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Rare genital defects seen in sons of men taking major diabetes drug (science.org)
209 points by jimmy2020 on March 29, 2022 | hide | past | favorite | 231 comments



Obese women’s offspring have double the risk of hypospadius, and women having babies after 40 have 4x the risk of hypospadius.

Metformin is a drug that men are probably 100x more likely to be on at 45 vs 25. Therefore men on metformin are far more likely to be reproducing with older (and likely obese) women.

I’m not saying this explains all the correlation, I’m just saying if the study doesn’t really make a good effort at addressing these confounders, its not worth reading.


From the artcile: "The numbers were small — 13 metformin-exposed boys were born with genital defects. But after the researchers adjusted for factors including parental ages and maternal smoking status, they found a 3.39-fold rise in the odds of a genital defect. “The rate per se was surprisingly high,” Wensink says."


> after the researchers adjusted for factors including parental ages and maternal smoking status

The exact adjustments made can change the solidity of the finding into anything from "rock solid" to "complete trash". Seemingly solid studies are routinely trashed by third party method reviewers that the initial peer reviewers missed. So we'll know better when they get around to it.


>But after the researchers adjusted for factors including parental ages and maternal smoking status, they found a 3.39-fold rise in the odds of a genital defect

If they didn't adjust for obesity, then it's really pointless to attribute this to the drug. Age and smoking status is not enough.


Why would you assume they didn't? They most likely did.


From the quote it says they only adjusted for age and smoking.


The quote says the factors included age and smoking not that they only included age and smoking.


I did indeed not read that properly. I'd have to check the actual publication. It's at least suspicious that they don't mention it, since obesity is probably the first thing you should think of when saying diabetes.


Adjusting for confounders on an n of 13 is statistically ridiculous.


It's not n=13 it's 13 with genetic defects.

Also not adjusting for confounders is statistically ridiculous. As well as n=13 studies.


i'll call n the total number of patients. if n * 9 / 1000 = 13, you'll find out that n is around 1400, which is a pretty high number in discovery studies. Maybe not for diabetes though, i remember hosting anonymized data from a lot more patients two years ago, i felt this was THE subject all the medical founding was put into (that and air quality and its effect studies).


The 90 day window for taking the drug and seeing an impact is in the studies favour though.

> the researchers saw no effect in offspring of men who took the drug earlier in life or in the year before or after the 90-day window of sperm production. “It really has to do with taking it in that window when the sperm … is being developed,” says senior author Michael Eisenberg, a urologist at Stanford Medicine.


If that is the case (90 days makes a difference in outcome) why even adjust for age and smoking?


The link is probably not causal but it is still important. Meaning there is probably an underlying issue that causes both diabetes and genital abnormalities.

See my other comment where I link it to a functional zinc deficiency.


They obviously control for age, at minimum.


"obviously" is an assumption; it's better to read the paper to confirm this, of course.


Whatever your opinion on metformin this study is not really providing strong enough evidence to take seriously. No one should give it any attention, except the researchers who will try and do a better one next time and hopefully can prove/disprove this important hypothesis.

The authors have done a lot of tests here. If you do enough tests, even on null data, you eventually get false positive results. Nevermind the effects of confounding which are difficult to control for effectively in a non-random study.

The smallest p-value I could find was P = 0.012. Which is for "elevated birth defect fre- quencies among metformin-exposed offspring". This comes from a table with 6 rows of models with different OR values. Presumably they did have p-values testing if those ORs were statistically different from OR == 1. Which means one should adjust p-values by dividing the significance threshold by 6. So, 0.05/6 = 0.0083 which is smaller than 0.012. So I would be very hesitant to say that the evidence points to metformin really causing this. At least based on this study.


The bonferoni correction is known to be overly restrictive, though. But yes, probably many more models were fit and results are questionable. The author will at least be able to claim a Science paper...

Also, adjustment of the p-value doesn't do anything to solve the flaws of hypothesis testing. But that's another debate entirely.


I believe it was published in Annals of Internal Medicine (impact factor of ~4). The link is to a news article in Science discussing the paper.


Ah, then I understand better. Was wondering why such a paper would be in Science.


Relevant xkcd:

https://xkcd.com/882/


I don't get why this is called rare in the article. It's not called that in the actual study, so the article seems to do some editorializing:

https://www.acpjournals.org/doi/10.7326/M21-4389

Looks like of the kids taken from dads taking metformin, .9% had a genital defect, which seems pretty high to me (defect in control is 0.24%). Granted, not as high as Thalidomide, but still, 9 in 1000 are not great odds.


I think it means the genital defect is normally rare, but is much more common in these kids?


Even .24% isn't that rare.

From NIH.gov:

"In the United States, a rare disease is defined as a condition that affects fewer than 200,000 people in the US."


That works out to 6.0341E-06%


A condition which would affect 6e-6%, or 0.000006% of the US population (330M) would affect 20 persons. 200000/330M = 0.0006 = 0.06%.


The deformity in the general population affects 0.24% of male babies, so 0.12% of the population.


GGP is still 4 orders of magnitude off.


Metformin is also sometimes used to induce ovulation in non-obese women of childbearing age with polycystic ovarian syndrome.[0] Luckily, this study seems to only show an effect if taken within the 90 day window before conception, so it seems to be doing something to the sperm, and not causing genetic changes. Also, of course, we'd want to see corroborating studies.

[0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200666/


> it seems to be doing something to the sperm, and not causing genetic changes.

To be clear, spermatogenesis takes roughly 75-120 days, so this is consistent with metformin causing genetic changes to the sperm when or after they are formed, with those genetic changes being propagated through the germ line to children conceived by the sperm. But it's true that the (very preliminary) data does not suggest that this is causing permanent genetic changes in the father.


I think "sometimes" is a bit weak here. My second-hand understanding (from multiple women who have gone through this) is that it's routinely the very first treatment tried for women with PCOS who are having trouble conceiving.


It’s sad seeing the crazy downstream multigenerational damage that massive sugar consumption is causing as obesity rates reach 50%.

Good luck future humanity.


Our leaders have been calling for a population decrease since around the time of the civil rights era, so maybe future-humanity gets a coincidental-but-desired outcome after all?

https://files.eric.ed.gov/fulltext/ED050960.pdf#page=10

"The time has come to ask what level of population growth is good for the United States. There was a period when rapid growth made better sense ks we sought to settle a continent and build a modern industrial Nation. And there was a period, in the 1930's, when a low birth rate was cause for concern. But these are new times and we have to question old assumptions and make new choices based on what population growth means for the Nation today."


Fringe leaders call for fringe positions all the time.

None of the authors of that paper were elected officials, and that view never became policy of any state.


> and that view never became policy of any state.

Not officially anyway: https://wtfhappenedin1971.com/


What leaders ask for is not necessarily what the population at large needs.


> so maybe future-humanity gets a coincidental-but-desired outcome after all?

If you fuck up the gene pool to get to that result I don't think you can call it "desired".


If we're going to decrease population then we should probably start finding ways to encourage reproducing only among the most genetically fit. There's a fine line to be walked with this line kind of thinking and itspast, but if we're going to so limit the pool of available physical and intellectual talent, we should make sure we minimize handicaps, obesity, addiction, mental illness, etc.

Hopefully, gene editing obviates the these concerns.


From what I recall reading about epigenetics, diabetes is caused by a too fast change in diet towards high calorie. After several generations the metabolism thriftiness goes down if the diet level remain the same, and thus diabetes rates will go down. Same concept happens in reverse when there is periods of famine.


Type 1 diabetes is an auto immune disease that destroys your pancreas.

Type 2 diabetes is an acquired and reversible disease that follows insulin resistance and it is caused by excessive amounts of glucose in your blood, which forces your pancreas to release an ever increasing amount of insulin which then is absorbed by fat cells until they hit insulin resistance, then it fills up muscle cells including your heart until they hit insulin resistance until the only place left for the glucose is inside your organs.

The easiest way to reverse diabetes or avoid heart surgery is to get a live glucose monitor and then do a ketogenic diet. It's non invasive and if done correctly is more effective than any surgery can ever hope to be.


> live glucose monitor

As my endocrinologist put it, diabetes is a disease about decision making.

Right now, there’s little evidence that a CGM actually helps Type 2 patients make better decisions. More information doesn’t lead to better decision making. Better decision making processes and changes to lifestyle lead to better decision making.

From 2020:

“Although continuous glucose monitoring may benefit patients with type 1 diabetes mellitus, there is limited evidence that it offers similar benefits in patients with type 2 diabetes, regardless of whether they are taking insulin.”

“Until we have research supporting continuous glucose monitoring for patients with type 2 diabetes, especially those not receiving regular insulin injections, there are no patient-oriented benefits to justify its great expense and additional hassles for patients and physicians.”

https://www.aafp.org/afp/2020/0601/p646.html


That's quite a claim. Do you have some sources for that?


My guess is that I read it in a book by Robert Sapolsky titled Why Zebras Don't Get Ulcers, but I won't reread the book just to give you the exact page number. It could also be one of the youtube talks by him where he go through epigenetics.

