 10.6 vs. 9.7 ± 6.6 mU/mL; P < 0.001) and glucose (94.4 ± 9.3 vs. 86.8 ± 5.3 mg/dL; P = 0.005), and lower DI (1,559 ± 984 vs. 2,024 ± 829 ×10−4 min−1; P = 0.03). Individuals with CLS in SAT exhibited upregulation of matrix metalloproteinase-9 and monocyte antigen CD14 genes, as well as several other genes belonging to the nuclear factor-κB (NF-κB) stress pathway. CONCLUSIONS Adipose tissue inflammation was equally distributed between sexes and ethnicities. It was associated with partitioning of fat toward VAT and the liver and altered β-cell function, independent of total adiposity. Several genes belonging to the NF-κB stress pathway were upregulated, suggesting stimulation of proinflammatory mediators.

The purpose of this study was to examine interrelationships between insulin-like growth factor 1 (IGF-1), IGF binding proteins (IGFBPs), and adiposity in 49 African-American and 77 Latino obese adolescents (15.3 ± 0.1 and 15.4 ± 0.2 years; BMI: 33.0 ± 0.7 and 35.0 ± 1.0 kg/m(2), respectively). Immunoradiometric assays were used to measure IGF-1, IGFBP-1, and IGFBP-3. Total fat and soft lean tissue were measured by dual-energy X-ray absorptiometry and visceral adipose tissue (VAT), subcutaneous abdominal adipose tissue (SAAT), and hepatic fat fraction (HFF) were measured by magnetic resonance imaging. IGF-1 levels were 23.1% higher and IGFBP-1 were 40.4% higher in African Americans compared to Latinos after adjustment for total lean and total fat mass. IGF-1 and IGFBP-1 were inversely correlated with BMI, total fat mass, VAT, and HFF (r = -0.20 to -0.33, P < 0.05) while IGFBP-1 was inversely correlated with SAAT (r = -0.22, P < 0.05). These relationships did not differ by ethnicity, however, the relationship between IGF-1 and SAAT, as well as IGFBP-1 and HFF, differed by ethnicity. Predicted mean IGF-1 levels were 30.7% higher for African Americans at the 75th compared to 25th percentile of SAAT and only 11.7% higher for Latinos. Predicted mean IGFBP-1 levels were 158% higher for African Americans at the 25th compared to the 75th percentile of HFF while IGFBP-1 levels were 1.7% higher for Latinos at the 75th compared to the 25th percentile. These results demonstrate that the relationship between IGF-1 and SAAT as well as IGFBP-1 and HFF are different in African-American and Latino adolescents and may contribute to the higher IGF-1 levels in African-Americans.

The consumption of fructose, largely in the form of high fructose corn syrup (HFCS), has risen over the past several decades and is thought to contribute negatively to metabolic health. However, the fructose content of foods and beverages produced with HFCS is not disclosed and estimates of fructose content are based on the common assumption that the HFCS used contains 55% fructose. The objective of this study was to conduct an objective laboratory analysis of the sugar content and composition in popular sugar-sweetened beverages with a particular focus on fructose content. Twenty-three sugar-sweetened beverages along with four standard solutions were analyzed for sugar profiles using high-performance liquid chromatography (HPLC) in an independent, certified laboratory. Total sugar content was calculated as well as percent fructose in the beverages that use HFCS as the sole source of fructose. Results showed that the total sugar content of the beverages ranged from 85 to 128% of what was listed on the food label. The mean fructose content in the HFCS used was 59% (range 47-65%) and several major brands appear to be produced with HFCS that is 65% fructose. Finally, the sugar profile analyses detected forms of sugar that were inconsistent with what was listed on the food labels. This analysis revealed significant deviations in sugar amount and composition relative to disclosures from producers. In addition, the tendency for use of HFCS that is higher in fructose could be contributing to higher fructose consumption than would otherwise be assumed.

