Reproducibility of in-home CFRD screening using continuous glucose monitoring and mixed meal tolerance test.

Background: Cystic fibrosis related diabetes (CFRD) is associated with insulin-remediable pulmonary decline, so early detection is critical. Continuous glucose monitors (CGM) have shown promise in screening but are not recommended by clinical practice guidelines. Little is known about the reproducibility of CGM results for a given patient. Methods: Twenty non-insulin treated adults and adolescents with CF placed an in-home CGM and wore it for two 14-day periods. Participants underwent a mixed meal tolerance test (MMTT) on day 5 of each 14-day period. Glycemic data from CGM 1 and CGM 2 were compared regarding published thresholds to define abnormality: percent time >140 mg/dL of ≥4.5%, percent time >140 mg/dL of >17.5%, and percent time >180 mg/dL of >3.4%. Results of the repeat MMTT were compared for peak glucose and 2-hour glucose thresholds: >140 mg/dL, >180 mg/dL, and >200 mg/dL. Results: For percent time >140 mg/dL of ≥ 4.5%, five of 20 subjects had conflicting results between CGM 1 and CGM 2. For percent time >140 mg/dL of >17.5% and >180 mg/dL of >3.4%, only one of 20 subjects had conflicting results between CGM 1 and CGM 2. On the MMTT, few participants had a 2-hour glucose >140 mg/dL. Peak glucose >140 mg/dL, 180 mg/dL, and 200 mg/dL were more common, with 10-37% of participants demonstrating disagreement between CGM 1 and CGM 2. Conclusions: Repeated in-home CGM acquisitions show reasonable reproducibility regarding the more stringent thresholds for time >140 mg/dL and >180 mg/dL. More data is needed to determine thresholds for abnormal mixed meal tolerance tests in CFRD screening.

Protein intake and postprandial hyperglycemia in children and adolescents with type 1 diabetes mellitus, a pilot study.

BACKGROUND AND AIMS: To describe the change in glucose and the resulting postprandial hyperglycemia (PPH) that occurs after dietary protein intake (PI) in children with type 1 diabetes (T1D). METHODS: We conducted a self-controlled, non-randomized, prospective pilot study in children with T1D who were given whey protein isolate drinks (carbohydrate-free, fat-free) of increasing protein amounts (0, 12.5, 25, 37.5, 50, and 62.5 gm) on 6 sequential nights. The glucose levels were monitored with continuous glucose monitors (CGM) and glucometers for 5 h after PI. PPH was defined as glucose elevations over baseline of ≥50 mg/dL. RESULTS: Thirty-eight subjects were recruited, and eleven subjects (6 females, 5 males) completed the intervention. Subjects had a mean (range) age of 11.6 (6-16) years, diabetes duration of 6.1 (1.4-15.5) years, HbA1c of 7.2 (5.2-8.6) % and weight of 44.5 (24.3-63.2) kg. PPH was detected in 1/11, 5/11, 6/10, 6/9, 5/9, and 8/9 subjects after receiving 0, 12.5, 25, 37.5, 50, and 62.5 gm of protein, respectively. CONCLUSIONS: In children with T1D, the association between PPH and PI was observed at smaller protein amounts compared to studies done in adults.

Psychological Characteristics and Goals of Caregivers Choosing Continuous Glucose Monitoring for Children With Type 1 Diabetes.

