Michala Holm Reichkendler

Body fat loss and compensatory mechanisms in response to different doses of aerobic exercise—a randomized controlled trial in overweight sedentary males

The amount of weight loss induced by exercise is often disappointing. A diet-induced negative energy balance triggers compensatory mechanisms, e.g., lower metabolic rate and increased appetite. However, knowledge about potential compensatory mechanisms triggered by increased aerobic exercise is limited. A randomized controlled trial was performed in healthy, sedentary, moderately overweight young men to examine the effects of increasing doses of aerobic exercise on body composition, accumulated energy balance, and the degree of compensation. Eighteen participants were randomized to a continuous sedentary control group, 21 to a moderate-exercise (MOD; 300 kcal/day), and 22 to a high-exercise (HIGH; 600 kcal/day) group for 13 wk, corresponding to ∼30 and 60 min of daily aerobic exercise, respectively. Body weight (MOD: -3.6 kg, P < 0.001; HIGH: -2.7 kg, P = 0.01) and fat mass (MOD: -4.0 kg, P < 0.001 and HIGH: -3.8 kg, P < 0.001) decreased similarly in both exercise groups. Although the exercise-induced energy expenditure in HIGH was twice that of MOD, the resulting accumulated energy balance, calculated from changes in body composition, was not different (MOD: -39.6 Mcal, HIGH: -34.3 Mcal, not significant). Energy balance was 83% more negative than expected in MOD, while it was 20% less negative than expected in HIGH. No statistically significant changes were found in energy intake or nonexercise physical activity that could explain the different compensatory responses associated with 30 vs. 60 min of daily aerobic exercise. In conclusion, a similar body fat loss was obtained regardless of exercise dose. A moderate dose of exercise induced a markedly greater than expected negative energy balance, while a higher dose induced a small but quantifiable degree of compensation.

Exercise training favors increased insulin-stimulated glucose uptake in skeletal muscle in contrast to adipose tissue: a randomized study using FDG PET imaging.

Physical exercise increases peripheral insulin sensitivity, but regional differences are poorly elucidated in humans. We investigated the effect of aerobic exercise training on insulin-stimulated glucose uptake in five individual femoral muscle groups and four different adipose tissue regions, using dynamic (femoral region) and static (abdominal region) 2-deoxy-2-[¹⁸F]fluoro-d-glucose (FDG) PET/CT methodology during steady-state insulin infusion (40 mU·m⁻²·min⁻¹). Body composition was measured by dual X-ray absorptiometry and MRI. Sixty-one healthy, sedentary [V(O2max) 36(5) ml·kg⁻¹·min⁻¹; mean(SD)], moderately overweight [BMI 28.1(1.8) kg/m²], young [age: 30(6) yr] men were randomized to sedentary living (CON; n = 17 completers) or moderate (MOD; 300 kcal/day, n = 18) or high (HIGH; 600 kcal/day, n = 18) dose physical exercise for 11 wk. At baseline, insulin-stimulated glucose uptake was highest in femoral skeletal muscle followed by intraperitoneal visceral adipose tissue (VAT), retroperitoneal VAT, abdominal (anterior + posterior) subcutaneous adipose tissue (SAT), and femoral SAT (P < 0.0001 between tissues). Metabolic rate of glucose increased similarly (~30%) in the two exercise groups in femoral skeletal muscle (MOD 24[9, 39] μmol·kg⁻¹·min⁻¹, P = 0.004; HIGH 22[9, 35] μmol·kg⁻¹·min⁻¹, P = 0.003) (mean[95% CI]) and in five individual femoral muscle groups but not in femoral SAT. Standardized uptake value of FDG decreased ~24% in anterior abdominal SAT and ~20% in posterior abdominal SAT compared with CON but not in either intra- or retroperitoneal VAT. Total adipose tissue mass decreased in both exercise groups, and the decrease was distributed equally among subcutaneous and intra-abdominal depots. In conclusion, aerobic exercise training increases insulin-stimulated glucose uptake in skeletal muscle but not in adipose tissue, which demonstrates some interregional differences.

Only minor additional metabolic health benefits of high as opposed to moderate dose physical exercise in young, moderately overweight men.

The dose–response effects of exercise training on insulin sensitivity, metabolic risk, and quality of life were examined.

