Adolescent diet and metabolic syndrome in young women: results of the Dietary Intervention Study in Children (DISC) follow-up study.

CONTEXT: Childhood diet is hypothesized to influence development of chronic disease in adulthood. OBJECTIVE: Our objective was to evaluate the long-term effects of a dietary intervention to reduce fat and increase fiber intake during childhood and adolescence on the prevalence of metabolic syndrome in young adult women. DESIGN: A follow-up study was conducted in 2006-2008, 9 yr after termination of the Dietary Intervention Study in Children (DISC). SETTING: The study took place at six DISC clinical centers in the United States. PARTICIPANTS: A total of 230 (76%) DISC female participants who were 25-29 yr old and had not been pregnant or breastfeeding in the previous 3 months participated in the follow-up study. INTERVENTION: There was no intervention between the end of the DISC trial and the follow-up visit. MAIN OUTCOME MEASURE: Metabolic syndrome was the primary study endpoint planned before data collection and was hypothesized to be less common in the intervention group participants. RESULTS: Metabolic syndrome was uncommon, and its prevalence did not differ by treatment group. However, after adjustment for nondietary variables, mean systolic blood pressures of intervention and control group participants were 107.7 and 110.0 mm Hg, respectively (P = 0.03), whereas mean fasting plasma glucose levels were 87.0 and 89.1 mg/dl, respectively (P = 0.01). Intervention group participants also had lower concentrations of large very-low-density lipoprotein particles, a marker of hepatic insulin resistance, compared with control group participants. Adjustment for current diet did not materially alter results. CONCLUSION: Consumption of a diet lower in fat and higher in fiber during childhood and adolescence may benefit glycemic control and blood pressure long term.

Adolescent diet and subsequent serum hormones, breast density, and bone mineral density in young women: results of the Dietary Intervention Study in Children follow-up study.

BACKGROUND: Adolescent diet is hypothesized to influence breast cancer risk. We evaluated the long-term effects of an intervention to lower fat intake among adolescent girls on biomarkers that are related to breast cancer risk in adults. METHODS: A follow-up study was conducted on 230 girls who participated in the Dietary Intervention Study in Children (DISC), in which healthy, prepubertal, 8 to 10 year olds were randomly assigned to usual care or to a behavioral intervention that promoted a reduced fat diet. Participants were 25 to 29 years old at follow-up visits. All tests of statistical significance are two-sided. RESULTS: In analyses that did not take account of diet at the time of the follow-up visit, the only statistically significant treatment group difference was higher bone mineral content in intervention group participants compared with usual care group participants; their mean bone mineral contents were 2,444 and 2,377 g, respectively. After adjustment for current diet, the intervention group also had statistically significantly higher bone mineral density and luteal phase serum estradiol concentrations. Serum progesterone concentrations and breast density did not differ by treatment group in unadjusted or adjusted analyses. CONCLUSIONS: Results do not support the hypothesis that consumption of a lower fat diet during adolescence reduces breast cancer risk via effects on subsequent serum estradiol and progesterone levels, breast density, or bone mineral density. It remains unclear, however, if the results are specific to the DISC intervention or are more broadly applicable. IMPACT: Modest reductions in fat intake during adolescence are unlikely to lower later breast cancer risk via long-term effects on the biomarkers measured.

Pathology of chronic hepatitis C in children: liver biopsy findings in the Peds-C Trial.

