5 ms·

We can keep running on the macronutrient treadmill, like we've been doing for 50 years, or we can find molecular evidence that jives with genetics. Check out t

We can keep running on the macronutrient treadmill, like we've been doing for 50 years, or we can find molecular evidence that jives with genetics. Check out this study, where they fed mice water, water+fructose, or water+fructose+BPA. At the end of the experiment, only the BPA containing solutions had elevated liver fat https://www.sciencedirect.com/science/article/pii/S0300483X12003617?via%3Dihub#fig0015 https://www.sciencedirect.com/science/article/pii/S0300483X1...

timr 8y ago
"We can keep running on the macronutrient treadmill, like we've been doing for 50 years, or we can find molecular evidence that jives with genetics." Yes, let's ignore 50+ years of established science that is parsimonious with everything we know about the molecular biology of insulin resistance, and dump it in favor of a fringe theory, based on a single paper about a mouse study, where there's not even a plausible explanatory mechanism. Folks, stop downvoting simply because someone provides a link. The parent is spouting pseudo-scientific nonsense.
- subcosmos 8y ago
  There are literally hundreds of papers on BPA and its links with diabetes. The only difference now is that we have the molecular culprit behind the trend. https://www.ucsusa.org/our-work/center-science-and-democracy/promoting-scientific-integrity/bisphenol-a.html https://www.ucsusa.org/our-work/center-science-and-democracy...
  - timr 8y ago
    "There are literally hundreds of papers on BPA and its links with diabetes." There are literally not. The review you've linked to cites a handful of papers involving minor effects observed in mouse studies. Moreover, the paper you originally cited proves nothing even approximating a mechanism. I'm not suggesting anything about the safety of BPA, but it's utter nonsense to claim that it is a more plausible explanation for the diabetes epidemic than sugar consumption. A few mouse studies do not change 50+ years of established science on the relationship between sugar and diabetes.
    - subcosmos 8y ago
      But is it really? Elevated blood glucose, as in Type 2 Diabetes, has LONG been known to be primarily driven by excessive production of glucose by the liver due to liver insulin resistance. In fact, the way that the drug metformin improves diabetes is by shutting that pathway down. http://diabetes.diabetesjournals.org/content/50/8/1807.short http://diabetes.diabetesjournals.org/content/50/8/1807.short Thats not dietary, thats the hormone insulin being ignored by the liver. This is further complicated by the fact that peripheral tissues, like muscle, are themselves insulin resistant. The TCF7L2 pathway has been shown to be down-regulated in all of these tissues in diabetics.
      - timr 8y ago
        TCF7L2 is a transcription factor. It is involved in many pathways in human biology, of which diabetes is one. Observing that it is downregulated in diabetics provides no evidence for or against any theories concerning BPA.
        subcosmos 8y ago
        It's also the most statistically significant gene, in the whole dang genome, associated with Type 2 Diabetes. And out of a compound library of 20k chemicals, BPA had the top effect on it. Seems significant to me Also worth noting that BPA has been shown to specifically effect the occupancy of TCF7L2 at transcription factor binding sites in Chip-Seq experiments. http://press.endocrine.org/doi/abs/10.1210/endo-meetings.2015.ED.1.FRI-299 http://press.endocrine.org/doi/abs/10.1210/endo-meetings.201... Lastly, before calling someone else's claims psuedoscientific, you may want to do some homework and check your previous biases. We could certainly use someone with your skills to help model BPAs interaction with the Androgen receptor. Might just save millions of lives....
