In starvation or ketosis, protein should have NO EFFECT on blood glucose level, not RAISE it.

From Blood Sugar is Stable:-

In a healthy person, BG (blood glucose) is held at a fairly constant value by a NFB (negative feed-back) loop. See Blood Glucose, Insulin & Diabetes.

When protein is eaten, this produces a glucagon response from pancreatic alpha cells, which tries to raise blood glucose level by stimulating the liver to convert liver glycogen plus water to glucose. Protein also produces an insulin response from pancreatic beta cells, which tries to lower blood glucose level by a) increasing glucose uptake from the blood and b) inhibiting HPG (hepatic glucose production). The net result is no change in BG level.

In extended fasting or on VLC (very low carbohydrate)/ketogenic diets, there's no liver glycogen left after ~1 day.
∴ The glucagon response has no effect on HGP.

The insulin response still has an effect, until the 1st phase insulin response is lost*.
∴ Blood glucose tries to decrease, but the HPAA keeps it steady by raising cortisol level.

RE How eating sugar & starch can lower your insulin needs: Blood glucose level on a VLC/ketogenic diet can be RAISED, due to the BG NFB HPAA (hypothalamic pituitary adrenal axis) loop not having a precise set point with the cortisol/adrenaline response (hyperglycaemia is not fatal, whereas hypoglycaemia can be fatal, as the brain always needs some glucose to function (~50%E from glucose)).

So, how come people on LCHF (low carbohydrate, high fat) diets can have normal or slightly low BG levels?

1. Luck. The BG NFB HPAA loop isn't very precise.

2. Excessive intake of Booze. Ethanol inhibits HGP (dunno about RGP (renal glucose production)).

3. Insufficient intake of Protein. This deprives the liver & kidneys of glucogenic amino acids (Alanine & Glutamine are the 2 main ones), forcing BG down and making the HPAA run open-loop and raise cortisol level. There's another source of Alanine & Glutamine available - Lean Body Mass. Uh-oh!


Consuming more protein on extended fasting or a VLC/ketogenic diet can result in higher BG level for three reasons.

1. It allows the HPAA to run closed-loop, as it's supposed to.

2. The lack of a 1st phase insulin response* in people with IR/IGT/Met Syn/T2D results in a temporary BG level spike with the intake of rapidly-absorbed proteins e.g. whey. There's an unopposed glucagon response, until the 2nd phase insulin response begins.

See http://care.diabetesjournals.org/content/early/2015/11/29/dc15-0750.abstract

*Long-term carbohydrate restriction causes loss of the 1st phase insulin response. See https://carbsanity.blogspot.co.uk/2013/10/insulin-secretion-in-progression-of.html

P.S. This only applies to people who have sufficient liver glycogen, due to them eating some (50 to 100g/day, say) carbohydrate.

3. Hepatic Insulin Resistance results in the insulin response inadequately suppressing Hepatic Glucose Production. As 50g of protein (an 8oz steak, say) yields ~25g of glucose from glucogenic amino acids, there's an increase in the amount of glucose entering circulation, which raises BG level.

See https://academic.oup.com/bja/article/85/1/69/263650

Low-carbohydrate diets: Green flags and Red flags.

Fun with flags. But first, a poem!
Atkins Antidote
 
Eating low carbohydrate what threat that poses?
Do my friends think I’m suffering from halitosis?
I’ve got these sticks for measuring ketoacidosis
I’m taking supplements but I don’t know what the dose is

I’m trying hard to keep in a state of ketosis
I’m not sure what the right amount of weight to lose is
I’m sure I’ve put on a pound just through osmosis
Is eating this way risking osteoporosis?

Are my kidneys wrestling with metabolic acidosis?
My store of liver glycogen I don’t know how low is
Who knows what the glycemic load of oats is?
Does anyone know if I can eat samosas?

Ian Turnbull (whose poetry is better than his science!)

I do. The answer's "No!" :-D

From https://forum.nationstates.net/viewtopic.php?f=23&t=13567&start=8925

The Green flags... 

1. For a person with Insulin Resistance, an ad-libitum low-carb diet results in more weight loss than an ad-libitum high-carb diet.

See How low-carbohydrate diets result in more weight loss than high-carbohydrate diets for people with Insulin Resistance or Type 2 Diabetes , for an explanation.

2. For a person with Type 1 Diabetes Mellitus (T1DM), a lowish-slowish-carb (~150g/day) diet results in minimal disturbances to blood glucose levels and minimal bolus insulin doses.

See Diabetes: which are the safest carbohydrates? , to see which foods should comprise the ~150g/day.

3. For a person with LADA or MODY, see 2.

4. For a person with Type 2 Diabetes Mellitus (T2DM), a LCLF 600kcal/day Protein Sparing Modified Fast can normalise BG in 1 week and reverse T2DM in 8 weeks (provided there are sufficient surviving pancreatic beta-cells). See https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168743/
"After 1 week of restricted energy intake, fasting plasma glucose normalised in the diabetic group (from 9.2 ± 0.4 to 5.9 ± 0.4 mmol/l; p = 0.003)." and
"Maximal insulin response became supranormal at 8 weeks (1.37 ± 0.27 vs controls 1.15 ± 0.18 nmol min−1 m−2)."

After 8 weeks, the diet is gradually changed to a healthy balanced diet containing carbs.

