Tag Archives: insulin resistance

Overweight Women Lose More Weight If Main Meal Is Lunch Rather Than Dinner

Conquer Diabetes and Prediabetes, Steve Parker MD

It may not matter whether you eat this particular low-carb meal at lunch or dinner

They say that to lose excess weight, you should eat breakfast like a king, lunch like a prince, and dinner like a pauper.

A recent study tested whether weight loss in dieting women was more effective by making lunch rather than dinner (evening meal) the main meal of the day. Over the course of 12 weeks, dieters making lunch their main meal lost 4 lb (2 kg) more than the other group. Furthermore, the lunch eaters had better improvement in their insulin resistance (as measured by HOMA-IR)

From the abstract:

“Background: The association between the time of nutrient intake and health has been described in a few studies. To our knowledge, no study has evaluated the relation between high energy intakes at lunch compared with at dinner on weight loss in overweight and obese subjects.

Objective: We compared the effect of high energy intake at lunch with that at dinner on weight loss and cardiometabolic risk factors in women during a weight-loss program.Design: Overweight and obese women [n = 80; body mass index (BMI; in kg/m2): 27–35; age: 18–45 y] were asked to eat either a main meal at lunch (LM) or a main meal at dinner (DM) for 12 wk while in a weight-loss program.

Conclusions: The consumption of higher energy intake at lunch compared with at dinner may result in favorable changes in weight loss in overweight and obese women after a weight-loss program of 12 wk. The consumption may also offer clinical benefits to improve insulin resistance.”

Source: Beneficial effect of high energy intake at lunch rather than dinner on weight loss in healthy obese women in a weight-loss program: a randomized clinical trial

I don’t have the full text of the research report, so I don’t know what kind of diet the women were on. The researchers seem to be based in both Iran and Great Britain. I don’t know the nationality of the women participating. The metabolism of Iranians may be different from Brits.

Steve Parker, M.D.

 

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Is Excessive Fructose Consumption the Cause of Type 2 Diabetes?

Lumps of Diabetes

Cubes of Diabetes?

A Pharm.D (Dr of Pharmacology) and a pair of MD’s surveyed much of the available scientific literature—both animal and human studies—and concluded that fructose is a major culprit in the rise of type 2 diabetes and prediabetes. Fructose does its damage by increasing insulin resistance. ScienceDaily has the details.

Be aware that their conclusion is certainly not universally accepted. I just read “Pathogenesis of type 2 diabetes mellitus” at UpToDate.com and saw no mention of fructose. Under dietary factors, they mainly talked about obesity and how that increases insulin resistance, leading to elevated blood sugars, while the reverse happens with weight loss. I haven’t looked at all the research so I have no definite opinion yet on the fructose-diabetes theory; I’m skeptical.

Fructose is a type of simple sugar. Common dietary sources of fructose are fruits, table sugar (aka sucrose, a 50:50 combination of glucose and fructose molecules), and high-fructose corn syrup (which is usually 42 or 55% fructose).

Damaging effects, if any, of fructose in these fruits may be mitigated by the fiber

Damaging effects, if any, of fructose in these fruits may be mitigated by the fiber

A few quotes from ScienceDaily:

“At current levels, added-sugar consumption, and added-fructose consumption in particular, are fueling a worsening epidemic of type 2 diabetes,” said lead author James J. DiNicolantonio, PharmD, a cardiovascular research scientist at Saint Luke’s Mid America Heart Institute, Kansas City, MO. “Approximately 40% of U.S. adults already have some degree of insulin resistance with projections that nearly the same percentage will eventually develop frank diabetes.”

*   *   *

While fructose is found naturally in some whole foods like fruits and vegetables, consuming these foods poses no problem for human health. Indeed, consuming fruits and vegetables is likely protective against diabetes and broader cardiometabolic dysfunction, explained DiNicolantonio and colleagues. The authors propose that dietary guidelines should be modified to encourage individuals to replace processed foods, laden with added sugars and fructose, with whole foods like fruits and vegetables. “Most existing guidelines fall short of this mark at the potential cost of worsening rates of diabetes and related cardiovascular and other consequences,” they wrote.

