METABOLIC DISEASE

The progression of metabolic disease ultimately culminates in a diagnosis of Type 2 Diabetes. Prior to the diagnosis of diabetes, you may be told you have metabolic syndrome or even "pre-diabetes." Some other terms associated with metabolic disease are "insulin resistance" and "non-alcoholic fatty liver disease." Below we will give a little bit of background on the estimated number of people afflicted with some form of metabolic disease and loosley define all the terms mentioned above, while describing the disease progression.

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By the Numbers

Diagnosis

Symptoms

Causes

Why is metabolic disease dangerous?

Prevention and Preservation

OVERVIEW

Metabolic disease is becoming almost ubiquitous today. It is estimated that about 50% of people have metabolic disease, manifested as insulin resistance in the muscle. The problem is that this manifestation is often not screened for and it can precede the diagnosis of diabetes by years (up to 13, according to one review).

This means being proactive is key. Unfortunately, given the limitations of our current healthcare system, it is required that you get involved in your own care and have an understanding of the problem. You don't have to be an expert in every facet of your health, but when it comes to metabolic disease you should feel confident asking your provider why they did or did not run a specific test and you should be comfortable asking for certain tests. Much like buying a new home, you want to have an idea of the red flags the inspector is looking for so that you aren't surprised by an issue down the road. Many of us don't take this approach to our health and are shocked when diagnosed with a chronic disease that we may have been able to see coming.

Some blood biomarkers for metabolic health include (not comprehensive):

Fasting Plasma Glucose
Fasting Insulin
Hemoglobin A1C (HbA1C or A1C)
Liver Function Testing
Triglycerides
HDL-C

Some assessments of metabolic health include:

Resting Metabolic Rate
Lactate Test with Exercise
Metabolic Efficiency Exercise Test
Oral Glucose Tolerance Test (OGTT)

The purpose of the metabolic and exercise tests is to get a sense of how well the body can utilize fat as fuel at rest and during exercise. If this ability is impaired, fat accumulation can contribute to the progression of metabolic disease. The OGTT can give us a sense of whether there is an insulin resistance problem well before there is an elevated blood glucose problem. This is a functional test that can assess both your glucose and insulin response to ingested glucose and the results can indicate if you have adequate or deteriorating insulin sensitivity.

Being proactive and aware of the lifestyle contributors to the disease can be enough to prevent it from ever taking hold. Once it does take hold, hope is not lost as it is reversible. Depending on the severity (insulin resistance to full blown diabetes), pharmaceutical interventions may be required, and more dramatic nutritional measures may need to be taken, but it is reversible. Deteriorating metabolic health can lead to a wide array of health complications, from retinopathy to neuropathy and stroke to heart attack. All these risks are real, but the preventive measures you can take right now can seriously improve prognosis.

By the Numbers

The CDC estimated that in 2019, 37.1 million U.S. adults (18 years or older) had diabetes. This is roughly 14.7% of the entire U.S. adult population. 8.5 million of these adults (about 23% of all adults with diabetes) were completely unaware they had it.

Among the same population of U.S. adults, 96 million had prediabetes in 2019. This is roughly 38% of the adult population, and of these individuals, only half were aware of their diagnosis.

Estimates of insulin resistance and metabolic syndrome are a little harder to grasp, and they do vary by geography, but it is estimated that somewhere between 1/3 and 1/2 of adults have the diagnosis in one way or another and are completely asymptomatic.

Based on the numbers above, the likelihood that you or a loved one is impacted by metabolic disease, somewhere on the spectrum is quite high. And that's a sobering and scary reality.

Diagnosis

Before explaining how diabetes/prediabetes is diagnosed, I want to point out that it is extremely important to pay attention to your metabolic health status WAY before diagnosis. By the time you have manifested clinical signs of diabetes or even prediabetes, a lot of issues have already taken hold that are simply not measured. With that said....

Common blood tests can be used to diagnose both diabetes and prediabetes. The same tests are used; however, different reference ranges define the diagnosis.

Fasting Plasma Glucose (FPG) is the test that is undoubtedly run any time you have blood work done and is usually the first sign of trouble. The results must be repeated in more than one instance given the variability that can occur in normal, healthy individuals. FPG is the amount of glucose (sugar) that is circulating in your blood following an overnight fast (8 hours). Glucose is our body's primary source of energy and is obtained through food. Therefore, when we eat, blood sugar rises, and when we have fasted, blood sugar should lower. When it doesn't go down in the absence of food, it is cause for concern.

