"Insulin Resistance" and it's effect of SHBG and T levels: What to do about it?

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    "Insulin Resistance" and it's effect of SHBG and T levels: What to do about it?


    OK, I get the whole concept of insulin resistance and our body's tendency to be too stupid for it's own good. I also get how a poor diet, etc can cause it and the long term health issues associated therewith.

    In my case, I have very low SHBG (11) and, of course, low T which may well be causally related. Several times here and with a Reproductive Endo @ Mass Gen'l I have heard that "insulin resistance" is likely a factor for me.

    What I don't get, however, is what I can DO about it. I already eat rather well and exercise regularly. What else can I do? Eliminate ALL sugar, caffeine and pretty much anything with taste? Should I quite my job and exercise 24/7? I am 6' and about 212. Yes, I could loose 15 lbs, but I'm still in decent shape, low T notwithstanding.

    Any thoughts or ideas? It's not like I never exercise, eat cake all day and would have an easy answer. What am I missing?

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    This is something I plan to ask Dr. Shippen about but since you will see him before me, let us know what he says. Hypothyroidism can lead to insulin resistance also so that is on thing to keep an eye on .....although I realize that may not apply to you. Otherwise I don't know what else to do except not to eat too much sugar or carbs.
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    Quote Originally Posted by farmerjohn View Post
    This is something I plan to ask Dr. Shippen about but since you will see him before me, let us know what he says. Hypothyroidism can lead to insulin resistance also so that is on thing to keep an eye on .....although I realize that may not apply to you. Otherwise I don't know what else to do except not to eat too much sugar or carbs.
    high cortisol, Low thyroid = low shbg as well
    •   
       

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    Some medical links that discuss the issue: Still sorting them out. Any input?


    Well, I have a few sites and links that discuss a definite relationship. One is there, all right, but what to do with it and a solution still eludes me. I suspect that this issue affects quite a few of us here. If we could make more sense out of it quite a few of us might benefit.

    I am not more than 15 lbs overweight, eat generally well and exercise regularly. The extra weight came only few years ago--right when all this BS started. There has to be a connection. Were I 100 lbs overweight and totally sedentary I'd have a rather obvious solution. Not sure what more I can realistically do and still go to work! Anyway, here are the links:

    http://jcem.endojournals.org/cgi/con...jc.2004-2190v1

    http://www.docguide.com/news/content...256BE3004E64AE

    http://jcem.endojournals.org/cgi/eletters/90/5/2636

    http://care.diabetesjournals.org/cgi...tract/27/4/861
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    Quote Originally Posted by anyman View Post
    Well, I have a few sites and links that discuss a definite relationship. One is there, all right, but what to do with it and a solution still eludes me. I suspect that this issue affects quite a few of us here. If we could make more sense out of it quite a few of us might benefit.

    I am not more than 15 lbs overweight, eat generally well and exercise regularly. The extra weight came only few years ago--right when all this BS started. There has to be a connection. Were I 100 lbs overweight and totally sedentary I'd have a rather obvious solution. Not sure what more I can realistically do and still go to work! Anyway, here are the links:

    INCREASING INSULIN RESISTANCE IS ASSOCIATED WITH A DECREASE IN LEYDIG CELL TESTOSTERONE SECRETION IN MEN -- Pitteloud et al., 10.1210/jc.2004-2190 -- Journal of Clinical Endocrinology & Metabolism

    News - Insulin Resistance Tied to Low Testosterone in Men: Presented at ENDO

    JCEM -- eLetters for Pitteloud et al., 90 (5) 2636-2641

    Association of Bioavailable, Free, and Total Testosterone With Insulin Resistance: Influence of sex hormone-binding globulin and body fat -- Tsai et al. 27 (4): 861 -- Diabetes Care
    You are addresing important issue.
    Looks like low SHBG leads or is caused by insuline resistance.
    Probably more complicated.
    At the moment I think the question would be
    how to raise SHBG ---> how to fight insuline resistance
    it is really same problem.

