John and Laura are pretty annoying, what with their games and science, so I have decided to kill them. I can’t abide a stabby mess, so I’ve devised a fiendishly clever way to despatch them that’ll never get back to me. My devious plan is even better than those detective stories where the murderer uses a shard of ice to stab the victim which, once melted, leaves no trace of the weapon.
You see, I’m poisoning them! But not via some dull Victorian melodramatic strychnine or arsenic-in-the-tea escapade, but by a scheme much more diabolical. Through my lizardy-wiles, slowly but surely, I’ve got John and Laura to change their diet completely, to my Diet of Demise. Instead of eating lots of important starch, vital heart-healthy-wholegrains and low-fat yoghurts, I’ve ripped the nutritive safety net from under them and have convinced them to eat loads of fat – even ArteryCloggingSaturatedFat – and oodles of cholesterol and loads of cancery animal products. And my master-stroke? I’ve ruthlessly got them to cut back the life-giving carbohydrates from their diets: Since the body runs on glucose – especially the brain – this means that any moment now, they’ll die of a heart attack, stroke, kidney failure, hypoglycaemia or mere no-sweet-sadness! Mwaa haa haaaa! Take that, video games and test tubes! Lucy shall be mine.
Or so I thought. But, horror of horrors, my very deadly scheme turns out, topsy turvy, to be rather healthy. How? Let me guide you along the devilish path that led to a peculiarly angelic destination.
Now, obviously, just telling John and Laura to eat themselves to death wouldn’t be convincing. So I had to string my web across a plausibly sturdy doorframe. Regular readers of this blog will know that Laura has PCOS, which means that ovulatory cycles don’t proceed like the clockwork one would desire, and when ovulation does happen, it often doesn’t lead to an egg viable for fertilisation. As part of her treatment, she’s taking metformin.
Metformin is a heroic old drug, primarily used by diabetics. It lowers blood sugar. And it makes insulin work more efficiently. So why is someone with PCOS taking a diabetic pill? And what’s efficient insulin got to do with making babies?
Our bodies regulate themselves via complicated inter-sloshings of hormones. Ideally, these hormones work together harmoniously, like some miraculous MGM dance sequence. Sometimes, though, the hormones start to bicker and the choreography falls apart, and we’re left with less Busby-Berkeley, more a tangle of Chuckle-Brothers and Eddie the Eagles, all piled up on a mountain of collapsed Saviles. It can get pretty chaotic pretty quickly, leaving the body’s systems flapping about like a torn endocrinological windsock in a hurricane. But that’s enough metaphors.
Insulin stands as one of the primary gatekeepers of hormonal heaven or hell. It’s an ancient, primal signalling hormone, used by everything from worms to giraffes – and we’re certainly not excluded. Sometimes, it’s thought of as little more than The Hormone Diabetics Need To Inject To Make Them Use Sugar Better. In reality, its influence and scope are far wider than that, and its disregulation has profound effects on all of us – not just those who suffer from diabetes. Along with its cocktail of related hormonal friends – like leptin, glucagon and ghrelin – it has profound effects on how we live and die.
Insulin has a large number of effects in the body, but they can all be summarised thus: when your pancreas is squirting out insulin, your body is being told to enter store-and-build mode. Without insulin, much of our nutrition could never be absorbed, and our muscles could never grow. Type 1 diabetics have faulty pancreases, which cannot produce insulin. This is why, without treatment, they can die of effective starvation, even if they eat until their stomaches burst. So insulin is very important indeed.
So insulin has a profound effect on whether our bodies are building or disassembling, storing or burning. But, as every diabetic knows, insulin has a very specific effect on blood sugar. How? Why? And what goes wrong?
When you eat any carbohydrate, the bit that isn’t fibre or fructose turns surprisingly quickly into glucose, which dissolves directly into your bloodstream. It doesn’t matter whether that carbohydrate is a bottle of Lucozade or a macrobiotic artisanal granary bap: it’s all cleaved into the same big pile of glucose molecules soon enough, and it works its way into your bloodstream just the same. This big pile of glucose represents both an opportunity and a problem. The opportunity is that all your cells can burn glucose as fuel – or, more accurately, they can convert it to ATP, which is the fuel-currency our bodies use universally. So if you’re running a marathon, your muscles will immediately lap up the glucose and push you over the finishing line.
Let’s assume you’re not running a marathon, though. Which is more common, I think, for the average video-game writer! What happens then, when your bloodstream suddenly has dissolved in it a bap-ful of glucose? On average, your body wants to have no more than a teaspoon or two of glucose within its bloodstream. Any less, and you’ll soon drop into a coma. Any more, and you’ll die of blood poisoning. Glucose is actually pretty dangerous stuff if it’s allowed to hang about, sticking to proteins and causing all sorts of metabolic chaos. So it needs to be dealt with quickly. When you get a large amount of glucose suddenly dumped into your bloodstream, your pancreas squirts out a large amount of insulin to compensate. The insulin attempts to force your muscle and fat cells to sequester this glucose, to clear it out of the blood and to store it safely. In one sense, your body doesn’t care what happens to the glucose – so long is it’s cleared out of the blood quickly. In another sense, your body thinks “hey, this could be useful energy, let’s not waste it”.
