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

I'm not an insulin denier as is obvious from my other blog posts. I'm still controlling my carbohydrate intake.
I'm not a food reward denier and I've been using food reward principles to lose some more weight.

The above post will probably annoy some people. Before wasting your time writing a comment, please note my Moderation Policy.

Hyperinsulinaemia and Insulin Resistance - An Engineer's Perspective.

Another techie post.

From http://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 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 = Less BG Production.
2) Muscle mass. More ISec = More BG imported to Muscle mass, via Glu-T4.
3) Fat mass. More ISec = More BG imported to Fat mass, 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 Rf) from 10,000ohms to 20,000ohms 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 infinite gain and infinite 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 infinite 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 has significant variation with varying Glucose input.

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

If ISec becomes insufficient (as in type 2 diabetes), there is insufficient negative feedback and BG goes up a bit. The same thing happens to the voltage on the idealised op amp's - terminal if its power supplies are 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. 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 import by down-regulating Glu-T4 and Glu-T2 (fat and liver cells also up-regulate their export of stuff) or rupture.

So, deplete your cells of glycogen by eating a diet that results in you unconsciously eating less and moving more. Also, do some higher-intensity exercises. 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.

A lot of my recent titles contain three items.

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 a roller-coaster blood glucose level after eating high-glycaemic carbohydrates. A rapidly-falling blood glucose level can cause 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!

Over-eating 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 to me.

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!

Testing hypotheses - a rant.

My brain just exploded! On Why conventional view of obesity / FR is wrong, ItsTheWoo wrote "...there is not a doubt in my mind obesity is entirely 100% an illness, a disorder... "

According to ItsTheWoo's hypothesis, the increasing incidence of obesity all around the world since 1970 is 100% caused by the increasing incidence of illness all around the world since 1970. Seriously, WTF?

According to Nigeepoo's hypothesis, the increasing incidence of obesity all around the world since 1970 is significantly caused by the increasing influence of Crap-in-a-Bag/Box/Bottle (CIAB) manufacturers on the population by cunning marketing and on the Government by bribery lobbying since 1970.

The former results in increasing consumption of CIAB and the latter results in increasing subsidies on the raw materials used for manufacturing CIAB, making CIAB cheaper (also more profitable) than natural foods, thus increasing consumption of CIAB. See Why are Twinkies cheaper than carrots?

There are other factors causing increased obesity e.g. increasing numbers of towns/cities which discourage walking. See also Determinants of the Variability in Human Body-fat Percentage.

Highly-engineered and highly-calorific CIAB encourages subconscious over-eating via Food Reward. The hyper-secretion of insulin (compensatory hyperinsulinaemia) caused by the subconscious over-eating of CIAB causes subconscious under-moving by inducing drowsiness and lethargy, sometimes followed by the munchies if blood glucose goes too low. Insulin is just a hormone that is secreted for the storage of stuff and a reduction in the burning of stuff. Don't blame insulin for doing its job. If you have zero insulin (e.g. untreated type 1 diabetes), your body stops storing stuff and starts burning stuff uncontrollably. Before the invention of insulin injections, people with type 1 diabetes usually died within 2 years.

Subconscious over-eating is good for the profits of CIAB manufacturers. An increasing number of dyslipidaemic/hypertensive/depressed/diabetic/demented/w.h.y. people is good for the profits of health-care providers and drug manufacturers. These organisations currently make huge profits, so it's not going to be easy to change anything that will reduce them.

I deleted the last part of my rant as it was a bit too ranty, but I'm reinstating it in a toned-down form as I've mentioned it in the comments.

ItsTheWoo continually conflates subconscious over-eating and under-moving with conscious over-eating and under-moving (gluttony and sloth). The vast majority of over-fat people become over-fat due to subconsciously over-eating and under-moving. A tiny minority of over-fat people are gluttonous and slothful.

Telling people to consciously Eat Less, Move More doesn't work. This doesn't mean that Eat Less, Move More doesn't work. It means that Eat Less, Move More has to be done subconsciously. This is where low-carb/paleo/real food diets come into their own.

Rant over.

Insulin Resistance: Solutions to problems.

Before I start on what may be the most important thing that I've ever written, here's "Don't Stop Movin" by S Club 7. It's a clue to what's coming.