    My current answer:
    Jan's BloodTest April13/2007

    MEGA SILYMARIN 900 MG 100 CAPS Item#00702
    ENHANCED CINNULIN PF W/GLUCOSE90 CAPS Item# 00967

    My SHBG is either 20 or 24
    Hemoglobin A1C=5.6
    Glucose, fasting=105
    Insuline, serum=5

    I am assuming it is not sewere yet, so I started on the two above supplements, hoping to lower my A1C.
    Second step would be to stop taking supplemets that lower SHBG.
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    Metabolic Syndrome
    http://www.lef.org/magazine/mag2006/...tabolic_01.htm
    ============================== ========
    Other than healthy diet and supplements:

    PHARMACEUTICAL OPTIONS FOR METABOLIC SYNDROME
    Drug companies are keenly interested in developing new drug treatments for people with metabolic syndrome. Unfortunately, due to the overwhelming drive by multibillion-dollar pharmaceutical companies to continually make profits, one of the very best drugs to help increase insulin sensitivity and improve blood sugar control (without promoting weight gain) is rarely mentioned. This drug, metformin, is currently off patent and very cost-effective.

    Metformin, which belongs to a class of drugs called biguanides, works in several different ways to improve insulin’s ability to work at the cellular level in tissues such as muscle and the liver. Metformin is not associated with weight gain—a major advantage over all other drugs used to treat diabetes. Of additional interest is that gene-chip research funded by Life Extension showed that metformin influences gene expression in ways similar to those of caloric restriction. This suggests that metformin may have potential anti-aging benefits in addition to its documented effects on blood sugar control.

    Other currently available drugs that may be useful in treating metabolic syndrome include the thiazolidinediones, a class of drugs approved for the treatment of diabetes.

    Thiazolidinediones include GlaxoSmithKline’s rosiglitazone (Avandia®) and Takeda/Eli Lilly’s pioglitazone (Actos®). Thiazolidinediones work by targeting PPARs (peroxisome proliferator-activated receptors), which are attractive drug targets for treating metabolic disease.

    PPARs help regulate the expression of genes involved in the storage and use of dietary fats. Two subtypes, PPAR alpha and PPAR gamma, have insulin-sensitizing effects.

    Among the new drugs in development for metabolic syndrome are AstraZeneca’s tesaglitazar, and Bristol-Myers Squibb’s muraglitazar.

    Individuals with kidney disease should not use metformin. Rosiglitazone (Avandia®) and pioglitazone (Actos®) should not be used by people with a history of congestive heart failure or liver disease. Please consult your doctor before using any pharmaceutical drug to treat metabolic syndrome.
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    Red face


    JanSz,

    Are you saying that you were able to raise your SHBG with those supplemebts?

    My SHBG has been tested many times over the past four years, and the highest value I've ever seen is 9!

    I'm thin, young, excercise, and my diet is processed food and bad carb free. (It only comes form vegetables, good grains, and a minimum of fruit (in that order.)

    Can anyone provide the average dose of metformin used to decrease the amount of insulin needed in the body?
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    Quote Originally Posted by ViolatedBird View Post
    JanSz,

    Are you saying that you were able to raise your SHBG with those supplemebts?

    My SHBG has been tested many times over the past four years, and the highest value I've ever seen is 9!

    I'm thin, young, excercise, and my diet is processed food and bad carb free. (It only comes form vegetables, good grains, and a minimum of fruit (in that order.)