See also https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)33102-1/fulltext and Roy Taylor - Reversing the irreversible: Type 2 diabetes and you. 4th Oct 2014

Compare the above results with the inferior results obtained in A Novel Intervention Including Individualized Nutritional Recommendations Reduces Hemoglobin A1c Level, Medication Use, and Weight in Type 2 Diabetes, which is 10 weeks of VLCVHF Nutritional Ketosis.


As Insulin Resistance is multi-factorial, ALL of the potential causes need to be addressed. Once this has been done, IR should be reversed, allowing restrictions on dietary carbohydrate intake to be lifted. See also Can supplements & exercise cure Type 2 diabetes?

The Red flags...

The low-carb diet is a temporary patch to ameliorate the symptoms of IR/IGT/Met Syn/T2D, a bit like replacing a blown fuse by sticking a nail in its place, to allow the house to function while you fix the problem by fitting a new fuse. Although a house functions with a nail instead of a fuse, it's not a good idea to spend the rest of your life without a fuse to protect the house from fire in the event of a short-circuit.

So, why do LCHF'ers want to spend the rest of their lives using a temporary patch to ameliorate the symptoms of their IR/IGT/Met Syn/T2D?

Long-term use of very-low-carb, very-high-fat, low protein diets (a.k.a. Nutritional Ketosis) is not recommended.

1. Cortisol and adrenaline levels increase due to insufficient glucose production from dietary protein, resulting in gradually-increasing fasting BG level. See How eating sugar & starch can lower your insulin needs and Survival of the Smartest (part 2) - Dr Diana Schwarzbein.

2. If you do too much high-intensity exercise, you may momentarily black-out, fall and hurt yourself. See "Funny turns": What they aren't and what they might be.

3. Insulin Resistance is bad and should be reversed, if at all possible. See Lifestyle-induced metabolic inflexibility and accelerated ageing syndrome: insulin resistance, friend or foe?

4. T2D causes carbohydrate intolerance and fat intolerance, resulting in high postprandial BG and high postprandial TG. See Lifestyle Intervention Leading to Moderate Weight Loss Normalizes Postprandial Triacylglycerolemia Despite Persisting Obesity.

5. Dyseverythingaemia isn't fixed. See When the only tool in the box is a hammer.

6. High-fat diets with no energy deficit result in high postprandial TG & high LDL-c. Postprandial lipaemia & high LDL-c are atherogenic. See Ultra-high-fat (~80%) diets: The good, the bad and the ugly.

7. Permanently-high NEFA (a.k.a. FFA). See Lack of suppression of circulating free fatty acids and hypercholesterolemia during weight loss on a high-fat, very-low-carbohydrate diet.

This raises the RR for Sudden Cardiac Death.

This also depletes beta cells causing loss of the 1st phase insulin response. See Chronic Exposure to Free Fatty Acid Reduces Pancreatic b Cell Insulin Content by Increasing Basal Insulin Secretion That Is Not Compensated For by a Corresponding Increase in Proinsulin Biosynthesis Translation.

Loss of the 1st phase insulin response causes Impaired Glucose Tolerance (IGT). See β-Cell dysfunction vs insulin resistance in type 2 diabetes: the eternal “chicken and egg” question

IGT causes high postprandial blood glucose after eating incidental carbohydrates. This is Metabolic Inflexibility, which isn't good.

8. Natural selection increases the incidence of a genetic impairment in the Inuit which reduces ketosis, inferring that reduced ketosis is an evolutionary advantage. Watch Inuit genetics show us why evolution does not want us in constant ketosis.

That's all for now.

Variations in weight change for a given Calorie change - An Engineer's Perspective.

Another techie post, inspired by Insulin Doesn't Regulate Fat Mass. Consider the inverting amplifier using an Op-Amp, below:-

From HERE

As the amplifier is inverting (i.e. a ↑ input on V_in results in a ↓ output on V_out), the feedback from V_out via R₂ opposes V_in via R₁ at the - terminal of the Op-Amp.

If R1 = R2 and V_in changes from 0V to 1V, the change in V_- (the voltage on the - terminal of the Op-Amp) varies with A (the magnitude of the Op-Amp gain) as follows*:-

A_____________Change in V_-(V)
∞_____________0
1,000,000_____~0.000001
1,000_________~0.001
100___________~0.01
10____________~0.08
8_____________0.1
5_____________~0.14
3_____________0.2
2_____________0.25
1_____________~0.33
0_____________0.5

As the body operates on biochemical principles, slopes of input/output transfer functions aren't steep at their steepest points. E.g.

From http://bja.oxfordjournals.org/content/85/1/69.long

Therefore, the gains in the various parts of the Leptin "adipostat" NFB loop are not very high. Therefore, there will be a significant variation in weight change vs Calorie change, and there will be significant variations in the variation due to loop gain variations from person to person.

Insulin Resistance makes the slopes of  the above input/output transfer functions shallower, reducing the gain in the system. This increases the variation in weight change vs Calorie change. For ways to reduce Insulin Resistance, see Insulin Resistance: Solutions to problems.

*In case anyone thinks that I've made the numbers up, here's the maths:-
Current in/out of the - terminal of the Op-Amp = 0.
∴ I_R1 = I_R2
I set R1 = R2 to keep the maths simple. By Ohm's Law, V = I * R.
∴ V_R1 = V_R2
With a 0V input:-
All currents & voltages = 0.

