No Influence of the Fat Mass and Obesity-Associated Gene rs9939609 Single Nucleotide Polymorphism on Blood Lipids in Young Males

The fat mass and obesity-associated gene (FTO) rs9939609 A-allele is linked to obesity and dyslipidemia, yet the independent influence of this polymorphism on blood lipids remains equivocal. We examined the influence of the FTO rs9939609 polymorphism on fasting and postprandial blood lipids in individuals homozygous for the risk A-allele or T-allele with similar anthropometric and demographic characteristics. 12 AA and 12 TT males consumed a standardized meal after fasting overnight. Blood samples were collected at baseline (−1.5 h), before the meal (0 h), and for five hours postprandially to measure lipid, glucose, and insulin concentrations. Time-averaged total area under the curve (TAUC) values (0–5 h) were calculated and compared between genotypes. Fasting triacylglycerol (TG), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, non-esterified fatty acid (NEFA), glucose, and insulin concentrations were similar between groups (p ≥ 0.293). TAUC for TG was similar in AAs and TTs (95% confidence interval (CI) −0.52 to 0.31 mmol/L/h; p = 0.606). Likewise, TAUC values were similar for NEFA (95% CI −0.04 to 0.03 mmol/L/h; p = 0.734), glucose (95% CI −0.41 to 0.44 mmol/L/h; p = 0.951), and insulin (95% CI −6.87 to 2.83 pmol/L/h; p = 0.395). Blood lipids are not influenced by the FTO rs9939609 polymorphism, suggesting the FTO-dyslipidemia link is mediated by adiposity and weight management is important in preventing FTO-related lipid variations.     

The reproducibility of estimates of critical power and anaerobic work capacity in upper-body exercise

The purposes of this study were to apply the linear power versus inverse of time relationship to high-intensity upper-body exercise and to assess the repeatability of the parameters critical power (CP) and anaerobic working capacity (AWC), using limits of agreement (Bland and Altman 1986). Sixteen active male subjects (aged 20–34 years), performed two sets of five constant-power exercises on an adapted cycle ergometer. There were no significant differences between mean estimates of CP [96 (16) W and 95 (17) W] and AWC [7457 (2011) J and 7608 (1684) J] from the first and second sets of bouts. Despite the lack of systematic bias, there was evidence of large random error. Ratio limits of agreement for time to exhaustion during constant-power exercises suggested that a repeat measurement might be expected in 95% of cases to be between 0.64 and 1.59 times the original measurement. The 95% limits of agreement for CP were –15 W to +17 W. The ratio limits of agreement for AWC suggest that in 95% of cases a repeat measurement might be between 0.57 and 1.67 times the original estimate. The results of this study suggest a poor repeatability of constant-power upper-body exercises to exhaustion, which may contribute to a poor repeatability of CP and AWC determined from the linear power versus inverse of time model. Electronic Publication     

Correct allometric analysis is always helpful for scaling flow‐mediated dilation in research and individual patient contexts

McLay et al. (Clin Physiol Funct Imaging (2017); DOI: 10.1111/cpf.12465 ) recently examined whether the allometric scaling of flow‐mediated dilation influenced the mean difference between samples of young and older adults compared with the traditional percentage change approach. They also explored whether a new scaling calculation improved the ability to obtain individually scaled flow‐mediated dilation. In our response to their study, we can demonstrate that McLay et al. (Clin Physiol Funct Imaging, 2017) have (i) managed to formulate a new scaling index which does nothing to remove the dependency of that index on baseline diameter and (ii) suggested, incorrectly, that the original allometric approach cannot be used to derive individually‐adjusted values of flow‐mediated dilation, which can be interpreted in a similar way to a percentage change.     

Lean Body Mass Associated with Upper Body Strength in Healthy Older Adults While Higher Body Fat Limits Lower Extremity Performance and Endurance

Impaired strength adversely influences an older person’s ability to perform activities of daily living. A cross-sectional study of 117 independently living men and women (age = 73.4 ± 9.4 year; body mass index (BMI) = 27.6 ± 4.8 kg/m²) aimed to assess the association between body composition and: (1) upper body strength (handgrip strength, HGS); (2) lower extremity performance (timed up and go (TUG) and sit to stand test (STS)); and (3) endurance (6-minute walk (SMWT). Body composition (% fat; lean body mass (LBM)) was assessed using bioelectrical impedance. Habitual physical activity was measured using the Minnesota Leisure Time Physical Activity Questionnaire (MLTPA) and dietary macronutrient intake, assessed using 24 h recalls and 3-day food records. Regression analyses included the covariates, protein intake (g/kg), MLTPA, age and sex. For natural logarithm (Ln) of right HGS, LBM (p < 0.001) and % body fat (p < 0.005) were significant (r² = 46.5%; p < 0.000). For left LnHGS, LBM (p < 0.000), age (p = 0.036), protein intake (p = 0.015) and LnMLTPA (p = 0.015) were significant (r² = 0.535; p < 0.000). For SMW, % body fat, age and LnMLTPA were significant (r² = 0.346; p < 0.000). For STS, % body fat and age were significant (r² = 0.251; p < 0.000). LBM is a strong predictor of upper body strength while higher % body fat and lower physical activity are associated with poorer outcomes on tests of lower extremity performance.     

The effectiveness of pharmaceutical interventions for obesity: weight loss with orlistat and sibutramine in a United Kingdom population-based cohort

Aims

Drug treatments for obesity have proven efficacy from randomized trials, but their effectiveness in routine clinical practice is unknown. We assessed the effects on weight and body mass index (BMI) of orlistat and sibutramine when delivered in routine primary care.

Methods

We used United Kingdom data from the Clinical Practice Research Datalink to estimate the effects of orlistat or sibutramine on weight and BMI over 3 years following treatment initiation. For comparison, we matched each patient with up to five obese patients receiving neither drug. Mixed effects linear regression with splines was used to model change in weight and BMI. Mean change with 95% confidence intervals (CI) was estimated.

Results

We identified 100 701 patients receiving orlistat, 15 355 receiving sibutramine and 508 140 non-intervention patients, with body mass index of 37.2, 36.6 and 33.2 kg m⁻², respectively. Patients receiving orlistat lost, on average, 0.94 kg month⁻¹ (0.93 to 0.95) over the first 4 months. Weight gain then occurred, although weight remained slightly below baseline at 3 years. Patients receiving sibutramine lost, 1.28 kg month⁻¹ (1.26 to 1.30) over the first 4 months, but by 3 years had exceeded baseline weight. Non-intervention patients had slight increases in weight throughout the 3 year period, with gains ranging between 0.01 and 0.06 kg month⁻¹.

Conclusions

Orlistat and sibutramine had early effects on weight loss, not sustained over 3 years. As new treatments for obesity are approved, their effectiveness should be measured in routine clinical practice, as effectiveness may be considerably less than seen in randomized trials.     

Metformin increases fasting plasma peptide tyrosine tyrosine (PYY) in women with polycystic ovarian syndrome (PCOS)

Objective The beneficial effects of metformin in patients with type 2 diabetes mellitus (T2DM) and polycystic ovarian syndrome (PCOS) are thought to be in part due to weight reduction. However, the mechanisms by which metformin causes weight loss are unclear. We sought to determine whether circulating levels of the anorectic gut hormone peptide tyrosine tyrosine (PYY) show any correlation with metformin‐induced weight loss. Design and patients We examined the acute effects of orally administrated metformin on fasting PYY levels in eight healthy normal‐weight female subjects. Subsequently, we evaluated the effects of 6 months metformin treatment on fasting PYY levels and anthropometric measurements in 20 women with PCOS. Results In normal‐weight females 10 days’ metformin treatment increased fasting PYY levels (P < 0·01). Similarly, in PCOS subjects metformin treatment increased fasting PYY concentrations (P < 0·05). In both groups a marked variation in PYY increase in response to metformin was observed. Long‐term metformin treatment was associated with improvements in weight (P < 0·05), BMI (P < 0·05), fasting glucose (P < 0·05) and menstrual frequency (P < 0·01). Interestingly, change in PYY levels were correlated with change in waist circumference (r = 0·55, P < 0·05). Conclusions Acute and chronic oral metformin administration increase fasting PYY levels and may contribute to metformin's weight loss effect. Further studies are now required to clarify whether changes in circulating PYY levels in response to metformin treatment can be used to predict which patients will subsequently lose weight long‐term and gain cycle restoration.