        deleted 8y ago
        [deleted]
        deleted 8y ago
        [deleted]
  - deleted 8y ago
    [deleted]
- joneston 8y ago
  It’s interesting to notice that what we have here is one industry being villified, and then possibly passing the buck, only to point at another industry as possibly to blame. It’s pretty interesting to think about how easy it is to muddy the waters like this. Something starts off as a direct medical concern, but then sprals into a secondary contamination problem. Both are bad. Plastics are bad for a variety of reasons, and sugars definitely contribute to obesity. But, horomonal factors really cannot be shrugged at. There’s some serious distortion affecting people for the past 20 or more years, and it’s nothing normal. Is it birth control pills being dumped down the drain, and recirculating into the drinking water? Is it ibuprofen messing with people who have over dosed on their analgesic NSAIDs? One thing’s for sure modern civilization has inteoduced many complications, all simultaneously, and that is likely the biggest mistake of all. Also, I’m not sure you’ve used the word “parsimonious” correctly? Are you trying to say they’ve been “very careful” or “strict”? I think it’d be more appropriate to replace it with “well aligned” or “concomitant” if a vocabulary word should be preferred.
cat199 8y ago
and yet, most everything came in glass until about 25 years ago..
- subcosmos 8y ago
  Thats about when things got really bad http://www.diabetesandenvironment.org/home/incidence http://www.diabetesandenvironment.org/home/incidence
baxtr 8y ago
But what about other countries than the US? Japan, Europe? They use lots of plastic too. I haven’t heard of a diabetes epidemic there yet though.
- harshreality 8y ago
  Trends in prevalence of diabetes in Asian countries, doi: 10.4239/wjd.v3.i6.110 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3382707/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3382707/ Diabetes in Asia and the Pacific: Implications for the Global Epidemic, https://doi.org/10.2337/dc15-1536 https://doi.org/10.2337/dc15-1536 ( http://care.diabetesjournals.org/content/39/3/472 http://care.diabetesjournals.org/content/39/3/472 ) Someone needs to do a dietary and sociological study of Vietnam, because it looks like they've been least affected by the diabetes epidemic, up until the early 2010s at least.
allover 8y ago
> We can keep running on the macronutrient treadmill, People reach obesity from overeating, no matter what their choice of calorie-dense foods, but it's typically sugar or fats, and sugar is the cheapest/most available. Being obese is clearly a causative factor towards T2B [1]. How are these obvious truths 'running on a treadmill'? [1] https://www.diabetes.co.uk/diabetes-and-obesity.html https://www.diabetes.co.uk/diabetes-and-obesity.html
- subcosmos 8y ago
  The treadmill is the endless debate over whether or not fats vs carbs are more obesogenic. This debate continues ad-nauseum and distracts from more nuanced explanations. High fat consumption raises inflammatory profiles through mechanisms that are poorly understood. Carbohydrates seem to cause similar inflammation, but this is largely do to advanced gylcation end-products created from fructose, specifically. Overeating is not interesting. The reason people do overeat is very interesting, and if you hit the literature you find that this is largely driven by damage to the hypothalamus by environmental exposure.
  - allover 8y ago
    > Overeating is not interesting. The reason people do overeat is very interesting What if it's not. What if people just overeat because life is boring, and food tastes good, and we all have differing levels of willpower & education on nutrition? > if you hit the literature you find that this is largely driven by damage to the hypothalamus by environmental exposure. Sounds like nonsense, can you elaborate?
    - subcosmos 8y ago
