Testosterone level in men with type 2 diabetes mellitus and related metabolic... - 0 views
www.ncbi.nlm.nih.gov/...PMC4364844
low T low Testosterone Diabetes Testosterone men male hormones metabolic syndrome
shared by Nathan Goodyear on 30 Mar 15
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defined by consistent symptoms and signs of androgen deficiency, and an unequivocally low serum testosterone level
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the threshold serum testosterone level below which adverse clinical outcomes occur in the general population is not known
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most population-based studies use the serum testosterone level corresponding to the lower limit, quoted from 8.7 to 12.7 nmol/L, of the normal range for young Caucasian men as the threshold
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Researchers tried to examine whether serum total or free testosterone would be a better/more reliable choice when studying the effect of testosterone. The results were mixed. Some reported significant associations of both serum total and free testosterone level with clinical parameters25, whereas others reported that only serum free testosterone26 or only serum total testosterone6 showed significant associations.
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−0.124 nmol/L/year in serum total testosterone
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In experimental studies, androgen receptor knockout mice developed significant insulin resistance rapidly
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In mouse models, testosterone promoted differentiation of pluripotent stem cells to the myogenic lineage
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testosterone decreased insulin resistance by enhancing catecholamine induced lipolysis in vitro, and reducing lipoprotein lipase activity and triglyceride uptake in human abdominal tissue in vivo
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by promoting lipolysis and myogenesis, testosterone might lead to improved insulin resistance
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testosterone regulated skeletal muscle genes involved in glucose metabolism that led to decreased systemic insulin resistance
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In the liver, hepatic androgen receptor signaling inhibited development of insulin resistance in mice
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independent and inverse association of testosterone with hepatic steatosis shown in a cross-sectional study carried out in humans
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In short, androgen improves insulin resistance by changing body composition and reducing body fat.
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Although a low serum testosterone level could contribute to the development of obesity and type 2 diabetes through changes in body composition, obesity might also alter the metabolism of testosterone
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In obese men, the peripheral conversion from testosterone to estrogen could attenuate the amplitude of luteinizing hormone pulses and centrally inhibit testosterone production
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leptin, an adipokine, has been shown to be inversely correlated with serum testosterone level in men
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Leydig cells expressed leptin receptors and leptin has been shown to inhibit testosterone secretion, suggesting a role of obesity and leptin in the pathogenesis of low testosterone
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Baltimore Longitudinal Study of Aging (BLSA) cohort made up of 3,565 middle-class, mostly Caucasian men from the USA, the incidence of low serum total testosterone increased from approximately 20% of men aged over 60 years, 30% over 70 years, to 50% over 80 years-of-age
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30–44% sex hormone binding globulin (SHBG)-bound testosterone and 54–68% albumin-bound testosterone
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As the binding of testosterone to albumin is non-specific and therefore not tight, the sum of free and albumin-bound testosterone is named bioavailable testosterone, which reflects the hormone available at the cellular level
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Serum total testosterone is composed of 0.5–3.0% of free testosterone unbound to plasma proteins
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alterations in SHBG concentration might affect total serum testosterone level without altering free or bioavailable testosterone
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listed in TableT
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A significant, independent and longitudinal effect of age on testosterone has been observed with an average change of −0.124 nmol/L/year in serum total testosterone28. The same trend has been shown in Europe and Australia
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Asian men residing in HK and Japan, but not those living in the USA, had 20% higher serum total testosterone than in Caucasians living in the USA, as shown in a large multinational observational prospective cohort of the Osteoporotic Fractures in Men Study
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subjects with chronic diseases consistently had a 10–15% lower level compared with age-matched healthy subjects
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In Caucasians, the mean serum total testosterone level for men in large epidemiological studies has been reported to range from 15.1 to 16.6 nmol/L
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Asians, higher values, ranging from 18.1 to 19.1 nmol/L, were seen in Korea and Japan
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Chinese middle-aged men reported a similar mean serum testosterone level of 17.1 nmol/L in 179 men who had a family history of type 2 diabetes and 17.8 nmol/L in 128 men who had no family history of type 2 diabetes
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The reduction of total testosterone was 0.4% per year in both groups
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HK involving a cohort of 1,489 community-dwelling men with a mean age of 72 years, a mean serum total testosterone of 19.0 nmol/L was reported
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pro-inflammatory factors, such as tumor necrosis factor-α in the testes, could locally inhibit testosterone biosynthesis in Leydig cells47, and testosterone treatment in men was shown to reduce the level of tumor necrosis factor-α
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In Asians, a genetic deletion polymorphism of uridine diphosphate-glucuronosyltransferase UGT2B17 was associated with reduced androgen glucuronidation. This resulted in higher level of active androgen in Asians as compared to Caucasians, as Caucasians' androgen would be glucuronidated into inactive forms faster.