Background: Continuous glucose monitoring (CGM) can improve glycemic outcomes in pediatric type 1 diabetes management. However, its impact on the psychosocial functioning of caregivers is less well described. The objectives of this pilot study were to explore caregiver reasons for adding CGM to their child's type 1 diabetes management, parental psychosocial function before initiating CGM, and the relationship between the two. Methods: Thirty-two families with a child with type 1 diabetes from Rainbow Babies and Children's Hospital diabetes clinics who were initiating CGM were recruited over 3 months. Before CGM initiation, the caregivers completed the Fear of Hypoglycemia Scale, State-Trait Anxiety Inventory, Problem Areas in Diabetes Scale, and a questionnaire assessing their primary reason for starting CGM. Participant characteristics and questionnaire results were summarized with descriptive statistics. Participants were grouped by reason for starting CGM, and results were compared among groups using ANOVA and reporting the global F test. Results: Fifty percent of respondents indicated that they were starting CGM to optimize glycemic control. The majority of parents (71.8%) expressed worry about helplessness during a hypoglycemic episode. There were no statistically significant differences in patient characteristics or questionnaire results between groups. Forty-three percent of participating families started using CGM during the study's 8-month follow-up period. The main reason (64%) for not starting CGM was not having the chance to start the process of obtaining a CGM system. There were no statistically significant differences between children who did and did not start CGM. Conclusion: Caregivers have different reasons for starting CGM for their child with type 1 diabetes. Further studies are needed to understand whether these reasons are related to differences in psychosocial functioning. Despite interest in starting CGM, there remain barriers to implementation.

Antibiotic Prescription in Young Children With Respiratory Syncytial Virus-Associated Respiratory Failure and Associated Outcomes.

OBJECTIVES: To describe antibiotic prescribing practices during the first 2 days of mechanical ventilation among previously healthy young children with respiratory syncytial virus-associated lower respiratory tract infection and evaluate associations between the prescription of antibiotics at onset of mechanical ventilation with clinical outcomes. DESIGN: Retrospective cohort study. SETTING: Forty-six children's hospitals in the United States. PATIENTS: Children less than 2 years old discharged between 2012 and 2016 with an International Classification of Diseases diagnosis of respiratory syncytial virus-associated lower respiratory tract infection, no identified comorbid conditions, and receipt of mechanical ventilation. INTERVENTIONS: Antibiotic prescription during the first 2 days of mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: We compared duration of mechanical ventilation and hospital length of stay between children prescribed antibiotics on both of the first 2 days of mechanical ventilation and children not prescribed antibiotics during the first 2 days of mechanical ventilation. We included 2,107 PICU children with respiratory syncytial virus-associated lower respiratory tract infection (60% male, median age of 1 mo [interquartile range, 1-4 mo]). The overall proportion of antibiotic prescription on both of the first 2 days of mechanical ventilation was 82%, decreasing over the study period (p = 0.004) and varying from 36% to 100% across centers. In the bivariate analysis, antibiotic prescription was associated with a shorter duration of mechanical ventilation (6 d [4-9 d] vs 8 d [6-11 d]; p < 0.001) and a shorter hospital length of stay (11 d [8-16 d] vs 13 d [10-18 d]; p < 0.001). After adjustment for center, demographics, and vasoactive medication prescription, antibiotic prescription was associated with a 1.21-day shorter duration of mechanical ventilation and a 2.07-day shorter length of stay. Ultimately, 95% of children were prescribed antibiotics sometime during hospitalization, but timing, duration, and antibiotic choice varied markedly. CONCLUSIONS: Although highly variable across centers and decreasing over time, the practice of instituting antibiotics after intubation in young children with respiratory syncytial virus-associated lower respiratory tract infection was associated with a shortened clinical course after adjustment for the limited available covariates. A prudent approach to identify and optimally treat bacterial coinfection is needed.

Lumacaftor/ivacaftor therapy is associated with reduced hepatic steatosis in cystic fibrosis patients.

