How NOT to treat diabetes – T2D 38

posted in: Diabetes, Health and Nutrition | 35

By the mid 1990s, the landmark DCCT trial has established the paradigm of glucotoxicity, in type 1 but not in type 2 diabetes. Still euphoric from the trial’s success, it seemed only a matter of time before tight blood glucose control was proven beneficial in type 2 diabetes as well.

Nobody stopped to consider exactly how giving insulin to hyperinsulinemic patients was going to help. Nobody paused to consider that insulin toxicity might outweigh glucotoxicity. So, borrowing heavily from the type 1 diabetes playbook, the use of insulin is increasingly used for type 2 diabetes as well.

Over the last decade, the number of patients using insulin rose 50% as almost 1/3 of diabetic patients in the United States use some form of insulin overall. This is slightly horrifying, considering that 90-95% of diabetes in the United States is T2D, where the use of insulin is highly questionable.

In particular, the priority was to reduce cardiovascular disease. While type 2 diabetes is associated with numerous complications including nerve, kidney and eye damage, the morbidity and mortality associated with cardiovascular diseases dwarfed those by an order of magnitude. Simply put, most diabetic patients died of cardiovascular disease.

The United Kingdom Prospective Diabetes study, known as the UKPDS, was going to be the study that would prove the benefits of intensive blood glucose control. Almost 4000 newly diagnosed type 2 diabetic patients were randomly assigned to two groups. One would follow conventional treatments and targets and the other group would receive intensive group with sulfonlyureas, metformin or insulin.

Sulphonylureas (SUs), have been in widespread use for the treatment of type 2 diabetes since 1946. They lower blood glucose by stimulating the body’s own production of insulin from the pancreas. Since type 1 diabetics have lost their ability to produce insulin, these medications are not appropriate.

The other widely used medication is metformin. Its use in the United States was temporarily halted due to concerns of side effects, but has been used extensively in Europe and Canada for fifty years. Metformin does not stimulating insulin, but instead blocks gluconeogenesis. This lowers the risk of hypoglycemia and weight gain because it does not increase insulin.

In the UKPDS study, the intensive treatment group targeted a fasting glucose of less than 6.0 mmol/L and successfully lowered the average A1C from 7.9% to 7.0%. But there was a price to be paid. Higher dosages of medication resulted in more weight gain, by an average of 2.9 kg (6.4 pounds). In particular, the insulin group gained the most weight, averaging 4 kg (8.8 pounds). Hypoglycemic reactions significantly increased, too. These side effects were expected, though. The question was whether the benefits would justify the side effects.

What benefits?

Published in 1998 the results were absolutely stunning. Intensive treatment produced almost no benefits. Expecting a slam-dunk like the DCCT trial, there was instead only some minor benefit in reducing eye disease. Glucotoxicity was the prevailing paradigm of treatment. But despite ten years of tight blood glucose control, there were no cardiovascular benefits. The discrepancy was shocking, but the story would get stranger still.

Metformin was considered separately from insulin and SUs in sub study UKDPS 34. Overweight type 2 diabetic patients were randomly assigned to either metformin or diet control. Metformin lowered the A1C from 8.0% to 7.4%. This was good, but not as good as the results with the more powerful insulin and SU medications.

Metformin reduced diabetes-related death by a jaw-dropping 42% decrease and the risk of heart attack by a whopping 39%. Metformin performed far superior to the insulin/ SU group despite the weaker blood glucose effect. Something was protecting the organs, but it had nothing to do with the blood glucose lowering effect. The specific type of diabetic medication used made a huge difference. Metformin could save lives, where SUs and insulin could not.

The glucotoxicity paradigm, proven in type 1 diabetes, had just failed miserably in type 2. Blood glucose was not the only player or even a major one. The most obvious concern was the well-known propensity of both SU and insulin to cause weight gain in patients that were already obese, which could lead to cardiovascular problems down the line. Metformin, which does not raise insulin, does not cause obesity and this certainly could have been the crucial difference.