      There is a specific part of the hypothalamus called the arcuate nucleus. It lacks a blood brain barrier, because the neurons there have a special function to sense blood-born hormones like insulin and leptin. When sensed, the brain interprets this as a "full tank of gas" and suppresses appetite while increasing metabolism. Since theres no blood brain barrier here, these neurons get damaged easily due to things in the blood. When that happens, they don't see leptin anymore, and obesity develops. Fructose and high fat diets have both been shown to cause inflammation here. (hypothalamic gliosis) heres a random selection of many papers http://diabetes.diabetesjournals.org/content/65/3/551.figures-only http://diabetes.diabetesjournals.org/content/65/3/551.figure... We also know that certain viruses show up in obese people (adenovirus36). As the field develops, I would not be surprised if labs demonstrate both viral infection of the hypothalamic ARC and damage by endocrine disruptors there.
harshreality 8y ago
There's a notable lack of dose-response relationship in most of the collected data, and n=12 for each group doesn't inspire confidence even if in some cases the p-value suggests significance. There are already a lot of measurements taken and included in the table where differences were not that large. Were other measurements taken and not reported in the table? Has anyone attempted to reproduce this? Most importantly, though, that study doesn't indicate whether the effects, if they end up being reproducible, are caused by BPA alone, or the combination of BPA+sugar. It's well known in other scenarios that toxins, when combined with inflammatory foods like sugar, are far worse than they are in the absence of inflammatory foods. I'm fairly convinced that BPA is slightly bad, I just think alternative plastics may turn out to have other compounds that are also bad, given horrible diets, and the best solution may be to fix the diet, rather than try to eliminate all toxins related to modern plastics (and the same argument may apply to pesticides). Other toxins from modern living will undoubtedly pop up, and if they all cause different and problematic diseases in combination with bad diets, but not so much in combination with good diets, how much energy do we really need to put into studying and eliminating toxins in a giant game of whack-a-mole?
- subcosmos 8y ago
  I havent yet seen other studies comparing BPA with carb ingestion, but I hope they are done. Its important to root out the effect since BPA lines every single soda-pop can. Aside from that though, there are many other mouse studies. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2605.2007.00832.x https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2605.... As well as studies showing that BPA in human urine is associated with insulin resistance and obesity https://academic.oup.com/jcem/article/97/2/E223/2836542 https://academic.oup.com/jcem/article/97/2/E223/2836542
- subcosmos 8y ago
  Note that this study specifically showed that fructose alone did not increase liver fat content unless BPA was present in the solution. See figure 3, but yes, I agree that it would have been nice if they tried BPA without the fructose. This really does make sense. When that pathway is suppressed, the adipogenic program is activated, which turns on the SREBP-1 pathway and stores lipid droplets. Without this pathway activated, fructose is processed and exported out of the liver, preventing harm to the liver. I would argue that we should really test every new manmade chemical against a library of our proteins before we synthesize anything new and introduce millions of tons of it to the world. Not doing so can have disasterous consequences. Samuel Epstein, before he died, documented a great many examples of horror stories we just barely averted. https://www.youtube.com/watch?v=rQoc6WP3QJo https://www.youtube.com/watch?v=rQoc6WP3QJo

