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Decoding diabetes.

Heart attacks, strokes, kidney disease. Cancers of the breast, colon, lung, ovary, liver, and bladder. Liver disease, lung disease, pneumonia and other infectious diseases. Having type 2 diabetes increases the risk of dying of those illnesses and more, according to a new compilation of 97 studies on 820,900 people. (1)

The average 50-year-old with diabetes dies six years earlier than the average 50-year-old without diabetes. For comparison, the average long-term smoker dies 10 years earlier than the average non-smoker.

Here's the latest on diabetes and how to lower your risk.

An estimated 11 percent of adults have diabetes. A quarter of them don't even know it. But that doesn't tell the whole story. Experts estimate that by 2050, one out of three adults will have the disease.

Among people over 65, one out of four already has diabetes. And another 35 percent of all adults (and half of those over 65) have prediabetes.

The good news: type 2 diabetes is almost entirely preventable. (2) "People who have a healthy weight and lifestyle have a 90 percent lower risk," says JoAnn Manson, professor of epidemiology at the Harvard School of Public Health.

Diabetes 101

If your fasting blood sugar is higher than 125, you have diabetes. (If it's higher than 100, you have prediabetes.)

It's easy to see why blood sugar soars in people who have type 1 diabetes. The beta-cells in their pancreas make no insulin, the hormone that acts like a key to admit blood sugar into cells, where it can be stored or burned for fuel. (One possible explanation: the body may destroy its own beta-cells in a misguided autoimmune attack.)

People who have type 2 diabetes (which accounts for 90 to 95 percent of cases) often make plenty of insulin, but the insulin doesn't work well.

"Their cells are resistant to the insulin, so the body needs to pump out more of it," explains Varman Samuel, assistant professor of medicine at the Yale School of Medicine. "And for a while, the beta-cells can compensate," so blood sugar levels stay under control.

But in many people, the pancreas can't keep up with the demand for insulin. "When the beta-cells poop out, you tip over into diabetes," says Samuel. Insulin output falls short, and blood sugar climbs.

"It's as though you're listening to loud music but you have wax in your ears," he suggests. "So you keep turning up the volume, but you still can't hear because the music isn't getting through. Then at some point, your speakers blow."

The question is: what sets off insulin resistance in the first place?

Insulin Resistance

It's hard to miss the first clue that explains insulin resistance. Roughly 80 percent of people with type 2 diabetes are overweight or obese.

"Excess body weight is by far the strongest risk factor for diabetes," says Harvard's JoAnn Manson, who heads the Division of Preventive Medicine at Brigham and Women's Hospital in Boston. And the "visceral" fat deep in your belly may boost the risk the most.

"If we could get people to a healthy weight, it could eliminate roughly half of all cases of diabetes," says Manson. "That's the big picture."

Obesity doesn't explain why we all--no matter how fat or thin--have a greater risk of diabetes as we get older. And genes, smoking, exercise, and diet also play a role. But for most people, the trouble starts when they eat too many calories, day after day.

"Any excess calories you eat are eventually turned into fat that needs to be stored," explains Kimber Stanhope, a molecular biologist at the University of California, Davis.

At first, the fat fits into your fat cells.

"Let's say your body is doing a good job of being able to store the fat," says Stanhope. "But once your fat cells get too large, they're less likely to continue to take up and retain more fat."

Some obese people may never become insulin resistant (or diabetic) because their bodies keep making new fat cells.

"Maybe they're just better at storing the fat because their fat ceils can get bigger or they can make more fat cells," notes Samuel. Others run out of storage room sooner. "They start to run into problems when the fat starts to spill over," he explains.

When there's no more room at the inn, the body stashes the fat wherever it can.

"It's called ectopic lipid," says Stanhope. "Fat is stored in tissues that aren't supposed to be storing it--like the liver, muscle, and pancreas."


Some scientists believe that misplaced fat is the key to insulin resistance. When insulin arrives at a cell, it signals a "glucose transporter" to ferry blood sugar (glucose) into the cell. (See "Insulin Resistance.") Ectopic fat may block the signal, suggest studies at Yale and elsewhere. (3)

"We think the initial insult is ectopic lipid in muscle or the liver or both," says Samuel.

Excess fat can also lead to low levels of chronic inflammation, which makes matters worse.

"When cells get overfat, some scientists call them 'angry fat' because they release inflammatory proteins," explains Sheri Colberg, professor of human movement sciences at Old Dominion University in Norfolk, Virginia.

In fact, some researchers contend that it's the inflammatory proteins that keep insulin from working well. (4)

Fatty Livers and Muscles

Scientists debate whether insulin resistance starts in the liver or the muscles, but one thing is clear: a fatty liver matters.

