Mediterranean diet adherence and metabolic syndrome in US adolescents.

The Mediterranean diet (MD) has been found to lower the risk of heart disease, stroke, and diabetes in adults. Little is known about its acceptance and relationship to cardiovascular risk markers in US adolescents. Using data from the National Health and Nutrition Examination Survey, years 2007-2014, we performed a cross-sectional analysis of adherence to the Mediterranean diet among a representative sample of US adolescents (n = 4223), factors that influence adherence, and whether adherence is associated with cardiometabolic risk factors including metabolic syndrome. MD adherence was calculated using the KIDMED scoring system. We found that overall MD adherence was very low among US adolescents, with Mexican American youths having higher adherence compared to other groups. Higher income was associated with greater adherence. There was low intake of key MD foods including olive oil and finfish. The unadjusted prevalence of metabolic syndrome was 6.6%. MD adherence was not associated with metabolic syndrome.

Nut consumption and metabolic syndrome in US adolescents.

OBJECTIVE: To determine whether nut intake is associated with the prevalence of metabolic syndrome in US adolescents. DESIGN: A cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) years 2003-2012. Anthropometric measurements, blood tests, 24 h diet recalls and demographic data were retrieved for participating adolescents. Metabolic syndrome was defined according to paediatric-modified Adult Treatment Panel III criteria. The exposure was defined as a nut intake ≥5 g/d. SETTING: USA. SUBJECTS: Individuals aged 12-19 years (n 2805). RESULTS: Nut consumption was associated with lower odds for metabolic syndrome (crude OR=0·25; 95 % CI 0·11, 0·55; P≤0·001). This effect was independent of age, sex, race/ethnicity and family income:poverty ratio (adjusted OR=0·27; 95 % CI 0·12, 0·61; P=0·002), and was stable after controlling for nutritional covariates including intake of sugar and total energy consumption (OR=0·36; 95 % CI 0·16, 0·81; P=0·014). CONCLUSION: Nut consumption of ≥5 g/d is independently associated with lower odds for metabolic syndrome in US adolescents.

Cystic Fibrosis-Related Diabetes in Children: An Update.

Cystic fibrosis-related diabetes mellitus (CFRD) is the most common endocrine complication of cystic fibrosis (CF), affecting more than 50% of patients by the 4th decade of life. CFRD is often preceded by worsening pulmonary status and nutritional decline. Treatment of CFRD is associated with improvements in body weight and pulmonary function and a reduction in pulmonary exacerbations. Because of the clinical significance of CFRD, diabetes screening with an oral glucose tolerance test (OGTT) is recommended annually for all patients with CF starting at age 10 years. The OGTT detects CFRD with greater sensitivity than random glucose or hemoglobin A1c testing. The first-line treatment for CFRD is insulin. The use of other treatments such as oral medications remains under study. [Pediatr Ann. 2016;45(9):e321-e326.].

In vitro and in vivo effects of IGF-I on adiposity in HIV-associated metabolic disease: a pilot study.

BACKGROUND AND AIMS: We tested the effects of recombinant insulin-like growth factor-I (IGF-I) in an adipocyte model of HIV lipodystrophy and in an open label study on body composition and metabolism in patients with HIV lipodystrophy. METHODS: The effects of IGF-I on ritonavir-induced adipocyte cell death were studied in vitro. We assessed lipid accumulation, IGF signaling, apoptosis, and gene expression. We conducted a 24-week open label trial of recombinant IGF-I in ten adults with HIV associated lipoatrophy. Laboratory assessments included glucose, insulin, lipids, and IGF-I. At weeks 0 and 24, body composition studies were performed including skinfold measurement, dual-energy x-ray absorptiometry, and computed tomography of the abdomen and thigh. RESULTS: In vitro, ritonavir increased delipidation and apoptosis of adipocytes, whereas co-treatment with IGF-I attenuated the effect. In the clinical study, subcutaneous adipose tissue did not increase in patients after treatment with IGF-I; however, there was a decrease in the proportion of abdominal fat (39.8 ± 7% vs. 34.6 ± 7%, p = 0.007). IGF-I levels increased with treatment (143 ± 28 µg/L at week 0 vs. 453 ± 212 µg/L at week 24, p = 0.002), whereas IGFBP-3 levels declined (3.554 ± 1.146 mg/L vs. 3.235 ± 1.151 mg/L, p = 0.02). Insulin at week 12 decreased significantly (90.1 ± 39.8 pmol/L vs. 33.2 ± 19.6 pmol/L, p = 0.002). There was a nonsignificant decrease in visceral adipose tissue (155.2 ± 68 cm² at week 0 vs. 140.6 ± 70 cm² at week 24, p = 0.08). CONCLUSIONS: Use of recombinant IGF-I may lower fasting insulin and abdominal fat in patients with lipoatrophy associated with HIV infection. Further evaluation of this agent for treatment of HIV-associated lipodystrophy may be warranted.

