Metabolical Chapter 2. “Modern Medicine” Treats Symptoms, Not Disease

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Metabolical Chapter 2. “Modern Medicine” Treats Symptoms, Not Disease

Author: Robert H. Lustig Publisher: New York, NY: HarperCollins Publishers. Publish Date: 2021-5-4 Review Date: Status:📚

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Government didn’t get involved for decades, because it’s harder to remove a chronic exposure than it is to prevent an acute one; especially when Big Business stands to make a profit.

The bottom line is if there’s going to be effective change in curtailing various acute and chronic diseases, public health supported by government regulation will ultimately be required. In each previous case, it’s proven successful. And of course, when government doesn’t assume responsibility, you get what happened in Flint, Michigan.

Then, in what amounted to a complete turnaround, the paradigm of government being the guardian of public health shifted. In 1940, Albert Alexander, a London constable, was the first human to receive a dose of penicillin for an acute facial infection that had spread to multiple abscesses and claimed his eye. Left untreated, it would have been fatal. His response to the medication was “remarkable.” But it didn’t last—the infection relapsed within six months, and Alexander died a year later. Nonetheless, the “Golden Age” of Modern Medicine was launched. Therapy targeted to the pathology. The right antibiotic could kill the right bacteria, and people got better. Screw prevention, which takes time, infrastructure, and investment. Now, you could achieve cure. There’s a pill for that. Targeted therapy via personal intervention became the unyielding goal of Modern Medicine.

That first Golden Age of Modern Medicine didn’t last even a decade. In 1947, four years after mass production of penicillin, the first bacterial species to develop resistance to the antibiotic reared its ugly head. And so the race was on to develop the next antibiotic—methicillin. And on and on. Since then, we’ve continued to chase the concept of targeted therapy, we think we have it within our sites, and yet cures continue to elude us.

We’ve now reached critical mass—of drug-resistant bacteria, that is. There are so many resistant species that they now can share intelligence; that is, they can transfer resistance genes between species; a Rise of the Resistance that would terrify all minions of the Empire. Our current crop of antibiotics is coming close to being useless. Add to that the fact that viral diseases are now even more dangerous and harder to control than bacteria ever were, as exemplified first by HIV in 1979, hantavirus in 1993, Ebola in 2014, and coronavirus in 2020. Even so, these aren’t even the biggest problems with Modern Medicine.

We believe we’re in a new Golden Age of Modern Medicine, as we now use high-tech screening of drugs, Big Data informatics, and genetic editing like CRISPR-Cas9 in an attempt to target therapy to the individual and the pathology. For certain genetic diseases, such as severe combined immunodeficiency disease (“bubble boy” disease), and maybe for sickle cell disease, or Tay-Sachs, such therapies that are targeted to the pathology will likely result in “cure.” And that’s great—for these one in ten thousand to one hundred thousand diseases. We’re even looking to use viruses to program an individual’s own immune cells to kill cancers in that same individual—the ultimate targeted therapy. We’re using robotics and cyberknives to reach surgical outcomes previously unimagined. At UCSF, my colleagues are harvesting stem cells from individuals with type 1 diabetes, using growth factors to differentiate them into pancreatic beta-cells in a petri dish, and then injecting them back into the patient to attempt to cure their diabetes. It’s true that patients who previously had no hope now have hope. Which is absolutely great—for those patients, and only if they can afford these treatments.

But these targeted cures are not even remotely close to addressing what is reducing life span and health worldwide. This scourge has no targeted cure despite what doctors may tell you, and is increasing morbidity, costing big dollars, and breaking healthcare in every country on the planet. Because today, for the chronic diseases that affect society the most, the cluster of NCDs folded in under the umbrella term metabolic syndrome (that cost 75 percent of healthcare dollars in the US and half of healthcare dollars around the world) are diseases that do not have one gene, or one pathway to target. These are multifactorial diseases with multiple morbidities. And while each existed before 1970, each has exponentially skyrocketed in prevalence and severity during the modern era, and all for the same reason.

Insulin 101

Before we go any further, I want to do a brief discussion of insulin and its role in NCDs (more in Chapter 7). We all need insulin—it’s the hormone that allows glucose (your body’s primary source of fuel) to enter the cells of your body so it can be burned. But insulin resistance occurs when the cells in your muscles, fat, and liver no longer respond to the insulin signal. The glucose can’t get in—the cells are starving—so they send signals to the pancreas to crank out even more, but to no avail. The glucose builds up in your blood at the same time that your cells are starving, adding insult to injury. You’ll see that it’s this condition that is the underlying cause of most of our troubles.