Published peer-reviewed commentary from 1999 reveals that concern was percolating about the real issue, exacerbating hyperinsulinemia in a patient with too much insulin already. Dr. Donnelly from the University of Nottinghmam, UK writes, “The findings could also be interpreted as indicating that insulin and sulphonylureas are equally harmful in the obese, possibly as a consequence of hyperinsulinaemia”.

This is not so difficult to understand. Intuitively, everybody understood that type 2 diabetes was closely linked to obesity. Drugs that would worsen the obesity are likely to worsen the diabetes, no matter what happens to the blood glucose.

Extended follow up of the original UKPDS study allowed detection of some cardiovascular benefits but relatively mild and much smaller than expected. Death rate was reduced by 13% in the insulin/SU group compared to a far more substantial 36% in the metformin group.

The paradigm of glucotoxicity was established for type 2 diabetes, but only barely. Blood glucose lowering medications had marginal benefits that required twenty years of follow up to become apparent. Unanswered questions remained about the differences between types of medications, particularly between those that raised insulin versus those that did not.

The rise and fall of the thiazolidinediones

As the obesity epidemic gained strength, type 2 diabetes relentlessly followed. For the large pharmaceutical companies, this meant only one thing – more potential customers and more potential profit. For many decades, the only available medications for type 2 diabetes were metformin, SUs and insulin. By the early 1990s, it had been eighty years since the development of insulin and fifty years since the introduction of the SUs. Metformin had been first used in the 1930s. Resources poured into the development of new classes of drugs.

By 1999, the first of these new drugs was ready for the primetime. Rosiglitazone and pioglitazone belonged to a class of drugs called thiazolidinediones (TZDs), which bound to the PPAR receptor in the adipocyte to amplify insulin’s effect. These drugs did not raise insulin levels but instead magnified insulin’s effects, both good and bad. This lowered blood glucose, but the also had other predictable adverse effects.

The biggest problem was the weight gain. Over the first six months, patients could reliably expect to gain three to four kg (6.6 – 8.8 pounds) of fat. Insulin encourages salt and water retention, leading to predictable side effects. Fluid retention typically manifested as swollen ankles, but sometimes progressed to frank heart failure – fluid accumulation in the lungs causing shortness of breath. Nevertheless, these were known effects and the benefits were felt to outweigh the risks.

The TZDs were released in 1999, and backed by multi million dollar promotion budgets, quickly became best sellers. They were the Harry Potter of the diabetes world. With almost unprecedented acceptance in the diabetes community, sales zoomed from zero to $2.6 billion in 2006.

The wheels started to fly off in 2007 with the publication of a meta-analysis in the influential New England Journal of Medicine. Unexpectedly, rosiglitazone increased the risk of heart attacks. The Federal Drug Administration (FDA) in the United States convened an advisory board in 2007 and similar deliberations were held in Europe. Twenty-four independent experts reviewed the available data and concluded that rosiglitazone indeed increased the risk.

There were also significant concerns about data tampering in the RECORD study, one of the largest trials that had ‘proved’ its safety. Subsequent FDA investigation proved that this concern was well placed. Rosiglitazone use was associated with a 25% higher risk of heart attack. Pioglitazone had its own troubles after being associated with a higher risk of bladder cancer.

By 2011, Europe, the UK, India, New Zealand and South Africa had all banned the use of rosiglitazone, although the FDA continued to allow its sales in the United States. However, the glow had faded. Sales shriveled. In 2012, sales had fallen to a paltry $9.5 million.

The debacle left some beneficial policy changes in its wake. All diabetes medications henceforth were required to conduct large-scale safety trials to safeguard the public interest. Dr. Clifford Rosen, the chairperson of that FDA committee identified the key problem. New diabetic drugs were approved based solely on their ability to lower blood glucose, under the unproven assumption that this would reduce cardiovascular burden. However, evidence to date, including the UKPDS and the smaller University Group Diabetes Program had failed to confirm these theorized benefits.

The Cochrane group, a well-respected independent group of physicians and researchers, estimated that glucose control was only responsible for a miniscule 5-15% of the risk of cardiovascular disease. Glucotoxicity was not the major player. It was barely even in the game. What followed, unfortunately confirmed Dr. Rosen’s misgivings.