    Can anyone provide the average dose of metformin used to decrease the amount of insulin needed in the body?
    Thank you for asking this question?
    Repeating my line of thought:
    Quote:
    Looks like low SHBG leads or is caused by insuline resistance.
    Probably more complicated.
    At the moment I think the question would be
    how to raise SHBG ---> how to fight insuline resistance
    it is really same problem.
    ============================== ===
    I am not a doctor.
    I think succesful work on insuline resistance should also increase SHBG.
    ----------------------------------------------------------
    My Hemoglobin A1C is slightly higher and my SHBG is not high (SHBG=20)
    After I found this on my Apr07 blood test, I started the two supplements, will know if they make difference after I test my blood.
    MEGA SILYMARIN 900 MG 100 CAPS Item#00702
    ENHANCED CINNULIN PF W/GLUCOSE90 CAPS Item# 00967
    ----------------------------------------------------------
    Metformin,
    I think it is (also?) ingredient of some other medicines.
    I googled this:
    Glucophage XR
    Riomet Solution
    Fortamet
    -----------------------------------------------------------
    Best that come to my mind will be to call LEF health advisors or LEF doctors and ask them question on how to deal with Metformin or other drugs that contain Metformin.
    Dr. Akhundova
    (800) 226-2370 ext. 7620
    -----
    Dr Gary Fields (same number, do not know ext)
    -----
    Dr John is on board of LEF
    -----------------------------------------------------------
    Some of my google searches on Metformin
    Metformin Information from Drugs.com

    Complete Metformin information from Drugs.com

    Complete Glucophage XR Extended-Release Tablets information from Drugs.com

    Glucophage Review, from Get the Skinny on Diets

    Complete Riomet Solution information from Drugs.com

    Fortamet Official FDA information, side effects and uses.
    ============================== ============================== ===
    Interesting how Fortamet pill is made
    "SYSTEM COMPONENTS AND PERFORMANCE
    Fortamet® was developed as an extended-release formulation of metformin hydrochloride and designed for once-a-day oral administration using the patented single-composition osmotic technology (SCOT™). The tablet is similar in appearance to other film-coated oral administered tablets but it consists of an osmotically active core formulation that is surrounded by a semipermeable membrane. Two laser drilled exit ports exist in the membrane, one on either side of the tablet. The core formulation is composed primarily of drug with small concentrations of excipients. The semipermeable membrane is permeable to water but not to higher molecular weight components of biological fluids. Upon ingestion, water is taken up through the membrane, which in turn dissolves the drug and excipients in the core formulation. The dissolved drug and excipients exit through the laser drilled ports in the membrane. The rate of drug delivery is constant and dependent upon the maintenance of a constant osmotic gradient across the membrane. This situation exists so long as there is undissolved drug present in the core tablet. Following the dissolution of the core materials, the rate of drug delivery slowly decreases until the osmotic gradient across the membrane falls to zero at which time delivery ceases. The membrane coating remains intact during the transit of the dosage form through the gastrointestinal tract and is excreted in the feces.
    ++++++++++++++++++++++++++++++ ++++++++++++++++++++++++++++++ +++++++
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    About - Health & Fitness - Drug Finder
    Metformin
    Fortamet™ | Glucophage® | Glucophage® XR | Glumetza™ | Riomet™
    ============================== ===========================




    Metformin
    About - Health & Fitness - Drug Finder

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    Quote Originally Posted by anyman View Post
    Well, I have a few sites and links that discuss a definite relationship. One is there, all right, but what to do with it and a solution still eludes me. I suspect that this issue affects quite a few of us here. If we could make more sense out of it quite a few of us might benefit.

    I am not more than 15 lbs overweight, eat generally well and exercise regularly. The extra weight came only few years ago--right when all this BS started. There has to be a connection. Were I 100 lbs overweight and totally sedentary I'd have a rather obvious solution. Not sure what more I can realistically do and still go to work!
    Reapportioning calories so that more come from protein and fat and fewer come from carbohydrate can help: the usual drill - drastically reduce or completely eliminate refined and simple carbs; even cut back on fruit - make sure that when you eat fruit, you combine it with some protein and fat - nuts and/or a little bit of cheese; healthy fats, lean protein. It works for almost anybody.
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    http://www.digitalnaturopath.com/cond/C655233.html
    Low SHBG
    Risk factors for Low SHBG:
    Aromatase
    Elevated Insulin Levels
    Low Progesterone or Estrogen Dominance
    ============================== ============================== ==========================
    Recommendations for Low SHBG:
    Weight Loss
    Gluten-free Diet
    Not recommended:
    DIM (di-indolmethane)/I3C (Indole-3-Carbinol)

    ============================== ============================== ==========================
    http://www.testocreme.com/prescribetestocreme.html
    Why monitor Estrone?