Impact of antiretroviral therapy on growth, body composition and metabolism in pediatric HIV patients.

Highly active antiretroviral therapy improves survival and growth in children with HIV infection. However, its use can be associated with adverse changes in body composition and metabolism. Bone mineral density can be adversely affected in HIV-positive children due to nutritional compromise or certain antiretrovirals. HIV-associated lipodystrophy, consisting of redistribution of adipose tissue, insulin resistance, and dyslipidemia, has also been described in children. Pediatric HIV patients may be at greater risk for these problems because of their longer potential lifetime exposure to these agents and because childhood is normally a period of rapid growth and tissue accretion. Healthcare providers for children with HIV infection must be aware of the potential complications associated with HIV antiretrovirals so that their antiviral efficacy can be balanced against their risk for side effects. In this review, we discuss the alterations in childhood growth and body composition that occur in HIV-infected children, and describe the impact of antiretroviral therapy on these outcomes. The problem of HIV-associated lipodystrophy syndrome in children is also discussed. Children with HIV should have their growth and body composition systematically monitored. Antiretroviral regimens should be tailored to optimize adherence and viral suppression while minimizing the potential for adverse side effects.

Energy expenditure in obesity associated with craniopharyngioma.

BACKGROUND AND PURPOSE: Obesity is a common yet incompletely understood complication of childhood craniopharyngioma. We hypothesized that craniopharyngioma is associated with specific defects in energy balance compared to obese control children. METHODS: Eleven craniopharyngioma patients were recruited for a study on body composition and energy balance. Eight subjects were obese. The obese craniopharyngioma patients had a mean age (+/-SD) of 11.2 +/- 1.7 years. The average body mass index z score was 2.33 (+/-0.32). A previously studied group of obese children (BMI z score 2.46 +/- 0.46) served as controls. Resting energy expenditure (REE) was determined by indirect calorimetry and body composition by dual energy X-ray absorptiometry in all children. RESULTS: Obese craniopharyngioma patient subjects had increased mean (+/-standard error) fat-free mass compared to obese controls (57% +/- 0.88 % vs 50.0% +/- 0.87%, p = 0.02). The obese craniopharyngioma patients had a 17% lower REE compared to values expected from the World Health Organization equation (1,541 +/- 112.6 vs 1,809 +/- 151.8 kcal; p = 0.01). In contrast, the obese control children had measured REE within 1% of predicted (1,647 +/- 33.2 vs. 1,652 +/- 40.2; p = 0.8). In a linear regression model, REE remained significantly lower than predicted after controlling for FFM. CONCLUSIONS: Lower REE may be a factor contributing to obesity in children with craniopharyngioma. Further study is needed into the mechanisms for reduced energy expenditure in patients with craniopharyngioma.

Interferon gamma attenuates insulin signaling, lipid storage, and differentiation in human adipocytes via activation of the JAK/STAT pathway.