If you’re eating a typical Western or American diet, you’ll reduce your fructose consumption by moving to the Mediterranean diet, the Advanced Mediterranean Diet, Low-Carb Mediterranean Diet, or the Paleobetic Diet.

RTWT.

Steve Parker, M.D.

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What Causes Type 2 Diabetes?

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Stop reading this sciencey post when you get bored

According to Roy Taylor, “type 2 diabetes is a potentially reversible metabolic state precipitated by the single cause of chronic excess intraorgan fat.” The organs accumulating fat are the liver and pancreas. He is certain “…that the disease process can be halted with restoration of normal carbohydrate and fat metabolism.” I read Taylor’s article published earlier this year in Diabetes Care.

[Do you remember that report in 2011 touting cure of T2 diabetes with a very low calorie diet? Taylor was the leader. The study involved only 11 patients, eating 600 calories a day for eight weeks.]

Dr. Taylor (M.D.) says that severe calorie restriction is similar to the effect of bariatric surgery in curing or controlling diabetes. Within a week of either intervention, liver fat content is greatly reduced, liver insulin sensitivity returns, and fasting blood sugar levels can return to normal. During the first eight weeks after intervention, pancreatic fat content falls, with associated steadily increasing rates of insulin secretion by the pancreas beta cells.

bariatric surgery, Steve Parker MD

Band Gastric Bypass Surgery (not the only type of gastric bypass): very successful at “curing” T2 diabetes if you survive the operation

Taylor’s ideas, by the way, dovetail with Roger Unger’s 2008 lipocentric theory of diabetes. Click for more ideas on the cause of T2 diabetes.

Here are some scattered points from Taylors article. He backs up most of them with references:

  • In T2 diabetes, improvement in fasting blood sugar reflects improved liver insulin sensitivity more than muscle insulin sensitivity.
  • The more fat accumulation in the liver, the less it is sensitive to insulin. If a T2 is treated with insulin, the insulin dose is positively linked to how much fat is in the liver.
  • In a T2 who starts insulin injections, liver fat stores tend to decrease. That’s because of suppression of the body’s own insulin delivery from the pancreas to the liver via the portal vein.
  • Whether obese or not, those with higher circulating insulin levels “…have markedly increased rates of hepatic de novo lipogenesis.” That means their livers are making fat. That fat (triglycerides or triacylglycerol) will be either burned in the liver for energy (oxidized), pushed into the blood stream for use elsewhere, or stored in the liver. Fatty acids are components of triglycerides. Excessive fatty acid intermediaries in liver cells—diglycerides and ceramide—are thought to interfere with insulin’s action, i.e., contribute to insulin resistance in the liver.
  • “Fasting plasma glucose concentration depends entirely on the fasting rate of hepatic [liver] glucose production and, hence, on its sensitivity to suppression by insulin.”
  • Physical activity, low-calorie diets, and thiazolidinediones reduce the pancreas’ insulin output and reduce liver fat levels.
  • Most T2 diabetics have above-average liver fat content. MRI scans are more accurate than ultrasound for finding it.
  • T2 diabetics have on average only half of the pancreas beta cell mass of non-diabetics. As the years pass, more beta cells are lost. Is the a way to preserve these insulin-producing cells, or to increase their numbers? “…it is conceivable that removal of adverse factors could result in restoration of normal beta cell number, even late in the disease.”
  • “Chronic exposure of [pancreatic] beta cells to triacylglycerol [triglycerides] or fatty acids…decreases beta cell capacity to respond to an acute increase in glucose levels.” In test tubes, fatty acids inhibit formation of new beta cells, an effect enhanced by increased glucose concentration.
  • There’s a fair amount of overlap in pancreas fat content comparing T2 diabetics and non-diabetics. It may be that people with T2 diabetes are somehow more susceptible to adverse effects of the fat via genetic and epigenetic factors.
  • “If a person has type 2 diabetes, there is more fat in the liver and pancreas than he or she an cope with.”
  • Here’s Dr. Taylor’s Twin Cycle Hypothesis of Etiology of Type 2 Diabetes: “The accumulation of fat in liver and secondarily in the pancreas will lead to self-reinforcing cycles that interact to bring about type 2 diabetes. Fatty liver leads to impaired fasting glucose metabolism and increases export of VLDL triacylglcerol [triglycerides], which increases fat delivery to all tissues, including the [pancreas] islets. The liver and pancreas cycles drive onward after diagnosis with steadily decreasing beta cell function. However, of note, observations of the reversal of type 2 diabetes confirm that if the primary influence of positive calorie balance is removed, the the processes are reversible.”
diabetic diet, etiology of type 2 diabetes, Roy Taylor, type 2 diabetes reversal