BACKGROUND: Hepatic steatosis is a common form of cystic fibrosis associated liver disease (CFLD) seen in an estimated 15%-60% of patients with cystic fibrosis (CF). The pathophysiology and health implications of hepatic steatosis in cystic fibrosis remain largely unknown. In the general population, hepatic steatosis is strongly associated with insulin resistance and type 2 diabetes. Cystic fibrosis related diabetes (CFRD) impacts 40%-50% of CF adults and is characterized by both insulin insufficiency and insulin resistance. We hypothesized that patients with CFRD would have higher levels of hepatic steatosis than cystic fibrosis patients without diabetes. AIM: To determine whether CFRD is associated with hepatic steatosis and to explore the impact of lumacaftor/ivacaftor therapy on hepatic steatosis in CF. METHODS: Thirty patients with CF were recruited from a tertiary care medical center for this cross-sectional study. Only pancreatic insufficient patients with CFRD or normal glucose tolerance (NGT) were included. Patients with established CFLD, end stage lung disease, or persistently elevated liver enzymes were excluded. Mean magnetic resonance imaging (MRI) proton density fat fraction (PDFF) was obtained for all participants. Clinical characteristics [age, sex, body mass index, percent predicted forced expiratory volume at 1 s (FEV1), lumacaftor/ivacaftor use] and blood chemistries were assessed for possible association with hepatic steatosis. Hepatic steatosis was defined as a mean MRI PDFF > 5%. Patients were grouped by diabetes status (CFRD, NGT) and cystic fibrosis transmembrane conductance regulator (CFTR) modulator use (lumacaftor/ivacaftor, no lumacaftor/ivacaftor) to determine between group differences. Continuous variables were analyzed with a Wilcoxon rank sum test and discrete variables with a Chi square test or Fisher's exact test. RESULTS: Twenty subjects were included in the final analysis. The median age was 22.3 years (11.3-39.0) and median FEV1 was 77% (33%-105%). Twelve subjects had CFRD and 8 had NGT. Nine subjects were receiving lumacaftor/ivacaftor. The median PDFF was 3.0% (0.0%-21.0%). Six subjects (30%) had hepatic steatosis defined as PDFF > 5%. Hepatic fat fraction was significantly lower in patients receiving lumacaftor/ivacaftor (median, range) (2.0%, 0.0%-6.4%) than in patients not receiving lumacaftor/ivacaftor (4.1%, 2.7-21.0%), P = 0.002. Though patients with CFRD had lower PDFF (2.2%, 0.0%-14.5%) than patients with NGT (4.9%, 2.4-21.0%) this did not reach statistical significance, P = 0.06. No other clinical characteristic was strongly associated with hepatic steatosis. CONCLUSION: Use of the CFTR modulator lumacaftor/ivacaftor was associated with significantly lower hepatic steatosis. No association between CFRD and hepatic steatosis was found in this cohort.

Dietary Intake and Eating-Related Cognitions Related to Sleep Among Adolescents Who Are Overweight or Obese.

OBJECTIVE : To examine associations of sleep duration and regularity with dietary intake and eating-related cognitions among adolescents who are overweight/obese. METHODS : Participants were 315 adolescents being evaluated through Healthy Kids, Healthy Weight. Outcomes were reported sleep duration and regularity (bedtime shift, wake-time shift, sleep duration shift). Major predictors were dietary intake (e.g., consumption of calories and sugar-sweetened beverages) and eating-related cognitions (food preoccupation, eating self-efficacy). RESULTS : Findings were that staying up (i.e., bedtime shift) and sleeping in later (i.e., wake-time shift) on weekends compared with weekdays significantly relates to drinking more sugar-sweetened beverages, the latter for males. Sleeping in on weekends was related to greater food preoccupation. CONCLUSIONS : Sleep regularity was the most important variable in its relationships with dietary intake. Evaluating sleep patterns and improving them with behavioral interventions should be considered as an additional weight loss strategy to promote dietary adherence.

Accuracy of the Spacelabs 90217 ambulatory blood pressure monitor in a pediatric population.

BACKGROUND: Ambulatory blood pressure monitoring techniques provide unique advantages for diagnosing hypertension, although few devices have been independently validated in the pediatric population. METHODS: We sought to validate the accuracy of ambulatory blood pressure monitoring with the Spacelabs 90217 monitor in children using a modified British Hypertension Society protocol. RESULTS: A total of 112 children, aged between 6 and 17 years, completed the study at one of the three participating centers. Overall, the monitor earned an 'A' for systolic blood pressure and 'B' for diastolic blood pressure. It performed slightly better among 6-12 year olds (A/A) compared with 13-17 year olds (A/B). CONCLUSIONS: We conclude that the Spacelabs 90217 monitor is an appropriate monitor for use in children who are 6 years of age or older.

