A brand new type of insulin-producing cell has been discovered hiding in the pancreas.

A missing piece of the diabetes puzzle.


Researchers have found a brand new type of insulin-producing cell hiding in plain sight within the pancreas, and they offer new hope for better understanding – and one day even treating – type 1 diabetes.

Type 1 diabetes occurs when a person’s own immune system kills off most of their insulin-producing beta cells. And seeing as insulin is the hormone that regulates our blood sugar, type 1 diabetics are left reliant on injecting themselves with insulin regularly.

 While the condition can usually be managed effectively, in order to properly treat it, researchers would need to find a way to regenerate a patient’s beta cells and prevent them from being attacked in future – something we’re getting better at, but ultimately has eluded scientists so far.

The discovery of these previously unnoticed cells in the pancreas – which the team are calling ‘virgin beta cells‘ – could offer a new route for regrowing healthy, mature beta cells – and also provides insight into the basic mechanisms behind the disease.

“We’ve seen phenomenal advances in the management of diabetes, but we cannot cure it,” said lead researcher Mark Huising from the University of California, Davis.

“If you want to cure the disease, you have to understand how it works in the normal situation.”

To get a better insight into exactly what happens in type 1 diabetes, the researchers studied both mice and human tissue.

Huising and his team were looking at regions inside the pancreas known as the islets of Langerhans, which in healthy humans and mice are the regions that contain the beta cells that detect blood sugar levels around the body and produce insulin in response.

 Researchers also know that the islets contain cells called alpha cells, which produce glucagon, a hormone that raises blood sugar. These alpha cells, combined with the blood sugar-lowering beta cells, are how the body regulates blood sugar levels.

But in patients with type 1 diabetes, two things go wrong: the beta cells are killed off by the body’s own immune system, and then they fail to regenerate.

In order to treat the disease, we need to find a way to overcome both of those problems.

For decades, scientists have been trying to do this, and they had long assumed that there was one main way for beta cells to be produced – through other adult beta cells dividing.

But after using new microscope techniques to study islet tissue in the lab, Huising and his team found a new type of cell scattered around the edges of the islets that no one had noticed before – and they looked a lot like immature beta cells, suggesting that maybe there was actually another way beta cells were being made.

Further study revealed that these new virgin beta cells could make insulin, but they didn’t have the receptors to detect glucose, so couldn’t function as mature beta cells.

But that wasn’t all the researchers found. They also observed some mature beta cells in the islets transitioning into alpha cells – representing a completely unexpected alpha cell generation pathway.

“There’s much more plasticity in the system than was thought,” said Huising.

It’s still very early days, and these new cells now need to be confirmed in live humans and animals – not just tissue in the lab. But the fact that we now have evidence that they exist opens up a whole avenue of research on type 1 diabetes and potential treatments.

According to Huising, there are three main reasons to get excited about the result: firstly, it represents a new beta cell population in both humans and mice that we had no idea about before, and secondly, it also provides a potential new source of beta cells that could be used to treat diabetics.

“Finally, understanding how these cells mature into functioning beta cells could help in developing stem cell therapies for diabetes,” a press release explains.

The research could also have benefits for type 2 diabetes, which occurs when beta cells become inactive and stop releasing or secreting insulin.

Source: Cell Metabolism.

Bionic pancreas device shows benefits in type 1 diabetes patients

An experimental three-part wearable device to manage glucose levels outperformed standard monitoring and insulin pump management regimes in adults and adolescents with type 1 diabetes.

This “bionic pancreas,” which consist of a small subcutaneous glucose sensor, automated insulin and glucagon pumps, and a wirelessly connected iPhone with a monitoring app, can correct for blood plasma glucose levels that are too high or too low.

The device kept blood sugar lower and prevented fluctuations better than normal monitoring via stick tests and manual pumps.

“A cure is always the end goal,” said lead developer Dr. Ed Damiano, a biomedical engineer at Boston University in Massachusetts, US who has a son with type 1 diabetes.

“As that goal remains elusive, a truly automated technology, which can consistently and relentlessly keep people healthy and safe from harm of hypoglycemia, would lift an enormous emotional and practical burden from the shoulders of people with type 1 diabetes, including my child and so many others.”