Researchers at Washington University in St. Louis matched 20 obese people according to high or low levels of liver fat or high or low levels of deep belly visceral fat. (5y)

"Liver fat was a better predictor of metabolic dysfunction than visceral fat," noted study author Samuel Klein at the Experimental Biology 2011 meeting in April in Washington, D.C.

Another sign that a fatty liver matters: it may explain why a modest drop in weight can get diabetes under control.

For example, in 2005, when researchers at Yale put eight obese people with diabetes on a low-calorie diet for seven weeks, their fasting blood sugar levels returned to normal. (6)

"They lost only about 18 pounds, and there was no change in muscle fat content," explains Samuel. However, 84 percent of their liver fat disappeared.

If you cut calories, "that will melt away that liver fat," says Samuel. "And once you do that, your liver responds much better to whatever insulin you make. It's enough to control your glucose metabolism."

How do you know if you have a fatty liver? "Most people don't get diagnosed," says Samuel.

"What gets picked up is when they go to the next step. If they develop inflammation in the liver--steatohepatitis--that shows up on routine blood tests. You would see that some liver enzymes are increased."

A fatty liver has been in the headlines lately, not so much to explain insulin resistance, but as evidence that too much sugar causes diabetes.


"Is Sugar Toxic?" asked the headline in the April 17 New York Times Magazine.

Unlike the starch in grains, which consists of long chains of glucose, most sugars--including ordinary table sugar (sucrose), high-fructose corn syrup (HFCS), and honey--are about half glucose and half fructose. It's the fructose half that has recently raised alarms.

"In animals, or at least laboratory rats and mice, it's clear that if fructose hits the liver in sufficient quantity and with sufficient speed, the liver will convert much of it to fat," wrote author Gary Taubes in The Times.

"This apparently induces a condition known as insulin resistance.... If what happens in laboratory rodents also happens in humans, and if we are eating enough sugar to make it happen, then we are in trouble." But so far, at least in humans, it's not clear that fructose causes diabetes.

Two studies have found a higher risk of the disease in people who consumed more fructose or glucose (though, surprisingly, not sucrose), while a third found no link with any sugars. (7-9)

Nor is it clear that fructose causes a fatty liver.

"It's a reasonable hypothesis," says the University of California's Kimber Stanhope. "A fatty liver can happen over the long term as a person gets fatter every year, but it may happen more quickly because fructose is a direct source of liver triglycerides."

However, she adds, "no direct connection between fructose consumption and fatty liver has been made yet in humans."

Researchers have come close, though. In a 2009 study, Stanhope fed 32 overweight or obese people (mostly in their SOs) 25 percent of their calories as either fructose- or glucose-sweetened beverages for 10 weeks each. (10)

(That's a high dose. Even American adults with the most sugar-laden diets get roughly 30 percent of their calories from added sugars, which means that about 15 percent comes from fructose and 15 percent from glucose. (11)

Both groups gained about three pounds, but the fructose drinkers were much worse off.

"They gained more visceral fat, they became more insulin resistant, their triglycerides went up more after eating, and their livers made more fat," says Stanhope. "That suggests that we may have had an increase in liver fat."

But the researchers didn't measure how much fat accumulated in the liver. "The technology was just getting developed at that time--so we can't say for sure."

Stanhope's new study, now under way, is pitting fructose against glucose, high-fructose corn syrup, and sucrose, but the liver results won't be ready until 2013.

"No one else has shown that liver fat increased when people consumed fructose except Luc Tappy," notes Stanhope.

In 2009, Tappy and colleagues at the University of Lausanne in Switzerland reported a rise in liver fat in healthy young men. (Two-thirds had a parent with type 2 diabetes.)

"But the men had their normal calorie allotment and then had a high dose of fructose on top of that," Stanhope points out.

How much? Tappy fed the men as much fructose as a person would get by drinking roughly four liters of soda a day in addition to their ordinary diet. (12) With the fructose, they were eating 35 percent more calories than usual.

"In that situation they saw an increase in fatty liver," says Stanhope. "But that would not be a typical amount of fructose or calories."

In fact, three years earlier, Tappy fed healthy young men (without a parent who had diabetes) as much fructose as a person would get by drinking two liters of

soda--and no extra calories--every day for a month. The fructose didn't boost their liver or muscle fat. (13)

What's more, Tappy's 2009 study didn't compare excess calories from fructose to excess calories from some other food. So it's possible that getting 35 percent extra calories from any food would cause a fatty liver.