    Estrone is the principal estrogen found in both the postmenopausal
    woman and the aged male. The increase in estrone is due to the increased conversion of androstenedione and T to estrone ( E1). There is evidence

    that high E1 levels may indicate increased tendency to cancer cell growth. Androstenedione (A) is a metabolic product of DHEA, and is a major source

    of E2 and E1 in women; therefore patients receiving DHEA should be monitored by saliva for increases in estrone to supra-physiological levels.

    ============================== ============================== =========================
    TRT in men with low SHBG
    http://forum.mesomorphosis.com/mens-...134237140.html

    My take home message:
    Another reason to go to Quest and get
    Estradiol, Bioavailable
    Estradiol, Free

    Actually this set would give better picture:
    0 iodine
    11 Zinc
    27 Hemoglobin A1C
    29 Lipoprotein (A) Lp(A)

    56 Cortisol AM/PM
    57 DHEA sulfate
    58 Prolactin
    49 Glucose, fasting
    50 Insuline, serum

    61 Progesterone
    62 Pregnenolone
    63 Estradiol, Bioavailable
    64 Estradiol, Free
    65 Estradiol, Fractionated, serum
    66 Estradiol, Ultra-sensitive (is part of fractionated)
    67 Estrone,serum (is part of fractionated)
    68 Estrogens, Total, Serum
    69 Testosterone, Free, Bio/Total (LC/MS/MS)
    70 Testosterone Total (included in T panel)
    71 Testosterone Free(included in T panel)
    72 Testosterone Bioavailable(included in T panel)
    73 SHBG(included in T panel)
    74 Albumin, serum(included in T panel)
    75 Dihydrotestosterone DHT

    Then do balancing act to keep
    A1C low
    Free T & E high but not over the top
    BioAvail T & E high but not over the top

    Never seen FreeE and BioAvailE results, wonder how will they corelate with E2 that we talk so often about.
    ++++++++++++++++++++++++++++++ ++++++++++++++++++++++++++++++ ++++++++++++++++++++++++++++++ ++
    SWALE
    http://forum.mesomorphosis.com/436652-post18.html
    You have to remember that elevating estrogen also tends to elevate SHBG concentration. Everyone is different, but generally you do not see high

    estrogen and low SHBG.
    ----
    So; when SHBG is low;
    Test all estrogens and SHBG
    Apply any regulating supplements gingerly.
    ++++++++++++++++++++++++++++++ ++++++++++++++++++++++++++++++ ++++++++++++++++++++++++++++++ ++
    MARIANCO
    http://forum.mesomorphosis.com/497692-post24.html
    TRT with Low SHBG is not simple to do because there are many other complicating factors such as:
    1. SHBG is reduced further by the increase in testosterone.
    2. Insulin resistance. Low SHBG is one sign of insulin resistance/diabetes. Insulin resistance can cause other hormone imbalances and impair nerve

    signal transmission.
    3. Hypothyroidism. Low SHBG may be a sign of inadequate thyroid hormone levels. Hypothyroidism is often present clinically though the lab tests are

    normal.
    4. The duration action of testosterone is shortened by low SHBG - making one prone to a roller coaster experiences.
    5. Testosterone can reduce thyroid hormone activity - resulting in anxiety or depressive symptoms depending on the severity of the reduction. There are

    multiple mechanisms of action which can cause this.
    6. Low SHBG may result in high free Testosterone. High Free testosterone is not necessarily good. For example, if estradiol levels and progesterone

    levels are normal, the high free testosterone may result in high blood pressure. Testosterone can either lower or raise blood pressure depending on its

    relationship to the other hormones.
    7. etc.

    Testosterone functions depend on its relationship with other hormones, neurotransmitters, and cytokines - these all are chemical messengers in the

    body. Low SHBG complicates matters but is not an unsolvable problem in most people.
    -----
    Lesson from #4---Increase frequency of T shots when SHBG is low.
    ++++++++++++++++++++++++++++++ ++++++++++++++++++++++++++++++ ++++++++++++++++++++++++++++++ ++
    MARIANCO
    http://forum.mesomorphosis.com/498387-post26.html

    Focusing on increasing SHBG is like treating a lab value rather than treating a patient.

