Failure of the Blood Glucose paradigm T2D 16

posted in: Diabetes, Health and Nutrition | 49

The current treatment paradigm of type 2 diabetes is the blood glucose paradigm. Under this paradigm, most of the toxicity of T2D is done by the hyperglycemia. Therefore, it follows that lowering blood glucose will amerliorate the complications even though we are not directly treating the T2D itself (high insulin resistance). The ACCORD study was a test of this glucotoxicity paradigm, and unfortunately, a complete and abject failure. Patients were randomized to tight blood glucose control versus usual control, with the expectation that tight control would show tremendous benefits. Instead, the trial proved there were none.

The mainstream media is picking up the fact that our current drug therapies for type 2 diabetes don’t seem to be of much use to anybody. The Canadian Broadcasting Company, for example, headlined that ‘New Study questions type 2 diabetes treatment – No evidence glucose lowering drugs help ward off complications”. Exactly right. Drugs don’t cure a dietary disease. Type 2 diabetes is a disease of insulin resistance and hyperinsulinemia. So why focus on lowering blood glucose, which is only the symptom? Isn’t that useless? Yes. Yes it is. You need to lower insulin, not glucose, because the disease is about too much insulin.

The problem is one of perspective. As long as you believe that hyperglycaemia is the main cause of morbidity, you expect that lowering blood glucose to provide benefits. The ACCORD proved this glucotoxicity paradigm is incorrect. Instead, the high blood glucose results from insulin resistance. That is the disease. And insulin resistance is due to hyperinsulinemia.

Imagine it this way. Type 2 diabetes is essentially a disease of too much glucose in your body. Not just the blood, but the entire body. If you fill up the cells of your body with glucose, pretty soon, no more can be pushed into the cells, so glucose spills over into the blood. But the underlying problem is an overflow problem. Insulin resistance is an overflow of glucose.

Using more insulin to move the toxic glucose from the blood into the cell accomplishes nothing. This is exactly what the study showed. If you have too much glucose in the body, you can do two things – don’t put any more in, or burn it off. Simply moving the glucose around the body so you can’t see it is not useful. And that’s what all these medications do.

Interestingly, the ACCORD study was not the first failure of the blood glucose paradigm. The UKDPS study was also unable to significantly reduce cardiovascular events or prevent deaths with intensive blood glucose lowering in type 2 diabetes. This was not even the first time that treatment increased death rates. The Veterans Affairs Diabetes Feasibility Trial also found an increase in death rates in the intensive group, but it was not statistically significant because of the small trial size. The earlier University Group Diabetes Program had also compared an intensive versus standard group. It, too was unable to find any benefit to intensive treatment. One certain subgroup, suing tolbutamide (a sulfonylurea medication that increases insulin) did have a higher death rate, though.

It would also start a parade of failures including the ADVANCE, VADT, ORIGIN, TECOS, ELIXA and SAVOR studies. It was not a single study that failed. There were multiple failures all over the world.

The failure should have burned away the prevailing glucotoxiciy paradigm like Enola Gay’s kiss. Certainly, at very high blood sugars there is harm to the body. But at the moderate levels of blood sugar seen in controlled type 2 diabetes, there was no benefit to further lowering. If you lower the blood glucose with medications such as insulin, there is no benefit. So clearly, the damage to the body does not result from glucotoxicity alone. The problem is that insulin itself in high doses can be toxic.erpeldinger1

All these trials used medications that don’t lower the insulin. Both insulin and sulphonylureas increase insulin levels. Metformin and DPP4 medications are neutral for insulin. TZDs like rosiglitazone do not increase insulin, but increase insulin action. If the problem is both insulin toxicity and glucotoxicity, then increasing insulin toxicity to reduce glucotoxicity is not a winning strategy. And all the studies were there to prove it.erpeldinger2

By 2016, a meta-analysis of all studies proved conclusively the futility of the blood glucose paradigm. Whether you are looking at overall deaths, heart attacks, or strokes, tight blood glucose lowering had no benefits at all.