Insulin resistance is the primary defect in metabolic syndrome, the cluster of NCDs. Insulin resistance manifests itself in a myriad of tissues and ways, which may vary from person to person. You may be overweight, or not. You might have high cholesterol, but maybe it’s normal. You might have high blood pressure, although it could be low. All of these are tissue-specific symptoms of metabolic dysfunction. Previously, doctors only diagnosed metabolic syndrome if you were obese. Now we know better. Even people who aren’t overweight develop metabolic syndrome. The issue is that doctors are still targeting obesity, which they think is the disease. Rather, it’s just another symptom.

Two other hormones also play a role in the hunger-satiety system. Leptin is a satiety hormone released from your adipocytes that tells your brain, “I have enough energy on board; I can stop eating.” Ghrelin is a hunger hormone released from your stomach that tells your brain, “I’m empty—feed me!” Normally, insulin does double duty—it tells your body to “store,” while it tells your brain to “stop eating.” When insulin is low and working right, both insulin and leptin counterbalance ghrelin and keep you weight-stable. But when you become insulin resistant, the leptin signal is blocked—now the ghrelin runs things, so you’re hungrier and storing like crazy. Therefore, the prime directive of metabolic therapy is “get the insulin down.” And that’s true, regardless of your weight.

Red herring refers to a clue that’s meant to be distracting. And that’s what obesity is—distracting. Everyone thinks that first you gain weight, and then you get sick. Yet, 80 percent of the time, it’s actually the other way around. First you get sick, then you gain weight. How do we know this? Because only 80 percent of obese people are metabolically ill. The other 20 percent of obese people are metabolically healthy. We even have a name for them—metabolically healthy obese (MHO). They will live a completely normal life, die at a completely normal age, have normal-length telomeres (the ends of the chromosomes that determine how sick you are and when you’ll die), and they won’t have exorbitant health insurance claims. The key is that these people have lots of subcutaneous fat, very little ectopic fat (fat in cells that shouldn’t have fat), normal metabolic function, and low insulin levels.

Obesity Is a “Red Herring”

How about the other 80 percent who are overweight and sick? They were sick first—they had metabolic syndrome—and that caused insulin resistance, which led to high insulin levels. But because their fat cells still responded to insulin, and that extra insulin allowed the fat cells to accumulate more energy, they got bigger. Therefore, their weight is a biomarker for their metabolic dysfunction.

When you look at the normal weight population, approximately 40 percent of those people also have metabolic syndrome—meaning they have metabolic dysfunction, insulin resistance, and high insulin levels (see Chapter 7). But for whatever reason, they’re just not obese. In some of them, their fat cells are insulin resistant, too, so energy doesn’t accumulate in the subcutaneous tissue. Instead they put it in other organs that shouldn’t have fat, such as muscle and the liver. This has spawned a new medical term with 1,500 citations in the literature called TOFI, or thin on the outside, fat on the inside.

And then there are the 20 percent of people who are overweight but not sick. Because the subcutaneous fat tissue can actually be protective, giving excess energy a nontoxic place to go. Just because they’re obese does not automatically mean that they harbor the egregious and deadly forms of fat in other organs where it shouldn’t be. Rather, it’s the ectopic fat that determines if they’ll develop diabetes or heart disease. In fact, my group at UCSF and others have shown that fat in the liver is the most predictive of whether someone will get diabetes in the future—which is why one mantra of this book is protect the liver. Furthermore, nonalcoholic fatty liver disease can lead to cirrhosis (scarring of the liver, which is lethal), just as can happen in chronic alcoholics. I’ve had to send two fifteen-year-old, four-hundred-pound boys for liver transplants, due to cirrhosis from soda consumption. We’ve even shown that kids with fatty liver disease also have fatty pancreas disease—and if your pancreas has fat in it, no wonder you can’t make enough insulin for your body’s needs.

Each of these conditions occurs in normal weight people, too! Obesity is just another symptom of the problem, not the problem itself. But Modern Medicine treats the biomarker (the weight) rather than the actual underlying pathology—and does a really crappy job of it.

