The Diabetes Epidemic

The CDC just released its latest estimate of diabetes prevalence in the US (1):

Diabetes affects 8.3 percent of Americans of all ages, and 11.3 percent of adults aged 20 and older, according to the National Diabetes Fact Sheet for 2011. About 27 percent of those with diabetes—7 million Americans—do not know they have the disease. Prediabetes affects 35 percent of adults aged 20 and older.

Wow-- this is a massive problem. The prevalence of diabetes has been increasing over time, due to more people developing the disorder, improvements in diabetes care leading to longer survival time, and changes in the way diabetes is diagnosed. Here's a graph I put together based on CDC data, showing the trend of diabetes prevalence (percent) from 1980 to 2008 in different age categories (2):

These data are self-reported, and do not correct for differences in diagnosis methods, so they should be viewed with caution-- but they still serve to illustrate the trend. There was an increase in diabetes incidence that began in the early 1990s. More than 90 percent of cases are type 2 diabetics. Disturbingly, the trend does not show any signs of slowing.

The diabetes epidemic has followed on the heels of the obesity epidemic with 10-20 years of lag time. Excess body fat is the number one risk factor for diabetes*. As far as I can tell, type 2 diabetes is caused by insulin resistance, which is probably due to energy intake exceeding energy needs (overnutrition), causing a state of cellular insulin resistance as a defense mechanism to protect against the damaging effects of too much glucose and fatty acids (3). In addition, type 2 diabetes requires a predisposition that prevents the pancreatic beta cells from keeping up with the greatly increased insulin needs of an insulin resistant person**. Both factors are required, and not all insulin resistant people will develop diabetes as some people's beta cells are able to compensate by hypersecreting insulin.

Why does energy intake exceed energy needs in modern America and in most affluent countries? Why has the typical person's calorie intake increased by 250 calories per day since 1970 (4)? I believe it's because the fat mass "setpoint" has been increased, typically but not always by industrial food. I've been developing some new thoughts on this lately, and potentially new solutions, which I'll reveal when they're ready.


* In other words, it's the best predictor of future diabetes risk.

** Most of the common gene variants (of known function) linked with type 2 diabetes are thought to impact beta cell function (5).

Eating Wheat Gluten Causes Symptoms in Some People Who Don't Have Celiac Disease

Irritable bowel syndrome (IBS) is a condition characterized by the frequent occurrence of abdominal pain, diarrhea, constipation, bloating and/or gas. If that sounds like an extremely broad description, that's because it is. The word "syndrome" is medicalese for "we don't know what causes it." IBS seems to be a catch-all for various persistent digestive problems that aren't defined as separate disorders, and it has a very high prevalence: as high as 14 percent of people in the US, although the estimates depend on what diagnostic criteria are used (1). It can be brought on or exacerbated by several different types of stressors, including emotional stress and infection.

Maelán Fontes Villalba at Lund University recently forwarded me an interesting new paper in the American Journal of Gastroenterology (2). Dr. Jessica R. Biesiekierski and colleagues recruited 34 IBS patients who did not have celiac disease, but who felt they had benefited from going gluten-free in their daily lives*. All patients continued on their pre-study gluten-free diet, however, all participants were provided with two slices of gluten-free bread and one gluten-free muffin per day. The investigators added isolated wheat gluten to the bread and muffins of half the study group.

During the six weeks of the intervention, patients receiving the gluten-free food fared considerably better on nearly every symptom of IBS measured. The most striking difference was in tiredness-- the gluten-free group was much less tired on average than the gluten group. Interestingly, they found that a negative reaction to gluten was not necessarily accompanied by the presence of anti-gluten antibodies in the blood, which is a test often used to diagnose gluten sensitivity.

Here's what I take away from this study:

1. Wheat gluten can cause symptoms in susceptible people who do not have celiac disease.
2. A lack of circulating antibodies against gluten does not necessarily indicate a lack of gluten sensitivity.
   
3. People with mysterious digestive problems may want to try avoiding gluten for a while to see if it improves their symptoms**.
4. People with mysterious fatigue may want to try avoiding gluten.
   

A previous study in 1981 showed that feeding volunteers a large dose of gluten every day for 6 weeks caused adverse gastrointestinal effects, including inflammatory changes, in relatives of people with celiac disease, who did not themselves have celiac (3). Together, these two studies are the most solid evidence that gluten can be damaging in people without celiac disease, a topic that has not received much interest in the biomedical research community.