The problem:
Insulin Resistance (IR) is a major problem for a significant percentage of the population in the developed world. It can cause:-

High fasting serum glucose, which increases the risk factor for Coronary Heart Disease.
High post-prandial serum glucose, which increases the risk factor for Coronary Heart Disease, Retinopathy, Neuropathy & Nephropathy (Kidney failure) amongst other things.
High serum cholesterol.
High serum triglycerides, which in conjunction with high serum cholesterol increases the risk factor for Coronary Heart Disease.
High serum Free Fatty Acids (a.k.a. FFAs a.k.a. NEFAs) from IR fat cells, which increases the risk factor for Sudden cardiac death and also worsens IR in liver & muscle cells.
High serum uric acid, which increases the risk factor for Gout & urate Kidney stones.
Hypertension, which raises the risk factor for Coronary Heart Disease, Strokes & Kidney failure.
Excessive appetite after eating high-GL carbohydrates, due to rebound low serum blood glucose, leading to overeating & obesity.
Lethargy after eating almost anything, but especially after eating high-GL carbohydrates, due to compensatory hyperinsulinaemia.
If IR is left untreated, it can deteriorate into type 2 diabetes. See Type 2 diabetes in the UK.

The cause and solutions:
1) "Bad" genes. My genes aren't particularly good, but it is possible to change the expression of your genes.

2) Full cells. A full cell is an IR cell. Consider Liver, Muscle and Fat cells:-

a) Liver cells: Liver cells are a 2-way street. "Stuff" (e.g. NEFAs, Glucose & Fructose) goes in and "stuff" (e.g. Ketones & Glucose) comes out. Glucose normally comes out of the liver at a rate of ~5g/hour to fuel the brain, but this can increase a lot under the control of Insulin, Glucagon & Cortisol. If more stuff goes in than comes out, liver glycogen stores fill up and vice-versa. When liver glycogen stores become full, liver cells down-regulate processes that produce liver glycogen e.g. hexokinase & Glu-T2 transporters. Liver cells effectively become IR to stop more stuff from going in.

However, fructose uses Glu-T5 transporters which are insulin-independent & fructokinase which has a high affinity for fructose, so fructose effectively "barges its way in" to the liver. This is why fructose is a problem for people who have permanently full liver glycogen stores.

b) Muscle cells: Muscle cells are a 1-way street as far as Glucose is concerned, though Amino Acids can go in & come out. Muscle glycogen cannot be used to produce serum glucose - it can only be used by muscles. When muscle glycogen stores become full, muscle cells down-regulate processes that produce muscle glycogen e.g. hexokinase & Glu-T4 transporters. Muscle cells effectively become IR to stop more stuff from going in.

As per It's all in a day's work (as measured in Joules), muscle cells use mostly fat at rest & lowish-intensity exercise. Glycogen usage increases rapidly as exercise intensity increases. Now do you see the significance of the music video above? Intense exercise (e.g. Running, Sprinting, Resistance training with weights, parts of High-Intensity Interval Training a.k.a. HIIT, parts of Tabata & parts of Zumba) depletes your muscle cells and makes them Insulin Sensitive.

This means that exercise is compulsory. I have been in denial for years. Then, Uh-oh! There may be trouble ahead... happened. See Increased Glucose Transport–Phosphorylation and Muscle Glycogen Synthesis after Exercise Training in Insulin-Resistant Subjects and Improvement in Glucose Tolerance After 1 Wk of Exercise in Patients With Mild NIDDM (hat-tip to Go Kaleo). See also Move More: Solutions to problems.

However, don't overdo it! You may have a funny turn, keel over & hurt yourself. See "Funny turns": What they aren't and what they might be.

c) Fat cells: Fat cells are a 2-way street. Fat cells are a bit like balloons that are full of holes. As stuff (e.g. NEFAs & glucose) goes in, the balloon expands to accommodate it. As more stuff goes in and the balloon gets bigger, the internal pressure increases and the holes get bigger, so stuff (e.g. NEFAs & glycerol) comes out at a faster rate. At some level of fullness, stuff comes out as fast as it goes in. At that point, fat cells are effectively IR. So, don't overstuff your fat cells by getting too fat. If you are already too fat, medium intensity exercise (e.g. Walking, Power Walking, Jogging, "Aerobics", parts of High-Intensity Interval Training a.k.a. HIIT, parts of Tabata & parts of Zumba) depletes your fat cells and makes them Insulin Sensitive.

