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Nathan Goodyear

Testosterone and glucose metabolism in men: current concepts and controversies - 0 views

    • Nathan Goodyear
       
      80% of E2 production in men, that will cause low T in men, comes from SQ adiposity.  This leads to increase in visceral adiposity.
  • Only 5% of men with type 2 diabetes have elevated LH levels (Dhindsa et al. 2004, 2011). This is consistent with recent findings that the inhibition of the gonadal axis predominantly takes place in the hypothalamus, especially with more severe obesity
  • Metabolic factors, such as leptin, insulin (via deficiency or resistance) and ghrelin are believed to act at the ventromedial and arcuate nuclei of the hypothalamus to inhibit gonadotropin-releasing hormone (GNRH) secretion
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  • kisspeptin has emerged as one of the most potent secretagogues of GNRH release
  • Consistent with the hypothesis that obesity-mediated inhibition of kisspeptin signalling contributes to the suppression of the HPT axis, infusion of a bioactive kisspeptin fragment has been recently shown to robustly increase LH pulsatility, LH levels and circulating testosterone in hypotestosteronaemic men with type 2 diabetes
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  • Interestingly, a recent 16-week study of experimentally induced hypogonadism in healthy men with graded testosterone add-back either with or without concomitant aromatase inhibitor treatment has in fact suggested that low oestradiol (but not low testosterone) may be responsible for the hypogonadism-associated increase in total body and intra-abdominal fat mass
    • Nathan Goodyear
       
      This does not fit with the research on receptors, specifically estrogen receptors.  These studies that the authors are referencing are looking at "circulating" levels, not tissue levels.
  • A smaller study with a similar experimental design found that acute testosterone withdrawal reduced insulin sensitivity independent of body weight, whereas oestradiol withdrawal had no effects
  • Obesity and dysglycaemia and associated comorbidities such as obstructive sleep apnoea (Hoyos et al. 2012b) are important contributors to the suppression of the HPT axis
  • This is supported by observational studies showing that weight gain and development of diabetes accelerate the age-related decline in testosterone
  • Weight loss can reactivate the hypothalamic–pituitary–testicular axis
  • The hypothalamic–pituitary–testicular axis remains responsive to treatment with aromatase inhibitors or selective oestrogen receptor modulators in obese men
  • Kisspeptin treatment increases LH secretion, pulse frequency and circulating testosterone levels in hypotestosteronaemic men with type 2 diabetes
  • Several observational and randomised studies reviewed in Grossmann (2011) have shown that weight loss, whether by diet or surgery, leads to substantial increases in testosterone, especially in morbidly obese men
  • This suggests that weight loss can lead to genuine reactivation of the gonadal axis by reversal of obesity-associated hypothalamic suppression
  • There is pre-clinical and observational evidence that chronic hyperglycaemia can inhibit the HPT axis
  • in those men in whom glycaemic control worsened, testosterone decreased
  • successful weight loss combined with optimisation of glycaemic control may be sufficient to normalise circulating testosterone levels in the majority of such men
  • weight loss, optimisation of diabetic control and assiduous care of comorbidities should remain the first-line approach.
    • Nathan Goodyear
       
      This obviously goes against marketing-based medicine
  • In part, the discrepant results may be due to the fact men in the Vigen cohort (Vigen et al. 2013) had a higher burden of comorbidities. Given that one (Basaria et al. 2010), but not all (Srinivas-Shankar et al. 2010), RCTs in men with a similarly high burden of comorbidities reported an increase in cardiovascular events in men randomised to testosterone treatment (see section on Testosterone therapy: potential risks below) (Basaria et al. 2010), testosterone should be used with caution in frail men with multiple comorbidities
  • The retrospective, non-randomised and non-blinded design of these studies (Shores et al. 2012, Muraleedharan et al. 2013, Vigen et al. 2013) leaves open the possibility for residual confounding and multiple other sources of bias. These have been elegantly summarised by Wu (2012).
  • Effects of testosterone therapy on body composition were metabolically favourable with modest decreases in fat mass and increases in lean body mass
  • This suggests that testosterone has limited effects on glucose metabolism in relatively healthy men with only mildly reduced testosterone.
  • it is conceivable that testosterone treatment may have more significant effects on glucose metabolism in uncontrolled diabetes, akin to what has generally been shown for conventional anti-diabetic medications.
  • the evidence from controlled studies show that testosterone therapy consistently reduces fat mass and increases lean body mass, but inconsistently decreases insulin resistance.
  • Interestingly, testosterone therapy does not consistently improve glucose metabolism despite a reduction in fat mass and an increase in lean mass
  • the majority of RCTs (recently reviewed in Ng Tang Fui et al. (2013a)) showed that testosterone therapy does not reduce visceral fat
    • Nathan Goodyear
       
      visceral and abdominal adiposity are biologically different and thus the risks associated with the two are different.
    • Nathan Goodyear
       
