Plasma apoM and S1P levels are inversely associated with mortality in African Americans with type 2 diabetes mellitus.

apoM is a minor HDL apolipoprotein and carrier for sphingosine-1-phosphate (S1P). HDL apoM and S1P concentrations are inversely associated with atherosclerosis progression in rodents. We evaluated associations between plasma concentrations of S1P, plasma concentrations of apoM, and HDL apoM levels with prevalent subclinical atherosclerosis and mortality in the African American-Diabetes Heart Study participants (N = 545). Associations between plasma S1P, plasma apoM, and HDL apoM with subclinical atherosclerosis and mortality were assessed using multivariate parametric, nonparametric, and Cox proportional hazards models. At baseline, participants' median (25th percentile, 75th percentile) age was 55 (49, 62) years old and their coronary artery calcium (CAC) mass score was 26.5 (0.0, 346.5). Plasma S1P, plasma apoM, and HDL apoM were not associated with CAC. After 64 (57.6, 70.3) months of follow-up, 81 deaths were recorded. Higher concentrations of plasma S1P [odds ratio (OR) = 0.14, P = 0.01] and plasma apoM (OR = 0.10, P = 0.02), but not HDL apoM (P = 0.89), were associated with lower mortality after adjusting for age, sex, statin use, CAC, kidney function, and albuminuria. We conclude that plasma S1P and apoM concentrations are inversely and independently associated with mortality, but not CAC, in African Americans with type 2 diabetes after accounting for conventional risk factors.

Quantification of sphingosine 1-phosphate by validated LC-MS/MS method revealing strong correlation with apolipoprotein M in plasma but not in serum due to platelet activation during blood coagulation.

Sphingosine 1-phosphate (S1P) is a signalling sphingolipid affecting multiple cellular functions of vascular and immune systems. It circulates at submicromolar levels bound to HDL-associated apolipoprotein M (apoM) or to albumin. S1P in blood is mainly produced by platelets and erythrocytes, making blood sampling for S1P quantification delicate. Standardisation of sampling is thereby of great importance to obtain robust data. By optimising and characterising the extraction procedure and the LC-MS/MS analysis, we have developed and validated a highly specific and sensitive method for S1P quantification. Blood was collected from healthy individuals (n = 15) to evaluate the effects of differential blood sampling on S1P levels. To evaluate correlation between S1P and apoM in different types of plasma and serum, apoM was measured by ELISA. The method showed good accuracy and precision in the range of 0.011 to 0.9 µM with less than 0.07 % carryover. We found that the methanol precipitation used to extract S1P co-extracted apoM and several other HDL-proteins from plasma. The platelet-associated S1P was released during coagulation, thus increasing the S1P concentration to double in serum as compared to that in plasma. Gel filtration chromatography revealed that the platelet-released S1P was mainly bound to albumin. This explains why the strong correlation between S1P and apoM levels in plasma is lost upon the clotting process and hence not observed in serum. We have developed, characterised and validated an efficient, highly sensitive and specific method for the quantification of S1P in biological material.

Mechanical muscle function, morphology, and fiber type in lifelong trained elderly.

PURPOSE: Maximal muscle contraction force and muscle mass are both reduced during the natural aging process. Long-term training may be used to attenuate this age-related loss in muscle function and muscle size. METHODS: Maximum isometric quadriceps strength (MVC), rate of force development (RFD), and muscle fiber composition and size (CSA) were studied in elderly individuals (68-78 yr) chronically exposed (> 50 yr) to either endurance (E) or strength (S) training, and in age-matched, untrained (U) elderly group. RESULTS: E and S showed greater MVC than did U. Contractile RFD was elevated in S compared with U, and S also demonstrated greater type II fiber CSA than did U and E. The proportion of type I fibers was greater in E compared with U and S. CONCLUSIONS: Muscle fiber size and mechanical muscle performance, particularly RFD, were consistently elevated in aged individuals exposed to chronic (i.e., lifelong) strength training. This relative preservation in muscle morphology and function may provide an important physical reserve capacity to retain muscle mass and function above the critical threshold for independent living at old age.