With a 1V input:-
V_R1 = 1 - V_-
V_R2 = V_- - V_out.  As V_out is negative, - V_out is positive.
- V_out = A * V_-
∴ V_R2 = V_- + (A * V_-)
∴ 1 - V_- = V_- + (A * V_-)
Rearranging:-
1 = (2 * V_-) + (A * V_-)
Dividing both sides by V_-:-
(1/V_-) = 2 + A
∴ V_- = 1/(2 + A)

Another penny drops: Why severe hyperinsulinamia can occur with a small increase in exogenous carbohydrate intake.

This blog post is a result of Vim's comments in the previous blog post. A penny suddenly dropped!

From http://bja.oxfordjournals.org/content/85/1/69.full

Insulin has a Chalonic (inhibitory) action on blood glucose level (via the liver, muscle mass & fat mass), blood FFA level (via fat mass) and blood ketone body level (via the liver).

As mentioned in the comments, GHB has a stimulant effect - up to a certain level of blood GHB. Beyond that level, there's a powerful sedative effect. This is because at low levels of exogenous ketone body input, insulin secretion increases slightly to reduce hepatic ketogenesis.

At a certain level of exogenous ketone body input, hepatic ketogenesis falls to zero and cannot be reduced any further. Any slight increase beyond this point in exogenous ketone body input, results in a large increase in insulin secretion, as the pancreas increases Ketone body-Stimulated Insulin Secretion to maximum in a (failed) attempt to reduce blood ketone body level.

Exactly the same thing happens with exogenous carbohydrate or BHB input.

At a certain level of exogenous carbohydrate input, hepatic glucogenesis falls to zero and cannot be reduced any further. Any slight increase beyond this point in exogenous carbohydrate input, results in a large increase in insulin secretion, as the pancreas increases Glucose-Stimulated Insulin Secretion to maximum in a (failed) attempt to reduce blood glucose level.

Nonequilibrium thermodynamics and energy efficiency in weight loss diets, by Richard D Feinman and Eugene J Fine.

From http://www.caloriegate.com/the-black-box/9-pictures-that-prove-beyond-a-reasonable-doubt-that-calories-dont-count

From Nonequilibrium thermodynamics and energy efficiency in weight loss diets:-

"Conclusion
Emphasis on kinetics and nonequilibrium thermodynamics provides a conceptual framework for understanding the effect of macronutrient composition on maintenance and change of body mass and possibly for analysis of adipocyte metabolism in general. The simple model presented is intended to be consistent with a general shift away from equilibrium thermodynamics and towards a more dynamic analysis of cellular processes."

Sounds plausible. There's only one thing wrong with Feinman et al's article - it's completely wrong!

Consider two rooms:-

Room "A" has an adjustable heater. The heater is adjusted until the room temperature is 20°C.

Room "B" has a radiator, controlled by a wall-stat set to 20°C. The radiator is on, and the room is at 20°C.

We have two rooms of the same size, at the same temperature.

If you plug in & turn on a 2kW fan heater in each room, what happens to the temperature in each room?

Room "A" gets warmer, because there is 2kW more heat power entering it.

Room "B" stays at 20°C, because the wall-stat reduces the heat power from the radiator by 2kW.

The human body stays at 37°C ±~2°C, because there's a Negative Feed-Back loop adjusting the heat power produced, via UCP's, futile cycles, thyroid hormones, shivering and heat conservation/wasting behaviours.

∴ Variable heat power generation due to variable Dietary Efficiency doesn't change E_out.

EDIT: By request, here's Figure 1 from the above study.

This suggests that fat mass & therefore weight can increase indefinitely - at maintenance energy intake, due to the effect of insulin on HSL. This, of course, is quite impossible!

From The Energy Balance Equation:-

Change in Body Stores = E_in (corr for digestion) - E_out (BMR/RMR + TEF + TEA + SPA/NEAT)
__BMR/RMR & TEA ∝ weight
∴ ↑ weight → ↑ E_out
__If E_in = constant, ↑ E_out → ↓ (E_in - E_out) → ↓ weight
∴ ↑ weight → ↓ weight
∴ Figure 1 is wrong.

How low & very low-carbohydrate diets don't work.

Having explained how low & very low-carbohydrate diets work, here are a few ways in which they don't work.

Uh, nope!

1. Hormonal clogs: This is a term used by Jonathan Bailor. I don't think he's referring to wooden shoes! The "clog", I'm guessing, is supposedly caused by that dastardly hormone insulin. Uh, nope!

See the following plots of RER vs exercise intensity after being on high-fat diet or low-fat diet.

RER = 0.7 ≡ 100%E from fat. RER ≥ 1.0 ≡ 100%E from carb.

The low-fat diet results in higher RER, so the body is burning a higher %E from carb and a lower %E from fat.

However, this doesn't make any difference to weight loss, as it's merely a substrate utilisation issue. In addition, when the body is burning a higher %E from carb, this depletes muscle glycogen stores faster, which lowers RER during the course of the exercise. So, it's not a problem.


2. Insulin: This is Gary Taubes' hypothesis. Insulin makes your body store carbohydrates as body fat. Uh, nope!

The only time that there's significant hepatic DNL is when there's chronic carbohydrate over-feeding. If you eat sensibly, there's no significant hepatic DNL.


