The nature of the initial event that produces insulin resistance at the beginning of overeating and weight gain has not been previously described. Insulin resistance—resistance to the effect of insulin—is the first step leading to diabetes and vascular disease in most American patients. In this study, researchers fed healthy men with ~6000 calories a day of the common U.S. diet [~50% carbohydrate (CHO), ~ 35% fat, and ~15% protein] for 1 week which produced a rapid weight gain of 8 pounds and the rapid onset (after 2 to 3 days) of whole body and fat tissue insulin resistance and excess oxidant production.
In fat tissue, increased oxidant production quickly oxidized numerous proteins, including proteins that transport glucose into the cell in response to increased insulin levels. That results in insulin resistance in real time. There are other mechanisms that quickly increase insulin resistance as well in response to overeating. The more carbs and sugar we eat, the higher the insulin levels in the blood after the meal. As you can see from the diagram, high insulin levels and excess food intake activate mTOR which kicks back to inhibit IRS 1 and interfere with insulin signaling. Overeating also increases asymmetric dimethylarginine (ADMA) production which increases oxidant generation as well. Oxidants also switch on mTOR to create further insulin resistance and produce abnormal arterial function within hours.
Here is the main point. Now we understand the diseases associated with insulin resistance at the level of epigenetics and molecular biology. Overeating produces excess oxidants, insulin resistance, and arterial abnormalities in a matter of days. When overeating is a regular pattern, these problems become persistent and they worsen. Diet, exercise, metformin, and empagliflozin switch off mTOR and switch on AMPK to precisely promote insulin sensitivity. We can treat these conditions much more precisely now. Let’s do it!
Yup! That’s how it kills people with already severely compromised cardiovascular and cerebrovascular systems!
After my recent flu episode (real flu, really sick,neg for coved x 2, had flu vaccination 9 days before), I lost about 10 pounds because I couldn't eat a thing for 5 days straight. Then just chicken soup for 3 more. In any case, I like the newer weight, and have resolved to lose more by not over eating, which I'm prone to do, especially after a couple of glasses of wine. So, knocking back on the wine, too. As my atrial fibrillation episodes seemed always to be associated with a heavy meal -- I suspect a strong vagal component -- I've noted few a-fib episodes as a bonus. So, all good. New target weight is 220, about what I weighed as a freshman in college, although I bulked up to 240 for football. All the best, David