Improved glycemic control either alone, or combined with antioxidant supplementation, fails to restore blood glutathione or markers of oxidative stress in adolescents with poorly controlled type 1 diabetes.

In earlier studies, we showed that adolescents with type 1 diabetes mellitus (T1DM) have significant glutathione (GSH) depletion and that GSH is reciprocally related to glycemic control. In both the general population and in those with diabetes, the use of over-the-counter antioxidant supplements is widespread. We hypothesized that improved glycemic control, alone or in combination with dietary antioxidants, would restore blood GSH pool. The study included 41 participants who were 15.8 ± 2.4 years of age (mean ± standard deviation) and with poorly controlled T1DM (hemoglobin A1c [HbA1c] 8.2 ± 0.6%). Erythrocyte GSH, and 3-nitrotyrosine, F2-isoprostane, and 8-hydroxy-2'-deoxy-guanosine (as markers of protein, lipid, and DNA oxidative stress, respectively) were determined in the postabsorptive state after blood glucose was maintained overnight near euglycemia. Participants were then randomized to a mix of antioxidants (vitamin C, selenium, zinc, vitamin E, ß-carotene) or placebo for 3 to 6 months, and diabetes management was intensified using CSII (n = 30) or multiple daily injections (n = 11) coupled with CDE phone calls and visits with a Nutritionist. A second, identical study was performed when/if a drop in HbA1c ≥0.5% was achieved. HbA1c levels dropped similarly in both groups (from 8.9 ± 1.0% to 7.9 ± 0.9% and 8.5 ± 0.6% to 7.7 ± 0.7% in placebo and antioxidant group, respectively). Neither total nor reduced GSH was altered by improved metabolic control. Markers of protein, lipid, and DNA oxidation remained unaltered. We conclude that, in youngsters with T1DM, neither a significant improvement in diabetes control over a 3-month period nor the regimen of dietary antioxidant supplied in the current study can mitigate oxidative stress. These findings suggest that, in adolescents with T1DM, (1) more sustained improvement of diabetes control may be needed to alleviate oxidative stress and (2) the putative benefit of antioxidant supplements remains to be proven.

Effects of Mixed Carotenoids on Adipokines and Abdominal Adiposity in Children: A Pilot Study.

Context: Carotenoids have been implicated in the regulation of adipocyte metabolism. Objective: To compare the effects of mixed-carotenoid supplementation (MCS) versus placebo on adipokines and the accrual of abdominal adiposity in children with obesity. Design and Setting: Randomized (1:1), double-blind, placebo-controlled intervention trial to evaluate the effects of MCS over 6 months in a subspecialty clinic. Participants: Twenty (6 male and 14 female) children with simple obesity [body mass index (BMI) > 90%], a mean age (± standard deviation) of 10.5 ± 0.4 years, and Tanner stage I to V were enrolled; 17 participants completed the trial. Intervention: MCS (which contains ß-carotene, α-carotene, lutein, zeaxanthin, lycopene, astaxanthin, and γ-tocopherol) or placebo was administered daily. Main Outcome Measures: Primary outcomes were change in ß-carotene, abdominal fat accrual (according to magnetic resonance imaging), and BMI z-score; secondary outcomes were adipokines and markers of insulin resistance. Results: Cross-sectional analysis of ß-carotene showed inverse correlation with BMI z-score, waist-to-height ratio, visceral adipose tissue, and subcutaneous adipose tissue (SAT) at baseline. MCS increased ß-carotene, total adiponectin, and high-molecular-weight adiponectin compared with placebo. MCS led to a greater reduction in BMI z-score, waist-to-height ratio, and SAT compared with placebo. The percentage change in ß-carotene directly correlated with the percentage change in SAT. Conclusions: The decrease in BMI z-score, waist-to-height ratio, and SAT and the concomitant increase in the concentration of ß-carotene and high-molecular-weight adiponectin by MCS suggest the putative beneficial role of MCS in children with obesity.

Does oral glutamine improve insulin sensitivity in adolescents with type 1 diabetes?

OBJECTIVE: The decline in insulin sensitivity (SI) associated with puberty increases the difficulty of achieving glycemic control in adolescents with type 1 diabetes (T1D). The aim of this study was to determine whether glutamine supplementation affects blood glucose by enhancing SI in adolescents with T1D. METHODS: Thirteen adolescents with T1D (HbA1C 8.2 ± 0.1%) were admitted to perform afternoon exercise (four 15-min treadmill/5-min rest cycles of exercise) on two occasions within a 4-wk period. They were randomized to receive a drink containing either glutamine (0.25 g/kg) or placebo before exercise, at bedtime, and early morning in a double-blind, crossover design. Blood glucose was monitored overnight, and a hyperinsulinemic-euglycemic clamp was performed the following morning. RESULTS: Blood glucose concentration dropped comparably during exercise on both days. However, the total number of nocturnal hypoglycemic events (17 versus 7, P = 0.045) and the cumulative probability of overnight hypoglycemia (50% versus 33%, P = 0.02) were higher on the glutamine day than on the placebo day. During clamp, glucose infusion rate was not affected by glutamine supplementation (7.7 ± 1 mg • kg-1 • min-1 versus 7.0 ± 1; glutamine versus placebo; P = 0.4). CONCLUSIONS: Oral glutamine supplementation decreases blood glucose in adolescents with T1D after exercise. Insulin sensitivity, however, was unaltered during the euglycemic clamp. Although the mechanisms involved remain to be elucidated, studies to explore the potential use of glutamine to improve blood glucose control are needed.