Plasma Sclerostin in HIV-Infected Adults on Effective Antiretroviral Therapy.

Sclerostin is linked to bone physiology and cardiovascular disease through the Wnt/ß-catenin signaling pathway. The goal of this study was to determine if sclerostin is related to bone physiology and cardiovascular disease during antiretroviral treatment in HIV-infected persons. This was a cross-sectional analysis from study entry into the Stopping Atherosclerosis and Treating Unhealthy bone with RosuvastatiN in HIV (SATURN) trial, an ongoing randomized trial comparing rosuvastatin to placebo in HIV-infected adults on antiretroviral therapy. Plasma sclerostin was measured at study entry by ELISA from participants with available samples. Spearman correlation and multivariable linear regression were used to test relationships between sclerostin and bone density or bone turnover and cardiovascular disease. Among 139 HIV-infected participants (median age 46 years, CD4 lymphocyte count 614 cells/µl), the median plasma sclerostin level was 444.1 (IQR 330.3, 570.1) pg/ml. Correlations were detected between sclerostin and age (r=0.26), lumbar spine Z-score (r=0.31), RANKL (r=-0.21), carotid intima-media thickness (CIMT, r=0.19), and sVCAM-1 (r=0.27), p<0.05. No significant correlations were detected between sclerostin and current (r=0.006) or nadir CD4 count (r=0.11). While associations between sclerostin, lumbar spine Z-score, and sVCAM-1 were robust to covariate adjustment (p<0.01), association with CIMT was no longer significant (p=0.08). Our findings provide preliminary support for a relationship between sclerostin and bone mineral density in HIV-infected persons. The Wnt/ß-catenin pathway should be investigated as a potential mechanism for loss of bone mineral density in treated HIV infection.

Risk of Social Media for Teens in an Urban Setting.

Purpose. To describe the self-reported risky behaviors associated with adolescent social media use. Methods. Adolescents ages 13 to 21 years were recruited from a large, urban academic center to complete a written survey regarding social media use. Results are presented as frequencies and percentage; nominal variables were compared using χ(2) analysis. Results. Almost all participants (93%) reported belonging to a social media site. The majority of adolescents (72%) access the Internet with a phone. Nearly half (49%) of participants accept friend requests from strangers, 42% send friend requests to strangers, and 55% of participants report meeting people from social media sites in person. Conclusion. Adolescents self-report engaging in a number of risky behaviors when they use social media. Teenagers' use of social media is an additional behavior that requires attention and monitoring.

Changes in fat mitochondrial DNA and function in subjects randomized to abacavir-lamivudine or tenofovir DF-emtricitabine with atazanavir-ritonavir or efavirenz: AIDS Clinical Trials Group study A5224s, substudy of A5202.

BACKGROUND: The effect of nonthymidine nucleoside reverse-transcriptase inhibitors (NRTIs) on fat mitochondrial DNA (mtDNA) content and function is unclear. METHODS: A5202 randomized antiretroviral therapy-naive human immunodeficiency virus-infected subjects to abacavir-lamivudine (ABC/3TC) versus tenofovir DF-emtricitabine (TDF/FTC) with efavirenz (EFV) or atazanavir-ritonavir (ATV/r). A5224s, substudy of A5202, enrolled 269 subjects with fat measurements by dual-energy x-ray absorptiometry and computed tomography. A subset of subjects underwent fat biopsies at baseline and week 96 for mtDNA content (real-time polymerase chain reaction) and oxidative phosphorylation nicotinamide adenine dinucleotide (reduced) dehydrogenase (complex I) and cytochrome c oxidase (complex IV) activity levels (immunoassays). Intent-to-treat analyses were performed using analysis of variance and paired t tests. RESULTS: Fifty-six subjects (87% male; median age, 39 years) were included; their median body mass index, CD4 cell count, and fat mtDNA level were 26 kg/m(2), 227 cells/µL, and 1197 copies/cell, respectively. Fat mtDNA content decreased within the ABC/3TC and TDF/FTC groups (combining EFV and ATV/r arms; median change, -341 [interquartile range, -848 to 190; P = .03] and -400 [-661 to -221; P < .001] copies/cell, respectively), but these changes did not differ significantly between the 2 groups (P = .57). Complex I and IV activity decreased significantly in the TDF/FTC group (median change, -12.45 [interquartile range, -24.70 to 2.90; P = .003] and -8.25 [-13.90 to -1.30; P < .001], optical density × 10(3)/µg, respectively) but not the ABC/3TC group. Differences between the ABC/3TC and TDF/FTC groups were significant for complex I (P = .03). CONCLUSIONS: ABC/3TC and TDF/FTC significantly and similarly decreased fat mtDNA content, but only TDF/FTC decreased complex I and complex IV activity levels. CLINICAL TRIALS REGISTRATION: NCT00118898.

