insulin

In the last article we discussed the complex relationship between body weight and type 2 diabetes (T2DM). We learned that although obesity is strongly associated with T2DM, a subset of “metabolically healthy obese” (MHO) people have normal blood sugar and insulin sensitivity and don’t ever develop diabetes.

In this article we’re going to talk about the mirror reflection of the MHO: the “metabolically unhealthy nonobese” (MUN). These are lean people with either full-fledged type 2 diabetes or some metabolic dysfunction, such as insulin resistance.

You might even be surprised to learn that skinny people can and do get T2DM. They are rarely mentioned in the media, and there isn’t much written about them in the scientific literature. Perhaps these folks have been overlooked because type 2 diabetes has been historically viewed as a disease of gluttony and sloth, a self-inflicted outcome of eating too much and not and not exercising enough. But the very existence of the MUN phenotype proves that there’s more to T2DM than overeating and a sedentary lifestyle.

Remember that one in three type 2 diabetics are undiagnosed. It’s possible that a significant number of these people that are lean. They don’t suspect they might have T2DM because they’re under the impression that it’s not a condition that affects thin people. This is one of the biggest dangers of the myth that “only fat people get diabetes”.

It’s well-known that high blood sugar can precede the development of T2DM for as long as ten years. It is during this time that many of the complications associated with diabetes – nerve damage, retinal changes, and early signs of kidney deterioration – begin to develop. This is why it’s just as important for lean people to maintain healthy blood sugar as it is for the overweight and obese.

It’s also important to understand that diabetes is not a disease. It’s a symptom. Every single person with T2DM, whether they are rail thin or morbidly obese, shares a single symptom: high blood sugar. Therefore, anything that interferes with the body’s regulation of blood sugar levels will cause type 2 diabetes.

What causes high blood sugar and T2DM in lean people?

Not surprisingly, the causes of T2DM in lean people are similar to the causes of T2DM in the obese. They can be loosely grouped into the following categories:

1. Genetics
2. Fatty liver
3. Inflammation
4. Autoimmunity
5. Stress

Let’s discuss each of them in turn.

Genetics

Studies of the lean, otherwise healthy offspring of type 2 diabetics has revealed that they are much more likely to be insulin resistant than the lean offspring of non-diabetics. One explanation for this is an inherited defect that causes mitochondrial dysfunction. People with this defect are not able to burn glucose or fatty acids efficiently, which causes lipotoxicity and an accumulation of fat inside of muscle cells.

I will discuss the contribution of genetics in more detail in the next article. What I want you to understand here is that the genetic mechanisms I described above are capable of causing insulin resistance and high blood sugar independently of overweight or obesity.

Fatty liver

Studies of lean, Asian Indian men have found that they have a 3- to 4-fold higher incidence of insulin resistance than their caucasian counterparts. They also have a much higher prevalence of non-alcoholic fatty liver disease (NAFLD) and hepatic (liver) insulin resistance.

NAFLD is an independent predictor of type 2 diabetes. Cross-sectional studies have shown that fatty liver and metabolic abnormalities occur together. It has also been proposed that fatty liver is not just a result, but also a cause of insulin resistance and type 2 diabetes.

Now, keep in mind that these Asian Indian men with NAFLD were not overweight. They were lean, and in some cases, even underweight. This proves that NAFLD occurs in lean people, and together with the evidence above, suggests that NAFLD may be a primary cause of insulin resistance and T2DM in lean people.

If you’re thinking NAFLD might be a rare problem confined to Asian Indian men, you should know that up to 30% (almost 1 in 3) of people in industrialized nations suffer from it. This is a disturbingly high prevalence of a condition that is known to progress to severe liver inflammation and cancer in a small percentage of people – in addition to contributing to T2DM and metabolic syndrome.

While there may be a genetic component that predisposes people to developing NAFLD, we also know that dietary factors play a significant role. Rodent studies have shown that feeding large amounts of sugar and industrial seed oils (like corn, safflower, sunflower, etc.) promote NAFLD, whereas saturated fats such as butter and coconut oil do not. And in human infants, tube-feeding with industrial seed oils causes severe liver damage, whereas the same amount of fat from fish oil does not.