I don't expect everyone to benefit from avoiding gluten. But for those who are really sensitive, it can make a huge difference. Digestive, autoimmune and neurological disorders associate most strongly with gluten sensitivity. Avoiding gluten can be a fruitful thing to try in cases of mysterious chronic illness. We're two-thirds of the way through Gluten-Free January. I've been fastidiously avoiding gluten, as annoying as it's been at times***. Has anyone noticed a change in their health?


* 56% of volunteers carried HLA-DQ2 or DQ8 alleles, which is slightly higher than the general population. Nearly all people with celiac disease carry one of these two alleles. 28% of volunteers were positive for anti-gliadin IgA, which is higher than the general population.

** Some people feel they are reacting to the fructans in wheat, rather than the gluten. If a modest amount of onion causes the same symptoms as eating wheat, then that may be true. If not, then it's probably the gluten.

*** I'm usually about 95% gluten-free anyway. But when I want a real beer, I want one brewed with barley. And when I want Thai food or sushi, I don't worry about a little bit of wheat in the soy sauce. If a friend makes me food with gluten in it, I'll eat it and enjoy it. This month I'm 100% gluten-free though, because I can't in good conscience encourage my blog readership to try it if I'm not doing it myself. At the end of the month, I'm going to do a blinded gluten challenge (with a gluten-free control challenge) to see once and for all if I react to it. Stay tuned for more on that.

Dairy Fat and Diabetes

Introduction

Having access to embargoed news from the Annals of Internal Medicine is really fun. I get to report on important studies at the same time as the news media. But this week, I got my hands on a study that I'm not sure will be widely reported (Mozaffarian et al. Trans-palmitoleic Acid, Metabolic Risk Factors, and New-Onset Diabetes in US Adults. Ann Internal Med. 2010). Why? Because it suggests that dairy fat may protect against diabetes.

The lead author is Dr. Dariush Mozaffarian, whose meta-analysis of diet-heart controlled trials I recently criticized (1). I think this is a good opportunity for me to acknowledge that Dr. Mozaffarian and his colleagues have published some brave papers in the past that challenged conventional wisdom. For example, in a 2005 study, they found that postmenopausal women who ate the most saturated fat had the slowest rate of narrowing of their coronary arteries over time (2). It wasn't a popular finding but he has defended it. His colleague Dr. Walter Willett thinks dietary fat is fine (although he favors corn oil), whole eggs can be part of a healthy diet, and there are worse things than eating coconut from time to time. Dr. Willett is also a strong advocate of unrefined foods and home cooking, which I believe are two of the main pillars of healthy eating.

Let's hit the data

Investigators collected two measures of dairy fat intake in 3,736 Americans:

1. 24 hour dietary recall questionnaires, six times. This records volunteers' food intake at the beginning of the study.
2. Blood (plasma phospholipid) content of trans-palmitoleate. Dairy fat and red meat fat are virtually the only sources of this fatty acid, so it reflects the intake of these foods. Most of the trans-palmitoleate came from dairy in this study, although red meat was also a significant source.

After adjustment for confounding factors, trans-palmitoleate levels were associated with a smaller waist circumference, higher HDL cholesterol, lower serum triglycerides, lower C-reactive protein, lower fasting insulin and lower calculated insulin resistance. Furthermore, people with the highest trans-palmitoleate levels had 1/3 the risk of developing diabetes over the three years volunteers were followed. Keep in mind, however, that this is an observational study and does not prove that dairy fat prevents diabetes.

Even though certain blood fatty acids partially represent food intake, they can also represent metabolic conditions. For example, people on their way to type II diabetes tend to have more saturated blood lipids, independent of diet (3, 4)*. So it's reassuring to see that dietary trans-palmitoleate intake was closely related to the serum level. The investigators also noted that "greater whole-fat dairy consumption was associated with lower risk for diabetes," which increases my confidence that serum trans-palmitoleate is actually measuring dairy fat intake to some degree. However, in the end, I think the striking association they observed was partially due to dairy fat intake, but mostly due to metabolic factors that had nothing to do with dairy fat**.

Here's a nice quote:

Our findings support potential metabolic benefits of dairy consumption and suggest that trans-palmitoleate may mediate these effects***. They also suggest that efforts to promote exclusive consumption of low-fat and nonfat dairy products, which would lower population exposure to trans-palmitoleate, may be premature until the mediators of the health effects of dairy consumption are better established.

Never thought I'd see the day! Not bad, but I can do better:

Our findings support eating as much butter as possible****. Don't waste your money on low-fat cream, either (half-n-half). We're sorry that public health authorities have spent 30 years telling you to eat low-fat dairy when most studies are actually more consistent with the idea that dairy fat reduces the risk obesity and chronic disease.