Mitochondrial function, inflammation, fat and bone in HIV lipoatrophy: randomized study of uridine supplementation or switch to tenofovir.

BACKGROUND: Lipoatrophy modestly improves when the thymidine analogue nucleoside reverse transcriptase inhibitor (tNRTI) is removed. In vitro, uridine (NucleomaxX(®); Pharma Nord, Vojens, Denmark) reversed tNRTI mitochondrial toxicity. METHODS: All patients had lipoatrophy on a tNRTI-containing regimen with HIV RNA<400 copies/ml. A randomized 48-week study switched patients from tNRTI to tenofovir (TDF) or added uridine (continuing tNRTI). End points were changes in limb fat (DEXA), subcutaneous abdominal fat mitochondrial DNA (mtDNA) and mitochondrial RNA (mtRNA), inflammation markers (soluble tumour necrosis factor receptors, high-sensitivity C reactive protein [hsCRP], interleukin-6 [IL-6], soluble vascular cell adhesion molecule 1), bone mineral density (BMD) of the hip and spine, HIV-1 RNA, CD4(+) T-cells and fasting metabolic parameters. RESULTS: Fifty patients were enrolled (n=24 TDF switch; n=26 uridine); median age 48 years; 54% white; 86% male; limb fat 4,494 g. Baseline characteristics were similar between groups. In the NucleomaxX(®) arm, mtRNA increased (all P<0.001), hsCRP and IL-6 increased (both P=0.02), whereas fat mtDNA decreased without changes in limb fat. In the TDF-switch arm, fat mtDNA and inflammation markers did not change; however, significant increases in mtRNAs (P<0.001), limb fat (409 g; IQR -59-1,155) and CD4(+) T-cell count (P=0.03), and decreases in total and hip BMD (median -3.3%; IQR -5.1-0; P=0.005) were observed. Between-group changes were significant for fat mtDNA, hsCRP, IL-6, limb fat and hip BMD. No correlation was found between changes in limb fat and those of fat mtRNA, inflammation markers or protease inhibitor duration. CONCLUSIONS: In HIV lipoatrophy, NucleomaxX(®) improved mtRNA, but worsened inflammation markers and fat mtDNA without changes in limb fat. Switching from a tNRTI to TDF for 48 weeks increased limb fat and fat mtRNA. Large decreases in total and hip BMD were seen after TDF switch.ClinicalTrials.gov identifier: NCT00119379.

Automated cerebrospinal fluid cell counts using the Sysmex XE-5000: is it time for new reference ranges?

The main objectives of the study were to compare manual and automated WBC counts on clear cerebrospinal fluid (CSF) samples. Clear CSF samples from 200 adults and children were studied. Cell counts were performed manually using a hemocytometer and then analyzed on the Sysmex XE-5000. Descriptive statistics and Spearman correlation for nonparametric data were used for method comparison. Manual WBC counts ranged from 0 to 702 cells/µL, and Sysmex counts ranged from 0 to 629 cells/µL. The Spearman rank correlation coefficient for the entire range of data was 0.77 (P < .001); however, the correlation was weaker at the low end of the data spectrum. For manual WBC ranges of 0 to 5 cells/µL and 0 to 10 cells/µL, the corresponding Sysmex 0 to 95th percentile ranges were 0 to 23 cells/µL and 0 to 27 cells/µL, respectively. The results suggest that larger studies are necessary to determine new reference ranges for automated CSF WBC counts.