Dress appropriately so that you don't feel cold. Feeling cold is what stimulates your appetite, not exercise. See Influence of resistance and aerobic exercise on hunger, circulating levels of acylated ghrelin, and peptide YY in healthy males. I go for a 30 minute walk each evening.

3) Deficiency in Vitamin D3.
See Hypovitaminosis D is associated with insulin resistance and ß cell dysfunction.
The effects of calcium and vitamin D supplementation on blood glucose and markers of inflammation in nondiabetic adults.
The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis.
A double-blind, randomized, placebo-controlled trial of the short-term effect of vitamin D3 supplementation on insulin sensitivity in apparently healthy, middle-aged, centrally obese men.
Plasma 25-hydroxyvitamin D concentration and metabolic syndrome among middle-aged and elderly Chinese individuals.
Vitamin D supplementation reduces insulin resistance in South Asian women living in New Zealand who are insulin resistant and vitamin D deficient - a randomised, placebo-controlled trial.

In January 2003, I had impaired Glucose Tolerance (fasting serum glucose = 6.8mmol/L & 2 hours post-75g glucose load serum glucose = 8.7mmol/L). A sandwich used to send me to sleep.

By September 2008, I had normal Glucose Tolerance (fasting serum glucose = 5.0mmol/L & 2 hours post-75g glucose load serum glucose = 3.7mmol/L). I also no longer suffered from hyperinsulinaemic drowsiness. I was also about the same weight that I was in 2003, so the improvement was not due to weight loss.

So, either use a UVB sun-lamp as per instructions to receive a sub-erythemal dose (not quite going pink) or get tested by your GP and supplement with Vitamin D3 accordingly. I take 5,000iu of Vitamin D3/day.

4) Deficiency in Magnesium.
For the top 999 foods highest in Magnesium per 100g serving, see HERE. I take ~4g of Epsom Salts/day (~400mg Mg/day). 

5) Deficiency in Vitamin K2.
See Vitamin K₂ prevents hyperglycemia and cancellous osteopenia in rats with streptozotocin-induced type 1 diabetes. Good sources of Vitamin K2 can be found HERE. I take a Vitacost Ultra Vitamin K with Advanced K2 Complex/day. Note: Warfarin/Coumadin works by depleting Vitamin K, so lots of Vitamin K2 makes Warfarin/Coumadin ineffective. 

6) Deficiency in Manganese. See Manganese supplementation protects against diet-induced diabetes in wild type mice by enhancing insulin secretion. For the top 999 foods highest in Manganese per 100g serving, see HERE.

7) Deficiency in, or excess of Copper w.r.t. Zinc. See Dietary copper supplementation restores β-cell function of Cohen diabetic rats: a link between mitochondrial function and glucose stimulated insulin secretion. For the top 468 foods highest in Copper per 100g serving, see HERE.

8) Deficiency in, or excess of Zinc w.r.t. Copper. See Zinc, pancreatic islet cell function and diabetes: new insights into an old story. For the top 999 foods highest in Zinc per 100g serving, see HERE.

9) Excessive intake of man-made trans-fats.
Base your diet on Real Food rather than manufactured food products.

10) Excessive intake of chemicals.
Don't swallow toothpaste (fluoride) or disclosing tablets (may contain iodine). Don't hold till receipts between your lips (may be coated in BPA). Don't slather too many chemicals on your skin.

Any other ideas for normalising insulin sensitivity?

Finally, the obligatory picture. Hannah Spearritt is rather nice. :-p

I nearly forgot! Today, when I arrived at mum's nursing home, I found her reading a book. She hasn't done that for over a year. She even knew that it was Wednesday. Ketogenic diet for the win. Mum now has a dual-fuel brain.

A blast from the past.

Look who's turned up on the BBC food boards after a 4-5 years absence. A big "Welcome back" to Zoë Harcombe, who has the site 'Why do you overeat? When all you want is to be slim' and The Harcombe Diet.

We agree on most things. The problem with counting Calories is that, if you reach your Calorie limit by 6pm, what do you do? Spend the rest of the evening hungry and go to bed with a rumbling tummy & hunger pangs? Or just have one teensy-weensy bite to eat, which turns into a "nom-a-thon"? I know what I would do, as I can resist anything.......except temptation!