35 Responses

  1. David Proffitt

    One typo…
    Published in 1998 the results were absolutely stunning. Intensive treatment produced almost benefits.

  2. Thank you for the great information. What is the title of Cochrane review (5-15%), I am trying to find it?

  3. Charlene

    What an eye opener. Thank you Dr Fung.

  4. According to Dr. Kraft’s extensive research, by the time t2 diabetes is diagnosed, the insulin resistance is so high and thus also the insulin response. Meaning there is a LOT of insulin in the system and it stays around for a long time. So Dr. Fung I’m trying to understand why you believe the exogenous insulin –which probably is a fraction of what the body is already producing — makes such a dramatic health, weight, etc difference. Thanks for explaining.

    • Hi Nomi,
      The body does not really produce much insulin; even in hyperinsulinemic states, the pancreas only produces a tiny amount and sends it directly to the liver.
      The insulin shot goes under the skin, which turns the body into an insulin pump. In order to have enough insulin hitting the liver, what is injected is a mega dose, compared to the insulin that the body produces.

  5. Christina Walsh

    I love how you bring to us information that you have researched and in such a way that it is easy for us to digest. It is so brilliant and refreshing to have someone “tell it like it is”. thank you so much Jason 🙂

  6. The final statement: “The Cochrane group, a well-respected independent group of physicians and researchers, estimated that glucose control was only responsible for a miniscule 5-15% of the risk of cardiovascular disease. ” Raises the question what is causing the 90%.
    What I found is that defective production of the most common of proteins, collagens, because of defective usage of Vitamin C is driving the pathology. A collection of research on this has been pasted at
    Evidence supports the taking of 1 gram or more of Vitamin C. I take 1. grams daily in the form of calcium ascorbate powder, and I am not diabetic or insulin resistant.

    • Noah Pennington

      Hi Jerome, thanks for sharing the link. I read through the material on the link between insufficient ascorbate acid and diabetes. Did you start taking the 1g supplement because you were pre-diabetic? What brand of supplement do you recommend and how long have you been using it?

      I am pre-diabetic and have been on low carb diet for two years, but I think I need to do more because my HA1C levels are in he low to mid 7’s.

  7. sten bjorsell

    Nomi, I am not so sure that exogenous insulin stays “a fraction of what the body is already producing “.
    Individuals with type 1 diabetes receive all their insulin from outside, and now often go on to become type 2, while type 2 sometimes end up producing no insulin, both examples depending 100% on exogenous insulin.
    As I see it, due to being too liberal too often with blood sugar increasing foods in the very first place that is driving insulin higher, faster than anything else.
    As Jason probably has pointed out already, changing to lesser carbs is not even on the pharmaceutical companies radar screen, as it would reduce potential demand for their products.
    This “follow the money insight” combined with bought off experts, often professors, and politicians are the reasons for that we have to find out all these things by ourselves and often fight doctors that haven’t realised where the stakes are. Thanks to JDr Jason Fing, and now many other honest like-minded doctors, it is possible at all!

    Type 2 diabetes is a disease of excessive insulin, or really a disease of progressively increasing insulin, that progressively reduces insulin sensitivity, because of too much insulin . All foods that add to insulin production must then be restricted, which very soon results in no need for exogenous insulin, proved by many examples. Combined with intermittent fasting fatty liver and pancreas is soon cleaned out and the elevated morning sugar starts to fall down into the normal region, without metformin or extra insulin before bedtime. But it is only savings in it for us, often life-saving.

    • Sten, following the comment from Naomi, do you have a sense of how long it takes to recover insulin sensitivity? I think this is key to understanding the seemingly contradictions in comparing humans to coal fired electric plants (Obesity Code) or a person who had to take a lesser paying job (Megan). I understand the two compartment model and insulin resistance blocking the body from metabolizing fat but, at some point, perhaps when or shortly after blood ketones show, the body accepts metabolizing fat (unlocking the freezer). Case in point, I’ve got very high (40mg/dl-80 mg/dl) ketone levels, acetone (20-50ppm) but still get cold feet. If cold feet is body throttling back then what explains the ketone levels (byproduct of fat metabolism)?