3. A Calorie isn't a Calorie, where weight change is concerned: This is Richard D Feinman's hypothesis. "A calorie is a calorie" violates the second law of thermodynamics, therefore there's a metabolic advantage with low-carbohydrate diets. Uh, nope!

Where to start? Evelyn Kocur knows her Physics, so I'll start there. See The first law of thermodynamics (Part 1) and The first law of thermodynamics (Part 2).

From Second Law of Thermodynamics:-
"Living organisms are often mistakenly believed to defy the Second Law because they are able to increase their level of organization. To correct this misinterpretation, one must refer simply to the definition of systems and boundaries. A living organism is an open system, able to exchange both matter and energy with its environment."

People on ketogenic diets excrete very few kcals as ketone bodies. See STUDIES IN KETONE BODY EXCRETION (PDF). There is no significant Metabolic Advantage with low-carbohydrate diets.

How low & very low-carbohydrate diets result in more weight loss than high-carbohydrate diets for people with Insulin Resistance or Type 2 Diabetes.

See The Battle of the Diets: Is Anyone Winning (At Losing?) for trials where insulin resistant people lose more weight on low-carbohydrate diets than on high-carbohydrate diets and insulin sensitive people lose more weight on high-carbohydrate diets than on low-carbohydrate diets.

If Gary Taubes's carbohydrate/insulin hypothesis of obesity is correct, everyone would lose more weight on low-carbohydrate diets than on high-carbohydrate diets. This isn't the case, therefore Gary Taubes's hypothesis is not correct.

Although insulin is involved, it has nothing to do with "Hormonal clogs" or "Insulin fairies".

The Aragon Insulin Fairy

The Energy Balance Equation

Change in Body Stores = Energy in - Energy out, where... 

Energy in = Energy entering mouth - Energy exiting anus, and... 

Energy out = BMR/RMR + TEF + TEA + SPA/NEAT

See The Energy Balance Equation to find out what the above terms mean.

People with Insulin Resistance (IR), Impaired Glucose Tolerance (IGT) & Type 2 Diabetes (T2DM) have excessive insulin secretion in response to meals (postprandial hyperinsulinaemia). See Hyperinsulinaemia and Insulin Resistance - An Engineer's Perspective.

People with Insulin Resistance (IR), Impaired Glucose Tolerance (IGT) & Type 2 Diabetes (T2DM) also have impaired/no 1st phase insulin response to a sudden rise in blood glucose level. This introduces a time-lag into the negative feed-back (NFB) loop that regulates blood glucose level. If the input rise-time is less than the time-lag in a NFB loop, the output of the NFB loop overshoots. This is standard NFB loop behaviour. See Control of overshoot for more information.

1. On a high-refined-carbohydrate or high-GL diet, blood glucose level rises rapidly, with a rise-time that's less than the time-lag in the blood glucose regulation NFB loop. Insulin secretion from the pancreas overshoots in a positive direction. The resulting postprandial hyperinsulinaemia results in down-regulation of insulin receptors in the brain, which reduces insulin action in the brain. When the insulin level eventually falls to normal a few hours later, the brain interprets a normal insulin level as hypoinsulinaemia. Hypoinsulinaemia results in ravenous hunger, as insulin is a short-term satiety/satiation hormone in the brain (leptin is a long-term satiety/satiation hormone in the brain). Ravenous hunger results in over-eating. Energy in increases. Postprandial hyperinsulinaemia also results in postprandial sleepiness. Energy out decreases. ∴ Body stores increase. There are also accusations of gluttony & sloth!

2. On a low-carbohydrate or low-GL diet, there are small fluctuations in blood glucose & insulin levels. There is no ravenous hunger. There is much less/no over-eating. Energy in decreases. There is no massive postprandial hyperinsulinaemia. There is much less/no postprandial sleepiness. Energy out increases. ∴ Body stores decrease.

In addition, there is a loss of water weight due to a loss of liver & muscle glycogen. This can be ~2kg in one day (it varies from person to person). Kidneys can increase their output of urine for hormonal reasons. This can increase water weight loss to ~5kg. See Why counting Calories and weighing yourself regularly can be a waste of time.

There are also other hormones involved. For a Facebook discussion with James Krieger that led to the updating of this post, see https://www.facebook.com/james.krieger1/posts/10153228943648587

In Metabolic Ward studies, food intake is tightly controlled, so postprandial hunger doesn't result in over-eating. Energy expenditure is also controlled, so postprandial sleepiness doesn't significantly affect energy expenditure. This is why varying Fat:Carb ratios (with Protein held constant) makes no significant difference to weight in a Metabolic Ward. See Energy intake required to maintain body weight is not affected by wide variation in diet composition.

Inter-personal variations in postprandial hyperinsulinaemia, postprandial sleepiness & energy out explain the inter-personal variations in weight gain seen under hypercaloric conditions. See Bray et al shows that a calorie *is* a calorie (where weight change is concerned).

Insulin Resistance can be fixed. See Insulin Resistance: Solutions to problems.

Type 2 Diabetes can also be fixed. See Reversing type 2 diabetes, the lecture explaining T2D progression, and how to treat it.

Aim to fix the problem. If it's impossible to fix the problem, a low-carbohydrate diet as an adjunct to medication is fine.

Resistance is useless!

