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Background: Integrated guidelines on cardiovascular health and risk reduction in children issued in 2011 newly recommended universal screening for dyslipidemia in children at 9 to 11 years and 17 to 21 years., Methods and Results: We determined the frequency and results of lipid testing in 301 080 children and adolescents aged 3 to 19 enrolled in 3 large US health systems in 2007 to 2010 before the 2011 guidelines were issued. Overall, 9.8% of the study population was tested for lipids. The proportion tested varied by body mass index percentile (5.9% of normal weight, 10.8% of overweight, and 26.9% of obese children) and age (8.9% of 9- to 11-year olds and 24.3% of 17- to 19-year olds). In normal weight individuals, 2.8% of 9- to 11-year olds and 22.0% of 17- to 19-year olds were tested. In multivariable models, age and body mass index category remained strongly associated with lipid testing. Sex, race, ethnicity, and blood pressure were weakly associated with testing. Abnormal lipid levels were found in 8.6% for total cholesterol, 22.5% for high-density lipoprotein-cholesterol, 12.0% for non-high-density lipoprotein-cholesterol, 8.0% for low-density lipoprotein-cholesterol, and 21% for triglycerides (age, 10-19 years). There was a strong and graded association of abnormal lipid levels with body mass index, particularly for high-density lipoprotein-cholesterol and triglycerides (2- to 6-fold higher odds ratio in obese when compared with that in normal weight children)., Conclusions: Lipid screening was uncommon in 9- to 11-year olds and was performed in a minority of 17- to 19-year olds during 2007 to 2010. These data serve as a benchmark for assessing change in practice patterns after the new recommendations for pediatric lipid screening and management., (© 2014 American Heart Association, Inc.)

Background: Some HIV protease inhibitors (PIs) have been shown to induce insulin resistance in vitro but the degree to which specific PIs affect insulin sensitivity in humans is less well understood., Methods: In two separate double-blind, randomized, cross-over studies, we assessed the effects of a single dose of ritonavir (800 mg) and amprenavir (1200 mg) on insulin sensitivity (euglycemic hyperglycemic clamp) in healthy normal volunteers., Results: Ritonavir decreased insulin sensitivity (-15%; P = 0.008 versus placebo) and non-oxidative glucose disposal (-30%; P = 0.0004), whereas neither were affected by amprenavir administration., Conclusion: Compared to previously performed studies of identical design using single doses of indinavir and lopinavir/ritonavir, a hierarchy of insulin resistance was observed with the greatest effect seen with indinavir followed by ritonavir and lopinavir/ritonavir, with little effect of amprenavir.

Purpose of Review: The metabolic syndrome is a constellation of physical and laboratory abnormalities including hypertension, hyperglycemia, hyperlipidemia and abdominal obesity. Over the past decade, the metabolic syndrome has emerged as a critically important risk factor for cardiovascular disease., Recent Findings: A large population-based cross-sectional analysis (the National Health and Nutrition Evaluation Survey III) found that the presence of the metabolic syndrome was associated with chronic kidney disease, defined as an estimated glomerular filtration rate of less than 60 ml/min per 1.73 m and was also associated with proteinuria. More recently, a prospective cohort study found that the presence of the metabolic syndrome was associated with incident chronic kidney disease by the same definition, even when excluding individuals with diabetes mellitus and hypertension. More studies are required to determine whether the relationship between the metabolic syndrome and chronic kidney disease is mainly mediated by hyperglycemia (with insulin resistance) and hypertension, or other metabolic or hemodynamic factors., Summary: The metabolic syndrome is associated with chronic kidney disease. Efforts aimed at determining the mechanisms underlying this association and strategies for the prevention of chronic kidney disease (or slowing the progression of chronic kidney disease) in affected patients should be research priorities in the future.

Purpose of Review: To review recent literature about the relationship between non-dialysis-requiring chronic kidney disease and cardiovascular disease as well as possible explanatory factors., Recent Findings: Reduced estimated glomerular filtration rate below 60 ml/min/1.73 m independently predicts the risk of death and cardiovascular events in persons with or without known cardiovascular disease as well as those undergoing coronary or peripheral arterial revascularization. This risk is not linearly associated with level of kidney function. Chronic kidney disease is associated with a larger burden of traditional vascular risk factors but is also linked to abnormalities in a variety of nontraditional pathways such as dysregulation of mineral metabolism and arterial calcification, vessel stiffness and endothelial dysfunction, insulin resistance, inflammation, malnutrition, and anemia, among others. Other novel kidney-specific proteins (e.g. renalase) may play direct mediating roles. The relative contribution of these factors to excess cardiovascular disease in chronic kidney disease remains unclear., Summary: Recent evidence demonstrates the importance of non-dialysis-requiring chronic kidney disease as a potent predictor of cardiovascular disease and its complications. Randomized trials should be performed to determine whether modification of traditional and nontraditional risk factors can reduce incident cardiovascular disease as well as which interventions can optimize treatment outcomes in persons with chronic kidney disease and cardiovascular disease.