    • Noah Pennington

      Hi Sten, thanks for sharing. You mention fasting to help clean out the fatty liver and pancreas… What kind of fasting Do you recommend?

  8. Sean Raymond

    The cause of hyperglycaemia is the wrong way around – it is not so much exogenous (dietary) glucose which raises blood glucose but the endogenous component which is far more important. See, Insulins main function is NOT to get glucose into the cells as we are told – the body has plenty of non Insulin dependent GLUT transporters to do that job – but rather, it is to shut down Hepatic glucose production via Gluconeogenesis and glycogenolysis. As Dr Fung mentions, this is why Metformin is effective – it reduces hepatic glucose output! Studies show that in insulin resistant states, glucose uptake is normal, in fact – it is actually higher in hyperglycaemia however endogenous glucose production outstrips the bodies ability to dispose of the rising circulating glucose. Quite how skeletal muscle can take in glucose when its main glucose transporter, insulin dependent GLUT 4, does not translocate to the cell surface is still a mystery to me. But it does – we know this occurs because in insulin resistant people, when they exercise glucose uptake into muscle increases despite no insulin and the insulin resistant state!

    I appreciate Dr Fung sharing his views as well as all the work he is putting into this, however I personally think he is incorrect regarding Insulins fattening effects- it simply does not cause adiposity in the presence of a calorie deficit. If this were true, consider this. Insulin resistant states means the body cannot respond to Insulin – therefore lipolysis is not shut down. Those who take Metformin lower sugar by reducing hepatic glucose production and NOT by increasing or sensitising the individual to the effects of Insulin. And so despite all that lipolysis we see no weight loss occurring (unless that person is specifically trying to). How can that be when we have someone not responding to insulin? Because Insulin is not the cause of obesity. Many metabolic ward studies now exist which have shown that reduced insulin levels does NOT cause weight loss. As I say repeatedly – lipolysis does not = lipid oxidation.

    • Sean Raymond

      I should add – I was referring to hyperglycemia in diabetics. Oh – some studies exist suggesting that Metformin can aid weight loss due to suppression of hunger. This is not reported in everyone. However, the point being made is it not due to Insulin or an enhanced state of lipolysis which they are certainly in as the insulin theory of obesity would have us believe.

    • [quote] it is not so much exogenous (dietary) glucose which raises blood glucose but the endogenous component which is far more important” [/quote]

      Then how would you explain the unmedicated insulin resistant T2 diabetic/pre diabetic who goes on a LC or IF diet and reduces his morning glucose from 126 to 86 and his A1C to under 6?

      • Sean Raymond

        Lori – low CHO or intermittent fasting approaches to diet help the body cope with the condition rather than fix it – i.e. less sugar into the system helps reduce the load. Reversal and or increased insulin sensitivity occurs with loss of adipose tissue, most importantly visceral fat.

        There are many questions I have regarding Diabetes, its pathogenesis and much more. Insulin resistance itself is deeply confusing, at times paradoxical and its cause open to a few theories

        I have no doubt some people improve their glucose profile on low CHO – by its definition it should be less burdensome whilst low CHO does tend to evoke weight loss due to reduced caloric intake – so this will help. There are always one off examples and people who just metabolically cope well/sometimes spectacularly to a given diet than another person. I have seen little improvement in fasting glucose with many diabetics who adopt low CHO and others who do better. Indeed, many studies exist showing very little improvement to glycaemic medication reduction when low CHO/Low calorie diets are compared. I was always disappointed when I looked at these studies as I expected better results – the idea that it is endogenous rather than exogenous glucose causing the glycaemia ties in with this.

        I am not here to bash low CHO (although I don’t hold to the insulin theory of obesity)- it is a useful option however I just saw a study where a group of T2DM patients stopped the need for insulin on a 80-90% diet of carbohydrate (sources were pulses, wholegrains etc). The diet relied on some alleged change of gut flora as it was vegan microbiotic sort of type, impractical for many – but the point was they took in a lot of CHO but still has improved glucose tolerance.

