Of interest, there is a section in that paper talking about how hormones regulate their own tissue sensitivity in general, and its not just a feature of insulin. This makes me wonder about sleep and melatonin. Failure to properly suppress melatonin during the day from inadequate light exposure may leave melatonin chronically elevated and thus reduce cells sensitivity to melatonin. So that when night-time comes around and its time to sleep, your less sensitive to melatonin due to it being elevated all day, and thus dont get a good nights sleep.
Is that a possibility?
Anyway, back to T2D, a more recent paper suggests that further evidence of fasting hyperinulinemia causing insulin resistance and T2D comes from patients undergoing gastric bypass surgery. ( Roux-en-Y ).
They argue that, during the development from lean healthy to obese to obese diabetic, there is a constant and consistent elevation in fasting insulin, indicated by the brown line in the graph below.
The remission of T2D and elevated glucose levels after surgery is shockingly rapid, and is accompanied by fasting insulin that is comparable to lean healthy controls within only 1 week post surgery. They argue that the changes in fasting insulin are independent of changes in either blood glucose, serum FFA, or insulin resistance, and therefore it is the reduction in fasting insulin which is primarily responsible for the remission of T2D.
I think this totally obliterates the idea that fatness causes insulin resistance and causes T2D, because glucose and insulin homeostasis is achieved without significant weight loss post surgery.
They also argue that, the elevated glucose levels seen in T2D is due to elevated gluconeogenic substrates like lactate and alanine driving elevated hepatic glucose production. Lowering fasting insulin improves insulin sensitivity and thus lowers lactate in the blood, which in turn lowers fasting glucose. ( the mechanism for this is fuzzy however ).
To me, it seems almost too obvious that fasting hyperinsulinemia would be the cause of T2D once your told that chronically elevated insulin levels causes severe insulin resistance. Some questions remain however.
1) How exactly does gastric bypass almost immediately cure fasting hyperinsulinemia? ( glp-1 hyper-secretion? )
2) What role, if any, does increased beta-cell mass have in this cure by gastric bypass? Does the beta-cell mass rapidly shrink after surgery? ( seems unlikely ).
I wonder, does high fasting BS indicate the fasting insulin is low?
ReplyDeleteFrom the graph we see that high fasting BS goes hand in hand with high fasting insulin.
DeleteI know it must seem like the high fasting BS is there BECAUSE insulin secretion isnt high enough. But the authors of the paper argue just the opposite. If it was true that insulin secretion wasnt doing a good enough job of controlling fasting BS, you would expect BS to rocket up after surgery when fasting insulin is reduced. but thats EXACTLY not what happens. lowering the insulin with the surgery actually lowers the fasting glucose.
My FBS got higher after adaptation to IF, especially exercising in a fasted state. Many people who eat ketogenic diets report the increase in the FBS .
Deletei think i read somewhere that bypass patients were prescribed a comparatively low-carb diet? talk about ironic, if true....
ReplyDeleteoh how stupid of me!, this affect of a chronically elevated hormone down-regulating its own receptors exists for leptin aswell. I just found a study by Friedman himself that hyperleptinemia causes leptin resistance.
ReplyDeleteThis is why obesity is associated with leptin resistance, the elevated leptin levels seen in obesity themselves CAUSE the leptin resistance. this is quite pro-found. I guess thats the leptin resistance paradox solved then.
Well duh! I remember Wooo saying that when she had her leptin measured it was extremely low, but she also responsed VERY strongly to leptin administration, which is further proof that low leptin automatically makes you super leptin sensitive.
http://www.ncbi.nlm.nih.gov/pubmed/20613882
This is why Rosedale, who wrote his book before leptin measurement was not available, said don't worry about it. Fix the insulin resistance, you fix the weight and the leptin resistance. If you go low carb, you don't need to measure anything, unless you are a diabetic or just curious.
ReplyDelete