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    Have We Really Demonstrated the Cardiovascular Safety of Antihyperglycemic Drugs?

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    graham64
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    Have We Really Demonstrated the Cardiovascular Safety of Antihyperglycemic Drugs?

    Post by graham64 on Sun Jan 07 2018, 21:36

    Rethinking the Concepts of Macrovascular and Microvascular Disease in Type 2 Diabetes

    Abstract
    A primary goal of the treatment of type 2 mellitus is the prevention of morbidity and mortality due to cardiovascular disease. However, antihyperglycemic drugs have the capacity to cause deleterious effects on the circulation, a risk that is not adequately reflected by the endpoints selected for emphasis in large-scale clinical trials that are designed to evaluate cardiovascular safety. The primary endpoint of the large-scale studies mandated by regulatory authorities focuses only on 3-4 events that depict only a limited view of the circulatory system.

    One of the most serious adverse effects of many glucose-lowering drugs is new-onset or worsening heart failure. Most antidiabetic drugs can aggravate heart failure because they exert antinatriuretic actions, and possibly, adverse effects on the myocardium. In addition, certain antihyperglycemic agents may worsen peripheral vascular disease and trigger cardiac arrhythmias that may lead to sudden death. Initiation of treatment with antidiabetic medications may also cause deterioration of the function of the kidneys, retina and peripheral nerves, which are typically regarded as reflecting microvascular disease.

    The current confusion about the cardiovascular effects of glucose-lowering drugs may be exacerbated by conceptual uncertainties about the classification of large and small vessel disease in determining the clinical course of diabetes. Physicians should not be falsely reassured by claims that a new treatment appears to have passed a narrowly-defined regulatory test. The management of diabetic patients often carries with it the risk of important cardiovascular consequences, even for drugs that do not overtly increase the risk of myocardial infarction or stroke.

    http://onlinelibrary.wiley.com/doi/10.1111/dom.13207/abstract


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    chris c
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    Re: Have We Really Demonstrated the Cardiovascular Safety of Antihyperglycemic Drugs?

    Post by chris c on Mon Jan 08 2018, 23:14

    Bugger, not on Sci-Hub yet Sad

    I recall research from yonks ago that showed while microvascular complications correlated to HbA1c, macrovascular complications correlated with postprandial glucose spikes.

    The elephant in the room is reducing glucose by jacking up insulin, as opposed to not eating the carbs in the first place and not spiking the insulin.

    Have some sugar, said the dietician.
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    Re: Have We Really Demonstrated the Cardiovascular Safety of Antihyperglycemic Drugs?

    Post by chris c on Sun Jan 28 2018, 23:27

    http://sci-hub.hk/10.1111/dom.13207

    haven't read it yet but I will.
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    graham64
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    Re: Have We Really Demonstrated the Cardiovascular Safety of Antihyperglycemic Drugs?

    Post by graham64 on Mon Jan 29 2018, 21:09

    @chris c wrote:http://sci-hub.hk/10.1111/dom.13207

    haven't read it yet but I will.

    Thanks Chris will add it to my reading list I've a lot to catch up on  Wink


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    Proving the LowCarb sceptics wrong for over ten years

    Not all cherubs are Angels  Wink nor all diabetics Bonkers  Rolling Eyes
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    chris c
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    Re: Have We Really Demonstrated the Cardiovascular Safety of Antihyperglycemic Drugs?

    Post by chris c on Wed Jan 31 2018, 22:43

    Another one warning against "tight control"

    http://bjgp.org/content/bjgp/67/655/85.full.pdf

    "Taking these limits into account, these
    trials enabled researchers to come to
    several conclusions on tight glycaemic
    control (HbA1c <7%)

    What has been shown
    • Tight glycaemic control does not reduce
    total or cardiovascular mortality.
    • It does not reduce the risk of stroke.
    • It does not reduce the risk of arteritis or
    amputation of the lower limbs.
    • It does not reduce, and may even
    increase, the risk of heart failure."

    Two obvious comments

    1) 7% is NOT tight control

    2) Almost certainly the effect is from drugs on a high carb diet and says nothing about the results of a low carb regime.

    While we're on the subject

    http://sci-hub.hk/10.2337/db17-0294

    Impact of Glycemic Variability on Chromatin Remodeling, Oxidative Stress and Endothelial
    Dysfunction in Type 2 Diabetic Patients with Target HbA1c levels

    another look at the differences between HbA1c and postprandial glucose spikes

    "Hence, glucose fluctuations
    contribute to chromatin remodelling, and may explain the persistent vascular dysfunction in T2D
    patients with target HbA1c levels.
    "

    now I have to find out what chromatin remodelling is . . .
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    Re: Have We Really Demonstrated the Cardiovascular Safety of Antihyperglycemic Drugs?

    Post by chris c on Sun Feb 11 2018, 22:15

    Resistance to Insulin-Mediated Glucose Disposal as a
    Predictor of Cardiovascular Disease
    JEANNIE YIP, FRANCESCO S. FACCHINI, AND GERALD M. REAVEN

    https://academic.oup.com/jcem/article/83/8/2773/2660508

    "In conclusion, approximately one of every five healthy, nonobese subjects in the most insulin-resistant tertile, followed for approximately 5 yr, had a serious clinical event. These data highlight the importance of insulin resistance as a predictor of CVD."

    Twenty years ago . . .

    Sponsored content

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