    The question I would have for a person with low SHBG is: What problems does one have?

    Is it low libido, high blood pressure, heart attack risk, depression, anxiety, lack of energy, impaired concentration, urinary frequency, gynecomastia, hot

    flashes, etc.?

    By identifying one's problems, it will be easier to see whether or not SHBG level contributes to the problem.

    SHBG has signaling properties of its own. It has its own receptors on cell membranes. When testosterone or estrogens are bound to SHBG, it can bind

    to its receptors and send its message to the cell. What happens afterwards is not clear. It may be related to the formation of more hormone receptors -

    but that is speculation at this point.

    SHBG helps prolong the duration of action of testosterone, DHT, and estrogens. Low SHBG will increase the amount of free hormone.

    Swings in hormone level may occur when low SHBG is present as destruction of the hormone is accelerated by having high free levels. This may

    cause problems experienced during testosterone replacement. For example, if estrogen is more quickly destroyed/metabolized and levels drop more

    quickly, one can get hot flashes or anxiety or hypertension, etc. If testosterone levels fluctuate from high to low, depression can occur as the day

    progresses.

    SHBG is made in the liver in response to levels of many hormones:
    1. Increasing Testosterone reduces SHBG
    2. Increasing DHT lowers SHBG
    3. Increasing DHEA lowers SHBG
    4. Increasing Growth Hormone lowers SHBG
    5. Increasing Insulin lowers SHBG
    6. Increasing Estrogen increases SHBG
    7. Increasing Thyroid Hormone increases SHBG

    The SHBG level is determine by the balance of the hormone levels.

    Given one's assumed goals in TRT (high libido, good energy, etc.), it may be difficult to increase SHBG without causing problems since SHBG is

    determine by a balance of hormones.

    For example, having high Testosterone and high DHEA is not a situation where SHBG is going to be high without corresponding problems with estrogen

    or thyroid.

    If anything, SHBG should be most often viewed as an indicator of a problem that needs to be solved - rather than as a problem itself.

    For example, SHBG is most commonly an indicator of high insulin levels - i.e. insulin resistance or diabetes. It would be then far more important to

    address insulin resistance or diabetes in treatment than to focus on SHBG.

    If low thyroid is a factor in low SHBG, addressing hypothyroidism is far more important.

    If low estradiol is a factor in low SHBG, addressing this is more important.

    If the low SHBG itself is a problem because it causes large swings in hormone levels, then working around this by achieving more stable hormone

    levels is indicated.

    More frequent dosing of testosterone may be required to stabilize levels. With testosterone cypionate or enanthate injections, dosing twice a week

    would be better than once a week.

    If frequent dosing of testosterone cannot be achieved with transdermals or injections, then a constant dose solution may be needed. This includes

    testosterone patches, the buccal system, or testosterone pellet insertions. Testosterone pellet insertions may be viewed as fairly drastic since it

    involves regular minor surgical procedures, but does give the most stable levels - so is a viable solution for the men with problems due to highly variable

    hormone levels resulting from low SHBG.

    If one suspects swings in hormone levels as a cause of problems, one can look for the swings in hormone levels by obtaining a peak and trough level of

    the hormones (e.g. total testosterone, estradiol, DHT, etc.). For testosterone injections, this is a level about 24-48 hours after an injection and a level

    just before the next injection. One can also obtain a midpoint level to fill out the level curve.
    ++++++++++++++++++++++++++++++ ++++++++++++++++++++++++++++++ ++++++++++++++++++++++++++++++ ++++++++++++++++++
    http://jcem.endojournals.org/cgi/con...jc.2005-1326v1
    Low SHBG, Total Testosterone, and Symptomatic Androgen Deficiency are Associated with Development of the Metabolic Syndrome in Non-Obese

    Men
    ============================== ============================== ============================== ==================
    Low SHBG and Estradiol by Dr. Marianco.
    Low SHBG and Estradiol by Dr. Marianco.