The study included a group of 20 adults (age ≥21) and 32 young people aged 12-21 with at least a 1-year history of type 1 diabetes who were also using insulin-pump therapy. [NEJM 2014; doi:10.1056/NEJMoa1314474]

Patients’ blood plasma glucose levels were closely monitored in person and remotely over two 5-day periods of bionic pancreas intervention and self-management with their own insulin pumps. Daily activities, including food intake and exercise, were unrestricted and patients were encouraged to behave as normal.

Among the adults, there were 37 percent fewer instances of hypoglycemia that required intervention during the bionic pancreas period (43 cases) compared with the control period (68 cases, p=0.15).

Among the adolescents, the instances of hypoglycemia more than halved when patients used the bionic pancreas, with 97 cases compared with 210 cases during the control period (p=0.72).

Mean glucose levels in both groups improved significantly overall and remained more consistent when monitored and controlled by the bionic pancreas compared with the control period (133±13 vs 159±30 mg per dL, p<0.001 in adults; 142±12 vs 158±27 mg per dL, p=0.004 in adolescents). This improved outcome was particularly important through the night, when patients, especially younger patients, are in danger of becoming hypoglycemic.

The most common adverse event associated with bionic pancreas use was nausea and vomiting. Patients using the bionic pancreas still had to perform stick tests to make sure the monitor was accurate.

The researchers noted that the device can overcorrect for glycemic control in patients who are already poorly controlled, although the repercussions of this require more study. The bionic device also requires wireless connectivity but this may be solved in future iterations with a single-unit device.

However, the researchers reported the current prototype was already a more seamless device for type 1 diabetes patients, for whom constant monitoring and manual adjustment of plasma blood glucose can be a heavy burden.

“The performance of our system in both adults and adolescents exceeded our expectations under very challenging real-world conditions,” Damiano said.

Today is World Diabetes Day


Let today be the beginning of the end of your diabetes. Today being the World Diabetes Day, there is no better a day to take a new step for the awareness of the lifestyle disease, Diabetes. Every year, World Diabetes Day is co-ordinated by the International Diabetes Federation (IDF) with a particular theme; between 2009 and 2013 the theme has been ‘education and prevention’.

The Discovery of Insulin.

Before the discovery of insulin, diabetes was a feared disease that most certainly led to death. Doctors knew that sugar worsened the condition of diabetic patients and that the most effective treatment was to put the patients on very strict diets where sugar intake was kept to a minimum. At best, this treatment could buy patients a few extra years, but it never saved them. In some cases, the harsh diets even caused patients to die of starvation.

pancreasDuring the nineteenth century, observations of patients who died of diabetes often showed that the pancreas was damaged. In 1869, a German medical student, Paul Langerhans, found that within the pancreatic tissue that produces digestive juices there were clusters of cells whose function was unknown. Some of these cells were eventually shown to be the insulin-producing beta cells. Later, in honor of the person who discovered them, the cell clusters were named the islets of Langerhans.

In 1889 in Germany, physiologist Oskar Minkowski and physician Joseph von Mering, showed that if the pancreas was removed from a dog, the animal got diabetes. But if the duct through which the pancreatic juices flow to the intestine was ligated – surgically tied off so the juices couldn’t reach the intestine – the dog developed minor digestive problems but no diabetes. So it seemed that the pancreas must have at least two functions:

  • To produce digestive juices
  • To produce a substance that regulates the sugar glucose

This hypothetical internal secretion was the key. If a substance could actually be isolated, the mystery of diabetes would be solved. Progress, however, was slow.

Banting’s Idea

In October 1920 in Toronto, Canada, Dr. Frederick Banting, an unknown surgeon with a bachelor’s degree in medicine, had the idea that the pancreatic digestive juices could be harmful to the secretion of the pancreas produced by the islets of Langerhans.

He therefore wanted to ligate the pancreatic ducts in order to stop the flow of nourishment to the pancreas. This would cause the pancreas to degenerate, making it shrink and lose its ability to secrete the digestive juices. The cells thought to produce an antidiabetic secretion could then be extracted from the pancreas without being harmed.

Early in 1921, Banting took his idea to Professor John Macleod at the University of Toronto, who was a leading figure in the study of diabetes in Canada. Macleod didn’t think much of Banting’s theories. Despite this, Banting managed to convince him that his idea was worth trying. Macleod gave Banting a laboratory with a minimum of equipment and ten dogs. Banting also got an assistant, a medical student by the name of Charles Best. The experiment was set to start in the summer of 1921.