OBJECTIVE Visceral adipose tissue (VAT) and hepatic fat are associated with insulin resistance and vary by sex and ethnicity. Recently, pancreatic fat fraction (PFF) has also been linked with increasing obesity. Our aim was to assess ethnic and sex differences in PFF and its relationship to other fat depots, circulating free fatty acids (FFA), insulin secretion and sensitivity, and inflammation in obese adolescents and young adults. RESEARCH DESIGN AND METHODS We examined 138 (40 males, 98 females) obese Hispanics and African Americans (13–25 years). Subcutaneous adipose tissue and VAT volumes, hepatic fat fraction (HFF), and PFF were determined by magnetic resonance imaging. Insulin sensitivity and β-cell function were assessed during an intravenous glucose tolerance test. RESULTS Hispanics had higher PFF than African Americans (7.3 ± 3.8 vs. 6.2 ± 2.6%, P = 0.03); this ethnic difference was higher in young adults compared with children and adolescents (ethnicity × age: P = 0.01). Males had higher PFF than females (P < 0.0001). PFF was positively correlated with VAT (r = 0.45, P < 0.0001), HFF (r = 0.29, P < 0.0001), and FFA (r = 0.32, P = 0.001). PFF positively correlated with inflammatory markers but lost significance when adjusted for VAT. In multiple stepwise regression analysis, VAT and FFA were the best predictors of PFF (adjusted R2 = 0.40). There were no significant correlations between PFF and markers of insulin sensitivity or β-cell function. CONCLUSIONS PFF is higher in Hispanics than African Americans, and this difference increases with age. In young obese individuals, PFF is related to VAT, HFF, and circulating FFA, thus possibly contributing to their increased risk for type 2 diabetes and related metabolic disorders.

Background: Recently, a genetic variant (rs738409; C/G) of the PNPLA3 gene was identified to be associated with increased hepatic fat deposition, and the effect was more pronounced in Hispanics. Animal models have also shown that PNPLA3 expression can be regulated by dietary carbohydrate. Objective: The aim of this study was to examine whether the influence of PNPLA3 genotype on hepatic fat is modulated by dietary factors in Hispanic children. Design: PNPLA3 was genotyped in 153 Hispanic children (75% female, ages 8‐18 y) by using the TaqMan method. Dietary intake was assessed by using three 24-h dietary recalls or diet records. Visceral adipose tissue (VAT), subcutaneous abdominal adipose tissue (SAAT), and hepatic fat fraction (HFF) were assessed in multiple abdominal slices by magnetic resonance imaging. Analysis of covariance was used to assess the diet · genotype interaction in liver fat, with the following a priori covariates: sex, age, energy, VAT, and SAAT. Results: HFF was influenced by a significant interaction between genotype and diet (genotype · carbohydrate, P = 0.04; genotype · total sugar, P = 0.01). HFF was positively related to carbohydrate (r = 0.31, P = 0.04) and total sugar (r = 0.34, P = 0.02) intakes but only in the GG group, independent of covariates. Dietary variables were not related to HFF in the CC or CG group or to other fat depots in all genotype groups. Conclusions: These findings suggest that Hispanic children carrying the GG genotype are susceptible to increased hepatic fat when dietary carbohydrate intake, specifically sugar, is high. Specific dietary interventions based on genetic predisposition in this population may lead to more effective therapeutic outcomes for fatty liver.

Context and Objective: The purpose of the present study was to investigate the cross-sectional and longitudinal associations of serum morning cortisol and aspects of insulin action in Latino children and adolescents (8–13 yr) at risk for type 2 diabetes. Design and Participants: The present study includes a cross-sectional analysis in 211 participants and a longitudinal analysis in a subset of 143 participants. Results: At baseline, cortisol was negatively associated with fasting glucose (r = 0.23; P < 0.01), β-cell function (disposition index, r = −0.24; P < 0.05), and acute insulin response to glucose (r = −0.27; P < 0.05). Baseline cortisol was also significantly related to the change in insulin sensitivity over 1 yr (r = −0.23; P < 0.05). These results did not differ by Tanner stage or sex. Conclusions: Cortisol contributes to the reduction in insulin sensitivity at an early age in Latino children and adolescents. Specifically, cortisol is negatively associated with potential compensatory mechanisms for insulin resistance, such as increased β-cell function and increased insulin release to a glucose challenge, by exacerbating the progression toward insulin resistance in this population. The results underline the relevance of glucocorticoid reduction for the prevention of metabolic disease in Latino children and adolescents.

