Early clues to metabolic syndrome

High insulin levels can slowly kill you

The term “metabolic syndrome” is confusing to both patients and physicians — mostly because it is currently “defined” using the following (source).

A better definition of metabolic syndrome would be to define it as Dr. Peter Attia does (source):

One way to think about metabolic disease is as a disorder in fuel processing. Whether we’re talking about hyperinsulinemia or type 2 diabetes, the fundamental problem is that the body is not doing a good job storing and accessing fuel.

As such, a person can technically be non-obese, yet still have metabolic dysfunction that leads to high insulin levels and/or high glucose levels.

What is insulin resistance and what is it so bad?

While the NCEP ATP III criteria are helpful to recognize metabolic syndrome, and it’s obvious that each of the defining components (abdominal obesity, hyperglycemia, dyslipidemia, and hypertension) are bad for your health. This said, in most, if not all cases, insulin resistance precedes clinically recognizable metabolic syndrome.

Normally, insulin tells the cells in the body to take up glucose from the bloodstream. After being taken up, it is either used for energy, or stored as glycogen or fat.

Insulin resistance is when the body doesn’t respond properly to insulin, which which first results in higher amounts of insulin being released from the pancreas to achieve the same effect, and then hyperglycemia (elevated blood sugars).

Many don’t realize that elevated insulin levels alone are harmful. Besides promoting obesity and weight gain by keeping adipose cells in storage mode more of the time, high insulin levels promote inflammation and are directly toxic to cells, and appear to be associated with a shorter lifespan.

How to detect metabolic syndrome and insulin resistance early?

So, you’re getting your labs checked every 3-4 months (not just yearly or less, right anon?) and want to see if you notice any clues that you might have insulin resistance. Here’s what you’re looking for with an intermittent lab check:

• Fasting glucose: Take this one with a grain of salt, because it literally only gives you information about what your blood sugar was at the very moment your blood was drawn. Nevertheless, if you see a number over 110, that’s really bad, as per the metabolic syndrome definition above. Personally, I never really want to see this above 100 unless there is a really good explanation (the person only slept 3 hours the night before and ate 2 bowls of ice cream before going to bed). Optimally, I like to see this in the 70-90 range.

• Hemoglobin A1c (HgbA1c). This test gives you the average blood sugar over the last 3 months or so (it depends a bit on the lifespan of your RBCs, which are influenced by a number of other factors). The results of the HgbA1c (given as a %) can be converted as follows (source):

Optimally, we’d like to see your average blood sugar under 100, which corresponds to a HgbA1c of 5.1% or less. The usual normal range of most labs goes up to 5.6%, which allows for an average blood sugar up to 114. Pre-diabetes (a terrible term) is often diagnosed when the HgbA1c is between 5.7-6.4% (average blood sugar of 117-137), and then diabetes is diagnosed when it is 6.5% or above (average blood sugar 140+).

Given some nuances of the HgbA1c test, I’m generally okay if people have a reading of 5.2 or 5.3%, but I want to monitor closely in this situation.

Fasting insulin. After a 8-12 hour fast, a person’s insulin levels should be as low, which suggests that your cells are sensitive to insulin. Similar to fasting glucose levels, this is another spot check, and can be elevated by numerous factors. Optimally, I like to see levels under 10 uIU/mL, although up to 12-15 uIU/mL can be acceptable. Currently, Labcorp lists 24.9 uIU/mL as the upper limit of normal, which I think is too high.

ALT (sometimes called SGTP). This is a transaminase enzyme that primarily comes from the liver, and elevated levels generally suggest some type of liver damage occurring. In modern times, one of the most common reasons for an ALT elevation is fatty liver (although medications/toxins and other causes should be ruled out as well).

Given obesity and fatty liver has become “normal” in our population, unfortunately, the “normal” range for ALT has gone up over time. Currently, Labcorp lists 44 IU/L as the upper limit of normal for ALT. With this in mind, it’s better for us to pursue more historically normal ALT levels (before epidemic levels of fatty liver) — so optimally, your ALT is under 30 IU/L.

Fasting triglycerides. If the triglycerides in your bloodstream are elevated while fasting, this suggests that your insulin levels are elevated because your cells are responding to the high levels of insulin by trying to store more fat — which is spilling out into the bloodstream. Optimally, your triglycerides are under 50-60 mg/dL, and you never really want to see them over 100 mg/dL. (Again, ignore the “normal” lab range which typically allows for triglycerides up to 150 mg/dL).

HDL. Elevated insulin levels decrease production and of HDL via several direct and indirect mechanisms. For our purposes, it’s helpful to know that low HDL levels are associated with increased risk of CVD. Optimally, I like to see someones HDL levels higher than their triglyceride levels, although it should be noted that testosterone replacement therapy typically decreases HDL levels (I generally ignore this marker unless HDL goes below 40 mg/dL while on TRT). An acceptable level of HDL is otherwise generally above 50 mg/dL.

Uric acid. High insulin levels lead to increased activity of the enzyme involved in producing uric acid, called xanthine oxidase. Most physicians only think about uric acid levels in regards to gout (which starts to occur when the uric acid is above 6.0 mg/dL), and many labs will allow for a uric acid up to 6.5 or 7.0 mg/dL. Optimally, your uric acid is below 4.5 mg/dL, although if you eat an extremely high purine diet (organ meats, shellfish/seafood), then we can allow for up to 5.0 mg/dL.

Still not sure?

Sometimes there are a few clues that a person might have some early metabolic syndrome/insulin resistance, and additional testing is needed. Typically the next test done is an OGTT, or oral glucose tolerance test, where a person consumes 75-100 g of pure glucose, and then measures glucose levels at intervals afterward. Technically this could be done at home if someone has a home glucose monitor and is able to purchases pure glucose and weighs out the proper amount. (There are several different OGTT protocols, but most start with a lower dose glucose challenge). If done in the office, insulin levels can also be measured at this time.

If results here are still unclear, I’d personally opt for the use of a continuous glucose monitor for a few weeks, which would give you a reading of your actual blood sugar levels, and would help you learn which foods/activities have significant negative effects on your blood sugars.