      • Sean Raymond

        Lori -, as an aside – as I mentioned in a previous post – it is very important to understand that lipolysis does NOT = lipid oxidation. Even if insulin is low, and lipolysis is activated as in the fasted state the fuel mix is NOT 100% fatty acids liberated from the fat stores whilst the body will only burn what it needs to. Numerous metabolic ward studies have now shown that reducing insulin does not = enhanced fat loss despite the anticipated increase in lipolysis. I repeat – the body will only burn what it needs to.

        In Dr Fung’s fed/fasted thread from a few weeks ago he builds an argument which says that the body can only burn either stored energy in the fasted state or dietary energy in the fed state but then seems to contradict this by saying when a person reduces their calorie intake from 2000 to 1500kcals (consumed in 6 small meals) they lose weight and the only reason this stops is due to set point theory where the body acts against the weight loss to prevent more by ramping down our BMR.

        How would weight loss achieved if that person ate 6 meals – presumably insulin levels would have been high and a fed state kept constant throughout the day? That does not appear to tally with the Insulin obesity theory.

        Dr Fung is doing interesting work, I am on his side in that I want to help people -but I simply do not think insulin is not the issue the way he and Taubes etc say. I also disagree with Dr Fung’s/Lustig et al ideas on Fructose also. There is much I do agree with him on however!

    • Thanks for that Sean. It makes sense from the perspective if the insulin’s role was to open the cells to accept glucose and, in the diabetic or someone with insulin resistance, that was not happening, the cell would die, would it not? If heart or brain cells started to die, that would have a pretty dire consequence to the body, would it not?

      • Sean Raymond

        Walt – cell death can happen for a number of reasons, such as low ATP levels, hypoxia for example. Not seen any studies showing cell death in diabetics due to inadequate glucose uptake – but diabetes is not an area I am a specialist in – perhaps there is literature addressing that? I think it is unlikely as non insulin dependent glucose uptake appears to be sufficient to take in glucose in diabetes as previously mentioned via non insulin sensitive GLUT transporters. The brain does not require insulin to take in glucose.

        I personally would like to see more studies confirming the up-regulation of non insulin dependent glucose uptake in hyperglycaemia to show it is not failure of our response to insulins glucose sensitising function which is key in hyperglycaemia. Insulin does promote glucose uptake, but it seems this is less important in raised blood sugars than its job in switching off gluconeogenesis and glycogenolysis when we eat. Because the lock and key idea to explain insulin function is such established dogma (it was I was taught to teach) I do not see those studies being done. But enough exist to provide evidence of what I have said (it is not my idea by the way).

    • Hi Sean in trying to make sense of all this I think I’m more aligned to your way of thinking…but gee the topic of diabetes is a tough gig…the more one reads the more it seems to do one’s head in. There are so many studies around that purport to show one thing or another in relation to blood sugar control/insulin resistance etc. I think I am sympathetic to insulin being a brake on Glucagon’s action (rather than being primarily a fat storage hormone). Insulin acts on enzymes to inhibit gluconeogenesis and glycogenolysis whereas glucagon stimulates these two pathways. That glucagon is the primary hormone in blood sugar regulation kind of makes sense considering that hypoglycaemia offers potentially life threatening and immediate health problems whereas hyperglycemia is more of a danger over time. As such, the body goes to great lengths to ensure that blood sugar is kept above around (I think) 3mmol/L. High fasting blood glucose must be a result of uncontrolled hepatic glucose production. I personally feel that carbs are being overly vilified, just as saturated fat and cholesterol were in the 70s, 80s and….well they still are. Carbs per se don’t make you any fatter than any other macronutrient BUT, they are very easy to overconsume, particularly those sugar laden beverages. If one over-consumes fat it is stored in the adipose tissue. When carbs are eaten, those that aren’t used for immediate cellular energy needs are first converted to glycogen in the muscle and liver. De novo lipogenesis will only occur once glycogen stores are full.

