Rapamycin Increases Mortality in db/db Mice, a Mouse Model of Type 2 Diabetes

#1
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Any rapamycin questions to ask Matt Kaeberlein?
#2

I said it in the post from Rapadmin and will say it here: flawed study, starts rapa at 4 months of age which is equivalent to a 13 year old human.

EDIT: I’m wrong.

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#3

Then edit and delete the post as people may not read your final comment.

#4

It is interesting to note that most of the diabetic mice died of inflammation instead of cancer as they usually do in other studies.

Takeaways for me:

  1. Don’t take Rapa if you are type 2 diabetic
  2. Take acarbose or Metformin to blunt Rapa’s diabetic enhancing effects.
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#5

The study puts the light on the importance of metabolic health and the additive effects of canagliflozin, Metformine, acarbose, berberine etc.

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#6

Obesity and diabetes both predispose to severe infections ( see Covid experience). In mice , the addition of rapa increased abscess formation in various tissues. Not sure that this also occurs in humans. No real evidence for that.

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#7

As someone with well controlled T2D, does this have implications for users like myself?

@RapAdmin

What are your thoughts?

Edit;

So reading the study, the researchers note that the cause of the Rapa toxicity was due to a leptin receptor mutation. Is there a way to test for this mutation?

#8

“The db/db mice we studied have been used extensively to study type 2 diabetes; they are hyperphagic and develop significant obesity, fasting hyperglycemia, and hyperinsulinemia by 6 weeks of age (40). The course of the disease is markedly influenced by genetic background with the most severe diabetic phenotype shown on the C57BL/KsJ background, for example, an uncontrolled rise in blood sugar, severe depletion of the insulin-producing beta cells of the pancreatic islets, and early deaths”.

The mice in the study had the most severe genetic predisposition to diabetes, obesity and early death, which most likely affected the outcome of feeding them rapamycin on a daily basis.

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#9

I’m not a doctor. I’ve not read the study… but if I had diabetes I would read it. It sounds like these mice have basically uncontrolled diabetes (or are very prone to get it), and obviously they are not taking any treatments to control it when they do get it. So its very different from your situation. At minimum, if I were diabetic, I’d be extra cautious and track blood glucose and lipids very closely and be more likely to take vacations from rapamycin.

I don’t think you have to worry about the specific gene mutation that they likely insert into this mouse model to make it diabetic prone, thats just a way for the researchers to make this transgeneic mouse and disease model for studying. It may or may not be an extremely good model for diabetes, but you probably have to assume for this case that its a reasonably good model for human diabetes, just to be safe.

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#10

I have found many people who are grossly obese and with uncontrollable diabetes. I think if these individuals took Rapamycin they would shorten their lives. IMHO, if you have controlled diabetes, you need to stay on top of your numbers so it doesn’t go out of bounds or else you may be decreasing your life expectancy with Rapa usage.

Trust the science. We know from mice studies

  1. Rapamycin + Metformin or acarbose EXTENDS life expectancy.
  2. Rapamycin + uncontrolled diabetes SHORTENS life expectancy.
  3. Rapamycin makes blood sugar levels higher thus aggravating diabetes.

We now have several studies that support this hypothesis.

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#11

@Krister_Kauppi This is the study.

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