John, were these patients put on insulin pumps with rapid-acting insulin infusions or were they given SC insulin injections at strategic times during their rehabilitation? I’m unclear on the trial protocol. The description sounds as though they were given insulin at timed intervals regardless of their blood glucose readings, which, to my thinking, is a formula for disaster. Surely the goal was to control the blood sugar levels and not just give insulin Willy-nilly?
It is my pleasure to inform you that finally the book written by Cambridge Graduated, Post Doctorate in immune-genetics, Doctorate in Epidemiology and 14 years professor of Virology Karina Acevedo Whitehouse has been translated into English. Since day 0, she has been one of the voices able to speak with plain knowledge, understanding and sympathy for the injured ones. It is so comprehensive and educative for any medical professional and also for average people since it is so well developed that can be understood by people with no biological education. Presentations of this book are taking place in Spain, Costa Rica, México, and she has worked with the WCH, Ryan Cole, Oyewale Tomori, J. Rose and others. This one does deserve to be read and shown to the decision makers in all the world and to the misled ones too. Please, take a look at it, it is worthy in every possible way.
This rang a bell somewhere in the recesses of my memory - in the hospitals where I worked as a junior doctor in early noughties they actually employed a full time DIGAMI diabetes specialist nurse to make sure we didn't overlook this important part of MI management. They even devised revised guidelines to address some of the risks of hypoglycaemia (https://diabetesonthenet.com/wp-content/uploads/jdn7-5-185-90-1.pdf). I'd completely forgotten about it and when I did my GP training a few years later it was no longer a thing.
I can think of a fair few examples over the years where it would have paid not to jump in with both feet to adopt new guidelines or novel treatments.
It again begs the question of what the journal editors were doing. The authors can submit whatever they want. But you’d like to think the editors would have some pride in what they print under their banner. Or perhaps they enjoy readers questioning what they’re smoking.
My initial reaction: How could anyone with even the most rudimentary understanding of physiology possibly believe that giving a drug to lower serum glucose levels during a period of maximal stress is a good idea? This would seem to be taking the unjustified demonization of carbohydrates to new levels of idiocy. It is probably true that there is no big pharma money bankrolling this study. But it does remind us that there is another significant force driving a lot of useless research. Career advancement is a huge motive for those in the academic research field. More publications lead to more success in bringing in the big grant money and climbing the academic ladder of success.
..."about the failure of good ideas and aggressive therapies as well as the strong draw to spin results"...without that marketing scheme, big pharma would go broke. It is these "new" drug therapies, most often no better than the old drug therapies, that spins the wheel of fortune for big pharma as these new products always carry exorbitant prices.
Following DIGAM1 results, there was no change in the management of AMI. IV Insulin was rarely used in ICUs. Of course, DIGAMI2 confirms the futility of IV Insulin during AMI. I appreciate if you could critically analyze the trials conducted with expensive molecules (with overwhelming involvement of sponsors of the trials) like PCSK9i, etc.
This whole discussion is based on the assumption that diabetics' increased cardiac risk is due to high blood glucose, when more recent evidence points to high insulin as the real culprit. Think about it. All the supposed risk factors - obesity, fatty liver, diabetes, high triglycerides, low HDL - are in fact caused by high insulin. So it's likely that the correlation between all these supposed risk factors and heart disease is just that - correlation, not causation. The real culprit behind all of them is likely high insulin. But while there are drugs to lower blood lipids, blood glucose, and obesity, pharma has no drug to sell to lower insulin. As a result, medicine will no doubt continue its blindness to the insulin/metabolic syndrome problem.
Great article! Thank you. I am a primary care internist. The only acute MI treatment I do is to give aspirin while we wait for 911 to arrive. On the other hand, I take care of these folks a decade or two after they've had their MIs and their sugars controlled or not in the ICU. I have long suspected that we underestimate the damage that hypoglycemia does to brains that may already have some chronic, low level ischemic and hypertensive insults. I would love to see a long term study on the cognition of people who have had tight glucose control during their acute events vs those who have had less tight control.
The liver throws sugar at pain and stress for a reason. Modern medicine keeps trying to prove that the body is making a mistake. If only doctors would address lifestyle and nutrition. If only doctors knew something about nutrition.