What I will do is a simple web search: https://pubmed.ncbi.nlm.nih.gov/18197594/ and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463748/

To quote the later study: "Given that risk for diabetes and its complications is linked to both genetic and environmental factors, it is not surprising that there are now more than 1,000 articles that address the intersection of diabetes and epigenetics or epigenomics"

The case study that I remember was studies done on Indigenous populations when they got introduced to a west-style diet by being integrated into west society. The following generations had higher rate of type 2 diabetes compared to children of existing demographics. There has also been a plentora of studies done on children born after the dutch hunger winter (https://en.wikipedia.org/wiki/Transgenerational_epigenetic_i...), where one of the finding was increased risk of glucose intolerance in adulthood.


It’s an extremely sad situation and will guarantee every single healthcare system eventually breaks down.


You're saying that it's a guarantee that every single healthcare system (in the world?) will break down because of _sugar consumption_? Seriously?


If sugar consumption is the leading factor in obesity, and if obesity is the leading factor in added pressure to the health care system, then... it's definitely a big preventable factor, I'd say.

But it's not absolutes. Anyway yeah, some lifestyle choices need to be addressed to reduce pressure on the health care system. Like how for two years now we've had certain measures in place like social distancing and facial masks, not to eradicate the virus (that would require extended full stay-at-home mandate lockdowns) but to keep pressure on the health care system manageable.


It is very close to the truth unfortunately. Maybe it won't break down but the vast majority of health care spending is there to undo the effects of a bad diet more than anything else.


That plus the inverted population pyramid. It's certainly plausible


Diabetes is really rough on the organs. Especially once the kidneys go, you need dialysis 3 times per week and the treatment takes hours. If a substantial fraction of the population needs that treatment, it's going to be rough. Plus the eye surgeries for glaucoma, and other kinds of organ failure.


> Especially once the kidneys go, you need dialysis 3 times per week and the treatment takes hours.

My grandpa went through this in 2020. He was a tough navy guy, and even he said "This is a half-assed way to live", stopped the dialysis, and passed away a few weeks later. Once you're on dialysis, there's not much of a chance of going back to a life without it.


can't decide if it's good or bad then that we somehow have universal care... but only for kidneys, lol https://www.npr.org/transcripts/131167638


Oh wow, thanks for the link. I had no idea that we covered kidney disease that way.


Yeah if birth rates stay low ( which they have now for a few decades esp in Western countries but true elsewhere), you’ll need either large scale immigration or lots of cash to service the social care system, which now has to service the growing number of the geriatric and chronically il


Almost every health care system is based on shared payment. Either insurance or socialized medicine, it's similar with a varying amount of pooling. If almost everybody is obese, us few healthy people may end up stuck paying for the fatties. And eventually, there will be too many fatties, they will vote that they can't be pooled separately so we have to pay even more, and there will at some point be too few of us.

IInsurance for me should be very low. I am in great shape by anybody's measure. But all the drunks, junkies, fatties, make my payments so high I've debated dropping medical insurance.


Why was this down voted? You're not wrong. Regardless of whether we have a private or socialized healthcare system, we simply won't be able to afford to continue delivering high quality care to everyone with chronic conditions caused by bad dietary choices and sedentary lifestyle. The resources just aren't there so we will increasingly have to ration care.


Why? Playing the devil's advocate here, 42% of the US population is obese right now. Why is it going to be impossible if that hits 60%, or 80%?

I ask this as someone with a BMI of 23 who puts a reasonable amount of effort into not becoming obese or overweight again. The personal benefits of not dying from cardiac arrest at 55 are very obvious, but I'm not clear on why healthcare systems won't be able to cope.


Healthcare is already about 20% of the US economy. Where do you think the additional money is going to come from to care for a major increase in diabetics? The rest of the economy doesn't produce enough of a surplus to sustain that.


A huge amount of spending goes towards the healthcare needs of the elderly, and obese people die early. Is there data that suggests increasing obesity increases overall healthcare costs, instead of decreasing them?

I can understand the argument that diabetes resources, specifically, will be strained. If overall costs don't rise, that's not a huge problem.


Obese patients on average cost about $2500 per year more than normal weight patients. Even though they die earlier they still increase overall healthcare costs.

https://www.jmcp.org/doi/10.18553/jmcp.2021.20410


All in all, we eat and live in a more healthy way then generations before.


No, we really don't. Just look at the way the obesity rate has steadily increased over the past several generations.

https://www.niddk.nih.gov/health-information/health-statisti...

Doctors are now seeing children come in fatty liver disease. That never used to happen.


I think it's safe to say both are true.

In general, we live in a healthier world. We know more about nutrition, cancer-causing chemicals, etc. We continue to make progress automating some of the most body-breaking jobs. Most of us (western world, anyways) have access to clean water.

But, a substantial portion of the US (and world?) population is making bad decisions about their diet which have life-altering side-effects like diabetes. The question then is "why?" We know a lot about nutrition and it's impact on our bodies. Is it advertising? Is it cost (McDonalds is more sometimes more affordable on a time+money basis than home-cooked food)? Is it just our tiny lizard brains REALLY like salt and sugar and Nestle etc know how to manipulate that?


> Doctors are now seeing children come in fatty liver disease. That never used to happen.

They used to die of malnutrition of all kinds. Not just because of being poor, but because of us not knowing this or that is necessary in food.

The physical work people used to do was body breaking fairly often. The chemicals people used to be in daily contact with were body damaging too.


Well now you're just making things up. Deaths from nutritional deficiency have always been extremely rare in the USA. Outside of some isolated cases of abuse or neglect or mental illness, only the poorest people ever died of malnutrition. It has never been among the leading causes of death. Knowing this or that is necessary in food is mostly just of academic interest and hasn't actually produced better health outcomes.


This is not true. The malnutrition of some kind is not rare and diseases from it were life. Malnutrition is not famine. It is lack of Iron and anemia. It is Rickets due to lacking calcium. It is missing any of vitamins - like being sickly in winter due to lack of vitamin C.

It is missing Iodine which is now commonly added to salt.

You can be overfed in calories and still suffer from malnutrition. Especially without science we have now. And whole classes of sicknesses caused by malnutrition don't exist anymore.


I believe this is intentional. If the ruling class wanted workers to live long, they'd force them to switch to oatmeals, fruits and water, while sugar would be a substance competing in price with cocaine.


So the ruling class is forcing you to eat sugar, and you don't have the option to choose for healthier food?


From a big picture, socio-economic point of view, yes, the ruling class (Fortune 500 CEOs and elected officials they donate to and lobby) are essentially forcing the poor, the unaware, the average Joe to eat a diet full of high-fructose corn syrup and other carbohydrates, which happens to be produced by giant agricultural companies.

Corn is a subsidized crop by the US Department of Agriculture—we pay farmers to grow it. See the documentary "King Corn" about two guys who didn't know the first thing about growing corn but still made a profit on 1 acre of corn [1].

It's often said your zip code is a huge indicator of many demographic stats and what food you have access to is one of them.

I've lived in food deserts and I can tell you getting healthy food can be quite an arduous task, especially if you rely on public transportation.

Recent data shows that 80%(!) of black women in the United States are obese [2].

This isn't an organic phenomenon; this level of obesity is the result of a system—some intentional and some not—at work.

[1]: https://www.kingcorn.net

[2]: https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=4&lvlid=2...


"are essentially forcing"

Except for the fact that poor immigrants from Bangladesh or Africa do not suffer from the same problem in the first generation, because they are still used to buying staples in the market and cooking traditional meals at home.

The same can actually be seen in UK and Western Europe.

The deadly fact that is compounding the situation is that cooking skills haven't been passed down in a large portion of the Western population for almost two generations now. People who do not know how to cook rely on highly processed stuff that can be heated in 2 minutes in a microwave. Reliance on this highly processed stuff is strongly correlated with bad health outcomes.


> The deadly fact that is compounding the situation is that cooking skills haven't been passed down in a large portion of the Western population for almost two generations now. People who do not know how to cook rely on highly processed stuff that can be heated in 2 minutes in a microwave. Reliance on this highly processed stuff is strongly correlated with bad health outcomes.

People either feel that they don't have time to prepare and cook or they see it as inefficient since it is much faster and cheaper to dine-out or takeaway.


>Except for the fact that poor immigrants from Bangladesh or Africa do not suffer from the same problem in the first generation

Give them a a couple years or so, and many of them will want to live the American lifestyle - eating out every day, and stocking their pantry with snacks they see on TV. The ones that don't face the consequences of being obviously foreign.

In America, marketing and psychological hackery are second only to law in terms of "forcing" people to do things.


Agree


> I've lived in food deserts and I can tell you getting healthy food can be quite an arduous task, especially if you rely on public transportation.

That's what food desert means. As in, no food. Therefore food must be imported. Therefore it's expensive. Sugar just happens to be a well-preserving food.

The solution is quite simple: Don't live in a food desert.


>The solution is quite simple: Don't live in a food desert.

For the people on HN who tend to skew towards wealthy white-collar work this is fine advice, but it's absolutely not possible for a lot of people from lower incomes. Not only can they not afford to move, they can't afford to leave their entire social support structures and build them anew.


They also can't afford to eat shit and have a shit life as a result.


Exactly, the notion that the poor are poor because they're inherently feckless and therefore deserve their poverty is an idea that's long past its sell-by date. These are the systemic issues of our day, and they won't be solved by sneering at the people affected.


Excuses. History is rife with entire peoples migrating to greener pastures. If they wanted to move and eat better, they would.