...said the Vogon guard. If that means nothing to you, watch this...


You probably know all about Insulin Resistance (IR) if you've read my blog for some time, as I may have mentioned it once or twice ;-) There's also Leptin Resistance (LR) in the brain, which reduces the amount of appetite suppression that leptin is supposed to produce. Robb Wolf's just written about Adrenaline Resistance (AR?) and chronically-high serum cortisol seems to induce Cortisol Resistance (CR?) in the hippocampus, resulting in poor short-term memory.

When the level of "X" in the blood is low most of the time, "X" receptors in the body up-regulate, so when the level of "X" in the blood goes high, it has an effect. When the level of "X" in the blood is high all of the time, "X" receptors in the body down-regulate, so when the level of "X" in the blood goes higher, it has a reduced effect.

The above suggests that regularly "grazing" on food is not a good idea, as this results in a fairly constant slightly elevated serum insulin level. Eating a meal, not eating for a few hours then eating another meal results in high serum insulin while the meal is being absorbed and low serum insulin for the rest of the time.

Gizmag: Injectable nanoparticles maintain normal blood-sugar levels for up to 10 days.

Fascinating technology featured in Gizmag & posted by someone HERE.

The nano-network that releases insulin in response to changes in blood sugar

"The injectable nano-network is made up of a mixture that contains nanoparticles with a solid core or insulin, modified dextran (which is commonly used to reduce blood viscosity), and glucose oxidase enzymes. When exposed to high levels of glucose, the enzymes convert glucose into gluconic acid, which breaks down the modified dextran to release the insulin. The gluconic acid and dextran, which are biocompatible, dissolve in the body, while the insulin brings the glucose levels under control.

The nanoparticles are given a positively or negatively charged biocompatible coating so that when they are mixed together, they are attracted to each other to form a “nano-network.” The positively charged coatings are made of chitosan, a material found in shrimp shells that has also found applications in self-healing car paint, while the negatively charged coatings are made of alginate, a material normally found in seaweed."

Wow! Cool bananas!

When the only tool in the box is a hammer...

Everything that needs fixing looks like a nail.

People with diabetes mellitus are issued with blood glucose meters - and nothing else.

For people with type 1 diabetes, that's fine. They lack insulin, so they have to inject insulin in the right amounts & types to keep their blood glucose levels within reasonable limits. Applying Bernstein's Law of small numbers by reducing glycaemic load to a minimum keeps blood glucose levels within reasonable limits (between 3 & 7mmol/L) most of the time. See also The problem with Diabetes.

For people with type 2 diabetes and excessive visceral (belly) fat (~85% of people with type 2 diabetes), that's not fine. Their disease is a disease of chronic excess intake relative to oxidation, causing fasting dyseverythingaemia
(hyperglycaemia, hypercholesterolaemia, hyperNEFAaemia, hypertriglyceridaemia, hyperuricaemia, etc). People who have type 2 diabetes don't have only postprandial hyperglycaemia - they also have postprandial hypertriglyceridaemia. See Lifestyle Intervention Leading to Moderate Weight Loss Normalizes Postprandial Triacylglycerolemia Despite Persisting Obesity. Postprandial hypertriglyceridaemia is atherogenic. See Ultra-high-fat (~80%) diets: The good, the bad and the ugly.

However, because the only tool in the box of someone with type 2 diabetes is a blood glucose meter, their disease looks like one of only hyperglycaemia. Applying Bernstein's Law of small numbers by reducing carbohydrate intake to a minimum keeps blood glucose levels within reasonable limits, but makes other things worse if energy from carbohydrates is replaced by energy from fats.

Only if energy from carbohydrates is reduced AND energy from fats isn't increased to compensate (i.e. eat a LCLF PSMF or Modified PSMF until sufficient visceral fat has been lost), does carbohydrate restriction help people with type 2 diabetes.

Impaired Glucose Tolerance: also between a rock and a hard place.

A high percentage of people with excessive visceral adiposity (belly fat) have Impaired Glucose Tolerance (IGT). This post is about them.

Image from http://carbsanity.blogspot.co.uk/2013/03/insulinproinsulinetc-in-normal-igt-and.html

IGT is caused by excessive NEFAs spewing into the blood and/or deficiencies and/or sedentariness.

If nothing is done about it, IGT will progress to full-blown Type 2 Diabetes, which will get worse and worse as per the graphs to the right of the IGT one.

To do something about it, see http://nigeepoo.blogspot.com/2011/02/insulin-resistance-solutions-to.html

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.

New treatment might put Type 2 diabetes in remission.

From:
http://www.ctvnews.ca/mobile/new-treatment-might-put-type-2-diabetes-in-remission-1.806064
"A new study by Toronto researchers on a new way to treat type 2 diabetes shows it may cause temporary remission of the disease in up to 75 per cent of patients.
 
The new treatment involves taking four shots of insulin -- the medication required by some diabetics to control blood sugar levels -- per day for just one month. This is a change from the usual treatment, which involves daily insulin shots over an extended period of time.

Patients develop diabetes when their pancreas can't produce enough insulin to lower blood sugar levels after meals. While medications can temporarily boost insulin production, many type 2 diabetics face a lifetime of daily insulin shots. Over time, patients with the disease can go on to suffer from a range of complications including blindness, heart disease, kidney problems and nerve damage.