Very nice article John. The first study is a poster child for what is wrong with so many clinical trials: they are designed so there is very little chance that a conclusion of any kind will be made at the end. Combine sample size samba (gaming the effect size to be more than the minimal clinically important difference) and having an unrealistically high estimate of the event rate is a recipe for futility, wasted resources, and raising ethical concerns about needlessly exposing patients in a setting where learning from them is unlikely. Contrast that with the design diagrammed here: https://hbiostat.org/bayes/bet/design
Great review of a problematic trial. We now know stress hyperglycemia is an independent risk factor for mortality in critical care settings. Mortality is worse for those without DM than those with DM suggesting the degree of hyperglycemia from baseline insulin resistance is a marker of the degree of the ischemic or infectious insult. The now appreciated U shaped curve of the Stress Hyperglycemia Ratio (SHR) in prognosis makes this even more complicated bc mild excursions from some insults seem beneficial while large excursions are almost always seen as ‘runaway’ pathology / severe inflammation, or life threatening ischemia (harbinger of poor prognosis). The analogy of sinus tachycardia as adaptive is key here as some SHRs may be a run of the mill ‘stress response’ but the vast majority should be thought of more like ‘AFib’ in critical illness. My suspicion is targeting a ‘moderate’ blood sugar (140-220) is helpful but the SHR and amount of insulin required to achieve that goal is likely more important to compare apples to apples than ‘aggressive’ vs ‘non aggressive’ arms.
I've adjusted my diet in accord with that hypothesis. 50 to 100 gm carbs a day, lots of meats and fish. I've lost 4 lbs in a month and a half though I wasn't trying to lose weight. Next blood panel due in 4 months. Interested in seeing how A1c, glucose and insulin look.
John, were these patients put on insulin pumps with rapid-acting insulin infusions or were they given SC insulin injections at strategic times during their rehabilitation? I’m unclear on the trial protocol. The description sounds as though they were given insulin at timed intervals regardless of their blood glucose readings, which, to my thinking, is a formula for disaster. Surely the goal was to control the blood sugar levels and not just give insulin Willy-nilly?
Dear Dr. John et al.
https://www.amazon.com/dp/9694392675
It is my pleasure to inform you that finally the book written by Cambridge Graduated, Post Doctorate in immune-genetics, Doctorate in Epidemiology and 14 years professor of Virology Karina Acevedo Whitehouse has been translated into English. Since day 0, she has been one of the voices able to speak with plain knowledge, understanding and sympathy for the injured ones. It is so comprehensive and educative for any medical professional and also for average people since it is so well developed that can be understood by people with no biological education. Presentations of this book are taking place in Spain, Costa Rica, México, and she has worked with the WCH, Ryan Cole, Oyewale Tomori, J. Rose and others. This one does deserve to be read and shown to the decision makers in all the world and to the misled ones too. Please, take a look at it, it is worthy in every possible way.
This rang a bell somewhere in the recesses of my memory - in the hospitals where I worked as a junior doctor in early noughties they actually employed a full time DIGAMI diabetes specialist nurse to make sure we didn't overlook this important part of MI management. They even devised revised guidelines to address some of the risks of hypoglycaemia (https://diabetesonthenet.com/wp-content/uploads/jdn7-5-185-90-1.pdf). I'd completely forgotten about it and when I did my GP training a few years later it was no longer a thing.
I can think of a fair few examples over the years where it would have paid not to jump in with both feet to adopt new guidelines or novel treatments.
It again begs the question of what the journal editors were doing. The authors can submit whatever they want. But you’d like to think the editors would have some pride in what they print under their banner. Or perhaps they enjoy readers questioning what they’re smoking.
My initial reaction: How could anyone with even the most rudimentary understanding of physiology possibly believe that giving a drug to lower serum glucose levels during a period of maximal stress is a good idea? This would seem to be taking the unjustified demonization of carbohydrates to new levels of idiocy. It is probably true that there is no big pharma money bankrolling this study. But it does remind us that there is another significant force driving a lot of useless research. Career advancement is a huge motive for those in the academic research field. More publications lead to more success in bringing in the big grant money and climbing the academic ladder of success.
