How Insulin Resistance Leads to Type 2 Diabetes

Now let’s discuss the relationship between type 2 diabetes and insulin sensitivity. We will also discuss medication adjustment for type 2 diabetes and hypertension while beginning a low-carbohydrate diet.

Insulin Sensitivity

Type 2 diabetes is caused by low insulin sensitivity rather than high blood glucose levels. When the body’s cells do not respond sufficiently to insulin signaling, glucose levels rise in the bloodstream.

A person who is insulin resistant is also carbohydrate intolerant. Some people tolerate carbs better than others, although there is not a clear consensus on why this is; physical activity level, genetics, and diet likely play a role.

Blood glucose levels over 126 mg/dL, or an A1c value over 6.5%, are often how type 2 diabetes is diagnosed. Hemoglobin A1c is a criterion because when blood glucose levels are elevated, sugar molecules will adhere to red blood cells in a process known as glycation. This marker indicates how often and how high blood glucose is elevated.

We normally expect that hemoglobin A1c levels will come down to normal levels after blood glucose control is achieved through the restoration of insulin sensitivity. But how quickly should that happen?

A1c is normally thought to represent the previous 90 days of glucose control because the average lifespan of red blood cells is 100-120 days. This means that it could take at least 1-3 months of intervention to see A1c levels come down toward normal ranges.

Fasting blood glucose levels of 100–125 mg/dL are considered diagnostic of “prediabetes.” When that level is found above 126 mg/dL, it is considered diagnostic of type 2 diabetes. Similarly, an A1c of 5.7–6.4% is prediabetic, and 6.5% or higher is diagnostic of type 2 diabetes.

Fasting insulin levels alone have a sensitivity of about 10% for detection of high insulin levels. What’s important is the insulin response after eating, because insulin levels eventually lower again, typically when fasting. If fasting insulin is elevated, it’s a definite sign of insulin resistance and is predictive of developing metabolic disease.

Insulin resistance occurs not only in the fat or muscle cells but also in almost all other systems because they almost all need fuel for function. Insulin is how that fuel gets into the cells.

Adipose Tissue and Insulin Resistance

It is important to note that while obesity is strongly associated with type 2 diabetes, it is not a requirement to develop the disease. Obesity is more the result of the condition than a cause of it. Insulin resistance can occur in someone with a normal BMI, as not all fat is equal.

Ectopic fat, which often accumulates around organs and is known as visceral fat in that case, has a far greater effect on promoting insulin resistance than subcutaneous fat. The “thin outside, fat inside TOFI" phenotype is an example of this, as is the person with an enlarged abdomen but normal proportions for the rest of their body.

Fat cells can increase in size and store more fat if insulin levels are high enough. Some people’s fat cells can also undergo fat hyperplasia, meaning that they can grow new fat cells. These people are thought to make up about 10% of obese people and can become quite obese without developing insulin resistance.

Some people will develop insulin resistance with very low subcutaneous fat, only depositing fat in the form of visceral fat. This can create a phenotype with good muscle definition but a somewhat enlarged abdomen, causing insulin resistance in someone who appears to be otherwise quite athletic.

As insulin resistance is a dysfunction of the insulin receptors at the cell level, it’s significant to note that it can occur in any tissue that responds to insulin—and that’s most tissues. It is possible to develop insulin resistance in muscle simply by not exercising, and it is possible to see the effects of insulin resistance on some cells or tissues before others.

Many health issues for which a cause is unknown may be triggered by localized insulin resistance, even in people who have not developed type 2 diabetes yet. This can include erectile dysfunction (ED), polycystic ovarian syndrome (PCOS), or other conditions.

Consuming a high-carbohydrate diet results in fat accumulation and insulin resistance. As fat cells reach their limit of lipid storage, additional triglycerides accumulate in the blood since they can no longer deposit their fat into fat cells.

Testing Ketones to Assess Fat and Glucose Metabolism

Revero provides urine test strips for daily testing of ketone levels. This is important because if ketones are elevated to a level that indicates a state of ketosis, insulin and glucose levels will also be better controlled. Respiratory quotients will be lower since ketosis means the body burns fat for fuel more than carbohydrates.

