Hyperinsulinemia
Can You Have Normal Blood Sugar and Still be at Risk for Metabolic Problems?

Hyperglycemia – High Blood Sugar

A healthy, well-regulated body keeps blood glucose (BG) within a relatively narrow range. When BG is 99 mg/dL (5.5 mmol/L), there’s only about a teaspoon — one teaspoon — of glucose in your entire bloodstream (1). When BG drops too low, or drops very quickly from a previously high level, signs and symptoms of hypoglycemia may occur, such as feeling shaky, dizzy, light-headed, nauseated, sweating, or having a racing heart. In very severe cases, seizures or unconsciousness may result.

On the other hand, hyperglycemia—blood sugar that’s very high—typically causes damage slowly and silently, over a long period of time, until the damage is so severe or widespread that a person begins to show signs and symptoms.

Common complications from type 2 diabetes (T2D) show us the harmful effects of chronically high blood glucose. These mostly involve damage to both small and large blood vessels, leading to eye damage (retinopathy), nerve damage (neuropathy), kidney damage (nephropathy), stroke, cardiovascular disease, poor or slow wound healing, and more.

With these things in mind, it’s obvious why maintaining a healthy blood glucose level is important. But as strange as it might sound, there’s a lot more to blood glucose than just blood glucose.

Diagnosing Type 2 Diabetes is Seriously Flawed

There’s a major flaw with how type 2 diabetes (T2D) is traditionally diagnosed. There’s typically only one thing measured when doctors suspect a patient has T2D: blood glucose. Here are the classifications, according to the American Diabetes Association (2):

Fasting BG, HbA1c, and the OGTT are all measures solely of blood glucose. The reason this is a problem is that for many people, blood glucose is normal, but it’s normal because it’s being kept in check by sky-high insulin. And a large body of research shows that chronically high insulin is the culprit in many serious health problems, even when glucose is normal.

Dr. Joseph Kraft, MD, coined the term “diabetes in-situ” or “occult diabetes” to describe this situation. Occult means hidden: the diabetes is hidden, or masked, by the high insulin. For many people, fasting glucose and HbA1c are the last things to rise. They are late indicators of metabolic dysfunction, and they become elevated only after one of two things has happened:

1. The pancreas can no longer pump out the inordinate amounts of insulin required to keep blood glucose within a safe range (sometimes called “beta cell burnout”).
2. The pancreas still secretes large amounts of insulin but some of the body’s cells no longer respond to it properly, resulting in high blood glucose. (These cells become resistant to the presence of insulin.)

This explains why many people are surprised by a diagnosis of type 2 diabetes or pre-diabetes. They — and their doctors — had been fooled into a false sense of security by glucose measurements that fell within normal ranges for years, perhaps decades, because insulin wasn’t being measured.

Hyperinsulinemia and Metabolic Syndrome: Chronically High Insulin

Having come from a checkup where their fasting glucose and A1c were normal, many people get a clean bill of health with regard to risk for T2D. But what if they know something isn’t right? They struggle to lose weight despite exercising and eating a healthy diet — or what they think is a healthy diet.

They have skin tags. Some women experience infertility or amenorrhea due to PCOS; men may be dealing with erectile dysfunction or an enlarged prostate gland. What about high blood pressure in people who dutifully avoid sodium, or high triglycerides in those who religiously follow a low-fat diet?

These are all signs and symptoms of chronically elevated insulin, independent of blood glucose levels.

Gerald Reaven, MD was one of the first physicians to recognize that several issues clustered together in patients ( 3). And because they clustered together, they likely had the same underlying cause. The issues that were often found together were:

• Abdominal obesity
• High triglycerides
• Low HDL
• High blood pressure
• Elevated fasting glucose

Not knowing what the underlying cause was, Dr. Reaven coined the term “syndrome X.” Over time, research revealed the unifying factor to be elevated insulin, and the name changed from syndrome X to metabolic syndrome. It could just as easily be called high insulin syndrome, and some doctors quite rightly call it insulin resistance syndrome ( 4).

Unlike “metabolic syndrome,” which may be a nebulous, unclear term to some people, calling it insulin resistance syndrome says loud and clear that the main problem is insulin. (Read more about insulin resistance in this past post from KetoDiet App.)

How Is Metabolic Syndrome Diagnosed?