..."about the failure of good ideas and aggressive therapies as well as the strong draw to spin results"...without that marketing scheme, big pharma would go broke. It is these "new" drug therapies, most often no better than the old drug therapies, that spins the wheel of fortune for big pharma as these new products always carry exorbitant prices.
Following DIGAM1 results, there was no change in the management of AMI. IV Insulin was rarely used in ICUs. Of course, DIGAMI2 confirms the futility of IV Insulin during AMI. I appreciate if you could critically analyze the trials conducted with expensive molecules (with overwhelming involvement of sponsors of the trials) like PCSK9i, etc.
This whole discussion is based on the assumption that diabetics' increased cardiac risk is due to high blood glucose, when more recent evidence points to high insulin as the real culprit. Think about it. All the supposed risk factors - obesity, fatty liver, diabetes, high triglycerides, low HDL - are in fact caused by high insulin. So it's likely that the correlation between all these supposed risk factors and heart disease is just that - correlation, not causation. The real culprit behind all of them is likely high insulin. But while there are drugs to lower blood lipids, blood glucose, and obesity, pharma has no drug to sell to lower insulin. As a result, medicine will no doubt continue its blindness to the insulin/metabolic syndrome problem.
Metformin helps lower insulin resistance so in essense lowers insulin levels
That is why it is considered the first line type 2 DM med, it does help the metabolic syndrome
Great article! Thank you. I am a primary care internist. The only acute MI treatment I do is to give aspirin while we wait for 911 to arrive. On the other hand, I take care of these folks a decade or two after they've had their MIs and their sugars controlled or not in the ICU. I have long suspected that we underestimate the damage that hypoglycemia does to brains that may already have some chronic, low level ischemic and hypertensive insults. I would love to see a long term study on the cognition of people who have had tight glucose control during their acute events vs those who have had less tight control.
The liver throws sugar at pain and stress for a reason. Modern medicine keeps trying to prove that the body is making a mistake. If only doctors would address lifestyle and nutrition. If only doctors knew something about nutrition.
Good article. Thank you
Very nice article John. The first study is a poster child for what is wrong with so many clinical trials: they are designed so there is very little chance that a conclusion of any kind will be made at the end. Combine sample size samba (gaming the effect size to be more than the minimal clinically important difference) and having an unrealistically high estimate of the event rate is a recipe for futility, wasted resources, and raising ethical concerns about needlessly exposing patients in a setting where learning from them is unlikely. Contrast that with the design diagrammed here: https://hbiostat.org/bayes/bet/design
Great review of a problematic trial. We now know stress hyperglycemia is an independent risk factor for mortality in critical care settings. Mortality is worse for those without DM than those with DM suggesting the degree of hyperglycemia from baseline insulin resistance is a marker of the degree of the ischemic or infectious insult. The now appreciated U shaped curve of the Stress Hyperglycemia Ratio (SHR) in prognosis makes this even more complicated bc mild excursions from some insults seem beneficial while large excursions are almost always seen as ‘runaway’ pathology / severe inflammation, or life threatening ischemia (harbinger of poor prognosis). The analogy of sinus tachycardia as adaptive is key here as some SHRs may be a run of the mill ‘stress response’ but the vast majority should be thought of more like ‘AFib’ in critical illness. My suspicion is targeting a ‘moderate’ blood sugar (140-220) is helpful but the SHR and amount of insulin required to achieve that goal is likely more important to compare apples to apples than ‘aggressive’ vs ‘non aggressive’ arms.
https://cardiab.biomedcentral.com/articles/10.1186/s12933-023-02005-0#:~:text=In%20conclusion%2C%20this%20study%20sheds,linked%20to%20increased%20mortality%20rates.
I have read that it is the increase of sugar/glucose in the blood which is a greater contributor to MI than high cholesterol levels.
I've adjusted my diet in accord with that hypothesis. 50 to 100 gm carbs a day, lots of meats and fish. I've lost 4 lbs in a month and a half though I wasn't trying to lose weight. Next blood panel due in 4 months. Interested in seeing how A1c, glucose and insulin look.