Impact of statin withdrawal on perceived and objective muscle function.

BACKGROUND AND AIMS: Statin-associated muscle symptoms (SAMS) are frequently reported. Nevertheless, few data on objective measures of muscle function are available. Recent data suggesting an important nocebo effect with statin use could confound such effects. The objective was to assess if subjective and objective measures of muscle function improve after drug withdrawal in SAMS reporters. METHODS: Patients (59 men, 33 women, 50.3±9.6 yrs.) in primary cardiovascular prevention composed three cohorts: statin users with (SAMS, n = 61) or without symptoms (No SAMS, n = 15), and controls (n = 16) (registered at clinicaltrials.gov, NCT01493648). Force (F), endurance (E) and power (P) of the leg extensors (ext) and flexors (fle) and handgrip strength (Fhg) were measured using isokinetic and handheld dynamometers, respectively. A 10-point visual analogue scale (VAS) was used to self-assess SAMS intensity. Measures were taken before and after two months of withdrawal. RESULTS: Following withdrawal, repeated-measures analyses show improvements for the entire cohort in Eext, Efle, Ffle, Pext and Pfle (range +7.2 to +13.3%, all p≤0.02). Post-hoc analyses show these changes to occur notably in SAMS (+8.8 to +16.6%), concurrent with a decrease in subjective perception of effects in SAMS (VAS, from 5.09 to 1.85). Fhg was also improved in SAMS (+4.0 to +6.2%) when compared to No SAMS (-1.7 to -4.2%) (all p = 0.02). CONCLUSIONS: Whether suffering from "true" SAMS or nocebo, those who reported SAMS had modest but relevant improvements in muscle function concurrent with a decrease in subjective symptoms intensity after drug withdrawal. Greater attention by clinicians to muscle function in frail statin users appears warranted. TRIAL REGISTRATION: This study is registered in clinicaltrials.gov (NCT01493648).

No benefit of vitamin D supplementation on muscle function and health-related quality of life in primary cardiovascular prevention patients with statin-associated muscle symptoms: A randomized controlled trial.

BACKGROUND: Statins are the leading lipid-lowering drugs, reducing blood cholesterol by controlling its synthesis. Side effects are linked to the use of statins, in particular statin-associated muscle symptoms (SAMS). Some data suggest that vitamin D supplementation could reduce SAMS. OBJECTIVE: The purpose of this study was to evaluate the potential benefits of the vitamin D supplement in a randomized controlled trial. METHODS: Men (n = 23) and women (n = 15) (50.5 ± 7.7 years [mean ± SD]) in primary cardiovascular prevention, self-reporting or not SAMS, were recruited. Following 2 months of statin withdrawal, patients were randomized to supplementation (vitamin D or placebo). After 1 month of supplementation, statins were reintroduced. Before and 2 months after drug reintroduction, muscle damage (creatine kinase and myoglobin) was measured. Force (F), endurance (E) and power (P) of the leg extensors (ext) and flexors (fle) and handgrip strength (FHG) were also measured with isokinetic and handheld dynamometers, respectively. The Short Form 36 Health Survey (SF-36) questionnaire and a visual analog scale (VAS) were administrated to assess participants' self-reported health-related quality of life and SAMS intensity, respectively. Repeated-measures analysis was used to investigate the effects of time, supplementation, and their interaction, according to the presence of SAMS. RESULTS: Despite no change for objective measures, subjective measures worsened after reintroduction of statins, independent of supplementation (VAS, SF-36 mental component score, all p < 0.05). However, no interaction between time and supplementation according to the presence of SAMS was observed for any variables. CONCLUSIONS: Vitamin D supplementation does not appear to mitigate SAMS.

Fitness, adiposopathy, and adiposity are independent predictors of insulin sensitivity in middle-aged men without diabetes

Adiposopathy, or sick fat, refers to adipose tissue dysfunction that can lead to several complications such as dyslipidemia, insulin resistance, and hyperglycemia. The relative contribution of adiposopathy in predicting insulin resistance remains unclear. We investigated the relationship between adiposopathy, as assessed as a low plasma adiponectin/leptin ratio, with anthropometry, body composition (hydrostatic weighing), insulin sensitivity (hyperinsulinemic-euglycemic clamp), inflammation, and fitness level (ergocycle VO2max, mL/kgFFM/min) in 53 men (aged 34-53 years) from four groups: sedentary controls without obesity (body mass index [BMI] <25 kg/m2), sedentary with obesity (BMI > 30 kg/m2), sedentary with obesity and glucose intolerance, and endurance trained active without obesity. The adiponectin/leptin ratio was the highest in trained men (4.75 ± 0.82) and the lowest in glucose intolerant subjects with obesity (0.27 ± 0.06; ANOVA p < 0.0001) indicating increased adiposopathy in those with obesity. The ratio was negatively associated with adiposity (e.g., waist circumference, r = −0.59, p < 0.01) and positively associated with VO2max (r = 0.67, p < 0.01) and insulin sensitivity (M/I, r = 0.73, p < 0.01). Multiple regression analysis revealed fitness as the strongest independent predictor of insulin sensitivity (partial R2 = 0.61). While adiposopathy was also an independent and significant contributor (partial R2 = 0.10), waist circumference added little power to the model (partial R2 = 0.024). All three variables remained significant independent predictors when trained subjects were excluded from the model. Plasma lipids were not retained in the model. We conclude that low fitness, adiposopathy, as well as adiposity (and in particular abdominal obesity) are independent contributors to insulin resistance in men without diabetes (AU)

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Fitness, adiposopathy, and adiposity are independent predictors of insulin sensitivity in middle-aged men without diabetes.