However, these failures were not enough to convince diabetic associations to embrace new treatment paradigms. They were set in their ‘glucose or bust’ mindset and nothing could change their minds. So they refused to change their treatment strategies despite proof that these were complete failures. Their strategy of ‘prescribe medication to lower blood glucose’ had no been proven to have no significant health benefits. So, reflecting upon this new information, they decided that the correct strategy is ‘prescribe medication to lower blood glucose’. O…M….G…

For example, the Canadian Diabetes Association in 2013 guidelines still continues to recommend a target A1C of 7%. Why? Haven’t we just proven that lowering A1C from 8.5% to 7% provides no benefit? Why would we give more medications for no benefit. Isn’t that totally stupid? Yes… Yes it is. But there you go. The CDA can’t very well say “We have no clue what you should do”, so they give guidelines that go directly AGAINST the available evidence. Kind of like a Bizarro world Evidence Based Medicine.

Then they write “Glycemic targets should be individualized”. If there should not be a target, then say so, dammit. This is precisely what this paper describes. There is no evidence for benefit of tight glcemic control, yet 95% of diabetic guidelines recommend target blood glucose and tight control. WTF??

 

guidelines-not-evidence-based

This slide compares the effect of tight glucose control on the outcomes of most importance to clinical medicine – death, heart attacks, strokes and amputation. Virtually all studies show there is no benefit for any of these outcomes.

Statements published that recommend tight control have been slowly dropping since the ACCORD study. When study after study comes out to refute the hypothesis, you might suspect something is up. In 2006, most published statements still recommended tight control. By 2016, only 25% did. That is, the overwhelming majority of experts knew that tight blood glucose control was irrelevant. So, why do we still obsess over blood glucose numbers in T2D?

Unfortunately, it’s likely because diabetes specialists have not yet understood that this disease is about hyperinsulinemia, not hyperglycaemia. The drug companies, on the other hand, are all to happy to leave the status quo, which is extraordinarily profitable for them.

 

 

49 Responses

  1. Excellent Jason – very high glucose not good for body – but striving to lower some moderate levels with expensive drugs is stupid.

    Fix both Insulin the Elephant (and glucose issues) by addressing root cause – LCHF, fasting and all the other sensible approaches… 🙂

  2. When I was taking insulin back in 2009 my weight started increasing at an alarming rate. I stopped taking it in august 2009 and all other diabetes meds. I still went to regular check ups over the next four years and most things appeared fine. After four years with no meds I started getting nerve pain in my feet.
    It was now 2013 and Dr Moseley’s 5/2 book had come out I also discovered the Diet Doctor. With this combo my nerve pain went away and I still haven’t touched any diabetes meds.
    I’m not advising anybody to do this, just saying it worked out for me.

    • I’m going to go out on a limb and advise people to do it. Or at least study it and consider it. (:->)

  3. Kevin Mattson

    I remember reading about the antiseptic revolution, and the cultural resistance by established surgeons, and other medical folks, to the mere inconvenience of washing hands between patients. With billions of (name your currency) at stake, in addition to professional reputations, licensing, and god knows how many other issues, will any weight of scientific osmotic pressure shift the paradigm? Waiting for the retirement or death of the old guard of medical societies is one thing, but will greed ever pass?

  4. Dr. Fung, I’m lost in the continuity.

    This is T2D 16

    I have T2D 13 dated June 9 2016, “A New Paradigm of Insulin Resistance.”

    Since then, There have been other posts, but none that I can find with T2D 14 or T2D 15 reference.

    Links to T2D 14 and T2D 15 would be appreciated. Thanks

  5. So how can we measure insulin levels? What is the alternative to testing blood glucose numbers?

  6. Tight glucose control and A1c goals are not in themselves the problem. It’s the methods you use to achieve those that are the issue.

    I can’t measure insulin at home but I can use a glucometer to make sure that the food I’m putting in my mouth isn’t going to provoke an out of whack insulin response.

    • sten bjorsell

      Same here. And morning fasting glucose is very good to check and regulated with foods. Result: lots of fats, and vegetables, no processed foods and careful with proteins give good readings. When water fasting for 2-3 days blood glucose have been just over 3 for me and since energy then is way up over normal, the “hypoglycemia” is matched with ketones. After a while no measurements needed, but glucose meter is good to “tune in”.

    • Slight problem: protein causes an insulin response. An insulin response can be caused just by thinking about food (eg, right before eating it), by anything sweet such as gum (even if sweetened by non-nutritive sweeteners), etc. For me, I found intermittent fasting to be more beneficial than just eating low carb and eating many meals per day (as we’re told we have to eat). Even though I was eating low carb, eating too many meals caused an insulin response that was not beneficial for someone who was insulin resistant. At one time, I also tried to have “sweet” low carb recipes, and I’ve given up on those, too, because of the insulin response.