OBJECTIVE A genome-wide study of adults identified a variant of PNPLA3 (rs738409) associated with ∼twofold higher liver fat. The purpose of this study was to examine the influence of PNPLA3 genotype on liver fat and other related metabolic outcomes in obese Hispanic children and adolescents. RESEARCH DESIGN AND METHODS Three hundred and twenty-seven Hispanics aged 8–18 years were genotyped for rs738409. One hundred and eighty-eight subjects had measures of visceral (VAT) and subcutaneous (SAT) adipose tissue volume and hepatic (HFF) and pancreatic (PFF) fat fraction by magnetic resonance imaging. One hundred and thirty-nine subjects did not have HFF measures but had extensive measures of insulin sensitivity and fasting lipids. RESULTS Liver fat in GG subjects was 1.7 and 2.4 times higher than GC and CC (11.1 ± 0.8% in GG vs. 6.6 ± 0.7% in GC and 4.7 ± 0.9% in CC; P < 0.0001), and this effect was observed even in the youngest children (8–10 years of age). The variant was not associated with VAT, SAT, PFF, or insulin sensitivity or other glucose/insulin indexes. However, Hispanic children carrying the GG genotype had significantly lower HDL cholesterol (40.9 ± 10.9 in CC vs. 37.0 ± 8.3 in CG vs. 35.7 ± 7.4 in GG; P = 0.03) and a tendency toward lower free fatty acid levels (P = 0.06). CONCLUSIONS These results provide new evidence that the effect of the PNPLA3 variant is apparent in Hispanic children and adolescents, is unique to fat deposition in liver as compared with other ectopic depots examined, and is associated with lower HDL cholesterol.

To investigate the feasibility of using IDEAL (Iterative Decomposition with Echo Asymmetry and Least squares estimation) fat-water imaging and the resultant fat fraction metric in detecting brown adipose tissue (BAT) in mice, and in differentiating BAT from white adipose tissue (WAT).Excised WAT and BAT samples and whole-mice carcasses were imaged with a rapid three-dimensional fat-water IDEAL-SPGR sequence on a 3 Tesla scanner using a single-channel wrist coil. An isotropic voxel size of 0.6 mm was used. Excised samples were also scanned with single-voxel proton spectroscopy. Fat fraction images from IDEAL were reconstructed online using research software, and regions of WAT and BAT were quantified.A broad fat fraction range for BAT was observed (40-80%), in comparison to a tighter and higher WAT range of 90-93%, in both excised tissue samples and in situ. Using the fat fraction metric, the interscapular BAT depot in each carcass could be clearly identified, as well as peri-renal and inguinal depots that exhibited a mixed BAT and WAT phenotype appearance.Due to BAT's multi-locular fat distribution and extensive mitochondrial, cytoplasm, and vascular supply, its fat content is significantly less than that of WAT. We have demonstrated that the fat fraction metric from IDEAL-MRI is a sensitive and quantitative approach to noninvasively characterize BAT.

