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ObjectiveTo compare body composition parameters estimated by air displacement plethysmography (ADP) to dual x-ray absorptiometry (DXA) in body mass index (BMI) classifications that include extremely obese (BMI≥40.0kg/m2), and to examine if differences between analyses were influenced by BMI.Design and MethodsFat free mass (FFM,kg), fat mass (FM,kg) and body fat (BF,%) were analyzed with both technologies.ResultsAll outcome measures of ADP and DXA were highly correlated (r≥0.95,P<0.001 for FFM, FM and BF), but Bland-Altman analyses revealed significant bias (P<0.01 for all). ADP estimated greater FFM and lower FM and BF (P<0.01 for all). BMI explained 27% of the variance in differences between FFM measurements (P<0.001), and 37% and 33% of the variances in differences between FM and BF measurements, respectively (P<0.001 for both). Within normal weight and overweight classifications, ADP estimated greater FFM and lower FM and BF (P<0.001 for all), but the opposite occurred within the extremely obese classification; ADP estimated lower FFM and greater FM and BF (P<0.05 for all).ConclusionsBody composition analyses by the two technologies were strongly congruent, but systematically different and influenced by BMI. Caution should be taken when utilizing ADP to estimate body composition parameters over a wide range of BMI classifications that include extremely obese.

Background Aging-related disease risk is exacerbated by obesity and physical inactivity. It is unclear how weight loss and increased activity improve risk in older adults. We aimed to determine the effects of diet-induced weight loss with and without exercise on insulin sensitivity, VO2peak, body composition, and physical function in older obese adults. Methods Physically inactive older (68.6 ± 4.5 years) obese (BMI 37.4 ± 4.9 kg/m 2) adults were randomized to: Health education control (HEC; n=25); Diet-induced weight loss (WL; n=31); or Weight loss and exercise (WLEX; n=28) for 6 months. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp, body composition by DXA and MRI, strength by isokinetic dynamometry, and VO2peak by graded exercise test. Results WLEX improved (p&lt;0.05) peripheral insulin sensitivity (+75 ± 103%) vs. HEC (+12 ± 67%); WL (+36 ± 47%) vs. HEC did not reach statistical significance. WLEX increased VO2peak (+7 ± 12%) vs. WL (-2 ± 24%), and prevented reductions in strength and lean mass induced by WL (p&lt;0.05). WLEX decreased abdominal adipose tissue (-16 ± 9%) vs. HEC (-3 ± 8%) and intermuscular adipose tissue (-15 ± 13 %) vs. both HEC (+9 ± 15%) and WL (+2 ± 11%) (p&lt;0.01). Conclusions Exercise with weight loss improved insulin sensitivity and VO2peak, decreased ectopic fat, and preserved lean mass and strength. Weight loss alone decreased lean mass and strength. Older adults intending to lose weight should perform regular exercise to promote cardiometabolic and functional benefits, which may not occur with calorie restriction-induced weight loss alone.

The nitrate-nitrite-NO pathway regulates NO synthase–independent vasodilation and NO signaling. Ingestion of inorganic nitrite has vasodilatory and blood pressure–lowering effects. Preclinical studies in rodent models suggest there may be a benefit of nitrite in lowering serum triglyceride levels and improving the metabolic syndrome. In a phase 2 study, we evaluated the safety and efficacy of chronic oral nitrite therapy in patients with hypertension and the metabolic syndrome. Twenty adult subjects with stage 1 or 2 hypertension and the metabolic syndrome were enrolled in an open-label safety and efficacy study. The primary efficacy end point was blood pressure reduction; secondary end points included insulin-dependent glucose disposal and endothelial function measured by flow-mediated dilation of the brachial artery and intima-media diameter of the carotid artery. Chronic oral nitrite therapy (40 mg/3× daily) was well tolerated. Oral nitrite significantly lowered systolic, diastolic, and mean arterial pressures, but tolerance was observed after 10 to 12 weeks of therapy. There was significant improvement in the intima-media thickness of the carotid artery and trends toward improvements in flow-mediated dilation of the brachial artery and insulin sensitivity. Chronic oral nitrite therapy is safe in patients with hypertension and the metabolic syndrome. Despite an apparent lack of enzymatic tolerance to nitrite, we observed tolerance after 10 weeks of chronic therapy, which requires additional mechanistic studies and possible therapeutic dose titration in clinical trials. Nitrite may be a safe therapy to concominantly improve multiple features of the metabolic syndrome including hypertension, insulin resistance, and endothelial dysfunction. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01681810.