Figure 6 from the article: Dr. Taylor’s Twin Cycle Hypothesis of Etiology of Type 2 Diabetes

  • The caption with Figure 6 states: “During long-term intake of more calories than are expended each day, any excess carbohydrate must undergo de novo lipogenesis [creation of fat], which particularly promotes fat accumulation in the liver.”
  • “The extent of weight gloss required to reverse type 2 diabetes is much greater than conventionally advised.” We’re looking at around 15 kg (33 lb) or 20% of body weight, assuming the patient is obese to start.  “The initial major loss of body weight demands a substantial reduction in energy intake. After weight loss, steady weight is most effectively achieved by a combination of dietary restriction and physical activity.”

Dr. Taylor doesn’t specify how much calorie restriction he recommends, but reading between the lines, I think he likes his 600 cals/day for eight weeks program. That will have a have a high drop-out rate. I suspect a variety of existing ketogenic diets may be just as successful and more realistic, even if it takes more than eight weeks. I wonder how many of the 11 “cures” from the 2011 study have persisted.

Steve Parker, M.D.

Reference: Taylor, Roy. Type 2 diabetes: Etiology and reversibility. Diabetes Care, April 2013, vol. 36, no. 4, pp:1047-1055.

Update December 16, 2013:

Some wild and crazy guys tried this method at home. Click for results.

h/t commenter PhilT.

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Deteriorating Brain Function Linked to High Insulin Levels and Insulin Resistance: Here’s How You Fight Back

dementia, memory loss, Mediterranean diet, low-carb diet, glycemic index, dementia memory loss

Don’t wait to take action until it’s too late

Insulin resistance and high blood insulin levels promote age-related degeneration of the brain, leading to memory loss and dementia according to Robert Krikorian, Ph.D.  He’s a professor in the Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati Academic Health Center.  He has an article in a recent issue of Current Psychiatry – Online.

Proper insulin signaling in the brain is important for healthy functioning of our brains’ memory centers.  This signaling breaks down in the setting of insulin resistance and the associated high insulin levels.  Dr. K makes much of the fact that high insulin levels and insulin resistance are closely tied to obesity.  He writes that:

“Waist circumference of ≥100 cm (39 inches) is a sensitive, specific, and independent predictor of hyperinsulinemia for men and women and a stronger predictor than body mass index, waist-to-hip ratio, and other measures of body fat.”

Take-Home Points

Dr. Krikorian thinks that dietary approaches to the prevention of dementia are effective yet underutilized.  He mentions reduction of insulin levels by restricting calories or a ketogenic diet: they’ve been linked with improved memory in middle-aged and older adults.

Dr. Krikorian suggests the following measures to prevent dementia and memory loss:

  • eliminate high-glycemic foods like processed carbohydrates and sweets
  • replace high-glycemic foods with fruits and vegetables (the higher polyphenol intake may help by itself)
  • certain polyphenols, such as those found in berries, may be particularly helpful in improving brain metabolic function
  • keep your waist size under 39 inches, or aim for that if you’re overweight

I must mention that many, perhaps most, dementia experts are not as confident  as Dr. Krikorian that these dietary changes are effective.  I think they probably are, to a degree.

The Mediterranean diet is high in fruits and vegetables and relatively low-glycemic.  It’s usually mentioned by experts as the diet that may prevent dementia and slow its progression.

Read the full article.

I’ve written before about how blood sugars in the upper normal range are linked to brain degeneration.  Dr. Krikorian’s recommendations would tend to keep blood sugar levels in the lower end of the normal range.

Steve Parker, M.D.

PS: Speaking of dementia and ketogenic, have you ever heard of the Ketogenic Mediterranean Diet?  (Free condensed version here.)