I propose an experiment, find someone to look after your savings and belongings for a while and move to a new city with nothing more than US$500 or equivalent. You may not have friends or family within seventy miles of this location, nor a pre-arranged place to stay. You can come back for your money and possessions at any point, but if you don't last more than six months then you have to do a write-up on HN of your experiences and admit that poverty is more difficult to get out of than your naïve assumption.


Yeah wow that is quite possibly the most tone-deaf thing I've ever read on here. Plenty of people don't have the option to simply "not live in a food desert".

I hate calling out privilege but this just smacks of privilege.


There is no one ruling class though; one part wants workers, the other wants to sell stuff. They're competing with each other. Muh free market.


Of course. But as it turns out, the medical industry is a great way of moving wealth from the middle class to the wealthy during end of life.


Metformin is the first resort in diabetes treatment. If it proves to truly increase birth defects by 40% that may have to change.

It was my doctor's first resort for me, but the side effects were too severe and I stopped it. He vaguely mentioned that it would help if I lost weight, but made no mention of what actually resolved my diabetes, a low carb diet. I hope that becomes the first resort. Apparently around here it's not even in the standard toolkit.


Wow, if they aren't suggesting dietary and exercise based solutions first, that's a huge red flag. Find a new doctor.


Prescriptions of diet and exercise are ineffective because many obese / type 2 diabetic people can't exercise self-control. That's why they're obese in the first place. It's way easier to take a pill than cut to 1500 calories a day for 2 years.


It is a harmful stereotype to label obese people as lacking willpower as you have done. Many obese people don’t have the resources (time, money) or tools (nutrition understanding) to improve their situation. Many have metabolic or familial history of obesity which has both physical and psychological (normalization) impact on their ability to control their weight. The former can be helped with diet and/or medication, the latter often causes them not to seek help.

Most people in the US live in poverty and make marginal spending food decisions based on money per dopamine reward unit rather than optimizing nutrition. McDonalds is cheap and unhealthy; fresh fruits and vegetables and the free time to educate oneself on proper nutrition, then cook healthy meals and do meal prep often cost more money and time than most can afford. As does proper exercise when you’re working 12 hours per day trying to make ends meet.

A less harmful way to phrase your point is that medication can help people who self-medicate with food overcome metabolic efficiency. I lost 40 pounds on semaglutide (Wegovy) so far this past year and dropping; exercise and diet alone didn’t work for me. I hope to eventually not rely on medication to maintain a healthy weight.


I would say it’s much more harmful to rationalize obesity as something that afflicts people according to their circumstances, rather than what it actually is, a direct outcome of a person’s intentional choices.

It’s also quite harmful to dramatize the solutions out to be something unattainable to many people. They are attainable to all people. The healthiest diet I’ve ever eaten was also the cheapest diet I’ve ever eaten, and almost everybody can get 30 minutes of low intensity exercise a day.


Nutrition and fitness are hardly a one-size-fits-all problem.

To take an example, my self, I am doing intermittent fasting and do moderate intensity exercise everyday for at least 30 minutes(gym, cycling, bouldering, etc). No matter what I do, I still have a muffin belly.


I also believed that for many years, that no matter what I do, I cannot control my weight.

Until one day I began to both weigh myself each day at the same hour with a precise digital scale and also weigh or measure by volume all the food that I eat.

After that moment, I reduced my weight by 2/3 and I have maintained easily any target weight. Even now, after some culinary orgy I easily gain a couple of pounds in a day, but then, by eating only measured quantities of food, I lose them after a week.

The reason why I have failed to control my weight during many years and most people also fail, is that if you eat until you are satiated, then it is guaranteed that you will not be able to control your weight, no matter how much exercise you do.

If you measure what you eat and you only eat pre-planned quantities, it is trivial to reduce how much you eat until you see that the next day you weigh slightly less (e.g. 100 grams less). Then you must keep eating such quantities until you reach the target.

If you do not respect your plan and you eat random extra snacks or drink sweet beverages, then of course you have no chance to control your weight.

It is much easier to follow a plan when you eat less meals per day, because they can be larger. When eating small meals many times per day it is far more difficult to stop after eating just a little. It is much easier to not start eating.


If you want to lose body fat you need a caloric deficit, squeezing a caloric surplus into a smaller window of the day isn’t going to do anything productive. Intermittent fasting itself has absolutely no benefit, it can only be useful if the fasting routine helps you maintain a caloric deficit.


>a direct outcome of a person’s intentional choices.

You mean like a politician promoting obesity inducing foods?

If it is really about individuals then obesity shouldn't be going up in African nations that quickly.


No food is specifically obesity inducing, and you personally are responsible for everything you choose to eat, not a politician.


> No food is specifically obesity inducing

This is false. Of course certain foods are metabolized in ways that are more likely to lead to obesity than others.


Absolute nonsense. Your food contains calories in the form of carbohydrates, protein and fat. None of those macronutrients are metabolized in a way that is likely to lead to obesity. Obesity comes from consuming more calories than you burn. It doesn’t matter at all where those calories come from.


I agree. After living and traveling abroad, it's easy to see America has an obese-default culture.

Most cities and towns have little walking or public transportation. Cheap, high-calorie, nutrient-poor food is easily available anywhere 24 hours a day. Restaurants have an abundance of large amounts of meat and carbohydrates drenched in low-quality oils and sugary seasonings.

You have to be consciously active to stay fit or cook the majority of your own food. People in a lot of other countries stay lean and aren't as obsessed with fitness as we are.


I lost 20 pounds, got off antidepressants and found love all within 6 months of leaving America at age 24.

I don’t really have a point, but there is a lot of poison for body and mind in that country.


Out of curiosity, where did you move to?


Cambodia


Gp probably could have stopped after:

> Prescriptions of diet and exercise are ineffective

Which seems to be true. If any advice your doctor could give yields no measurable difference, is there really a point to giving it?


Agree, mostly. Primary care doctors in the US are often limited to 15-30 minutes per patient for routine matters. Referrals to nutritionists / dieticians and other expensive options often lack follow through, or aren’t offered in the first place because prescribing is so much easier. Medical professionals have a duty to arm patients with the information needed to make good choices about their health, but often shirk that duty due to inconvenience or these kinds of time limits. In a perfect world, access to medical professionals would be less scarce and at least the tools (nutrition info) would not be an issue. The medical system really isn’t designed for obese people on multiple levels in the US, and it isn’t designed for good long-term outcomes…yet.


Most systems, like Epic, will print out the standard info and counseling related to your conditions and medications when you get your paperwork at the end of the visit. That's easy and takes almost no time.


Considering the root(?) commenter said that a low carb diet did in fact work for them even though they had to go research it on their own, it sounds like it was effective.


A lot of diets work at least in the short/medium term, for those that have selection bias and "completed" them.

That's very much _not_ the same thing as a doctor recommending or prescribing them having any effect.


There's no talk of completion. This isn't a "diet", it's a diet. We aren't using it as some colloquial meaning for losing weight, etc. This is about a lifelong dietary change to address excessive carbohydrate intake.

If it doesn't have "any effect" then I guess all type 1 diabetics are already dead?

The point still stands - doctors should be counseling diabetics on dietary changes, even if they are being prescribed medication. Some patients can improve their condition and overall health to the point that they can stop the medication. If you disagree with this, please, show me some sources. As for mine, you can check the AMA, AHA, ADA, and PubMed (American Medical/Heart/Diabetes Associations).


People weren't obese ages ago, and I am sure that's not because of better nutritional education.

It's a multifactorial problem.


People didn’t have McDonalds and cars ages ago. Barn-raising, (manual) farming, and hunting are hard energy-intensive work. Our calorie output required to survive dropped while the calorie inputs available cheaply dramatically increased. That is all part of “overcome metabolic efficiency.” :-)


It's easy to demonize fast-food but that's not even the worst of it.

High-fructose corn syrup has been added to so many foods that didn't have it 10-20 years ago.

The second or third ingredient on a bottle of ketchup, for example, is high-fructose corn syrup. You can get ketchup that doesn't have high-fructose corn syrup added to it; often it's a natural or organic brand that often costs more than the regular brand.

And depending on where someone lives, brands without refined sugars may not be readily available. Google "food desert" and see what comes up.

It was literally impossible a generation or two ago to ingest the amount of carbohydrates the average American gets just from eating prepared and processed foods today.


> It's easy to demonize fast-food but that's not even the worst of it. High-fructose corn syrup has been added to so many foods that didn't have it 10-20 years ago.

We should just count ready-meals etc. as 'fast-food' too, no good reason that it implicitly refers to 'restaurants' only really.

> The second or third ingredient on a bottle of ketchup, for example, is high-fructose corn syrup.

Interesting, that didn't sound right to me (but it has been a long time since I've had it) - found this: https://www.truthorfiction.com/heinz-ketchup-ingredients-u-s... (tldr just sugar in the UK)


The obesity epidemic is a lot more recent than barn-raising days. Even in the 90s people were considerably skinnier.


> People didn’t have McDonalds and cars ages ago. Barn-raising, (manual) farming, and hunting are hard energy-intensive work. Our calorie output required to survive dropped

Not saying I know any better, but at it's face I don't buy this. The change in day-to-day activity doesn't feel like it would account for the difference from just the 80s to now.