What we don't agree on is that Calories don't count. I say that they do. So does Lyle McDonald and Anthony Colpo. For people who are restrained to a hospital bed, changing the relative proportions of carbohydrate & fat (keeping protein constant) in their diet makes no difference whatsoever to their long-term weight gain/loss (ignoring glycogen + water weight differences). What it does make a difference to is how much these restrained people would beg for food. On a high-carb diet, I was much hungrier than when I was on a low-carb diet. This is why I ate way too much on the former diet (& got fat) and ate much less on the latter diet (& got slim).

It's thought that Insulin is the only hormone responsible for body-fat storage. This isn't correct.

Insulin makes the body store glucose (from dietary carbohydrates) and amino acids (from dietary proteins) and stops the body from burning fats. Therefore, having chronically-high serum insulin levels (hyperinsulinaemia) is not desirable for people wishing to burn body-fat for fuel.

As we all know, dietary carbohydrate raises serum insulin levels by raising blood glucose. See http://www.mendosa.com/gilists.htm.

However, dietary protein also raises serum insulin levels. See http://www.mendosa.com/insulin_index.htm.

Eating most fats with carbohydrates raises serum insulin levels even higher still, although fats lower the glucose response. See http://jn.nutrition.org/cgi/reprint/133/8/2577.pdf. What do junk foods mostly consist of? High-GI carbohydrates + fats. However, omega-3 fats reduce the hyperinsulinaemia caused by the other fats. See http://diabetes.diabetesjournals.org/cgi/reprint/53/suppl_1/S166.pdf.

Eating fat on its own does not raise serum insulin levels. See http://intl.ajcn.org/cgi/reprint/75/3/505.pdf. However, it's still possible to gain body-fat by eating too many Calories of dietary fat. Acylation Stimulating Protein (ASP) makes the body store dietary fat as body-fat. See http://www.jlr.org/cgi/reprint/30/11/1727.pdf.

The amount of food that free-living people (i.e. people who are not restrained to a hospital bed) eat depends mostly on their appetites. This is affected by the food that they eat (the low blood glucose that follows hyperinsulinaemia causes severe hunger pangs) and also advertisements. Watch this Google video of Adam Curtis' BBC documentary The Century Of The Self - Part 1 of 4.

I hope that you all had a good Christmas.

Carbohydrates: Dogs' Doodads or Spawn of Satan?

Depending on which side of the fence you're on, Carbohydrates are either the Dogs' Doodads or the Spawn of Satan. As I get older, I prefer to sit on the fence. Let's start with the basics.

What are Carbohydrates?
Carbohydrates are so named because they have the generic formula (CH2O)n. C is carbon and H2O is water hence Carbo-Hydrate. There are several different types.

1) Sugars. There are monosaccharides, the most common being Glucose (a.k.a. Dextrose), Fructose and Galactose. There are disaccharides, the most common being Sucrose, Lactose and Maltose. Disaccharides are 2 monosaccharides linked by a glycosidic bond formed by a condensation reaction (removal of a water molecule, usually by an enzyme). Disaccharides have to be hydrolysed (have a water molecule added back in, usually by an enzyme) into monosaccharides before they can be absorbed in the gut.
Sugars are simple carbohydrates.

2) Starches. These are chains of glucose molecules linked by glycosidic bonds. Starches have to be hydrolysed into glucose molecules before they can be absorbed. There are unbranched chains like amylose which is also known as resistant starch. There are branched chains like amylopectin and maltodextrin. Glycogen is a branched chain "animal starch" that is synthesised inside muscle and liver cells and which can be rapidly converted back into glucose inside cells.

3) Non-Starch Polysaccharides (NSPs). These are also known as fibre/fiber and there are 2 types: soluble (e.g. pectin, beta-glucan & cellulose) and insoluble (e.g. bran). These aren't absorbed, but gut bacteria can feed on soluble fibre/fiber. Starches and NSPs are complex carbohydrates.

For more information, see http://en.wikipedia.org/wiki/Carbohydrate

The amount of carbohydrate that someone needs varies from person to person and increases with the intensity and volume of exercise done. See Everyone is Different. What are the best carbs to eat? "Complex" ones from "wholegrain" cereals? Not necessarily.

