Resistance to Weight Loss

I just can't lose weight no matter what I try.  I went on WW and ate 1000 cal/day and didn't lose weight.  Or even, I've cut out all carbs, dairy, gluten, omega 6's, etc. from my diet and I still can't lose weight.  

How many times have we heard statements like these?   Can they be true?  Are we destined to be fat?  It seems to me that any number of overweight and obese folks have uttered something like this at one point or another and/or flirted with the notion that they are just destined to be so for the rest of their lives.  These people seem to be convinced that they have "messed up" or "broken" metabolisms that cannot be fixed.   Is that true?  As regards obesity and metabolism, the only thing that can't be reversed is a certain point in the progression of T2 diabetes -- that being beta-cell damage.  (The popular belief that this occurs because we exhaust or wear out our beta cells with excessive insulin requirements is probably not the case.  Rather, my research leads to lipotoxicity of the pancreas leading to death of the cells being the primary cause).    

Presuming your condition has not progressed to this stage, it appears that your metabolism CAN indeed be fixed.  In most cases it boils down to insulin RESISTANCE, not insulin per se.  Taubes' would tell you that high insulin levels (both basal and post prandial) are the reason you can't lose weight, because insulin has you fats "locked" away in your fat cells unable to escape.   True?  Nope!  As I've posted several times before, insulin resistance is not caused by eating a lot of foods that trigger its release, it is caused primarily by an accumulation of lipids and/or lipid metabolites in the cells as a result of chronic positive energy balance and/or stuffed adipose tissue.  The way things are supposed to work, we metabolize mixed fuels at all times, but carbs and proteins are given preference.  Therefore lipid oxidation (fat burning) rates go down when we eat carbs and go up when we're in a fasted state.  Whether we burn carbs or fats doesn't seem to alter the total fuel requirements by much if at all (the whole metabolic advantage thing).

But Taubes and Atkins (and New Atkins authors Westman, Volek & Phinney) would have you believe that if you are obese and hyperinsulinemic due to being insulin resistant, you don't have a lot of fats available to your cells for fuel.  These would be those free fatty acids (NEFA/FFA).  One problem with this.  Obesity and insulin resistance are associated with both elevated insulin levels AND elevated NEFA!!  How can that be?  It's all about the insulin resistance that seems to develop in the fat cells FIRST ... not last.  Insulin's role in adipose tissue is to suppress lipolysis.  When adipocytes develop IR, lipolysis is suppressed less, the body has a hard time keeping fat stored where it belongs.

The thing that is needed to lose fat mass -- e.g. deplete the fat cells -- is a chronic caloric deficit.  Improved insulin sensitivity will improve one's metabolic profile, but it's not likely to have much effect on weight loss per se, except indirectly how the deranged BG, NEFA, etc. may effect mood and energy levels and appetite signaling.  


MM said…

Your blog has been so enlightening. I so appreciate it. I have more stupid questions. I feel like everything I thought I knew about insulin has been shown to be utterly wrong. I want to make sure I understand. So, here are my questions.

A type 2 diabetic eats a potato (my dad is type 2), and his blood sugar shoots up over 200. The glucose is from the potato and not the liver, right? So, what prevents cells from taking up the glucose? It isn't that they've down-regulated their insulin receptors, because they don't need insulin to take up glucose. Is it that the glucose is competing for entry into cells with FFA? (or NEFA? And what's the difference?) Thanks so much!
CarbSane said…
Insulin is not required for glucose clearance, but it does facilitate it by increasing the number of GLUT transporters (and/or by activating them, not 100% sure on that off the top of my head). So in diabetics, glucose does still get into the cells but not as rapidly as if they had an appropriate insulin response/sensitivity. So I think it is overly simplistic to say that diabetic hyperglycemia is due JUST to the liver producing too much.

I think that T2 is a very murky diagnosis because I've seen it based on (as told by those with T2 diagnoses) as little as a high FBG level, and/or an accompanying oral glucose tolerance test (OGTT). If someone's BG doesn't come down normally, it seems to me that without knowing the corresponding insulin levels we don't know what we're dealing with. High fasting insulin is indicative of insulin resistance but tells us nothing about the person's insulin response to carbs (or protein). If the person has IR, the treatment should be to improve insulin sensitivity, but if the person has beta cell damage, then they lack the acute insulin response to a meal. In that case, either insulin treatment and/or ways to increase this response makes more sense (e.g. some amino acids can dramatically improve insulin responses in diabetics).

NEFA = FFA Non-esterified = free. I usually use both because about half the articles I read use NEFA, half FFA.

While glucose and FFA's do compete metabolically for the fuel mix, it's pretty much been shown that they don't compete for transport into the cells. Near as my research seems to indicate, it is the buildup of fatty acid metabolites (diacylglycerols and ceramides) in and around the mitochondria that lead to the cells to lose their sensitivity to insulin.