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What Causes Type 2 Diabetes?

Prediabetes and type 2 diabetes are epidemics because of excessive consumption of refined sugars and starches, and lack of physical activity.  I can’t prove it; nevertheless that’s my impression after years of pondering the nutrition science literature.

I could be wrong.  I reserve the option to change my mind based on evidence as it becomes available.  That’s one of the great things about science.  Accurately identifying the cause of diabetes could provide strong clues about optimal prevention and treatment strategies.

Genetics undoubtedly plays a major role in diabetes, but the gene pool hasn’t changed much over the last several decades as type 2 diabetes rates have soared.

The problem in type 2 diabetes and prediabetes is that the body cannot handle ingested carbohydrates in the normal fashion. In a way, dietary carbohydrates (carbs) have become toxic instead of nourishing. This is a critical point, so let’s take time to understand it.

NORMAL DIGESTION AND CARBOHYDRATE HANDLING

The major components of food are fats, proteins, and carbohydrates. We digest food either to get energy, or to use individual components of food in growth, maintenance, or repair of our own body parts.

We need some sugar (also called glucose) in our bloodstream at all times to supply us with immediate energy. “Energy” refers not only to a sense of muscular strength and vitality, but also to fuel for our brain, heart, and other automatic systems. Our brains especially need a reliable supply of bloodstream glucose.

In a normal, healthy state, our blood contains very little sugar—about a teaspoon (5 ml) of glucose. (We have about one and a third gallons (5 liters) of blood circulating. A normal blood sugar of 100 mg/dl (5.56 mmol/l) equates to about a teaspoon of glucose in the bloodstream.)

Our bodies have elaborate natural mechanisms for keeping blood sugar normal. They work continuously, a combination of removing and adding sugar from the bloodstream to keep it in a healthy range (70 to 140 mg/dl, or 3.9 to 7.8 mmol/l). These homeostatic mechanisms are out of balance in people with diabetes and prediabetes.

By the way, glucose in the bloodstream is commonly referred to as “blood sugar,” even though there are many other types of sugar other than glucose. In the U.S., blood sugar is measured in units of milligrams per deciliter (mg/dl), but other places measure in millimoles per liter (mmol/l).

When blood sugar levels start to rise in response to food, the pancreas gland—its beta cells, specifically—secrete insulin into the bloodstream to keep sugar levels from rising too high. The insulin drives the excess sugar out of the blood, into our tissues. Once inside the tissues’ cells, the glucose will be used as an immediate energy source or stored for later use. Excessive sugar is stored either as body fat or as glycogen in liver and muscle.

When we digest fats, we see very little direct effect on blood sugar levels. That’s because fat contains almost no carbohydrates. In fact, when fats are eaten with high-carb foods, they tend to slow the rise and peak in blood sugar you would see if you had eaten the carbs alone.

Ingested protein can and does raise blood sugar, usually to a mild degree. As proteins are digested, our bodies can make sugar (glucose) out of the breakdown products. The healthy pancreas releases some insulin to keep the blood sugar from going too high.

In contrast to fats and proteins, carbohydrates in food cause significant—often dramatic—rises in blood sugar. Our pancreas, in turn, secretes higher amounts of insulin to prevent excessive elevation of blood glucose. Carbohydrates are easily digested and converted into blood sugar. The exception is fiber, which is indigestible and passes through us unchanged.

During the course of a day, the pancreas of a healthy adult produces an average of 40 to 60 units of insulin. Half of that insulin is secreted in response to meals, the other half is steady state or “basal” insulin. The exact amount of insulin depends quite heavily on the amount and timing of carbohydrates eaten. Dietary protein has much less influence. A pancreas in a healthy person eating a very-low-carb diet will release substantially less than 50 units of insulin a day.

To summarize thus far: dietary carbs are the major source of blood sugar for most people eating “normally.” Carbs are, in turn, the main cause for insulin release by the pancreas, to keep blood sugar levels in a safe, healthy range.

Hang on, because we’re almost done with the basic science!