Banting and Best with a diabetic dog
Banting, right, and Best, left, with one of the diabetic dogs used in experiments with insulin.
Credits: University of Toronto Archives

The Experiment Begins

Banting and Best began their experiments by removing the pancreas from a dog. This resulted in the following:

  • It’s blood sugar rose.
  • It became thirsty, drank lots of water, and urinated more often.
  • It became weaker and weaker.

The dog had developed diabetes.

Experimenting on another dog, Banting and Best surgically ligated the pancreas, stopping the flow of nourishment, so that the pancreas degenerated.

After a while, they removed the pancreas, sliced it up, and froze the pieces in a mixture of water and salts. When the pieces were half frozen, they were ground up and filtered. The isolated substance was named “isletin.”

The extract was injected into the diabetic dog. Its blood glucose level dropped, and it seemed healthier and stronger. By giving the diabetic dog a few injections a day, Banting and Best could keep it healthy and free of symptoms.

Banting and Best showed their result to Macleod, who was impressed, but he wanted more tests to prove that their pancreatic extract really worked.

Banting and Best's laboratory Banting’s and Best’s laboratory, where insulin was discovered. 
Credits: University of Toronto Archives

Extended Tests

For the increased testing, Banting and Best realized that they required a larger supply of organs than their dogs could provide, and they started using pancreases from cattle. With this new source, they managed to produce enough extract to keep several diabetic dogs alive.

A dog and a cowThe new results convinced Macleod that they were onto something big. He gave them more funds and moved them to a better laboratory with proper working conditions. He also suggested they should call their extract “insulin.” Now, the work proceeded rapidly.

In late 1921, a third person, biochemist Bertram Collip, joined the team. Collip was given the task of trying to purify the insulin so that it would be clean enough for testing on humans.

During the intensified testing, the team also realized that the process of shrinking the pancreases had been unnecessary. Using whole fresh pancreases from adult animals worked just as well.

Testing on Humans

The team was eager to start testing on humans. But on whom should they test? Banting and Best began by injecting themselves with the extract. They felt weak and dizzy, but they were not harmed.

Collip continued his work to purify the insulin. He also experimented with trying to find the correct dosage. He learned how to diminish the effect of an insulin overdose with glucose in different forms. He discovered that the glucose should be as pure as possible. Orange juice and honey are good examples of foods rich in glucose.

A human and honeyIn January 1922 in Toronto, Canada, a 14-year-old boy, Leonard Thompson, was chosen as the first person with diabetes to receive insulin. The test was a success. Leonard, who before the insulin shots was near death, rapidly regained his strength and appetite. The team now expanded their testing to other volunteer diabetics, who reacted just as positively as Leonard to the insulin extract.

The Nobel Prize

The news of the successful treatment of diabetes with insulin rapidly spread outside of Toronto, and in 1923 the Nobel Committee decided to award Banting and Macleod the Nobel Prize in Physiology or Medicine.

The decision of the Nobel Committee made Banting furious. He felt that the prize should have been shared between him and Best, and not between him and Macleod. To give credit to Best, Banting decided to share his cash award with him. Macleod, in turn, shared his cash award with Collip.

The Nobel Prize in Physiology or Medicine for insulin has been much debated. It has been questioned why Macleod received the prize instead of Best and Collip. However, Macleod played a central role in the discovery of insulin. It was he who supported the project from the beginning. He supervised the work and it is also most likely that Macleod’s contacts in the scientific world helped the team in getting a speedy recognition of their discovery.

Frederick G. Banting and John Macleod were awarded the Nobel Prize in Physiology or Medicine in 1923 “for the discovery of insulin.”

The Legacy of Insulin

Banting, Macleod, and the rest of the team patented their insulin extract but gave away all their rights to the University of Toronto, which would later use the income from insulin to fund new research.

Very soon after the discovery of insulin, the medical firm Eli Lilly started large-scale production of the extract. As soon as 1923, the firm was producing enough insulin to supply the entire North American continent.

Although insulin doesn’t cure diabetes, it’s one of the biggest discoveries in medicine. When it came, it was like a miracle. People with severe diabetes and only days left to live were saved. And as long as they kept getting their insulin, they could live an almost normal life.

