Insulin Resistance Predicts a Variety of Age-related Diseases

In the last post, I reviewed a study by Gerald Reaven's group showing that insulin resistance strongly predicts the risk of cardiovascular disease over a 5-year period. In 2001, Reaven's group published an even more striking follow-up result from the same cohort (1). This study shows that not only does insulin resistance predict cardiovascular disease risk, it also predicts a variety of age-related diseases, including hypertension, coronary heart disease, stroke, cancer, type 2 diabetes, and even overall mortality risk.

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New Study Strengthens the Case that LDL Causes Heart Disease

There is little remaining doubt in the scientific/medical community that high levels of LDL, so-called "bad cholesterol", cause heart disease. Yet in some alternative health circles, the debate continues. A new study adds substantially to the evidence that LDL plays a causal role in heart disease.

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Is Meat Unhealthy? Part III

When we consider the health impacts of eating meat, cardiovascular disease is the first thing that comes to mind. Popular diet advocates often hold diametrically opposed views on the role of meat in cardiovascular disease. Even among researchers and public health officials, opinions vary. In this post, I'll do my best to sort through the literature and determine what the weight of the evidence suggests.

Ancel Keys and the Seven Countries Study

Ancel Keys was one of the first researchers to contribute substantially to the study of the link between diet and cardiovascular disease. Sadly, there is a lot of low-quality information circulating about Ancel Keys and his research (1). The truth is that Keys was a pioneering researcher who conducted some of the most impressive nutritional science of his time. The military "K ration" was designed by Keys, much of what we know about the physiology of starvation comes from his detailed studies during World War II, and he was the original Mediterranean Diet researcher. Science marches on, and not all discoveries are buttressed by additional research, but Keys' work was among the best of his day and must be taken seriously.

One of Keys' earliest contributions to the study of diet and cardiovascular disease appeared in an obscure 1953 paper titled "Atherosclerosis: A Problem in Newer Public Health" (2). This paper is worth reading if you get a chance (freely available online if you poke around a bit). He presents a number of different arguments and supporting data, most of which are widely accepted today, but one graph in particular has remained controversial. This graph shows the association between total fat intake and heart disease mortality in six countries. Keys collected the data from publicly available databases on global health and diet:

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Corrections to the New Review Paper on Dietary Fat and Cardiovascular Risk

The meta-analysis by Chowdhury et al. raised quite a furor from certain segments of researchers and the popular media. I find this reaction interesting. I usually write about obesity, which is a topic of great interest to people, but my post about the review paper received more than twice my usual traffic. People whose findings or opinions are questioned by the paper are aggressively denouncing it in the media, even calling for retraction (1). This resembles what happens every time a high-profile review paper is published that doesn't support the conventional stance on fatty acids and health (e.g., Siri-Tarino et al. [2], which despite much gnashing of teeth is still standing*). I'm not sure why this issue in particular arouses such excitement, but I find it amusing and disturbing at the same time. This kind of reaction would be totally out of place in most other fields of science, where aggressive public media outbursts by researchers are usually frowned upon.

As it turns out, the critics have a point this time. Significant errors were uncovered in the original version of the meta-analysis, which have been corrected in the current version (3). These include the following two errors, one of which alters the conclusion somewhat:

• The outcome of one observational study on omega-3 fatty acids was reported as slightly negative, when it was actually strongly positive. This changes the conclusion of the meta-analysis, making it somewhat more favorable to omega-3 consumption for cardiovascular protection.
• The authors left out two studies on omega-6 fatty acids. These didn't change the overall conclusions on omega-6.

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New Review Paper on Dietary Fat and Heart Disease Risk

A new review paper on dietary fatty acids and heart disease risk was just published by Dr. Rajiv Chowdhury and colleagues in the Annals of Internal Medicine-- one of the top medical journals (1). The goal of the paper is to comprehensively review the studies evaluating the effect of dietary fatty acids on heart (coronary) disease. The review covers observational and intervention studies pertaining to saturated, monounsaturated, trans, omega-6 polyunsaturated, and omega-3 polyunsaturated fats. The paper is notable for its comprehensiveness (inclusion criteria were very lax).

Here is a summary of the results:

• In observational studies that measured diet, only trans fat was related to cardiovascular risk. Saturated, monounsaturated, and polyunsaturated fats were unrelated to risk.
• In observational studies that measured circulating concentrations of fatty acids, long-chain polyunsaturated fatty acids (DHA, DPA, EPA, AA) were associated with lower risk. The dairy-fat-derived margaric acid (17:0) was also associated with lower risk. No other fatty acids were related to risk, including trans fatty acids.
• In controlled trials, supplementation with omega-3 or omega-6 fatty acids did not alter risk.

The authors conclude:

In conclusion, the pattern of findings from this analysis did not yield clearly supportive evidence for current cardiovascular guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of saturated fats. Nutritional guidelines on fatty acids and cardiovascular guidelines may require reappraisal to reflect the current evidence.

My view

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Does "Metabolically Healthy Obesity" Exist?

Obesity is strongly associated with metabolic alterations and negative health outcomes including diabetes, cardiovascular disease, and some types of cancer (1, 2, 3, 4). Excess body fat is one of the primary causes of preventable health problems and mortality in the United States and many other affluent nations, ranking in importance with cigarette smoking and physical inactivity. Obesity is thought to contribute to disease via the metabolic disturbances it causes, including excess glucose and lipids in the circulation, dysregulated hormone activity including insulin and leptin, and inflammatory effects. This immediately raises two questions:

1. Does metabolically healthy obesity exist?
2. If so, are metabolically healthy obese people at an elevated risk of disease and death?

Does metabolically healthy obesity exist?

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Neuronal Control of Appetite, Metabolism and Weight

Last week, I attended a Keystone conference, "Neuronal Control of Appetite, Metabolism and Weight", in Banff. Keystone conferences are small, focused meetings that tend to attract high quality science. This particular conference centered around my own professional research interests, and it was incredibly informative. This post is a summary of some of the most salient points.

Rapid Pace of Scientific Progress

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