Fructose, especially the high-fructose corn syrup (HFCS) found in sodas, candy and several packaged and refined foods, is perhaps the most significant dietary cause of NAFLD. The liver processes fructose by converting it to fat. The more fructose consumed, the more fatty the liver becomes. Feeding rodents high amounts of fructose promotes NAFLD, and the consumption of soft drinks (by humans) can increase the prevalence of NAFLD independently of metabolic syndrome.

Let me say that again: high fructose intake can cause fatty liver disease independently of overweight, obesity or type 2 diabetes. Do you think that might be a problem in a country where soft drinks account for nearly 10% of total caloric intake?

Since fructose is handled by the liver in the same way the liver handles alcohol, excess fructose produces a similar range of problems as alcohol abuse: hypertension, high triglycerides and low HDL, obesity, cirrhosis and insulin resistance.

Inflammation

In the study of lean Asian Indian men above with T2DM, it was found that they had a 2-fold increase in plasma levels of the inflammatory protein IL-6 when compared to lean subjects without T2DM. In a previous article I showed that chronic, low-grade inflammation associated is an important mechanism in decreasing insulin signaling and causing insulin resistance in muscle, liver and fat cells.

Also, inflammation has been shown to precede the development of diabetes. Infusion of inflammatory cytokines into healthy, normal weight mice causes insulin resistance, and people with other chronic inflammatory conditions are at higher risk of developing T2DM. For example, about one-third of chronic Hepatitis C patients develop T2DM, and those with rheumatoid arthritis are also at higher risk.

Autoimmunity

Up until recently, type 1 and type 2 diabetes were seen as distinct entities. It was understood that type 1 diabetes (or insulin-dependent diabetes) was caused by autoimmune destruction of the beta cells of the pancreas, leading to decreased insulin production, whereas type 2 diabetes was caused by insulin resistance of the liver, muscle and fat cells.

However, recent research has demonstrated that the line separating these two conditions may be much blurrier than previously thought. It is now known that type 1 diabetes, which normally begins in childhood, may slowly develop later in life. This form is referred to as latent autoimmune diabetes (LADA) or more informally as type 1.5 diabetes.

Studies suggest that type 1 diabetes in adults is frequently misdiagnosed as T2DM, and up to 10% of adults with T2DM may actually have the autoimmune form.

Even more relevant to this article is the finding that fully 1 in 4 lean people with T2DM produce antibodies to GAD, the same enzyme in the pancreas that is attacked in type 1 autoimmune diabetes.

These findings suggest that a significant number of lean people with T2DM may be suffering from autoimmune diabetes. This will obviously require a different treatment strategy than those who have the non-autoimmune form. (The way to find out whether you’re in this group is to have your GAD antibodies tested. It’s a fairly standard blood test and is available through Labcorp and Quest.)

(Interestingly enough, approximately 5% of patients with autoimmune thyroid conditions also produce antibodies to GAD. So if you have Hashimoto’s or Graves’ disease along with blood sugar symptoms that don’t respond to dietary changes, you should have your GAD antibodies checked.)

Stress

Under conditions of stress, the body produces higher levels of the hormone cortisol. Cortisol plays a number of important roles, but one of it’s primary functions is to raise blood sugar. This is an incredibly helpful evolutionary mechanism that is part of the “fight or flight” response that prepares us to deal with a challenge or threat.

However, that mechanism was only designed for short bursts of stress. Chronic stress as we experience it today – like worrying about getting audited by the IRS, driving in traffic, and suffering from degenerative disease – wasn’t part of our early ancestors’ lives. This means that our bodies aren’t prepared to deal with the effects of chronic stress, which include chronically elevated levels of cortisol.

Why? Because cortisol is capable of raising blood sugar to unhealthy levels even when a person is fasting. What that also means is that you can be lean, eat a perfect diet, and still have high blood sugar (and thus T2DM) if you suffer from chronic stress. I’ll be writing more about the connection between stress and diabetes in a future article.