BACKGROUND: To date, no studies have assessed the longitudinal changes of dietary intake on metabolic risk factors in Latino youth. OBJECTIVE: We assessed the relation between changes in dietary intake, specifically sugar and fiber intakes, with changes in adiposity and risk factors for type 2 diabetes in a longitudinal analysis of overweight Latino youth. DESIGN: Overweight Latino youth (n = 85; aged 11-17 y) underwent the following measures over 2 y [mean (+/-SD) time difference was 1.5 +/- 0.5 y]: dietary intake by 2-d diet recalls, body composition by dual-energy X-ray absorptiometry and magnetic resonance imaging, and glucose and insulin indexes by oral- and intravenous-glucose-tolerance tests. Partial correlations and repeated-measures analysis of covariance assessed the relation between changes in dietary intake with changes in adiposity and glucose and insulin indexes, independent of the following a priori covariates: sex, Tanner stage, time between visits, and baseline dietary and metabolic variables of interest. RESULTS: Increases in total dietary fiber (g/1000 kcal) and insoluble fiber (g/1000 kcal) were associated with decreases in visceral adipose tissue (VAT) (r = -0.29, P = 0.02, and r = -0.27, P = 0.03, for total dietary and insoluble fiber, respectively), independent of baseline covariates and change in subcutaneous abdominal adipose tissue. Participants who had decreased total dietary fiber (mean decrease of 3 g . 1000 kcal(-1) x d(-1)) had significant increases in VAT compared with participants who had increased total dietary fiber (21% compared with -4%; P = 0.02). No other changes in dietary variables were related to changes in adiposity or metabolic variables. CONCLUSION: Small reductions in dietary fiber intake over 1-2 y can have profound effects on increasing visceral adiposity in a high-risk Latino youth population.

a b s t r a c t Objective:The objective of this study was to examine the influence of persistence of the metabolic syn- drome (Mets) and its individual components over a 3-year period on carotid intima media thickness (CIMT) in overweight Latino children. Methods:Ninety-seven healthy male and female overweight Latino children (mean age at baseline: 11.0±1.8 years) were assessed for MetS on four annual evaluations and classified according to the persis- tence of MetS: NEVER (0 annual visits with the MetS,n=53), INTERMITTENT (1 or 2 visits with the MetS, n=28), and PERSISTENT (3 or 4 visits with the MetS,n=16). CIMT was measured with high-resolution B-mode ultrasound (7.9±0.7 months after the most recent MetS assessment; mean age: 14.6±1.8 years). Results:PERSISTENT MetS was associated with significantly higher CIMT (0.647±0.018mm compared to 0.600±0.007mm in those who NEVER had MetS,p

Aims While the disposition index provides a useful measure of B-cell function, its calculation requires the performance of a frequently sampled intravenous glucose tolerance test (FSIVGTT). Recently, the demonstration of a hyperbolic relationship between indices of insulin secretion and insulin sensitivity derived from the oral glucose tolerance test (OGTT) has led to the introduction of two novel OGTT-based measures of B-cell function analogous to the disposition index: (i) the insulin secretion-sensitivity index-2 (ISSI-2) (defined as the ratio of the area-under-the-insulin-curve to the area-under-the-glucose curve, multiplied by the Matsuda index) and (ii) insulinogenic index (IGI)/fasting insulin. However, neither of these two measures has been directly compared with the disposition index. Methods Two hundred and thirteen non-diabetic children (122 boys, 91 girls) underwent both OGTT and FSIVGTT, allowing for the calculation of ISSI-2, IGI/fasting insulin and the disposition index. Results ISS1-2 and IGI/fasting insulin were strongly correlated with each other (r = 0.82, P < 0.0001). Both measures correlated with the disposition index, with ISSI-2 showing a modestly stronger association (ISSI-2: r = 0.24, P = 0.0003; IGI/fasting insulin: r = 0.21, P = 0.0022). Standardized linear regression analyses confirmed that the relationship between log ISSI-2 and the disposition index (standardized regression coefficient = 0.224, P = 0.001) was stronger than that between log IGI/fasting insulin and the disposition index (standardized regression coefficient = 0.166, P = 0.015). Conclusions The OGTT-derived measures ISSI-2 and IGI/fasting insulin exhibit modest correlations with the disposition index. These relationships require further assessment in other patient populations.