timr 8y ago

"We can keep running on the macronutrient treadmill, like we've been doing for 50 years, or we can find molecular evidence that jives with genetics." Yes, let's ignore 50+ years of established science that is parsimonious with everything we know about the molecular biology of insulin resistance, and dump it in favor of a fringe theory, based on a single paper about a mouse study, where there's not even a plausible explanatory mechanism. Folks, stop downvoting simply because someone provides a link. The parent is spouting pseudo-scientific nonsense.

subcosmos 8y ago
There are literally hundreds of papers on BPA and its links with diabetes. The only difference now is that we have the molecular culprit behind the trend. https://www.ucsusa.org/our-work/center-science-and-democracy/promoting-scientific-integrity/bisphenol-a.html https://www.ucsusa.org/our-work/center-science-and-democracy...
- timr 8y ago
  "There are literally hundreds of papers on BPA and its links with diabetes." There are literally not. The review you've linked to cites a handful of papers involving minor effects observed in mouse studies. Moreover, the paper you originally cited proves nothing even approximating a mechanism. I'm not suggesting anything about the safety of BPA, but it's utter nonsense to claim that it is a more plausible explanation for the diabetes epidemic than sugar consumption. A few mouse studies do not change 50+ years of established science on the relationship between sugar and diabetes.
  - subcosmos 8y ago
    But is it really? Elevated blood glucose, as in Type 2 Diabetes, has LONG been known to be primarily driven by excessive production of glucose by the liver due to liver insulin resistance. In fact, the way that the drug metformin improves diabetes is by shutting that pathway down. http://diabetes.diabetesjournals.org/content/50/8/1807.short http://diabetes.diabetesjournals.org/content/50/8/1807.short Thats not dietary, thats the hormone insulin being ignored by the liver. This is further complicated by the fact that peripheral tissues, like muscle, are themselves insulin resistant. The TCF7L2 pathway has been shown to be down-regulated in all of these tissues in diabetics.
    - timr 8y ago
      TCF7L2 is a transcription factor. It is involved in many pathways in human biology, of which diabetes is one. Observing that it is downregulated in diabetics provides no evidence for or against any theories concerning BPA.
      - subcosmos 8y ago
        It's also the most statistically significant gene, in the whole dang genome, associated with Type 2 Diabetes. And out of a compound library of 20k chemicals, BPA had the top effect on it. Seems significant to me Also worth noting that BPA has been shown to specifically effect the occupancy of TCF7L2 at transcription factor binding sites in Chip-Seq experiments. http://press.endocrine.org/doi/abs/10.1210/endo-meetings.2015.ED.1.FRI-299 http://press.endocrine.org/doi/abs/10.1210/endo-meetings.201... Lastly, before calling someone else's claims psuedoscientific, you may want to do some homework and check your previous biases. We could certainly use someone with your skills to help model BPAs interaction with the Androgen receptor. Might just save millions of lives....
        deleted 8y ago
        [deleted]
        deleted 8y ago
        [deleted]
- deleted 8y ago
  [deleted]
joneston 8y ago
It’s interesting to notice that what we have here is one industry being villified, and then possibly passing the buck, only to point at another industry as possibly to blame. It’s pretty interesting to think about how easy it is to muddy the waters like this. Something starts off as a direct medical concern, but then sprals into a secondary contamination problem. Both are bad. Plastics are bad for a variety of reasons, and sugars definitely contribute to obesity. But, horomonal factors really cannot be shrugged at. There’s some serious distortion affecting people for the past 20 or more years, and it’s nothing normal. Is it birth control pills being dumped down the drain, and recirculating into the drinking water? Is it ibuprofen messing with people who have over dosed on their analgesic NSAIDs? One thing’s for sure modern civilization has inteoduced many complications, all simultaneously, and that is likely the biggest mistake of all. Also, I’m not sure you’ve used the word “parsimonious” correctly? Are you trying to say they’ve been “very careful” or “strict”? I think it’d be more appropriate to replace it with “well aligned” or “concomitant” if a vocabulary word should be preferred.

cat199 8y ago

and yet, most everything came in glass until about 25 years ago..

subcosmos 8y ago
Thats about when things got really bad http://www.diabetesandenvironment.org/home/incidence http://www.diabetesandenvironment.org/home/incidence

baxtr 8y ago

But what about other countries than the US? Japan, Europe? They use lots of plastic too. I haven’t heard of a diabetes epidemic there yet though.

harshreality 8y ago
Trends in prevalence of diabetes in Asian countries, doi: 10.4239/wjd.v3.i6.110 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3382707/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3382707/ Diabetes in Asia and the Pacific: Implications for the Global Epidemic, https://doi.org/10.2337/dc15-1536 https://doi.org/10.2337/dc15-1536 ( http://care.diabetesjournals.org/content/39/3/472 http://care.diabetesjournals.org/content/39/3/472 ) Someone needs to do a dietary and sociological study of Vietnam, because it looks like they've been least affected by the diabetes epidemic, up until the early 2010s at least.

