summarize this "As devastating as it is, cirrhosis is not the only end point I’m worried
about here. I care about NAFLD and NASH—and you should too—because
they represent the tip of the iceberg of a global epidemic of metabolic
disorders, ranging from insulin resistance to type 2 diabetes. Type 2 diabetes
is technically a distinct disease, defined very clearly by glucose metrics, but I
view it as simply the last stop on a railway line passing through several other
stations, including hyperinsulinemia, prediabetes, and NAFLD/NASH. If you
find yourself anywhere on this train line, even in the early stages of NAFLD,
you are likely also en route to one or more of the other three Horsemen
diseases (cardiovascular disease, cancer, and Alzheimer’s disease). As we will
see in the next few chapters, metabolic dysfunction vastly increases your risk
for all of these. So you can’t fight the Horsemen without taking on metabolic
dysfunction first.
Notice that I said “metabolic dysfunction” and not “obesity,” everybody’s
favorite public health bogeyman. It’s an important distinction. According to
the Centers for Disease Control (CDC), more than 40 percent of the US
population is obese (defined as having a BMI
[*2] greater than 30), while
roughly another third is overweight (BMI of 25 to 30). Statistically, being
obese means someone is at greater risk of chronic disease, so a lot of
attention is focused on the “obesity problem,” but I take a broader view:
obesity is merely one symptom of an underlying metabolic derangement, such
as hyperinsulinemia, that also happens to cause us to gain weight. But not
everyone who is obese is metabolically unhealthy, and not everyone who is
metabolically unhealthy is obese. There’s more to metabolic health than
meets the eye.
As far back as the 1960s, before obesity had become a widespread
problem, a Stanford endocrinologist named Gerald Reaven had observed that
excess weight often traveled in company with certain other markers of poor
health. He and his colleagues noticed that heart attack patients often had both
high fasting glucose levels and high triglycerides, as well as elevated blood
pressure and abdominal obesity. The more of these boxes a patient checked,
the greater their risk of cardiovascular disease.
In the 1980s, Reaven labeled this collection of related disorders
“Syndrome X”—where the X factor, he eventually determined, was insulin
resistance. Today we call this cluster of problems “metabolic syndrome” (or
MetSyn), and it is defined in terms of the following five criteria:
1. high blood pressure (>130/85)
2. high triglycerides (>150 mg/dL)
3. low HDL cholesterol (<40 mg/dL in men or <50 mg/dL in women)
4. central adiposity (waist circumference >40 inches in men or >35 in
women)
5. elevated fasting glucose (>110 mg/dL)
If you meet three or more of these criteria, then you have the metabolic
syndrome—along with as many as 120 million other Americans, according to
a 2020 article in JAMA. About 90 percent of the US population ticks at least
one of these boxes. But notice that obesity is merely one of the criteria; it is
not required for the metabolic syndrome to be diagnosed. Clearly the problem
runs deeper than simply unwanted weight gain. This tends to support my view
that obesity itself is not the issue but is merely a symptom of other problems.
Studies have found that approximately one-third of those folks who are
obese by BMI are actually metabolically healthy, by many of the same
parameters used to define the metabolic syndrome (blood pressure,
triglycerides, cholesterol, and fasting glucose, among others). At the same
time, some studies have found that between 20 and 40 percent of nonobese
adults may be metabolically unhealthy, by those same measures. A high
percentage of obese people are also metabolically sick, of course—but as
figure 3 illustrates, many normal-weight folks are in the same boat, which
should be a wake-up call to all. This is not about how much you weigh. Even
if you happen to be thin, you still need to read this chapter.
"