Dr. Bernard Zinman, the director of the Leadership Sinai Centre for Diabetes and lead researcher of the study, explained how the new treatment works to CTV News. According to Zinman, by giving type 2 diabetics concentrated levels of insulin for a month early on in their disease, their pancreas, in effect, gets a "a break."

"The diabetes in essence goes away because their own pancreas now can make enough insulin," he said.

After the month on concentrated doses, patients are required to take another type of medication to "maintain" the remission, said Zinman.

Zinman said that the period of remission may eventually wear off, and so he sees the possibility of a future "top-up" treatment, which would last another month.

While the remission period can vary in patients, the prospect of improving pancreatic function is an exciting development in diabetes research, said Dr. Ravi Retnakaran, co-researcher of the study.

"This is a very novel and exiting way of treating diabetes that could have important implications," said Retnakaran.

For patients involved in the study, the treatment has had a major impact on their quality of life. Francoise Hebert was diagnosed with type 2 diabetes in November 2010. Seven months ago she enrolled in the study, and while she found the four daily insulin doses challenging, her blood sugar levels are now normal.

Hebert now happily tells people she "no longer has the disease," and enjoys knowing she's delayed any progression of diabetes-related complications.

"It feels fabulous," she said with a laugh. "It feels absolutely wonderful."

In addition to having her diabetes go into remission, Hebert says she's also learned how to eat better and hopes to eventually be able to get her weight under control.

Type 2 diabetes is primarily caused by an unhealthy diet and physical inactivity.

The research team at Mount Sinai Hospital hopes to have study results in a year or two, as well as more safety data on the medication."

Can very-low-carb diets impair your mental faculties?

I wanna tell you a story...

In 2006, I had a test done on my pituitary gland*, called an Insulin Shock Test. It was pretty much what it said on the tin. I laid on a hospital bed, I was injected with an overdose of insulin and I was monitored for blood glucose and growth hormone levels every 30 minutes.

My blood glucose fell and fell and fell and fell until it reached ~1.5mmol/L (~27mg/dL). What happened was interesting. I came out in a cold sweat and developed a tremor. Apart from that, I felt fine. The consultant in charge was chatting to me and I was chatting to him. Eventually, I was given a sandwich, a yoghurt and a banana to eat.

Some time later, when I had stopped sweating and shaking, the consultant returned and told me that I had become confused. My brain had ceased to function correctly due to a lack of blood glucose (the insulin had totally suppressed serum FFAs and ketones, so there were no other brain fuels available), but I was too mentally-impaired to know that I was mentally-impaired. As far as I was concerned, everything was fine & dandy. This is like the Dunning-Kruger effect.

Referring to Blood Glucose, Insulin & Diabetes, as blood glucose falls due to either starvation or a lack of dietary carbohydrate, insulin falls and glucagon rises, stimulating the liver to convert liver glycogen into glucose for export to the blood. Eventually, liver glycogen becomes depleted and blood glucose falls again. The pituitary gland notices this and secretes AdrenoCorticoTropic Hormone (ACTH) which stimulates the adrenal cortex to secrete cortisol. The adrenal glands are also stimulated to secrete adrenaline (a.k.a. epinephrine). Cortisol increases the conversion of amino acids and other substrates into glucose by the liver and kidneys. If blood glucose continues to fall, the pituitary gland secretes growth hormone (GH), which has an anti-insulin effect.

From http://anthonycolpo.com/boosting-growth-hormone-with-diet-training-fact-or-fiction-part-2/:-
"after the zero-carb phase, subjects reported symptoms of hypoglycemia that included weakness, irritability, mental confusion, nausea, hunger, cold sweating and disturbed co-ordination. GH levels were higher during exercise after the low-carb phase, but so too were levels of other fuel mobilizing hormones such as epinephrine, glucagon, and cortisol." Epinephrine, glucagon, and cortisol are stress hormones. Chronically-high blood levels of stress hormones disrupt sleep and cause irritable, aggressive behaviour.

Ethanol inhibits gluconeogenesis in the liver (possibly also in the kidneys) resulting in worse hypoglycaemia. Worse hypoglycaemia results in more ACTH & adrenaline secretion and worse hypercortisolaemia, which can adversely affect the hippocampus, impairing memory.

In conclusion, if you want to eat a very-low-carb diet, long-term:-1) Don't do much high-intensity exercise. See "Funny turns": What they aren't and what they might be.
2) Don't drink much (if any) booze.

*My pituitary gland failed the test by secreting only 40% the amount of GH that it was supposed to. For six months, I was given GH to inject using a special pen with a 8mm x 0.3mm needle. By the end of the six month trial, I had perfected the art of painless injection. The trial was discontinued due to lack of any noticeable benefit (17 days supply of GH @0.3mg/day cost £120!).

Type 2 diabetes in the UK.

From Insulin usage in type 2 diabetes mellitus patients in UK clinical practice: a retrospective cohort-based analysis using the THIN database:-

"Importantly, this analysis has been conducted using routine data from UK clinical practice, which allows an insight into how patients are managed in current UK practice. In summary, this study demonstrates a persisting delay both in oral therapy escalation and insulin initiations in patients with type 2 diabetes, with a relative reduction in the effectiveness of oral therapy escalation. There is an apparent threshold HbA1C of > 8.5% beyond which additional oral therapy in routine practice appears unlikely to achieve an HbA1C target ≤ 7.0%.
This study thus highlights the need for more timely escalation of glucose-lowering therapy, including insulin initiation, in order to limit unnecessary patient exposure to hyperglycaemia and associated serious consequences, such as macro-vascular and micro-vascular complications."

