Theoretical construct into blocks of actigraphic-derived sleep parameters.

Actigraphic parameters can provide indication of people's sleep quality during their daily lives. However, there is a need for clear guidelines on the understanding of the different actigraphic parameters. The present study aims to propose a conceptual and theoretical framework for known actigraphic-derived parameters, which is able to describe the alternation between rest and wake phases during the nocturnal sleep, explaining their main characteristics and interrelations that can be replicated in future studies. Forty Sport Sciences students at the University of Milan (20 males; mean age ± SD, 22 ± 3 y) completed the validated Italian version of Morningness-Eveningness Questionnaire (MEQ) and wore an actigraph (Motion Watch 8®, Cambridge Neurotechnology, Cambridge, UK) for seven days. A framework was developed to depict the interactions between the actigraphic parameters and how they objectively describe sleep, according to which the parameters are organized into three different functional blocks related to different aspects of sleep. Correlations analyses were conducted to explore the relationships among the primary actigraphic parameters within and across the functional blocks. The proposed framework is a purely theoretical construct that provides a simple interpretation of known actigraphic parameters guiding researchers and practitioners in the use of these parameters either for research or clinical purposes.

Sex Differences in Rest-Activity Circadian Rhythm in Patients With Metabolic Syndrome.

Rest-Activity circadian Rhythm (RAR) can be used as a marker of the circadian timing system. Recent studies investigated the relationship between irregular circadian rhythms and cardiovascular risk factors such as hypertension, obesity, and dyslipidemia. These factors are related to the Metabolic Syndrome (MS), a clustering of metabolic risk factors that increases the risk of several cardiovascular and metabolic diseases. This cross-sectional analysis aimed to explore the RAR characteristics by actigraphy in subjects with MS, particularly in relation to sex and MS parameters, using parametric and non-parametric analyses. Distinguishing the characteristics of RAR based on sex could prove useful as a tool to improve the daily level of activity and set up customized activity programs based on each person's circadian activity profile. This study showed that female participants exhibited higher values than male participants in the Midline Estimating Statistic of Rhythm (MESOR) (243.3 ± 20.0 vs 197.6 ± 17.9 activity count), Amplitude (184.5 ± 18.5 vs 144.2 ± 17.2 activity count), which measures half of the extent of the rhythmic variation in a cycle, and the most active 10-h period (M10) (379.08 ± 16.43 vs 295.13 ± 12.88 activity count). All these parameters are indicative of a higher daily activity level in women. Female participants also had lower Intradaily Variability (IV) than male participants (0.75 ± 0.03 vs 0.85 ± 0.03 activity count), which indicates a more stable and less fragmented RAR. These preliminary data provide the first experimental evidence of a difference in RAR parameters between male and female people with MS.

Binge Eating Disorder: What Is the Role of Physical Activity Associated with Dietary and Psychological Treatment?

Binge eating patients present lower physical activity levels, which could be associated with lower exercise capacity. Specific physical activity can ensure broad beneficial results relating to eating disorders, depression, and body mass index (BMI) in bulimia; however, research on binge eating disorder (BED) is scarce. Our study aimed to investigate the effects of specific training as an addition to conventional treatment of eating disorder symptoms, anthropometric characteristics, and physical performance. Nineteen women with BED were included in a dietary and cognitive-behavioral therapy program. After medical examination, 10 women carried out Combined Aerobic and Anaerobic Exercise Training in addition to conventional treatment (CAAET group), whereas the remaining 9 followed the conventional treatment alone (CTRL group). All of the measurements were assessed before and after six months of treatment. In both groups, we observed a significant decrease in binge episodes, weight, and body mass index, and an increase in exercise capacity. Moreover, the CAAET group presented a greater improvement in aerobic performance than that observed in the CTRL group. Our results suggest that both interventions similarly improved BED symptoms. The addition of physical activity could be important in the long-term maintenance of both weight loss and reduction in binge episodes in BED patients.

The multidisciplinary therapy in binge eating disorder is able to influence the interdaily stability and sleep quality?

