Metabolic Inflexibility: What it really means.

Here's a picture from Metabolic Flexibility and Insulin Resistance.

The Metabolically-Inflexible (MI) & Insulin Resistance

Here's another picture.

Fig 2. ● = Metabolically-Flexible (MF). ○ = Metabolically-Inflexible (MI).

Salient points:
1) Excessively high serum FFA a.k.a. NEFA is bad.
2) Respiratory Quotient (RQ) a.k.a. Respiratory Exchange Ratio (RER) changes due to dietary changes are more sluggish in the MI than in the MF.
3) Under Insulin Clamp conditions, RQ/RER is lower in the MI than in the MF, due to impairment of glucose oxidation and non-oxidative glucose disposal.

I have posted this because of Danny Roddy's post Is Supplemental Magnesium A Surrogate For Thyroid Hormone? , which leads onto A Bioenergetic View of High-Fat Diets.

In the first article, Danny Roddy writes:-
"Additionally, taking magnesium while actively engaging in a diet or lifestyle that reduces the respiratory quotient (e.g., high-fat diet, light deficiency, excessive exercise) seems pretty silly. For example, as a rule, diabetics have a reduced respiratory quotient (Simonson DC, et al. 1988), tend to have higher levels of free fatty acids or NEFA (Kahn SE, 2006), and are often deficient in magnesium (De Valk HW, 1999)."

The second sentence (diabetics have a reduced respiratory quotient...and are often deficient in magnesium) seems to contradict the first sentence (...taking magnesium while actively engaging in a diet or lifestyle that reduces the respiratory quotient seems pretty silly).

Simonson DC, et al. 1988 is Oxidative and non-oxidative glucose metabolism in non-obese type 2 (non-insulin-dependent) diabetic patients.
"In conclusion, during the postabsorptive state and under conditions of euglycaemic hyperinsulinaemia, impairment of glucose oxidation and non-oxidative glucose disposal both contribute to the insulin resistance observed in normal weight Type 2 diabetic patients. Since lipid oxidation was normal in this group of diabetic patients, excessive non-esterified fatty acid oxidation cannot explain the defects in glucose disposal."

Impaired glucose oxidation with normal lipid oxidation lowers RQ/RER. Therefore, lower RQ/RER must be bad, right? Wrong. From the above study:-
"...euglycaemic insulin clamp studies were performed..."
Remember Salient point 3)? Simonson DC, et al. 1988 is an insulin clamp study, the results of which don't apply to free-living people (who aren't insulin clamped).

See also Determinants of the variability in respiratory exchange ratio at rest and during exercise in trained athletes. RER/RQ increases & decreases with increases & decreases in exercise intensity. This is Metabolic Flexibility (MF). Sorry, Danny.

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.

Type 2 diabetes: between a rock and a hard place.

About 85% of type 2 diabetics have excessive visceral adiposity (belly fat). This post is about them.

Which is better - the rock or the hard place?

 

1) The rock:

This is serum glucose. People with type 2 diabetes can measure their own serum glucose. Eating carbohydrates makes serum glucose increase, the rate of increase being proportional to the glycaemic index and the magnitude of the increase being proportional to the grams of carbs consumed. By limiting the intake of dietary carbohydrates, large spikes in serum glucose can be avoided. The occasional spike above 7.8mmol/L (140mg/dL) doesn't hurt. It's spending long periods of time above 7.8mmol/L that's harmful (by glycation).

A low-carb diet (~150g/day of carbohydrate) halves serum glucose fluctuations compared to a higher-carb diet (~300g/day of carbohydrate). A very-low-carb diet (~75g/day of carbohydrate) further halves serum glucose fluctuations compared to the low-carb diet. This seems like an improvement, at first glance.

2) The hard place:

This is the invisible "elephant in the room", as it's not measured by doctors and people with type 2 diabetes can't measure it themselves. It's serum Non-Esterified Fatty Acids, or NEFAs (a.k.a. Free Fatty Acids, or FFAs). Serum NEFAs are high when fasting and fall after eating foods that raise serum insulin (carbs & certain proteins). People with type 2 diabetes and excessive visceral fat (belly fat) have higher-than-normal serum NEFAs due to adipocyte insulin resistance (IR). See Insulin Resistance: Solutions to problems.

Just like with serum glucose, there's nothing wrong with serum NEFAs going up & down. It's chronically-high serum NEFAs that's harmful (except during periods of caloric restriction). See Showing posts sorted by relevance for query NEFA "type 2 diabetes" .

See Fig. 1 in Lack of suppression of circulating free fatty acids and hypercholesterolemia during weight loss on a high-fat, low-carbohydrate diet. On a very-low-carb (less than 50g/day carbs) diet that's not calorie-restricted, serum insulin remains low all of the time. To insulin-haters, that sounds like a good thing. Unfortunately, it means that there is no insulin spike to suppress serum NEFAs by shifting the balance of NEFAs going in/coming out of fat cells. Serum NEFAs stay high all of the time, which is harmful.

Therefore, people who have type 2 diabetes and excessive visceral fat and who are permanently on a very-low-carb diet that's not calorie-restricted are harming themselves.