Sex-associated differences in free fatty acid flux of obese adolescents.

CONTEXT: In obesity, increases in free fatty acid (FFA) flux can predict development of insulin resistance. Adult women release more FFA relative to resting energy expenditure (REE) and have greater FFA clearance rates than men. In adolescents, it is unknown whether sex differences in FFA flux occur. OBJECTIVE: Our objective was to determine the associations of sex, REE, and body composition with FFA kinetics in obese adolescents. PARTICIPANTS: Participants were from a convenience sample of 112 non-Hispanic white and black adolescents (31% male; age range, 12-18 years; body mass index SD score range, 1.6-3.1) studied before initiating obesity treatment. MAIN OUTCOME MEASURES: Glucose, insulin, and FFA were measured during insulin-modified frequently sampled iv glucose tolerance tests. Minimal models for glucose and FFA calculated insulin sensitivity index (SI) and FFA kinetics, including maximum (l0 + l2) and insulin-suppressed (l2) lipolysis rates, clearance rate constant (cf), and insulin concentration for 50% lipolysis suppression (ED50). Relationships of FFA measures to sex, REE, fat mass (FM), lean body mass (LBM) and visceral adipose tissue (VAT) were examined. RESULTS: In models accounting for age, race, pubertal status, height, FM, and LBM, we found sex, pubertal status, age, and REE independently contributed to the prediction of l2 and l0 + l2 (P < .05). Sex and REE independently predicted ED50 (P < .05). Sex, FM/VAT, and LBM were independent predictors of cf. Girls had greater l2, l0 + l2 and ED50 (P < .05, adjusted for REE) and greater cf (P < .05, adjusted for FM or VAT) than boys. CONCLUSION: Independent of the effects of REE and FM, FFA kinetics differ significantly in obese adolescent girls and boys, suggesting greater FFA flux among girls.

Effects of metformin on body weight and body composition in obese insulin-resistant children: a randomized clinical trial.

OBJECTIVE: Metformin can decrease adiposity and ameliorate obesity-related comorbid conditions, including abnormalities in glucose homeostasis in adolescents, but there are few data evaluating the efficacy of metformin among younger children. Our objective was to determine whether metformin treatment causes weight loss and improves obesity-related comorbidities in obese children, who are insulin-resistant. RESEARCH DESIGN AND METHODS: This study was a randomized double-blind placebo-controlled trial consisting of 100 severely obese (mean BMI 34.6 ± 6.6 kg/m(2)) insulin-resistant children aged 6-12 years, randomized to 1,000 mg metformin (n = 53) or placebo (n = 47) twice daily for 6 months, followed by open-label metformin treatment for 6 months. All children and their parents participated in a monthly dietitian-administered weight-reduction program. RESULTS: Eighty-five percent completed the 6-month randomized phase. Children prescribed metformin had significantly greater decreases in BMI (difference -1.09 kg/m(2), CI -1.87 to -0.31, P = 0.006), body weight (difference -3.38 kg, CI -5.2 to -1.57, P < 0.001), BMI Z score (difference between metformin and placebo groups -0.07, CI -0.12 to -0.01, P = 0.02), and fat mass (difference -1.40 kg, CI -2.74 to -0.06, P = 0.04). Fasting plasma glucose (P = 0.007) and homeostasis model assessment (HOMA) insulin resistance index (P = 0.006) also improved more in metformin-treated children than in placebo-treated children. Gastrointestinal symptoms were significantly more prevalent in metformin-treated children, which limited maximal tolerated dosage in 17%. During the 6-month open-label phase, children treated previously with placebo decreased their BMI Z score; those treated continuously with metformin did not significantly change BMI Z score further. CONCLUSIONS: Metformin had modest but favorable effects on body weight, body composition, and glucose homeostasis in obese insulin-resistant children participating in a low-intensity weight-reduction program.

A pilot study of interpersonal psychotherapy for preventing excess weight gain in adolescent girls at-risk for obesity.

OBJECTIVE: Interpersonal psychotherapy (IPT) is effective at reducing binge episodes and inducing weight stabilization in obese adults with binge eating disorder. METHOD: We piloted the administration of IPT to girls at-risk for excess weight gain (BMI 75th-97th percentile; IPT-WG) with and without loss of control (LOC) eating. Thirty-eight girls (12-17 years) were randomized to IPT-WG or a standard-of-care health education group. RESULTS: All 38 girls completed the programs and all follow-up visits through 6 months. Thirty-five of 38 returned for a complete assessment visit at 1 year. Among girls with baseline LOC (n = 20), those in IPT-WG experienced greater reductions in such episodes than girls in health education (p = .036). Regardless of LOC status, over 1 year girls in IPT-WG were less likely to increase their BMI as expected for their age and BMI percentile (p = .028). DISCUSSION: IPT-WG is feasible and acceptable to adolescent girls at-risk for adult obesity and may prevent excess weight gain over 1 year.

Laboratory assessment of the food intake of children and adolescents with loss of control eating.