In the absence of HIV infection, changes in adipose tissue and lipid levels, HIV protease inhibitor therapy increases fasting glucose levels,suggestive of hepatic insulin resistance. After 4 weeks of indinavir treatment in nine HIV-negative healthy men, fasting glucose production and glycogenolysis were significantly increased. During the euglycemic hyperinsulinemic clamp, indinavir blunted the ability of insulin to suppress glucose production. Therefore, indinavir worsens hepatic insulin sensitivity, increasing endogenous glucose production.

Background: Therapy with HIV protease inhibitors (PI) has been shown to worsen glucose and lipid metabolism, but whether these changes are caused by direct drug effects, changes in disease status, or body composition is unclear. Therefore, we tested the effects of the PI combination lopinavir and ritonavir on glucose and lipid metabolism in HIV-negative subjects., Methods: A dose of 400 mg lopinavir/100 mg ritonavir was given twice a day to 10 HIV-negative men. Fasting glucose and insulin, lipid and lipoprotein profiles, oral glucose tolerance, insulin sensitivity by euglycemic hyperinsulinemic clamp, and body composition were determined before and after lopinavir/ritonavir treatment for 4 weeks., Results: On lopinavir/ritonavir, there was an increase in fasting triglyceride (0.89 +/- 0.15 versus 1.63 +/- 0.36 mmol/l; P = 0.007), free fatty acid (FFA; 0.33 +/- 0.04 versus 0.43 +/- 0.06 mmol/l; P = 0.001), and VLDL cholesterol (15.1 +/- 2.6 versus 20 +/- 3.3 mg/dl; P = 0.05) levels. There were no changes in fasting LDL, HDL, IDL, lipoprotein (a), or total cholesterol levels. Fasting glucose, insulin, and insulin-mediated glucose disposal were unchanged, but on a 2 h oral glucose tolerance test glucose and insulin increased. There were no changes in weight, body fat, or abdominal adipose tissue by computed tomography., Conclusion: Treatment with 4 weeks of lopinavir/ritonavir in HIV-negative men causes an increase in triglyceride levels, VLDL cholesterol, and FFA levels. Lopinavir/ritonavir leads to a deterioration in glucose tolerance at 2 h, but there is no significant change in insulin-mediated glucose disposal rate by euglycemic hyperinsulinemic clamp.

Objective: To determine whether treatment with growth hormone (GH) enhances thymopoiesis in individuals infected with HIV-1., Methods: Five HIV-1-infected adults were treated with GH for 6-12 months in a prospective open-label study. Immunological analyses were performed before GH treatment and repeated at 3 month intervals after GH initiation. Thymic mass was analysed using computed tomography with quantitative density and volume analysis. Analysis of circulating lymphocytes, including naive and memory T cell subsets, was performed using multiparameter flow cytometry., Results: GH treatment was associated with a marked increase in thymic mass in all GH recipients. Circulating naive CD4 T cells also increased significantly in all patients during GH therapy, suggesting an enhancement of thymopoiesis., Conclusion: GH has significant effects on the human immune system, including the reversal of thymic atrophy in HIV-1-infected adults. De-novo T cell production may thus be inducible in immunodeficient adults.

Background: Therapy with HIV protease inhibitors (PI) causes insulin resistance even in the absence of HIV infection, hyperlipidemia or changes in body composition. The mechanism of the effects on insulin action is unknown. In vitro studies suggest that PI selectively and rapidly inhibit the activity of the insulin-responsive glucose transporter GLUT-4. We hypothesized that a single dose of the PI indinavir resulting in therapeutic plasma concentrations would acutely decrease insulin-stimulated glucose disposal in healthy human volunteers., Methods: Randomized, double-blind, cross-over study comparing the effect of 1200 mg of orally administered indinavir and placebo on insulin-stimulated glucose disposal during a 180-min euglycemic, hyperinsulinemic clamp. Six healthy HIV-seronegative adult male volunteers were studied twice with 7 to 10 days between studies., Results: There were no significant differences in baseline fasting body weight, or plasma glucose, insulin, lipid and lipoprotein levels between placebo- and indinavir-treated subjects. During steady-state (t60-180 min) insulin reached comparable levels (394 +/- 13 versus 390 +/- 11 pmol/l) and glucose was clamped at approximately 4.4 mmol/l under both conditions. The average maximum concentration of indinavir was 9.4 +/- 2.2 microM and the 2-h area under the curve was 13.5 +/- 3.1 microM.h. Insulin-stimulated glucose disposal per unit of insulin (M/I) decreased in all subjects from 14.1 +/- 1.2 to 9.2 +/- 0.8 mg/kg.min per microUI/ml (95% confidence interval for change, 3.7-6.1; P < 0.001) on indinavir (average decrease, 34.1 +/- 9.2%). The non-oxidative component of total glucose disposal (storage) decreased from 3.9 +/- 1.8 to 1.9 +/- 0.9 mg/kg.min (P < 0.01). Free fatty acid levels were not significantly different at baseline and were suppressed equally with insulin administration during both studies., Conclusions: A single dose of indinavir acutely decreases total and non-oxidative insulin-stimulated glucose disposal during a euglycemic, hyperinsulinemic clamp. Our data are compatible with the hypothesis that an acute effect of indinavir on glucose disposal in humans is mediated by a direct blockade of GLUT-4 transporters.