Salsalate is poorly tolerated and fails to improve endothelial function in virologically suppressed HIV-infected adults.

In this 13-week, open-label, randomized study of the anti-inflammatory salsalate versus usual care, there were no significant improvements in flow-mediated dilation of the brachial artery, endothelial activation, inflammation or coagulation markers, homeostasis model assessment of insulin resistance or lipoproteins with salsalate or between groups in virologically suppressed, HIV-infected adults on antiretrovirals. Tinnitus and transaminitis occurred frequently in the salsalate group. Dose reduction due to toxicities encountered and low level of inflammation may explain these results.

Development and validation of a questionnaire to assess carbohydrate and insulin-dosing knowledge in youth with type 1 diabetes.

OBJECTIVE The American Diabetes Association advocates insulin regimens for youth with type 1 diabetes that involve adjusting insulin dose based on carbohydrate intake and blood glucose level. Implementing these regimens requires knowledge about carbohydrate content of foods and subsequent calculations of insulin dose, skills that may be difficult to gauge in practice. Therefore, we sought to develop and validate a questionnaire, the PedCarbQuiz (PCQ), to assess carbohydrate and insulin-dosing knowledge in youth with type 1 diabetes. RESEARCH DESIGN AND METHODS After development by an expert panel, the PCQ was administered to 75 youth with type 1 diabetes or their parents. Reliability was assessed by Cronbach alpha and split-half testing. To assess validity, scores were correlated with A1C, expert assessments, parent educational level, and complexity of insulin regimen. RESULTS PCQ mean score was 87 +/- 9.7% (range 42-98%). Cronbach alpha was 0.88, and correlation of split halves was 0.59 (P < 0.0001). Higher PCQ scores correlated significantly with lower A1C (r = -0.29, P = 0.01) and expert assessments (r = 0.56, P < 0.001). Scores were significantly higher in parents with college degrees than in those without (P = 0.01) and in participants with more complex insulin regimens (P = 0.003). CONCLUSIONS The PCQ is a novel, easily administered instrument to assess knowledge about carbohydrates and insulin dosing calculations. Initial analyses support the reliability and validity of the PCQ.

Parental anxiety and medical comprehension within 24 hrs of a child's admission to the pediatric intensive care unit*.

OBJECTIVE: Admission of a child to the pediatric intensive care unit (PICU) can create high-parental anxiety. The authors examined the factors that contribute to parental anxiety and the effect of parental anxiety on comprehension of medical information within 24 hrs of a child's admission to the PICU. The physician's recognition of parental anxiety related to their child's hospitalization was also evaluated. DESIGN: Prospective cohort study with a convenience sample of primary caregivers of critically ill children. SETTING: Twenty-bed PICU at an urban tertiary children's hospital. SUBJECTS: The primary caregivers of 35 children with Pediatric Risk of Mortality III scores >or=7 admitted to the PICU as well as PICU fellows. INTERVENTIONS: Parental anxiety was assessed with the State-Trait Anxiety Inventory, a validated tool used to measure both the temporary (State) and long-standing (Trait) anxiety in adults. Comprehension of medical information was assessed by an open-ended questionnaire. Physician assessment of parental anxiety was measured by multiple-choice questionnaire. MEASUREMENTS AND MAIN RESULTS: Of the 34 parents completing the State-Trait Anxiety Inventory, 21 (62%) had State Anxiety that was significantly higher than a validated sample of patients with generalized anxiety disorder. The child's need for mechanical ventilation was the only significant predictor of high-parental State Anxiety (p = .03). Among the 28 parents completing the questionnaire of comprehension of medical information, 26 (93%) demonstrated excellent or fair comprehension. Physicians had generally low recognition of parental anxiety but were significantly more likely to rate a parent's anxiety as high if the child was on mechanical ventilation. CONCLUSION: Parental anxiety is high following a child's admission to the PICU. Physicians failed to recognize high-parental anxiety in nearly one third of the parents. Despite the high anxiety associated with a child's admission to the PICU, parents seem to understand their children's medical issues within the first 24 hrs.

