The "Insulin Resistance Saga" - Part III: Where Has All the Sweetness Gone? Plus: Bullied to Eat Twinkies

Figure 1: Obese highschool students have a 111% (boys) and 76% (girls) increased risk of relational bullying. (Kukaswadia. 2011)

[Note: This is a direct sequel to the last installment] Delicious! "Milk and vanilla and not a single bacteria in it! How much better can it get?" You are sitting at your desk in the elementary school and dream yourself back to the Kindergarten, when Mrs. Youesdeay's attacks against your Snickers bars still was the only thing you had to fear. Mrs. Undarstant is nice. She likes you. You always do your homework, never complain or talk to others during the lessons. Unfortunately, the latter is in parts a consequence of the fact that the other kids don't like you. "Fatso!", "No, I don't want to hold his hand, Mrs. Undarstant. His hands are sweaty and gooey from the candy he is constantly scoffing down.", ... and these are only the friendlier abuses and rejections you are facing on a daily basis.

"Are they secretly removing all the sugar from my foods?"

You take a look a the ingredient milk of your vanilla milk. "E407? Hmm... as long as its fat-free, it won't hurt, but I wonder if they have changed the formula. I mean, this stuff used to be sweet like crazy and now? It tastes like water." You have gotten used to these kind of inner-monologues over the years. Since Jeany had moved away, when you were in first grade, you have become more and more isolated. School, homework, Playstation, TV, ... that's what your day usually looks like. You take another look at the now empty bottle of vanilla milk. "They must have changed something..."

Image 1: If you "supplement" normal weight "lightly active" subjects with a daily dose of Lucozade Sport for one month you will increase their sweet preference by +130% (Gondivkar. 2009)

Did you know that acquired hypogeusia and ageusia, i.e. the reduced ability and the inability to taste, in this case, sweets, is a common feature in type II diabetics? In a 2009 study by Gondivkar et al. 62.5% of the type II diabetics had an impaired sweet taste reception (vs. 12.5% in the control subjects) and 15% of the untreated type II diabetics had a complete loss of sweet taste perception (Gondivkar. 2009)! A more recent study shows that the reduction in the ability to taste sweet goes hand in hand with obesity and is not something that arises all of a sudden (just as type II diabetes isn't). Sartor et al. did not only find that obese subjects had a -23% reduced sweet taste perception (compared to normal weight controls), but also that normal weight, "lightly active" adults developed a similar reduction in sweet taste perception and a 2.3-fold increase in sweet preference after only one month of soft drink (~760 ml/day) "supplementation" (Sartor. 2011).

What you obviously don't know is that the thing "they" changed is not the product formula, let alone its sugar or sweetener content, but rather your perception of the formerly obtrousively sweet combination of saccharine, aspartame and the high fructose corn-syrup they use in your lactose free vanilla milk as a replacement for the milk sugar. Aside from the habituation effect, the years of chocolate coated healthy whole-grain cereals, Snickers bars, Vanilla milk and peanut butter sandwiches for breakfasts, have taken their toll on your baseline insulin sensitivity. What used to be a pleasant inrush of glucose into your cells, has already become more of a trickle. Your triglyceride levels are on a constant rise and if it were not for the constant delivery of glucose from the high carb, low fat foods, of which your mother hopes that they will help you lose at least some of the superfluous pounds, your brain would long have switched you over into fat burning mode.

Figure 1: With the constant influx of glucose and the overproduction of triglycerides your body can neither use glucose nor fat as a fuel effectively; the one thing both signals, i.e. glucose => insulin signaling, as well as the cortisol (stress) + high triglyceride signaling have in common - and this does in fact still work - is that they will induce the storage of energy in your ever-expanding adipose tissue.

With the divergent signals your body is receiving (cf. figure 1), neither your glucose, nor your fat metabolism is working properly. It is like you were telling your metablism to go to the left, while pushing him further to the right with every of the four peanut butter sandwiches that were waiting for you in your bag, before...well, before John decided that "You are already fat enough fatso, let me eat those sandwiches!".

John is always right and the fatso should not eat peanut butter sandwiches

Image 2: Dr. Haub did not do fat kids like yourself a favor, when he lost 27 pounds in two months on what was purportedly a diet consisting of nothing but chocolate bars, chips, biscuits, pizza, doughnuts and sugary cereals (in fact, he used protein shakes and multi-vitamins to make sure he does not do permanent damage).