  7. Diagnosed prediabetic with hypothyroidism in January, I had gained 40 pounds in 2015. Started 16-18 hour daily fasting intervals 5-6 days a week in mid January but plateaued at 20 pounds lost in June. I discovered this blog a month ago, it took about a week to go through it all. Added a weekly 64 hour fast a few weeks ago and the pounds started dropping again and I feel great with more energy. Backed off to a 40 hour fast last week and it looks like that may be enough for now. If not I’ll look at adding a second 40 hour fast each week as this seems easier for me than the 64 hour fast. Thanks so much Dr. Fung!

  8. Jason, “One certain subgroup, suing tolbutamide” should read ” One certain subgroup, using tolbutamide”

  9. Jason, you might want to recheck this sentence: “Their strategy of ‘prescribe medication to lower blood glucose’ had no been proven to have no significant health benefits.”

  10. Jason, “The drug companies, on the other hand, are all to happy” should read “The drug companies, on the other hand, are all too happy”

  11. The best way to discover the truth concerning health and health care is to experience health building (holistic health, alternative healing, complementary medicine, taking responsibility for one’s own health, whatever people want to call it) for one’s self, as people here with Dr. Fung are experiencing left and right. The more that they do experience real health building, the more that they will learn to disrespect the conventional medical authorities.

  12. Let’s just stop eating sugar and flour and keep it simple to solve the problem. We do not need donuts to live!

  13. Dr Fung. I’ve always been curious about this. From your office to the Canadian Diabetes Association offices is what? Ten miles as the crow flies ?

    Has anyone from the CDA ever called you up and said “Gee, Jason. Looks like you are doing some great things out there in Scarborough. Could you come over and meet with us so we can learn to help patients too? What can we do to help you, Dr Fung?”

    Or is that a silly question?

    • I would guess that the majority of their funding comes from Pharma. The phrase “bite the hand that feeds you” comes to mind here.

      As Dr. Fung has said earlier, there’s a lot of money at stake here, right down to individuals’ salaries.

      Why change your tune when you can make lots of money by sticking to the story that every doctor was taught in medical school? Seems like a safe, profitable strategy.

    • More likely they are meeting with their lawyers trying to figure out ways to shut him up…as is being done in Australia and South Africa…

  14. So what’s the answer? All I see is a bunch of digital diarrhea.

  15. If hyperglycemia is the symptom of too much insulin is it right to conclude then that hyperglycemia is natural response (read a feature of human development not a flaw a la John Durrant) intended to save the body from storing additional sugar where there is no room? I’m not T2 so I don’t know what the dangers are of not addressing the hyperglycemia. Is there greater damage done to the patient by cramming sugar into the body rather than letting it course through their blood? Doesn’t the excess sugar eventually get expelled naturally in the urine?

    • Hi Nick,
      Whether it’s right or wrong I don’t know but those were my thoughts back in 2009. I also had some faith in the wisdom of the human body.

  16. “Enola Gay kiss” you paint word pictures that are funny and stay with me. Wish we could measure our insulin resistance like we can our blood glucose. I can get my insulin level every 3 months but that may not be more meaningful that a frog hair to tell me what my insulin resistance is.

    • All you need is fasting triglycerides and glucose to guesstimate insulin resistance fairly accurately.

      “A novel criterion for identifying metabolically obese but normal weight individuals using the product of triglycerides and glucose”

      SH Lee et al, 2015

      “The TyG index is a simple marker that correlates well with the degree of insulin resistance measured by hyperinsulinemic-euglycemic clamp studies.”

      TyG index Method:
      Multiply fasting TG and BG.
      Divide by 2
      Run Natural Log (ln) [NOT (log)]

      Men with values over 8.82 and women with values over 8.73 are most likely to be insulin resistant and have double the chance of developing type 2 diabetes in the future.

      Handy PDF with the formula from Dr. Georgia Ede:
      http://www.diagnosisdiet.com/wp-content/uploads/2015/08/insulin-resistance-tests.pdf

      • Thank you sharing this paper, I have been looking for an insulin proxy and this one looks great !

      • Thanks for sharing. I have been reading the published reports available on the development of this proxy for insulin resistance. It looks good to me.

  17. What does it mean to increase insulin action but not insulin?

    • Increasing insulin action actually means increasing your body’s sensitivity to it. Thus, the insulin’s activities are able to do more even though the dose of insulin has not been increased.

