Recent technical advances allow detection of several hundred volatile organic compounds (VOCs) in human exhaled air, many of which reflect unidentified endogenous pathways. Our group has previously estimated plasma glucose levels in healthy adults during a standard oral glucose tolerance test via exhaled VOC analysis. As a result of the metabolic characteristics of hyperglycemia in the diabetic (low insulin and increased free fatty acids and ketones), we hypothesized that different exhaled VOC profiles may be present in children with type 1 diabetes mellitus (T1DM) during spontaneous hyperglycemia. Exhaled methyl nitrate strongly correlated specifically with the acute, spontaneous hyperglycemia of T1DM children. Eighteen experiments were conducted among 10 T1DM children. Plasma glucose and exhaled gases were monitored during either constant euglycemia (n ‫؍‬ 5) or initial hyperglycemia with gradual correction (n ‫؍‬ 13); all subjects received i.v. insulin and glucose as needed. Gas analysis was performed on 1.9-liter breath samples via gas chromatography using electron capture, flame ionization, and mass selective detection. Among the Ϸ100 measured exhaled gases, the kinetic profile of exhaled methyl nitrate, commonly present in room air in the range of 5-10 parts per trillion, was most strongly statistically correlated with that of plasma glucose (P ‫؍‬ 0.003-0.001). Indeed, the kinetic profiles of the two variables paralleled each other in 16 of 18 experiments, including repeat subjects who at different times displayed either euglycemia or hyperglycemia.exhaled gases ͉ volatile organic compounds ͉ gas chromatography ͉ plasma glucose T he analysis of volatile organic compounds (VOCs) has been recognized for decades as a diagnostic tool with great potential for application to human breath, and several attempts have been made to use this technique for metabolic monitoring. However, intrinsic difficulties in measurement and analysis have resulted in inconsistent results, severely limiting its practical applicability.Recent advances in VOC analytical technology may have reduced the impact of these technical issues, lowering detection limit of measurable gas concentrations, and increasing the repeatability and stability of measurements. Indeed, in recent years a rising number of studies centered on exhaled VOC clinical applications have been generated (1-5). Most studies, however, are focused on the detection of single disease markers, i.e., exhaled gas profiles constantly present in definite groups of patients, independent of their moment-by-moment metabolic changes. We believe that this approach, while having the potential of detecting important diagnostic markers, greatly underutilizes exhaled gas analysis. Exhaled gas profiles are likely involved in endogenous metabolic processes and are, therefore, constantly changing in response to the extremely complex human endogenous biochemical milieu. The extreme versatility of exhaled gas analysis (combining simultaneous measurements of 100 or more exhaled gases in each ...

Lee J, Ngo J, Blake DB, Meinardi S, Pontello AM, Newcomb R, Galassetti PR. Improved predictive models for plasma glucose estimation from multi-linear regression analysis of exhaled volatile organic compounds. J Appl Physiol 107: 155-160, 2009. First published May 7, 2009 doi:10.1152/japplphysiol.91657.2008.-Exhaled volatile organic compounds (VOCs) represent ideal biomarkers of endogenous metabolism and could be used to noninvasively measure circulating variables, including plasma glucose. We previously demonstrated that hyperglycemia in different metabolic settings (glucose ingestion in pediatric Type 1 diabetes) is paralleled by changes in exhaled ethanol, acetone, and methyl nitrate. In this study we integrated these gas changes along with three additional VOCs (2 forms of xylene and ethylbenzene) into multi-linear regression models to predict plasma glucose profiles in 10 healthy young adults, during the 2 h following an intravenous glucose bolus (matched samples of blood, exhaled and room air were collected at 12 separate time points). The four-gas model with highest predictive accuracy estimated plasma glucose in each subject with a mean R value of 0.91 (range 0.70 -0.98); increasing the number of VOCs in the model only marginally improved predictions (average R with best 5-gas model ϭ 0.93; with 6-gas model ϭ 0.95). While practical development of this methodology into clinically usable devices will require optimization of predictive algorithms on large-scale populations, our data prove the feasibility and potential accuracy of breath-based glucose testing. breath analysis; exhaled gases; hyperglycemia; intravenous glucose tolerance test VOLATILE ORGANIC COMPOUNDS (VOCs) present in human breath are potentially ideal biomarkers of endogenous metabolic processes, as human breath samples can be collected noninvasively and painlessly in virtually any condition. Many of these VOCs may be important by-products of physiological or altered endogenous metabolic pathways and can conceivably be developed into prognostic, diagnostic, and monitoring tools for a variety of biomedical fields. Only in recent years have advances in analytical technology drastically reduced prior measurement difficulties, allowing detection of hundreds, possibly thousands, of VOCs in human exhalates at extremely low concentrations (the best technology currently available allows measurements as low as 10 parts per quadrillion by volume). Most of the current studies applying this technology in a number of laboratories from various countries, however, are still at an exploratory stage (27), while concrete, practical applicability of this concept has been limited to a handful of gases present in exhaled breath at relatively high concentrations, such as exhaled acetone in diabetic ketoacidosis (20, 26) or exhaled urea in gastric H. pylori infection (16).An intriguing application of this technology is the identification and kinetic measurement of exhaled biomarkers of carbohydrate metabolism, with the downstream goal of developing portable devic...

