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Nathan Goodyear

Testosterone Replacement Therapy Improves Metabolic Parameters in Hypogonadal Men with ... - 0 views

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    Testosterone therapy lowered HgbA1c in poorly controlled Diabetics.  These patients were followed out to 52 weeks.  Testosterone therapy, as is lifestyle change, a long term strategy of Diabetes control.  Studies in controlled Diabetics have not shown a reduction in HgbA1c consistently.  Total cholesterol and waist circumference were also reduced.
Nathan Goodyear

[Evaluation of relationships between pla... [Pol Merkur Lekarski. 2014] - PubMed - NCBI - 0 views

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    Men with Metabolic Syndrome have lower Total Testosterone values.  Symptoms correlated with age: older men associated with increased symptoms.  This study only found lot T at 6.5%.  The authors in this study have come up with a new box--andropenia.  I don't know what the heck that is and how that helps clients.  If symptoms are present and if levels are on the decline, then symptomatic hypogonadism is present.  I know the logic seems simple, but it appears hard to follow in the science.  I don't see this any different then type II diabetes.  At 126 you have diabetes, but at 125, we don't know what to do with you but see us next year and you will have diabetes and we will know what to do because you are in the box of diabetes.
Nathan Goodyear

JAMA Network | JAMA Surgery | Three-Year Outcomes of Bariatric Surgery vs Lif... - 0 views

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    new study finds that bariatric surgery outperforms lifestyle interventions in improving glucose control in obese individuals.  On the surface this seems interesting, but the lifestyle interventions were based on the Diabetes Prevention program.  The diabetes prevention program doesn't do well in glucose control in any clients (see increasing diabetes rates), so it should be no surprise that bariatric surgery outperforms a program that doesn't work
Nathan Goodyear

Mortality and Other Important Diabetes-Related Outcomes With Insulin vs Other Antihyper... - 0 views

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    not sure if I posted this previously, but new study finds that insulin should be the last thing given to a type II diabetic.  Insulin doubles mortality rate.
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
Nathan Goodyear

Evaluation of the hypothalamic-pituitary-gonadal a... [Andrology. 2013] - PubMed - NCBI - 0 views

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    Increasing glucose levels associated with declining LH pulses in men with type II diabetes.  This is one proposed mechanism for low T in men.  There has been great debate about if Low T was in part the cause of Diabetes or an effect of diabetes.  This proposes that low T is due to a decreased LH pulse as a result of rising glucose.
Nathan Goodyear

Circulating Estrone Levels Are Associated Prospectively With Diabetes Risk in Men of th... - 0 views

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    A cross-sectional study of 1,458 men over a 13 years found an increase risk of diabetes incidence with elevated Estradiol and Estrone levels.  The greatest association was found with Estrone.  This should come as no surprise to anybody as type II diabetes is clearly associated with increasing weight and this is the source of 80% of estrogen production in men.
Nathan Goodyear

ScienceDirect - Food and Chemical Toxicology : Neuroprotective effect of ginger on anti... - 0 views

  • A marked decrease in anti-oxidant marker enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), reduced glutathione (GSH) and increase in malondialdehyde (MDA) was observed in the diabetic rats
  • inger may be used as therapeutic agent in preventing complications in diabetic patients.
  • These results suggest that ginger exhibit a neuroprotective effect by accelerating brain anti-oxidant defense mechanisms and down regulating the MDA levels to the normal levels in the diabetic rats
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    Ginger reduces oxidative stress in diabetic rat model
Nathan Goodyear

Testosterone restores insulin sensitivity in patients with diabetes and hypogonadism | ... - 0 views

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    This is the abstract from oral presentation at AACE in Las Vegas from May.  Small study finds reduction in fat mass, increase in muscle mass, increase in insulin sensitivity, and reduction in inflammation signaling with Testosterone therapy in men with low Testosterone.  These men were type 2 diabetics.  This is consistent with prior published literature.  However, men without diabetes, this association is hard to reproduce. The degree of glucose control also effects the response to Testosterone therapy i.e. the worse the glucose control, the more the response from Testosterone.   Also of note, those men with hypogonatrophic hypogonadism had decreased insulin receptor expression, decreased insulin sensitivity, and decreased GLUT-4 expression versus eugonadal men.  Remember from prior studies, it is the conversion of Testosterone to DHT that increases GLUT-4 transcription, translocation, and expression.
Nathan Goodyear

Colonic Microbiota Encroachment Correlates With Dysglycemia in Humans - Cellular and Mo... - 0 views

  • most (86%) were overweight, many (45%) were obese
  • third (14 out of 42) had diabetes
  • in obese persons with diabetes, bacteria could be found in the dense inner mucus and in close proximity to the epithelium
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    Gut bacteria proximity, not just balance and diversity, to mucosa lining linked to systemic inflammation and insulin resistance in type II diabetes.  The role of type II diabetes may simply be the gut.  This has been called metabolic endotoxemia.
Nathan Goodyear

Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-l... - 0 views

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    study finds very low calorie diet reversed diabetes. The greatest weight loss was associated with greatest remission of diabetes at 86% with >15 kg weight loss.
Nathan Goodyear

Mechanisms of Pancreatic β-Cell Death in Type 1 and Type 2 Diabetes - 0 views

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    inflammation leads to death of pancreatic beta cells and result in diabetes.
Nathan Goodyear

Imbalance in Sex Hormone Levels Exacerbates Diabetic Renal Disease - 0 views

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    Diabetes associated with low serum testosterone.  This study points to a 4.7 fold decrease.  This is accompanied by a 2.9 fold increase in estradiol.  Castration worsened this imbalance by decreasing the testosterone level further.  Likely the low T and increased aromatase activity aid in the development of diabetic renal disease. Numerous studies have shown that testosterone therapy improves glucose homeostasis.
Nathan Goodyear

Hypoadiponectinemia in Obesity and Type 2 Diabetes: Close Association with Insulin Resi... - 0 views

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    obesity and type II diabetes found to be associated with low adiponectin and elevated insulin as found in insulin resistance.  This study revealed the inverse relationship of adiponectin and insulin resistance.  The interesting thing is that inflammation causes insulin resistance.  Here you can see the inflammation-insulin resistance-low adiponectin-obesity-diabetes link.
Nathan Goodyear

Zinc and diabetes--clinical links and molecul... [J Nutr Biochem. 2009] - PubMed - NCBI - 0 views

  • Zinc supplementation of animals and humans has been shown to ameliorate glycemic control in type 1 and 2 diabetes, the two major forms of diabetes mellitus, but the underlying molecular mechanisms have only slowly been elucidated. Zinc seems to exert insulin-like effects by supporting the signal transduction of insulin and by reducing the production of cytokines, which lead to beta-cell death during the inflammatory process in the pancreas in the course of the disease
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    Zn show to help in glycemic control in both type I and II diabetics.  It appears to do this through inflammation reduction and thus improved insulin/Receptor signal transduction.   Also of note, antibodies against Zn transporter have been found in type I DM.
Nathan Goodyear

D-chiro-inositol metabolism in diabetes mellitus - 0 views

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    d-chiro-inositol levels shown to be low in diabetics.  Thus, d-chiro-inositol would prove to be helpful in diabetes management.  D-chiro-inositol is a secondary messenger in insulin signaling
Nathan Goodyear

Oxidative Stress and Stress-Activated Signaling Pathways: A Unifying Hypothesis of Type... - 0 views

  • In patients with diabetes, LA levels are reduced (48, 74, 103). LA has long been used for the treatment of diabetic neuropathy in Germany
  • evidence indicates that it increases insulin sensitivity in patients with type 2 diabetes
  • LA has been shown to 1) quench free radicals, 2) prevent singlet oxygen-induced DNA damage, 3) exhibit chelating activity, 4) reduce lipid peroxidation, 5) increase intracellular glutathione levels, and 6) prevent glycation of serum albumin (73, 74). LA is able to reduce oxidative stress-mediated NF-κB activation in vitro (74, 108, 109) and in patients with type 2 diabetes
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  • Activation of NF-κB can also be blocked by several other thiol-containing antioxidants including N-acetyl-l-cysteine (NAC)
  • Other clinically available antioxidants reported to have antiinflammatory, antioncogenic, and/or antiatherogenic properties that have been shown to block the activation of NF-κB include resveratrol (115, 116), (-)-epicatechin-3-gallate (117), pycnogenol (118), silymarin (119), and curcumin (120)
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    Great read!  If you want to see how free radicals and oxidative stress contribute to inflammation and disease (DM in this case), read this article.
Nathan Goodyear

Diabetes mellitus and the risk of dementia: The Ro... [Neurology. 1999] - PubMed - NCBI - 0 views

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    the use of insulin in diabetes is associated with a 430% increase risk of developing dementia.  Wow!!  Just the present of Diabetes, almost doubled the risk.  Add in extra insulin and it is like throwing fuel to the fire that exists in the brain.
Nathan Goodyear

Total Testosterone Levels and the Effect of Sildenafil on Type 2 Diabetics with Erectil... - 0 views

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    Interesting study. In this study group, 36% of type II diabetes with ED had low Testosterone.  This fits with the estimated 40% of those with Diabetes have low T. What is really interesting about this study is that the degree of improvement with ED by Sildenfafil was dependent on the Testosterone level in the low T group.  Meanining that Testosterone therapy in these men would probably be more of a therapy directed at the cause and not Sildenafil.  Of course, the Testosterone therapy would benefit glucose regulation as well documented in the literature.
Nathan Goodyear

[Plasma testosterone, obesity, metabolic syndrome and diabetes]. - Abstract - Europe Pu... - 0 views

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    Androgen deprivation therapy leads to insulin resistance, metabolic syndrome, and type II diabetes in men. Testosterone therapy in men with IR, obesity, metabolic syndrome, and type II Diabetes will result in improved cardiovascular risk.  
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