Simple vs Complex
TV ads for breakfast cereals bang on about the wholegrain goodness of complex carbohydrates releasing energy slowly. The terms "Simple" and "Complex" actually refer purely to the chemical structure of a carbohydrate and have nothing to do with how fast they turn into blood glucose in the body. The Glycaemic Index (GI) (or Glycemic Index if you're American) relates to how fast carbohydrates turn into blood glucose in the body. See http://www.mendosa.com/gilists.htm for a list of 750 foods and their GI & GL (GL = Glycaemic Load = GI/100 x carb content per serving). Here are a few extracts. Note: a GI of 55 is low; a GL of 10 is low.

The last three items in the list are all simple carbs. As you can see, some wholegrain complex carbs turn into blood sugar faster than simple carbs. This because the wholegrains have been ground into powder which is rapidly digested and absorbed, despite the presence of fibre/fiber.

As fructose has such a low GI, does this mean that we can eat as much of it as we like? No. When we eat fructose, it passes from the small intestine into the portal vein and goes straight to the liver. As liver cells contain an enzyme called fructokinase (which has a high affinity for fructose), all dietary fructose is absorbed by the liver where it tops-up liver glycogen. Liver glycogen is also topped-up by glucose (obtained from the digestion of starchy carbs). Once liver glycogen stores are full, any further fructose is converted into.......triglycerides. High serum triglycerides are heart-unhealthy. See Cholesterol And Coronary Heart Disease.

Why is GI important? When we eat carbohydrates, they raise blood glucose levels. Pancreatic beta cells secrete a hormone called insulin, which allows more glucose to pass into cells (by moving Glu-T4 transporters inside the cells). When more glucose enters cells, glucose levels in the blood fall. It's a negative feedback loop. For millions of years, we lived on a diet of natural, unrefined carbohydrates and so the secretion of insulin never had to change blood glucose levels very rapidly.

When unnatural, refined, high-GI carbs are eaten, blood glucose levels rise much faster. This results in over-secretion of insulin (hyperinsulinaemia). This shuttles too much glucose into cells and results in.......low blood glucose. Rapidly-falling and low blood glucose levels cause feelings of severe hunger and cravings to eat more carbs. It's a vicious circle. Hyperinsulinaemia also has other bad effects on the body. See http://www.mercola.com/2001/jul/14/insulin.htm to learn about Insulin and its Metabolic Effects.

GI has a weakness because adding fats and some proteins to high-GI foods lowers the GI but can increase the insulin response. Saturated fats, monounsaturates and omega-6 polyunsaturates raise the insulin response to carbs.

There is another index called the Insulin Index (II). See http://www.mendosa.com/insulin_index.htm.
The II contains a few surprises. Some proteins (e.g. the whey in milk & yoghurt) produce a large insulin response. As over-secretion of insulin can cause low blood glucose which causes severe hunger pangs, it's not something that someone who wants to lose body-fat really wants. Therefore,the consumption of foods with an II greater than 60 should be minimised for optimum fat loss. So take it easy with the baked beans ("my carbohydrates are exceedingly complex"). Overcooking foods raises their GI & II and baked beans are well-overcooked in a sugary sauce. EDIT: I now know that insulinogenic proteins are also glucogenic, so there is no low blood glucose.

On the other hand, refrigerating some foods lowers their GI & II by changing the starch in them into resistant starch, even if the food is subsequently re-heated. Rice & potatoes are two such foods.

As the terms "simple" and "complex" are meaningless in terms of carbohydrates' effects in the body, I prefer to use the terms "slow" and "fast". In a nutshell, slow carbs are good and fast carbs are bad. These terms can be applied to proteins, too. Egg is slow and whey is fast. Sticking to mostly slow foods keeps blood glucose and insulin levels stable, which results in better appetite control and better health, too.

It was soaring serum insulin levels that were sending me to sleep after carby meals years ago. Postprandial hyperinsulinaemia results in amino acids being shuttled into cells. However, L-tryptophan isn't shuttled into cells, so the level of this amino acid in the blood rises relative to others. As L-tryptophan competes with other amino acids to cross the blood-brain barrier, now that the competition has been removed, more L-tryptophan enters the brain. It's converted into 5-hydroxytryptophan (5-HTP), then serotonin & melatonin. High melatonin levels in the brain cause sleepiness.

So remember, "Right carbs, right amounts, right times."

Blood Glucose, Insulin & Diabetes

Diabetes is afflicting an increasing percentage of the population as time goes by. Even athletes like Sir Steven Redgrave can get it. This article tries to explain the workings of the body's blood glucose (BG) regulation system and what can go wrong with it.