allover 8y ago

> We can keep running on the macronutrient treadmill, People reach obesity from overeating, no matter what their choice of calorie-dense foods, but it's typically sugar or fats, and sugar is the cheapest/most available. Being obese is clearly a causative factor towards T2B [1]. How are these obvious truths 'running on a treadmill'? [1] https://www.diabetes.co.uk/diabetes-and-obesity.html https://www.diabetes.co.uk/diabetes-and-obesity.html

subcosmos 8y ago
The treadmill is the endless debate over whether or not fats vs carbs are more obesogenic. This debate continues ad-nauseum and distracts from more nuanced explanations. High fat consumption raises inflammatory profiles through mechanisms that are poorly understood. Carbohydrates seem to cause similar inflammation, but this is largely do to advanced gylcation end-products created from fructose, specifically. Overeating is not interesting. The reason people do overeat is very interesting, and if you hit the literature you find that this is largely driven by damage to the hypothalamus by environmental exposure.
- allover 8y ago
  > Overeating is not interesting. The reason people do overeat is very interesting What if it's not. What if people just overeat because life is boring, and food tastes good, and we all have differing levels of willpower & education on nutrition? > if you hit the literature you find that this is largely driven by damage to the hypothalamus by environmental exposure. Sounds like nonsense, can you elaborate?
  - subcosmos 8y ago
    There is a specific part of the hypothalamus called the arcuate nucleus. It lacks a blood brain barrier, because the neurons there have a special function to sense blood-born hormones like insulin and leptin. When sensed, the brain interprets this as a "full tank of gas" and suppresses appetite while increasing metabolism. Since theres no blood brain barrier here, these neurons get damaged easily due to things in the blood. When that happens, they don't see leptin anymore, and obesity develops. Fructose and high fat diets have both been shown to cause inflammation here. (hypothalamic gliosis) heres a random selection of many papers http://diabetes.diabetesjournals.org/content/65/3/551.figures-only http://diabetes.diabetesjournals.org/content/65/3/551.figure... We also know that certain viruses show up in obese people (adenovirus36). As the field develops, I would not be surprised if labs demonstrate both viral infection of the hypothalamic ARC and damage by endocrine disruptors there.

harshreality 8y ago

There's a notable lack of dose-response relationship in most of the collected data, and n=12 for each group doesn't inspire confidence even if in some cases the p-value suggests significance. There are already a lot of measurements taken and included in the table where differences were not that large. Were other measurements taken and not reported in the table? Has anyone attempted to reproduce this? Most importantly, though, that study doesn't indicate whether the effects, if they end up being reproducible, are caused by BPA alone, or the combination of BPA+sugar. It's well known in other scenarios that toxins, when combined with inflammatory foods like sugar, are far worse than they are in the absence of inflammatory foods. I'm fairly convinced that BPA is slightly bad, I just think alternative plastics may turn out to have other compounds that are also bad, given horrible diets, and the best solution may be to fix the diet, rather than try to eliminate all toxins related to modern plastics (and the same argument may apply to pesticides). Other toxins from modern living will undoubtedly pop up, and if they all cause different and problematic diseases in combination with bad diets, but not so much in combination with good diets, how much energy do we really need to put into studying and eliminating toxins in a giant game of whack-a-mole?

subcosmos 8y ago
I havent yet seen other studies comparing BPA with carb ingestion, but I hope they are done. Its important to root out the effect since BPA lines every single soda-pop can. Aside from that though, there are many other mouse studies. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2605.2007.00832.x https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2605.... As well as studies showing that BPA in human urine is associated with insulin resistance and obesity https://academic.oup.com/jcem/article/97/2/E223/2836542 https://academic.oup.com/jcem/article/97/2/E223/2836542
subcosmos 8y ago
Note that this study specifically showed that fructose alone did not increase liver fat content unless BPA was present in the solution. See figure 3, but yes, I agree that it would have been nice if they tried BPA without the fructose. This really does make sense. When that pathway is suppressed, the adipogenic program is activated, which turns on the SREBP-1 pathway and stores lipid droplets. Without this pathway activated, fructose is processed and exported out of the liver, preventing harm to the liver. I would argue that we should really test every new manmade chemical against a library of our proteins before we synthesize anything new and introduce millions of tons of it to the world. Not doing so can have disasterous consequences. Samuel Epstein, before he died, documented a great many examples of horror stories we just barely averted. https://www.youtube.com/watch?v=rQoc6WP3QJo https://www.youtube.com/watch?v=rQoc6WP3QJo