What Causes Type 2 Diabetes, and How Can it be Prevented?

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In the comments of the last post, we've been discussing the relationship between body fatness and diabetes risk.  I think this is really worth understanding, because type 2 diabetes is one of the few lifestyle disorders where 1) the basic causes are fairly well understood, and 2) we have effective diet/lifestyle prevention strategies that have been clearly supported by multiple controlled trials.

Insulin resistance is an inability of tissues to "hear" the insulin signal properly, leading to poor blood glucose handling and other metabolic problems in processes that depend on insulin.  In my interview with Aitor Calero, I made the statement that the main cause of insulin resistance is excess body fat.  To be more precise, body fatness is the main modifiable cause*-- genetic makeup is another major factor that you're stuck with regardless of lifestyle.  Diabetes is caused by insulin resistance plus the eventual failure of the insulin-secreting pancreatic beta cells.  Some people become obese and insulin resistant, but their beta cells never fail, and therefore they do not become diabetic.  This has a strong genetic component, as Gretchen mentioned in the comments.  If you look at genetic loci associated with type 2 diabetes risk, most of them are in genes that regulate the pancreas, although the strongest obesity locus FTO is also a diabetes risk factor (0).

Regardless, there can be no question that body fatness is tightly associated with diabetes risk.  For example, in the Health Professionals Follow-up study, among 52,000 men, body mass index (a rough estimate of fatness) predicted the risk of developing diabetes over five years (1).  A BMI of 25 or more suggests overweight, and a BMI of 30 or more suggests obesity.  The data are striking:

A person with a BMI over 35 in this study (solidly obese) had a 42 times higher risk of developing diabetes than someone with a BMI of less than 23 (lean but not skinny).  People who straddled the line of obesity had a 6.7 times higher risk.  Furthermore, this relationship was not restricted to the obese.  Let's blow up the first four points and take a closer look:

Having a BMI of 24-24.9, which isn't even considered overweight, was associated with a 50 percent higher risk of diabetes, and going just over the cusp of overweight yielded a 120 percent increase in risk.  Therefore at nearly all levels of BMI, higher BMI strongly predicted the risk of developing diabetes.  This has been repeatedly confirmed. 

As I've explained in the past, multiple lines of evidence suggest that this is because excess body fat causes insulin resistance, which in turn increases the risk of developing diabetes* (1A, 1B). 

I understand that this is frustrating to people who carry excess fat and have a hard time losing it.  For many people, fat loss is a real challenge, and achieving true leanness is unlikely.  If that's you, I have some good news.  First of all, you can reduce your diabetes risk without losing a pound, by exercising regularly, eating a whole food diet, and managing sleep and stress effectively.  Second, you can greatly reduce your diabetes risk by losing as little as 11 pounds (5 kg).

This was demonstrated by the striking results of the Diabetes Prevention Program study, involving 3,234 pre-diabetic volunteers (2).  In this study, a combination of weight loss (via calorie-restricted low-fat diet) and exercise reduced the risk of developing diabetes by a full 58 percent over 2.8 years.  A similar trial in Finland a year earlier produced a virtually identical result (3), and similar results have come from trials in India, Japan, and China (4, 5, 6).  This kind of risk reduction is virtually unheard of in lifestyle modification trials, particularly considering the typical half-hearted adherence-- this shows that the intervention was striking directly at the heart of the problem.  It's possible that weight loss via a different diet (e.g. Paleo) would have been even more effective, but we won't know for sure until it's tested.

A follow-up study tried to determine which aspect of the DPP intervention was most important for diabetes risk reduction (7).  Here's what they found:

Weight loss was the dominant predictor of reduced diabetes incidence (hazard ratio per 5-kg weight loss 0.42 [95% CI 0.35-0.51]; P less than 0.0001). For every kilogram of weight loss, there was a 16% reduction in risk, adjusted for changes in diet and activity. Lower percent of calories from fat and increased physical activity predicted weight loss. Increased physical activity was important to help sustain weight loss. Among 495 participants not meeting the weight loss goal at year 1, those who achieved the physical activity goal had 44% lower diabetes incidence.

There you have it, folks.  We know how to prevent type 2 diabetes, and it's not magic.  These simple steps will reduce your risk:

1. If you're overweight, lose fat if you can, even as little as a few pounds
2. Exercise regularly
3. Eat a healthy diet

* I simplify for a general audience, but it's probably more complicated than this.  Cellular energy overload causes insulin resistance, and this occurs when fat tissue expands to the point where it no longer efficiently traps fatty acids, exposing tissues throughout the body to excess energy.  In addition, enlarged fat depots tend to become inflamed, and inflammation contributes to insulin resistance.  So the causality is probably something like this: excess energy intake leads to excess fat mass, which leads to poor fatty acid trapping and inflammation in fat cells, which leads to cellular energy excess and inflammation in lean tissues, which leads to insulin resistance.  Although the full story is more nuanced, it is nevertheless fair and accurate to distill this down to the statement that excess body fat causes insulin resistance and diabetes.  This is true even though there is not a 1:1 correspondence between obesity and insulin resistance.