Wednesday, 2 February 2011

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. If left untreated, it can deteriorate into type 2 diabetes. See Type 2 diabetes in the UK.

IR can cause:-

High fasting & postprandial serum glucose, which increases the risk factor for Coronary Heart Disease, Retinopathy, Neuropathy & Nephropathy (Kidney failure), amongst other things. 
High fasting & postprandial serum triglycerides, which increases the risk factor for Coronary Heart Disease. See Postprandial lipoprotein clearance in type 2 diabetes: fenofibrate effects.
High serum cholesterol, which 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, leading to overeating & obesity.
Lethargy/sleepiness after eating almost anything, but especially after eating high-GL carbohydrates, due to postprandial hyperinsulinaemia.

Possible causes (IR is multi-factorial) and solutions:

1. "Bad" genes. My genes aren't particularly good, but it is possible to change the expression of genes. See below.

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 is transported by Glu-T5 transporters which are insulin-independent & taken up by 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.

The Protein-Sparing Modified Fast (PSMF) depletes liver glycogen and liver & pancreatic fat rapidly. See also Reversing type 2 diabetes, the lecture explaining T2D progression, and how to treat it.

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

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.

3. Empty (of glycogen) cells.
If carbohydrate intake is too low (say, less than 50g/day), physiological Insulin Resistance develops in order to spare glucose for the brain (as parts of the brain run on glucose only) and red blood cells. This is reversible on increasing carbohydrate intake. People who are on ketogenic diets are advised to increase their carbohydrate intake for a few days prior to taking an Oral Glucose Tolerance Test. See HIGH CARBOHYDRATE DIETS AND INSULIN EFFICIENCY.

4. 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/Metabolic Syndrome/Prediabetes (fasting serum glucose = 6.0mmol/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 carbohydrate-induced comas. I was also about the same weight that I was in 2003, so the improvement wasn't due to weight loss. Hypovitaminosis D was the primary contributor to my IR.

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.

5. Deficiency in Magnesium.
See Magnesium and type 2 diabetes. For the top 999 foods highest in Magnesium per 200kcal serving, see HERE. I take ~4g of Epsom Salts/day (~400mg Mg/day). 

6. 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 Carlson Labs, Vitamin K2, 5 mg/day. See Supplement Alert! Carlson Labs Vitamin K2 MK-4 (Menatetrenone). 
Note: Warfarin/Coumadin works by depleting Vitamin K, so lots of Vitamin K2 makes Warfarin/Coumadin ineffective. 

7. 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.

8. 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.

9. 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.

10. Excessive intake of man-made trans-fats.
Base your diet on whole, minimally-refined foods rather than manufactured food products.

11. Excessive intake of chemicals.
Don't swallow toothpaste (fluoride) or disclosing tablets (as they 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.

12. More than one of the above. See A tale of the unexpected & an analogy.

Any other ideas?

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.


chmeee said...

Re muscles. When exercising - and this is important - muscles cells will also take up glucose, even in the (relative - 'cos you always have at least some in your circulation )absence of insulin. Exercise ( via AMPK ? ) stimulates a secondary pool of GLUT4 which then go get glucose. Perhaps most importantly, this can last for betwen 24 to 36hours, and is in part why exercise is recommended for diabetics etc and also why they tell you not to let much more than a day to pass between exercising. Re HIIT. As well as promoting the above, it also very rapidly empties muscle glycogen stores. In intensive exercise, the cells cannot get sufficient fuel quickly enough from the circulation, so the muscle glycogen stores get used up rapidly and HIIT is one of the best ways of doing this. So when you've finished exercising, the muscle cells will immediately replenish this. All of which, in addition to the above, helps keep your blood glucose levels down.

HIIT has other advantages.To have a good effect on glucose ( plus lipids etc ) you don't have to do too much, and not for very long.

See: It would have been nice to see the experiment done with diabetics.

And you don't need to do much ! Ideal for people who don't like to spend too long, and it can be anything, not just running. Before you ask, I do other things also.

Nearly forgot, yes I am a Fawlty Towers fan. Classic !

Nigel Kinbrum said...

Hi chmeee,

I did try HIIT - once. I didn't get away with it. After a 5-second sprint at full pelt (during which, stuff shot out of my shirt pocket!), I glowed buckets of sweat for ages afterwards. Not good.

I also have a long body and short, stumpy legs. I'm built for comfort, not speed!

I think I'll stick to Zumba.

chmeee said...

Hi Nigel

I run, sometimes intervals, a few times a week. Depending on the weather, and my mood. Also a rowing machine and an exercise bike are great for HIIT. Just 20 minutes...... :) But if Zumba works for you then great. Keep it up, ( As the actress said to the archbishop. Yes, the older and cornier a joke, the better !) As we know, you have to find something that works for you and that you can stick with. Can't say I'd like it though. Best is my iPod, switch off from whatever exercise I'm doing, at least partly, and get it over with. Though there is a certain satisfaction in completing it I guess. And exercise / running in the country, where I live, can be nice and is supposedly more beneficial. So green and peaceful. I'll stop now before I turn into a tree-hugger. :)

Nigel Kinbrum said...