"It was not possible," wrote Tappy, "to determine whether the increase in [liver fat] was due to energy overconsumption or to the specific effects of fructose."

Stanhope's bottom line: "There is enough data associating fructose consumption with metabolic disease--diabetes, heart disease, fatty liver, high blood triglycerides--to consume it with caution."

And since we get glucose from all carbs but fructose only from sugars, the only way to limit fructose is to limit sugars.

"I've had people argue with me right and left that if people overeat, it doesn't matter what those calories are," says Stanhope. "Our study showed that it does matter."

Sugar-Sweetened Beverages

"In the Nurses' Health Study, sugarsweetened beverages were linked to an increased risk of diabetes," says Harvard's JoAnn Manson. (14)

It's not just the nurses. In 2010, researchers pooled data from eight studies on a total of more than 300,000 people to see if diabetes was linked to sugar-sweetened beverages--soft drinks, fruit drinks, iced tea, energy drinks, vitamin water, you name it.

Those who consumed the most sugary drinks (typically one or two servings a day) had a 26 percent higher risk of diabetes than those who drank the least (less than one serving a month). (15)


"Weight gain is part of the story," notes Manson. Women who drank more soda were also more likely to gain weight than women who drank less.

"Liquid calories may not curb your appetite as much as solid calories do," she explains. But sugar-sweetened beverages were linked to a higher risk of diabetes even when her study compared women who weighed the same.

"People may get more of a swing in blood sugar when they drink sugar-sweetened beverages," she suggests. "When you eat sugar in solid foods, where it's mixed in with protein and fat, that may slow the absorption, so there's less demand on the pancreas to produce insulin."


"Magnesium is understudied and underappreciated for its effect on both glucose tolerance and cardiovascular disease," says Manson.

In a study that tracked 85,000 women for 18 years and 42,000 men for 12 years, those who consumed the most magnesium (about 375 milligrams a day for women and 450 mg a day for men) from food and supplements combined had a 33 percent lower risk of diabetes than those who consumed the least (220 mg a day for women and 270 mg a day for men). (16)

Another study found lower blood insulin levels and a lower risk of diabetes in women who consumed the most magnesium. (17)

"It's biologically plausible that magnesium would have an effect on glucose tolerance and insulin sensitivity," notes Manson.

Small studies have already tested magnesium supplements on people who have diabetes. And magnesium

supplements (365 mg a day) have lowered insulin resistance and fasting blood sugar levels in overweight people who don't have diabetes. (18)

"Larger trials are needed," says Manson. "We're designing one now."

In the meantime, it makes sense to eat magnesium-rich foods like whole grains, leafy greens, beans, nuts, and coffee, rather than take a supplement. Taking high doses (more than 350 mg) of magnesium leads to mild diarrhea or other gastrointestinal complaints in some people.

"Much more research needs to be done, but magnesium is looking very promising," says Manson.

Whole Grains

When researchers pooled data from six studies of more than 286,000 participants, they estimated that for every two servings of whole grains you eat a day, your risk of diabetes drops by 21 percent. (19)

Why? "Whole grains lead to smaller fluctuations in blood sugar and insulin than refined grains and sugars," says Manson. "Whole grains may also lead to more satiety. Refined carbs can lead to hunger and increased food intake due to the wide swings in blood sugar."

But, she cautions, "people who eat whole grains tend to exercise more, smoke less, and have a healthier dietary pattern." And those things could help account for the link.


When researchers examined nine studies on more than 193,000 people, they found that those who drank four to six cups of regular coffee a day had a 28 percent lower risk of diabetes than those who drank no more than two cups a day. (20)

"Decaf is also associated with a lower risk of diabetes, so something other than the caffeine in coffee beans appears to be responsible," says Manson. "The mechanism isn't known."

Vitamin D

Some studies find a lower risk of diabetes in people who have higher levels of vitamin D. (21) Others do not. (22)

"The research has been very inconsistent," says Manson. "We see totally divergent findings."

One possible explanation: the higher your weight, the lower your blood levels of vitamin D.

"Vitamin D gets sequestered in fat tissue, so any time you see a correlation with body weight, low levels of vitamin D can appear as a risk factor if you don't control for body weight," explains Manson.

The VITAL (Vitamin D and Omega-3 Trial) study that Manson is leading should help clarify vitamin D's role. Roughly 20,000 men (age 60 or older) and women (65 or older) will take

vitamin D (2,000 IU a day) and/or omega-3 fats (1,000 mg a day) or a placebo for five years.

The goal: to see if either supplement affects the risk of cancer, heart disease, diabetes, memory loss, or other health problems. (To see if you're eligible to participate, go to


"We saw a slight increased risk of diabetes with fish and omega-3s in the Nurses' Health Study," says Manson. "But other studies show lower risk."

