Method for controlled mitochondrial perturbation during phosphorus MRS in children.

UNLABELLED: Insulin resistance is increasingly prevalent in children and may be related to muscle mitochondrial dysfunction, necessitating development of mitochondrial assessment techniques. Recent studies used phosphorus magnetic resonance spectroscopy (P-MRS), a noninvasive technique appealing for clinical research. P-MRS requires exercise at a precise percentage of maximum volitional contraction (MVC). MVC measurement in children, particularly in those with a disease, is problematic because of variability in perception of effort and motivation. We therefore developed a method to predict MVC using maximal calf muscle cross-sectional area (MCSA) to assure controlled and reproducible muscle metabolic perturbations. METHODS: Data were collected from 66 sedentary 12- to 20-yr-old participants. Plantarflexion MVC was assessed using an MRI-compatible exercise treadle device. MCSA of the calf muscles were measured from magnetic resonance images. Data from the first 26 participants were used to model the relation between MVC and MCSA (predicted MVC = 24.763 + 0.0047 MCSA). This model was then applied to the subsequent 40 participants. RESULTS: MVC versus model-predicted mean MVC was 43.9 ± 0.8 kg versus 44.2 ± 1.81 (P = 0.90). P-MRS results when predicted and MVC were similar showed expected changes during MVC-based exercise. In contrast, MVC was markedly lower than predicted in four participants and produced minimal metabolic perturbation. Upon repeat testing, these individuals could perform their predicted MVC with coaching, which produced expected metabolic perturbations. CONCLUSIONS: Compared with using MVC testing alone, using magnetic resonance imaging to predict muscle strength allows for a more accurate and standardized P-MRS protocol during exercise in children. This method overcomes a major obstacle in assessing mitochondrial function in youths. These studies have importance as we seek to determine the role of mitochondrial function in youths with insulin resistance and diabetes and response to interventions.

Urinary matrix metalloproteinase activities: biomarkers for plaque angiogenesis and nephropathy in diabetes.

Diabetic complications of nephropathy and accelerated atherosclerosis are associated with vascular remodeling and dysregulated angiogenesis. Matrix metalloproteinases (MMP) modify extracellular matrix during vascular remodeling and are excreted in urine of patients with vascular malformation or tumor angiogenesis. We hypothesized that urinary MMP activities would be sensitive biomarkers for vascular remodeling in diabetic complications. Activities of MMP-2, MMP-9, and its complex with neutrophil gelatinase-associated lipocalin (NGAL/MMP-9) were measured by substrate gel zymography in urine from nondiabetic (ND) and type 1 diabetic (T1D) rodents that were susceptible to both T1D-induced plaque angiogenesis and nephropathy, or nephropathy alone. Additionally, these urine activities were measured in ND and T1D adolescents. Urinary MMP-9, MMP-2, and NGAL/MMP-9 activities were increased and more prevalent in T1D compared with ND controls. Urinary MMP-2 activity was detected in mice with T1D-induced plaque neovascularization. In nephropathy models, urinary NGAL/MMP-9 and MMP-9 activities appeared before onset of albuminuria, whereas MMP-2 was absent or delayed. Finally, urinary MMP activities were increased in adolescents with early stages of T1D. Urinary MMP activities may be sensitive, noninvasive, and clinically useful biomarkers for predicting vascular remodeling in diabetic renal and vascular complications.

HIV testing in emergency departments in the United States: a national survey.

OBJECTIVES: In 2006, the Centers for Disease Control and Prevention (CDC) published recommendations for HIV testing in health care settings, calling for nontargeted opt-out rapid HIV screening in most settings, including emergency departments (EDs). Although a number of ED-based testing strategies exist, it is unclear to what extent they are used. The objective of this study is to survey academic and community EDs throughout the United States to determine ED-based HIV testing practices. METHODS: This was a cross-sectional survey study of all academic EDs and a weighted random sample of all community-based EDs in the United States. A standardized survey instrument was developed and administered with an Internet-based survey platform, followed by direct contact and mail. The survey included domains related to perceived HIV testing barriers, whether HIV testing was performed and methods used, and familiarity with the CDC recommendations and whether they had been adopted. RESULTS: Of the 131 total academic sites and the 435 community sites, 99 (76%) and 150 (35%) completed the survey, respectively. A larger proportion of academic sites believed HIV testing was needed (P=.02) and a larger proportion actually provided HIV testing (65% versus 50%; P=.04). Among the academic and community EDs that provided testing, 74% and 62% performed diagnostic testing, 26% and 22% performed targeted screening, and 16% and 6% performed nontargeted screening, respectively. A larger proportion of academic EDs reported receiving external funding to support testing (23% versus 4%; P=.001), whereas a large proportion of community sites considered costs a significant barrier to testing (P=.03). A larger proportion of academic EDs reported being familiar with the 2006 CDC recommendations (64% versus 40%; P<.001), although only 26% and 37% reported having implemented any part of them, respectively. CONCLUSION: Academic EDs only make up approximately 3% of all EDs in the United States. Significant differences exist between academic and community EDs as they relate to performing HIV testing. Increased efforts should be made to improve the ability of community EDs to provide this service.

Insulin resistance in adolescents with type 1 diabetes and its relationship to cardiovascular function.

CONTEXT: Cardiovascular disease is the major cause of death in adults with diabetes, yet little is specifically known about the effects of type 1 diabetes (T1D) on cardiovascular outcomes in youth. Although insulin resistance (IR) likely contributes to exercise and cardiovascular dysfunction in T2D, IR is not typically considered a contributor in T1D. OBJECTIVE: We hypothesized that cardiopulmonary fitness would be reduced in T1D youth in association with IR and cardiovascular dysfunction. DESIGN AND PARTICIPANTS: This cross-sectional study at an academic hospital included 12 T1D adolescents compared with 12 nondiabetic controls, similar in age, pubertal stage, activity level, and body mass index. OUTCOME MEASURES: Cardiopulmonary fitness was measured by peak oxygen consumption (VO(2)peak) and oxygen uptake kinetics (VO(2)kinetics), IR by hyperinsulinemic clamp, cardiac function by echocardiography, vascular function by venous occlusion plethysmography, intramyocellular lipid by magnetic resonance spectroscopy, and body composition by dual-energy x-ray absorptiometry. RESULTS: T1D adolescents had significantly decreased VO(2)peak, peak work rate, and insulin sensitivity compared with nondiabetic adolescents. T1D youth also had reduced vascular reactivity and evidence of diastolic dysfunction and left ventricular hypertrophy. Despite their IR and reduced cardiovascular fitness, T1D youth had paradoxically normal intramyocellular lipid, waist to hip ratio, and serum lipids and high adiponectin levels. In multivariate analysis, IR primarily, and forearm blood flow secondarily, independently predicted VO(2)peak. CONCLUSIONS: T1D youth demonstrated IR, impaired functional exercise capacity and cardiovascular dysfunction. The phenotype of IR in T1D youth was unique, suggesting a pathophysiology that is different from T2D, yet may adversely affect long-term cardiovascular outcomes.