OK, now you’re going to tell me about your Uncle Marvin, who went on a strict diet, started exercising, and his diabetes disappeared. And while this can absolutely work at the individual level, it doesn’t work at the societal level. Yes, the relative risk (RR) for lifestyle interventions in preventing diabetes is 0.61—that means, if you can carry out those interventions, your risk for diabetes goes down 39 percent. Sounds good, right? And if you’re one of the people for whom it works, fantastic. But the RR is not the important factor. The number needed to treat (NNT)—the number of people who have to go on a diet and lose weight to prevent one case of diabetes—is twenty-five. That’s right, twenty-five people have to diet and exercise insanely to prevent one of them from progressing on to developing diabetes.

No doubt, you’ve also watched some TV-doctor show where the guest dropped weight, their diabetes got better, their insulin went down, and they got a makeover. Cue studio applause. But it’s actually the other way around. Their insulin didn’t go down because their weight went down—their weight went down because their insulin went down. How do we know this? Because at UCSF, we got children’s insulins to go down without losing any weight, simply by getting them off dietary sugar. What they lost as a result was liver fat, which then made them insulin sensitive. Again, obesity is a red herring. Forget the obesity. Fix the metabolic problem. And Modern Medicine doesn’t.

Roto-rooting LDL

We all need cholesterol to survive; it’s an integral part of membranes and the precursor of steroid hormones. If you don’t consume cholesterol, your body makes it—it’s that important. You’ve probably heard that there’s “good” cholesterol and “bad” cholesterol. Doctors measure the bad stuff and tell you to lower it.

Let’s start with low-density lipoprotein cholesterol (LDL-C), the ostensible villain, the “classic” biomarker of risk for a future heart attack. Clinicians are taught to treat LDL-C with statins; but do statins actually work to reduce heart attacks?

Cholesterol (and more specifically LDL-C) emerged as a risk factor from the Framingham Heart Study, an observational study in Massachusetts that started after World War II and continues today. The takeaway was that if you had very high LDL-C you were more likely to suffer a heart attack. But when the data were analyzed, unless LDL-C was very high (over 200), it wasn’t a risk factor. In fact, patients with really high LDL-C levels often have a genetic disorder (I’m one of the lucky carriers). Your LDL-C level is for the most part genetically determined. Conversely, those with LDL-C levels less than 70 develop relatively little heart disease. Yes, there seems to be a genetic protection at the low end, and risk at the high end.

But for the rest of the population, LDL-C is not a great predictor of who will suffer a heart attack. It’s true that the HR ratio (hazard risk ratio; a measure of difference in risk versus the general population) of LDL-C is 1.3, which means that if your LDL-C is high, you have a 30 percent increase in risk for a heart attack. But correlation doesn’t mean causation. For example, if LDL-C is truly the bad boy of heart disease, as the Medical Establishment says, then why, when you remove younger people from the analysis and just look at older people (greater than sixty years), do high LDL-C levels correlate with longevity? Maybe, once you factor out the people with genetic reasons for high LDL-C (like those with genetic disorders), then LDL-C isn’t really so bad. Or maybe we’re measuring the wrong biomarker.

Let’s say you go see your provider, who tells you that you have high LDL-C. Nine times out of ten you’re going to walk out of that office with a prescription for a statin, which inhibits cholesterol synthesis. The current mindset among clinicians is to downshift everyone’s LDL-C through low-fat diet and drugs. Because that’s what they’re trained to do. I would know. I’m one of them. But really how beneficial are statins, and for what? Despite governmental recommendations to eat low-fat and despite a high prescription rate of statins, at a population level LDL-C levels haven’t change appreciably. It isn’t just the pill that’s the problem. The recommendation of a low-fat diet is just as bad (see Chapter 12).