Appetite regulation in overweight, sedentary men after different amounts of endurance exercise: a randomized controlled trial

Weight loss induced by endurance exercise is often disappointing, possibly due to an increase in energy intake mediated through greater appetite. The aim of this study was to evaluate fasting, postprandial, and postexercise appetite regulation after an intervention prescribing two amounts of endurance exercise. Sixty-four sedentary, overweight, healthy young men were randomized to control (CON), moderate-dose (MOD: ≈ 30 min/day), or high-dose (HIGH: ≈ 60 min/day) endurance exercise for 12 wk. Along with subjective appetite ratings, plasma ghrelin, glucagon, insulin, peptide YY3-36, glucose, free fatty acids, and glycerol were measured during fasting and in relation to a breakfast meal and an acute bout of exercise, both at baseline and at follow-up. Ad libitum lunch energy intake was evaluated 3 h after the breakfast meal. Despite different amounts of endurance exercise, the subjects lost similar amounts of fat mass (MOD: 4.2 ± 0.5 kg; HIGH: 3.7 ± 0.5 kg). Fasting and postprandial insulin decreased ≈ 20% in both exercise groups (P < 0.03 vs. CON). Appetite measurements were not upregulated in the fasting and postprandial states. On the contrary, fasting and postprandial ratings of fullness and postprandial PYY3-36 increased in HIGH (P < 0.001 vs. CON). Ad libitum lunch energy intake remained unchanged over the course of the intervention. In both exercise groups, plasma ghrelin increased in relation to acute exercise after training. Thus neither moderate nor high doses of daily endurance exercise increased fasting and postprandial measures of appetite, but a high dose of exercise was associated with an increase in fasting and meal-related ratings of fullness and satiety.

Changes in peak fat oxidation in response to different doses of endurance training

The effect of different doses of endurance training on the capacity to oxidize fat during exercise in sedentary, overweight men and assessment of variables associated with changes in peak fat oxidation (PFO) were evaluated. Young, sedentary, overweight men were randomized to either the high‐dose (HIGH, 600 kcal/day, n = 17) or moderate‐dose (MOD, 300 kcal/day, n = 18) endurance training groups or controls (CON, n = 15). PFO and peak oxygen uptake (VO2 peak) were measured using indirect calorimetry, body composition using dual‐energy x‐ray absorptiometry, and protein levels of mitochondrial enzymes determined by Western blotting. PFO increased in both MOD [1.2 mg/kg fat‐free mass (FFM)/min, 95% confidence interval (CI): 0.08:2.3, P = 0.03] and HIGH (1.8 mg/kg FFM/min, CI: 0.6:2.9, P < 0.001) compared with CON. Skeletal muscle expression of citrate synthase, β‐hydroxyacyl‐CoA dehydrogenase, and mitochondrial oxphos complexes II‐V increased similarly in MOD and HIGH. Stepwise multiple linear regression analysis with backward elimination of individual variables correlated with changes in PFO revealed increases in cycling efficiency, FFM, and VO2 peak as the remaining associated variables. In conclusion, PFO during exercise increased with both moderate‐ and high‐dose endurance training. Increases in PFO were mainly predicted by changes in VO2 peak, FFM, and cycling efficiency, and less with skeletal muscle mitochondrial enzymes.

A Prospective Study Comparing 99mTc-Hydroxyethylene-Diphosphonate Planar Bone Scintigraphy and Whole-Body SPECT/CT with 18F-Fluoride PET/CT and 18F-Fluoride PET/MRI for Diagnosing Bone Metastases