  18. Go Jason!! Your book should be out soon…pre-ordered it and looking forward to it.

  19. Measure fasting insulin?
    Why?
    Why not just use 3 of the Insulin lowering techniques?
    16 8 intermittent fasting everyday
    Low carb 30 grams or less
    And .6 grams of protein per kilo of weight.

    What else? Time!
    Eric

    • Is that an over simplification? I am still having a problem with LC vs VLC. Doesn’t this issue rightfully need to differentiate simple carbs from complex, well, for one thing. Next I don’t use MFP to watchdog my calories in so much as distribution of calories. By default, as I recall, MFP sets daily carb, unspecified, to 50% of the daily calories. I dropped it to 30%, with protein at 20% and fat at 50% It shows that carb percentage as 113g. From the nutrition/Nutrients page I seem to avg 65g/day which is roughly half of the 113. Interpreting what I am reading here my carb intake, irrespective of sugar/white flour or Kale, is grossly too high. From OC, Dr Fung makes the point, hopefully this is the point he made, that carbs with fiber is OK as the fiber acts as a mitigating factor (the whole ‘antidote’ argument). From my days on Atkins years ago, I’d call under 30g of carbs VLC. I didn’t get the sense from multiple readings of OC that Dr Fung was at all advocating for ketogenic diets. In fact, in the context of Atkins, he points out that diet ultimately fails as well as LCHF and HCLF. So now I am somewhat confused.

      • Hello Walt,

        A few weeks back I did an experiment where I had 150 grams of white sugar only daily for a fortnight. I got similar results you would get from fasting or going very low calorie, lost weight, lowered blood sugar, lowered blood pressure etc. You may draw the conclusion that types of carbs matter less and amounts matter more?
        This site focuses on keeping insulin low and the arguments for that are very reasonable but if you eat a lot of fat aren’t you just delaying the clearance of sugar from your blood? Could it not be more beneficial having faster clearance of sugar?
        Just wondering out loud.

        • Hi Jin,
          Here is the thrust of my issue with the focus by some on here for VLC. Getting to the heart of the matter, Dr Fung in OC, starting on pg 219 under “What to Eat”..

          1) Reduce your consumption of added sugars. (check!)
          2) Reduce your consumption of refined grains (check!) note: this would be sugar and flour, right? In this section “Carbohydrates should be enjoyed in their natural, whole, unprocessed form…”.
          3) Moderate your protein intake. (check!)
          4) Increase your consumption of natural fats. (check!) I read that to mean nuts as well as meat.
          5) Increase your consumption of protective factors (fibers and vinegar).

          So why the focus on something straight out of Atkin’s induction phase?

      • Dr. Fung believes the Atkins diet fails because people tend to regain some weight over time in tests of these types of diets. Unfortunately, the dieters increase their carb intake (e.g., to 130+ grams/day), which is no longer Atkins. Did the diet fail or the dieters?

        The Atkins diet never failed me. However, I was eating 5+ meals per day, each of which caused an insulin response. That’s when I started intermittent fasting to change the times when I eat food and protein. And that helped.

        Now, I’m combining a ketogenic diet (very low carb) with intermittent fasting. Overall, I’m down about 55 pounds from where I started: 20 using low carb; 30 using low carb + IF; 5 using low carb + IF + high fat + trying to remain in ketosis. I’ve only been trying to stay in ketosis for a short while.

  20. somebody help me…..every different MD, NP,PA….HAS DIFFERENT PLANS…none really work….my triglycerides have been ignored by all branches of medicine for 20 years. Minimum time on visits spent….Ignored Let next doctor deal with it….careful what you write down, scares 95% medical people. Take oral meds, insulin. Read about study at Birmingham Al. Had good response with cardiac med that releases another hormone from pancreas. Any updates on this or other studies? Really need someone to help me understand some of this on consistent basis. Not many people have time. Current doctor
    is new to practice, so far really great. Again time constraints. One time was 930pm when I left, others still in waiting room. Never felt hurried or ignored

  21. What about T1? They should have low insulin level unless they have perfect A1c? (which most don’t have) so their average insulin level should be lower than people in general or normal (except occasionally when they are low) unless they are T2 also, and still they have higher ‘overall deaths, heart attacks, or strokes’.
    So surely it is not as simple as you say, blood sugar does play a role.