You deserve a break

CARBOHYDRATE  HANDLING  IN  DIABETES  &  PREDIABETES

Type 2 diabetics and prediabetics absorb carbohydrates and break them down into glucose just fine. Problem is, they can’t clear the glucose out of the bloodstream normally. So blood sugar levels are often in the elevated, poisonous range, leading to many of the complications of diabetes.

Remember that insulin’s primary function is to drive blood glucose out of the bloodstream, into our tissues, for use as immediate energy or stored energy (as fat or glycogen).

In diabetes and prediabetes, this function of insulin is impaired.

The tissues have lost some of their sensitivity to insulin’s action. This critical concept is called insulin resistance. Insulin still has some effect on the tissues, but not as much as it should. Different diabetics have different degrees of insulin resistance, and you can’t tell by just looking.  (There are several other hormones involved in regulation of blood sugar.)

Did you know that people who work at garbage dumps, sewage treatment plants, and cattle feedlots get used to the noxious fumes after a while? They aren’t bothered by them as much as they were at first. Their noses are less sensitive to the fumes. You could call it fume resistance. In the same fashion, cells exposed to high insulin levels over time become resistant to insulin.

Insulin resistance occurs in most cases of type 2 diabetes and prediabetes. So what causes the insulin resistance? It’s debatable. In many cases it’s related to overweight, physical inactivity, and genetics. A high-carbohydrate diet may contribute. A few cases are caused by drugs. Some cases are a mystery.

To overcome the body tissue’s resistance to insulin’s effect, the pancreas beta cells pump even more insulin into the bloodstream, a condition called hyperinsulinemia. Some scientists believe high insulin levels alone cause some of the damage associated with diabetes. Whereas a healthy person without diabetes needs about 50 units of insulin a day, an obese non-diabetic needs about twice that to keep blood sugars in check. Eventually, in those who develop diabetes or prediabetes, the pancreas can’t keep up with the demand for more insulin to overcome insulin resistance. The pancreas beta cells get exhausted and start to “burn out.” That’s when blood sugars start to rise and diabetes and prediabetes are easily diagnosed. So, insulin resistance and high insulin production have been going on for years before diagnosis. By the time of diagnosis, 50% of beta cell function is lost.

Steve Parker, M.D.

EXTRA  CREDIT  FOR  INQUISITIVE  MINDS

You’ve learned that insulin’s main action is to lower blood sugar by transporting it into the cells of various tissues. But that’s not all insulin does. It also 1) impairs breakdown of glycogen into glucose, 2) stimulates glycogen formation, 3) inhibits formation of new glucose molecules by the body, 4) promotes storage of triglycerides in fat cells (i.e., lipogenesis, fat accumulation), 5) promotes formation of fatty acids (triglyceride building blocks) by the liver, 6) inhibits breakdown of stored triglycerides, and 7) supports body protein production.

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In T2 Diabetes, Which Comes First: High Insulin Levels or Insulin Resistance?

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I couldn’t find a decent picture of a liver or pancreas, so this will have to do….

Excessive insulin output by the pancreas (hyperinsulinemia) is the underlying cause of type 2 diabetes, according to a hypothesis from Walter Pories, M.D., and G. Lynis Dohm, Ph.D.  The cause of the hyperinsulinemia is a yet-to-be-identified “diabetogenic signal” to the pancreas from the gastrointestinal tract.

This is pretty sciencey, so you’re excused if you stop reading now.  You probably should.

They base their hypothesis on the well-known cure or remission of many cases of type 2 diabetes quite soon after roux-en-y gastric bypass surgery (RYGB) done for weight loss.  (Recent data indicate that six years after surgery, the diabetes has recurred in about a third of cases.)  Elevated fasting insulin levels return to normal within a week of RYGB and remain normal for at least three months.  Also soon after surgery, the pancreas recovers the ability to respond to a meal with an appropriate insulin spike.  Remission or cure of type 2 diabetes after RYGB is independent of changes in weight, insulin sensitivity, or free fatty acids.

Bariatric surgery provides us with a “natural” experiment into the mechanisms behind type 2 diabetes.

The primary anatomic change with RYGB is exclusion of food from a portion of the gastrointestinal tract, which must send a signal to the pancreas resulting in lower insulin levels, according to Pories and Dohm.