In order to trigger a diagnosis of metabolic syndrome, a person has to show at least three of these five criteria (5):

• Large waist circumference: > 35 inches (89 cm) for women; > 40 inches (102 cm) for men
• High triglycerides: > 150 mg/dL (1.7 mmol/L)
• Low HDL: < 50 mg/dL (1.3 mmol/L) for women; < 40 mg/dL (1.04 mmol/L) for men
• Hypertension: ≥ 130/85 mmHg
• Elevated fasting glucose: ≥ 100 mg/dL (5.6 mmol/L)

Notice something missing? Something gravely important?

That’s right: the official diagnostic criteria for metabolic syndrome — insulin resistance syndrome — do not include elevated insulin! The underlying factor driving the illness is not even taken into consideration.

Signs & Symptoms of Chronic Hyperinsulinemia

Keep in mind that with regard to metabolic syndrome, it’s not necessary to have all five issues above to be diagnosed. Having three or more, or using medication to control them, is sufficient to prompt the diagnosis. But even if you have just one or two of those, it’s worth exploring whether you have chronically high insulin.

Here are some of the many conditions associated with chronic hyperinsulinemia, even when glucose is normal — and remember, this is only a few of them!

• Hypertension ( 6)
• Obesity ( 7)
• Cardiovascular disease ( 8)
• PCOS ( 9)
• Gout ( 10)
• Erectile dysfunction ( 11)
• Benign prostate hyperplasia (BPH) ( 12)
• Skin tags ( 13)
• Migraines ( 14)
• Vertigo, tinnitus, Ménière’s disease ( 15)
• Alzheimer’s disease ( 16)

Do Only Obese People Suffer from Insulin Resistance?

Something else to keep in mind is that while insulin resistance is often associated with overweight or obesity, millions of people at a “normal” body weight or with a healthy body mass index (BMI) may have chronically high insulin and be at risk for serious health problems.

Researchers even have a name for this, when there are clear signs and symptoms of metabolic dysregulation in people at a normal body weight: normal weight obesity ( 17). So while a slim and trim physique looks nice on the outside, it’s no guarantee of health on the inside. (You might even have heard this called “TOFI” – thin outside, fat inside.

These people have a buildup of fat in and around their abdominal organs, especially the liver and pancreas. This is called visceral fat, and while fat stored on our hips, thighs and arms might be aesthetically unpleasing to some, evidence indicates visceral fat is much more harmful for metabolic health. In fact, the accumulation of fat in the liver may be a primary driver of type 2 diabetes.) After all, not everyone with cardiovascular disease, gout, or hypertension is obese. What they do likely have, however, is chronically high insulin.

How to Measure Insulin: Fasting Insulin and HOMA-IR

Unfortunately, unlike for blood glucose and ketones, there’s no hand-held meter for you to test your own insulin levels at home. The biochemical assay required to measure insulin is more complex than those for glucose and ketones, and at this time the technology isn’t available to fit it into a small, portable device. No doubt enterprising engineers are working on it, though, because they know it’s a zillion-dollar idea! For now, you’ll need to work with your doctor to order the relevant tests. (If you’re in the US, you might be able to order to your own lab tests.)

The easiest way to assess your insulin status is with a fasting insulin test. Reference ranges vary among different laboratories. According to the Mayo Clinic, the reference value for fasting insulin is 2.6-24.9 µIU/mL (18). However, most physicians who use low-carb and ketogenic diets in their practices prefer to see fasting insulin below 10 µIU/mL, and some would say that below 5 µIU/mL is even better.

Bottom line: if your fasting insulin is in the double digits, it’s too high.

Another helpful measurement regarding insulin sensitivity is HOMA-IR. HOMA-IR is short for homeostatic model assessment of insulin resistance. This is a great tool because it takes into account both glucose and insulin. It tells you how much insulin your body has to produce to keep your glucose at a certain level: that is, how hard your pancreas has to work to maintain homeostasis — a glucose level that’s neither too high nor too low. So it’s a much more useful indicator than fasting glucose alone.