It’s true that fewer people are actually dying of heart attacks in the US and other high-income countries (although low-income countries still have high mortality rates). But that statistic belies the truth. While fewer are dying of heart attacks, more people are suffering them. Of course rising numbers could be due to improved recognition, ambulance response time, emergency room functioning, the clot-buster tissue plasminogen activator (tPA), and heart attack post-care. But the real story is that more people are suffering heart attacks with lower LDL-Cs than before, because the standard fasting lipid profile—the blood test ordered by your practitioner to test your cholesterol—assumes that all LDL particles are the same. There are two different LDLs, but the lipid profile test measures them together. The majority (80 percent) of circulating LDL species are called large buoyant or type A LDL, which are increased by dietary fat consumption. This is the species reduced by eating low-fat or by taking statins. However, large buoyant LDL is cardiovascularly neutral—meaning it’s not the particle driving the accumulation of plaque in the arteries leading to heart disease. Then there’s a second, less common (only 20 percent) LDL species called small dense or type B LDL. There is some debate as to whether or not it’s the actual perpetrator of the plaque, but it doesn’t matter; small dense LDL is predictive of risk for a heart attack. The problem is that statins will lower your LDL-C because they’re lowering the type A LDL, which is 80 percent of the total; but they’re not doing anything to the type B LDL, which is the problematic particle.

Over the years, medical guidelines have continually expanded the number of individuals for whom statin therapy is recommended. Proponents argue that statins are “life-savers” and that “people will die” if they discontinue their medicine. Prominent researchers from reputable universities have declared that “everyone over fifty” should be on a statin to reduce their risk of CVD. Without a doubt they lower LDL-C. No argument, if the goal is reducing LDL-C, statins are a simple way to do it. And if you have a genetic disorder, they’re a necessary way to do it. But do they reduce the risk of heart attack across the board? Without a doubt they don’t! Almost assuredly, statins are reducing the large buoyant LDL but not doing anything about the small dense LDL—therefore the risk of a first heart attack remains unchanged. Conversely, up to 20 percent of statin users demonstrate some form of side effect, often quite serious. There’s now a burgeoning literature that statins increase glucose intolerance and risk for both diabetes and weight gain. Is it that, by acting on the liver, statins worsen insulin resistance? Or could it be the inverse—that statin use makes people think they can eat whatever they want because they are now impervious to any cardiovascular risk? It could be both.

So, are statins good or bad? If you don’t need to take statins, then why would you incur risk of a side effect, which could include muscle breakdown, kidney failure, and type 2 diabetes? The real question is, good or bad for whom? For you? Your provider needs to know, but nine times out of ten, they don’t. But are they good or bad for the insurance company, which gets to increase your rates for a preexisting condition (still true, even with the advent of Obamacare)? And good or bad for the drug manufacturer, who makes a fortune peddling their “cures”? And good or bad for the government, who are influenced by Big Pharma (see Chapter 6), and who follows the dictum that their voting contingencies will live longer?

Recognizing that the data on statins and heart attack are industry-generated (and likely best-case scenario), the increase of median life expectancy in those with heart disease thought to be the best candidates for statins over a five-year period is a meager four days. Four days? Really? And that’s a reason for the whole world to be taking them?

What we’ve learned in this futile exercise is that reducing LDL-C with statins is targeting the wrong pathology. It reduces the benign type A large buoyant LDL but the type B small dense LDL is unaffected. This is important because the problematic small dense LDL-C is a sign of insulin resistance and metabolic dysfunction. Yet the LDL-C level has become so important to Modern Medicine (i.e., the statin manufacturers) that the American Heart Association has advocated to reduce the LDL-C even lower. Indeed, the AHA has developed definitive criteria as to who needs treatment.

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Meanwhile, pharma companies sold patients and doctors globally close to $1 t r i ll i o n w or t h o f s t a t in s; c l ose t o$ 400 billion in the US alone. That is a pretty hefty haul for a four-day improvement in morbidity and mortality in otherwise healthy people.

Even the American Academy of Pediatrics says that eight-year-olds with high LDL-C need to be treated with statin therapy. I practiced pediatrics for forty years, twenty-four of them focused on obesity, diabetes, and lipid problems. Want to guess how many children I treated with statins? Five—in twenty-four years. Not because I’m a therapeutic nihilist. Not because I didn’t know what LDL was. In fact, I didn’t give them statins because I did know what LDL was. It was a marker of the problem, not the problem itself. And when I got my patients’ insulin down by getting them off processed food, their LDL and their triglycerides both came down as well.

What about other drugs that lower LDL? There are other newer drugs on the market, for instance ezetimibe (Zetia), which reduces intestinal cholesterol absorption, and evolocumab (Repatha), an inhibitor of an enzyme, which when blocked helps the liver clear more LDL. These drugs definitely reduce LDL-C, but thus far there are no data for either drug on cardiovascular risk reduction. Because the real problem is metabolic dysfunction due to insulin resistance—and statins do nothing to fix that. Processed food is the true upstream cause, but we refuse to own up to it. In Chapter 9, I’ll show you what you should look for in your lab data to diagnose your own metabolic disease, how to interpret it, and what to do about it.