How does the body regulate blood glucose?
At any given moment, there's about 4.5g of glucose circulating in your blood (5mmol/L x 180g x 5L). As the brain alone uses about 6g of glucose per hour in the absence of ketones, blood glucose (BG) level could fall to zero within an hour if we ate no sugary/starchy carbs. If we ate a mere 5g of glucose, BG level could double. As very low BGs are fatal and very high BGs damage proteins by a process called glycation (a bit like caramelisation), the body keeps BG levels within fairly tight limits by the use of a negative feedback (NFB) control system.

How does a negative feedback control system work?
NFB systems consist of a non-inverting (more in → more out) part, which in this case are the islet cells of Langerhans (a.k.a. pancreatic beta cells), as increasing BG level results in increasing insulin secretion. It's actually a bit more sophisticated than that. Beta cells can store insulin and dump it into the blood if there is a sudden increase in BG level. This is analogous to the accelerator pump in a carburettor, which dumps petrol into the engine if you slam your foot on the accelerator pedal, i.e. it produces a rapid response. The dumping of insulin from beta cell storage is known as the Phase 1 insulin response. If this (or the accelerator pump) fails, there is a lag in the response; this will become significant below.

Increasing BG level results in increasing insulin secretion from beta cells and is known as the Phase 2 insulin response.

The other part of a NFB system is the inverting (more in → less out) feedback part, which in this case is split into three parts, all working in parallel. They are:

1. Liver - increasing insulin level results in decreasing Hepatic Glucose Production.
2. Muscle cells - increasing insulin level shifts GLU-T4 transporters which shuttle glucose from the blood into cells, decreasing BG level.
3. Fat cells - increasing insulin level shifts GLU-T4 transporters which shuttle glucose from the blood into cells, decreasing BG level.

What can go wrong?
There are three main types of diabetes:

1) Type 2 diabetes. This is by far the most common (about 95% of all cases) and is usually caused by abdominal obesity. Type 2 diabetes has two main mechanisms going on. The first is a progressive insulin resistance of target tissues, possibly caused by increased levels of saturated fatty acids being fed to the liver from abdominal fat stores, chronically-high BG and insulin levels caused by chronically over-consuming high glycaemic load carbohydrates, possibly accompanied by large amounts of saturated fat and/or large amounts of omega-6 fat. A sedentary lifestyle lowers the sensitivity of muscle cells to insulin. Insulin resistance also has a hereditary link. It may also be linked to a Vitamin D deficiency, see here.

Insulin resistance weakens the feedback in the NFB system, resulting in further increased BG and insulin levels (hyperinsulinaemia). Increased BG level causes increased damage to beta cells by glycation. Increased insulin level causes further insulin resistance as target tissues become increasingly insensitive (a bit like louder and louder music making you progressively deafer and deafer). Eventually, beta cells become too damaged to secrete sufficient insulin and insulin levels begin to fall. This results in a massive rise in BG level and this is now full-blown Type 2 diabetes. There are five main treatments for Type 2 diabetes:

1. Lifestyle interventions - reduced intake of high glycaemic load carbohydrates and/or increased intake of omega-3 fats and/or increased intake of Vitamin D3 and/or increased intense exercise and/or loss of abdominal fat.
2. Sulphonylureas - drugs which stimulate beta cells to secrete even more insulin. Unfortunately, that's a bit like flogging a dying horse as it doesn't address the problems caused by weakened feedback and eventual beta cell failure is inevitable, resulting in the need for insulin injections.
3. Biguanide drugs such as Metformin - increase insulin sensitivity in target tissues. This strengthens the feedback in the NFB system, which results in reduced BG and insulin levels. This combined with lifestyle interventions can return the NFB system to normal operation.
4. Thiazolidinediones - also increase insulin sensitivity in target tissues, e.g. muscle and fat, as well as possibly improving the secretory function of beta cells.
5. Insulin injections take the strain off beta cells, but may worsen insulin resistance.