John is the nightmare of your sleepless dreams and your stressful days. He is the "cool kid" everyone looks up to and when John says that "...the fatso should not eat those, right?" This is only a rhetorical questions. After all, John is always right. You have learned that the hard way - several times of the last years. Although John had never hurt you physically, all the fat you had accumulated of the years could hardly disguise all the wounds each of his countless comments and jokes had left in your soul.

The bell rang! "Will I make it to the candy vending machine and back during the 5-minute break?" Your thoughts were revolving around a pack of Twinkies. "They worked for this professor on TV, right? If I don't eat the sandwich and just the pack of Twinkies as a breakfast. I mean, they have less calories than those sandwiches." You were looking over to John, who was gobbling his peanut butter sandwiches. When he realized that you were staring at him he said: "What's up fatso, you could be a little more appreciative of what I am doing for you!" It was grotesque, John had been eating your sandwiches probably 4 out of 5 days in the last months and still looked leaner than ever. "How can that be?" The bell rang another time. The break was over and you decided that it would probably be best not to eat anything today....

[to be continued...]

The "Insulin Resistance Saga" - Part II: Jimmy has Asthma and My Daddy Eats Five Cheeseburgers and Three Large Servings of French Fries in One Sitting!

Image 1: In 2009 10% of all US children had at least a mild form of asthma. 57% of these children had had at least one asthma attack in the year before. And in the year 2007, 9 people died of an asthma attack on each of the 365 days of the year (CDC. 2007-2009)... yet our understanding of the nutrition-cleanliness-autoimmune axis is still in its infancy while millions of dollars are spent on a non-sensical "war on cholesterol", every day.
  

[Note: This is a direct sequel to the last installment] There she is, Mrs Youesdeay... you hated her. Her and her healthy greens: "Good morning my dear! I see your mommy is in a hurry today?... Good morning Mrs. Singleparent!" Mrs. Youesdeay was standing there, her usual half-anorexic vegan self, staring right into your eyes." It was as if she was saying: "Gimme those peanut-butter sandwiches my dear!" To escape this fate, you had made it a habit to hurry right past her and into the grey building with its unique smell. Mrs. Youesdeay always said that it was smelling of cleanliness... but how could something smell of cleanliness? You have been dwelling over this for some time now, but were not been able to come up with a solution. Jimmy started to cough. "I wonder whether his does this deliberately!" - it is the same ritual every morning. You obviously cannot know that Jimmy's asthma attacks, of which everyone keeps telling you that they are a result of the dangerous house dust - how on earth can some dust be dangerous? - are in fact triggered by the "smell of cleanliness" - or rather the toxic air-pollutants which form, when the vapor from the anti-bacterial cleaning products the cleaners are pouring over the floor by the liter every morning at 4am, right before you and your friends arrive at the kindergarten and the air fresheners Mrs. Youesdeay has placed in regular intervals all over the building mingle (Nazaroff. 2004).

"Jimmy is getting onto my nerves, really!" As usual, Jeany, your best friend, had been the first to arrive at the Kindergarten. You wonder why she does not want to tell you what her mommy did for a living, but in the end, it did not matter, anyway. You take your lunchbox out of your bag and check whether the peanut-butter sandwiches are still there. "You never know, what Mrs. Youesdeay is up to..." The sandwiches are still there and the Snickers bars, as well. Now, that your catecholamine levels are slowly returning to baseline your blood sugar is dropping back to the alarmingly low levels which made you yawn, when you got out of the car, at 7am.

Five past seven, high time for one of those Snickers bars!

Image 2: Takeru Kobayashi is only the most prominent of a new generation of media-hyped "food athletes" and questionable rolemodels for our children (img welt.de).

You grab one of the Snickers and scoff it down with two bites. This way you can make sure that Mrs. Youesdeay, who is still dealing with Jimmy's every morning asthma attack, is not going to see it. While you are waiting for the soothing and gratifying effect of the sugar rush to set in, you are heading over to the shelf with your name - the first (and only) word you can read - and take the half-finished of you, your mommy and your daddy at McDonald's... that was only half a year ago! In those days, when you were still a happy family. "My daddy can eat 5 Cheesburgers and 3 large servings of French fries!", you say. Your own personal record is 3 Happy Meals and in retrospective you were sure that you had finished the fourth one, as well, if you had not insisted on the super-size Fanta, but had stuck to those ridiculous standard sizes. One day, you would beat this tiny Japanese hot-dog eater, ...

... 69+1 hot dogs? that cannot be so difficult, right?