Note that if you have been low carb before, you may not show urine ketones anymore since your body is already good at utilizing the ketones for energy. It just doesn’t waste ketones in the urine.

Treating the Labs: High Blood Glucose

Today, type 2 diabetes is most often diagnosed with elevated blood glucose, even though we know that blood glucose only becomes elevated after a long period, perhaps years, of elevated insulin. People are treated for this diagnosis based on blood glucose levels, not insulin sensitivity, which is the true cause.

This is the single major reason why mainstream interventions for type 2 diabetes do not result in remission; they are only focusing on the effect or symptom, not the cause of the disease. Some medications such as sulfonylureas which increase insulin release may worsen insulin resistance. That’s because the drugs raise insulin concentrations, and elevated insulin levels are a cause of insulin resistance.

A similar situation exists when type 2 diabetics are given insulin injections. Adding more insulin when levels are already very high can worsen the outcome over time.

The consumption of a high-carbohydrate diet is the single factor that promotes elevated insulin levels, insulin resistance, and type 2 diabetes. Many factors influence how quickly this happens, including genetics, inflammation, and level of physical activity. Addressing the issue with a low-carbohydrate or ketogenic diet is the most logical way to treat the root cause, which is insulin resistance.

Research has revealed that type 2 diabetics have better weight loss, cholesterol, and control of blood pressure on low-carbohydrate diets. It has even been shown that the total calorie count of the diet doesn’t matter as long as the carbohydrates are below an individual’s threshold.

Of note, improvements in blood sugar, A1c, and insulin sensitivity occur before any meaningful weight loss. A 2019 paper published in the International Journal of Environmental Research and Public Health showed conclusively that low-carbohydrate diets could even help patients improve their glycemic control to the point that medication was sometimes no longer necessary.

Changes in Blood Sugar and Blood Pressure on the Ketogenic Diet

Because a low-carbohydrate diet addresses the underlying causes of insulin resistance and type 2 diabetes, medications may need to be adjusted. Recognizing the symptoms of low blood glucose is critical. When still taking diabetic medication, blood sugar will gradually decrease on a low-carbohydrate diet. These changes can happen in the span of a few days, so it is important to be on the lookout for them.

Symptoms of low blood glucose may include feeling shaky, irritable, nauseous, light-headed, or perspiring uncontrollably. However, in a state of ketosis, these symptoms may not occur as the brain can use ketones in place of glucose. In this case, regular blood glucose testing would be the first thing to reveal low glucose levels.

A similar situation exists with blood pressure medications. When consuming a high-carbohydrate diet, the body retains sodium and water. This combination boosts blood pressure due to volumetric increases.

When starting a low-carbohydrate diet, there is often a rapid weight loss caused by the body releasing this sodium and water accumulation. If taking blood pressure medication, the blood pressure may drop below safe levels.

Symptoms of low blood pressure can include dizziness, often on rising from a sitting or squatting position, fatigue, or fainting.

If taking blood pressure medications or blood sugar medications during the Revero program, dosages will need to be adjusted by the Revero provider as the treatment progresses and insulin sensitivity improves.

During nutritional ketosis, fasting blood glucose may be slightly elevated early in the morning due to the “dawn phenomenon,” which happens when the body produces cortisol to awaken us. This slight boost of catecholamines will also raise blood glucose levels somewhat, which is normal.

Slightly elevated glucose at other times is normal on a ketogenic diet due to “adaptive glucose sparing.” It’s because the muscles and much of the body are using fats for fuel, so glucose levels can remain slightly elevated, perhaps just over 100, because the glucose isn’t being used for much. In the presence of low levels of insulin, this is not an issue. The problems caused by metabolic disease are a result of high insulin, not slightly elevated glucose.

Revero providers may also elect to adjust glucose medications such that blood glucose levels remain slightly elevated, as this is far safer in the short term than being at risk for hypoglycemic events.