BACKGROUND: Loss of control (LOC) eating in youth predicts excessive weight gain. However, few studies have measured the actual energy intake of children reporting LOC eating. OBJECTIVE: The objective was to characterize the energy intake and macronutrient composition of "normal" and "binge" laboratory meals in nonoverweight and overweight boys and girls with LOC eating. DESIGN: Children aged 8-17 y (n = 177) consumed 2 lunchtime meals ad libitum from a multi-item food array after being instructed to either binge eat (binge meal) or to eat normally (normal meal). Prior LOC eating was determined with a semistructured clinical interview. RESULTS: Participants consumed more energy at the binge meal than at the normal meal (P = 0.001). Compared with youth with no LOC episodes (n = 127), those reporting LOC (n = 50) did not consume more energy at either meal. However, at both meals, youth with LOC consumed a greater percentage of calories from carbohydrates and a smaller percentage from protein than did those without LOC (P < 0.05). Children with LOC ate more snack and dessert-type foods and less meats and dairy (P < 0.05). LOC participants also reported greater increases in postmeal negative affect at both meals than did those without LOC (P < or = 0.05). Secondary analyses restricted to overweight and obese girls found that those with LOC consumed more energy at the binge meal (P = 0.025). CONCLUSIONS: When presented with an array of foods, youth with LOC consumed more high-calorie snack and dessert-type foods than did those without LOC. Further research is required to determine whether habitual consumption of such foods may promote overweight. This trial was registered at clinicaltrials.gov as NCT00320177.

Insulin resistance, hyperinsulinemia, and energy intake in overweight children.

OBJECTIVE: To examine the relationship between energy intake during a buffet meal and indexes of insulin dynamics in overweight children. STUDY DESIGN: Ninety-five nondiabetic, overweight (body mass index > or = 95th percentile) children (age 10.3 +/- 1.4 years) selected lunch from a 9835-kcal buffet eaten ad libitum after an overnight fast. The associations between energy intake and measures of insulin dynamics, in the postabsorptive state and during a 2-hour hyperglycemic clamp, were determined. Covariates in the statistical model included race, sex, skeletal age, fat-free mass, fat mass, socioeconomic status, and number of foods in the buffet rated as acceptable. RESULTS: Energy intake was positively associated with the fasting homeostasis model assessment for insulin resistance index (beta = 0.24, P = .042), fasting insulin/glucose ratio (beta = 0.24, P = .044), first-phase insulin (beta = 0.23, P = .032), and first-phase C-peptide (beta = 0.21, P = .046); energy intake was negatively associated with clamp-derived insulin sensitivity (beta = -0.29, P = .042). Each 10% decrease in clamp-derived insulin sensitivity predicted a 27-kcal greater energy intake. CONCLUSIONS: Insulin resistance and hyperinsulinemia are associated with greater energy intake after an overnight fast in overweight children. These associations suggest mechanisms whereby insulin resistance may contribute to excessive weight gain in children.

Obesity following kidney transplantation and steroid avoidance immunosuppression.

Obesity is an important co-morbidity within end-stage renal disease (ESRD) and renal transplant populations. Previous studies have suggested that chronic corticosteroids result in increased body weight post-transplant. With the recent adoption of steroid-sparing immunosuppressive strategies, we evaluated the effect of these strategies on body mass index (BMI) after renal transplantation. We examined 95 renal transplant recipients enrolled in National Institutes of Health clinical transplant trials over the past three yr who received either lymphocyte depletion-based steroid sparing or traditional immunosuppressive therapy that included steroids for maintenance immunosuppression. Recipients were overweight prior to transplant and no significant differences existed in pre-transplant BMI among treatment groups. Regardless of therapy, BMI increased post-transplant in all recipients. The BMI increase consisted of an average weight gain of 5.01 +/- 7.12 kg (mean, SD) post-transplant. Additionally, in a number of recipients placed on maintenance steroids, subsequent withdrawal at a mean of 100 d post-transplant had no impact on weight gain. Thus, body weight and BMI increase following kidney transplantation, even in the absence of steroids. Thus, patients gain weight after renal transplantation regardless of the treatment strategy. Steroid avoidance alone does not reduce risk factors associated with obesity in our patient population.

Preventing excessive weight gain in adolescents: interpersonal psychotherapy for binge eating.

The most prevalent disordered eating pattern described in overweight youth is loss of control (LOC) eating, during which individuals experience an inability to control the type or amount of food they consume. LOC eating is associated cross-sectionally with greater adiposity in children and adolescents and seems to predispose youth to gain weight or body fat above that expected during normal growth, thus likely contributing to obesity in susceptible individuals. No prior studies have examined whether LOC eating can be decreased by interventions in children or adolescents without full-syndrome eating disorders or whether programs reducing LOC eating prevent inappropriate weight gain attributable to LOC eating. Interpersonal psychotherapy, a form of therapy that was designed to treat depression and has been adapted for the treatment of eating disorders, has shown efficacy in reducing binge eating episodes and inducing weight stabilization among adults diagnosed with binge eating disorder. In this paper, we propose a theoretical model of excessive weight gain in adolescents at high risk for adult obesity who engage in LOC eating and associated overeating patterns. A rationale is provided for interpersonal psychotherapy as an intervention to slow the trajectory of weight gain in at-risk youth, with the aim of preventing or ameliorating obesity in adulthood.

