Hacker Newsnew | past | comments | ask | show | jobs | submitlogin
Insulin at 100 (diatribe.org)
62 points by crapvoter on July 20, 2021 | hide | past | favorite | 10 comments


So, I have a couple of issues with the text.

1. The article describes the reduction in use of insulin in type 2 diabetes as a bad thing. No. It is a good thing. Type 2 diabetes is caused by having too much blood glucose, the body producing more insulin to lower it, fat cells absorbing the glucose, and then this cycle continuing until there is so much energy stored in fat tissue that the amount of insulin required to keep it there is really high, and eventually the body can't produce that much insulin any more. Injecting more insulin stabilises the blood glucose level yes, but it does it by cramming more energy into fat cells that are already full. Diet, exercise, and other glucose-lowering drugs are a much better treatment. Taking insulin just makes you dependent on insulin and potentially even less healthy. Removing the stored energy by some other method (for instance SGLT2-inhibitors make you pee out glucose in your urine[0]) can make you more healthy. If you're up for it and dedicated enough, fasting can often completely reverse type 2 diabetes. The record for the longest fast is 382 days [1]

2. The article says that "what no one predicted was that GLP-1 agonists and SGLT-2 inhibitors have been shown to reduce the risk of both heart and kidney disease". This should be the least surprising thing in the entire world. Most of the management of diabetes these days is to try and get blood glucose levels stable, specifically because of the consequent benefits in reducing the risk of various diseases, including heart and kidney disease. If you have diabetes, your doctor will be trying to reduce these risks, because they are what people with diabetes tend to die from in the long term. That includes giving heart medication. You can live with blood glucose levels out of whack for a long time without noticing anything particularly untoward, but it will be constantly causing damage. So, was anyone surprised that drugs that lower blood glucose can reduce cases of diseases caused by high blood glucose levels? No, they were not - it was obvious.

[0] https://www.fda.gov/drugs/postmarket-drug-safety-information... [1] https://en.wikipedia.org/wiki/Angus_Barbieri%27s_fast


I second that. Looks to me that the author is more knowledgeable in T1 than T2, and is almost categorizing the latter as a subspecies of the former, for example:

> Some type 2 patients wrongly associate insulin with personal failure surrounding diet or exercise

Well, I don't want to be that person, but to me the association is tangible.


There is a tipping point beyond which type 2 diabetes gets a positive feedback loop, which can make it extremely hard to treat with diet/exercise/drugs. Also, the beta cells in your body that produce insulin can wear out through exhaustion at having to produce so much insulin. Once that has happened, then injecting insulin is necessary.

Some people falsely think this means that your type 2 diabetes has progressed to type 1, but that's not true - it is still type 2, just more severe. Type 1 is a completely different disease, but with some similar symptoms.

I quite understand the "personal failure" part of this. You inject insulin if the diet/exercise/drugs weren't good enough to stop the disease progressing.

However it should also be noted that a decent number of people do actually develop type 1 diabetes late in life. Typically they will be misdiagnosed with type 2 diabetes, because doctors tend to assume that diabetes late in life must be type 2. If this happens, a progression on to insulin injections is nigh-inevitable, regardless of how much diet/exercise/drugs they have. There are a few tests that can help distinguish these patients - firstly they tend to be thin, but secondly the auto-antibodies that caused the destruction of the beta cells can often be detected in their blood.


> but secondly the auto-antibodies that caused the destruction of the beta cells can often be detected in their blood.

That's actually really interesting, I still have got much to learn (and you seems to know that stuff pretty well, thanks for sharing!).


Do we know why the blood glucose gets too high? From what I understand our cells reduce the number of insulin receptors which leads them to absorb less glucose and hence lead to increased blood glucose. But the reason for this insulin resistance is still sort of up for debate. Atleast this is what I understood.


There are a few theories out there, and the truth is probably a mixture of them along with some we don't know about.