Firefighters and police officers have the third highest prevalence of obesity among 41 male occupational groups in the United States (US). However, few studies have examined the relationship of firefighter working conditions and health behaviors with obesity. This paper presents a theoretical framework describing the relationship between working conditions, health behaviors, and obesity in firefighters. In addition, the paper describes a detailed study plan for exploring the role of occupational and behavioral risk factors in the development of obesity in firefighters enrolled in the Orange County Fire Authority Wellness Fitness Program. The study plan will be described with emphasis on its methodological merits: adopting a participatory action research approach, developing a firefighter-specific work and health questionnaire, conducting both a cross-sectional epidemiological study using the questionnaire and a sub-study to assess the validity of the questionnaire with dietary intake and physical activity measures, and evaluating the strengths and weaknesses of the body mass index as an obesity measure in comparison to skinfold-based percent body fat. The study plan based on a theoretical framework can be an essential first step for establishing effective intervention programs for obesity among professional and voluntary firefighters.

Objective:  An imbalance of pro‐/anti‐inflammatory cytokines may accelerate diabetic vascular complications and interfere with proper wound healing. Currently, limited available literature suggests that plasma concentrations of certain pro‐ and anti‐inflammatory cytokines may be altered during hyperglycemia/diabetes mellitus. It is still unclear, however, whether these concepts also apply to children with diabetes, and whether alterations in circulating cytokine levels are a permanent feature of diabetes or an acute effect of fluctuating glucose concentrations. Methods:  Twenty‐two children with type 1 diabetes mellitus (T1DM) were studied. In 13 children, postprandial morning plasma glucose was >11.1 mmol/L at least once (hyperglycemic group, or HyG group); in 9 subjects, plasma glucose never exceeded 10.6 mmol/L (non‐hyperglycemic group, or non‐HyG group). After admission, intensive euglycemia (5.0–6.1 mmol/L) was achieved in all participants via intravenous insulin and dextrose for at least 90 min. Blood samples were drawn every 30 min to determine plasma levels of 14 cytokines and chemokines. Results:  Interleukin IL‐1α, IL‐4, and IL‐6 were elevated in HyG group compared with non‐HyG not only when plasma glucose was elevated but also during the first 2 h following return to euglycemia. The levels of the other 11 cytokines were not significantly different. Conclusions:  Specific cytokines (IL‐1α, IL‐4, and IL‐6) are acutely elevated during hyperglycemia in children with T1DM, and these elevations persist for hours after hyperglycemia has been corrected. Therefore, aside from glycemic control, additional therapeutic measures against elevated proinflammatory signals may be necessary for preventing vascular complications in children with hyperglycemic diabetes.

To evaluate the effects of a 12-month exercise intervention using either high-impact step aerobic exercise or moderate-intensity strength training on areal bone mineral density (aBMD) we studied 51 untrained women, aged 20-35 years, for this study. Whole body and heel and wrist aBMD were measured by dual-energy X-ray absorptiometry (DXA, Hologic or PIXI Lunar). Subjects were randomly assigned to: impact-loaded step aerobic exercise (SA, n=15), moderate-intensity lower body strength training (ST, n=16) or non-exercise control (CON, n=20). Data analysis only included those who completed 95% of each training routine and attended at least 80% of all sessions. Group differences in aBMD, leg press strength and urinary cross-link deoxypridinoline (μDPD) were analysed using analysis of variance. After a 12-month intervention, the SA elicited an increase in aBMD of the heel (4.4%, p<0.05) and leg press strength (15%, p<0.05), relative to baseline. Meanwhile, the ST showed an increase in leg press strength (48%, p<0.05) with no significant increase in aBMD at any measured site. Similar and unchanged μDPD was observed in all 3 groups at baseline, 6 and 12 months. In conclusion, a 12-month high-impact step aerobic exercise resulted in a significant increase in the heel aBMD in untrained young women, who complied with the exercise regimen. A moderate intensity strength training intervention of similar duration had no effect on aBMD although leg strength increased significantly.