We prospectively evaluated and compared the diagnostic performance of 99mTc-hydroxyethylene-diphosphonate (99mTc-HDP) planar bone scintigraphy (pBS), 99mTc-HDP SPECT/CT, 18F-NaF PET/CT, and 18F-NaF PET/MRI for the detection of bone metastases. Methods: One hundred seventeen patients with histologically proven malignancy referred for clinical pBS were prospectively enrolled. pBS and whole-body SPECT/CT were performed followed by 18F-NaF PET/CT within 9 d. 18F-NaF PET/MRI was also performed in 46 patients. Results: Bone metastases were confirmed in 16 patients and excluded in 101, which was lower than expected. The number of equivocal scans was significantly higher for pBS than for SPECT/CT and PET/CT (18 vs. 5 and 6, respectively; P = 0.004 and 0.01, respectively). When equivocal readings were excluded, no statistically significant difference in sensitivity, specificity, positive predictive value, negative predictive value, or overall accuracy were found when comparing the different imaging techniques. In the per-patient analysis, equivocal scans were either assumed positive for metastases (“pessimistic analysis”) or assumed negative for metastases (“optimistic analysis”). The percentages of misdiagnosed patients for the pessimistic analysis were 21%, 15%, 9%, and 7% for pBS, SPECT/CT, PET/CT, and PET/MRI, respectively. Corresponding figures for the optimistic analysis were 9%, 12%, 5%, and 7%. In those patients identified as having bone metastases according to the reference standard, SPECT/CT, 18F-NaF PET/CT, and PET/MRI detected additional lesions compared with pBS in 31%, 63%, and 71%, respectively. Conclusion: 18F-NaF PET/CT and whole-body SPECT/CT resulted in a significant reduction of equivocal readings compared with pBS, which implies an improved diagnostic confidence. However, the clinical benefit of using, for example, 18F-NaF PET/CT or PET/MRI as compared with SPECT/CT and pBS in this patient population with a relatively low prevalence of bone metastases (14%) is likely limited. This conclusion is influenced by the low prevalence of patients with osseous metastases. There may well be significant differences in the sensitivity of SPECT/CT, PET/CT, and PET/MRI compared with pBS, but a larger patient population or a patient population with a higher prevalence of bone metastases would have to be studied to demonstrate this.

A prospective study comparing 99mTc-HDP planar bone scintigraphy and whole-body SPECT/CT with 18F-fluoride PET/CT and 18F-fluoride PET/MRI for diagnosing bone metastases

We prospectively evaluated and compared the diagnostic performance of 99mTc-hydroxyethylene-diphosphonate (99mTc-HDP) planar bone scintigraphy (pBS), 99mTc-HDP SPECT/CT, 18F-NaF PET/CT, and 18F-NaF PET/MRI for the detection of bone metastases. Methods: One hundred seventeen patients with histologically proven malignancy referred for clinical pBS were prospectively enrolled. pBS and whole-body SPECT/CT were performed followed by 18F-NaF PET/CT within 9 d. 18F-NaF PET/MRI was also performed in 46 patients. Results: Bone metastases were confirmed in 16 patients and excluded in 101, which was lower than expected. The number of equivocal scans was significantly higher for pBS than for SPECT/CT and PET/CT (18 vs. 5 and 6, respectively; P = 0.004 and 0.01, respectively). When equivocal readings were excluded, no statistically significant difference in sensitivity, specificity, positive predictive value, negative predictive value, or overall accuracy were found when comparing the different imaging techniques. In the per-patient analysis, equivocal scans were either assumed positive for metastases (“pessimistic analysis”) or assumed negative for metastases (“optimistic analysis”). The percentages of misdiagnosed patients for the pessimistic analysis were 21%, 15%, 9%, and 7% for pBS, SPECT/CT, PET/CT, and PET/MRI, respectively. Corresponding figures for the optimistic analysis were 9%, 12%, 5%, and 7%. In those patients identified as having bone metastases according to the reference standard, SPECT/CT, 18F-NaF PET/CT, and PET/MRI detected additional lesions compared with pBS in 31%, 63%, and 71%, respectively. Conclusion: 18F-NaF PET/CT and whole-body SPECT/CT resulted in a significant reduction of equivocal readings compared with pBS, which implies an improved diagnostic confidence. However, the clinical benefit of using, for example, 18F-NaF PET/CT or PET/MRI as compared with SPECT/CT and pBS in this patient population with a relatively low prevalence of bone metastases (14%) is likely limited. This conclusion is influenced by the low prevalence of patients with osseous metastases. There may well be significant differences in the sensitivity of SPECT/CT, PET/CT, and PET/MRI compared with pBS, but a larger patient population or a patient population with a higher prevalence of bone metastases would have to be studied to demonstrate this.

