The link between obesity insulin resistance, and other chronic diseases

Dr. Mercola

More than 2.1 billion people, or close to 30 percent of the global population, are overweight or obese, and obesity is responsible for about five percent of all deaths each year, worldwide.¹ In the US, nearly one in five deaths is now associated with obesity.
That obesity factors into your mortality risk isn't so surprising when you consider just how many chronic and serious disease it's associated with.
In the US, just eight obesity-related diseases account for 75 percent of all healthcare costs! Type 2 diabetes, hypertension, heart disease, non-alcoholic fatty liver disease (NAFLD), dementia, and cancer are among them, but there are many others as well.
When you consider that two hallmarks of obesity are insulin/leptin resistance and chronic inflammation, you can begin to recognize that excess weight is fertile ground for a wide array of other ailments—many of which can cut your life significantly short.

The Links Between Obesity, Insulin Resistance, and Other Chronic Diseases

Previous research has shown that fat tissue secretes an inflammatory factor called CXCL5 that is linked to insulin resistance² and participates in the development of type 2 diabetes.³
When you're insulin resistant, your cells have become seriously impaired in their ability to respond to the insulin your body makes. At the heart of this problem is a diet too high in sugar (especially processed fructose).
While you can be insulin resistant and lean, obesity places far greater stress on your cells, which makes insulin resistance more probable. Insulin resistance is at the core of nearly every chronic degenerative disease and is typically what needs to be addressed first to turn around any disease.
Research⁴ shows that chronic overeating places stress on the endoplasmic reticulum (ER)—the membranous network found inside the mitochondria of your cells. And when the ER receives more nutrients than it can process, it signals the cell to dampen the sensitivity of the insulin receptors on the surface of the cell.
Thus continuously eating more than your body really needs promotes insulin resistance by the mere fact that your cells are stressed by the work placed on them by the excess nutrients. This also helps explain why intermittent fasting (as well as other forms of calorie restriction) is so effective for reversing insulin resistance and increasing longevity.
Once your insulin resistance worsens, the concentration of glucose in your blood begins to rise, and elevated glucose contributes to the development of diabetes.
According to a recent meta-review,⁵ the preponderance of research clearly shows that once you reach 18 percent of your daily calories from added sugar, there's a two-fold increase in metabolic harm that promotes prediabetes and diabetes.
It's important to realize that type 2 diabetes is not caused by lack of insulin, which is why taking insulin is one of the worst things a diabetic can do. You have plenty of it.
Your cells have simply lost their sensitivity to it because there's too much, and/or in the case of chronic overeating, your cells shut down the insulin receptors to "catch a break," as it were, because they're overloaded. As noted in one 2007 paper⁶ discussing the mechanisms of obesity-associated insulin resistance:

"In the past decade, a large number of endocrine, inflammatory, neural, and cell-intrinsic pathways have been shown to be dysregulated in obesity.
Although it is possible that one of these factors plays a dominant role, many of these factors are interdependent, and it is likely that their dynamic interplay underlies the pathophysiology of insulin resistance."

In essence, obesity is a marker for other chronic diseases, but it's really the insulin resistance that typically (but not always) accompanies obesity that drives all of these other pathologies.
For example, research⁷ has shown that insulin resistance strongly predicts the risk of cardiovascular disease over a five-year period.
A follow-up study⁸ published in 2001, using the same cohort, discovered that insulin resistance also predicts a number of other age-related diseases, including hypertension, coronary heart disease, stroke, cancer, and all-cause mortality risk.
Interestingly, over the course of this six-year long study, NONE of the middle-aged participants in the least insulin-resistant group developed disease or died, compared to 36 percent of those in the most insulin-resistant group. According to the authors:

"The fact that an age-related clinical event developed in approximately 1 out of 3 healthy individuals in the upper tertile of insulin resistance at baseline, followed for an average of 6 years, whereas no clinical events were observed in the most insulin-sensitive tertile, should serve as a strong stimulus to further efforts to define the role of insulin resistance in the genesis of age-related diseases."