Trends of fluoroquinolone-resistant Escherichia coli amongst urinary isolates in children: a 10 year surveillance study.

We evaluated 3122 children with E. coli urinary isolates over a 10 year period in order to assess the emergence of fluoroquinolone resistance. Susceptibilities remained stable; however, hospitalized children had a statistically higher risk of developing fluoroquinolone-resistant isolates when compared with outpatients. Stewardship monitoring of fluoroquinolone use amongst hospitalized children is warranted.

Effects of aggregate and individual antibiotic exposure on vancomycin MICs for Staphylococcus aureus isolates recovered from pediatric patients.

We evaluated the evolution of vancomycin MICs for Staphylococcus aureus and their relationship with vancomycin use among hospitalized children. S. aureus isolates recovered from sterile sites were prospectively tested for vancomycin susceptibility using the Etest between 1 April 2000 and 31 March 2008. Vancomycin MICs were grouped into three categories: ≤ 1, 1.5, and 2 µg/ml. The association between vancomycin MICs and aggregate vancomycin use and individual patient vancomycin exposure 6 months prior to the documented infection was assessed. The geometric mean values for vancomycin MICs for S. aureus fluctuated over time without a significant trend (P = 0.146). Of the 436 patients included in the study, 363 (83%) had methicillin-susceptible S. aureus (MSSA) and 73 (17%) had methicillin-resistant S. aureus (MRSA) infections. The rate of isolates with a vancomycin MIC of 2 µg/ml increased from 4% (2 of 46) in 2000 to 2001 to 24% (11 of 46) in 2007 to 2008, despite a decrease in vancomycin use (r = -0.11; P = 0.825). The percentage of isolates with a vancomycin MIC of 2 µg/ml was higher for MRSA (15%; 11 of 73) than for MSSA strains (5.2%; 19 of 363) (χ(2) = 9.2; P = 0.01). Individual patient vancomycin exposure was not associated with a higher vancomycin MIC. In the unadjusted model, in which we compared patients with S. aureus infections with MICs of ≤ 1 µg/ml, the odds ratios of exposure rates for patients with isolates with MICs of 1.5 µg/ml and 2 µg/ml were 1.02 (P = 0.929) and 1.13 (P = 0.767), respectively. In our experience, the geometric means of vancomycin MICs from S. aureus isolates recovered from hospitalized children oscillated over time and were not associated with previous individual patient vancomycin exposure or aggregate vancomycin use.

Nutrigenetic response to omega-3 fatty acids in obese asthmatics (NOOA): rationale and methods.

Uncontrolled asthma is a major cause of hospitalizations and emergency room visits. Factors including obesity, African ancestry and childhood are associated with increased asthma severity. Considering the high morbidity caused by asthma, relatively few classes of drugs exist to control this common disease. Therefore, new therapeutic strategies may be needed to reduce asthma's impact on public health. Data suggest that a high fat diet that is deficient in omega-3 fatty acids could promote both obesity and excessive inflammation, resulting in greater asthma severity. Small trials with supplemental omega-3 fatty acids have been conducted with encouraging but inconsistent results. The variability in response seen in past trials may be due to the past subjects' genetics (specifically ALOX5 rs59439148) or their particular asthma phenotypes. Therefore, the "Nutrigenetic response to Omega-3 Fatty acids in Obese Asthmatics (NOOA)" trial is currently underway and was designed as a randomized, double-blind, placebo controlled intervention study to determine if supplemental omega-3 fatty acids improves symptoms among obese adolescents and young adults with uncontrolled asthma. Here we report the design and rationale for the NOOA trial. Participants were given either 3.18 g daily of eicosapentaenoic acid and 822 mg daily docosahexaenoic acid, or matched control soy oil, for 24 weeks. Change in the asthma control questionnaire score was the primary outcome. Secondary outcomes included spirometry, impulse oscillometry, exacerbation rate, airway biomarkers, systemic inflammation, leukotriene biosynthesis and T-lymphocyte function. NOOA may lead to a new therapeutic treatment strategy and greater understanding of the mechanistic role of diet in the pathogenesis of asthma.

Insulin resistance and adiposity in relation to serum ß-carotene levels.

