Gene expression profiling and association of circulating lactoferrin level with obesity-related phenotypes in Latino youth.

BACKGROUND/OBJECTIVES: Low-grade inflammation is an underlying feature of obesity and identifying inflammatory markers is crucial to understanding this disease. Therefore, the purpose of this study was twofold: (i) to perform a global microarray analysis and (ii) to investigate the role of lactoferrin (LTF), one of the most altered genes, in relation to obesity in Latino youth. METHODS: Non-diabetic Latino youth (71 males/92 females; 15.6 ± 3.2 years) were studied. A subset of 39 participants was randomly selected for global microarray analysis profiling from the whole blood sample. Serum LTF was compared between lean (n = 78) and overweight/obese (n = 85) participants. RESULTS: Microarray analysis revealed that a total of 1870 probes were altered in expression ≥1.2-fold and P < 0.05 in overweight/obese participants compared with lean. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis revealed significant enrichment for pathways including toll-like receptor (TLR) and B cell receptor signalling pathways. LTF and TLR5 were increased in expression by 2.2 and 1.5 fold, respectively, in the overweight/obese participants. Increased LTF concentrations were significantly associated with high risk of obesity-related phenotypes (all P < 0.05). CONCLUSIONS: Our data suggest that increased LTF is associated with obesity risk among Latino youth. This finding is discordant to what has been shown in adults and suggests that age may modulate the association between LTF and obesity-related health.

Effects of a diabetes prevention programme on weight-specific quality of life in Latino youth.

OBJECTIVE: To examine the effects of a diabetes prevention programme on weight-specific Quality of Life (QOL) in obese Latino youth. METHODS: Fifteen obese Latino adolescents (body mass index % = 96.4 ± 1.2; age = 15.0 ± 1.0) completed a 12-week culturally grounded, community-based intervention designed to improve physical and psychosocial health. Weight-specific QOL was assessed by the Youth Quality of Life-Weight module and compared with age, sex and ethnicity-matched lean youth. RESULTS: At baseline, intervention youth exhibited significantly lower weight-specific QOL compared with lean youth (70.8 ± 5.4 vs. 91.2 ± 2.2, P = 0.002). However, following the intervention, total weight-specific QOL increased by 21.8% among obese youth (70.8 ± 5.4 to 86.2 ± 4.3, P < 0.001) and was no longer different from lean controls. Significant increases in weight-specific QOL were noted across all subdomains including self (45.7%), social (11.9%) and environmental (36.2%) despite the fact that weight did not change (90.6 ± 6.8 to 89.9 ± 7.2, P = 0.44). The improvements in QOL were maintained for up to 12 months after the intervention. CONCLUSION: Weight-specific QOL among obese Latino youth can be improved through lifestyle interventions to a level similar to lean peers. Further, weight loss may not be necessary to observe improvements in QOL.

Lifestyle intervention improves lipoprotein particle size and distribution without weight loss in obese Latino adolescents.

Childhood obesity is associated with a pro-atherogenic phenotype contributing to increased cardiovascular disease (CVD) risk. This single-arm pilot study examined the effects of a lifestyle intervention on lipoprotein particle size and cholesterol distribution in obese Latino adolescents. Fifteen obese Latino adolescents (15.0 ± 1.0 years) completed a 12-week nutrition education and exercise intervention. Low-density lipoprotein (LDL) particle size and distribution of cholesterol in lipoprotein subclasses were determined via polyacrylamide gel electrophoresis. The intervention resulted in increases in mean LDL particle size (269.3 ± 3.4 to 271.6 ± 2.9 Å, P = 0.0003) and cholesterol in large high-density lipoprotein (HDL) subfractions (22.4 ± 11.2 to 26.8 ± 10.6% area, P = 0.007) along with decreases of cholesterol in small LDL (1.6 ± 2.0 to 0.6 ± 1.2% area, P < 0.01) and HDL subfractions (23.2 ± 9.4 to 19.0 ± 6.7% area, P = 0.05). These improvements were observed independent of changes in weight (90.7 ± 26.2 to 89.9 ± 27.8 kg, P > 0.05) and suggest that lifestyle modification in obese youth may reduce cardiovascular risk by shifting lipoprotein particle size and cholesterol distribution to a less atherogenic phenotype.

Adiponectin and leptin are independently associated with insulin sensitivity, but not with insulin secretion or beta-cell function in overweight Hispanic adolescents.

The aim of the study was to investigate the independent effects of leptin and adiponectin on insulin sensitivity as well as insulin secretion and beta-cell function in overweight Hispanic adolescents. Despite pubertal changes in hormone secretion, studies investigating the independent effect of both hormones on insulin sensitivity and beta-cell function in adolescents are lacking. In a cross-sectional study, 175 overweight Hispanic adolescent boys (n=101) and girls (n=74) with a family history of diabetes were recruited and insulin sensitivity (SI), acute insulin response to glucose (AIR), disposition index (DI), body composition, total serum adiponectin, and leptin were assessed. Over age, leptin significantly increased in girls but not in boys (p for age x gender interaction=0.005) while adiponectin was similar in boys and girls. Leptin was not correlated to adiponectin. Leptin (partial r=-0.180; p=0.019) and adiponectin (partial r=0.230; p=0.003) predicted SI independent of age, gender, body fat, lean body mass, and Tanner stage but together, they explained 5% of the unique variation in SI (p for R (2)-change<0.001). Leptin or adiponectin were not related to AIR or DI. With regard to SI, AIR, and DI, no significant gender, age, or Tanner stage interactions were observed suggesting similar effects of adiponectin and leptin among gender, age, and Tanner stages. Leptin and adiponectin were independently associated with SI, but not with insulin secretion or beta-cell function.