> while the calorie inputs available cheaply dramatically increased.

This I buy much more, confounded with maybe the specifics of the nutrients available.


Even a small change in average daily activity can account for a large difference. If you cut your total daily energy expenditure by just 50 kcal (the equivalent of walking less than a mile) while keeping intake the same then you can gain up to 5 lb in one year. Add that up over a few years and suddenly you're obese.


You're right in one way, but not another. Small increases in caloric content can have a large and counter-intuitive impact due to the nature of systems in equilibrium: just one small soda or candy bar a day above your equilibrium will drive large weight gains.

But you're not factoring in the fact that as your weight increases so does your idle energy costs, meaning that as you gain weight you burn more calories doing nothing. Put another way, if today you burn 1500 calories a day idle, and you start eating 2000 calories a day - at some point you will reach an equilibrium, likely well before you're obese.

I'm also in the camp that thinks that lifestyle explanation for rises in obesity is completely unsubstantiated.


Not to mention increase in sugars in foods; soda pops also drastically increased from 8oz to 20oz. Combined with even small decreases in activity can add up quickly.


Robert Lustig talks about this quite a bit. The data shows widespread obesity in modern times is a direct result of all the added sugars in the standard American diet.


What about other countries? America might be leading the way, but a lot of European countries brag about "only" having a 1 in 4 obesity rate, which is still incredible.


Nutritional science got better at making people fat.


It's much more harmful to obsess over the optics of something potentially offensive at the expense of reality. None of the excuses you listed hold any ground.

Time: it costs about 20 minutes to cook a simple, basic fresh meal. With a single weekly groceries delivery (or visit to the store), you're covered for some 5-6 main meals as well as breakfast and lunch. Are you telling me Americans don't have 20 minutes to prepare a meal yet do have that time, or more, to eat out? I've been home cooking 6 days a week for 2 decades. It costs LESS time, not more.

The average American watches over 3 hours of TV, or TV-like experiences in their leisure time, but they don't have 20 mins to cook a meal? I guess they all get home from work and fall asleep?

Costs: Rice, potatos, bread, vegetables and lean meats...please do the math for me how this is unaffordable? They are incredibly cheap commodities.

"Most people in the US live in poverty".

Now they do not. The US is in the top 5 of median incomes worldwide, one of the richest countries in the world. If you dismiss Luxembourg and UAE, the USA is in the top 3. It's not a monetary issue.

Further, 12 hour work days are an anomaly, not a standard. And even 12 hours is not an excuse. Exercise isn't the core of the issue, junk food is.

Time needed to educate on nutrition: your parents or school should have done that, but here goes: don't eat garbage. Cut down on fats, sugars. Education completed. But it's not an educational issue as the person sitting in McDonalds knows exactly what's up.

It most definitely is a willpower issue as every other excuse does not hold ground. People in other countries have less time and less money, and still don't have this issue at this scale.

Please know that this is a not a burn at obese people, I fully sympathize with the difficulty of lifestyle changes, even more so in a culture like the US where the environment seems stacked up against healthy eating.

But we need to attempt to come to real and realistic root causes, and time and money are not the core issues. It creates this illusion that if only economic conditions would improve, we'd all be eating healthier, which is false.

The issue is cultural.


Youve identified the chain but keep it going: stress and lack of sleep!

Ubiquitous coffee, economic pressure, overpriced and weak preventative healthcare system, social pressure, status anxiety, housing insecurity, political threats, public-facing crimes, rampant racism. These all test our self-control around food.


None of those things help, yet none of those things prevent healthy living. For the simple reason that healthy living does not cost a lot of time or money.

Like I said, home cook 5-6 days per week, which costs little time or money. None of the issues you mention prevent you from doing it. Exercise costs no money at all.

I don't mean to dismiss your reasons as if they don't matter at all, I'm stating they are a trap. They provide a shield to hide behind. If only all of that would improve, I'd be healthier. This imaginary utopian society will not make you healthier. You become healthier by stop eating crap.

Nobody's going to do that for you, but you.


I agree abt the importance of home cooking, bit if you have a chance, look into how stress affects digestion. The same food can affect the body differently based on its stress state.


There is no digestive condition that causes the body to metabolise more calories than you consume.


No, it's the lack of will power, with few exceptions. Most of the food these days, even expensive food, has atrocious amount of calories, so to burn one cookie-worth of energy one would have to do a stupid amount of weight lifting. For example, lifting a 50 lbs dumbbell 3 feet high burns just 5 calories, while a small cookie I have on my plate has 200 calories. That's 40 times to lift that dumbbell just to burn 1 cookie.

Edit: or let's take a look at cheese. I've found some pretty expensive cheese in my fridge, packed into small cube boxes, because otherwise its price per pound would be offensive. So we might expect that cheese would do better than cookies. The nutrinion facts label on its reverse begins with "serving size: 2 table spoons, 120 calories" - a borderline fradulent label that's trying to hide the fact that the small chunk of cheese has 600 calories in it.


Bullshit, and my response is a bit tangential, sorry. Obesity isn't a defect of self-control, it's a systematic metabolic disease that makes these people ravenous yet ingest enormous amount of calories.

Low carb eating has been successful outside of the mainstream lie of "eat more whole grains" because it simply avoids the foods that worsen runaway metabolic syndrome; the common advice is just to "eat less", while these poor people are ravenous and gain fat on whole foods 2,000 kcal diets. CICO doesn't mean anything in a vacuum if one way of eating causes you to be constantly hungry, and the other teaches your body to make use of its great amount of stored energy.

Obesity is eating the same food that previously kept you healthy, but now makes you sick and hungry.

Here's abundance of doctors and researchers talking about it: https://www.youtube.com/c/lowcarbdownunder/search?query=diab...

Here's one I've watched and can recommend: Prof. Robert Lustig - 'Sugar, metabolic syndrome, and cancer': https://www.youtube.com/watch?v=jpNU72dny2s


> Prescriptions of diet and exercise are ineffective because many obese / type 2 diabetic people can't exercise self-control. That's why they're obese in the first place.

Research continues its trend against this statement.

1) One problem is the fact that the number of fat cells in the body is conserved after some point. So, if you grew lots of fat cells as a child, sucks to be you, you're now stuck with them as an adult.

2) Caloric consumption has been tracked and cross referenced between countries, and obesity doesn't always correlate with it. Apparently, there are other things going on. Some of these seem to be environmental.

3) Fat cells "remember" your weight when they were formed. Once you become obese, your body fights your attempts to lose weight all the way down until those cells die off and are replaced (about 10% per year or so). It takes MASSIVE amounts of willpower to fight your own body over years.

4) Exercise is practically useless for weight loss. The body demands a fixed number of calories (up until you're doing something at the level of extreme training) and shunts the available calories between systems. Exercise has lots of benefits. Weight loss just isn't one of them.

5) I do agree that nothing in the US helps you avoid gaining weight. Portion sizes are gigantic (a "personal" pizza in the US is a full pizza in Naples). Walking or bicycling is rarely useful for most people. Sugar gets added to everything (For example: Austin, TX has been a particular victim of this--gigantic glasses of unsweetened iced tea used to be the default a decade or so ago but has been replaced by sweetened or double-sweetened iced tea (which used to be limited to the Southeastern states)).


#4 is surprisingly difficult for people to understand. It seems to fly in the face of what weight loss is expected to entail.

Strength training, on the other hand, is (at least I hear) helpful in losing weight.


#4 is t correct, or rather it’s helpful but in a counter intuitive way. On its face, it’s very hard to exercise away a donut, but daily exercise causes your metabolism to pickup and you burn more calories for the rest of the day. Additionally, the more muscle you have the more your body will burn calories, so for weight loss it’s best to start with strength training (and not bullshit “toning” exercises) and then move into cardio.


I agree with a part of what you say, e.g. that exercise is almost useless for weight loss.

I know these theories about the number of fat cells and about their slow replacement, etc. Nevertheless, they do not match my experience.

I have been obese during about 15 years. Then I began to measure precisely the quantities of food that I eat and after almost a year I reduced my weight to only two thirds from that of the previous year. Since then, another 15 years have passed, during which I controlled easily my weight, also by eating most of the time only carefully measured quantities of food.

During my weight loss, I was concerned about possible problems, precisely because I had also heard these theories about the fat cells that you have mentioned.

However, I have not seen any evidence for them. Before losing weight, climbing stairs was difficult, it felt like carrying a huge backpack, and I could not even see my lower body due to my belly.

After losing weight, not only all physical activities became easy, but even if there was a very large reduction in waist circumference, so initially the skin remained rather loose, after not a long time it adjusted, so no signs of the former size remained.

There were no problems whatsoever caused by the weight loss, but I had to retain forever the habit of eating according to a plan, because any day when I eat outside the plan, I immediately gain weight.

If you do not eat enough food to keep alive all your cells, some cells must die (after you have already consumed most of the internal energy supplies stored in fat). It is very unlikely that your internal regulation mechanisms will not ensure that the unused fat cells will die before cells that are in active use, e.g. muscle cells. So that theory about the constancy of the fat cell number can be true only while you are still eating some excess food or while you have not lost most of the fat reserves yet.


> Exercise is practically useless for weight loss. The body demands a fixed number of calories (up until you're doing something at the level of extreme training) and shunts the available calories between systems. Exercise has lots of benefits. Weight loss just isn't one of them.