We have recently shown that rest-activity circadian rhythm significantly differed in women with Binge Eating Disorder (BED) compared to the Ctrl group. In details, patients with BED exhibited significantly reduced levels of MESOR and Amplitude with respect to the Ctrl group. In addition, in this previous study, the results of the actigraphic sleep monitoring provided no evidence of differences in sleep parameters between the two groups. We expanded the original sample obtaining a total of 28 volunteered women, 14 BED women, and 14 Ctrl. We recorded in all 28 participants a 5-day actigraphic monitoring to detect the rhythmometric parameters, interdaily stability, intradaily variability, L5, M10, and sleep parameters. During the study, BED's women group kept an individual multidisciplinary therapy lasting five weekly days, from Monday to Friday, consisting in cognitive-behavioral therapy and nutritional program, administered in outpatient care from 8:00 a.m. at 5:00 p.m. The combination of both our previous and current study supports the conclusion that the sleep quality of the BED group is significantly better compared to Ctrl. The non-parametric indexes showed how interdaily stability, significantly correlated to sleep efficiency, was higher in BED group compared to the Ctrl group, indicating a better synchronization of rest-activity circadian rhythm. In conclusion, the maintenance of a regular lifestyle, such as imposed by the multidisciplinary therapy, is important to avoid alterations in the sleep-wake cycle, particularly in patients with eating disorders.

Rest-activity circadian rhythm in breast cancer survivors at 5 years after the primary diagnosis.

Rest-activity circadian rhythm (RAR) is a marker of the circadian timing system. Particular attention has been given to RAR characteristics in cancer diseases. Specifically, alterations of RAR parameters have been found, at different stages of clinical pathway, in breast cancer (BC) patients. No studies to date have analyzed RAR alterations in breast cancer survivors several years after the diagnosis. The aim of this study was to determine RAR by actigraphy in a population of BC survivors at 5 years after the primary diagnosis, and to compare their RAR characteristics with healthy controls. The study sample was 28 women: 15 BC survivors at 5 years from the primary diagnosis (BC-group) and 13 healthy controls (Ctrl-group), matched for age and body mass index. All participants have been monitored for 7 days by actigraphy to evaluate RAR. A statistically significant circadian rhythm (T = 24) was found in all 28 subjects (p < .001). The group analysis revealed a significant RAR both in BC- and Ctrl-group (p < .001). The acrophase was not different between the BC- and Ctrl-group (15:09 vs. 15:01 hr:min in BC- and Ctrl-group, respectively). In contrast, the MESOR (Midline Estimating Statistic of Rhythm) and the amplitude were lower in the BC-group with respect to the Ctrl-group. Indeed, the MESOR was 192.0 vs. 276.4 activity counts in BC- and Ctrl-group, respectively (p < .001), while the amplitude was 167.0 vs. 222.6 activity counts in BC- and Ctrl-group, respectively (p < .001). These results provide the first experimental evidence of alterations in RAR parameters in BC survivors at 5 years after the primary diagnosis. Larger studies with a prospective design are needed to assess the role of RAR in the quality of life and prognosis in BC survivors.

Single bout of low-intensity exercise produces modestly favorable changes in glycemic and lipidemic profiles after ingestion of non-isoglucidic breakfasts.

OBJECTIVES: The aim of this study was to investigate the acute effects of low-intensity exercise on the postprandial hormonal and metabolic milieu induced by breakfast consumption. METHODS: Exercise began 100 min after the initiation of breakfast consumption and consisted of cycling at 40% of maximum oxygen uptake for 20 min. Three different breakfasts were used to elicit the postprandial state: B1 = skimmed milk (125 mL) and 30g corn flakes; B2 = skimmed milk (220 mL), 200 g apple, 30 g cocoa cream-filled sponge cake; B3 = skimmed milk (125 mL), 50 g bread, 150 g apple, and 15 g hazelnut and cocoa spread. Nineteen young healthy participants (8 M/11 F; body mass index 22.7 ± 0.5 kg/m2; age 31 ± 0.7 y) consumed the three breakfasts, as well as an oral glucose load (50-g oral glucose tolerance test), under either resting or exercise conditions, in a randomized-crossover fashion. Blood glucose, insulinemia, ghrelinemia, lipidemia, and satiety were measured throughout the studies. To evaluate the metabolic effects of exercise, the changes that glucose, insulin, ghrelin, free fatty acid exhibited in the interval 90 to 120 min were analyzed with a two-way repeated measures analysis of variance (factor 1: type of oral test; factor 2: resting/exercise condition). RESULTS: No interaction between the two factors was found for any of the examined variables. Light exercise produced a modest, significant decrease in blood glucose levels (P = 0.004) and a modest, significant increase in free fatty acid levels (P = 0.002) with respect to the resting condition. CONCLUSIONS: These findings suggest that short, mild exercise has beneficial effects on postprandial metabolism and this may have direct bearing on the issue of counteracting the epidemic rising of sedentary lifestyle of the general population.

Effect of Sugar versus Mixed Breakfast on Metabolic and Neurofunctional Responses in Healthy Individuals.

We investigated the effects of glucose and diverse breakfasts on glucose increment and ghrelin suppression and cognitive processing of sensory information assessed by frontal P300 evoked potentials. In a randomized crossover design, 12 healthy individuals (6M/6F; BMI 22.2 ± 0.4 kg/m2; 27 ± 1.3 years, mean ± SEM) underwent 50 g OGTT (A) and 3 breakfasts (B1: milk and cereals; B2: milk, apple, and chocolate cream-filled sponge cake; B3: milk, apple, bread, and hazelnut chocolate cream) to assess plasma glucose-, insulin-, and ghrelin excursions. An electroencephalography was performed before and 100 min after consumption of each load to measure the latency of frontal P300 evoked potentials as index of cognitive performance. Breakfasts B1 and B2 exhibited significantly lower glycemic and insulinemic responses as compared to A. Breakfast B3 exhibited significantly lower glycemic, but not insulinemic response, as compared to A. Final plasma ghrelin inhibition was more pronounced, albeit not significantly, in all breakfasts with respect to A. P300 latency tended to decrease following each of the three breakfasts, but B3 was the only breakfast capable to elicit a statistically significant reduction in P300 latency with respect to A (p < 0.01), suggesting ameliorated cognitive performance. Such amelioration was correlated with the 2-hour final inhibition of plasma ghrelin concentration (r = 0.61, p = 0.01).

Predicting the actigraphy-based acrophase using the Morningness-Eveningness Questionnaire (MEQ) in college students of North Italy.

Actigraphy is the reference objective method to measure circadian rhythmicity. One simpler subjective approach to assess the circadian typology is the Morningness-Eveningness Questionnaire (MEQ) by Horne and Ostberg. In this study, we compared the MEQ score against the actigraphy-based circadian parameters MESOR, amplitude and acrophase in a sample of 54 students of the University of Milan in Northern Italy. MEQ and the acrophase resulted strongly and inversely associated (r = -0.84, p < 0.0001), and their relationship exhibited a clear-cut linear trend. We thus used linear regression to develop an equation enabling us to predict the value of the acrophase from the MEQ score. The parameters of the regression model were precisely estimated, with the slope of the regression line being significantly different from 0 (p < 0.0001). The best-fit linear equation was: acrophase (min) = 1238.7-5.49·MEQ, indicating that each additional point in the MEQ score corresponded to a shortening of the acrophase of approximately 5 min. The coefficient of determination, R2, was 0.70. The residuals were evenly distributed and did not show any systematic pattern, thus indicating that the linear model yielded a good, balanced prediction of the acrophase throughout the range of the MEQ score. In particular, the model was able to accurately predict the mean values of the acrophase in the three chronotypes (Morning-, Neither-, and Evening-types) in which the study subjects were categorized. Both the confidence and prediction limits associated to the regression line were calculated, thus providing an assessment of the uncertainty associated with the prediction of the model. In particular, the size of the two-sided prediction limits for the acrophase was about ±100 min in the midrange of the MEQ score. Finally, k-fold cross-validation showed that both the model's predictive ability on new data and the model's stability to changes in the data set used for parameter estimation were good. In conclusion, the actigraphy-based acrophase can be predicted using the MEQ score in a population of college students of North Italy.

Protective Effect of Aerobic Physical Activity on Sleep Behavior in Breast Cancer Survivors.

HYPOTHESES: Sleep disorders are associated with an increased risk of cancer, including breast cancer (BC). Physical activity (PA) can produce beneficial effects on sleep. STUDY DESIGN: We designed a randomized controlled trial to test the effect of 3 months of physical activity on sleep and circadian rhythm activity level evaluated by actigraphy. METHODS: 40 BC women, aged 35-70 years, were randomized into an intervention (IG) and a control group (CG). IG performed a 3 month of aerobic exercise. At baseline and after 3 months, the following parameters were evaluated both for IG and CG: anthropometric and body composition measurements, energy expenditure and motion level; sleep parameters (Actual Sleep Time-AST, Actual Wake Time-AWT, Sleep Efficiency-SE, Sleep Latency-SL, Mean Activity Score-MAS, Movement and Fragmentation Index-MFI and Immobility Time-IT) and activity level circadian rhythm using the Actigraph Actiwatch. RESULTS: The CG showed a deterioration of sleep, whereas the IG showed a stable pattern. In the CG the SE, AST and IT decreased and the AWT, SL, MAS and MFI increased. In the IG, the SE, IT, AWT, SL, and MAS showed no changes and AST and MFI showed a less pronounced change in the IG than in the CG. The rhythmometric analysis revealed a significant circadian rhythm in two groups. After 3 months of PA, IG showed reduced fat mass %, while CG had improved weight and BMI. CONCLUSION: Physical activity may be beneficial against sleep disruption. Indeed, PA prevented sleep worsening in IG. PA can represent an integrative intervention therapy able to modify sleep behaviour.

Dynamics of thermographic skin temperature response during squat exercise at two different speeds.

Low intensity resistance training with slow movement and tonic force generation has been shown to create blood flow restriction within muscles that may affect thermoregulation through the skin. We aimed to investigate the influence of two speeds of exercise execution on skin temperature dynamics using infrared thermography. Thirteen active males performed randomly two sessions of squat exercise (normal speed, 1s eccentric/1s concentric phase, 1s; slow speed, 5s eccentric/5s concentric phase, 5s), using ~50% of 1 maximal repetition. Thermal images of ST above muscles quadriceps were recorded at a rate of 0.05Hz before the exercise (to determine basal ST) and for 480s following the initiation of the exercise (to determine the nonsteady-state time course of ST). Results showed that ST changed more slowly during the 5s exercise (p=0.002), whereas the delta (with respect to basal) excursions were similar for the two exercises (p>0.05). In summary, our data provided a detailed nonsteady-state portrait of ST changes following squat exercises executed at two different speeds. These results lay the basis for further investigations entailing the joint use of infrared thermography and Doppler flowmetry to study the events taking place both at the skin and the muscle level during exercises executed at slow speed.

Physical Attributes and NFL Combine Performance Tests Between Italian National League and American Football Players: A Comparative Study.

Vitale, JA, Caumo, A, Roveda, E, Montaruli, A, La Torre, A, Battaglini, CL, and Carandente, F. Physical attributes and NFL Combine performance tests between Italian National League and American football players: a comparative study. J Strength Cond Res 30(10): 2802-2808, 2016-The purpose of this study was to examine anthropometric measurements and the results of a battery of performance tests administered during the National Football League (NFL) Combine between American football players who were declared eligible to participate in the NFL Combine and football players of a top Italian team (Rhinos Milan). Participants (N = 50) were categorized by position into 1 of 3 groups based on playing position: skill players (SP) included wide receivers, cornerbacks, free safeties, strong safeties, and running backs; big skill players (BSP) consisted of fullbacks, linebackers, tight ends, and defensive ends; lineman (LM) included centers, offensive guards, offensive tackles, and defensive tackles. A 1-way analysis of variance followed by the Tukey-Kramer post hoc test was used for comparisons between Italian players by playing position. Ninety-five percent CIs were used for comparisons between American and Italian football for the NFL Combine performance tests. Significant differences for all the variables between the 3 playing categories were observed among the Italian players; LM had higher anthropometric and body composition values than SP (p < 0.001) and BSP (p < 0.001), whereas LM performed significantly worse in the physical tests, except for the 225-lb bench press test when compared with SP (p < 0.002). American football players presented significantly higher anthropometric values and test performance scores when compared with Italian players. Administrators of professional football teams in Italy need to improve the player's physical attributes, so the gap that currently exists between American and Italian players can be reduced, which could significantly improve the quality of American football in Italy.