Prediabetes = FPG >100 mg/dL

Diabetes = FPG >126

A1C is a common test but is not routinely ordered. It is usually ordered upon suspicion of a problem (i.e. you have risk factors for diabetes like being overweight, blood cholesterol abnormalities, sedentary lifestyle, etc.). It is a method that allows us to get an idea of what your blood glucose levels have been over time (about 3 months). In short, glucose links itself to our red blood cells. We know how many red blood cells (in a percentage) should have that link. When the percentage of red blood cells with the glucose link begins to rise, it is a sign that blood glucose levels are chronically elevated. This is more indicative of a problem than FPG because FPG is a snap-shot, while A1C is a look over time (although not perfect).

Prediabetes = A1c > 5.7%

Diabetes = A1C > 6.5%

Oral Glucose Tolerance Test (OGTT) is not routinely ordered and is in fact rarely ordered proactively. This is a test that assesses the ability of the body to "tolerate" ingested (eaten) glucose. As I mentioned, eating will raise our blood sugar. But this elevation should not be overly dramatic, and it should be short-lived. For this test, the patient has FPG measured and is then instructed to drink a pure glucose drink (Glucola). Blood is then sampled 2 hours later, evaluating blood glucose levels. The beauty of this test, even if you are only looking at blood glucose levels, is that it provides us a functional test result for your body in real-time. We can assess how well your body is able to take in glucose from food and then repurpose it in the body, either for fuel or for storage. In someone who is metabolically unwell, they will be very inefficient in utilizing the glucose and we will see high levels of blood glucose upon the completion of the test.

Prediabetes = Blood Glucose 140-199 mg/dL

Diabetes = Blood Glucose > 200mg/dL

A Note on Metabolic Syndrome: "Metabolic Syndrome" is collection of risk factors that are all associated with increased risk of chronic disease development (heart disease, stroke, diabetes). There are 5 risk factors under the syndrome's umbrella, and in order to be diagnosed, you have to present with at least 3. They are as follows:

Abdominal Obesity: This is having a large waist circumference (Women >35 inches, Men >40 inches) measured at the belly button. This is an indication of high "visceral fat," which is highly toxic to the body, synonymous with the dreaded "apple shape."
High Blood Pressure: Blood pressure of 130/80 mm/Hg or higher is a warning sign. Blood pressure is discussed more in the cardiovascular disease page
Elevated Fasting Blood Glucose: Defined as a value > 100 mg/dL as described above
High Triglyceride Levels: Defined as > 150 mg/dL.
Low HDL Cholesterol: Defined as <40 mg/dL in men and < 50 mg/dL in women.

It is estimated that up to 1/3 people in the U.S. suffer from metabolic syndrome, and unfortunately many are completely unaware.

The image above, courtesy of https://diabetes.org/diabetes/a1c/diagnosis highlights the 3 major tests for diagnosis. Hemoglobin A1C (A1C), Fasting Plasma Glucose (FPG) and Oral Glucose Tolerance Test (OGTT).

Are there Symptoms?

Unfortunately, symptoms are not a requirement of diabetes, at least not until it is already fairly severe.

According to the CDC, some common symptoms are as follows:

Frequent urination (peeing), especially at night
Thirst
Persistent hunger
Blurred vision
Numb/tingling hands or feet
Extreme fatigue/lethargy
Sores/cuts/bruises heal slowly

The issue is that diabetes, or more accurately metabolic disease, is present long before these symptoms manifest. Since most of the symptoms above are associated with chronically high levels of blood glucose, we are missing the underlying cause and are therefore late to treatment.

So, are there symptoms of diabetes? In some cases, and really only in severe cases, yes. Most often, the disease works in the background and is only discovered upon routine bloodwork at an annual physical examination (as mentioned above). It is critical to stay on top of your primary care, and as you will learn, it is just as important to be proactive and advocate for optimal care.

What Causes Diabetes (the simple version):

There are a few important take home points from this graphic:

The root of the problem is an imbalance in energy in vs energy out. This means eating too much and exercising too little is a trigger to set off this cascade. Added sugar can be especially problematic as it causes sharp rises in blood glucose and insulin, but also because it usually leaves us feeling hungry (rather than full) and it can be consumed in very high doses very quickly (drinking a can of cola).
We generally don't identify an issue in metabolism until you are diagnosed with diabetes or prediabetes. With more rigorous screening and attention to detail, we can identify the early stages of metabolic disease based on simple blood biomarkers. But you have to know what to look for.
Modifying the first input in this pathway (energy in vs energy out) can be powerful enough to stop metabolic disease progression. But the further down the line you get, the more work it takes to reverse the disease.