There is relatively little information in the literature on the histopathology of chronic hepatitis C in children. The Peds-C Trial, designed to test the efficacy and safety of peginterferon alfa-2a and ribavirin in children, provided an opportunity to examine liver biopsies from 121 treatment-naïve children, ages 2 to 16 (mean, 9.8 years) infected with the hepatitis C virus (HCV) and with no other identifiable cause for liver disease, signs of hepatic decompensation, or another significant nonhepatic disease. Liver biopsies were scored for inflammation, fibrosis, steatosis, and other histological features. Inflammation in the biopsy was minimal in 42%, mild in 17%, moderate in 38%, and severe in only 3%. Five had bridging fibrosis, and 2 had cirrhosis. Steatosis was absent in 56%, minimal in 34%, and mild in 10%. Inflammation scores correlated with fibrosis scores, serum alanine aminotransferase levels, and duration of infection, but not with age, body mass index z score, or HCV genotype. Fibrosis scores correlated with inflammation but not with age, HCV genotype, body mass index z score, or steatosis parameters. Steatosis correlated with serum alanine aminotransferase levels and body mass index z scores; overweight children had more fibrosis than the non-overweight. In conclusion, in this cohort of HCV-infected children, inflammation, fibrosis, and steatosis were milder than reported for treatment-naïve adults with chronic hepatitis C, but there were several with bridging fibrosis or cirrhosis. The positive correlation of inflammation with duration of infection and fibrosis and of obesity with fibrosis suggest that children with chronic hepatitis C will be at risk for progressive liver disease as they age and possibly acquire other comorbid risk factors.

Immune activation set point during early HIV infection predicts subsequent CD4+ T-cell changes independent of viral load.

Although generalized T-cell activation is an important factor in chronic HIV disease pathogenesis, its role in primary infection remains poorly defined. To investigate the effect of immune activation on T-cell changes in subjects with early HIV infection, and to test the hypothesis that an immunologic activation "set point" is established early in the natural history of HIV disease, a prospective cohort of acutely infected adults was performed. The median density of CD38 molecules on CD4+ and CD8+ T cells was measured longitudinally in 68 antiretroviral-untreated individuals and 83 antiretroviral-treated individuals. At study entry, T-cell activation was positively associated with viremia, with CD8+ T-cell activation levels increasing exponentially at plasma HIV RNA levels more than 10,000 copies/mL. Among untreated patients, the level of CD8+ T-cell activation varied widely among individuals but often remained stable within a given individual. CD8+ T-cell activation and plasma HIV RNA levels over time were independently associated with the rate of CD4+ T-cell loss in untreated individuals. These data indicate that immunologic activation set point is established early in HIV infection, and that this set point determines the rate at which CD4+ T cells are lost over time.

Time trends in primary HIV-1 drug resistance among recently infected persons.

CONTEXT: Transmission of multiclass drug-resistant human immunodeficiency virus type 1 (HIV-1) may increase with wider use of antiretroviral therapy. OBJECTIVE: To determine trends in prevalence of HIV-1 drug resistance among recently infected individuals in a geographic area with a high penetration of antiviral treatment. DESIGN, SETTING, AND PATIENTS: Consecutive case series of 225 patients referred to a San Francisco, Calif, hospital with recent HIV-1 infection from June 1996 through June 2001. MAIN OUTCOME MEASURE: Time trends in the prevalence of genotypic and phenotypic primary drug resistance. RESULTS: Mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) steadily increased from 0% in 1996-1997 to 12 (13.2%) in 2000-2001 (P =.01). There was 1 mutation associated with protease inhibitor resistance in 1996-1997 (2.5%) and there were 7 (7.7%) in 2000-2001 (P =.25). Genotypic resistance to nucleoside reverse transcriptase inhibitors (NRTIs) initially decreased and then returned to prior levels (P =.007 for test of homogeneity). Genotypic resistance to 2 or more classes of drugs increased from 1 (2.5%) to 12 (13.2%) (P =.004), but only 1 infection (1.2%) in the latter period was resistant to all 3 classes of agents (P =.58). Primary phenotypic resistance decreased for NRTIs from 21% to 6.2% (P =.03) and increased for NNRTIs from 0 to 8 (9.9%) (P =.02). Phenotypic resistance increased for protease inhibitors from 2.6% to 6.2% (P =.32). Median time to virologic suppression (<500 copies/mL) during therapy was 12 weeks for patients with genotypic evidence of resistance compared with 5 weeks for patients with drug-sensitive infections (P =.02). CONCLUSIONS: The frequency of primary resistance to NNRTIs is increasing, although resistance to all available classes of antiretroviral therapy remains rare. Genotypic resistance testing in recently infected persons predicts time to viral suppression during therapy.