If you have a high LDL-C level, your provider is likely to tell you to eat a low-fat diet. Similar to statins, while your LDL will go down, it’s only affecting the large buoyant LDL and not the small dense LDL, which is the actual problem. In fact, small dense LDL rises because they are responsive to dietary refined carbohydrate (i.e., fiberless food) and especially sugar consumption, which is what is substituted in lieu of the dietary fat. One of the most compelling arguments against LDL-C as the primary target of CVD prevention or treatment is the Lyon Diet Heart Study. The adoption of a Mediterranean diet for secondary prevention (after you’ve already had a heart attack) reduced the risk for recurrence. It’s clear that eating a Real Food diet, devoid of processed food (how they eat in Lyon) delivered far more impressive results when compared with statins—without the side effects and at a much lower cost. And this diet is decidedly not low-fat. Given that statins can give the illusion of CVD protection yet cause serious side effects, stopping statins and eating Real Food may paradoxically save more lives and improve quality of life.

Your fasting lipid profile test also measures another particle, which is much more egregious than LDL—triglycerides. The level of these particles tells you how your liver is doing. The HR ratio for triglycerides and heart disease is 1.8 (meaning that if they’re high, you have an 80 percent increased risk for heart attack) compared to LDL-C at 1.3. Further, the main reason for high triglycerides has nothing to do with LDL-C; rather, it’s the refined carbohydrates and sugars in your diet. Again, the #1 risk factor for heart disease isn’t LDL-C; it’s the insulin resistance of metabolic syndrome, of which triglyceride is a much better biomarker than LDL-C. In fact, the largest study of heart attacks in the US revealed that 66 percent of the victims had metabolic syndrome. And the primary driver? Insulin resistance. And its primary driver? Our out-of-control sugar consumption. Insulin resistance can be in part measured by your triglyceride level (see Chapter 9), which is a better predictor of death by heart attack than high LDL-C ever was.

The Blood Pressure Blow-out

Everyone agrees that hypertension (high blood pressure) is bad for you. When they strap on the blood pressure cuff in the doctor’s office, what they’re measuring is how well your heart is working, and how well it’s perfusing the rest of your body with blood. There are two numbers that convey this information: systolic blood pressure (the first number), which indicates how much pressure your blood is exerting against your artery walls when the heart beats; and diastolic blood pressure (the second number), which indicates how much pressure your blood is exerting against your artery walls while the heart is resting between beats.

In 1974, fifty-three million Americans had hypertension; that number has now doubled to one hundred million Americans. In the years between 1988 and 2017, the percentage of hypertensive patients taking medication quadrupled from 7 percent to 31 percent. This isn’t just diagnosis creep (even though the AHA recently lowered the systolic blood pressure threshold from 130 to 125). Once upon a time, fifty years ago, the diagnosis of hypertension was made when the systolic blood pressure was 100 plus the patient’s age. So hypertension in a forty-year-old was a systolic of 140. But this dropped to 130 in the 1980s as hypertension treatments started flooding the market, and Big Pharma advocated putting more people on more drugs. And now, hypertension is the #1 risk factor for death globally. Each 5-point rise in blood pressure increases your risk for death by 10 percent.

First problem of tackling hypertension: you can lower blood pressure in anybody with enough medicine. But what about side effects? You could experience weakness, dizziness, fainting, muscle cramps, or vomiting, or develop electrolyte imbalances. In general, lowering blood pressure is a good idea, but there’s still a 1 to 2 percent risk for death. For example, older people on blood pressure medicines could faint and break their hips—and falls are the leading cause of fatal and nonfatal injuries in older adults. Not a good look when the treatment is worse than the disease. There’s an increased mortality in older adults whose blood pressure is less than 130 as a result of the medication.

But is it the blood pressure, or the stuff that comes along with the blood pressure? Most people in the US who are being treated for mild hypertension (140 to 160, or 90 to 110) are taking some medication. However, patients with mild hypertension show no benefit from blood pressure reduction whatsoever in terms of cardiovascular disease, stroke, and death. Fixing the numbers doesn’t fix the patient. Furthermore, patients need to know these statistics before they’re placed on any blood pressure medications. Their doctors won’t tell them because they don’t know; they’re taught to push the pill. Which is where this book comes in—to explain that changing your diet can reverse metabolic syndrome more effectively and without side effects.