Your muscles can only store and use a certain amount of glucose before they start to ignore insulin’s signals. This is especially true if you’re sprawled on the sofa and not, say, running a marathon or lifting weights. So insulin forces the excess glucose into the fat cells instead. Which then get fatter. This is a clever solution: not only does it clear the dangerous excess of glucose out of the blood, but it also gives you extra stored fuel for when food supplies are low. Well, it would be a clever solution if food supplies ever did become low. For most of us, barren “winter” never does actually arrive. Instead, our bodies constantly get more and more glucose – potatoes, cakes, rice, sweets, Special-K – which our bodies have to store away hysterically, for a rainy day that never comes.
So, our bodies squirt out a load of insulin as an emergency response to a whole glut of glucose that needs to leave our bloodstream pronto. Pretty much every time we have a bowl of porridge or drink a Coke. The priority is to clear the stuff out. The body can’t be precious about carefully waiting to see how much stuff you glut down. So it overshoots its insulin. Just to be safe. And because it overshoots, an hour or two later, your blood sugar is too low, and so you suddenly crave another bun, an additional packet of crisps or a further can of Fanta. And you get another go on the glucose roller-coaster.
Eventually, even the most exciting loop-the-loop gets dull. Eventually, our muscles and even fat cells start to ignore the repeated hysterical insulin signals. To a degree, our bodies are federations of independent organisms, and our cells start to be concerned about their own “well being”, so to speak. They have no further capacity to store this excess glucose, and so politely start ignoring insulin’s insistent messages. And blood sugar thus rises, as our cells decide there’s no room at their inn. The pancreas then becomes more insistent, pumping out even more insulin, to overcome our body’s resistance to storing this excess glucose. And so parts of our body get into a defensive arms race with other parts of our body. This doesn’t sound like it’d end well. And it doesn’t.
Once the awkward standoff between our pancreas, bloodstream and cells is established, we’re in a state of Insulin Resistance. Loads of insulin swills around, excess blood sugar abounds, engorged fat cells get increasingly reluctant to store more. At this point, we have what’s been called Metabolic Syndrome, and are on the way to diabetes and other unpleasant diseases. Type 2 diabetes occurs when we’re so insulin resistant that our pancreas can no longer manufacture enough insulin to overcome our angry cells’ reluctance to store the torrents of damaging glucose. Eventually, the beta-cells of the pancreas can even burn out completely in the effort to produce the gushloads of insulin necessary to bully the cells to deal with the excess glucose. Our body’s angry civil war is fraught with corpses and carnage.
It gets worse: the liver desperately tries to process this excess glucose, and converts it locally to fat. The fat gets secreted in the liver and around other organs, where it causes inflammation and other problems. Not pretty at all. And much worse than the externally evident fat that lies on your hips.
Even if you aren’t insulin resistant, and everything’s working perfectly, insulin has another trick up its sleeve: while it’s being produced, your body remains strictly in storage-only mode. As we mentioned above, insulin’s primordial role is to keep the body storing and building. It’s like your body’s own stingy accountant, constantly shoving stuff into long term savings. For most of our evolutionary history, this was quite a clever strategy. After all, you find a glut of blackberries, out comes the insulin and shoves them into storage for use in winter. For many of us, though, as we said, this winter just never comes.
So we eat food that promotes insulin. Our body is locked in storage mode. We literally cannot burn any of the fat that lies copious on our body while insulin’s about. And so a distressing amount of that doughnut gets added to our hips, without ever having a chance at fuelling us. And, crucially, it doesn’t fuel us. Which is why, an hour later, just as the insulin is dissipating, the hormone’s done too good a job at sweeping all the sugar out of our blood greedily and miserly, and we grab another doughnut in response at this apparent metabolic emergency. We’re not greedy or stupid. In a very real sense, our body’s immediate needs have barely been fed by the first doughnut, even with its calorific excess. And with the second doughnut, out comes more insulin, and yet again, any possibility of spending some of that savings account is thwarted. And so we get fatter and fatter, and yet we cannot use any of this fat to fuel ourselves, so we also get hungrier and hungrier. And our body, realising we have a peculiar fuel-partitioning emergency, slows down our metabolism and we become tired and listless and certainly not in the mind to do any exercise.
Thus, as science writer Gary Taubes has pointed out: with our modern insulinogenic diets, the hormonal imbalance that makes us fat is what, ironically, also makes us hungry and “slothful”. It’s not about morals. It’s about chemicals.
…To be continued.
Your explanation of IR is excellent. Well done. I shall use some of your analogies.