The pubertal transition has been identified as a time of risk for development of type 2 diabetes, particularly among vulnerable groups, such as African Americans (AAs). Documented ethnic differences in insulin secretory dynamics may predispose overweight AA adolescents to risk for type 2 diabetes. The objectives of this longitudinal study were to quantify insulin secretion and clearance in a cohort of 90 AA and European American (EA) children over the pubertal transition and to explore the association of genetic factors and adiposity with repeated measures of insulin secretion and clearance during this critical period. Insulin sensitivity was determined by intravenous glucose tolerance test (IVGTT) and minimal modeling; insulin secretion and clearance by C-peptide modeling; genetic ancestry by admixture analysis. Mixed-model longitudinal analysis indicated that African genetic admixture (AfADM) was independently and positively associated with first-phase insulin secretion within the entire group (P < 0.001), and among lean children (P < 0.01). When examined within pubertal stage, this relationship became significant at Tanner stage 3. Total body fat was a significant determinant of first-phase insulin secretion overall and among obese children (P < 0.001). Total body fat, but not AfADM, was associated with insulin clearance (P < 0.001). In conclusion, genetic factors, as reflected in AfADM, may explain greater first-phase insulin secretion among peripubertal AA vs. EA; however, the influence of genetic factors is superseded by adiposity. The pubertal transition may affect the development of the β-cell response to glucose in a manner that differs with ethnic/genetic background.

Acute effects of high-sugar/low-fiber meals vs low-sugar/high-fiber meals on hormones and behavior were studied in 10 overweight Latina females, age 11 to 12 years, using a crossover design. In this exploratory pilot study, participants arrived fasted at an observation laboratory on two occasions and randomly received either a high-sugar/low-fiber meal or a low-sugar/high-fiber meal at each visit. Glucose, insulin, and leptin were assayed from serum drawn at 0, 15, 30, 60, 90, and 120 minutes. Ad libitum snacks were provided at 120 minutes. Physical activity was measured using an observational system that provides data on time spent lying down, sitting, standing, walking, and in vigorous activity. Data were collected between March 2005 and July 2006. In the high-sugar/low-fiber condition, glucose and leptin levels decreased more slowly, glucose levels were higher at 60 minutes (111.2 mg/dL vs 95.4 mg/dL, P=0.03), and leptin levels were higher at 90 minutes (49.3 ng/mL vs 46.7 ng/mL, P=0.017) than in the low-sugar/high-fiber condition. Meals did not affect insulin or ad libitum dietary intake. Sitting, standing, lying down, and vigorous activity differed by condition, but not walking. Participants were significantly more active in the first 30 to 60 minutes after the high-sugar/low-fiber meal, but after 60 minutes there was a trend for activity to be lower after the high-sugar/low-fiber meal vs the low-sugar/high-fiber meal. High-sugar meals sustain glucose and leptin levels longer, which may play an important role in modulating levels of physical activity in this group at high risk for obesity-related disease.

Obesity is a well-known risk factor for multiple chronic diseases, including diabetes, heart disease, fatty liver disease, and some forms of cancer. !e mechanisms of these relationships are unclear and may be speci"c for each disease. !e most likely explanations of why increased body fat causes multiple health problems include the mediating roles of hyperinsulinemia and insulin resistance, body fat distribution, including ectopic fat deposition in peripheral tissues, and in#amma tory mediators. Prior work in this area suggests that there are distinct ethnic di$erences in these obesity-related phenotypes that are evident early in life, and may help explain ethnic di$er ences in the incidence and prevalence of obesity-related disease outcomes. !e purpose of this article is to sum marize these di$erences speci"cally in Hispanics and African Americans. !e focus on these two ethnic groups is based on (i) they are the two largest ethnic minority groups in the United States and (ii) they share a similar propensity for obesity and insulin resistance, but markedly di$erent pro"les for obesity-related disease outcome, creating an informative comparative contrast. !ese comparisons yield two di$erent pro"les that could represent di$erent pathways to obesity-related diseases.