Moderate Intensity Training Impact on the Inflammatory Status and Glycemic Profiles in NOD Mice.

The nonobese diabetic (NOD) mouse represents a well-established experimental model analogous to human type 1 diabetes mellitus (T1D) as it is characterized by progressive autoimmune destruction of pancreatic ß-cells. Experiments were designed to investigate the impact of moderate-intensity training on T1D immunomodulation and inflammation. Under a chronic exercise regime, NOD mice were trained on a treadmill for 12 weeks (12 m/min for 30 min, 5 d/wk) while age-matched, control animals were left untrained. Prior to and upon completion of the training period, fed plasma glucose and immunological soluble factors were monitored. Both groups showed deteriorated glycemic profiles throughout the study although trained mice tended to be more compensated than controls after 10 weeks of training. An exercise-induced weight loss was detected in the trained mice with respect to the controls from week 6. After 12 weeks, IL-6 and MIP-1ß were decreased in the trained animals compared to their baseline values and versus controls, although not significantly. Morphometric analysis of pancreata revealed the presence of larger infiltrates along with decreased α-cells areas in the control mice compared to trained mice. Exercise may exert positive immunomodulation of systemic functions with respect to both T1D and inflammation, but only in a stringent therapeutic window.

Chronotype influences activity circadian rhythm and sleep: differences in sleep quality between weekdays and weekend.

Several studies have shown the differences among chronotypes in the circadian rhythm of different physiological variables. Individuals show variation in their preference for the daily timing of activity; additionally, there is an association between chronotype and sleep duration/sleep complaints. Few studies have investigated sleep quality during the week days and weekends in relation to the circadian typology using self-assessment questionnaires or actigraphy. The purpose of this study was to use actigraphy to assess the relationship between the three chronotypes and the circadian rhythm of activity levels and to determine whether sleep parameters respond differently with respect to time (weekdays versus the weekend) in Morning-types (M-types), Neither-types (N-types) and Evening-types (E-types). The morningness-eveningness questionnaire (MEQ) was administered to 502 college students to determine their chronotypes. Fifty subjects (16 M-types, 15 N-types and 19 E-types) were recruited to undergo a 7-days monitoring period with an actigraph (Actiwacth® actometers, CNT, Cambridge, UK) to evaluate their sleep parameters and the circadian rhythm of their activity levels. To compare the amplitude and the acrophase among the three chronotypes, we used a one-way ANOVA followed by the Tukey-Kramer post-hoc test. To compare the Midline Estimating Statistic of Rhythm (MESOR) among the three chronotypes, we used a Kruskal-Wallis non-parametric test followed by pairwise comparisons that were performed using Dunn's procedure with a Bonferroni correction for multiple comparisons. The analysis of each sleep parameter was conducted using the mixed ANOVA procedure. The results showed that the chronotype was influenced by sex (χ(2) with p = 0.011) and the photoperiod at birth (χ(2) with p < 0.05). Though the MESOR and amplitude of the activity levels were not different among the three chronotypes, the acrophases compared by the ANOVA post-hoc test were significantly different (p < 0.001). The ANOVA post-hoc test revealed the presence of a significant difference (p < 0.001) between the M-types (14:32 h) and E-types (16:53 h). There was also a significant interaction between the chronotype and four sleep parameters: Sleep end, Assumed Sleep, Immobility Time and Sleep Efficiency. Sleep Efficiency showed the same patterns as did Assumed Sleep and Immobility Time: the Sleep Efficiency of the E-types was poorer than that of the M- and N-types during weekdays (77.9% ± 7.0 versus 84.1% ± 4.9 and 84.1% ± 5.2) but was similar to that measured in the M- and N-types during the weekend. Sleep Latency and Movement and Fragmentation Index were not different among the three chronotypes and did not change on the weekend compared with weekdays. This study highlights two key findings: first, we observed that the circadian rhythm of activity levels was influenced by the chronotype; second, the chronotype had a significant effect on sleep parameters: the E-types had a reduced sleep quality and quantity compared with the M- and N-types during weekdays, whereas the E-types reached the same levels as the other chronotypes during the weekends. These findings suggest that E-types accumulate a sleep deficit during weekdays due to social and academic commitments and that they recover from this deficit during "free days" on the weekend.