    • I remember from reading Petro Dobromylskyj’s block that insulin’s most important job is to lock fat in fat cells so body must use excess (toxic) glucose first. If insulin is high all the time, you can’t loose weight from fat cells.

      I believe that resistance to accept insulin’s share to obesity comes to fact that then you must admit that refined carbs like sugar and flour are the reason for obesity and then whole agriculture industry must be changed. Too many has too much to loose.

      • Sean Raymond

        JR62 – Insulins most important job is certainly NOT to lock fat into cells – that way of thinking is used to frame insulin as the cause of fatness when this is just not the case. Insulin dose not stop you losing weight, glucose is not toxic and refined carbohydrates’ are not the cause of the obesity crisis. Overconsumption of such foods is closer to the answer than blaming isolated foods or macronutrient’s.

        • Thanks for your input. I’ve been on very low carbs for two years but something very odd started happening.

          My periods reduced from 30 days to 20 days. The blood was brown and not red and would continue on for 41 days. I became anaemic from loss of blood

          After lots of prodding and a threat of a hysterectomy, my Dr found the culprit. My body was stressed stealing progesterone from my endocrine system.

          So I reintroduced unrefined carbs. (Except white rice because of the arsenic in brown rice) back into my diet and started getting sleep again, tension, depressive.thoughts and anxiety disappeared, happy neurotransmitters returned. I didn’t realize low carbs could create so much stress on a body.

          I am now eating small portions of carbs with my two meals per day. Still fasting 16 hrs. My sugar has dropped because my body is no l
          onger stressed

          Muscles are bigger with less protein.

          Cortisol is one of the biggest causes of excess glucose! Moderate carbs is our saviour not our enemy but I wouldn’t have listened to anyone back then.

  9. sten bjorsell

    Lori, I agree totally.
    I was even only pre-diabetic and it worked wonders for me. The high morning blood sugar went completely for me when followed up with Intermittent Fasting, IF.

    • Sean Raymond

      I am glad you have had success with IF – these diets may work in a number of ways to help improve blood sugars although actual studies into them have not been conclusive. I am personally interested in the metabolic benefits of IF independent of weight loss.

      If the style of IF implemented was timed feeding, i.e. eating within a given time frame during the day – this may benefit our chrono-biology where we eat at times more in line with our circadian rhythm so that we eat when our metabolism is most efficient. IF may improve ectopic fat reduction due to the nature of extended fasts (not proved as yet) whilst IF appears to cause an overall calorie reduction. 5:2 diets or alternate day fasts do not seem to cause compensatory eating on the feed days. Weight loss is good for blood sugar control.

      In any case, well done.

  10. I just wonder why jason fung never answers these questions

    • Nomi,

      He probably would love to answer these questions but he’s a busy guy and can only carve out enough time to get the post put up. I’ve noticed that he sometimes does reply though. I think it’s just a matter of him having enough time.

    • Nomi, yes, I am sure he is busy but, more importantly, he legally can not give out what could be construed as medical advice to ‘patients’ he isn’t treating. I have not seen him reply in years, and even back then only rarely.

  11. Hi Dr. Fung,

    I wonder if you’ve had a chance to see the new documentary out on Netflix called What the Health – it claims that meat is the main driver of diabetes…I’d love to hear your opinion on this documentary when you have a chance. I’ve heard a lot of my friends talking about it, and I think it’s total misinformation!

    • I’d love to hear what he has to say too. I’ve seen that documentary and as everyone knows you can get pretty much any study to highlight your agenda with the right word judo but I find it amazing that there are so many professionals that counter the LCHF and IF plan. I’ve personally lost 30 lbs and got my doc to take me off of Losartan for hyper tension by following this plan, so I know it works. A buddy of mine has lost 70 lbs following this plan.

  12. I’m sitting here in the hospital visiting my father who is in for breathing related issues and has been prescribed metformin. (He uses this med as a crutch to eat carbs and sugar). Since the stay, he had a CT scan that uses a contrast dye that clashes with metformin. What is he prescribed instead? Yes, insulin. The nurse just came in and tested his blood glucose, it was 261!!!. His average is 95-115. (On metformin) Then right after, they gave him a snack of strawberry ice cream!!! Wtf?!? He had a fruit cup for lunch??!! And a peach medley??!! Wtf?!!?
    I’m sure stress from being in the hospital can cause a rise in the blood glucose, but I don’t understand why they’re feeding him sugar!?