OBJECTIVE—To examine changes in risk factors in overweight and obese Hispanic children at high risk of developing type 2 diabetes. RESEARCH DESIGN AND METHODS—We recruited 128 overweight/obese Hispanic children with a family history of type 2 diabetes primarily from clinics in East Los Angeles. Children were evaluated annually for 4 years with an oral glucose tolerance test, applying American Diabetes Association criteria to define diabetes and pre-diabetes. Insulin sensitivity (Si), acute insulin response (AIR) to glucose, and β-cell function (BCF) were determined from frequently sampled intravenous glucose tolerance tests, and total body fat by dual-energy X-ray absorptiometry and intra-abdominal and subcutaneous abdominal adipose tissue (IAAT and SAAT) by magnetic resonance imaging were assessed in years 1, 2, and 4. RESULTS—No subjects developed type 2 diabetes, 40% never had pre-diabetes, 47% had intermittent pre-diabetes with no clear pattern over time, and 13% had persistent pre-diabetes. At baseline, those with persistent pre-diabetes had lower BCF and higher IAAT. In repeated measures, Si deteriorated regardless of pre-diabetes, and there was a significant effect of pre-diabetes on AIR (42% lower in pre-diabetes; P = 0.01) and disposition index (34% lower in pre-diabetes; P = 0.021) and a significant interaction of pre-diabetes and time on IAAT (greater increase over time in those with pre-diabetes; P = 0.034). CONCLUSIONS—In this group of Hispanic children at high risk of type 2 diabetes, 1) pre-diabetes is highly variable from year to year; 2) the prevalence of persistent pre-diabetes over 3 years is 13%; and 3) children with persistent pre-diabetes have lower BCF, due to a lower AIR, and increasing visceral fat over time.

Aims To investigate the importance of a maternal and paternal family history of Type 2 diabetes and their combined association with plasma leptin and adiponectin levels in overweight Latino children with a family history of Type 2 diabetes (T2DM). Methods This cross-sectional study investigated the combined association of a maternal and paternal family history of T2DM with leptin and adiponectin in 175 overweight Latino children (age 11.1 ± 1.7 years). All subjects had a family history of T2DM. Plasma adiponectin and leptin levels, body fat measured by dual-energy X-ray absorptiometry, Tanner stage, age and insulin sensitivity were assessed. Results After adjustment for age, gestational diabetes, insulin sensitivity and body fat, a combined maternal and paternal family history of T2DM was associated with higher leptin concentrations ( P = 0.004) compared with a maternal or paternal family history alone. This association was most pronounced at Tanner stage 1 ( P for interaction family history × tanner stage = 0.022). The presence of a combined maternal and paternal family history of T2DM accounted for 4% ( P = 0.003) of the variation in leptin concentrations. No such combined association was observed for adiponectin levels. Conclusions Maternal and paternal family history of T2DM may have an additive impact on leptin, but not on adiponectin levels independent of adiposity and insulin sensitivity in overweight Latino children. This may contribute to a further clinically relevant deterioration of metabolic health in this population.

Little is known about the relationship between diet and metabolic health in Latino children, a population at increased risk for diabetes. The present study evaluates diet composition and the metabolic syndrome in a cross-sectional sample of 109 overweight Latino children aged 10 to 17 years with a family history of type 2 diabetes. Dietary intake was assessed by two 24-hour recalls. Associations between nutrients and features of the metabolic syndrome were examined using multiple linear regression and analysis of covariance. Log cholesterol intake was positively associated with log systolic blood pressure (β=0.034, P =0.017) and log soluble dietary fiber intake was inversely associated with log waist circumference (β=−0.069, P =0.036). Log soluble fiber intake was significantly higher in participants with 0 features compared to those with 3+ features of the metabolic syndrome ( P =0.046), which translates to 5.2 g vs 4.1 g soluble fiber daily. No other significant associations were found between dietary variables and either the individual features of the metabolic syndrome or the clustering of metabolic syndrome components. Increases in soluble fiber through the daily consumption of fruits, vegetables, and beans may improve metabolic health in Latino children.