    • Well, T1 diabetics have lots of insulin because they are taking it. That is the definition of type 1, they are “insulin dependent”. And by the time they are having their cardiac events they have been diabetic and on insulin for many years.

      • But why would a type 1 take more insulin than a none diabetic produces, the definition of Type 1 is ‘cant produce insulin’, so they need to inject, so they need to inject the same amount that a none diabetic produces naturally, nothing more, unless they are type 2 also.

  22. Nita Watkins

    I stopped lantis and metformin…..I’ve been very faithful to lchf diet for about 8 weeks…..my glucose numbers are still running 200+ ……I have a dr apt in 11 days…..how long does it take to lower the readings? (I was taking 4 ….500 metforminER and about 20 units of Lantus twice a day)

    • When eating LCHF you take in less glucose, now either your values goes down or you reduce your medication.
      If you are lucky you get to the state where you don’t need medication and have good glucose values, or if not you get to a better state (which you seams to have gotten to) where your insulin is reduced and you have same glucose.
      Now you can either increase insulin or metformin a bit (not as much as before) get both less mediciation and better values, or stay as you are. Hopefully the reduced insulin will make you loose weight, which hopefully will reduce your insulin need which hopefully will make you glucose values better. But this will take time, depending on how much weight you can loose.

  23. Nita Watkins

    I haven’t gotten any replies…maybe I didn’t do it right?

  24. I’ve been on a LCHF diet for 3 years. intermittently fast on occasion and take 1000 mg of metformin a day. I’m trying to lower my BG levels, hence A1c. I realize the insulin level is the problem, not the BG. My reason is trying to increase my overall health, recover from coronary artery disease, reduce T2 pre-diabetes, maintain a healthy weight and keep energy levels high. I feel what I’m doing is working. My A1c is now 5.5, male 6’0″, 162 lbs, 67 yo, feeling good. Am I incorrectly assuming eating LC all the time, getting a lot of exercise, intermittently fasting will lower my insulin levels?

    • Insulin levels are driven primarily by carbohydrates. Fasting drops blood sugar levels quite efficiently but you must work closely with your doctor to adjust your prescription(s).

      Exercise will decrease glycogen somewhat but it’s best use is for retaining muscle mass during weight loss. To understand why this is consider a carb-dependent marathon runner who “hits the wall” around mile 20. The roughly 100 calorie burn it takes to run one mile multiplied by 20 miles is 2,000 calories which happens to be the total average amount of muscle glycogen contained in the body. A carb-dependent runner has effectively “run out of gas” at that point so down they go.

      Now consider that a piece of dry white toast contains around 100 calories. You could choose to eat it and run that mile taking 10-20 minutes to do so, or you can take zero minutes to skip the toast, avoid the resulting insulin hit, and spend the next 10-20 minutes doing something else.

  25. I get your theory but I’m confused.
    ACCORD is a travesty of an example of tight glucose control since it used poly pharmacy to do so and didn’t address dietary or lifestyle.

    Secondly
    ACCORD’s figures and tables prove their reasoning wrong.
    More ANY cause deaths occurred in the higher a1c group than the lower, while more heart deaths occurred in the lower-could not have been a ‘byproduct’ of the method and medications used?

    Thirdly
    The Hisayama Heart Study in Japan strongly correlated heart incidence to a1c and found that as one’s a1c fell so did heart incidence.

    Fourth
    The process of complications is it not pretty much explained by the pylol pathway?

    Fifth
    Boil it down
    Heart attacks are linked to inflammation for the most part AND insulin is very inflammatory- no argument there-but then why did Hisayama find that heart incidence fell as a1c lowered?

    Last
    Dr Fung
    I respect you but please answered my last two points here.

    How can you call a diabetic ‘essentially cured’
    with a rising a1c you did in one of your videos.
    If the a1c is rising are glucose and insulin levels according your theory. Glucose levels are well established at causing damage and complications at very slight elevations above non diabetic normal, the low to mid 5 range and the patient you pronounced ‘essentially cured’ was well above 6.0 and almost to 7.

    Why take the fringe theory when Dr Bernstein’s methods of low carb, proper medication dosage, proper supplementation and exercise have proven to be so effective at restoring normal glucose levels, preventing future and reversing existing complications?

    I do not believe that either Glucose or insulin alone are the sole cause of complications but I do think the evidence for Glucose being the major culprit exists.

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