    • They want to get him on insulin so they can feel done good and important job. Advice someone to change diet is not like doing “important” job as patient himself has that essential part to do.

  13. Hi Jason,

    Need your advice on the effectiveness of IF/Fasting on chronic kidney disease?
    My dad has a substantial proteinuria – attributed to hypertension and possibly pre-diabetes.
    Right now he’s under several medications, not sure if this condition is reversible.

  14. HI I need Help I am trying to quit taking Insulin I use very little CARBS Although I am losing Inches I am not losing Kg
    My bedtime Blood Glucose in around 7 and my Am Blood sugars are 9
    Some say it’s the Dawn Phenomenon
    I am Elderly and Very Obese I blame a lot of my weight on Lantus Insulin 130 Mg Nightly
    I have not taken Lantus for 4 days now I have used Humalog 6mg for Blood Sugars over 8.5 But I see no Lowering
    I find Dr. Fung’s writing is a bit over my head I really do not understand his valuable Blogs
    Can any of you followers share how to 1) stop the Insulin 2) continue to Lose the weight
    Thank You
    Regards AL

  15. If we want to look at the pathogenesis of hyperglycemia, which is what we call diabetes although it’s just one manifest symptom of it, we need to look at the whole picture, what causes it, what worsens it. So we know that this is caused primarily by hormonal imbalances, primarily an imbalance of hormones secreted by the islet cells of the pancreas, which are insulin, amylin, and glucagon.

    Guess what though? Type 2 diabetes presents itself with an excess of all 3 of these. In addition, incretin hormones also rise, as does adrenal hormones, cortisol most notably.

    So these hormones are all in excess with T2DM, and we know how these excesses cause and worsen the disease. Too much insulin leads to too much glucotoxicity and lipotoxicity, it’s the lipotoxicity that does us in the most actually, most notably by poisoning our alpha cells in our pancreas, the ones that secrete the hormone glucagon, and glucagon is the hormone behind our high blood sugar, period.

    So now you have insulin and glucagon too high once enough damage is done to see diabetic hyperglycemia, and these other hormones end up elevated as well along the way.

    So what do we do to treat this? Well we primarily elevate insulin even further, which is of course real bad news and like Dr. Fung describes it, this is like giving alcohol to treat alcoholism.

    So when we do that, the damage from the insulin increases, and glucagon goes up further. Insulin is also inflammatory and this causes cortisol to go up as well, and cortisol does reduce inflammation but it’s main function is actually to raise glucose levels, so this is a bad idea.

    Amylin gets secreted in excess with type 2’s, as do the incretin hormones, so looking to return all these hormones to normal levels is a great idea and necessary even if we ever expect to get better. What do they do though? They give us amylin to inject, and they have both injections and orals to elevate incretins.

    Like using insulin, you can see temporary reductions in blood sugar with all this stuff, but when you worsen our hormonal resistance to all these hormones, and that’s what we do, you’re just going to get worse and worse and require more and more medication. What a concept though if you make money selling this stuff though!

    So when I see things like insulin reduces glucotocity, on the contrary, high insulin is the cause of glucotoxicity, and someone can eat the worst diet out there, loads of carbs and sugar, and not have high blood sugar at all, provided that they don’t get poisoned by too much insulin for too long, it is only then when glucotoxicity starts rearing its ugly head, along with the rest of the metabolic disorders this produces.

  16. Liz Grimes

    My question is: Once someone has their diabetes under control with low carb/high fat diet and intermittent fasting, they have no signs of kidney damage, eye damage, but do have neuropathy that they can tell is improving, do they need to continue taking a preventive drug (losartan) to prevent kidney or eye damage ? Doctor wants to continue the drugs to prevent diabetic damage to kidneys and eyes yet for over a year a1c has been 5.5. Once controlled like this, will organ damage occur anyway?

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