    --------------------------------------------------------------------------------

    The most common cause of low SHBG is excessive insulin - i.e. insulin resistance. Insulin resistance in turn leads to a cascade of events which results

    other hormone imbalances such as low testosterone production, suboptimal thyroid hormone activity, adrenal fatigue, etc.

    Factors which together in a balance determine SHBG are:
    1. Anabolic hormones generally reduce SHBG. These include testosterone, DHEA, insulin, DHT, and growth hormone.
    2. Thyroid hormone, Estrogens, and Progesterone (by increasing estrogen receptors/sensitivity), increase SHBG.

    In the absence of insulin resistance, the most common other cause of low SHBG is a very high level of other anabolic hormones - most frequency high

    testosterone from TRT. Those who use anabolic steroids at high doses often drive their SHBG to near zero.

    When total testosterone is between 650 to 1000 ng/dl, and a person still has zero sex drive, I would look for other causes for sexual dysfunction - e.g.

    other hormone, neurotransmitter, or immune system problems.

    Raising SHBG does not necessarily increase the risk for Alzheimer's disease. It is important to keep in mind the factors which lead to the risk of

    Alzheimer's disease.

    Insulin resistance (i.e. excessive insulin levels) causes low SHBG. It also greatly increases the risk of Alzheimer's disease because it results in a higher

    level of inflammatory cytokine production (Cytokines are the chemical messengers of the immune system). It is the inflammation which is one of the

    underlying factors which leads to Alzheimer's disease.

    SHBG level is most often a signal of the overall status of multiple hormone levels. The balance may give an indication of whether one is in an pro-

    inflammatory state or anti-inflammatory state - with inflammation leading to disease such as Alzheimer's disease, heart disease, strokes, cancer, etc.

    Some hormones such as some estrogens and insulin can lead to inflammation leading to illness. And other hormones such as the androgens (except

    DHT), growth hormone, and thyroid hormone, can lead to an antiinflammatory state, reducing the risk for illness. The balance determines the person's

    risk for illness.

    What estradiol level is best for any individual often needs to be determined by trial and error. It is unique for each individual. Most do best around 30

    pg/ml. But some do best at lower and higher levels. For example, I have a 65 y.o. patient with a total testosterone of 840 ng/dl and an estradiol of 47

    pg/ml. He's having the time of his life - able to make love numerous times each night - after more than a decade of having no sex. The estradiol level

    works for him without side effects. Some may do better with much loser levels of estradiol - the response is highly individualistic.

    Even with low SHBG - which is difficult to correct since it depends on the balance of so many hormones - when the other hormones and

    neurotransmitters are optimized, sex drive and the ability to have an erection can often return.

    When total testosterone is supraphysiologic - i.e. over 1000 ng/dl - problems with libido and erections may occur. Testosterone increases dopamine in

    the brain in order to increase sex drive, reduce depression, give pleasure to activities. The problem is that dopamine is a very fragile

    neurotransmitter/hormone in its effects. Too high a dopamine level can cause tolerance to dopamine. This is similar to how one can develop tolerance

    to drugs such as cocaine and amphetamines which increase dopamine levels in the brain to cause their high. This can lead to the loss of libido when

    high testosterone levels are maintained for long periods of time.

    Conversely, when one is deprived of testosterone (and hence dopamine) for long periods of time due to hypogonadism, one can get a high during the

    first few weeks of testosterone treatment since the brain becomes supersensitive to dopamine when it has been deprived of it (e.g. making more

    dopamine receptors to pick up the weaker dopamine signals). Unfortunately, as the brain then gets use to the higher dopamine levels, it will develop

    some tolerance, and libido will drop off - though we often wish that hopefully a good amount remains.

    ============================== ============================== ============================== ==================
    http://www.google.com/search?q=low+s...e7&rlz=1I7ADBF





    http://forum.mesomorphosis.com/mens-...4237140-2.html
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    Ok what is the turn over rate for when give a specific regime to treat shbg imabalnces that it will show up in the blood. Meaning will it take 6 weeks to see change or 4 months in the shbg to be altered from baseline reading ?
  

  
 

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