It's not just her studies. "At least as many studies suggest benefit as harm. The evidence is inconsistent and difficult to understand."

It's not clear why some studies find that fish eaters have a slightly higher

risk. (23) Among the possibilities: fish may have high levels of pollutants like PCBs and dioxin. (24)

The good news: "We're doing a trial to look at glucose tolerance," says Manson. The study will piggyback on the VITAL trial.

"We'll look at blood sugar changes after two years and the incidence of diabetes after five years of taking about a grain of EPA and DHA a day. So eventually we'll have more data."



Surplus calories are turned into fat and stored in your subcutaneous and visceral fat cells. When those cells fill up, the body stashes fat in muscles and the liver. A fatty liver and visceral fat are most closely linked to insulin resistance and diabetes.



When insulin docks in the receptors on cell membranes, that should signal glucose transporters to let glucose (blood sugar) into the cell. But if you are insulin resistant, some glucose transporters never get the message. (Others don't need insulin to let glucose in.) That leaves excess glucose in the blood, so the pancreas has to pump out more insulin. If it can't keep up, blood sugar rises and you have diabetes.


Most people who have prediabetes--and many others who have diabetes-don't know it. The only way to find out is to get your blood sugar tested (at least every three years starting at age 45). Your risk is higher if you:

* are age 45 or older

* are overweight (see table)

* are African-American, Hispanic/Latino-American, Asian-American, Pacific Islander, or American Indian

* have a parent, brother, or sister with diabetes

* have high blood pressure (above 140 over 90)

* have low HDL ("good") cholesterol (less than 40 for men; less than 50 for women)

* have high triglycerides (250 or more)

* had diabetes when pregnant or gave birth to a large baby (over 9 pounds)

* are active fewer than three times a week

Source: Adapted from
Overweight starts at:

  Height     Weight (lbs.)     Height     Weight (lbs.)
(no shoes)   (no clothes)    (no shoes)   (no clothes)

  4'10"           119           5'8"           164
  4'11"           124           5'9"           169
   5'0"           128          5'10"           174
   5'1"           132          5'11"           179
   5'2"           136           6'0"           184
   5'3"           141           6'1"           189
   5'4"           145           6'2"           194
   5'5"           150           6'3"           200
   5'6"           155           6'4"           205
   5'7"           159

The Bottom Line

* The best way to dodge diabetes is to lose (or not gain) extra pounds.

* Limit sweets, especially sugar-sweetened drinks. Even the naturally occurring sugars in 100% fruit juice may raise your risk.

* Eat leafy greens, whole grains, beans, and nuts to boost your magnesium.

* Get the RDA for vitamin D (600 IU a day up to age 70 and 800 IU over 70) from supplements or foods fortified with vitamin D.

* Do at least 30 minutes of brisk walking or other aerobic exercise every day.

* Shoot for 2 or 3 strength training sessions a week. Each should include 8 to 12 repetitions of 8 to 10 exercises.

(1) N. Engl. J. Med. 364: 829, 2011.

(2) N. Engl. J. Med. 345: 790, 2001.

(3) Lancet 375: 2267, 2010.

(4) J. Clin. Invest. 116:1793, 2006.

(5) Proc. Natl. Acad. Sci. USA 106: 15430, 2009.

(6) Diabetes 54: 603, 2005.

(7) Am. J. Clin. Nutr. 71: 921, 2000.

(8) J. Nutr. 137:1447, 2007.

(9) Diabetes Care 26: 1008, 2003.

(10) J. Clin. Invest. 119:1322, 2009.

(11) JAMA 303: 1490, 2010.

(12) Am. J. Clin. Nutr. 89:1760, 2009.

(13) Am. J. Clin. Nutr. 84:1374, 2006.

(14) JAMA 292: 927, 2004.

(15) Diabetes Care 33: 2477, 2010.

(16) Diabetes Care 27:134, 2004.

(17) Diabetes Care 27: 59, 2004.

(18) Diab. Obesity Metab. 13:281, 2011.

(19) PLoS Med. 4: e261, 2007.

(20) JAMA 294: 97, 2005.

(21) Diabetes Care 33: 2021, 2010.

(22) Diabetes Care 34: 628, 2011.

(23) Am. J. Clin. Nutr. 90:613, 2009.

(24) Diabetes Care 29:1638, 2006.
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Author:Liebman, Bonnie
Publication:Nutrition Action Healthletter
Article Type:Cover story
Geographic Code:1USA
Date:Jun 1, 2011
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