And why is so much of the population hypertensive now? Why is its prevalence rising? Does the whole country actually need to be taking a blood pressure pill? The UK documented a 40 percent reduction in stroke between 2006 and 2012 via the simple public health maneuver of forcing the food companies to reduce the amount of salt allowed in processed foods. This strategy worked because the government targeted the pathology, recognizing that a primary cause was processed food, rather than just the symptom of being hypertensive. Reducing salt in the UK cost nothing, while the overall cost of pills for the whole population with high blood pressure was north of $3.3 billion in 2006.

So, is salt really the villain we make it out to be? Currently, the FDA suggests that we consume a maximum of 2.3 grams per day, and only 1.5 grams for those with hypertension. This admonishment exists despite our current median salt consumption of 6.9 grams per day, a tripling over what we actually need. Then again, our recent ancestors, prior to refrigerators, would consume over 15 grams of salt per day! In the bad old days of clipper ship fishing without engines or refrigeration, the fish would have to be salt-cured to protect them from bacterial infestation and contamination. You survived in the winter because you salt-cured your meat and fish in the spring.

So why didn’t 15 grams of salt a day cause our ancestors to stroke out routinely? The reason is because the kidney is very adept at excreting excess sodium. But there’s one thing that inhibits sodium excretion by the kidney—insulin resistance. High insulin levels increase blood pressure, even with relatively low sodium intake. And many people are insulin resistant—and those people do need to lower their salt as a treatment of the disease. It isn’t just the salt—it’s also our processed food.

Just a Spoonful of Sugar Helps the Blood Pressure Go Up

What dietary maneuver can fix blood pressure even faster? How about sugar restriction? See Fig. 2–1a,b to see how sugar raises your blood pressure more than salt. Sugar also causes liver fat accumulation, insulin resistance, and increased diastolic blood pressure. Sugar restriction quite rapidly reduces both systolic and diastolic blood pressure, as long as the patient in question doesn’t have preexisting kidney disease.

So what’s the most effective method of treatment: lowering salt, getting rid of sugar, or taking blood pressure medication? If you take processed food out, you’ve lowered salt and sugar, and you wouldn’t need the medicine.

Figure 2–1: a) Pathway of liver glucose metabolism. More information can be found in Chapter 7, under “Cell Bio 101.” Only 20 percent of a glucose load enters the liver, and the majority is turned into glycogen (liver starch) for storage. A small amount of glucose will undergo glycolysis (the first step of glucose metabolism, which doesn’t need oxygen) to the breakdown product pyruvate. Pyruvate can then enter the mitochondria to be burned via the Krebs cycle all the way to carbon dioxide and water, capturing energy in the form of the chemical adenosine triphosphate (ATP)—the energy is in the phosphates. b) Pathway of liver fructose metabolism. 100 percent of a fructose load enters the liver. Fructose leads to loss of phosphates from ATP, generating of uric acid, which reduces nitric oxide, your blood vessels’ relaxing agent, which leads to hypertension. Most of the fructose is turned into pyruvate, the mitochondria become overwhelmed, and the excess generates liver fat, which causes insulin resistance. High insulin interferes with satiety, driving further consumption.

Blood Glucose—Dude, Are You High?

Let’s talk about hyperglycemia (high blood glucose)—the classic symptom of diabetes. First of all, there are two kinds of diabetes: type 1 is due to insulin deficiency (an autoimmune destruction of the pancreas) and is usually associated with children (although some adults can get it); type 2 is due to insulin resistance (see above), the key driver of metabolic syndrome and usually associated with adults (although some children, especially ones I see in my clinic, can get it).

A fasting blood glucose level is the common test ordered by your doctor in addition to testing your cholesterol. This test administered on type 2 diabetics will reflect high and fluctuating glucose levels. Another blood test for chronically high blood glucose levels is the diabetes biomarker hemoglobin A1c. If you have type 2 diabetes and run high blood glucose levels, you’re at increased risk for disease in several organs, such as retinopathy (eye), neuropathy (peripheral nerves), and nephropathy (kidney). And when diagnosed, your clinician is likely to prescribe medications such as oral hypoglycemics (glucose-lowering agents) and injectable insulin to lower blood glucose and hemoglobin A1c.