This Is What Happens to Your Body When You Exercise

Story at-a-glance

  • One of the key health benefits of exercise is that it helps normalize your glucose, insulin, and leptin levels by optimizing insulin/leptin receptor sensitivity
  • Exercise-improved insulin/leptin receptor sensitivity is perhaps the most important factor for optimizing your overall health and preventing chronic disease
  • Exercise also encourages your brain to work at optimum capacity by causing your nerve cells to multiply, strengthening their interconnections, and protecting them from damage
  • Unexpected side effects of exercise include improved sexual function, changes in gene expression, clearer skin, and improved mood and sleep
  • Research shows that the “secret” to increased productivity and happiness on any given day is a long-term investment in regular exercise, and a little each day appears to go further than a lot once or twice a week.

One of the key health benefits of exercise is that it helps normalize your glucose, insulin, and leptin levels by optimizing insulin/leptin receptor sensitivity. This is perhaps the most important factor for optimizing your overall health and preventing chronic disease.


But exercise affects your body in countless other ways as well—both directly and indirectly. Here, however, even the most unexpected side effects are almost universally beneficial. For example, as illustrated in the featured article,1 side effects of exercise include but are not limited to:

What Happens in Your Body When You Exercise?

The featured article in Huffington Post2 highlights a number of biological effects that occur, from head to toe, when you exercise. This includes changes in your:

    • Muscles, which use glucose and ATP for contraction and movement. To create more ATP, your body needs extra oxygen, so breathing increases and your heart starts pumping more blood to your muscles.

Without sufficient oxygen, lactic acid will form instead. Tiny tears in your muscles make them grow bigger and stronger as they heal.

    • Lungs. As your muscles call for more oxygen (as much as 15 times more oxygen than when you’re at rest), your breathing rate increases. Once the muscles surrounding your lungs cannot move any faster, you’ve reached what’s called your VO2 max—your maximum capacity of oxygen use. The higher your VO2 max, the fitter you are.
    • Heart. As mentioned, your heart rate increases with physical activity to supply more oxygenated blood to your muscles. The fitter you are, the more efficiently your heart can do this, allowing you to work out longer and harder. As a side effect, this increased efficiency will also reduce your resting heart rate. Your blood pressure will also decrease as a result of new blood vessels forming.
    • Brain. The increased blood flow also benefits your brain, allowing it to almost immediately function better. As a result, you tend to feel more focused after a workout. Furthermore, exercising regularly will promote the growth of new brain cells. In your hippocampus, these new brain cells help boost memory and learning. As stated in the featured article:

“When you work out regularly, your brain gets used to this frequent surge of blood and adapts by turning certain genes on or off. Many of these changes boost brain cell function and protect from diseases such as Alzheimer’s, Parkinson’s or even stroke, and ward off age-related decline.”

A number of neurotransmitters are also triggered, such as endorphins, serotonin, dopamine, glutamate, and GABA. Some of these are well-known for their role in mood control. Exercise, in fact, is one of the most effective prevention and treatment strategies for depression.

    • Joints and bones, as exercise can place as much as five or six times more than your body weight on them. Peak bone mass is achieved in adulthood and then begins a slow decline, but exercise can help you to maintain healthy bone mass as you get older.

Weight-bearing exercise is actually one of the most effective remedies against osteoporosis, as your bones are very porous and soft, and as you get older your bones can easily become less dense and hence, more brittle — especially if you are inactive.

Your Brain Health Is Directly Related to Exercise

A related article published by Lifehacker.com3 focuses exclusively on brain-related changes that occur when you exercise. While I just mentioned that neurotransmitters, chemical messengers in your brain, such as mood-boosting serotonin, are released during a bout of exercise, that doesn’t account for all the benefits your brain reaps.

“If you start exercising, your brain recognizes this as a moment of stress. As your heart pressure increases, the brain thinks you are either fighting the enemy or fleeing from it. To protect yourself and your brain from stress, you release a protein called BDNF (Brain-Derived Neurotrophic Factor). This BDNF has a protective and also reparative element to your memory neurons and acts as a reset switch. That’s why we often feel so at ease and like things are clear after exercising,” Leo Widrich writes.