An HbA1C of 7.0% still results in macro-vascular and micro-vascular complications. If someone develops type 2 diabetes in the UK, the NHS isn't going to save them. They have to save themselves.

See also Having Diabetes and Car Insurance and Applying for a Driving Licence and Informing the DVLA. Basically, developing type 2 diabetes in the UK sucks.

People who have Impaired Glucose Tolerance need to take action to prevent their condition from deteriorating into full-blown Type 2 diabetes. See http://nigeepoo.blogspot.co.uk/search/label/Diabetes.

Dr. Richard K Bernstein on insulin for type 2 diabetics, and some definitions.

Dr. Richard K Bernstein:-

Dr. Richard Bernstein, the world's leading low-carb diabetologist, says in Diabetes: The Basics:-
"Many people (including the parents of diabetic children) view having to use insulin as a last straw, a final admission that they are (or their child is) a diabetic and seriously ill. Therefore they will try anything else - including things that will burn out their remaining beta cells - before using insulin. Many people in our culture have the notion that you cannot be well if you are using medication. This is nonsense, but some patients are so convinced that they must do things the “natural” way that I practically have to beg them to use insulin, which is as “natural” as one can go. In reality, nothing could be more natural. Diabetics who still have beta cell function left may well be carrying their own cure around with them - provided they don’t burn it out with high blood sugars and the refusal to use insulin."

Some definitions:-

From Low-carbohydrate diet:-
"The term "low-carbohydrate diet" is generally applied to diets that restrict carbohydrates to less than 20% of caloric intake, but can also refer to diets that simply restrict or limit carbohydrates."
A typical woman consumes ~2000kcals/day. A typical man consumes ~2,500kcals/day. Therefore...

Very-low-carb diet = <10% energy from carbs ≡ <~50 or ~62.5g carbs/day.
Low-carb diet = <20% energy from carbs ≡ <~100 or ~125g carbs/day.
"Healthy eating" = >55% energy from carbs ≡ >~275 or ~344g carbs/day.

It’s the Calories, Stupid.

I thought I'd mark my return to blogging by taking the piss out of a certain Diet Doctor for his post It’s the Insulin, Stupid, who takes (and tweaks) Fig 7A from Hyperinsulinemia Drives Diet-Induced Obesity Independently of Brain Insulin Production.

At first glance, Fig 7A looks like a CIH believer's dream come true (apart from the words "High Fat Diet").

Hyperinsulinemia → Obesity.

Obesity is caused by too much insulin. Game, Set and Match to insulin.

Not so fast! Let's take a look at the rest of Fig 7.

Figure 7. Revisiting the Current Model of Obesity and Type 2 Diabetes(A) The most widely accepted model of the pathogenesis of obesity and type 2 diabetes posits that a high-fat diet leads to obesity and insulin resistance (there is debate about the relative order and causality of these). In this widely held view, insulin resistance then leads to hyperinsulinemia, which is followed by β cell exhaustion, and then type 2 diabetes. The accepted model is incompatible with our results that put the insulin hypersecretion genetically upstream of obesity.(B) Our data support a model whereby insulin levels must be kept low to maintain energy expenditure in white adipose tissue via the expression of Ucp1. Our data do not address the order of subsequent events after obesity (outside the yellow box), such as insulin resistance and/or type 2 diabetes, since they were not observed in our studies. In other words, the effects of insulin gene dosage on obesity are independent of sustained changes in glucose homeostasis or insulin resistance.

↑ Peripheral Hyperinsulinemia → ↓ Uncoupling Proteins (WAT) → ↓ Energy Expenditure → ↑ Obesity.

Obesity is caused by a reduction in energy expenditure in these mice. Game, Set and Match to The Energy Balance Equation. It’s the Calories, Stupid. In these mice, energy expenditure is strongly influenced by insulin levels. In humans, not a lot. In humans, insulin can act as a stimulant or a sedative.

I'm not an insulin denier as is obvious from my other blog posts. I'm still restricting my carbohydrate intake to ~125g/day from whole foods.

I'm not a food reward denier. I've been using food reward principles to lose weight.

This post will probably annoy some people. Before wasting your time writing a comment, please read my Moderation Policy.

Hyperinsulinaemia and Insulin Resistance - An Engineer's Perspective.

Another techie post.

From https://en.wikipedia.org/wiki/Negative_feedback_amplifier

There's been some arguing discussion over whether Hyperinsulinaemia (HI) causes Insulin Resistance (IR). My answer is...Yes and No.

HI increases IR, long-term. See Downregulation and upregulation: The Insulin Receptor and Insulin oscillation.

HI doesn't increase IR, short-term. How can I claim this? The above diagram represents a Negative Feedback (NFB) control system, which is how Blood Glucose is regulated.

"Input" represents Glucose from digested sugars and starches. The arrow pointing at AOL represents Blood Glucose (BG). The triangle containing AOL represents pancreatic beta cells. "Output" represents Insulin Secretion (ISec). More BG = More ISec.

