New Evidence Strengthens the Link Between Hypothalamic Injury, Obesity, and Insulin Resistance

Obesity involves changes in the function of brain regions that regulate body fatness and blood glucose, particularly a region called the hypothalamus.  My colleagues and I previously showed that obesity is associated with inflammation and injury of the hypothalamus in rodent models, and we also presented preliminary evidence that the same might be true in humans.  In our latest paper, we confirm this association, and show that hypothalamic injury is also associated with a marker of insulin resistance, independently of BMI.

Introduction

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.

Is Meat Unhealthy? Part V

In this post, I'll examine the possible relationship between meat intake and type 2 diabetes.  Type 2 diabetes is the most common form of diabetes, and it is strongly linked to lifestyle factors.

Non-industrial cultures

Non-industrial cultures have an extremely low prevalence of diabetes, whether they are near-vegan or near-carnivorous.  This is supported by blood glucose measurements in a variety of cultures, from the sweet potato farmers of the New Guinea highlands to the arctic Inuit hunters.  Here is what Otto Schaefer, director of the Northern Medical Research Unit at Charles Camsell hospital in Edmonton, Canada, had to say about the Inuit in the excellent book Western Diseases (Trowell and Burkitt, 1981):

Obesity → Diabetes

A new study adds to the evidence that the prevalence of type 2 diabetes is rapidly increasing in the US, and our national weight problem is largely to blame.

The Centers for Disease Control (CDC) currently estimates that a jaw-dropping 33 percent of US men, and 39 percent of US women, will develop diabetes at some point in their lives (1).  Roughly one out of three people in this country will develop diabetes, and those who don't manage it effectively will suffer debilitating health consequences.  Has the risk of developing diabetes always been so high, and if not, why is it increasing?

In the same issue of the Annals of Internal Medicine as the low-carb vs. low-fat study, appears another study that aims to partially address this question (2).

Metabolic Effects of a Traditional Asian High-carbohydrate Diet

A recent study supports the notion that an 'ancestral diet' focused around high-starch agricultural foods can cultivate leanness and metabolic health.

John McDougall gave Christopher Gardner a hard time at the McDougall Advanced Study Weekend.  Dr. Gardner conducts high-profile randomized controlled trials (RCTs) at Stanford to compare the effectiveness of a variety of diets for weight loss, cardiovascular and metabolic health.  The "A to Z Study", in which Atkins, Zone, Ornish, and LEARN diets were pitted against one another for one year, is one of his best-known trials (1).

Dr. McDougall asked a simple question: why haven't these trials evaluated the diet that has sustained the large majority of the world's population for the last several thousand years?  This is an agriculturalist or horticulturalist diet based around starchy foods such as grains, tubers, legumes, and plantains, and containing little fat or animal foods.  Researchers have studied a number of cultures eating this way, and have usually found them to be lean, with good cardiovascular and metabolic health.  Why not devote resources to studying this time-tested ancestral diet?  I think it's a fair question.

Help Advance Diabetes Research

A University of Virginia researcher named Hannah Menefee contacted me recently to ask for our help.  She and her colleagues are conducting a study on how people with type 2 diabetes use Facebook to manage their health, and how that technology can be leveraged to support effective health communication.

If you have type 2 diabetes, and you'd like to participate in the study, please join their Diabetes Management Study Facebook group.  There, you'll receive more information about the study, you'll receive a short survey, and you may be invited into one of the study phases.

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?

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

Dogs Eating Carbs

Five years ago, I had an interesting conversation with a veterinarian friend about dog food.  We were talking about diabetes in one of the dogs she was treating, and I remarked "that's what happens when you feed a carnivore carbohydrate".  She gave me a funny look.  At the time, I was seeing the world through the low-carb lens, and I remember thinking how bizarre it was that she didn't yield to my impeccable logic.  As they say, live and learn.

The journal Nature published a fascinating paper on the evolution of the domestic dog today (1).  Researchers compared the genome of wolves and domestic dogs to see what genetic changes accompanied domestication.

Calories and Carbohydrate: a Natural Experiment

In the lab, we work hard to design experiments that help us understand the natural world.  But sometimes, nature sets up experiments for us, and all we have to do is collect the data.  These are called "natural experiments", and they have led to profound insights in every field of science.  For example, Alzheimer's disease is not usually considered a genetic disorder.  However, researchers have identified rare cases in which AD is inherited in a simple genetic manner.  By identifying the genes involved, and what they do, we were able to increase our understanding of the molecular mechanisms of the disease.

The natural experiment I'll be discussing today began in 1989 with the onset of a major economic crisis in Cuba. This coincided with the loss of the Soviet Union as a trading partner, resulting in a massive economic collapse over the next six years, which gradually recovered through 2000. 

New Review Paper by Yours Truly: High-Fat Dairy, Obesity, Metabolic Health and Cardiovascular Disease

My colleagues Drs. Mario Kratz, Ton Baars, and I just published a paper in the European Journal of Nutrition titled "The Relationship Between High-Fat Dairy Consumption and Obesity, Cardiovascular, and Metabolic Disease".  Mario is a nutrition researcher at the Fred Hutchinson Cancer Research Center here in Seattle, and friend of mine.  He's doing some very interesting research on nutrition and health (with an interest in ancestral diets), and I'm confident that we'll be getting some major insights from his research group in the near future.  Mario specializes in tightly controlled human feeding trials.  Ton is an agricultural scientist at the University of Kassel in Germany, who specializes in the effect of animal husbandry practices (e.g., grass vs. grain feeding) on the nutritional composition of dairy.  None of us have any connection to the dairy industry or any other conflicts of interest.