Compliance with physical exercise: Using a multidisciplinary approach within a dose-dependent exercise study of moderately overweight men

Aims: Sixty-one healthy, sedentary, moderately overweight young men participated in a randomised controlled trial to examine the effects of two different doses of endurance exercise on health behaviour and exercise compliance. Methods: Participants were randomised to a sedentary control group, a moderate (MOD; 300 kcal/day) or a high-dose (HIGH; 600 kcal/day) endurance exercise group for 12 weeks. A sub-set of the subjects were interviewed using pre-determined, qualitative questions to elucidate physical activity and health behaviour. In combination with the Theory of Planned Behaviour (TPB), a post hoc thematic analysis was conducted to connect qualitative and quantitative data in a joint analysis. Results: Of the subjects interviewed, exercise compliance expressed as 95% CI was [96.8; 103%] in the MOD group and [82.9; 99.6%] in the HIGH group. The different doses of daily exercise equally improved various metabolic health parameters. The MOD group was untroubled by the exercise load and had a positive attitude towards exercise. The HIGH group expressed increased fatigue, less positivity and perceived exercise as time-consuming. The MOD group described themselves as more energetic, and thereby may have increased physical activity levels in areas of their everyday lives that were not related to the intervention. Conclusions: A multidisciplinary approach provided explanations for similar effects of two different doses of exercise. This could not have been determined via either qualitative or quantitative methodology alone. The preconditions of the TBP were fulfilled, and it represents a methodological model to explain the high degree of compliance and motivation to exercise.

Effect of Different Doses of Exercise on Sleep Duration, Sleep Efficiency and Sleep Quality in Sedentary, Overweight Men

Objective: To evaluate the dose-response effect of aerobic exercise on sleep duration, sleep efficiency and sleep quality in previously sedentary, moderately overweight men. Methods: In a randomized, controlled trial, 53 sedentary Caucasian men aged between 20 and 40 years (VO2- max 25%) completed a 13-week aerobic exercise intervention consisting of either a physical activity energy deficit of 600 kcal day -1 (HIGH: n=18), 300 kcal day -1 (MOD: n=18), or being sedentary (CON: n=17). The endpoints were sleep duration (objectively measured by actigraphy over 3 days), sleep efficiency (3-day actigraphy), and subjectively rated sleep quality (Pittsburgh Sleep Quality Index). Results: Because of missing sleep data, a total of 32 subjects were included in the present analysis (CON: n=12, MOD: n=12, HIGH: n=8). A significant increase in sleep duration was observed in HIGH (80 ± 30 min, p=0.03). However, the change was not significantly different from the change in CON. Sleep efficiency tended to decrease in HIGH (p=0.05), and there was a tendency towards an improved sleep quality within MOD and HIGH (p=0.08 in both). Conclusion: Our study suggests that a high daily dose of aerobic exercise for 13 weeks increases sleep duration, tends to decrease sleep efficiency, and tends to improve subjective sleep quality in sedentary, moderately overweight men. Because our sample included relatively young and sleep-efficient individuals, future studies should examine the dose-response effects of aerobic exercise on sleep parameters in older adults with sleeping problems.

Calibrated image-derived input functions for the determination of the metabolic uptake rate of glucose with [18F]-FDG PET.

PurposeWe investigated the use of a simple calibration method to remove bias in previously proposed approaches to image-derived input functions (IDIFs) when used to calculate the metabolic uptake rate of glucose (Km) from dynamic [18F]-FDG PET scans of the thigh. Our objective was to obtain nonbiased, low-variance Km values without blood sampling. Materials and methodsWe evaluated eight previously proposed IDIF methods. Km values derived from these IDIFs were compared with Km values calculated from the arterial blood samples (gold standard). We used linear regression to extract calibration parameters to remove bias. Following calibration, cross-validation and bootstrapping were used to estimate the mean square error and variance. ResultsThree of the previously proposed methods failed mainly because of zero-crossings of the IDIF. The remaining five methods were improved by calibration, yielding unbiased Km values. The method with the lowest SD yielded an SD of 0.0017/min – that is, below 10% of the muscle Km value in this study. ConclusionPreviously proposed IDIF methods can be improved by using a simple calibration procedure. The calibration procedure may be used in other studies, thus obviating the need for arterial blood sampling, once the calibration parameters have been established in a subgroup of participants. The method has potential for use in other parts of the body as it is robust with regard to partial volume effects.