OBJECTIVE: To determine the effects of placebo vs an encapsulated supplement of fruit and vegetable juice concentrate (FVJC) on serum ß-carotene levels, insulin resistance, adiposity, and subclinical inflammation in boys. STUDY DESIGN: Thirty age-matched prepubertal boys (9 lean and 21 overweight (OW); age range, 6-10 years) were studied. All participants received nutrition counseling and were randomized to receive FVJC or placebo capsules for 6 months. Total cholesterol, triglycerides, lipid corrected ß-carotene, serum retinol, glucose, insulin, retinol binding protein-4, leptin, adiponectin, leptin-to-adiponectin ratio, high-sensitivity C-reactive protein, and interleukin-6 were measured before and after the 6-month intervention. Homeostasis model assessment-insulin resistance (HOMA-IR), acute insulin response to intravenous glucose, along with abdominal fat mass (dual-energy x-ray absorptiometry) were also determined. RESULTS: Baseline ß-carotene concentrations correlated inversely with HOMA-IR, leptin-to-adiponectin ratio, and abdominal fat mass (P ≤ .01). FVJC intake increased ß-carotene concentrations (P ≤ .001) but did not influence retinol or retinol binding protein-4. Retinol insufficiency <1.047 µM was present in 18% of the entire cohort at baseline and in 37% at 6 months. HOMA-IR decreased after supplementation in the OW cohort, when adjusted for percent weight change (P = .014). The percent change in abdominal fat mass increased in the placebo group and decreased in the FVJC group (P = .029). CONCLUSIONS: A 6-month supplementation with FVJC in the presence of nutritional counseling was associated with an increase in serum ß-carotene concentrations and a reduction in adiposity in conjunction with an improvement in insulin resistance in OW boys.

Implementing medication reconciliation in outpatient pediatrics.

OBJECTIVE: To describe the implementation of a system-wide, electronic medical record (EMR)-based quality improvement intervention targeting medication reconciliation (MedRec) in outpatient pediatrics and to test variables associated with the performance of MedRec. METHODS: This was a retrospective study using serial cross-sections of outpatient pediatric visits over a 5-year period set in a multispecialty children's integrated health care network in Florida, Delaware, Pennsylvania, and New Jersey. We reviewed 2 745 523 outpatient pediatric visits between 2005 and 2010. In 2007, the performance of MedRec was identified as critical to improving patient safety at our organization. A comprehensive intervention involved changes in the EMR, automated generation of medication lists, educational modules, and provider compliance reports. In 2009, quality-based financial incentives to physicians to perform MedRec were added. The outcome measure was documentation of MedRec performance. RESULTS: MedRec improved consistently over time, from a nadir of 0% in 2005 to a maximum of 71% in 2010. Performance of MedRec varied according to practice location as the intervention was rolled out. Throughout the study period, documentation of MedRec was consistently less likely for sick visits (adjusted odds ratio [aOR] for each year ranged from 0.44 to 0.68) but more likely if the provider placed a medication order during the visit (aOR: 1.70-2.15). Beginning in 2009, visits with providers eligible for the quality-based financial incentive were more likely to have had MedRec performed (aOR: 2.02 [2009] and 2.31 [2010]). CONCLUSIONS: A system-wide, EMR-based, outpatient pediatric quality improvement intervention was successful in improving documentation of the performance of MedRec, a national patient safety goal.

Effects of growth hormone and nutritional therapy in boys with constitutional growth delay: a randomized controlled trial.

OBJECTIVE: To examine whether supplemental nutrition augments the anabolic actions of growth hormone (GH) in boys with constitutional delay of growth and maturation (CDGM). STUDY DESIGN: We conducted a randomized, controlled trial at an outpatient clinical research center. Subjects were 20 prepubertal boys (age, 9.3 ± 1.3 years) with CDGM (height standard deviation score, -2.0 ± 0.5; bone age delay, 1.8 ± 0.8 years; body mass index standard deviation score, -1.2 ± 1.0; peak stimulated GH, 15.7 ± 7.7 ng/mL), who were randomized (n = 10/group) to 6 months observation or daily nutritional supplementation, followed by additional daily GH therapy in all for another 12 months. t tests and repeated measures analyses of variance compared energy intake, total energy expenditure (TEE), growth, hormones, and nutrition markers. RESULTS: Energy intake was increased at 6 months within the nutrition group (P = .04), but not the observation group, and TEE was not statistically different within either group at 6 months. Addition of 6 months GH resulted in higher energy intake and TEE in the GH/nutrition group at 12 months (P < .01), but not in the GH group versus baseline. Height, weight, lean body mass, hormones, and nutrition markers increased comparably in both groups throughout 18 months. CONCLUSION: Boys with CDGM use energy at an accelerated rate, an imbalance not overcome with added nutrition. GH therapy increases growth comparably with or without added nutrition in these patients.