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Compared with Caucasians, the frequency of this deletion polymorphism of UGT2B17 was 22-fold higher in Asian subjects
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Other researchers have suggested that environmental, but not genetic, factors influenced serum total testosterone
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The basal and ligand-induced activity of the AR is inversely associated with the length of the CAG repeat chain
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In the European Male Aging Study, increased estrogen/androgen ratio in association with longer AR CAG repeat was observed
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a smaller number of AR CAG repeat had been shown to be associated with benign prostate hypertrophy and faster prostate growth during testosterone treatment
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In India, men with CAG ≤19 had increased risk of prostate cancer
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the odds of having a short CAG repeat (≤17) were substantially higher in patients with lymph node-positive prostate cancer than in those with lymph node-negative disease or in the general population
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assessing the polymorphism at the AR level could be a potential tool towards individualized assessment and treatment of hypogonadism.
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In elderly men, there was reduced testicular response to gonadotropins with suppressed and altered pulsatility of the hypothalamic pulse generator
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a significant, independent and longitudinal effect of age on serum total testosterone level had been observed
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A significant graded inverse association between serum testosterone level and insulin levels independent of age has also been reported in Caucasian men
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Low testosterone is commonly associated with a high prevalence of MES
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most studies showed that changes in serum testosterone level led to changes in body composition, insulin resistance and the presence of MES, the reverse might also be possible
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MES predicted a 2.6-fold increased risk of development of low serum testosterone level independent of age, smoking and other potential confounders
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Other prospective studies have shown that development of MES accelerated the age-related decline in serum testosterone level
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In men with type 2 diabetes, changes in serum testosterone level over time correlated inversely with changes in insulin resistance
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weight loss by either diet control or bariatric surgery led to a substantial increase in total testosterone, especially in morbidly obese men, and the rise in serum testosterone level was proportional to the amount of weight lost
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To date, published clinical trials are small, of short duration and often used pharmacological, not physiological, doses of testosterone
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In the population-based Osteoporotic Fractures in Men Study cohort from Sweden, men in the highest quartile of serum testosterone level had the lowest risk of cardiovascular events compared with men in the other three quartiles (hazard ratio [HR] 0.70
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low serum total testosterone was associated with a significant fourfold higher risk of cardiovascular events when comparing men from the lowest testosterone tertile with those in the highest tertile
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Shores et al. were the first to report that low serum testosterone level, including both serum total and free testosterone, was associated with increased mortality
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low serum total testosterone predicted increased risk of cardiovascular mortality with a HR of 1.38
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low serum total testosterone increased all-cause (HR 1.35, 95% CI 1.13–1.62, P < 0.001) and cardiovascular mortality (HR 1.25
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European Association for the Study of Diabetes 2013 suggested there was an inverse relationship between serum testosterone level and acute myocardial infarction
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Diabetic men in the highest quartile of serum total testosterone had a significantly reduced risk of acute MI when compared with those in the lower quartiles
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serum total testosterone level in the middle two quartiles at baseline predicted reduced incidence of death compared with having the highest and lowest levels
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Nice review of Testosterone levels and some of the evidence linking Diabetes with low T. However, the conclusion by the authors regarding what is causing the low T in men with Diabetes is baffling. The literature does not point to one cause, it is clearly multifactorial--obesity, inflammation, high aromatase activity...I would suggest the authors continue their readings in the manner.