This is sort of true but also sort of not. The body doesn't require a fixed amount of calories exactly, a specific body composition does. If you put on muscle the amount of calories the body demands goes up.


Some people do change. Point in case would be grandparent(?) stating that they changed to a low carb diet that fixed their issue.


That's why you give them a continuous glucose monitor.


As I said in another comment, a CGM for Type 2 is not shown to improve outcomes.


One of my scariest adulthood realizations is that doctors are like everybody else; fallible. And that being certified means you're good at studying, but doesn't always mean you're good at what you've studied.

Not trying to discredit medical professionals or the amount of work they put in. I'm sure the majority are intelligent, conscientious and good at their jobs.


> Not trying to discredit medical professionals... I'm sure the majority are ... good at their jobs

I'm sure half of them are below average


Below average compared to the patient? The problem is that it's true way too often.


That’s not very informative without knowing what the average is.


I have encountered a large number of excellent medical professionals, to whom I am greatly indebted for how they helped members of my family or myself.

Unfortunately I have also encountered an about equal number of medical professionals who have been grossly incompetent.

What I consider to have been by far the greatest mistake that I have made in my life, a mistake which had irremediable consequences, was to have excessive faith in the competence of some well-paid medical professionals.

Both my parents had the bad luck of being misdiagnosed the first time when they had some medical problems (for completely unrelated causes). In both cases the correct diagnostic was discovered by other medical doctors, but only after many months, when their conditions had become much worse.

Because of the delayed diagnostics, both their lives were shortened by maybe 4 to 5 years.

After the correct diagnostics, I have read the appropriate medical textbooks and I have discovered that in both cases my parents had presented the typical ensemble of symptoms described in the textbooks, they were not some weird cases, easily misdiagnosed.

For the correct diagnostics, the first doctors should have recognized the textbook symptoms and they should have sent them to the appropriate investigations that were necessary to confirm their maladies.

Instead of that, they have chosen the lazy way of saying that they do not need any further investigations because old people complain all the time for various minor problems and they have prescribed them some useless treatments.

If I would have been more skeptical about medical fallibility, I should have sought a second opinion since the beginning, but unfortunately I did not.


True, the field is vast. But I expect that a doctor should know the basics of a common condition. If they aren't counseling diabetics about carbs... wtf is going on? It would be different if it were a rare or complex topic, but even then the Epic system that most places use have standard printouts with information for patients.


It might be much like a dentist lecturing you on brushing your teeth. You’re in there because you don’t. The dentist might resent this, stuck with disgusting idiot after disgusting idiot in their mind. Alan watts says the dentist should make peace with it. Maybe you know you’re meant to brush your teeth but you don’t remember to, or a tooth fell out after brushing once and you thought it caused it etc. Some people avoid the dentist completely because of being ashamed of that lecture/disappointment. Then there’s the seeming popular “victim blaming is a hate crime” angle of doing anything more than prescribing something. Anecdotally, the super rare, in tales: old man doctor, who calls you a dumbass and tells you how it is straight is a treasured item. Various comedians have bits as such. Much like a professor who sees right through your self deceptions and justifications. They want their delusions shattered. To other people though the insolence and condescension that they perceive from that same person is seen as trash, doctors and professors should of course empathise with me instead of putting me down kind of thing. They don’t want their delusions handled too roughly. Trash or treasure. It’s not an even field though because if you did the “wrong” thing, the former doesn’t get the most useful help to them but the latter may try and bring down professional consequences upon thee. Which is probably why the mystical “no heck’s given” doctor is always old/bitter in the stories.


I don't have a source since I read it in a magazine at a doctors office 10 years ago, but I recall an article about how recommending diet and exercise had no meaningful increase in patients actually doing those things in a study. Combined with some patients being offended by the suggestion, the article made the case to no longer make the recommendation because it didn't work anyway!


Of course they start with diet/exercise - but ask yourself how many patients you think take that advice… high blood sugar is a really serious problem and the unfortunate reality is that people are very resistant to lifestyle changes — so the least harm is often to medicate.


Literally, the root(?) commenter said diet was not discussed. They had to find out about a low carb diet on their own, and it worked.


Sure, but that's almost certainly an exaggeration where OP gets to cosplay as the 'hero' in their story -- every single treatment protocol in every single medical setting for diabetes starts with a low-carb diet and exercise.

Literally the top of the 'treatment' section on WebMD:

> Managing type 2 diabetes includes a mix of lifestyle changes and medication. Lifestyle changes: You may be able to reach your target blood sugar levels with diet and exercise alone.

And the section on preventing type 2:

> Adopting a healthy lifestyle can help you lower your risk of diabetes.

> Lose weight. Dropping just 7% to 10% of your weight can cut your risk of type 2 diabetes in half.

> Get active. Thirty minutes of brisk walking a day will cut your risk by almost a third.

> Eat right. Avoid highly processed carbs, sugary drinks, and trans and saturated fats. Limit red and processed meats.

https://www.webmd.com/diabetes/type-2-diabetes


It was not an exaggeration. I was morbidly obese at the time, and the doctor almost completely ignored that condition for the roughly five years that I saw him. He did once recommend that I always eat a salad at the start of dinner. That was it.

When he saw that I was losing weight and that my A1C was heading downward, he asked what I was doing. I told him about the carb restriction. He looked down, smiled, shook his head, and said nothing. That was the end of it.


Try and Spend some time on any forum related to chronic illness. Tons of doctors who don’t keep up with even basic research / guidelines on their own speciality.


High blood sugar levels are doing damage right now.

Nothing wrong with starting on a therapy while trying to institute a diet and exercise change. The doctor would be negligent if they said "let's try diet and exercise", then after 6 months of damage say "nope, that didn't work, let's try metformin".


Yeah, I sort of mentioned that in one of the other comments. Even when they start the meds, they should be trying to fix the underlying cause like dietary issues. Hopefully it would help make the medication more effective.

It's something else to not even counsel a diabetic about carbs.


You will be hard pressed to find a doctor that talks nutrition.

It took me four years to force my doctor to test my serum zinc levels. When she did they found I was deficient. She did not know what to do, nor did it even seem to impact or shock her.

Zinc sulphate gave my life back to me. (Lupus, mood disorder) You would think that my doctor would share this with everyone. But no.


Interesting. A family member was having memory issues and the doctors were very supportive of our idea to look at the possibility of testing blood levels and taking supplements or changing diet based on the findings.


Medical care is not distributed evenly in the U.S.

I think my issue was I was already disabled and on Medicare diagnosed with Bipolar disorder which is caused by my immune disregulation, probably Lupus.

https://apm.amegroups.com/article/view/60122/html

Anyway, it is difficult for the doctors to get medicare to cover these tests. I also insisted she perform a serum amino acid test which revealed several high amino acids including all of the branched chain amino acids. She had to make up reasons to get them to cover the tests even though I have all these issues, including poor kidney function.

There is defiantly a stigma with how they treat people with mood disorders. Any physical complaint was always treated as it it were something I was imagining. I was only luckyy that my mother and brother has Ankylosing Spondylitis because even though I still had to fight to get an MRI for my lower back pain and they found I was in the early stages of the disease as well.

She said now that she had the nutritional results she did not know what to do with them and she could not even send me to a specialist.


Ah, true, coverage can be an issue. We were willing and able to pay out of pocket for tests, if needed.

So were they hesitant to do the test at all, or was it that they didn't know how to order it for your insurance to cover it? That would be a big difference in my mind. Most doctors don't fight having blood tests done if there's at least some rationale for why to do it. They're so common and low risk.

Yeah, I have had doctors just totally dismiss things when they know nothing about them (like saying things that are unsupported and contrary to new research). I have also had doctors say they didn't know but would do some research (good sign, but less common).


She was hesitant because of my mood disorder diagnosis. She frankly admitted that. What I feel changed her mind is that I asked here what caused my mood disorder. She said she did not know. So I asked why she is not doing everything to help me find out.

But all this too extensive logging, research, and persuasion on my part.

To emphasize the issue I have had with doctors on medicare; I had IBS-D, a flare up so bad, for over a month. I went to a doctor, they took one fecal test which showed nothing. They did not reply to my continuing issue so I went back to them. The doctor said exactly this; "What do you want me to do about it?" I lost it. Yelled at him so loudly others came into the office. They never sent me to a gastro doc. I need up curing it on my own by using my understanding of my genetics and diet changes.


Assumption makes an ass, but I think he means first line treatment when it comes to medicine. I’m sure that both nurse & doctor wholly recommended lifestyle changes.


If you read the comment they said there was mention of losing weight but nothing about a low carb diet. Carbs are something any diabetic person should be counseled on, even if being placed on a medication.


>Find a new doctor.

why would someone need to go to a doctor to tell them that


If they are in that situation it stands to reason they might not have that knowledge. It seems the grandparent(?) is an example of that when it came to low carb diet.


Virta Research has peer reviewed research supporting this approach. They have been successful with getting many type-2 diabetes patients into remission primarily using low carb diets. If you're insulin resistant then the first step has to be eliminating basically all sugar.

https://www.virtahealth.com/resource-type/research


> Metformin is the first resort in diabetes treatment

First resort for T2 diabetes. T1 diabetics have to go on insulin immediately, there's no other option.