Recent reports demonstrate T-cell infiltration of adipose tissue in early obesity. We hypothesized that interferon (IFN) gamma, a major T-cell inflammatory cytokine, would attenuate human adipocyte functions and sought to establish signaling mechanisms. Differentiated human adipocytes were treated with IFNgamma +/- pharmacological inhibitors prior to insulin stimulation. [(3)H]Glucose uptake and AKT phosphorylation were assessed as markers of insulin sensitivity. IFNgamma induced sustained loss of insulin-stimulated glucose uptake in human adipocytes, coincident with reduced Akt phosphorylation and down-regulation of the insulin receptor, insulin receptor substrate-1, and GLUT4. Loss of adipocyte triglyceride storage was observed with IFNgamma co-incident with reduced expression of peroxisome proliferator-activated receptor gamma, adiponectin, perilipin, fatty acid synthase, and lipoprotein lipase. Treatment with IFNgamma also blocked differentiation of pre-adipocytes to the mature phenotype. IFNgamma-induced robust STAT1 phosphorylation and SOCS1 mRNA expression, with modest, transient STAT3 phosphorylation and SOCS3 induction. Preincubation with a non-selective JAK inhibitor restored glucose uptake and Akt phosphorylation while completely reversing IFNgamma suppression of adipogenic mRNAs and adipocyte differentiation. Specific inhibition of JAK2 or JAK3 failed to block IFNgamma effects suggesting a predominant role for JAK1-STAT1. We demonstrate that IFNgamma attenuates insulin sensitivity and suppresses differentiation in human adipocytes, an effect most likely mediated via sustained JAK-STAT1 pathway activation.

Retinol saturase promotes adipogenesis and is downregulated in obesity.

Adipocyte differentiation is controlled by many transcription factors, but few known downstream targets of these factors are necessary for adipogenesis. Here we report that retinol saturase (RetSat), which is an enzyme implicated in the generation of dihydroretinoid metabolites, is induced during adipogenesis and is directly regulated by the transcription factor peroxisome proliferator activated receptor gamma (PPARgamma). Ablation of RetSat dramatically inhibited adipogenesis but, surprisingly, this block was not overcome by the putative product of RetSat enzymatic activity. On the other hand, ectopic RetSat with an intact, but not a mutated, FAD/NAD dinucleotide-binding motif increased endogenous PPARgamma transcriptional activity and promoted adipogenesis. Indeed, RetSat was not required for adipogenesis when cells were provided with exogenous PPARgamma ligands. In adipose tissue, RetSat is expressed in adipocytes but is unexpectedly downregulated in obesity, most likely owing to infiltration of macrophages that we demonstrate to repress RetSat expression. Thiazolidinedione treatment reversed low RetSat expression in adipose tissue of obese mice. Thus, RetSat plays an important role in the biology of adipocytes, where it favors normal differentiation, yet is reduced in the obese state. RetSat is thus a novel target for therapeutic intervention in metabolic disease.

Psychosocial status in adolescents undergoing bariatric surgery.

BACKGROUND: Little is known about the psychosocial status of adolescents who undergo bariatric surgery. Our objective was to describe the psychological and behavioral characteristics of patients in this age group who underwent bariatric surgery at our institution. METHODS: A review of clinical charts of patients aged 14-21 years who had bariatric surgery at our institution between 2000 and 2005 was conducted. Abstracted data included clinical information and the results of a psychosocial evaluation consisting of a clinical interview with a psychologist and self-reported data from the Weight and Lifestyle Inventory and the Beck Depression Inventory-II. RESULTS: Twenty-five patient records were reviewed. Nineteen patients (76%) were female. The mean (+/-SD) age was 18.7 +/- 1.6 years, and mean body mass index was 50.6 +/- 7.9 kg/m(2). Depression was the most common psychiatric comorbidity (68%). Abnormal eating behaviors were frequent and included binge eating (48%), rapid eating (44%), having guilt associated with eating (36%), eating until uncomfortably full (36%), loss of control (24%), eating without hunger (24%), and eating alone (20%). Sixteen patients were judged to be appropriate for surgery by the bariatric surgery team; surgery was delayed for nine patients primarily because of concerns about ability to adhere to the postoperative diet. These patients were recommended for additional dietary counseling and/or psychotherapeutic treatment prior to surgery. CONCLUSIONS: Among adolescent bariatric surgery candidates, depression and aberrant eating behaviors were very common. Early identification and management of these conditions may enable most of these patients to undergo bariatric surgery and optimize the likelihood for a successful outcome.