Obesity Will Soon Overtake Smoking as Lead Cause of Cancer

For decades, smoking was one of the leading causes of cancer, but that's about to change.
Obesity will likely claim the lead spot as the principal cause of 10 different types of cancer within the next decade, according to cancer specialists who discussed the trend at this year's American Society of Clinical Oncology (ASCO) conference in Chicago.

"They said spiraling rates of obesity meant that cancer – once seen as a disease of old age – was now increasingly being diagnosed up to two decades earlier than in the past. Their figures suggest one in five cancer deaths in Britain is caused by excess weight," The Telegraph⁹ reports.

The links between obesity and cancer are quite clear, and excess weight can increase your risk of cancer rather significantly. For example, obese women increase their risk of womb cancer by 600 percent.
Your risk for breast, prostate, colon, and all the other gynecological cancers is also elevated, primarily due to the hormone imbalances associated with obesity, which tend to fuel tumor growth.
Researchers have also found a correlation between obesity and increased risk for cancer relapse.¹⁰ Overweight survivors of prostate cancer treatment were found to have a three percent higher rate of relapse compared to their slimmer counterparts. They also had seven percent higher odds of the cancer spreading.

Exercise Should Be Prescribed as Part of Cancer Treatment, Experts Say

Fortunately, researchers are also starting to recognize the power of lifestyle changes over drug prescriptions (although there's still plenty of research looking at pharmaceutical solutions, such as a compound that blocks the the sugar and nutrient pipeline in immune cells.¹¹) As noted in the featured article:¹²

"Separately, experts yesterday said exercise was such a 'potent' force against cancer that it should be prescribed as part of disease treatment. Researchers said women with breast cancer could reduce mortality by up to 50 percent with half an hour's moderate exercise, five times a week, compared with those who are inactive.
The results were based on a study of mice... Studies in men with prostate cancer also suggested vigorous exercise was linked to reduction of between 40 and 50 percent in mortality. 'Exercise creates a hostile environment for cancer cells,' the researchers said."

Endocrine-Disrupting Chemicals Add to the Obesity Epidemic

Excess dietary sugar and lack of exercise are not the only factors influencing your weight. Research shows environmental and dietary toxins also play a role—and perhaps a significant one. As recently reported by Scientific American:¹³

"A new study¹⁴ suggests the long-held industry assumption that bisphenol-A breaks down safely in the human body is incorrect. Instead, researchers say, the body transforms the ubiquitous chemical additive into a compound that might spur obesity.
The study is the first to find that people's bodies metabolize bisphenol-A (BPA) — a chemical found in most people and used in polycarbonate plastic, food cans and paper receipts — into something that impacts our cells and may make us fat."

When you're exposed to BPA, it takes about six hours for your liver to metabolize approximately half of the concentration. Up to 90 percent of what your liver metabolizes is eventually excreted, but the fact that it's metabolized and excreted doesn't mean it's harmless. By treating mouse and human cells with the BPA metabolite, called BPA-Glucuronide, the researchers showed the cells had a "significant increase in lipid accumulation," which is an indication that the cells are turning into fat cells.
What this means is that the BPA metabolite is not inactive, as was previously assumed. It's actually quite biologically active, so we cannot make blanket statements (assumptions, really) saying that since it's a metabolite, it's inactive and therefore has no health effects. As noted by one of the study's authors: "Hopefully this [study] stops us from making assumptions about endocrine disrupting chemicals in general."