Hi again chmeee,

I live in a small town, so I have to watch out for uneven pavements, pedestrians, cars & bikes. Anything faster than a power walk is very uncomfortable for me and hard on my joints.

I do have a rowing machine with hydraulic pistons and I also have a pair of dumbells. I might just dust them off.

CarbSane said...

Good news on your Mum Nigee. I'll pop back with a few comments later :)

Margaret said...


Reading your piece here since you gave me the link at CarbSane's blog - hi! I like your summary of IR, especially the note about vitamin D. Some authors reckon low vitamin D is what historically triggered a hibernation response that encourages fat storage, since sun exposure is lower in winter. There are definite links with obesity and IR.

Another note about the filling up of fat cells though - remember that insulin causes adipocyte differentiation, therefore encourages the formation of more fat cells to take up the overflow.

BTW, I'm a Fawlty Towers fan too -are you British? I am a Brit living in the USA. Interesting.

Nigel Kinbrum said...

Hi Margaret,

Welcome to my blog. I'm not too sure about the fat cell differentiation thing. I was under the impression that there had to be pre-adipocytes available to turn into adipocytes.

I'm British and live in N.E. Hampshire near the Hampshire/Berkshire/Surrey borders. I'm definitely not from Barcelona!

Galina L. said...

I liked the music. Thank you, Nigel for the video. it is very easy to feel happy while dancing.
Do they provide some brain-stimulating activities at your mom's house? How long ago did she changed her diet? Good luck with that!

Galina L.

Nigel Kinbrum said...

Hi Galina,

I love's in my blood! I shall carry on embedding music videos, as the graphics for them hardly slow down page loading.

There aren't enough brain-stimulating activities at mum's nursing home. The carers are so busy either inserting food in one end, wiping excreta off the other end or doing paperwork, that they don't have time to talk to the residents. I talk to all of the residents on mum's floor (and other floors, as I'm passing through) as much as possible.

On Friday, I gave a balloon to a chair-bound lady who had worse dementia than mum and who rarely spoke. She smiled and said thank you! I'm going to make some more music CDs (of stuff that I bought on vinyl years ago). I think that everyone will like "Abba's Greatest Hits". Mum certainly did.

I changed mum's diet only recently. She responded immediately. There were some cock-ups with mum's diet due to failure of communication in the nursing home. I soon sorted that out.


Galina L. said...

I love ABBA myself more than any other group and even got my 18 years old son to be a fan of ABBA. More chances he would bring that music into my nursery house if I would end in one.
You are fortunate that they listened to you about your mom's treatment.

Nigel Kinbrum said...

I do, I do, I do, I do, I do!

Once I got mum's GP on-side, the nursing home couldn't really say no to mum's new diet.

I got mum a couple of large pots of Rachel's organic bio yoghurt with 5% organic coconut on Friday. It's absolutely lush (it contains organic cream as well) and she loved it.

Galina L. said...

Yesterday I read your posts about Alzheimer. It is so sad! I am sorry for your mom and my heart goes to you and her.
My grandma who is over 90 is in the nursery house herself. My mother never visits her because she was aggressively attacked couple of times by my grandmother before she was placed into assisted care facility. Grandma thought that some petty items were stolen from her and it caused attacks.At 89 my she was surprisingly strong. Mom understands mentally it is all illness, but still very afraid on subconscious level. I don't want to push mother because she is not young herself. What a terrible illness!

lightcan said...

So, does that mean that you like blondes?

Nigel Kinbrum said...

Yes. I also like brunettes! Blue & green are my favourite eye colours.

majkinetor said...

Very nice post and explanations.
The Vitamin D section is especially important. Nothing can replace Sun, IMO. Thyroid must function correctly as it activates D. This translates to more Iodine for most people. If you use synthetic Vitamin D3 use it with Vitamin K2 MK-7 (vitamin D will boost calcium metabolism and depending on your diet and age and Mg status, calcium might finish in soft tissues, all of which K2 prevents).

Nigel Kinbrum said...

Hi majkinetor,

I agree that UVB exposure > supplements, but I'm not an "outdoors" kind of person and England is quite Northerly, so the sun isn't high enough in the sky for a lot of the time.

I therefore supplement with 5,000iu/day of Healthy Origins, Vitamin D3, 5,000 IU, 360 Softgels (use discount code NIG935 to get $5 off the first order. Standard shipping $4)

I also supplement with 15mg twice a week of VRP Ultra K2

As I have pituitary dysfunction & have no TSH, I am prescribed 125ug/day levothyroxine.

ProudDaddy said...

Do you have an opinion on hyperglucagonemia as the first step towards T2? I found (and lost) an article postulating that alpha cells go haywire first. I find this interesting because the number of studies involving insulin number in the tens of thousands, yet we still can't stem the dramatic increase in diabetes. When we can't figure out what's happening, maybe we're looking at the wrong potential causes. (Note I said maybe.)

Nigel Kinbrum said...

I'm not convinced. I read that T2DM could be treated by killing pancreatic alpha cells, but I think that it's treating the symptoms (hyperglycaemia), not the cause of T2DM.

ELMM is difficult if the diet is wrong. Many people are eating the wrong diet & have a sedentary lifestyle due to lethargy caused by eating the wrong diet.