Acute growth hormone administration causes exaggerated increases in plasma lactate and glycerol during moderate to high intensity bicycling in trained young men.

We studied the acute effects of a single, sc GH dose on exercise performance and metabolism during bicycling. Seven highly trained men [age, 26 +/- 1 yr (mean +/- SEM); weight, 77 +/- 3 kg; maximal oxygen uptake, 65 +/- 1 ml O(2).min(-1).kg(-1)] performed 90 min of bicycling 4 h after receiving 7.5 IU (2.5 mg) GH or placebo in a randomized, double-blinded, cross-over design trial. A standardized pre-exercise meal was given 2 h before exercise. Blood was sampled at rest and during exercise and analyzed for GH, IGF-I, glucose, lactate, insulin, glycerol, and nonesterified fatty acids (NEFA). In the placebo trial, all subjects completed the exercise protocol without any difficulties. In contrast, two subjects were not able to complete the exercise protocol in the GH trial, and one subject barely managed to complete the protocol. In addition, GH administration resulted in exaggerated increases in plasma lactate concentrations during exercise (P < 0.0001). The combined lipolytic effect of GH and exercise, evidenced by increased plasma glycerol and serum NEFA concentrations, was 3-fold greater than the effect of exercise alone (P < 0.0001), but this increased substrate availability did not result in increased whole body fat oxidation (indirect calorimetry). Plasma glucose was, on average, 9% higher during exercise after GH administration compared with placebo (P < 0.0001). We conclude that a single, relevant GH dose causes exaggerated increases in plasma lactate and glycerol as well as serum NEFA during 90 min of subsequent bicycling at moderate to high intensity. The exaggerated increase in plasma lactate may be associated with substantially decreased exercise performance.

GH administration changes myosin heavy chain isoforms in skeletal muscle but does not augment muscle strength or hypertrophy, either alone or combined with resistance exercise training in healthy elderly men.

GH administration, either alone or combined with resistance exercise training (RT), has attracted interest as a means of increasing muscle mass and strength in the elderly. In the present study, 31 healthy, elderly men [age, 74 +/- 1 yr (mean +/- SEM)] were assigned to either RT [3 sessions/wk, 3-5 sets of 8-12 repetition maximum (RM)/session] + placebo (n = 8), RT + GH (n = 8), GH (n = 8), or placebo (n = 7) in a randomized, placebo-controlled, double-blinded (RT + placebo and RT + GH) or single-blinded (GH or placebo) design. Measurements of: 1) isokinetic quadriceps muscle strength; 2) quadriceps muscle power; 3) quadriceps muscle fiber type, size, and myosin heavy chain (MHC) composition; 4) quadriceps cross-sectional area (CSA) [nuclear magnetic resonance imaging (NMRI)]; 5) body composition (dual-energy x-ray absorptiometry scanning); and 6) GH-related serum markers were performed at baseline and after 12 wk. The final GH dose was 1.77 +/- 0.18 IU x d(-1) (approximately 7.2 +/- 0.8 microg x kg(-1) x d(-1)). GH alone had no effect on isokinetic quadriceps muscle strength, power, CSA, or fiber size. However, a substantial increase in MHC 2X isoform was observed with GH administration alone, and this may be regarded as a change into a more youthful MHC composition, possibly induced by the rejuvenating of systemic IGF-I levels. RT + placebo caused substantial increases in quadriceps isokinetic strength, power, and CSA; but these RT induced improvements were not further augmented by additional GH administration. In the RT + GH group, there was a significant decrease in MHC 1 and 2X isoforms, whereas MHC 2A increased. RT, therefore, seems to overrule the changes in MHC composition induced by GH administration alone. Changes in body composition confirmed previous reports of decreased fat mass, increased fat-free mass, and unchanged bone mineral content with GH administration. A high incidence of side effects was reported. Our results do not support a role for GH as a means of increasing muscle strength or mass, either alone or combined with RT, in healthy elderly men; although GH administration alone may induce changes in MHC composition.