Above is a simplified way to think about how diabetes, specifically Type 2 Diabetes, is caused (Type 1 diabetes is a completely different disease).

Why is Diabetes/Metabolic Disease Dangerous?

Metabolic disease is at the foundation of many of the chronic diseases people from which people suffer. The chronic elevations in glucose and insulin are known to cause problems both at the "macro" and "micro" vascular levels, meaning the big blood vessels and the small.

Small Vessel Disease

Prolonged elevation of blood glucose is destructive to the very small vessels within our body. These high levels of glucose trigger a variety of toxic pathways that contribute to the destruction of the small vessels of the body. Specifically, small vessels include those in the eyes, the kidneys and those that supply nerves in our arms, legs, hands and feet.

A chronically elevated blood glucose level can lead to retinopathy (damage to the blood vessels of the eye) which can result in blindness. The damage to the kidneys can ultimately lead to renal disease which can result in the need for dialysis. Peripheral neuropathies are caused by the damage to the nerves and results in numbness, pain, tingling and even undetected wounds of the feet due to the lack of sensation.

Large Vessel Disease

This disease of the vessels like the coronary arteries (arteries of the heart), the brain and the limbs. Patients with diabetes are at up to 2.5 times more risk to die of heart disease than those without diabetes. Diabetics are more likely to have strokes and peripheral vascular disease (this is where blood struggles to make it through the arms and legs, leading to pain and inability for wounds to heal). Diabetes even increases the risk of cognitive decline.

As mentioned above, the metabolic syndrome (abdominal obesity, high blood pressure, elevated blood glucose, elevated triglycerides, reduced HDL-C) increases the risk of heart disease. Sadly, metabolic disease can cause issues with blood cholesterol and blood lipids. So elevated blood glucose associated with metabolic disease is independently a risk factor, but it can lead to the development of additional risk factors that dramatically increase risk.

The Sooner the Better

Yes, once an individual is diagnosed with diabetes, or even prediabetes, their risk for all these devastating diseases jumps up. But what about the build up to the diagnosis? Is that dangerous?

There is evidence that fasting glucose and glucose tolerance begin deteriorating 3 years prior to diagnosis of diabetes and insulin sensitivity is reduced up to 5 years before diagnosis.

Additionally, a study demonstrated that an increase in HbA1c by 1% was associated with a 20-30% increase in cardiovascular events. This was true even if your increase by 1% left you in a "healthy" range, defined as being <5.7%.

There is a growing body of literature (summarized a bit here) that not only changes in HbA1c and fasting glucose can have negative consequences on health, but even day-to-day or within-day variability is dangerous. This is where continuous glucose monitors (CGM's) can be useful. And this is not only for the diabetic, but this can be useful for anyone who wants to optimize their metabolic health. Understanding what types of meals trigger you blood glucose to skyrocket is incredibly valuable, but the continuous nature of the monitors allows for the formulation of lifestyle modification based on data. Poor sleep, stress and lack of activity can all cause blood glucose levels to spike in addition to diet.

How to Prevent Diabetes and Preserve Metabolic Health

Here are a few helpful insights that can be used to reduce the likelihood of developing metabolic disease.

Know your numbers: This goes well beyond knowing you fasting glucose or HbA1c. You should know your liver function tests, HDL-C and Triglycerides, Insulin, Uric Acid and more. It is important to review these labs with a qualified healthcare professional who can interpret the complexities of these biomarkers.
Exercise: Long duration, steady-state exercise (think running, brisk walking, biking, etc.) is shown to improve our ability to utilize glucose in the muscle. This type of exercise will help us burn up the fat that is at the root of most of the metabolic dysregulation and can go a long way in improving health.
Diet: Depending on where you are on the continuum (being proactive about metabolic health vs diagnosed with diabetes), the nutritional approach varies. Generally, eating only as many calories as you need is a good rule of thumb. This means avoiding empty calories and mindless eating, but the further down the road to diabetes you go, the more you need to pay attention to things like how many carbohydrates you are eating. Carbohydrate restriction may be necessary once diagnosed with diabetes to reverse its progression but can be helpful at any stage.
Experiment: You can go ahead and try a CGM through a company like Levels, Supersapiens or Veri to get an idea of what your glucose levels are (they run anywhere from $100-200/month) or you can buy a simple over the counter blood glucose monitor with test strips and manually test after meals, upon waking and intermittently during the day. Getting a sense of what your blood glucose levels is never a bad idea.