Why would fasting blood sugar levels fall so soon after RYGB?  To understand, you have to know that fasting glucose levels primarily reflect glucose production by the liver (gluconeogenesis).  It’s regulated by insulin and other hormones.  Insulin generally suppresses gluconeogenesis.  The lower insulin levels after surgery should raise fasting glucose levels then, don’t you think?  But that’s not the case.

Pories and Dohm surmise that correction of hyperinsulinemia after surgery leads to fewer glucose building blocks (pyruvate, alanine, and especially lactate) delivered from muscles to the liver for glucose production.  Their explanation involves an upregulated Cori cycle, etc.  It’s pretty boring and difficult to follow unless you’re a biochemist.

The theory we’re talking about is contrary to the leading theory that insulin resistance causes hyperinsulinemia.  Our guys are suggesting it’s the other way around: hyperinsulinemia causes insulin resistance.  It’s a chicken or the egg sort of thing.

If they’re right, Pories and Dohm say we need to rethink the idea of treating type 2 diabetes with insulin except in the very late stages when there may be no alternative.  (I would add my concern about using insulin secretagogues (e.g., sulfonylureas) in that case also.)  If high insulin levels are the culprit, you don’t want to add to them.

We’d also need to figure out what is the source of the “diabetogenic signal” from the gastrointestinal tract to the pancreas that causes hyperinsulinemia.  A number of stomach and intestinal hormones can affect insulin production by the pancreas; these were not mentioned specifically by Pories and Dohm.  Examples are GIP and GLP-1 (glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1).

Keep these ideas in mind when you come across someone who’s cocksure that they know the cause of type 2 diabetes.

Steve Parker, M.D.

Reference:  Pories, Walter and Dohm, G. Lynis.  Diabetes: Have we got it all wrong?  Hyperinsulinism as the culprit: surgery provides the evidence.  Diabetes Care, 2012, vol. 35, p. 2438-2442.

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What Causes Type 2 Diabetes?

“Beats me. I teach math!”

I have no simple answer for you, unfortunately.

You can lower your risk of type 2 diabetes significantly by avoiding overweight and obesity, by exercising regularly, and by choosing the right parents.  These provide clues as to the causes of diabetes.  The Mediterranean diet also prevents diabetes.

UpToDate.com offers a deceptively simple answer:

Type 2 diabetes mellitus is caused by a combination of varying degrees of insulin resistance and relative insulin deficiency. [Insulin is the pancreas hormone that lowers blood sugar.] Its occurrence most likely represents a complex interaction among many genes and environmental factors, which are different among different populations and individuals.

So, what causes the insulin resistance and relative insulin deficiency?

Understanding the pathogenesis [cause] of type 2 diabetes is complicated by several factors. Patients present with a combination of varying degrees of insulin resistance and relative insulin deficiency, and it is likely that both contribute to type 2 diabetes. Furthermore, each of the clinical features can arise through genetic or environmental influences, making it difficult to determine the exact cause in an individual patient. Moreover, hyperglycemia itself can impair pancreatic beta cell function and exacerbate insulin resistance, leading to a vicious cycle of hyperglycemia causing a worsening metabolic state.

The UpToDate article then drones on for a several thousand words discussing mouse studies, various genes, free fatty acids, adiponectin, leptin, amylin, insulin secretion, insulin resistance, impaired insulin processing, insulin action, body fat distribution, inflammation, various inflammatory markers, low birth weight, high birth rate, prematurity, etc.  More excerpts:

Increased free fatty acid levels, inflammatory cytokines from fat, and oxidative factors, have all been implicated in the pathogenesis of metabolic syndrome, type 2 diabetes, and their cardiovascular complications.

Insulin resistance may, at least in part, be related to substances secreted by adipocytes [fat cells] (“adipokines” including leptin adiponectin, tumor necrosis factor alpha, and resistin).

Type 2 diabetes most likely represents a complex interaction among many genes and environmental factors.

That’s the simplest answer I can give now.

Steve Parker, M.D.

Reference: “The Pathogensis of Type 2 Diabetes Mellitus”  by David K McCulloch, MD, and R Paul Robertson, MD, at UpToDate.com, updated June 2012, and accessed November 19, 2012.

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