Deterioration in glucose and lipid metabolism is associated even with modest ALT elevations. Hepatic fat accumulation in childhood obesity is strongly associated with the triad of insulin resistance, increased visceral fat, and hypoadiponectinemia. Hence, hepatic steatosis may be a core feature of the metabolic syndrome.

Cigarette smoking may selectively enhance VSWM and attentional deficits in smokers with schizophrenia, which may depend on nAChR stimulation. These findings may have implications for understanding the high rates of smoking in schizophrenia and for developing pharmacotherapies for cognitive deficits and nicotine dependence in schizophrenia.

OBJECTIVE-To explore whether an imbalance between the visceral and subcutaneous fat depots and a corresponding dysregulation of the adipokine milieu is associated with excessive accumulation of fat in the liver and muscle and ultimately with insulin resistance and the metabolic syndrome.RESEARCH DESIGN AND METHODS-We stratified our multi-ethnic cohort of 118 obese adolescents into tertiles based on the proportion of abdominal fat in the visceral depot. Abdominal and liver fat were measured by magnetic resonance imaging and muscle lipid (intramyocellular lipid) by proton magnetic resonance spectroscopy.RESULTS-There were no differences in age, BMI Z score, or fat-free mass across tertiles. However, as the proportion of visceral fat increased across tertiles, BMI and percentage of fat and subcutaneous fat decreased, while hepatic fat increased. In addition, there was an increase in 2-h glucose, insulin, c-peptide, triglyceride levels, and insulin resistance. Notably, both leptin and total adiponectin were significantly lower in tertile 3 than 1, while C-reactive protein and interleukin-6 were not different across tertiles. There was a significant increase in the odds ratio for the metabolic syndrome, with subjects in tertile 3 5.2 times more likely to have the metabolic syndrome than those in tertile 1.CONCLUSIONS-Obese adolescents with a high proportion of visceral fat and relatively low abdominal subcutaneous fat have a phenotype reminiscent of partial lipodystrophy. These adolescents are not necessarily the most severely obese, yet they suffer from severe metabolic complications and are at a high risk of having the metabolic syndrome.

The link between adiponectin levels and a strong marker of inflammation, CRP, is independent of insulin resistance and adiposity in obese children and adolescents. Adiponectin may be one of the signals linking inflammation and obesity. Thus, adiponectin may function as a biomarker of the metabolic syndrome in childhood obesity.

OBJECTIVE -Impaired glucose tolerance (IGT) is a pre-diabetic state of increasing prevalence among obese adolescents. The purpose of this study was to determine the natural history of progression from normal glucose tolerance (NGT) to IGT in obese adolescents.RESEARCH DESIGN AND METHODS -We determined the evolution of ␤-cell function, insulin sensitivity (S I ), and glucose tolerance in a multiethnic group of 60 obese adolescents over the course of approximately 30 months. Each subject underwent three serial 3-h oral glucose tolerance tests. Dynamic, static, and total ␤-cell responsivity (⌽ d , ⌽ s , and ⌽ tot , respectively) and S i were assessed by oral C-peptide and glucose minimal models. The disposition index (DI), which adjusts insulin secretion for S i , was calculated.RESULTS -At baseline, all 60 subjects had NGT. Seventy-seven percent (46 subjects) maintained NGT over the three testing periods (nonprogressors), whereas 23% (14 subjects) developed IGT over time (progressors). At baseline, percent fat and BMI Z score were comparable between the groups. Fasting plasma glucose, 2-h glucose, glucose area under the curve at 180 min, and ⌽ d were significantly different between the two groups at baseline, whereas S i was comparable between the two groups. Over time, although S i remained unchanged in nonprogressors, it steadily worsened by ϳ45% (P Ͼ 0.04) in progressors. ␤-Cell responsivity decreased by 20% in progressors, whereas it remained stable in nonprogressors. The DI showed a progressive decline in progressors compared with a modest improvement in nonprogressors (P ϭ 0.02).CONCLUSIONS -Obese adolescents who progress to IGT may manifest primary defects in ␤-cell function. In addition, progressive decline in S i further aggravates ␤-cell function, contributing to the worsening of glucose intolerance.