They have yet to see the other option for type 1 dates, but they are getting close.

https://www.aacc.org/science-and-research/scientific-shorts/...

https://link.springer.com/article/10.1186/s40199-015-0127-4

https://www.cambridge.org/core/journals/nutrition-research-r...

https://www.e-cep.org/journal/view.php?number=20125555368

I believe that Type 1, being classified and "autoimmune disease", can be reversed.


IMO relative percents should really not be used when trying to consider the impact of things because it gives you no clue about it. If the rate of something is 1 in 1 million then a 40% increase means your odds of having an issue go from negligible to negligible, but a 40% increase makes it sound much scarier. I think the reason for that is that a 40% increase subconsciously tickles our "40% of" intuition, even when we consciously understand that's not what it means.

That said in this case the 40% is genuinely scary, because it's a jump from 3.3% with birth defects to 5.2%, or in other words nearly 1 in 50 babies (1.9% of births) standing to be affected by this issue. Although just quickly skimming their numbers, the sample size is unclear to me. That jump was driven by only 13 birth defects among those taking the drug, based on what the article says is a sample of 1.1 million births.


Unfortunately the vast vast majority of people won't commit to a big lifestyle change like that in the first place, and a big majority of the people that due end up not following through. So most doctors won't bother suggesting it as a legitimate option because for most people it kind of isn't.


"So most doctors won't bother suggesting it as a legitimate option because for most people it kind of isn't."

This is just flat wrong and borders on malpractice for deceptive counseling. Even if a patient is unlikely to accept an option, they still need to be presented with the best/standard options. This is also the lowest risk and highest gain option with a proven track record. I would stop seeing a doctor who is not presenting all the standard options and would rather just have me pop pills.


So first off I never said I agreed with those doctors' reasoning and love that I'm getting downvoted despite it being a reply to a comment literally exemplifying what I'm talking about, and several other people are commenting things among similar lines.

It happens and I don't agree with it, but I totally understand why they do it. General practitioners and family practice doctors see dozens to hundreds of patients every week, and they get maybe half an hour with each patient and they know that out of the 300 people they see, maybe two or three of them will actually commit to the lifestyle changes they need to control their condition. So instead they optimize for what's going to work for the majority of their patients and skip straight to medication.


At some point in every doctor's career, there is a point where they decide to let us eat cake.


Doctors aren't supposed to decide much of anything for us, especially lifestyle choices. But they should at least present the appropriate options once.


> So most doctors won't bother suggesting it

If you put it as:

- exercise to live longer and healthier, to have a better life in literally every aspect

vs

- take X and Y pills until you die, it'll cost you up to xxx thousand dollars over your lifespan, will cause serious side effects and will not solve the root cause

I bet people would be at least consider the first option.

The problem is that the pharma industry works the same way as the food industry, their business model is to sell you things you need on a regular schedule and the for as long as possible.


> made no mention of what actually resolved my diabetes, a low carb diet. I hope that becomes the first resort

Doctors know that if they compared "taking Metformin" to "eating a low-carb diet," the low-carb diet would win hands down. But that's not the comparison that's relevant for them, because it's not a choice they get to make. They have to choose between "advising someone to take Metformin" and "advising someone to eat a low-carb diet." The results of the latter are negligible on average.


It isn't a choice.

It's quite practical to do both.


You're right in a limited way, but the way it was put to me, doctors don't see it as possible to effectively pitch both approaches in the same session with a patient. You probably won't see them a second time, so you have to lead with the pills and concentrate on the pills. It's your one shot to get them on a medication that will extend and improve their life if there is one for their condition, like metformin or a statin, so even though you mention dietary changes, you're not making a realistic effort at convincing them to try it, because that would involve a lot more time and discussion and coaching about what a healthy diet is. You focus on the medication because getting them to take medication daily is a realistic goal that will succeed with a decent percentage of patients.

Also, if you stress the dietary approach too much, a lot of patients will eventually ask, "If I make the dietary changes, is it possible I can avoid taking medication?" and you have to say "yes" and now the odds are you'll never see them again and they won't get either. So you mention the dietary changes, just so they know it's effective if they're inclined to go that route, but you focus on getting them to take medication.

It's definitely a sad compromise aimed at the average patient, and doctors hate it.


The Diabetes Code is a great book about reversing diabetes through dietary intervention. The author discusses exactly what you're saying here: surprisingly few doctors know how effective a low-carb diet is at treating and curing type 2 diabetes.


Agree. If you have diabetes I highly recommend making Jason Fung your doctor by reading his books, watching his videos, and taking his advice.


Are you able to go back to a regular diet or is this more about managing diabetes and keep doing it long term?


If by "regular diet" you mean a typical American diet including large portions of foods with high glycemic index then no. If you want to keep the disease in remission then it has to be a permanent lifestyle change.


> In the United States, prescriptions to 18- to 49-year-olds with type 2 diabetes grew from fewer than 2200 in 2000 to 768,000 in 2015.

What the hell… that has to be a mistake? What is going on? Can poor lifestyle really cause this massive increase in young people with diabetes??


It's an increase in a particular treatment for a disease, which is only a contingent proxy for the disease itself. A change on that scale could plausibly be explained by a change in the standard approach to treatment or diagnostic criteria. Wouldn't be surprised if insurance played a role somehow.


Treatment guidelines change all the time. Last time I checked metformin is now the the 1st drug therapy for type II diabetes and even "pre-diabetes".

It's basically "oh, your blood sugar might be an issue, let's start with metformin" where in the past it was "lets try a bunch of others things and just watch your levels for a bit"


This. I have a few family members who struggle with blood sugar levels. Their doctors are quick to turn to pills instead of lifestyle/diet and monitoring. Likely because lifestyle/diet changes are hard and not very successful. Most of them have managed to adapt and deal without the pills, but it does take regular monitoring and they're all still borderline (pre-diabetic, I think is the term).


Despite being used in Europe since the '50s, Metformin wasn't introduced in the US until 1995.


Ah right, that is surprisingly late, and would likely explain the numbers.


that doesn't say that diagnoses increased that much, just that this particular drug has become a much more popular way to treat it.


It’s so interesting that type 2 diabetes is curable with diet.

Type 1 is incurable.

My point is that the psychology of eating is so strong that people would rather take a drug that pass on birth defects to the future than change eating habits.

And I’m a person coming from struggling with just those habits. I think if someone could come up with a treatment to adjust mindsets - it would change healthcare forever and end the need for drugs like Metaform.


Don't forget a lot of food is engineered and marketed to create those habits in the first place. In the end it falls on the person but I can see it being extremely difficult if you're growing up in the wrong environment with a shitty diet and a particular brain.


Type 2 diabetes is not curable with diet. Some (but not all) cases of type 2 can be _prevented_ by proper diet (i.e. avoiding obesity). There is no known diet that cures any type of existing diabetes.


Type-2 diabetes can't be cured, but it can be put into permanent remission with diet for many patients. Virta Health has peer-reviewed research supporting this approach.

https://www.virtahealth.com/resource-type/research


> Type-2 diabetes can't be cured, but it can be put into permanent remission

This is such a weird thing to say. If it never comes back you cured it. It's like saying a cold or cancer cannot be cured, but it can be put into permanent remission.

It likely takes the agency away from people and apologizes for the failures of the medical industry.


I think your might not understand the medical terminology. There is a distinct difference between curing an acute infectious disease versus putting a chronic condition into remission. In the majority of cases, cancer can't be cured either; it usually isn't possible to eliminate 100% of malignant cells so if the patient survives long enough then the same cancer will eventually return. While a low-carb diet can often put type-2 diabetes into remission, if the intervention is removed then the condition will return.

This is not a failure of the medical industry and no apology is needed.


What I am saying the medical terminology is the problem.

> if the intervention is removed then the condition will return.

If the interventions preventing covid are removed the condition will return. Do you get that?

On cancer; we all have malignant cells, all the time. everyone right now has cancer cells in their body.

https://news.cancerresearchuk.org/2018/04/18/science-surgery...

Not smoking is an intervention against getting "too much" cancer.

> While a low-carb diet can often put type-2 diabetes into remission, if the intervention is removed then the condition will return

Low carb diets do not cure diabetes. They treats diabetes. The cure to diabetes (type 2) is not engaging in a lifestyle that causes diabetes, which probably results from causing a zinc deficiency.

You can avoid diabetes like you can avoid COVID.


I don't understand your point. Most people including me don't engage in daily ongoing interventions to avoid COVID-19. Everyone can expect to get infected with SARS-CoV-2 (probably multiple times) but only a subset of those infections will cause clinically significant COVID-19 symptoms.

https://www.medpagetoday.com/opinion/vinay-prasad/94646

Good lifestyle choices can usually prevent type-2 diabetes, but prevention is different from curing an existing condition. That's just medical reality and changing terminology wouldn't impact that.

The zinc deficiency hypothesis is interesting but remains unproven, and can't possibly explain large increases in diabetes. This would be a good area for further research.


> The zinc deficiency hypothesis is interesting but remains unproven

Just be clear, if the hypothesis was proven it would not be a hypothesis anymore, but would be a theory.