Objective-A prospective, cross-sectional, observational study in pre-and term infants was performed to compare multimodal measurements of body composition namely, limb ultrasound, bone quantitative ultrasound and dual X-ray absorptiometry (DXA).Patients and Methods-102 preterm and term appropriate for gestational age infants were enrolled from the newborn nursery and neonatal intensive care unit. Infants were included when they were medically stable, in an open crib, on full enteral feeds and within one week of anticipated discharge. Correlations among the various measurements of body composition were performed using standard techniques. A comparison between preterm infant (born at 28-32w) reaching term to term born infants was performed.Results and Conclusions-Limb ultrasound estimates of cross sectional areas of lean and fat tissue in a region of tissue (i.e., the leg) were remarkably correlated with regional and whole body estimates of fat free mass and fat obtained from DXA suggesting the potential usefulness of muscle ultrasound as an investigative tool for studying aspects of body composition in this fragile population. There was a weak but significant correlation between quantitative ultrasound measurements of bone strength and DXA derived BMD. Preterm infants reaching term had significantly lower body weight, length, head circumference, muscle and fat cross sectional area, bone SOS, whole body and regional lean body mass, fat mass and BMD compared to term born infants. Current post-natal care and nutritional support in preterm infants is still unable to match the in-utero environment for optimal growth and bone development. The use of relatively simple bedside, non invasive body composition measurements may assist in the understanding how changes in different components of body composition early in life affect later growth and development.

. Effect of prior hyperglycemia on IL-6 responses to exercise in children with type 1 diabetes. Am J Physiol Endocrinol Metab 290: E833-E839, 2006. First published December 6, 2005 doi:10.1152/ajpendo.00445.2005.-The proinflammatory cytokine interleukin-6 (IL-6) may modulate the onset and progression of complications of diabetes. As this cytokine increases after exercise, and many other exercise responses are altered by prior glycemic fluctuations, we hypothesized that prior hyperglycemia might exacerbate the IL-6 response to exercise. Twenty children with type 1 diabetes (12 boys/8 girls, age 12-15 yr) performed 29 exercise studies (30-min intermittent cycling at ϳ80% peak O2 uptake). Children were divided into four groups based on highest morning glycemic reading [blood glucose (BG) Ͻ 150, BG 151-200, BG 201-300, or BG Ͼ 300 mg/dl]. All exercise studies were performed in the late morning, after hyperglycemia had been corrected and steadystate conditions (plasma glucose Ͻ120 mg/dl, basal insulin infusion) had been maintained for Ն90 min. Blood samples for IL-6, growth factors, and counterregulatory hormones were drawn at pre-, end-, and 30 min postexercise time points. At all time points, circulating IL-6 was lowest in BG Ͻ 150 and progressively higher in the other three groups. The exercise-induced increment also followed a similar doseresponse pattern (BG Ͻ 150, 0.6 Ϯ 0.2 ng/ml; BG 151-200, 1.2 Ϯ 0.8 ng/ml; BG 201-300, 2.1 Ϯ 1

Pediatric obesity, a major risk factor for cardiovascular diseases and diabetes, has steadily increased in the last decades. Although excessive inflammation and oxidation are possible biochemical links between obesity and cardiovascular events in adults, little information is available in children. Furthermore, effects of gender and fitness on the interaction between dyslipidemia and oxidative or inflammatory stress in children are mostly unknown. Therefore, we measured systemic markers of oxidation (F2-isoprostanes, F2-IsoP, and antioxidants) and inflammation (interleukin-6, IL-6, and leukocyte counts) and metabolic variables in 113 peripubertal children (55 obese, Ob, age and gender-adjusted BMI%≥95th, 25F; 15 overweight, OW, BMI% 85th–95th, 8F; 43 normoweight, CL, 25F). Overall, when compared to CL, Ob displayed elevated F2-IsoP (99±7 vs. 75±4 pg/mL, p<0.005), IL-6 (2.2±0.2 vs. 1.5±0.3 pg/mL, p<0.005), elevated total WBC and neutrophils, and altered levels of total cholesterol, LDL-C, HDL-C, triglycerides, free fatty acids, glucose, and insulin (all p<0.005). This pattern was independent of gender and not caused by reduced fitness in Ob. Our data indicate that alterations in metabolic control and a concomitant increase in inflammation and oxidative stress occur early in life in obese children, likely exposing both genders to a similar degree of increased risk of future cardiovascular diseases.