The regular corn syrup from the Snickers bar is doing its job pretty decently, your blood sugar rises and your thoughts stop wandering from topic to topic. Now, you are ready to go. You grab your pencil and begin to draw one of those creamy milk-shakes onto the already over-laden meal tray your mother is carrying. Meanwhile, your pancreas is pumping out insulin like crazy, but the constant influx of long-chain fatty acids from your digestive tract and the triglycerides your liver is still producing from the "corn sugar" (for those who are not aware, this is the new name for high fructose corn-syrup) that is responsible for the unbelievable sweet taste of your "healthy whole grain cereals", along with your chronically elevated cortisol levels, are tricking your body to believe that those free and glycerol-bonded fatty acids must be coming right from the adipose tissue, from which they are liberated in order to preserve your blood glucose levels from falling back into the hypoglycemic abyss and shut down the insulin-induced glucose transport into your brain and muscle cells by -50% (Thiébaud. 1982; Roden. 1996; Shulman. 2000).

"Vanilla or chocolate?"

Mrs. Youesdeay is passing out the low-fat vanilla and chocolate milk that is part of your governmentally sponsored breakfast, here at the Kindergarten. You grab one of the 100% vanilla-free yellowish brews, open the lid and avail yourself of another 10g of sugar and a whole host of artificial flavorings. "Mrs. Youesdeay?", you hear Carlson say. "Mrs. Youesdeay, that is not raw milk, is it? My daddy said that I must never drink raw milk, because it will make me sick and go to the hospital... that happens to 1000s of people every year, my daddy says!" You drop the PET bottle with your vanilla milk and stare over to Mrs. Youesdeay. "You don't have to be afraid Carlson. The USDA and our government are making sure that those scrupulous farmers are made accountable. Our milk is pasteurized and homogenized!"

Did you know that carrageenan (E407), also known as Ammonium Carrageenan, Calcium Carrageenan, Potassium Carrageenan, Sodium Carrageenan, Chondrus Extract or Irish Moss), a emulgator and stabilizer that is used whenever the fat that is giving real foods their unique texture is removed (such as in "your" no-fat vanilla or chocolate milk), is a potent pro-inflammatory agent? In a 2010 study from the University of Illinois (Bhattacharyya. 2010), it stimulated the inflammatory effects TNF-alpha in colonic epithial cells and inhibited its apoptotic (inducing programmed cell-death) effects and thusly set the stage for the development of colon cancer.

You pick the bottle back up and empty the rest of the 0.33l of milk not being aware that the mould-derived vanillin in it is only one of the 7 listed E-numbers and countless unlisted chemicals, of which you can safely assume that their addition to raw milk would solve the "problem" with bacterial contamination in no time ...

[to be continued...]

Intermittent Thoughts on Insulin Resistance: Fats, Carbs & Lack of Exercise - Where is Our Scapegoat? Plus: Chicken or Egg - Which Came First Obesity or Insulin Resistance?

Image 1: You may think it's ugly because it is not comply with the current beauty ideal, but this small quantity of subcutaneous is probably rather a sign for high insulin sensitivity, than resistance.

In the last installment of this series, I tried to establish a new, a certainly unconventional perspective on a physiological process many people consider the #1 plague of the 21st century: Insulin resistance. As it turned out, the desensitization of our cells to insulin and the subsequently reduced glucose uptake into the cells, can be an advantage. In the course of a marathon, for example, it helps our bodies to maintain a relatively stable blood sugar level and shift from a largely glucose-dependent to a more fat-dependent metabolic state. The existence of this often overlooked beneficial side of insulin resistance does yet bring up the question, why insulin resistance and obesity usually go hand in hand. I mean, if insulin resistance turns you into a fat burning machine, how come that obese people, of which many (but not all!) are in fact profoundly insulin resistant, don't just burn off the superfluous body fat? And how come that the number or normal weight persons with insulin resistance or type II diabetes is steadily increasing?

Obesity and insulin resistance, chicken, egg or just a huge misunderstanding?

To answer these and many related questions we will first have to look at the context in which both develop: The affluent western convenience society,  with its sedentary fast-food munching, coke-guzzling citizens. Yet while I suppose that we (and all experts) the culprit lies somewhere within one of the attributes to "citizens", there are huge differences at least with regard to what different individuals identify as the main culprit.

1. There are the friends of mathematics, who have no clue of either physics or the physiology of the human body, who will say that the underlying problem lies with the first attribute, i.e. lack of exercise, or more precisely, a positive "energy balance"
    
2. The second group of "experts", believe that all the fatty grease from the burgers and french fries would be paving its way from our intestines outwards to our bellies (well, sort of ;-), recommend a healthy low-to-no fat diet as the one size-fits it all solution to insulin resistance and obesity and apparently believe that this will also cure heart disease, prevent cancer and diabetes - you know the whole litany
    
3. Thirdly, there are the low-to-no-carbers who believe in the doctrine of Dr. Atkins and thusly hold the firm believe that the third attribute (as well as the buns of the burgers and the fries, themselves, obviously), i.e. the overconsumption of carbohydrates in general and high fructose corn syrup in particular is to blame for the current misery.