Thermal imaging of exercise-associated skin temperature changes in trained and untrained female subjects.

Heat dissipation during sport exercise is an important physiological mechanism that may influence athletic performance. Our aim was to test the hypothesis that differences exist in the dynamics of exercise-associated skin temperature changes between trained and untrained subjects. We investigated thermoregulation of a local muscle area (muscle-tendon unit) involved in a localized steady-load exercise (standing heels raise) using infrared thermography. Seven trained female subjects and seven untrained female controls were studied. Each subject performed standing heels raise exercise for 2 min. Thermal images were recorded prior to exercise (1 min), during exercise (2 min), and after exercise (7 min). The analysis of thermal images provided the skin temperature time course, which was characterized by a set of descriptive parameters. Two-way ANOVA for repeated measures detected a significant interaction (p = 0.03) between group and time, thus indicating that athletic subjects increased their skin temperature differently with respect to untrained subjects. This was confirmed by comparing the parameters describing the speed of rise of skin temperature. It was found that trained subjects responded to exercise more quickly than untrained controls (p < 0.05). In conclusion, physical training improves the ability to rapidly elevate skin temperature in response to a localized exercise in female subjects.

Postprandial triglyceride profile after a standardized oral fat load is altered in growth hormone (GH)-deficient adult patients and is not improved after short-term GH replacement therapy.

OBJECTIVE: Adult growth hormone deficiency (GHD) has detrimental effects on metabolic profile, leading to an increased cardiovascular mortality and morbidity. Above all, disturbance in postprandial triglyceride metabolism is of major concern because of the crucial role of triglyceride-rich lipoproteins in atherogenesis. The majority of previous studies on GH replacement have shown favourable changes in the fasting lipid profile. Aim of this study is to investigate whether this beneficial effect is exerted also on postprandial triglyceride (TG) metabolism. PATIENTS AND METHODS: We challenged nine GHD patients with a standardized fat loading meal at baseline and after 6 months of GH replacement therapy. Nine healthy control subjects were similarly tested under baseline conditions. Blood samples were obtained before and up to 8 h after fat loading for serum lipid analysis. RESULTS: We found that GHD patients with fasting TG level in the normal range (1·29 ± 0·31 mm) had a delayed postprandial TG clearance compared to healthy controls (triglyceride level at 8 h, 3·82 ± 0·83 vs 1 ± 0·06 mm P < 0·01), and the postprandial hypertriglyceridaemia was not corrected by 6 months of GH therapy. CONCLUSIONS: This study has shown for the first time that GHD adult patients have a higher postprandial triglyceridaemia compared to healthy controls when challenged by a standardized fat load and that this atherogenic feature is not normalized by short-term GH treatment despite a decrease in visceral fat mass described during the replacement therapy.

Comparative evaluation of simple indices of graft function after islet transplantation.

BACKGROUND: Several simple measures of graft function after islet transplantation have been proposed but a comparative evaluation is lacking. Here, we compared the performance of five indices of ß-cell function: ß-score, transplant estimated function (TEF), homeostasis model assessment (HOMA) 2-B%, C-peptide/glucose ratio, and Secretory Units of Islets in Transplantation (SUIT). METHODS: Two cohorts of transplanted patients were analyzed. Cohort 1 consisted of 14 recipients with type 1 diabetes of islet transplantation whereas cohort 2 consisted of 21 recipients with type 1 diabetes of cultured islet cell graft. The five surrogate indices were compared against the first- and second-phase insulin response to arginine in cohort 1, and against the C-peptide response to a hyperglycemic clamp in cohort 2. RESULTS: We found that the performances of the five surrogate indices were close one to each other in cohort 1. The correlation coefficients ranged 0.62 to 0.67 and 0.62 to 0.68 against the first- and second-phase insulin response to arginine, respectively. In cohort 2, we found that the ß-score, TEF, C-peptide/glucose ratio, and SUIT were reasonably well correlated with the clamp response (correlation coefficients were in the range 0.71-0.81), whereas HOMA2-B% showed a modest performance (r=0.54). HOMA2-B% could not be evaluated in one patient whose fasting glucose concentration level was below the lower bound indicated by the HOMA calculator (3 mmol/L). SUIT could not be evaluated in three patients whose fasting glucose concentration was below the glucose threshold of the SUIT formula (3.43 mmol/L). CONCLUSION: In summary, no single index outperformed the others. Nevertheless, when the benefit to cost ratio is considered, TEF stands out for its good performance at a very low cost.