> can't possibly explain large increases in diabetes

You cannot say it is not possible when there is so much evidence that it is possible. Tell me how many people you know diagnosed with diabetes have their doctor get their serum and urinary zinc tested?

https://www.sciencedirect.com/science/article/abs/pii/000293...

"Twenty-five percent of these patients had depressed serum zinc concentrations, and all demonstrated hyperzincurla."

100% had high urinary zinc. 100%. This point to a functional deficiency of zinc. 25% had a true deficiency. It might be that the levels of zinc that we have deemed adequate are not adequate for all people.

and this is a great short peice: https://www.proquest.com/openview/4aaebeab5e4ac98c2d1c3ced49...

The time for research is over, it is time to include serum and urinary zinc testing part of the standard of care for physicians.

And who will pay for this research on a low cost option to reverse diabetes when so much money is to be made on new medications>

> Most people including me don't engage in daily ongoing interventions to avoid COVID-19.

Same could be said for cancer and diabetes. You are probably unknowingly intervening against disease. As far as COVID, you will note the obese are more likely to suffer worse outcomes. So for whatever reason someone watches their weight, even vanity, they are helping prevent themselves from COVID.

> prevention is different from curing an existing condition

My mother prevented her self from having the symptoms of having the symptoms of diabetes occur again by changing her diet. How is that different from curing it?

Listen, what is a disease but a collection of symptoms? If I have no symptoms, where is the disease? If I had diabetes, but was never diagnosed, and I treated myself with a diet to make it go away, would a doctor diagnose diabetes when my blood sugar was normal? Funny, it sounds like you are saying doctors causes permanent diseases?


> It likely takes the agency away from people

Everything we do around the topic of obesity is about palliative care for people's feelings. Health At Every Size, societal disdain for fat-shaming, etc. Medicating people with statins and insulin management drugs instead of directing them to put down the fucking fork and move occasionally.

Hundreds of thousands of Americans eat themselves to death every year. It is far and away the leading cause of early death, with COVID years additionally highlighting the fact that the VAST majority of deaths under the age of 60 were among the cohort who think donuts and beer constitute an appropriate dinner.

But instead of trying to save these people's lives, we are trying to spare their precious feelings, with the insane irony of the situation being that obesity itself is a STRONG predictor of depression. As if telling people that chugging a case of Pepsi per day is totally fine because you're beautiful as you are is going to save their mental health from the vagaries of the practically inevitable Zoloft drip they'll need to be on to keep the 9mm out of their mouth.

> and apologizes for the failures of the medical industry.

Our culture around obesity is absolutely batshit insane. And yes, medicalizing the symptoms rather than public hangings for food industry executives and widespread re-adoption of fat shaming is a HUGE factor in this.

edit: Sorry to be somewhat animated about this topic, but I am a former fatass who was, like many many Americans, victimized by the food and advertising industries, and eventually came to hate myself enough to strip off the fat and keep it off for well over a decade. And my "negative self talk" has led to being a MUCH happier person. It drives me INSANE that this culture is killing so many of us and wrecking our mental health, but we choose to make it worse.


If I could share with you here the chart of my cholesterol reduction I achieved after drastically changing my omega 6 to omega 3 ratio in my diet... But also the changes to my mood, my Lupus, my kidney function, etc...

And yes, obesity, fat cells are immune cells and they are inflammatory under a poor diet. And this ignorance of the nature of obesity is even more important with SARS2 running around rampant.

I will only say that obesity combined with nutrient deficiency is more important than obesity alone.

https://www.nature.com/articles/d42859-021-00051-w In a healthy body, adipose tissue plays a positive role, serving as reservoir of energy in times of food scarcity. Fat tissue is also full of immune system cells. And in lean, healthy individuals, it secretes factors that are anti-inflammatory and protective.

If, however, the fat tissue becomes unhealthy, as often happens in people with obesity, it can become dysfunctional and secrete hormones and other chemical signals that promote chronic low-grade inflammation.


The thing is, Type 2 is not even a disease. Its just an imbalance of glucose. So there is really nothing to cure, its just about bringing back your blood glucose levels in balance so that the liver and pancreas can begin to function correctly again.

Of course there could be irreversible damage to those organs and that would be really bad (Several relatives who died of this).

But you are partly right. There can be remission and back to normal with lifestyle changes and Type 2. Substantial studies and clinical evidence shows this.


Type-2 diabetes is characterized more by insulin resistance than by an imbalance of glucose. And glucose isn't really something you "balance" in relation to another substance anyway. In order to be metabolically healthy you have to keep glucose levels in the appropriate range, and that will generally prevent the onset of insulin resistance.


Hmmm. My mother was able to stop taking insulin for her type 2 by changing her diet after doctors told her she would need insulin for the rest of her life. Are you saying it was all in her head?

I have no idea why people keep saying this.


Please remember that this changes with age, diet and activity levels. If you can fine tune the diet and monitor glucose levels using CGM/AGM's to precise levels over each and every minute throughout the day/week/years., then it is pretty well possible to get a lot more mileage with the diet alone. Glucose spikes are easy to miss unless monitored this way and could easily be more damaging.


Curable in all cases or just early after a type II diagnosis? I think once you lose it that's it.

The pancreas insulin output is low that's type II diabetes. From my understanding the pancreas, an organ, is damaged and can't regenerate like all organs except the liver (sort of). Like a rotten tooth can't regrow an organ once damaged there's no repair. Pancreatitis is what I'd see as a reversible situation since it's inflammation of the pancreas but not damaged yet.


I both agree and disagree with you. Asking the average human to resist the efforts of multi-billion dollar companies using powerful psychological science to get people to buy their junk food seems a lot to ask.

Coca-cola successfully got entire nations to change from their traditional drinks to soda pop using propaganda.

I think we need to deal with the American Oligarchs/Megacorps in a very serious manner and very soon.


I only knew Metformin by name from HNers using it as an anti-aging wonder drug over the years: https://hn.algolia.com/?dateRange=all&page=0&prefix=false&qu...


It is also beginning to be prescribed by many of the subscription medication/doctor businesses that are springing up, powered by VC cash and looking to build strong forward flowing subscription businesses. Their model is:

- find areas that aren’t medically serious (speaking relatively, and in relation to life threatening - erectile dysfunction and male pattern baldness)

- run people through online questionnaires

- get an online subscription runner stamped by a doc on their payroll

- send out generic medications that they get cheap, package them nicely, and make bank on markup

- catch them on the next condition they roll along to

The last year I’ve seen a lot of them shifting into metformin (after finasteride and viagra/cialis) for weight loss


Do you see this as a bad thing? As someone who doesn't have any insurance, I'm extremely grateful for these. I don't want to have to go through the current medical racket where unless you pay a doc $300 you won't be allowed to purchase the medication you want. And then of course there's the follow up appointments, a "med check" where they can bill you $150 every 90 to 180 days just to hear you say, "yep, things are fine."


Good or bad, it's the logical conclusion given the free market, healthcare, and the Internet. The real problem is the "as someone without insurance" bit, the bigger question is what is best for society?


In responding to your example first - to start with, I live and practice in a country where it isn't a choice between healthcare and food on the table. Beyond that, I believe that it is a basic human right to have free healthcare. The next bit is a bit more complex. I don't think it is right or sensible to advertise medications to people directly. The US is almost alone amongst industrialised/western countries in having prescription medications being directly advertised to consumers. From my time in the US as a medical student, I saw directly how that changed the patient-doctor relationship, and I don't believe in a positive way. So - I don't think it's right that there's a medical racket that fleeces you to see a doctor, but I don't think it's right that you decide your prescription anyway. On the other hand, it should (speaking of an idealised utopian world) be easy to get refills of medications that have been appropriately prescribed.

So here is where it gets interesting with the VC-backed Subscription healthcare model. I did a touch of consulting for one starting in Australia (well, it would probably be a stretch to call it consulting but I sat down with the founders as they were running through their spin-up process).

My concerns are that you can't just prescribe anything to anyone, and for the vast majority of prescription medications there are often side-effects that need to be monitored (some of which can be serious), as well as inappropriate prescribing. The 2 examples the company I was talking to were Finasteride as well as Viagra. Seperating these two out, my concerns with Erectile Dysfunction are that it could be inappropriately funnelling everyone into prescription treatment, when there is in a reasonable percentage of cases other psychological issues that are impinging on erectile function, and whilst it might be all well and good to get viagra to get to the end result, it is also missing the broader holistic picture of aiming to achieve better health.

For finasteride, there are a reasonable percentage of people who experience quite unwanted side-effects, from gynaecomastia to erectile dysfunction. Since the target audience is young men, these effects are often more psychologically concerning than the cosmetic issue they were trying to solve with a serious prescription medication and I was concerned about follow-up, referral and support in these instances.

I was able to be reassured by them that they had adequate safeguards in place and good clinical governance oversight to achieve good all round care and then we split ways. I have no idea if they have or are maintaining those protections; additionally I have recently heard they have been pulled infront of the regulators here in Australia for cutting a few corners so my suspicion is that the money and growth hacking has gotten the better of their product development.

Ultimately it is going to be an interesting bounce between both the regulation and the inevitable clinical disasters that will pop up. There's no doubt there is room for innovation in the space, and I feel that there is certainly a way to do it safely - ensure that, for certain conditions, you can answer a few questions, get your medication, and still have safe follow-up, and do this in a innovative way that reduces overall demands on a healthcare professional for a full sit-down (ie wrap up a bunch of the bullshit in algorithms and decision trees and take care of a lot of the back room stuff).