Heart Disease—Another Major Killer Closely Associated with Obesity

Excessive sugar consumption and obesity is also closely associated with heart- and cardiovascular disease. One recent Journal of the American Medical Association (JAMA) study¹⁵ concluded that "most US adults consume more added sugar than is recommended for a healthy diet," and that there's "a significant relationship between added sugar consumption and increased risk for cardiovascular disease mortality."
The 15-year long study, which included data for 31,000 Americans, found that those who consumed 25 percent or more of their daily calories as sugar were more than twice as likely to die from heart disease as those who got less than 10 percent of their calories from sugar.
On the whole, the odds of dying from heart disease rose in tandem with the percentage of added sugar in the diet regardless of the age, sex, physical activity level, and body-mass index. A 2014 study¹⁶ came to very similar results.
Here, those who consumed the most sugar — about 25 percent of their daily calories — were twice as likely to die from heart disease as those who limited their sugar intake to seven percent of their total calories.
Other recent research¹⁷ found that young adults who drank beverages sweetened with high-fructose corn syrup (HFCS) increased their risk factors for heart disease within just two weeks.
Research presented during the 2013 American Heart Association's Epidemiology and Prevention/Nutrition, Physical Activity, and Metabolism Scientific Sessions suggested sugary beverages are to blame for about 183,000 deaths worldwide each year, including 133,000 diabetes deaths, 44,000 heart disease deaths, and 6,000 cancer deaths.
In the US alone, an estimated 25,000 annual deaths are attributed to the consumption of sweetened beverages like soda.
Part of the problem is that HFCS found in soda and other sweetened drinks actually causes more severe metabolic dysfunction because it's more readily metabolized into fat than any other sugar. The fact that refined fructose is far more harmful to your health than other sugars was recently highlighted in a meta-review published in the Mayo Clinic Proceedings.¹⁸
Of the different sugars available, refined fructose is probably the absolute worst, as it's broken down very much like alcohol, damaging your liver and causing mitochondrial and metabolic dysfunction in the same way as ethanol and other toxins.

The Links Between Fructose, Uric Acid, Kidney Disease, and Cardiovascular Disease

Kidney disease is another health problem associated with excessive fructose consumption,¹⁹ and kidney disease in turn may elevate your risk for cardiovascular disease. Interestingly, according to Dr. Richard Johnson, your uric acid level can help identify your susceptibility to fructose damage; it essentially acts as a marker for fructose toxicity. According to the latest research in this area, the safest range of uric acid is between 3 and 5.5 milligrams per deciliter, but there appears to be a steady relationship between uric acid levels, blood pressure, and cardiovascular risk, even down to the range of 3-4 mg/dl. Many obese individuals tend to have significantly elevated uric acid levels, some as high as 10 mg/dl.
The way you would use this information is quite simple. If your uric acid is elevated above 4 mg/dl for men and 3.5 mg/dl for women, you need to eliminate as much fructose from your diet as possible until your uric acid level has normalized, in order to avoid the toxic effects of fructose, which includes insulin resistance. That said, elevated uric acid²⁰ also appears to be predictive of chronic kidney disease (CKD), as evidenced by studies in which renal disease is induced in rats by raising their uric acid levels. And as noted in a 2013 paper:²¹

"Gout was considered a cause of CKD in the mid-nineteenth century, and, prior to the availability of therapies to lower the uric acid level, the development of end-stage renal disease was common in gouty patients... In addition, many subjects with gout also had coexistent conditions such as hypertension and vascular disease, leading some experts to suggest that the renal injury in gout was secondary to these latter conditions rather than to uric acid per se...
Renewed interest in uric acid as a cause of CKD occurred when it was realized that invalid assumptions had been made in the arguments to dismiss uric acid as a risk factor for CKD. The greatest assumption was that the mechanism by which uric acid would cause kidney disease would be via the precipitation as crystals in the kidney, similar to the way it causes gout. However, when laboratory animals with CKD were made hyperuricemic, the renal disease progressed rapidly despite an absence of crystals in the kidney."

Last but not least, a recent analysis²² of 24 studies suggests that your kidney health may actually be a more potent indicator of your cardiovascular disease risk than blood pressure and cholesterol. Compared to those with healthy kidneys, those with kidney disease were twice as likely to develop cardiovascular disease. So in summary, avoiding elevated uric acid (another effect of which is painful gout), kidney disease, and cardiovascular disease again boils down to controlling your refined sugar/processed fructose consumption.