The box containing ß represents three things that work in parallel to reduce Blood Glucose.
1) The Liver. More ISec = Hepatic Glucose Production rate decreased.
2) Muscle mass. More ISec = Glucose intake to Muscle mass rate increased, via Glu-T4.
3) Fat mass. More ISec = Glucose intake to Fat mass rate increased, via Glu-T4.
The three things aren't of equal strength, but they provide overall negative feedback.

If overall negative feedback is halved due to doubling of overall IR in the above three paths, ISec doubles. If you don't believe me, see Idealised Negative Feedback Inverting Amplifier using an idealised op amp on WolframAlpha. Double the value of resistance 2 (the negative feedback resistor R2). and the output voltage on the inverting amplifier doubles from -10V to -20V.

The idealised Negative Feedback Inverting Amplifier using an idealised op amp on WolframAlpha is interesting in that an idealised op amp (the triangle with + and - inputs) has infinity gain and ±infinity voltage on its power supplies. As a result, there is zero volts (output voltage divided by infinity) between the idealised op amp's + terminal and its - terminal. If the idealised op amp's + terminal is connected to 0V (a.k.a. "Earth"), its - terminal is at 0V (a.k.a. "Virtual Earth") and has zero variation, whatever the input voltage. An actual op amp has a voltage gain of ~140dB (~10,000,000), so an output voltage of -10V can be achieved with a voltage of 1uV (one millionth of a Volt) on its - terminal.

If pancreatic beta cells had a zero threshold and infinity gain like an idealised op amp, BG would be zero and have zero variation with varying Glucose input. Pancreatic beta cells actually have a positive threshold and low gain, so BG is positive and varies slightly with varying Glucose input.

If ISec becomes zero (as in type 1 diabetes), there is zero negative feedback and BG increases. The same thing happens to the voltage on the idealised op amp's - terminal if its power supplies are 0V instead of ±infinity.

If ISec becomes insufficient (as in type 2 diabetes), there is insufficient negative feedback and BG increases. The same thing happens to the voltage on the idealised op amp's - terminal if its power supplies are limited to ±5V.

Having established that ISec is proportional to overall IR, what would happen if overall IR was proportional to ISec? If ISec doubled, overall IR would double, which would double ISec, which would double overall IR, ad infinitum. ISec would increase to maximum instantly. THIS DOESN'T HAPPEN. Therefore, IR doesn't increase in proportion to ISec, short term.

Long-term, increased ISec increases IR for a variety of reasons, one of them being that increased ISec increases the rate at which cells fill with glycogen. Once full of glycogen, cells must down-regulate their intake by down-regulating Glu-T4 and Glu-T2 (fat and liver cells also up-regulate their output of stuff) or burst.

Reduce your IR by addressing all of the factors in Insulin Resistance: Solutions to problems.

Chris Highcock emailed me a link to Muscular strength and markers of insulin resistance in European adolescents: the HELENA Study.

A comment, a simile and insanity.

1) The comment: I'm just about to leave the following comment on Peter (Hyperlipid)'s blog post Insulin and the Rewards of overfeeding. I thought that it was so good at summing-up, I'll post it here first!
"All,

Insulin increases the amount of glucose & FFAs entering fat cells, muscle cells & the liver.

Insulin decreases the amount of glycerol & FFAs exiting fat cells & the amount of glucose exiting the liver.

Hyperinsulinaemia (which can produce sedation) results when one or more of the following tissues loses insulin sensitivity:- fat cells, muscle cells & the liver.

So, why do people keep saying that hyperinsulinaemia locks nutrients away in fat cells only, thus robbing other cells of nutrients, thus causing lethargy?

The relative insulin sensitivity of tissues determines the relative partitioning of nutrients into those tissues.

When tissues lose sensitivity to insulin, blood glucose control becomes impaired. This results in roller-coaster blood glucose levels after eating high-glycaemic carbohydrates. A rapidly-falling blood glucose level causes ravenous hunger. I have experienced this during medically-monitored tests (OGTTs & an insulin shock test).

Low-carb/ketogenic diets don't result in a roller-coaster blood glucose level and therefore don't cause ravenous hunger. Simples!

Overeating due to ravenous hunger is NOT gluttony, just as under-moving due to sedation is NOT sloth.

THIS is gluttony."

EDIT: This didn't go in my comment but should have:- "Low-carb/ketogenic diets result in the avoidance of moreish & calorific foods such as sweets, chocolate, cake, biscuits, pizza, Pringles etc. A single bite of such foods has a negligible effect on blood glucose & insulin levels, but encourages another bite and another and another ad nauseam, due to Food Reward.


2) The simile: I use similes. I used the simile "As happy as a pig in shit" in a comment somewhere on Woos blog. Now, you may (or may not) have noticed that my user-name is Nigeepoo. We Brits are obsessed by two things - The weather and our bowel movements. I find things to do with poo and farting amusing (schoolboy humour, I know!). I used the simile "As happy as a pig in shit" because it is amusing.


3) The insanity: According to Woo in the following comment:-
"Re: the comment...Sorry, not convinced.
You are basically refusing to admit your choice of words implied moral judgement. The phrase "happier than a pig in shit" is always applied to examples of people being content in immorality/bad behavior particularly gluttony and sloth... unless it is used ironically. Only an autistic or a non-english speaker would believe this crap."

Woo, you are as mad as a March hare. IMO of course, like everything I write. Duh!