Adiposopathy, or sick fat, refers to adipose tissue dysfunction that can lead to several complications such as dyslipidemia, insulin resistance, and hyperglycemia. The relative contribution of adiposopathy in predicting insulin resistance remains unclear. We investigated the relationship between adiposopathy, as assessed as a low plasma adiponectin/leptin ratio, with anthropometry, body composition (hydrostatic weighing), insulin sensitivity (hyperinsulinemic-euglycemic clamp), inflammation, and fitness level (ergocycle VO2max, mL/kgFFM/min) in 53 men (aged 34-53 years) from four groups: sedentary controls without obesity (body mass index [BMI] <25 kg/m(2)), sedentary with obesity (BMI > 30 kg/m(2)), sedentary with obesity and glucose intolerance, and endurance trained active without obesity. The adiponectin/leptin ratio was the highest in trained men (4.75 ± 0.82) and the lowest in glucose intolerant subjects with obesity (0.27 ± 0.06; ANOVA p < 0.0001) indicating increased adiposopathy in those with obesity. The ratio was negatively associated with adiposity (e.g., waist circumference, r = -0.59, p < 0.01) and positively associated with VO2max (r = 0.67, p < 0.01) and insulin sensitivity (M/I, r = 0.73, p < 0.01). Multiple regression analysis revealed fitness as the strongest independent predictor of insulin sensitivity (partial R (2) = 0.61). While adiposopathy was also an independent and significant contributor (partial R (2) = 0.10), waist circumference added little power to the model (partial R (2) = 0.024). All three variables remained significant independent predictors when trained subjects were excluded from the model. Plasma lipids were not retained in the model. We conclude that low fitness, adiposopathy, as well as adiposity (and in particular abdominal obesity) are independent contributors to insulin resistance in men without diabetes.

Irisin is more strongly predicted by muscle oxidative potential than adiposity in non-diabetic men

Numerous controversies surround the peptide hormone irisin. Although implicated as a myokine promoting the browning of adipose tissue in rodents, its roles in humans remain unclear. Contradictory results have also been found with respect to the relationships between adiposity or metabolic health and plasma irisin levels in humans. We investigated the relationship between irisin levels and body composition (hydrostatic weighing), insulin sensitivity (hyperinsulinemic-euglycemic clamp), fitness level (ergocycle VO2max) and skeletal muscle metabolic profile in 53 men (aged 34–53 years) from four groups: sedentary non-obese controls (body mass index [BMI] <25 kg/m2), sedentary obese (BMI >30 kg/m2), sedentary obese glucose-intolerant, and non-obese highly trained endurance active. Baseline plasma irisin levels were significantly different between groups, being lowest in trained men (140.6 ± 38.2 ng/mL) and highest in metabolically deteriorated glucose-intolerant subjects (204.0 ± 50.5 ng/mL; ANOVA p = 0.01). Including all subjects, irisin levels were positively associated with adiposity (e.g. fat mass, r = 0.430, p < 0.01) and negatively associated with fitness (r = −0.369, p < 0.01), insulin sensitivity (M/I, r = −0.355, p < 0.01) and muscle citrate synthase (CS) activity (r = −0.482, p < 0.01). Most correlations lost statistical significance when excluding active individuals, except for insulin resistance (r = −0.413, p < 0.01) and CS (r = −0.462,p < 0.01). Multiple regression analyses reveal CS as the strongest independent predictor of irisin levels (r 2 range 0.214 to 0.237). We conclude that muscle oxidative potential is an important factor linked to circulating irisin levels

Irisin is more strongly predicted by muscle oxidative potential than adiposity in non-diabetic men.

Numerous controversies surround the peptide hormone irisin. Although implicated as a myokine promoting the browning of adipose tissue in rodents, its roles in humans remain unclear. Contradictory results have also been found with respect to the relationships between adiposity or metabolic health and plasma irisin levels in humans. We investigated the relationship between irisin levels and body composition (hydrostatic weighing), insulin sensitivity (hyperinsulinemic-euglycemic clamp), fitness level (ergocycle VO2max) and skeletal muscle metabolic profile in 53 men (aged 34-53 years) from four groups: sedentary non-obese controls (body mass index [BMI] <25 kg/m(2)), sedentary obese (BMI >30 kg/m(2)), sedentary obese glucose-intolerant, and non-obese highly trained endurance active. Baseline plasma irisin levels were significantly different between groups, being lowest in trained men (140.6 ± 38.2 ng/mL) and highest in metabolically deteriorated glucose-intolerant subjects (204.0 ± 50.5 ng/mL; ANOVA p = 0.01). Including all subjects, irisin levels were positively associated with adiposity (e.g. fat mass, r = 0.430, p < 0.01) and negatively associated with fitness (r = -0.369, p < 0.01), insulin sensitivity (M/I, r = -0.355, p < 0.01) and muscle citrate synthase (CS) activity (r = -0.482, p < 0.01). Most correlations lost statistical significance when excluding active individuals, except for insulin resistance (r = -0.413, p < 0.01) and CS (r = -0.462, p < 0.01). Multiple regression analyses reveal CS as the strongest independent predictor of irisin levels (r(2) range 0.214 to 0.237). We conclude that muscle oxidative potential is an important factor linked to circulating irisin levels.