A widely used retinoic acid receptor antagonist induces peroxisome proliferator-activated receptor-gamma activity.

Nuclear receptors (NRs) are transcription factors whose activity is regulated by the binding of small lipophilic ligands, including hormones, vitamins, and metabolites. Pharmacological NR ligands serve as important therapeutic agents; for example, all-trans retinoic acid, an activating ligand for retinoic acid receptor alpha (RARalpha), is used to treat leukemia. Another RARalpha ligand, (E)-S,S-dioxide-4-(2-(7-(heptyloxy)-3,4-dihydro-4,4-dimethyl-2H-1-benzothiopyran-6-yl)-1-propenyl)-benzoic acid (Ro 41-5253), is a potent antagonist that has been a useful and purportedly specific probe of RARalpha function. Here, we report that Ro 41-5253 also activates the peroxisome proliferator-activated receptor gamma (PPARgamma), a master regulator of adipocyte differentiation and target of widely prescribed antidiabetic thiazolidinediones (TZDs). Ro 41-5253 enhanced differentiation of mouse and human preadipocytes and activated PPARgamma target genes in mature adipocytes. Like the TZDs, Ro 41-5253 also down-regulated PPARgamma protein expression in adipocytes. In addition, Ro 41-5253 activated the PPARgamma-ligand binding domain in transiently transfected HEK293T cells. These effects were not prevented by a potent RARalpha agonist or by depleting cells of RARalpha, indicating that PPARgamma activation was not related to RARalpha antagonism. Indeed, Ro 41-5253 was able to compete with TZD ligands for binding to PPARgamma, suggesting that Ro 41-5253 directly affects PPAR activity. These results vividly demonstrate that pharmacological NR ligands may have "off-target" effects on other NRs. Ro 41-5253 is a PPARgamma agonist as well as an RARalpha antagonist whose pleiotropic effects on NRs may signify a unique spectrum of biological responses.

Hypoadiponectinemia, dyslipidemia, and impaired growth in children with HIV-associated facial lipoatrophy.

OBJECTIVE: To compare growth, lipids and adipocytokines in HIV-positive children with and without lipoatrophy. PATIENTS: Eleven HIV-positive children with facial lipoatrophy, and 22 age- and sex-matched HIV-positive controls without signs of fat abnormality. METHODS: Clinical data including height, physical examination findings, medications, markers of viral control, cholesterol, and triglycerides were retrieved from the medical charts. Serum samples were analyzed for adiponectin, inflammatory markers, and high density lipoprotein cholesterol (HDL). RESULTS: Lipoatrophy was associated with higher triglycerides (330 vs 133 mg/dl, p = 0.0003), lower HDL (33 vs 48 mg/dl, p = 0.02), and a greater frequency of hypercholesterolemia (total cholesterol > 200 mg/dl; 64% vs 23%, p < 0.03). Adiponectin was 53% lower in patients with lipodystrophy (6.9 microg/ml vs 14.8 microg/ml, p = 0.005), however there was no difference in the inflammatory markers soluble TNFa receptor 2 or interleukin 6. Strikingly, despite similar BMI z-scores and virological control, lipoatrophic patients were shorter by 1 standard deviation score (p = 0.03). CONCLUSIONS: The presence of facial lipoatrophy in a child with HIV infection is a marker for significant metabolic derangements including dyslipidemia and hypoadiponectinemia, and suggests the need for careful growth evaluation.

HIV protease inhibitor-specific alterations in human adipocyte differentiation and metabolism.