Cardiorespiratory fitness of asthmatic children and validation of predicted aerobic capacity.

INTRODUCTION: Predicted aerobic capacity (PAC) was estimated by submaximal exercise test and compared with monitored aerobic capacity (MAC) measured by laboratory conditions [maximal oxygen uptake (VO(2peak))] in 18 children and adolescents, 10 asthmatics and 8 matched controls. OBJECTIVES: To compare aerobic capacity between asthmatic children and controls, to estimate the agreement between PAC and MAC and observe for trend of PAC. MATERIALS AND METHODS: The design was prospective, 4 years (PAC) and cross-sectional (MAC and VO(2peak)). Non-parametric Wilcoxon rank sums were applied for statistical evaluation; the method of Bland and Altman estimated the agreement between PAC and MAC; P < 0.05. RESULTS: PAC at baseline and follow-up, and MAC at follow-up, showed significant differences between groups (P < 0.05), and the mean difference between PAC and MAC at follow-up was -1.0 mLO(2)/min/kg [non-significant (ns)], indicating that PAC had a bias towards underestimation as compared with MAC. Limits of agreement, mean difference [+/-2 standard deviations (SD)], ranged from -8.5 to 6.5 mLO(2)/min/kg, indicating good agreement between the two measurements. No trend of PAC was observed (ns). Physical activity level and subjective health showed no differences between groups, or level and categories, respectively. CONCLUSION: The asthmatic participants presented with lower aerobic capacity than controls in both PAC and MAC; therefore, results confirmed the validity of the PAC method. Data warrant exploration by large-scale paediatric asthma epidemiology.

Yacht type and crew-specific differences in anthropometric, aerobic capacity, and muscle strength parameters among international Olympic class sailors.

Physical fitness and muscular strength are important performance factors for Olympic class sailors, but the physical demands vary greatly between yacht classes, and limited information is available regarding the physical demands for the different crew positions. In the present paper, strength and aerobic capacity data from elite Olympic sailors are presented and compared with previous findings. Furthermore, a system for classification of Olympic class sailors is suggested. Peak aerobic capacity (peak oxygen uptake, VO(2peak)) and maximal isometric and isokinetic muscle strength of the knee extensors and flexors were assessed, together with the hamstring/quadriceps strength ratio (H/Q ratio). Peak aerobic capacity (ml O(2) . min(-1) . kg(-2/3)) was as follows: males - static hikers (n = 5) 215, s = 7; dynamic hikers (n = 8) 252, s = 17; trapezing helmsmen (n = 6) 234, s = 15; trapezing crew (n = 10) 239, s = 16; females - dynamic hikers (n = 6) 194, s = 16; trapezing crew (n = 2) 200, s = 13. Strength data for hikers, presented as peak moments (normalized to body weight) obtained during eccentric, isometric, and concentric contraction (Nm . kg(-1)) respectively were as follows: males - quadriceps: 3.66 (s = 0.68), 3.97 (s = 0.66), 1.82 (s = 0.34); hamstrings: 1.93 (s = 0.22), 1.38 (s = 0.41), 1.05 (s = 0.21); females - quadriceps: 3.84 (s = 0.71), 3.81 (s = 0.58), 1.60 (s = 0.28); hamstrings: 1.75 (s = 0.23), 1.10 (s = 0.16), 0.84 (s = 0.13). The peak moment based H/Q ratios for slow eccentric and concentric contractions were 0.42 (s = 0.11) and 0.39 (s = 0.04) for males and 0.43 (s = 0.06) and 0.39 (s = 0.04) for females respectively. Elite Olympic class sailors demonstrated high VO(2peak) values comparable to those observed in other non-endurance sports. The strength data revealed very high quadriceps strength for hikers, which is likely a result of the high muscle forces encountered during sailing, and a low H/Q ratio. To ensure optimal knee joint stabilization during sailing and other training activities, it is suggested that hikers should counter this strength imbalance by performing additional strength training for the hamstrings muscle group.

