Saturday 11 May 2013

Type 2 diabetes: your good signalling's gonna go bad.

A little bit of Tammy Wynette.

 

Good signalling:

There's a famine. You've got nothing to eat. Your body's glycogen stores have just run out. What happens next? As food intake is zero, serum insulin level is minimised, so lipolysis (fat mobilisation) is maximised. Serum NEFAs are maximised. High serum NEFAs provides fuel for tissues that utilise NEFAs (e.g. skeletal muscle) and a "stop utilising glucose!" signal, in conjunction with low serum insulin.

High serum NEFAs and low serum insulin increase ketogenesis in the liver, to give the parts of the brain that can utilise ketones an alternative choice of fuel, to reduce glucose utilisation to a minimum. Ditto for nerves. Glucose utilisation must be minimised during a famine, as it's generated by the liver & kidneys from glucogenic amino acids, obtained from lean body mass (LBM) by hypercortisolaemia.

Gone bad:

You're a type 2 diabetic with a fat belly. For reasons that I don't fully understand (better blood supply? close proximity to liver?), belly fat deposits spew NEFAs into the blood at a much higher rate than arm, boobs, love-handles, bum & thigh fat deposits. On a very-low-carb diet (less than 50g/day carbs), serum insulin level is minimised, so lipolysis (fat mobilisation) is maximised. Serum NEFAs are maximised. High serum NEFAs provides fuel for tissues that utilise NEFAs (e.g. skeletal muscle) and a "stop utilising glucose!" signal, in conjunction with low serum insulin.

A type 2 diabetic with a fat belly has underlying insulin resistance, due to over-full muscle, adipose and/or liver cells (making the liver spew glucose into the blood at too fast a rate, and the muscles & adipocytes take it out of the blood at too slow a rate). The very-low-carb diet makes the underlying insulin resistance worse and high serum NEFAs in a milieu of caloric sufficiency or excess wreak havoc. Serum glucose level increases. Serum LDL-c level increases. Serum TG level increases. Serum just about everything level increases, except for serum HDL-c level, which decreases.

7 comments:

William Lagakos said...

agreed. Also, when in caloric deficit a lot of those NEFAs are getting burned in muscle, whereas in caloric excess they're getting deposited where they shouldn't be.

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