Mitochondrial RNA and DNA alterations in HIV lipoatrophy are linked to antiretroviral therapy and not to HIV infection.

BACKGROUND: The aim of this study was to assess the effect of antiretroviral therapy (ART) versus HIV on mitochondria in fat. METHODS: Subcutaneous fat was collected from 45 HIV-infected patients on ART with lipoatrophy, 11 HIV-infected ART-naive patients and nine healthy controls. Three mitochondrial transcripts: NADH dehydrogenase subunit 1 (ND1), cytochrome B (CYTB) and NADH dehydrogenase subunit 6 (ND6) genes were quantitated using TaqMan probes and normalized to nuclear-encoded ribosomal L13. RESULTS: ND1/L13 and CYTB/L13 were lower in HIV-positive patients on ART with lipoatrophy versus ART-naive patients (3.4 versus 7.2 [P=0.017] and 2.5 versus 4.6 [P=0.006], respectively). No difference was found between ART-naive patients and controls (P>0.70). ND6/L13 was similar between all groups. Dual-energy X-ray absorptiometry-measured limb fat and mitochondrial DNA in fat were also lower in HIV-positive patients on ART with lipoatrophy versus HIV-infected, ART-naive patients (4,382 versus 7,662 g [P=0.02] and 726 versus 1,372 copies/cell [P=0.03], respectively), but no difference was found between ART-naive and controls. In a multiple regression analysis, limb fat correlated with all three mitochrondrial RNA, whereas mitochondrial DNA did not correlate with mitochondrial RNA or limb fat. CONCLUSIONS: In contrast to ART-naive patients, HIV-positive patients on ART with lipoatrophy had significant depletion in mitochondrial DNA in fat and mitochondrial RNAs. This suggests that mitochondrial toxicity in lipoatrophy could be driven by ART and not by HIV itself. In addition, mitochondrial RNA abnormalities, and not mitochondrial DNA depletion, could be a key driving force behind lipoatrophy.

Increased carotid intima media thickness and cardiac biomarkers in HIV infected children.

OBJECTIVES: To assess carotid intima media thickness (IMT) and cardiac biomarkers in HIV infected children on antiretroviral therapy (ART). METHODS: This was a single site, cross sectional, controlled observational study. We assessed carotid IMT, homocysteine, high-sensitivity C-reactive protein and myeloperoxidase levels in HIV infected children on stable ART for >or= 6 months. Carotid IMT was reported as internal carotid artery (ICA) and common carotid artery (CCA) thickness; left and right sides were measured separately. Groups were compared using appropriate two-sample tests. RESULTS: Of the 62 subjects enrolled, 31 were HIV positive (50%), 66% were female, and 69% were African-American. Median CD4% was 32% and 26 patients (84%) had HIV-1 RNA< 400 copies/ml. Sixteen patients had been taking protease inhibitors for a median duration of 27 months. None had hypertension or smoked. HIV infected children had higher HOMA-IR, waist-to-hip ratio, cholesterol, triglycerides, myeloperoxidase and lower homocysteine levels. Left and right CCA IMT, and left and right ICA IMT were significantly higher in the HIV infected group. Significant predictors of carotid IMT measurements in uninfected controls were body mass index and homocysteine, but only the duration of ARV therapy was predictive of IMT in the HIV infected group. CONCLUSION: Higher levels of carotid IMT and some cardiac markers were found in ART treated HIV infected children when compared to matched uninfected controls. These results suggest that HIV infected children receiving ART may be at increased risk of cardiovascular disease.