We have previously shown that cardiorespiratory fitness predicts increasing fat mass during growth in white and African-American youth, but limited data are available examining this issue in Hispanic youth. Study participants were 160 (53% boys) overweight (BMI>or=85th percentile for age and gender) Hispanic children (mean+/-s.d. age at baseline=11.2+/-1.7 years). Cardiorespiratory fitness, assessed by VO2max, was measured through a maximal effort treadmill test at baseline. Body composition through dual-energy X-ray absorptiometry and Tanner stage through clinical exam were measured at baseline and annually thereafter for up to 4 years. Linear mixed models were used to examine the gender-specific relationship between VO2max and increases in adiposity (change in fat mass independent of change in lean tissue mass) over 4 years. The analysis was adjusted for changes in Tanner stage, age, and lean tissue mass. In boys, higher VO2max at baseline was inversely associated with the rate of increase in adiposity (beta=-0.001, P=0.03); this effect translates to a 15% higher VO2max at baseline resulting in a 1.38 kg lower fat mass gain over 4 years. However, VO2max was not significantly associated with changes in fat mass in girls (beta=0.0002, P=0.31). In overweight Hispanic boys, greater cardiorespiratory fitness at baseline was protective against increasing adiposity. In girls however initial cardiorespiratory fitness was not significantly associated with longitudinal changes in adiposity. These results suggest that cardiorespiratory fitness may be an important determinant of changes in adiposity in overweight Hispanic boys but not in girls.

Background: Few studies have examined the relation between dietary carbohydrate quality, adiposity, and insulin dynamics in children. Objective: The objective of the study was to determine which aspects of dietary carbohydrate, specifically dietary sugar, fiber, glycemic index, or glycemic load, are associated with adiposity and insulin dynamics in overweight Latino children. Design: We examined 120 overweight Latino children (10‐17 y old) with a family history of type 2 diabetes. Dietary intake was determinedbyrepeated24-hdietrecalls.Adipositywasassessedby usingtotal-bodydual-energyX-rayabsorptiometry.Insulindynamics [insulin sensitivity (SI), acute insulin response, and disposition index (an index of ! -cell function)] were measured by using a frequently sampled intravenous-glucose-tolerance test. Results: After adjustment for covariates, total sugar (g/d) was positively correlated with body mass index (BMI; in kg/m 2 ), BMI z scores, and total fat mass (r ! 0.20, r ! 0.22, and r ! 21, respectively; P " 0.05) and negatively correlated with SI and disposition index (r ! # 0.29 and r ! # 0.24, respectively; P " 0.05). Dietary fiber, glycemic index, and glycemic load were not significantly correlatedwithadiposityorinsulindynamicsbeforeoraftercontrol for covariates. Regression analyses showed that total sugar intake explained an additional 3.4%, 4.6%, and 2.4% of the variance in BMI,BMIzscores,andtotalfatmass,respectively,andanadditional 5.6%and4.8%ofthevarianceinSIanddispositionindex(P" 0.05), respectively, after control for covariates. Conclusion: In this cohort, total sugar intake, rather than glycemic index or glycemic load, was associated with higher adiposity measures, lower SI, and lower measures of insulin secretion. Am J Clin Nutr 2007;86:1331‐8.

OBJECTIVE— The purpose of this article was to examine metabolic risk factors for type 2 diabetes in children and adolescents as a function of maternal versus paternal family history of type 2 diabetes and to examine whether differences in these risk factors emerge during adolescent growth. RESEARCH DESIGN AND METHODS— A total of 247 overweight Latino children (baseline age = 11.1 ± 1.7 years) with a parental history of type 2 diabetes were followed annually for 5 years (2.2 ± 1.2 observations/child) with measures of insulin sensitivity, acute insulin response to glucose, and disposition index. Longitudinal linear mixed-effects modeling was used to evaluate the influence of maternal versus paternal family history of type 2 diabetes on changes in diabetes risk factors over age. RESULTS— Insulin sensitivity and the disposition index decreased over age (β = −0.052 and β = −0.033, P < 0 0.01). Acute insulin response to glucose and fasting and 2-h glucose increased (β = 0.019, β = 0.002, and β = 0.003, P < 0.01). Declines in insulin sensitivity were significantly greater in participants whose maternal grandmothers had a history of type 2 diabetes (β = −0.03, P = 0.03). Declines in the disposition index (β = −0.02, P = 0.04) and increases in fasting glucose were significantly influenced by a maternal history of type 2 diabetes (β = 0.60, P < 0.05). CONCLUSIONS— Maternal but not paternal family history for diabetes may have a significant impact on insulin dynamics, becoming more pronounced during growth in overweight Latino adolescents. Further research is clearly warranted.