Master class on insulin resistance

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Tincup
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Master class on insulin resistance

Post by Tincup »

Peter Attia interviews Gerald Shulman, M.D., Ph.D on insulin resistance
This is a technical podcast. My bottom line - fasting, low intensity (Zone 2?), long duration exercise and caloric restriction to prevent IR.

Gerald’s background and interest in metabolism and insulin resistance (4:30);
Insulin resistance as a root cause of chronic disease (8:30);
How Gerald uses NMR to see inside cells (12:00);
Defining and diagnosing insulin resistance and type 2 diabetes (19:15);
The role of lipids in insulin resistance (31:15);
Confirmation of glucose transport as the root problem in lipid-induced insulin resistance (40:15);
The role of exercise in protecting against insulin resistance and fatty liver (50:00);
Insulin resistance in the liver (1:07:00);
The evolutionary explanation for insulin resistance—an important tool for surviving starvation (1:17:15);
The critical role of gluconeogenesis, and how it’s regulated by insulin (1:22:30);
Inflammation and body fat as contributing factors to insulin resistance (1:32:15);
Treatment approaches for fatty liver and insulin resistance, and an exciting new pharmacological approach (1:41:15);
Metformin’s mechanism of action and its suitability as a longevity agent (1:58:15);
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aphorist
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Re: Master class on insulin resistance

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I was pleasantly surprised to find this Shulman interview in my podcast list for Attia. I've gone through it once, but need to do it at least 1 more time.

I would add going for a walk after a meal (i.e. AMPK-mediated GLUT4 translocation) as a recommendation to insulin resistance. Additionally other alternatives that raise mitochondrial uncoupling (i.e. cold exposure, eating a hot pepper) improve glucose homeostasis.

I've read several of Shulman's papers and they are pretty interesting. This is the best overview/review he's written. I will leave it here in case anyone else comes across this thread.

Samuel VT, Shulman GI. The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux. J Clin Invest. 2016 Jan;126(1):12-22. doi: 10.1172/JCI77812. Epub 2016 Jan 4. PMID: 26727229; PMCID: PMC4701542.

https://pubmed.ncbi.nlm.nih.gov/26727229/
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Re: Master class on insulin resistance

Post by kiksuyapi »

Thank you Tin Cup and aphorist. I came to the threads today looking for a deep dive on IR and metformin. Appreciate your footprints here on the trail.
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Re: Master class on insulin resistance

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kiksuyapi wrote:I came to the threads today looking for a deep dive on IR and metformin.
You might also look at studies regarding the time of day that you eat. Here's a short press release from last year's Endocrine Society meeting.

https://www.endocrine.org/news-and-advo ... 2-diabetes

There are a lot of studies in PubMed about timing of meals, specifically eTRF if you're doing a smaller eating window. They include healthy (vs diabetic or obese) cohorts, and suggest eating earlier, when insulin sensitivity is naturally higher will improve insulin sensitivity. I've started switching up my eating pattern to earlier in the day, first meal by 8:30ish, and will see if a few months down the road I see any difference in my labs.

Note, there is one study that found a suggestion of different metabolic phenotypes, perhaps based on genetics and other daily lifestyle influences, so YMMV.
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Re: Master class on insulin resistance

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SusanJ wrote: Sun Apr 03, 2022 10:26 am I've started switching up my eating pattern to earlier in the day, first meal by 8:30ish, and will see if a few months down the road I see any difference in my labs.
Thanks. I have read a little on this. I do IF but my window starts later in the morning. Will give this a try and see if anything shifts.
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Re: Master class on insulin resistance

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Here's a study I've bookmarked that is a good start for the details.

Early Time-Restricted Feeding Improves 24-Hour Glucose Levels and Affects Markers of the Circadian Clock, Aging, and Autophagy in Humans (2019)
Collectively, our data suggest that eTRF improves several facets of health through both circadian- and fasting-related mechanisms. eTRF improves glycemic control by lowering 24-hour glucose levels, reducing glycemic excursions, and potentially by improving insulin signaling. Importantly, some of these improvements in glycemic excursions may be driven not only by eating earlier in the day but also by having a short inter-meal interval, suggesting that TRF interventions with longer inter-meal intervals may be less effective at improving glucose levels.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627766/
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Re: Master class on insulin resistance

Post by kiksuyapi »

Thanks!
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