The paper is organized into three sections:

1. A comprehensive review of the observational studies that have examined the relationship between high-fat dairy and/or dairy fat consumption and obesity, metabolic health, diabetes, and cardiovascular disease.
2. A discussion of the possible mechanisms that could underlie the observational findings.
3. Differences between pasture-fed and conventional dairy, and the potential health implications of these differences.

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

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.

An Interview with Dr. C. Vicky Beer, Paleo-friendly MD

As I was preparing my recent article on the Paleo diet (1), I interviewed a local Paleo-friendly MD named C. Vicky Beer.  I was only able to include a snippet of the interview in the article, but I thought WHS readers would be interested to read the rest of the interview with Dr. Beer:

What Causes Insulin Resistance? Part VII

In previous posts, I outlined the factors I'm aware of that can contribute to insulin resistance.  In this post, first I'll list the factors, then I'll provide my opinion of effective strategies for preventing and potentially reversing insulin resistance.

The factors

These are the factors I'm aware of that can contribute to insulin resistance, listed in approximate order of importance.  I could be quite wrong about the order-- this is just my best guess. Many of these factors are intertwined with one another. 

What Causes Insulin Resistance? Part VI

In this post, I'll explore a few miscellaneous factors that can contribute to insulin resistance: smoking, glucocorticoids/stress, cooking temperature, age, genetics and low birth weight.

Smoking

Smoking tobacco acutely and chronically reduces insulin sensitivity (1, 2, 3), possibly via:

1. Increased inflammation
2. Increased circulating free fatty acids (4)

Paradoxically, since smoking also protects against fat gain, in the very long term it may not produce as much insulin resistance as one would otherwise expect.  Diabetes risk is greatly elevated in the three years following smoking cessation (5), and this is likely due to the fat gain that occurs.  This is not a good excuse to keep smoking, because smoking tobacco is one of the most unhealthy things you can possibly do.  But it is a good reason to tighten up your diet and lifestyle after quitting.

What Causes Insulin Resistance? Part V

Previously in this series, we've discussed the role of cellular energy excess, inflammation, brain insulin resistance, and micronutrient status in insulin resistance.  In this post, I'll explore the role of macronutrients and sugar in insulin sensitivity.

Carbohydrate and Fat

There are a number of studies on the effect of carbohydrate:fat ratios on insulin sensitivity, but many of them are confounded by fat loss (e.g., low-carbohydrate and low-fat weight loss studies), which almost invariably improves insulin sensitivity.  What interests me the most is to understand what effect different carbohydrate:fat ratios have on insulin sensitivity in healthy, weight stable people.  This will get at what causes insulin resistance in someone who does not already have it.

What Causes Insulin Resistance? Part IV

So far, we've explored three interlinked causes of insulin resistance: cellular energy excess, inflammation, and insulin resistance in the brain.  In this post, I'll explore the effects on micronutrient status on insulin sensitivity.

Micronutrient Status

There is a large body of literature on the effects of nutrient intake/status on insulin action, and it's not my field, so I don't intend this to be a comprehensive post.  My intention is simply to demonstrate that it's important, and highlight a few major factors I'm aware of.

What Causes Insulin Resistance? Part III

As discussed in previous posts, cellular energy excess and inflammation are two important and interlinked causes of insulin resistance.  Continuing our exploration of insulin resistance, let's turn our attention to the brain.

The brain influences every tissue in the body, in many instances managing tissue processes to react to changing environmental or internal conditions.  It is intimately involved in insulin signaling in various tissues, for example by:

• regulating insulin secretion by the pancreas (1)
• regulating glucose absorption by tissues in response to insulin (2)
• regulating the suppression of glucose production by the liver in response to insulin (3)
• regulating the trafficking of fatty acids in and out of fat cells in response to insulin (4, 5)

Because of its important role in insulin signaling, the brain is a candidate mechanism of insulin resistance.

What Causes Insulin Resistance? Part II

In the last post, I described how cellular energy excess causes insulin resistance, and how this is triggered by whole-body energy imbalance.  In this post, I'll describe another major cause of insulin resistance: inflammation. 

Inflammation

In 1876, a German physician named W Ebstein reported that high doses of sodium salicylate could totally eliminate the signs and symptoms of diabetes in certain patients (Berliner Klinische Wochenschrift. 13:337. 1876). Following up on this work in 1901, the British physician RT Williamson reported that treating diabetic patients with sodium salicylate caused a striking decrease in the amount of glucose contained in the patients' urine, also indicating an apparent improvement in diabetes (2).  This effect was essentially forgotten until 1957, when it was rediscovered.

What Causes Insulin Resistance? Part I

Insulin is an ancient hormone that influences many processes in the body.  Its main role is to manage circulating concentrations of nutrients (principally glucose and fatty acids, the body's two main fuels), keeping them within a fairly narrow range*.  It does this by encouraging the transport of nutrients into cells from the circulation, and discouraging the export of nutrients out of storage sites, in response to an increase in circulating nutrients (glucose or fatty acids). It therefore operates a negative feedback loop that constrains circulating nutrient concentrations.  It also has many other functions that are tissue-specific.

Insulin resistance is a state in which cells lose sensitivity to the effects of insulin, eventually leading to a diminished ability to control circulating nutrients (glucose and fatty acids).  It is a major contributor to diabetes risk, and probably a contributor to the risk of cardiovascular disease, certain cancers and a number of other disorders. 

Why is it important to manage the concentration of circulating nutrients to keep them within a narrow range?  The answer to that question is the crux of this post.