Exercise-induced rib stress fractures: influence of reduced bone mineral density.

Exercise-induced rib stress fractures have been reported frequently in elite rowers during the past decade. The etiology of rib stress fractures is unclear, but low bone mineral density (BMD) has been suggested to be a potential risk factor for stress fractures in weight-bearing bones. The present study investigated BMD in seven Danish national team rowers with previous rib stress fracture (RSF) and 7 controls (C) matched for gender, age, height, weight and training experience. Total body scan and specific scans of the lumbar spine (L2-L4), femoral neck and distal radius were performed using a DEXA scanner. The RSF subjects showed significantly lower L2-L4 BMD: RSF: 1.22+/-0.05 g cm(-2) (mean+/-SEM) (median 1.19 g cm(-2), range 1.02-1.37 g cm(-2)) compared to C: 140+/-0.04 g cm(-2) (median 1.41 g cm(-2), range 1.27-1.57 g cm(-2)) (P=0.028). The present results suggest that low bone mineral density may be a potential risk factor for the development of exercise-induced rib stress fractures in elite rowers.

Effects of 2 wk of GH administration on 24-h indirect calorimetry in young, healthy, lean men.

The present study was designed as a randomized, double-blind placebo (Plc)-controlled study to determine the effect of 2 wk of growth hormone administration (GH-adm.) on energy expenditure (EE) and substrate oxidation in healthy humans. Sixteen young healthy men were divided into two groups. The study consisted of two 24-h measurements (indirect calorimetry), separated by 2 wk of either Plc or GH injections (6 IU/day). At baseline, no significant differences were observed between the two groups in any of the measured anthropometric, hormonal, or metabolic parameters, neither did the parameters change over time in the Plc group. GH-adm. resulted in a 4.4% increase in 24-h EE (P < 0.05) and an increase in fat oxidation by 29% (P < 0.05). However, a decrease in the respiratory quotient was only observed in the postabsorptive phase after an overnight fast (0.84 +/- 0.1 to 0.79 +/- 0.1, P < 0.05). Furthermore, lean body mass (LBM) was increased by GH-adm. only [62.8 +/- 2.5 kg (baseline) vs. 64.7 +/- 2.4 kg (after), P < 0.001]. In conclusion, GH-adm. increases 24-h EE, which may be partly explained by increased LBM. Furthermore, GH-adm. stimulates fat combustion, especially in the postabsorptive state.

No effect of growth hormone administration on substrate oxidation during exercise in young, lean men.

The purpose of this study was to examine the effects of increased fat availability induced by growth hormone (GH) administration on the oxidative metabolism during exercise. Seven well-trained males (age 25 +/- 2 years (mean +/- S.E.M.); peak oxygen consumption : 62 +/- 1 ml min(-1) kg(-1) (completed four randomised trials: 120 min bicycling at 55% 4 h after receiving either 7.5 IU (2.5 mg) GH or placebo (Plc), and during rest after receiving either GH or Plc. In all studies a standardized meal was given 2 h after GH or Plc injection. GH administration resulted in an approximately 60-fold increase in serum GH concentration at rest (P < 0.0001) and during exercise (P < 0.0001). The increase in serum GH was followed by an increase in circulating glycerol at rest (8%, P < 0.0001). When combined with exercise the increase in plasma glycerol was more pronounced (GH: 716% of baseline versus Plc: 328%, P < 0.0001). However, this increase in fat mobilization did not increase fat oxidation during exercise (indirect calorimetry). In conclusion, GH administration combined with aerobic exercise increased lipolytic parameters substantially more than exercise alone, but did not further augment whole body fat oxidation.