Here’s how HOMA-IR is calculated:

Glucose in mass units (mg/dL)
HOMA-IR = (Glucose × Insulin) / 405

Glucose in molar units (mmol/L)
HOMA-IR = (Glucose × Insulin) / 22.5

Just like with fasting insulin, reference ranges and opinions on what’s optimal vary. According to Ted Naiman, MD, a low-carb and keto-oriented physician, here’s how to use HOMA-IR to gauge your insulin sensitivity:

• Excellent insulin sensitivity: ≤ 1
• Average insulin sensitivity: 1.75
• Insulin resistant: ≥ 2.75

HOMA-IR is useful because it gives you a clearer picture than fasting glucose alone. There are many reasons fasting glucose can be slightly higher than expected in people on ketogenic diets, so it’s helpful to have something that gives you a bit more information than glucose in isolation. Here’s an example of HOMA-IR in action:

Patient A’s fasting glucose is higher than Patient B’s, but Patient A’s insulin is much lower. By taking both glucose and insulin into account, the HOMA-IR scores shows that even with a lower fasting glucose, Patient B is at greater risk for metabolic complications down the road. Their body has to work harder and they require much more insulin in order to maintain a healthy glucose level.

The Kraft Test: Beyond Fasting Insulin

If your fasting insulin is in the double digits, it’s a sure sign something is awry. But if your fasting insulin is normal, it doesn’t automatically mean that all is well. Just like with blood glucose, in some people, the fasting insulin level is normal, but it rises very high after meals, and takes a long time to come back down to the baseline level. In some people, it might not even come down fully before the next meal. So it’s possible to have a fasting insulin level in the optimal range but have high insulin throughout most of the rest of the day.

In most people living with signs and symptoms of hyperinsulinemia, the fasting insulin will be elevated. But if your fasting insulin level is normal, yet your body is giving you clear signs that you have high insulin, consider the Kraft test.

How Does the Kraft Test Work?

Named for Dr. Joseph Kraft, the physician mentioned earlier, who pioneered the research identifying the harms of chronic hyperinsulinemia in people with normal glucose, the Kraft test is a variation on the oral glucose tolerance test.

The OGTT measures your body’s glucose levels in response to 75 grams of liquid glucose. (Some labs use 100 grams.) It’s performed in a lab or a doctor’s office, and it starts off with a baseline or fasting glucose measurement. After that sample is taken, you drink the glucose solution, and your blood glucose is measured one and two hours later.

Where the Kraft test shines is that instead of measuring only glucose, insulin is also measured, and instead of it being a 2-hour test, it’s extended to 5 hours. With these two small changes, the Kraft test provides a staggering amount of information you won’t get from a standard OGTT. It was through performing tens of thousands of these modified OGTTs that Dr. Kraft uncovered the staggering scope of diabetes in-situ — the people with normal glucose as a result of dangerously high insulin.

Is the Kraft Test Suitable for Those Following a Low-Carb Diet?

The Kraft test is not generally recommended if you’re following a low-carb or keto diet. The truth is, if you’re keeping carbs low, staying physically active, managing your stress levels, and getting enough sleep, the test simply isn’t necessary. If you’re happy with the results you’re getting from your diet and lifestyle, why would you want to drink 75 grams of liquid glucose?

On the other hand, if you feel like you’re doing everything right, yet you’re still dealing with signs and symptoms of a condition known to be driven primarily by high insulin, it might be worth it to see your glucose and insulin in action together, especially if your fasting levels for both are normal. (Meridian Valley Labs has a nice overview of the Kraft insulin and glucose patterns if you’d like to see more. And if you’d like to learn more about Dr. Kraft’s important work, and why anyone with cardiovascular disease not associated with type 2 diabetes is simply undiagnosed, his book, Diabetes Epidemic & You is a good read.)

…And a Word of Caution

If you’ve been ketogenic or low-carb for a while and you’d like to do a Kraft test just out of curiosity, you will need to “carb up” for a few days beforehand. Just as your body took a few days to transition from running primarily on carbs to running primarily on fat, you’ll have to get your body re-accustomed to using a large amount of glucose before doing a Kraft test.

Without this re-acclimation period, you might get a false result: you’ll look like you have out-of-control diabetes when you’re actually perfectly healthy. This makes sense: your body simply isn’t used to dealing with a big wallop of glucose like that all at once anymore.

If you’re a long-time low-carber or keto dieter and you’re interested in the Kraft test, keto-savvy physicians recommend consuming 100-150 grams of carbohydrate per day for seven days before doing the test. (The same holds true for a standard OGTT as well.) But remember, for most keto dieters, this test isn’t necessary.