Coke and Pepsi Need to Acknowledge Soda's Impact on Diabetes Rates

You're probably aware of Coca-Cola and Pepsi's obesity-prevention campaigns, offering advice on how to maintain your weight while still indulging in their assortment of beverages. Their recommendations usually focus on exercising more and opting for zero- or low-calorie beverages sweetened with artificial sweeteners instead of high fructose corn syrup (HFCS)—scientific data showing they promote obesity and metabolic dysfunction to the same or greater degree than HFCS be damned...
Many consumers react positively to such campaigns. However, you never see these companies addressing the issue of diabetes—which their products are a principal promoter of—and when researchers tested out consumers' reactions to anti-diabetes messages, the attitudes were far less favorable, which is probably why Coke and Pepsi refuse to address it. As reported by PR Newser²³ a couple of years ago:

"When the ad was changed to send an anti-diabetes message... participants' attitudes toward the brand became 37 percent more negative. That's a huge shift in reaction. 'People are not willing to punish the brand for obesity, which seems like a lifestyle problem. But diabetes is considered a disease, and many consumers see the parent brand as contributing to it,' said Kurt Carlson, a Georgetown marketing professor who oversaw the study."

The fact that Coke and Pepsi are willfully ignoring the issue doesn't make it any less relevant, and truly, if we want to see real changes within the industry, we need to press them on this issue, and force them to acknowledge their role in the diabetes epidemic. Eventually, I wouldn't be surprised if the soda industry ends up facing class-action lawsuits similar to those filed against the tobacco industry, as sodas and other sweetened beverages are now well linked to the obesity and diabetes epidemic.
Coca-Cola also admits to targeting teens (and has previously targeted children through in-school advertising and product placement). In an effort to quiet critics, Coke has made attempts to rebrand itself with a new, healthier image. Alas, their new "Coke Life," a low-calorie, low-sugar stevia-sweetened soda served in a green can²⁴ is just another green-washed soda, on par with filtered cigarettes... Filter or not, it's still harmful and certainly should not be advertised to kids as a way to make their day more "fun" or "enjoyable." There's nothing enjoyable about diabetes.

The Good News: Obesity, Diabetes, Heart Disease, and Cancer Are All Preventable

Nearly one in five US deaths is associated with obesity, and one in every three deaths is attributed to cardiovascular disease, which includes heart attacks and stroke. According to a 2013 report²⁵ from the US Center for Disease Control and Prevention (CDC), of the 800,000 cardiovascular disease deaths occurring in the US each year, a quarter of them —or about 200,000—could be prevented through simple lifestyle changes.
Personally, I believe the rate of prevention could be far higher than that—especially if great attention was paid to sugar/fructose consumption and elimination of insulin resistance.
According to statistics found in the Credit Suisse Research Institute's 2013 study²⁶ Sugar Consumption at a Crossroads, up to 40 percent of US healthcare expenditures are for diseases directly related to the overconsumption of sugar. We actually spend more than a trillion dollars each year fighting the damaging health effects of sugar!
To protect your health, please consider restricting your fructose consumption to 25 grams per day or less. If you're overweight or have a disease such as cancer, diabetes, or heart disease (or are at high risk for them) then you're probably better off further reducing your fructose intake to 15 grams per day or less (and this includes all sources—HFCS, sugar, honey, agave, fruit, fruit juice, maple syrup, etc.)
Doing this will help you normalize your insulin- and leptin levels, thereby reducing your risk of not only diabetes and heart disease, but also a long list of other chronic health problems.
Key to success when cutting out added sugar is to replace the lost calories (energy) with high quality healthy fat, which includes avocados; butter made from raw grass-fed organic milk; raw dairy; organic pastured egg yolks; coconuts and coconut oil; unheated organic nut oils; raw nuts and seeds; and grass-fed and finished meats.
Obesity, diabetes, heart disease and cancer—all of these issues tend to be feared by most people. But the solution—the most effective prevention—is within your own control. Reverse the amount of sugar to healthy fats in your diet (less sugar/non-vegetable carbs, more fat), and you'll see your risk factors start fading away