Combined association of maternal and paternal family history of diabetes with plasma leptin and adiponectin in overweight Hispanic children.

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 x 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.

Leptin-to-adiponectin ratio as independent predictor of insulin sensitivity during growth in overweight Hispanic youth.

Because leptin and adiponectin are counter-regulated in vivo and exert opposing effects on glucose metabolism, fat oxidation and insulin sensitivity, the ratio of leptin-to-adiponectin has been investigated as a potential atherogenic index, suggesting that the index is a better biomarker for atherosclerotic risk in obese Type 2 diabetic patients than either leptin or adiponectin alone. However, no information is available regarding the leptin-to-adiponectin ratio during adolescence in Hispanic adolescents. Therefore, the present study was designed to investigate the leptin-to-adiponectin ratio during growth and to establish whether the leptin-to-adiponectin ratio is a better predictor for insulin sensitivity compared to leptin and adiponectin alone in a regression model. From the age of 8 to 14, the leptin-to-adiponectin ratio increased from 2.0+/-0.8 to 5.8+/-2.2 in girls, with no significant change noted in boys (gender x age interaction p=0.007). In a multiple regression analysis, including both adiponectin and leptin as independent variables, leptin and adiponectin explained 5% of the variation in insulin sensitivity independent of gender, age, Tanner stage, total fat mass and lean body mass (p for R2-change <0.001). The leptin-to-adiponectin ratio also explained 5% of the variation in insulin sensitivity, after controlling for the same covariates (p for R2-change <0.001). These data indicate that the leptin-to-adiponectin ratio is not a better predictor of insulin sensitivity during growth than the additive effects of leptin and adiponectin levels.

Cardiovascular fitness and physical activity in children with and without impaired glucose tolerance.

OBJECTIVE: To examine differences in cardiovascular fitness (VO(2max)) and physical activity levels in overweight Hispanic children with normal glucose tolerance (NGT) vs impaired glucose tolerance (IGT). PARTICIPANTS: A total of 173 overweight (BMI percentile 97.0 +/- 3.1) Hispanic children ages 8-13 years with a family history of type 2 diabetes. METHODS: VO(2max) was measured via a maximal effort treadmill test and open circuit spirometry. Physical activity was determined by questionnaire. Glucose tolerance was established by a 2-h oral glucose challenge (1.75 g of glucose/kg body weight). IGT was defined from an oral glucose tolerance test as a 2-h plasma glucose level > or =140 and <200 mg/dl. RESULTS: IGT was detected in 46 of the 173 participants (approximately 27%); no cases of type 2 diabetes were identified. No significant differences were found between youth with NGT and those with IGT in absolute VO(2max) (2.2 +/- 0.6 vs 2.1 +/- 0.5 l/min), VO(2max) adjusted for gender, age, and body composition (2.2 +/- 0.2 vs 2.1 +/- 0.2 l/min), or recreational physical activity levels (8.7 +/- 8.2 vs 6.9 +/- 6.2 h/week). CONCLUSION: Overweight Hispanic youth with IGT exhibit similar levels of VO(2max) and physical activity compared to their NGT counterparts. Longitudinal analyses are necessary to determine whether fitness/activity measures contribute significantly to diabetes risk over time in this group.

Insulin sensitivity, insulin secretion and beta-cell function during puberty in overweight Hispanic children with a family history of type 2 diabetes.

OBJECTIVE: To examine cross-sectional differences in insulin sensitivity, insulin secretion and beta-cell function during puberty in overweight Hispanic boys and girls with a family history of type 2 diabetes. STUDY DESIGN AND PARTICIPANTS: This cross-sectional, observational study included 214 8-13-y-old Hispanic children with a BMI percentile > or = 85th percentile and family history of type 2 diabetes. METHODS AND ANALYSES: Participants underwent a physical examination, body composition measures, oral glucose tolerance test (OGTT), and frequently-sampled intravenous glucose tolerance test. Unadjusted and adjusted general linear models (GLM) tested whether insulin/glucose dynamics differed by Tanner stage and gender. RESULTS: Unadjusted group comparisons showed that fasting insulin increased whereas insulin sensitivity (SI) and the disposition index (DI) (a measure of pancreatic beta-cell function) decreased across Tanner stage groups (all P < 0.05). No differences in the acute insulin response to glucose (AIRg), fasting glucose or 2-h glucose were found. After adjusting for covariates, there was no independent effect of Tanner stage on SI (P = 0.9) or AIRg (P = 0.2), but DI was slightly lower in later Tanner stages suggesting decreased beta-cell function in the more mature groups (P = 0.10). CONCLUSIONS: Overweight Hispanic children with a family history of type 2 diabetes may represent a unique population given that pubertal insulin resistance was not evident once analyses controlled for body composition. Longitudinal analyses are required to determine whether the slightly diminished beta-cell function in later Tanner stages plays a role in the development of type 2 diabetes.

Pediatric obesity and insulin resistance: chronic disease risk and implications for treatment and prevention beyond body weight modification.

The study of childhood obesity has continued to grow exponentially in the past decade. This has been driven in part by the increasing prevalence of this problem and the widespread potential effects of increased obesity in childhood on lifelong chronic disease risk. The focus of this review is on recent findings regarding the link between obesity and disease risk during childhood and adolescence. We describe recent reports relating to type 2 diabetes in youth (2), prediabetes (69, 166), metabolic syndrome (33, 35), polycystic ovarian syndrome (77), and nonalcoholic fatty liver disease (58, 146), and the mediating role of insulin resistance in these conditions. In addition, we review the implications of this research for the design of more effective treatment and prevention strategies that focus more on the improvement of obesity-related metabolic abnormalities and chronic disease risk reduction than on the conventional energy balance approach that focuses on weight management.