So why do these medications lead to increased mortality? Initially, it looked like these medicines made things better. There was an initial reduction in amputations in dialysis with intensive blood glucose control. But the rates of type 2 diabetes continue to climb, and the potential side effects of these meds, which can include dizziness, drowsiness, heartburn, gastrointestinal distress, and seizures, continue to accrue. In fact, the side effects of glucose-lowering meds are responsible for 100,000 ER visits in the US per year. Again, these meds are treating the symptom, not the cause.

The fact of the matter is it’s not really about blood glucose. Blood glucose is just the indirect measurable proxy for the real culprit—which is the blood insulin level. Insulin is the real bad guy in this story—it is its own risk factor, and while high blood glucose can trigger an insulin response, most of the time your blood insulin is unrelated to blood glucose. We know this at a basic molecular level, because of seminal mouse studies done by Dr. C. Ron Kahn’s lab at Joslin Diabetes Center in Boston. Kahn’s lab constructed eight separate tissue-specific insulin receptor knockout (IRKO) models. Each mouse was genetically engineered to be missing their insulin receptor in a different organ (normally, both mice and humans have insulin receptors in every organ), and therefore insulin has different effects in each mouse. The scientists took the insulin receptor out of the liver, brain, fat cells, brown adipose tissue, muscle, beta-cells, vascular smooth muscle, or kidney. Each mouse developed some form of pathology, none were healthy. But the pathologies were all different from each other. Interestingly, only the liver and the brain IRKO mice developed high blood glucose, and only the brain IRKO mouse became obese and developed metabolic syndrome. And even more interestingly, the kidney IRKO mouse had normal blood glucose, but developed diabetic kidney disease anyway. These various mice show that the cause of the disease is not the high blood glucose—it’s the insulin! And this isn’t just in mice—we know this is true in humans as well. Because when people with type 1 diabetes (insulin deficiency) are diagnosed, they have normal kidneys, and it takes about ten to twenty years of bad glucose control before they develop kidney disease. Yet, people with metabolic syndrome (insulin resistant) already have kidney disease even before their glucose levels start to rise.

The reason for this dichotomy is because insulin is both good for you—because it lowers blood glucose to prevent microvascular disease—and bad for you in that it increases the smooth muscle around the coronary arteries or in the kidney, leading to narrowing, and more risk for a heart attack or kidney failure. Let me explain why. Insulin has two actions in cells: 1) metabolic (lowers glucose, stores energy); and 2) cell proliferation (meaning growth and division). Every insulin molecule your pancreas makes is both good and bad for you, all at the same time—short-term gain (blood-glucose lowering) for long-term pain (vascular dysfunction and cancer). This dichotomous effect of insulin has been seen in every intensive blood glucose control study, such as the UK Prospective Diabetes Study (UKPDS), the Action to Control Cardiovascular Risk in Diabetes Study (ACCORD) on the effects of rosiglitazone, the Veterans Affairs Diabetes Trial (VADT), and the Action in Diabetes and Vascular Controlled Evaluation (ADVANCE), which actually had to be stopped midstream because of the increase in patient mortality from large vessel disease (heart disease). We need insulin to survive, but if we are insulin resistant, adding extra insulin lowers glucose only at the expense of contributing to chronic disease. Short-term gain for long-term pain.

Treat the Symptoms, or Reverse the Disease?

Debates over treatment of symptoms versus reversal of disease are rampant throughout the medical literature. What these arguments demonstrate is that treatment can be targeted and individualized (thus preserving “personal liberty”), but it can exact a hefty cost—not just to the patient, but also to society.

Conversely, prevention doesn’t need to be targeted—it can be global, across the board, therefore saving money and lives. Managing metabolic syndrome disease is 75 percent of the total healthcare budget; and we’re not really treating it—we’re papering it over, which means that the costs are cumulative. Morbidity keeps costing until you die, and people are dying earlier, not paying into the system, and therefore costing more.

Modern Medicine works downstream of the problem by treating the symptoms, rather than working upstream to treat the cause. Doctors continue to fill the wrong prescription over and over. And it’s breaking the bank and costing us our lives.

🔮 The Cosmos

Metabolical Chapter 2. “Modern Medicine” Treats Symptoms, Not Disease

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