However, firstly, type 2 diabetes starts out with no significant increase in blood glucose. The reason for this is that the body is very good at self-regulating (homeostasis), so it just produces a bit more insulin to keep glucose levels about right. This happens in the pre-diabetes stage. The insulin tells the fat cells to convert glucose into fat and store it, which causes people to put on weight. Type 2 diabetes should be viewed as a disease of too much insulin required, rather than too much glucose present. Yes, there ends up being too much glucose, but the primary problem is that you are giving the body too much energy to store, and it needs to produce too much insulin in order to do that.

This leads into one reason for insulin resistance - the fat cells that are already full need a higher and higher level of insulin to persuade them to keep that energy stored there. Adding more insulin gets them to cram more in, but there is a limit to how much they can.

Another possible reason for insulin resistance is constant high levels of insulin in the blood. Like a drug which you become resistant to if you are constantly taking it, your cells probably get resistant to the insulin. Insulin is secreted in response to high blood glucose and food intake. So there are two things that can cause a constant high level of insulin. The first is if fat cells are full, and they need a high insulin level to stop them dumping the stored energy back into the blood in the form of glucose. The second is if you're constantly snacking. For that reason, it is a real benefit to have a decent long stretch of the day when you don't eat anything. It used to be quite normal to have an evening meal at 6:30pm, and then not eat anything until breakfast the next morning, which gives the body a nice 12-ish-hour session each day of low insulin levels that allow resistance to recover. It's one reason why the 5-2 diet (where you eat normally for five days and then fast or severely diet for two days, every week) is successful.


Basically with Type 2 diabetes it is runaway inflammation with a genetic makeup that causes the insulin receptors to get less efficient. Insulin is the key that allows the glucose to get transferred into a cell. Once the body is starving for carbohydrates it begins a process to break down fats and even protein into an energy source. This produces toxins, ketones. That is a brief overview of the biggest factors. To prevent, or reverse this downward spiral, eating better will help and there is a simple life hack. Melatonin upregulates insulin receptors, this works for everyone not just already diagnosed diabetics. With Type 1 autoimmune diabetes melatonin can reduce insulin requirements but won't eliminate the need for insulin. With Type 2 and with prediabetes melatonin along with minding your diet can have a dramatic effect. Increasing the ratio of unsaturated fats (health plant oils not palm oil) like olive oil and increasing plant based protein sources like eating beans, peas or lentils for some of your meals will help reduce the risk of diabetic complications. Another hack if you go with any amount of a plant based diet is to eat raw miso from the tub or to carefully make it into broth with water under 130 fahrenheit. Miso is full of microbes that make plant protein more digestible and useable by the body than any other source.


> Once the body is starving for carbohydrates it begins a process to break down fats and even protein into an energy source. This produces toxins, ketones.

You may want to read some (hopefully) unbiased information on that subject : https://en.wikipedia.org/wiki/Ketone_bodies https://en.wikipedia.org/wiki/Ketogenesis

For example:

> Both [two of the three types of ketone bodies] are 4-carbon molecules that can readily be converted back into acetyl-CoA [which can directly fuel the krebs cycle] by most tissues of the body, with the notable exception of the liver.

Which is not really matching the definition of 'toxins'.

In my mind, saying that ketone bodies are toxins could be suggested in the fact that ketoacidosis is a real threat when a metabolism is affected by T1. But, again, T1 is not T2, and it's not the condition of a healthy metabolism, which is fully capable of handling ketone bodies, even thriving on it (glucose is fine, too, I'm not trying to sell that line).


Oh thanks, I've been T1 since 1982, so I'm not surprised that science has improved. Keto-acidosis is a toxic state for T1 diabetics at least, I'm not sure if T2 can handle them better.


Although the article mentions Eli Lilly as the first manufacturers of human insulin made through genetic engineering, that technology actually came from Genentech located in South San Francisco.

Since Genentech was a small biotech company without a lot of money or manufacturing capability they outsourced it to Eli Lilly who was already a leader in the insulin market.

https://www.gene.com/stories/cloning-insulin




Guidelines | FAQ | Lists | API | Security | Legal | Apply to YC | Contact

Search: