What is the cause of Type 2 diabetes?

Many people associate Type 2 diabetes with blood sugar problems. This is largely due to something most people would be happy to never hear.

Essentially, physicians back in the day observed that the urine of people with diabetes mellitus tasted sweet. Patients dumped glucose into their urine because there was too much in their blood.

While it’s clear that elevated blood glucose is a primary concern of physicians treating Type 2 diabetes, focusing solely on glucose ignores other problems. There is also an elevation in triglycerides.

You can read about the drawbacks of focusing on glucose in a wonderful article written nearly 30 years ago. What if Minkowski had been ageusic? An alternative angle on diabetes. It ponders how much further along we’d be had we focused on all metabolic aspects of diabetes and not just sugar.

Unfortunately, this part of the discussion goes missing and goads people into believing that low carbohydrate diets cure Type 2 diabetes. They are certainly great at lowering the glycemic response to meals, but they don’t cure Type 2 diabetes.

If you follow the internet and authors of popular low carbohydrate diet books, chronically elevated blood glucose levels due to a high carbohydrate diet lead to high insulin levels(Hyperinsulinemia). Over time, hyperinsulinemia drives insulin resistance, which causes ever-increasing blood glucose levels and greater body fat.

While certainly an interesting hypothesis, it’s not the actual sequence of events nor supported by the literature. A new paper shines a light on what’s driving insulin resistance, and it’s not a high carbohydrate diet.

In fact, the cause of Type 2 diabetes appears to have more to do with something independent of blood sugar. And this paper far better explains the rest of the data than a high carbohydrate diet.

The cause of Type 2 diabetes: What causes hyperinsulinemia

It’s important to begin this discussion with the idea that insulin does many things other than lower blood glucose by driving it into cells. It also suppresses glucose output by the liver and suppresses the release of free fatty acids by fat tissue.

Therefore, hyperinsulinemia may be driven by these factors just as much as high glucose. Consequently, insulin resistance causes dysregulation in these processes as well. With this in mind, we can take a dive into this paper.

One common thread in the Type 2 diabetes literature is that losing weight corrects Type 2 diabetes. It doesn’t matter how you achieve this, it can be a low carbohydrate diet or a low fat diet. Losing just 10% of your weight can put your Type 2 diabetes in remission.

But if high carbohydrate diets are driving Type 2 diabetes by driving hyperinsulinemia which drives insulin resistance, why does weight loss in general cause remission. Furthermore, why do some obese people have high insulin but normal glucose levels?

This paper eloquently describes the sequence of events as well as how weight loss puts Type 2 diabetes into remission.

They looked at a few groups of people in this paper:

• Lean people with normal insulin and glucose
• Obese people with high insulin but normal glucose
• Obese people with high insulin and high glucose

A second part of the study looked at:

• Lean people with normal insulin and glucose
• Obese people with normal insulin and glucose
• Obese people with high insulin and glucose

With this in mind, they found that one factor consistently predicted insulin sensitivity, and it wasn’t glucose. It was free fatty acids.

The cause of Type 2 diabetes: Sequence of events

This paper found some really interesting things that many have theorized based on the literature. Overeating causes expansion of fat cells and increased release of free fatty acids due to fat cell lipolysis.

As a consequence, elevated free fatty acids in the blood cause a greater release of insulin from the pancreas. This suppresses lipolysis in fat cells to help decrease free fatty acids in the blood.

They found a progressive increase in free fatty acids in the blood that predicted insulin levels. In the first part of the study, they found FFAs to be progressively elevated as follows:

Lean subjects–>Obese high insulin/normal glucose–>Obese high insulin/high glucose

Furthermore, in the second part of the study, in which all participants had normal glucose levels:

Lean subjects & Obese subjects with normal insulin–>Obese subjects with high insulin

The paradigm this presents is that creating a positive energy balance leads to increased accumulation of fat. At some inflection point, excess fat mass causes the release of free fatty acids due to lipolysis in fat cells. In response, the pancreas secretes insulin to inhibit lipolysis in fat cells.

This response helps keep fatty acids in the blood in check. However, this elevates insulin levels which leads to insulin resistance. As a consequence, other important actions of insulin, such as glucose output by the liver and blood glucose levels, become dysregulated.

This explains why fat loss in general puts type 2 diabetes in remission. Reducing fat mass decreases the release of free fatty acids in the blood, which decreases insulin production. It doesn’t matter how you lose weight, losing fat frees up space.

While low carbohydrate diets may improve blood glucose levels, the true goal should be to reduce fasting insulin. To do this, weight loss is the key, not carbohydrate restriction.

Conclusion

Type 2 diabetes is often assumed to be simply a disorder of blood glucose regulation by most individuals, and therefore, chronic carb overcounsumption is the cause of Type 2 diabetes. However, this is not at all supported by the data.

The consensus in the science is that it is a consequence of a chronic, unremitting calorie surplus. This paper supports this notion that it’s the energy surplus leading to excess fat accumulation that drives Type 2 diabetes.

This data indicates that the sequence of events leading to Type 2 diabetes begins by the release of free fatty acids into the blood, and not chronic carbohydrate overconsumption. In response to high plasma free fatty acids, the pancreas secretes insulin to inhibit lipolysis in fat cells.

This leads to chronic hyperinsulinemia which induces insulin resistance. As a result, insulin sensitive tissues such as muscle and fat tissue do not respond to insulin, and fail to pull glucose from the blood. In addition, the insulin resistant liver produces too much glucose and releases it into the bloodstream.

However, it’s important to interpret these results with caution as there are a couple of caveats.

First, this model describes the cause of Type 2 diabetes when driven by obesity. It does not preclude that there could be other causes of Type 2 diabetes.

Secondly, one can induce an acute form of insulin resistance by overconsuming calories or being sedentary. In this setting, free fatty acids do not predict insulin level.

In conclusion, the cause of Type 2 diabetes in obese people is an energy excess that causes the spillover of fatty acids into the blood, causing hyperinsulinemia, and eventual insulin resistance.

But is there are cheat code foe this? Is there are “hack” we can use to fix this problem sooner rather than later? Next week we’ll discuss a study implying that this may be the case.

Note: This blog has been published and can be found here.