2) Type 1 diabetes. This is much less common (about 5% of all cases) and is caused by an autoimmune disease. One possible mechanism is as follows: Due to an increase in Zonulin (see here ), the gut becomes more permeable than it should (a.k.a. Leaky Gut Syndrome) and allows protein fragments to pass into the blood. These are destroyed by antibodies. However, if a protein fragment happens to have the same sequence of amino acids as a protein in our own body, the antibodies then set about destroying parts of our own body. Examples of this are gluten (proteins found in wheat, rye, barley and oats) producing antibodies in the blood that can destroy the gut causing Coeliac Disease or skin cells causing Dermatitis Herpetiformis or mucous membranes causing Sjogren's Syndrome or brain cells causing Cerebellar Ataxia. As there is an association between the consumption of cows' milk and the incidence of type 1 diabetes (see here ), it's quite possible that, in susceptible individuals, fragments of casein protein enter the blood in this way resulting in antibodies that destroy pancreatic beta cells. Another possible mechanism is autoimmune attack after a viral infection. Once all of the beta cells are destroyed, no insulin is secreted and insulin injections are required. If some beta cells survive, there is a possibility that normal BG level can be maintained if sugary/starchy carbohydrate intake is reduced.

3) Latent Autoimmune Diabetes of Adulthood (LADA). The percentage of cases with this is unknown as it is often misdiagnosed as type 2 diabetes. This is a slow developing diabetes that is more like type 1 in origin (autoimmune with antibodies) but is often misdiagnosed as type 2 because of the age at diagnosis and the relatively slow progression of the disease (slow compared to type 1 but fast compared to type 2). See here. It is believed that Sir Steven Redgrave has this. Whether or not his autoimmune disease was triggered by a huge intake of milk (to build those Olympic-winning muscles), we will never know.

What else can go wrong?
As stated earlier, loss of the Phase 1 insulin response can occur. This usually happens when beta cells are chronically over-secreting insulin due to a chronically-high intake of sugary/starchy carbs and are unable to store any. This results in a lag in insulin response. This isn't a problem if low glycaemic load carbs are eaten and BG levels change only a little or very slowly. However, if high glycaemic load carbs are eaten, this produces a large and rapid rise in BG level. If a NFB loop with a lag in it is presented with a sudden change in input level, its output overshoots. This results in too much insulin being secreted, which eventually results in low BG levels! This is known as rebound hypoglycaemia. The solution? Stick to low glycaemic load carbs.

Where does blood glucose come from if I haven't eaten?
When no sugary/starchy carbs are being digested, BG starts to fall. Adrenaline and noradrenaline (catecholamine hormones) are secreted by the adrenal medulla into the blood and also by sympathetic neurons. Like glucagon (see below), they stimulate the mobilisation of glycogen and triacylglycerols (stored fats) by triggering the production of cyclic AMP (adenosine monophosphate). Adrenaline and noradrenaline differ from glucagon in that their glucose-producing effect is greater in muscle glycogen than in liver. They also inhibit the uptake of glucose by muscle. Instead, fatty acids released from adipose tissue are used as fuel. Adrenaline also stimulates the secretion of glucagon and inhibits the secretion of insulin. Thus, catecholamines such as adrenaline and noradrenaline increase the amount of glucose released into the blood by the liver and decrease the utilization of glucose by muscle.

Pancreatic alpha cells secrete glucagon. This hormone mobilises the conversion of liver glycogen into glucose. The liver only stores about 70g of glycogen, but when combined with water, a larger mass of glucose is generated. Eventually, liver glycogen stores become depleted and BG level falls again. Glucagon also stimulates gluconeogenesis in the liver & kidneys, which is the production of glucose from non-carbohydrate precursors, like the conversion of glucogenic amino acids, such as glutamine, into glucose. See Liver and Kidneys Synthesize Glucose. This causes slow muscle wastage unless there is sufficient protein intake to provide the necessary amino acids. When BG falls to about 3.3mmol/L, the pituitary gland kicks-in and secretes ACTH (adrenocorticotropic hormone) which stimulates the release of cortisol from the adrenal cortex. Cortisol further stimulates gluconeogenesis in the liver & kidneys. When BG level falls to about 2mmol/L, the pituitary secretes GH (Growth Hormone) which has an anti-insulin effect.

What else does insulin do?
Insulin has many metabolic effects in the body apart from lowering BG level. It's a very anabolic hormone and an insulin spike is usually desired post workout to maximise the uptake of glucose and amino acids by muscle cells. There's nothing wrong with the occasional short-term insulin spike. It's chronically-high insulin levels that cause long-term health problems like high blood pressure and clogging of arteries.