But after 9 years as a doctor and a health-tech founder, I am also convinced that there are a number of elements of health that just do not scale, at least not with anything like the technology we currently have (ie well developed expert systems - I am also fairly fundamentally convinced that the use of AI for diagnosis and the black-box internals is going to cause issues due to uncertainty over where the fuzzy edge lies)

So - TLDR: do I see VC driven subscription prescription as a bad thing? No, but also potentially yes


For finasteride I agree, as it decreases DHT, which is not exactly a useless hormone. It shouldn't be prescribed to anyone, as you have said. I don't necessarily agree for the Viagra/Cialis. Generally cialis is safer than viagra, with less side effects. But their mechanism of action is quite simple and doesn't cascade to a lot of other body functions, inhibition of PDE5. Viagra also inhibits PDE6 more, thats why you get a blue-ish tint to your vision, and PDE1, which is more dangerous and can cause tachycardia. Cialis inhibits PDE11 more, which affects skeletal muscles and the prostate. That's why Cialis is sometimes prescribed for BPH, and why bodybuilders take cialis as a supplement (drive more blood into the skeletal muscles, decrease blood pressure).

Getting to your point of "other psychological issues" that can result in ED. Cialis and Viagra are there for one specific case of ED, which isn't caused psychologically. If you can get an erection in the morning, while you're sleeping, PDE5 inhibitors won't help.

Of course, the less drugs you take, the better, easier on your kidneys and liver. No drugs are without side effects, PDE5 inhibitors have them, but they are mild and can be diagnosed easily. Of course, dose is important, and health issue history needs to be taken into consideration.


I agree that viagra/cialis are generally safe for the majority of people. I guess the question with regard to the subscription prescription model is what are the subset of medications that fall into the right risk profile for the model to work effectively? It's a pretty small subset without adequate safeguards!


> If you can get an erection in the morning, while you're sleeping, PDE5 inhibitors won't help.

Did you mean to say can’t?


Nope. If you can get an erection in the morning, the vasodilatation mechanism works, so Cialis/Viagra won't help. If the mechanism works, but you still cannot get an erection when you're with your partner, the problem could be psychological, say you're not attracted anymore to your partner, anxiety, stress, all stopping you from getting aroused. And you need those neurons or endotheliums to fire. Another example is drugs that are vasoconstricting, stimulants like amphetamines or cocaine, which even though create a high arousal state, they are so vasocontricting that it's hard to achieve an erection (so Cialis/Viagra helps, but it's not indicated to combine drugs that combat eachother).


Interesting, and thank you for the clarification.

I think it’s probably more of a spectrum and not a binary thing, and so you can have layers of physiological and psychological impediments, and one could also feed the other.


> it should (speaking of an idealised utopian world) be easy to get refills of medications that have been appropriately prescribed.

I must be living in Utopia then, I thought it was Norway! :-)

When I run out of my blood pressure pills I can spend a couple of minutes online to send a message to my doctor. He spends a few seconds online to renew my prescription and then I can go to any pharmacy to pick up three months of pills. For the rest of the year I just go to a pharmacy to pick up a repeat when I run out.


I have a similar set up in the UK - I hit the "request repeat prescription" button in my GP's app, they nod it through and send it to my chosen pharmacy, then a nice person from the pharmacy delivers it the next day. No shady business models required! :D


The difference is that I don't have to specify which chemist, I can go to any one and just present my ID, they can then look up the prescriptions.


I expect those guys will start pushing SGLT2 inhibitors (gliflozins) next.


I just discovered that apparently that is exactly what they’re doing, not metformin presently. And there a planned shift to GLP1s - but the injectables present some interesting administration aspects


Metformin is also pretty bad when comes to impact to testosterone levels, at least in most men. The exact mechanism that this happens is that it saps the cholesterol from your blood. This cholesterol would otherwise be used for T production by the testes.


"The researchers analyzed records from more than 1.1 million babies born in Denmark between 1997 and 2016, using the country’s comprehensive medical registries to connect data on births, paternal metformin prescriptions, and birth defects."

Did they look for any defect correlated with any drug? Because if they did, random chance alone would find something.

Anyone read the actual study?


I sought it out after seeing this link and found it to be very unimpressive. Science would do well to delete this article spruiking pretty trash science.

P-values seem to be carefully hidden (not in the tables) and as far I could tell were not passing FDR. A lot of models were displayed in various tables and very few of them even had OR CIs that didn't overlap 1.


Hopefully if they didn't apply Bonferroni correction, the study wouldn't pass peer review.


This doesn't change that Metformin is an extremely useful drug. Even people without the official indication take it because it reduces propensity for weight gain and cancer.

Maybe don't take it before trying to get pregnant. Also maybe this needs to get confirmed in larger studies and in other countries.


Any clues on the mechanism? Wouldn't this require altering the DNA of the sperm?


It's possible that the mechanism is epigenetic, albeit unlikely. The sad truth is that this is probably now present in lots of genomes, and in the absence of eugenics or genome modification to correct the fault, will add to the slow and burgeoning medicalisation of the whole population, as the end of natural selection for baseline health multiplies disorders over time.


> "...because tens of millions of people worldwide take metformin, chiefly for type 2 diabetes."

In nearly all cases, T2 is preventable. That is, unlike T1, there are things an individual can do to not reach T2.


On a micro level, most cases of T2 are preventable. On the macro level, many aren't: food deserts have higher rates of diabetes and heart disease, and the people who live in those areas are frequently "stuck" there for socioeconomic and racial reasons.

There are also subgroup susceptibilities in play: Asians and people with Hispanic backgrounds are disproportionately represented among American T2 diabetics[1]. Recent studies suggest these groups are actually underdiagnosed still, since the dominant T2 tests are less reliable on them[2].

[1]: https://www.cdc.gov/diabetes/library/socialmedia/infographic...

[2]: https://jamanetwork.com/journals/jama/fullarticle/2757817?gu...


Yes. But again...food deserts - in the country that put a man on the moon - certainly solvable. And certainly such efforts are more ethical than rolling genetic defect dice. But we're led to believe it's Big Pharma or nothing? That's an injustice to Truth.

https://www.ted.com/talks/ron_finley_a_guerrilla_gardener_in...


Thank you for the references.


This is true for probably a majority of health problems in wealthy countries.


Your point being…?


I'm 26 and have been on Metformin for almost a decade at this point and will probably be on it until I die. Thankfully though, children are not in my future.


Please get your serum zinc levels tested. I am saying this from experience and knowledge.


I'm obese and of south asian ancestry, so there's no real question as to why my insulin sensitivity is shot, but I'll add zinc to the list next time I do bloodwork.


Wait ... 86 million scrips for Metformin? Roughly 1 IN 3 people in the US?

That can't possibly be right. What am I missing?


A single patient may receive multiple prescriptions per year, so the number of patients will be lower than the number of prescriptions. According to this source the number of patients taking metformin is 17 million.

https://clincalc.com/DrugStats/Drugs/Metformin


Patients will normally get multiple scripts per year. A typical script might only provide one month's worth of medication, perhaps with 3 to 6 "repeats" before needing a new script.


The anti-aging community is also studying metformin


My hypothesis is that a functional zinc deficiency is the cause of most cases of diabetes, and by taking metformin, it will at least, not correct a zinc deficiency, and probably make it worse.

To begin I would like to share that I was born with an undecended testicle (cryptorchidism) that had to be removed surgically when I was 3. My brother was born with hypospadia. I have been studying the genetics and environmental issues around these for the last 15 years.

I carry several high risk genes for diabetes but probably the most relevant is that I carry the homozygous risk alleles for rs2466293 in SLC30A8 which is a zinc transporters gene. So I absorb zinc more slowly than most people.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428214/

"Conclusion ZnT8A detection increases T1D diagnosis rate even in mixed populations. SLC30A8 rs2466293 was associated with T1D predisposition in non-European descents."

I had my serum zinc tested and it was low. So now I need to take 240mg of Zinc Sulphate and eat a lot of oysters to keep my zinc levels up.

I was diagnosed with Lupus and now I no longer present constant symptoms.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544280/

"Ikaros family zinc finger 1(IKZF1) encodes a lymphoid-restricted zinc finger transcription factor named Ikaros that regulates lymphocyte differentiation and proliferation as well as self-tolerance. Increasing evidence indicates that IKZF1 could contribute to the pathogenesis of autoimmune diseases."

So also understand that my mother had diabetes, an immune disorder, and a mood disorder, all of them linked to zinc deficiency.

So, in studies zinc deficiency has been linked to diabetes:

https://www.mdpi.com/260782

"Zinc deficiency is a risk factor for obesity and diabetes."

And genital abnormalities: (This is just one study, but there are hundreds like it.)

https://www.karger.com/Article/Fulltext/441988

"WT1 is a transcriptional regulator with various functions including signalling in both the embryonic kidneys and gonads. Mutations in this zinc finger transcription factor are associated with Denys-Drash or Frasier syndromes, which result in a broad range of malformations including hypospadias."

So I do not think the problem is metformin. I think the problem is doctors not providing patients with diabetes a full nutritional workup and ignoring the role of nutrition in human health.




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