      yet low T is associated with an increase in visceral adiposity--confusing!
  • testosterone therapy decreases SHBG
  • testosterone is inversely associated with total cholesterol, LDL cholesterol and triglyceride (Tg) levels, but positively associated with HDL cholesterol levels, even if adjusted for confounders
  • Although observational studies show a consistent association of low testosterone with adverse lipid profiles, whether testosterone therapy exerts beneficial effects on lipid profiles is less clear
  • Whereas testosterone-induced decreases in total cholesterol, LDL cholesterol and Lpa are expected to reduce cardiovascular risk, testosterone also decreases the levels of the cardio-protective HDL cholesterol. Therefore, the net effect of testosterone therapy on cardiovascular risk remains uncertain.
  • data have not shown evidence that testosterone causes prostate cancer, or that it makes subclinical prostate cancer grow
  • compared with otherwise healthy young men with organic androgen deficiency, there may be increased risks in older, obese men because of comorbidities and of decreased testosterone clearance
  • recent evidence that fat accumulation may be oestradiol-, rather than testosterone-dependent
wheelchairindia9

Electronic Wheel chair - 0 views

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    Golden Technologies takes all the worry out of purchasing a power wheelchair. Designers blend the most technologically advanced components with superior designs to provide with the almost in quality, comfort and style. Motorized wheelchairs to enter bike lanes if a sidewalk isn't available or passable by wheelchair. Wheelchair users would be required to yield the right-of-way to bikers. The proposal also adds motorized wheelchairs to current law affecting vehicles and bicycles on the road, including the required three foot law between bikers and drivers. Supporters bill would help wheelchair users get around quickly and that areas without sidewalks are often difficult to navigate. It's the standard chair, with the main frame attaches to the front. This isn't a futuristic design as such, but a very good way of maintaining or building strength in those who are bound to a wheelchair, and may hope to walk again in their future. Personally, this bike is pretty cool. It's got a front frame similar to a chopper, with the added comfort of a chair appose to a saddle. A new module is set to transform electric powered wheelchairs into communication hubs. An powerchair is more compact and has a better turning radius than an electric scooter; making it is easier to navigate narrow doorways and tight turns. Another advantage of the powerwheelchair is that its armchair joystick does not require an upright posture like an electric scooter's handlebars. Most power wheelchairs can also be taken apart and stowed, while scooters usually can't. Powerwheelchairs are also usually less expensive than scooters. For many disabled people, the only way to move around is by using a wheelchair. Those who cannot powered wheelchairs propel themselves with their arms, which often leads to fatigue, pain, and even permanent damage to arms and shoulders. BENEFITS: Activates circulation system and improves cardio-pulmonary function. Helps prevent decubitus sores. Improves bowel regu
Nathan Goodyear

Free triiodothyronine: a novel predictor of postoperative atrial fibrillation -- Cerill... - 0 views

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    Conclusions: Low basal fT3 concentration can reliably predict the occurrence of postoperative Atrial Fibrillation in Coronary-bypass patients
Nathan Goodyear

Leisure-Time Running Reduces All-Cause and Cardiovascular Mortality Risk - 0 views

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    Runners have a 30% lower all-cause mortality and a 45% cardiovascular mortality compared to non-runners in study.  What is interesting, is that only 5-10 minutes a day at very slow speeds is all that is required to receive these benefits.  As other studies have now shown, more is not necessarily better.
wheelchairindia9

Weight Cuff - 0 views

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    Tynor Weight Cuff Tynor Weight cuffs are used to exercise ailing joints to build strength and aid recovery. Tynor Weight Cuff is flexible and cushion, so it does not injure. Recommended for use to improve muscle tone, muscle mass, strength and stamina. Tynor Weight Cuff Features Offers 1 kg resistance when wrapped around Weight is wrapped in comfortable and soft fabric Used to build muscles, flexibility or to lose weight Can be secured easily around to prevent injuries or accidents Cuff is safe to be used during everyday activities as well Tynor Weight Cuff Measurements Sizes Available: 1/2 Kg / 1Kg / 2 Kg
Nathan Goodyear

Estrogenic regulation of skeletal muscle proteome: a study of premenopausal women and p... - 0 views

  • Female aging is characterized by menopausal change in sex steroid hormones concomitant to increase in aging-related decrements in skeletal muscle performance that can be attenuated by HRT use
  • The major canonical pathways found to be differentially regulated included mitochondrial dysfunction, oxidative phosphorylation, glycolysis, and TCA-cycle, strong indicators for affected energy metabolism
  • E2 to exert anti-apoptotic effects in muscle progenitor cells by improving mitochondrial function
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  • E2 is a major regulator of human skeletal muscle signaling in women
  • After menopause, when ovarian E2 production is ceased, the prevalence of cardio-metabolic diseases increases. Our result that different trajectories of the energy pathways in the skeletal muscle may be regulated by E2 provides candidate molecules as key targets for future interventions to prevent or treat postmenopausal metabolic dysregulation
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    Study finds Estradiol regulates human skeletal muscle cell signaling (mitochondrial function, oxidative phosphorylation, glycolysis, and TCA cycle) in study of pre/post menopause women through proteome analysis. This study would have been complete if they had carried to search beyond that of protein to epigenetics.
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