Children's descriptions of the foods consumed during loss of control eating episodes.

Binge and loss of control (LOC) eating appear to be common among youth; however, little is known about the foods consumed during such eating episodes. Two-hundred forty-nine children, age 6-18 years, were interviewed to determine if they engaged in eating episodes with LOC over the past month. In the absence of reported LOC eating, overeating episodes or normal meals without LOC were recorded. Participants were asked to describe the type and quantity of foods eaten during an episode. Eighty-one children reported LOC eating episodes and 168 reported no such episodes (No LOC). Although total energy intake did not differ between LOC and No LOC episodes, LOC episodes consisted of a lower percentage of calories from protein (14.2+/-0.7 v. 18.0+/-0.7%, p<.001) and a higher percentage from carbohydrates (49.8+/-1.6 v. 45.2+/-1.1%, p<.05). Specifically, LOC episodes consisted of a higher percentage of calories from snacks (13.2+/-2.7 v. 7.4+/-1.2%, p<.05) and desserts (18.1+/-3.1 v. 12.8+/-1.5%, p<.05). The quality of LOC episodes may help explain why LOC eating promotes excessive weight gain among children who report such episodes.

Reduced methylprednisolone clearance causing prolonged pharmacodynamics in a healthy subject was not associated with CYP3A5*3 allele or a change in diet composition.

The influence of diet and genetics was investigated in a healthy white person who had distinctly low methylprednisolone clearance. Pharmacokinetic and pharmacodynamic parameter values were similar on 2 occasions during the consumption of a low-carbohydrate diet and a Weight Watchers diet, indicating that the decreased clearance was unlikely attributable to a change in diet composition. Although the subject was found to be homozygous for CYP3A5*3, genetic findings were not significant for a number of other CYP3A4 and CYP3A5 allelic variants. Because of the high prevalence of CYP3A5*3/*3 in whites and because 5 of 7 white control subjects are also homozygous for CYP3A5*3, this genotype cannot fully explain the reduced metabolism of the drug. Other genetic or contributing factors might have been involved. New polymerase chain reaction-based genotyping methods for functionally defective CYP3A5*6, *8, *9, and *10 alleles were developed in this study. These assays will be useful for CYP3A5 genotype analysis in future clinical studies.

Solid organ transplantation at the National Institutes of Health: development of a research-based transplantation practice.

The National Institutes of Health has established a clinical transplant research program focusing on translational research in kidney transplantation. The program has been developed with a multidisciplinary approach under a common administrative structure that integrates transplant physicians and surgeons with clinical laboratory and data analysis support personnel. The program has achieved excellent clinical outcomes despite focusing exclusively on investigational methods and serving a diverse and medically complex patient population. Novel approaches toward consenting, computer integration, and tissue acquisition have been layered over interventional and observational studies to serve the scientific mission while delivering quality transplant care.

Comparison of methods to assess change in children's body composition.

BACKGROUND: Little is known about how simpler and more available methods to measure change in body fatness compare with criterion methods such as dual-energy X-ray absorptiometry (DXA) in children. OBJECTIVE: Our objective was to determine the ability of air-displacement plethysmography (ADP) and formulas based on triceps skinfold thickness (TSF) and bioelectrical impedance analysis (BIA) to estimate changes in body fat over time in children. DESIGN: Eighty-six nonoverweight and overweight boys (n = 34) and girls (n = 52) with an average age of 11.0 +/- 2.4 y underwent ADP, TSF measurement, BIA, and DXA to estimate body fatness at baseline and 1 +/- 0.3 y later. Recent equations were used to estimate percentage body fat by TSF measurement (Dezenberg equation) and by BIA (Suprasongsin and Lewy equations). Percentage body fat estimates by ADP, TSF measurement, and BIA were compared with those by DXA. RESULTS: All methods were highly correlated with DXA (P < 0.001). No mean bias for estimates of percentage body fat change was found for ADP (Siri equation) compared with DXA for all subjects examined together, and agreement between body fat estimation by ADP and DXA did not vary with race or sex. Magnitude bias was present for ADP relative to DXA (P < 0.01). Estimates of change in percentage body fat were systematically overestimated by BIA equations (1.37 +/- 6.98%; P < 0.001). TSF accounted for only 13% of the variance in percentage body fat change. CONCLUSION: Compared with DXA, there appears to be no noninvasive and simple method to measure changes in children's percentage body fat accurately and precisely, but ADP performed better than did TSF or BIA. ADP could prove useful for measuring changes in adiposity in children.