What are these studies suggesting that dairy fat may be protective, you ask? That will be the topic of another post, my friends.


*Probably due to uncontrolled de novo lipogenesis because of insulin resistance. Many studies find that serum saturated fatty acids are higher in those with metabolic dysfunction, independent of diet. They sometimes interpret that as showing that people are lying about their diet, rather than that serum saturated fatty acids don't reflect diet very well. For example, in one study I cited, investigators found no relationship between dietary saturated fat and diabetes risk, but they did find a relationship between serum saturated fatty acids and diabetes risk (5). They then proceeded to refer to the serum measurements as "objective measurements" that can tease apart "important associations with diabetes incidence that may be missed when assessed by [food questionnaires]." They go on to say that serum fatty acids are "useful as biomarkers for fatty acid intake," which is true for some fatty acids but not remotely for most of the saturated ones, according to their own study. Basically, they try to insinuate that dietary saturated fat is the culprit, and the only reason they couldn't measure that association directly is that people who went on to develop diabetes inaccurately reported their diets! A more likely explanation is that elevated serum saturated fatty acids are simply a marker of insulin resistance (and thus uncontrolled de novo lipogenesis), and had nothing to do with diet.

**Why do I say that? Because mathematically adjusting for dairy and meat fat intake did not substantially weaken the association between phospholipid trans-palmitoleate and reduced diabetes risk (Table 4). In other words, if you believe their math, dairy/meat fat intake only accounted for a small part of the protective association. That implies that healthy people maintain a higher serum phospholipid trans-palmitoleate level than unhealthy people, even if both groups eat the same amount of trans-palmitoleate. If they hadn't mentioned that full-fat dairy fat intake was directly associated with a lower risk of diabetes, I would not find the study very interesting because I'd have my doubts that it was relevant to diet.

***I find it highly doubtful that trans-palmitoleate entirely mediates the positive health outcomes associated with dairy fat intake. I think it's more likely to simply be a marker of milk fat, which contains a number of potentially protective substances such as CLA, vitamin K2, butyric acid, and the natural trans fats including trans-palmitoleate. In addition, dairy fat is low in omega-6 polyunsaturated fat. I find it unlikely that their fancy math was able to tease those factors apart, because those substances all travel together in dairy fat. trans-palmitoleate pills are not going to replace butter.

****That's a joke. I think butter can be part of healthy diet, but that doesn't mean gorging on it is a good idea. This study does not prove that dairy fat prevents diabetes, it simply suggests that it may.

Choline and Fatty Liver

I've been writing about non-alcoholic fatty liver disorder (NAFLD) since the early days of this blog, because it's an alarmingly common disorder (roughly a quarter of Americans affected) that is typically undiagnosed. It often progresses into its more serious cousin non-alcoholic steatohepatitis (NASH), an inflammatory condition that causes liver damage and can progress to cancer. In a number of previous posts, I pinpointed excess sugar and seed oil consumption as culprits in NAFLD and NASH (1, 2, 3, 4, 5).

Chris Masterjohn recently published two very informative posts on NAFLD/NASH that add a major additional factor to the equation: choline (6, 7). Choline is an essential nutrient that's required for the transport of fat out of the liver (8). NAFLD can be caused, and cured, simply by removing or adding dietary choline, and it appears to be dominant over other dietary factors including fat, sugar and alcohol. Apparently, certain researchers have been aware of this for some time, but it hasn't entered into the mainstream consciousness.

Could that be because the richest dietary sources are liver and eggs*? Choline is also found in smaller amounts in a variety of whole animal and plant foods. Most people don't get the officially recommended amount. From a recent review article (9):

Mean choline intakes for older children, men, women, and pregnant women are far below the adequate intake level established by the [Institute of Medicine]. Given the importance of choline in a wide range of critical functions in the human body, coupled with less-than-optimal intakes among the population, dietary guidance should be developed to encourage the intake of choline-rich foods.

I've dubbed beef liver the Most Nutritious Food in the World, Nature's Multivitamin, and I'll probably invent other titles for it in the future. Add yours to the comments. Learn to love liver! I think it's an excellent food to eat on a weekly basis.

Head over to Chris's blog and read about the classic studies he unearthed. And add The Daily Lipid to your RSS reader, because there's more interesting material to come!

The Sweet Truth about Liver and Egg Yolks
Does Choline Deficiency Contribute to Fatty Liver in Humans?


* For the brave: brain is actually the richest source of choline.