Genetic polymorphisms of the enzymes involved in DNA methylation and synthesis in elite athletes.

Physical exercise induces adaptive changes leading to a muscle phenotype with enhanced performance. We first investigated whether genetic polymorphisms altering enzymes involved in DNA methylation, probably responsible of DNA methylation deficiency, are present in athletes' DNA. We determined the polymorphic variants C667T/A1298C of 5,10-methylenetetrahydrofolate reductase (MTHFR), A2756G of methionine synthase (MTR), A66G of methionine synthase reductase (MTRR), G742A of betaine:homocysteine methyltransferase (BHMT), and 68-bp ins of cystathionine ß-synthase (CBS) genes in 77 athletes and 54 control subjects. The frequency of MTHFR (AC), MTR (AG), and MTRR (AG) heterozygous genotypes was found statistically different in the athletes compared with the control group (P=0.0001, P=0.018, and P=0.0001), suggesting a reduced DNA methylating capacity. We therefore assessed whether DNA hypomethylation might increase the expression of myogenic proteins expressed during early (Myf-5 and MyoD), intermediate (Myf-6), and late-phase (MHC) of myogenesis in a cellular model of hypomethylated or unhypomethylated C2C12 myoblasts. Myogenic proteins are largely induced in hypomethylated cells [fold change (FC)=Myf-5: 1.21, 1.35; MyoD: 0.9, 1.47; Myf-6: 1.39, 1.66; MHC: 1.35, 3.10 in GMA, DMA, respectively] compared with the control groups (FC=Myf-5: 1.0, 1.38; MyoD: 1.0, 1.14; Myf-6: 1.0, 1.44; MHC: 1.0, 2.20 in GM, DM, respectively). Diameters and length of hypomethylated myotubes were greater then their respective controls. Our findings suggest that DNA hypomethylation due to lesser efficiency of polymorphic MTHFR, MS, and MSR enzymes induces the activation of factors determining proliferation and differentiation of myoblasts promoting muscle growth and increase of muscle mass.

Dynamic insulin sensitivity index: importance in diabetes.

The classical minimal model (MM) index of insulin sensitivity, S(I), does not account for how fast or slow insulin action takes place. In a recent work, we proposed a new dynamic insulin sensitivity index, S(I)(D), which is able to take into account the dynamics of insulin action as well. The new index is a function of two MM parameters, namely S(I) and p(2), the latter parameter governing the speed of rise and decay of insulin action. We have previously shown that in normal glucose tolerant subjects S(I)(D) provides a more comprehensive picture of insulin action on glucose metabolism than S(I). The aim of this study is to show that resorting to S(I)(D) rather S(I) is even more appropriate when studying diabetic patients who have a low and slow insulin action. We analyzed insulin-modified intravenous glucose tolerance test studies performed in 10 diabetic subjects and mixed meal glucose tolerance test studies exploiting the triple tracer technique in 14 diabetic subjects. We derived both S(I) and S(I)(D) resorting to Bayesian and Fisherian identification strategies. The results show that S(I)(D) is estimated more precisely than S(I) when using the Bayesian approach. In addition, the less labor-intensive Fisherian approach can still be used to obtain reliable point estimates of S(I)(D) but not of S(I). These results suggest that S(I)(D) yields a comprehensive, precise, and cost-effective assessment of insulin sensitivity in subjects with impaired insulin action like impaired glucose tolerant subjects or diabetic patients.