Objective: To determine effects of physical activity (PA) with diet-induced weight loss on energy metabolism in adults with severe obesity. Methods: Adults with severe obesity (n 5 11) were studied across 6 months of intervention, then compared with controls with less severe obesity (n 5 7) or normal weight (n 5 9). Indirect calorimetry measured energy metabolism during exercise and rest. Markers of muscle oxidation were determined by immunohistochemistry. Data were presented as medians. Results: The intervention induced 7% weight loss (P 5 0.001) and increased vigorous PA by 24 min/wk (P 5 0.02). During exercise, energy expenditure decreased, efficiency increased (P 0.03), and fatty acid oxidation (FAO) did not change. Succinate dehydrogenase increased (P 5 0.001), but fiber type remained the same. Post-intervention subjects' resting metabolism remained similar to controls. Efficiency was lower in post-intervention subjects compared with normal-weight controls exercising at 25 W (P 0.002) and compared with all controls exercising at 60% VO 2peak (P 0.019). Resting and exercise FAO of post-intervention subjects remained similar to adults with less severe obesity. Succinate dehydrogenase and fiber type were similar across all body weight statuses. Conclusions: While metabolic adaptations to PA during weight loss occur in adults with severe obesity, FAO does not change. Resulting FAO during rest and exercise remains similar to adults with less severe obesity.

Study Design: Pilot non-randomized clinical trial Objectives: To examine the feasibility, acceptability and preliminary efficacy of performing handcycling high intensity interval training (HIIT) for six weeks in wheelchair users with spinal cord injury. Setting: Participant’s home Methods: Participants completed pre and post graded exercise stress tests, exercise surveys and six weeks of handcycling HIIT. The HIIT program consisted of two weekly, 25 minute supervised at-home sessions (2-3 min warm-up, then 10 intervals of cycling with a ratio of 1 minute work at 90% peak power output (PPO) to 1 minute recovery at 0-20% PPO, then 2-3 min cool-down). Real-time power output and heart rate were recorded via sensors and a bike computer. The sensor data were analyzed to evaluate training efficacy. Results: Seven of the 10 enrolled participants (70%) completed the study. All but one completed the required 12 sessions. The participants met at least one of the HIIT target intensity criteria in 76 out of 89 total sessions (85.4%) performed. Participants expressed a high level of enjoyment on the Physical Activity Enjoyment Scale, mean (SD) = 114.8 (11.3), and satisfaction with the overall experience. Five of the seven participants (71%) who completed the study felt an increase in endurance, function and health. Objective physiological changes showed mixed results. Conclusions: Six weeks of handcycling HIIT appears to be safe, feasible and acceptable. A longer HIIT work interval may be needed to elicit significant physiological responses. Future investigation of the feasibility and efficacy of differing HIIT parameters is needed.

III.

Introduction: Although nitrate and nitrite have traditionally been considered to be inert and potentially toxic metabolites of nitric oxide (NO) oxidation, it is now appreciated that both can be recycled to bioactive NO. Recent evidence suggests that the human nitrate-nitrite-NO pathway mediates signaling through NO to reduce blood pressure and endothelial function. The effects of oral nitrite on insulin sensitivity, however, are not known. Therefore, we developed the investigational drug, oral inorganic sodium nitrite, to assess its therapeutic effects. Methods: Our goal was to examine the effect of 12 weeks of open-label oral sodium nitrite 40 mg three times daily in this pilot study. We employed hyperinsulinemic-euglycemic clamps to assess insulin sensitivity, flow mediated dilation (FMD) to measure endothelial function, and pulse wave velocity (PWV) and carotid intima media thickness (IMT) to measure arterial stiffening and thickening, respectively, in obese adults with metabolic syndrome and uncontrolled hypertension. Results: Eighteen subjects were recruited with mean age 53 years, BMI 41 kg/m2 and BP 147/88 mmHg and 72% were female. Following 12 weeks of nitrite treatment, systolic (-10 mmHg), diastolic (-13 mmHg) and mean arterial pressures were reduced (-12 mmHg; all p&lt;0.001). Insulin stimulated glucose disposal tended to improve (14%; 7.4±0.7 at baseline to 8.4±0.8 mg/kg/min post, p=0.08) after oral nitrite treatment compared to baseline. Carotid IMT decreased from 0.762±0.02 at baseline to 0.727±0.03 mm post (p&lt;0.01), and FMD and PWV trended towards improvement with oral sodium nitrite treatment. There were no changes in body weight, BMI, fasting glucose, HbA1c or lipids. Conclusion: Oral sodium nitrite treatment is a promising therapeutic to improve insulin sensitivity, blood pressure and arterial thickening in at-risk obese adults with metabolic syndrome and uncontrolled hypertension. Disclosure K.S. Hughan: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company. N.L. Helbling: None. S.J. Anthony: None. J. DeLany: None. B.H. Goodpaster: None. M. Gladwin: Other Relationship; Self; National Institutes of Health, Globin Solutions, Bayer AG.