OBJECTIVE: Human immunodeficiency virus (HIV) patients on antiretroviral regimens frequently develop a syndrome of abnormal fat distribution, insulin resistance, and dyslipidemia. This lipodystrophic syndrome has been most closely linked to the use of HIV protease inhibitors (PIs). Several mechanisms have been postulated to explain these adverse effects of PIs, based largely on studies of rodent adipocytes. Intriguingly, atazanavir, a newer PI equally effective against HIV, is associated with fewer signs of lipodystrophy. We hypothesized that the less deleterious clinical effects of atazanavir would be reflected in physiological differences observed in PI-treated adipocytes. RESEARCH METHODS AND PROCEDURES: We compared the effects of atazanavir and an older PI associated with lipodystrophy, ritonavir, on differentiation, gene expression, adipocytokine secretion, and insulin signaling in a human adipocyte cell line. RESULTS: Ritonavir inhibited human adipocyte differentiation and induced apoptosis to a greater extent than atazanavir. Treatment of mature adipocytes with ritonavir, but not atazanavir, also selectively decreased insulin signaling. Moreover, ritonavir also selectively decreased expression of adiponectin, an insulin-sensitizing adipocytokine, while inducing interleukin-6, a proinflammatory cytokine implicated in insulin resistance. DISCUSSION: These data suggest that the distinct metabolic side effect profiles of these PIs could be a consequence of their differential effects on adipocyte physiology.

Nutritional supplementation with trans-10, cis-12-conjugated linoleic acid induces inflammation of white adipose tissue.

Conjugated linoleic acids (CLAs) are conjugated dienoic isomers of linoleic acid. Many people supplement their diets with CLAs to attempt weight loss, and the trans-10,cis-12 isomer (t10,c12-CLA) of CLA reduces adiposity in animal models and humans. However, CLA treatment in mice causes insulin resistance that has been attributed to the lipoatrophic state, which is associated with hyperinsulinemia and hepatic steatosis. Here, we investigated the effect of t10,c12-CLA on adipose tissue inflammation, another factor promoting insulin resistance. We confirmed that t10,c12-CLA daily gavage performed in mice reduces white adipose tissue (WAT) mass and adiponectin and leptin serum levels and provokes hyperinsulinemia. In parallel, we demonstrated that this CLA isomer led to a rapid induction of inflammatory factors such as tumor necrosis factor-alpha and interleukin-6 gene expression in WAT without affecting their serum levels. In vitro, t10,c12-CLA directly induced IL-6 secretion in 3T3-L1 adipocytes by an nuclear factor-kappaB-dependent mechanism. In vivo, however, the lipoatrophic adipose tissue of CLA-treated mice was notable for a dramatic increase in macrophage infiltration and gene expression. Thus, CLA supplementation directly induces inflammatory gene expression in adipocytes and also promotes macrophage infiltration into adipose tissue to a local inflammatory state that contributes to insulin resistance.

Adult heights attained by children with hypothalamic/chiasmatic glioma treated with growth hormone.

Hypothalamic/chiasmatic gliomas (H/CG) in children are commonly accompanied by endocrine dysfunction due to mass effects of the tumor itself or as a consequence of tumor therapy, with GH deficiency (GHD) being the most common disorder. We report the height outcomes of GH-treated H/CG patients with GHD. We reviewed the records of 14 GHD patients with H/CG who were treated with human GH. A comparison group of non-GH-treated H/CG patients was also identified. Heights were expressed as sd scores (SDS). For GH-treated patients, the mean initial height was -0.7 +/- 0.3 (+/-se). Their mean final height was -0.3 +/- 0.3. The mean change in height SDS for the GH-treated group was +0.4. The mean initial and final height SDS for the non-GHD patients were 0.6 (se = 0.4) and 0.0 (se = 0.4), respectively. The mean change in height SDS was -0.6. The GHD patients had significantly lower initial height SDS compared with the non-GHD patients (P = 0.01) and had a significantly greater change in their height SDS (P = 0.04). GH treatment for H/CG patients restores much of their growth potential and improves adult height to within normal limits.

Vasopressin and desmopressin in central diabetes insipidus: adverse effects and clinical considerations.

The management of central diabetes insipidus has been greatly simplified by the introduction of desmopressin (DDAVP). Its ease of administration, safety and tolerability make DDAVP the first line agent for outpatient treatment of central diabetes insipidus. The major complication of DDAVP therapy is water intoxication and hyponatremia. The risk of hyponatremia can be reduced by careful dose titration when initiating therapy and by close monitoring of serum osmolality when DDAVP is used with other medications affecting water balance. Herein we review the adverse effects of DDAVP and its predecessor, vasopressin, as well as discuss important clinical considerations when using these agents to treat central diabetes insipidus.