I guess, if we just voted on which is the "right" hypothesis, the results would not be very balanced. This may thusly be lustig (which means "funny" in German ;-), but would not contribute any deeper insights into the etiology of either or both of the aforementioned phenomena, which were - just in case your brain is either suffering from a lack of glucose (this would indicate you tend towards position 3) or already sugar coted, like the guaranteed fat-free lolly in mouth - obesity and insulin resistance. I would thusly suggest that we put aside our idiological biases, of which I just want to casually mention that they are largely determined by our personal success / failure with exercise and or low fat or low carb diets, for a few minutes and take another look through our "our body knows best"-glasses.

Hey body, are you waiting for the great famine?

Image 2: These kids are obviously
preparing for the big famine.

When we look through these glasses at the (morbidly) obese diabetic end-products of a painfully slow process, which - for most people - stretches over the better third of their lives, the often touted "only the fattest survive(d) the famine" hypothesis would be the only  reasonable explanation for all the mess. That is actually quite nice, because we would thusly be able to blame our "thrifty" genes, lean back and wait for the famine to come, when all those anorexic cover models will eventually parish while we would take advantage of the glucose sparing effects the insulin resistant state we are in has to offer and live off the truckloads of body fat we have accumulated over the years happily ever after.

Now, even we assume that the aforementioned cover models were not only anorexic, but also stupid enough not to slaughter and cannibalize us before they starve (I guess the low fat fraction and the vegans among them would chose the latter ;-), the fattest among us will probably still be the first, not the last to die.

Did you really tell me not to eat that pie, body? Am I just a glutenous slob?

While it may be correct that we are evolutionary designed to store energy in the form of body fat (not calories, cf. "1lbs of fat does not equal 3500kcal"), our "our body knows best"-glasses allow us to see that our fat tissue is well aware of its own limitations and uses a broad range of adipokines, most prominently leptin, to inform the brain and the other organs about its current filling level. Now, the infamous "free will", a purported privilege of the glorious human race, would obviously allow us to ignore the clamor that is coming from our hips, bellies and buttocks, and at least in the "just a little chubby"-stage of the process this may in fact be part of the reason - "Ah, granny, I am full, but that delicious last piece cake will still fit in!"

After years on granny's delicious cakes, and another 50lbs of pure fat on our hips and amidst our organs, our "free will" is yet going to be the least of our problems. Now that our adipose tissue is crying at the same decibel level as the engines of one of those Airbus A380 mega jumbos and our brains (I am talking about their "unconscious" part here) are long deaf, it is almost too late to make better use of our "free will" and finally refuse yet another piece of one of granny's oh-so-delicious pies.

I am fat! How can I be hungry and still gain, not lose weight?

Image 3: There comes a time, when it is not only about making the "wrong" food choices. A time, when neither the apple nor granny's pie will satisfy your hunger, and your cells will be starving within an nutritious cocktail of partially oxidized fatty acids and sticky glucose molecules... yet still, or I should say, exactly for that reason simply "cutting calories" won't solve the problem.

As paradoxical as it may sound, when the number of pies we have stored all over our bodies exceeds a certain limit, our ability to assess and whats more important, to use those valuable energy stores to an extend which will fool the regulatory systems of our bodies to believe that we are starving. And when we look through our glasses, we will see that - at least on a cellular level - this is in fact the case: With the mitochondria of our cells blazing up in flames and the malfunctioning glucose pumps, many of which do not even reach into the blood stream anymore (I guess you understand the reference to non-translocated GLUT-4 transporters ;-), only minuscule amounts of the exorbitant amounts of glucose, which have already begun to clutter the cell surfaces, are finding their way into the cell. And the little additional energy the malfunctioning mitochondria are deriving from the fatty acids which are by now leaking uncontrollably from the porous fat cells, is neither enough to live, nor so little that they would die...

If you are interested in the prequel of this story, which - as it has become increasingly fashionable ever since the release of the "first" three part of the Star Wars saga - will reveal why and how many of us betray the force... ah,  pardon the regulatory mechanisms of our bodies, you will have to wait for the next installment of this series. So make sure you stay tuned during the 7-days science break ;-)