Simultaneously, your brain releases endorphins, another stress-related chemical. According to researcher MK McGovern, the endorphins minimize the physical pain and discomfort associated with exercise. They’re also responsible for the feeling of euphoria that many people report when exercising regularly.

Scientists have been linking the benefits of physical exercise to brain health for many years, but recent research4, 5 has made it clear that the two aren’t just simply related; rather, it is THE relationship. The evidence shows that physical exercise helps you build a brain that not only resists shrinkage, but increases cognitive abilities. Exercise encourages your brain to work at optimum capacity by causing your nerve cells to multiply, strengthening their interconnections, and protecting them from damage. There are multiple mechanisms at play here, but some are becoming more well-understood than others.

The rejuvenating role of BDNF is one of them. BDNF activates brain stem cells to convert into new neurons. It also triggers numerous other chemicals that promote neural health. Further, exercise provides protective effects to your brain through:

  • The production of nerve-protecting compounds
  • Improved development and survival of neurons
  • Decreased risk of heart and blood vessel diseases
  • Altering the way damaging proteins reside inside your brain, which appears to slow the development of Alzheimer’s disease

Both Fasting and Exercise Trigger Brain Rejuvenation

Growing evidence indicates that both fasting and exercise trigger genes and growth factors that recycle and rejuvenate your brain and muscle tissues. These growth factors include BDNF, as just mentioned, and muscle regulatory factors, or MRFs.

These growth factors signal brain stem cells and muscle satellite cells to convert into new neurons and new muscle cells respectively. Interestingly enough, BDNF also expresses itself in the neuro-muscular system where it protects neuro-motors from degradation. (The neuromotor is the most critical element in your muscle. Without the neuromotor, your muscle is like an engine without ignition. Neuro-motor degradation is part of the process that explains age-related muscle atrophy.)

So BDNF is actively involved in both your muscles and your brain, and this cross-connection, if you will, appears to be a major part of the explanation for why a physical workout can have such a beneficial impact on your brain tissue. It, quite literally, helps prevent, and even reverse, brain decay as much as it prevents and reverses age-related muscle decay.

This also helps explain why exercise while fasting can help keep your brain, neuro-motors, and muscle fibers biologically young. For more information on how to incorporate intermittent fasting into your exercise routine for maximum benefits, please see this previous article. Sugar suppresses BDNF, which also helps explain why a low-sugar diet in combination with regular exercise is so effective for protecting memory and staving off depression.

This Is Your Brain on Exercise

BDNF and endorphins are two of the factors triggered by exercise that help boost your mood, make you feel good, and sharpen your cognition. As mentioned by Lifehacker, they’re similar to morphine and heroin in their action and addictiveness—but without any of the harmful side effects. Quite the contrary! So, how much do you have to exercise in order to maintain a sunnier disposition and better memory long-term?

According to a 2012 study6 published in the journal Neuroscience, the “secret” to increased productivity and happiness on any given day is a long-term investment in regular exercise. And a little each day appears to go further than a lot once or twice a week.

“Those who had exercised during the preceding month but not on the day of testing generally did better on the memory test than those who had been sedentary, but did not perform nearly as well as those who had worked out that morning,” the authors note.

The reasons for this can perhaps be best perceived visually. Take a look at these images, showing the dramatic increase in brain activity after a 20 minute walk, compared to sitting quietly for the same amount of time.

There is a minor caveat, however. The researchers also discovered that exercise does not affect the brains of all people in exactly the same way. Some people, about 30 percent of people of European Caucasian descent, have a BDNF gene variant that hinders post-exercise BDNF production. The people with this BDNF variant did not improve their memory scores, even when exercising regularly, as significantly as those without this variant. Still, the research clearly suggests that—with individual variations as to the degree—regular exercise will cumulatively enhance your memory and other brain functions.

You Don’t Need to Train Like an Athlete to Reap the Benefits of Exercise

If you are sedentary there is hope for you. In her book, The First 20 Minutes: Surprising Science Reveals How We Can Exercise Better, Train Smarter, Live Longer, New York Times bestselling author Gretchen Reynolds addresses the issue of exercise as a way to improve longevity and happiness as well.7

“The first 20 minutes of moving around, if someone has been really sedentary, provide most of the health benefits. You get prolonged life, reduced disease risk – all of those things come in in the first 20 minutes of being active,” she said in a 2012 interview8.

Two-thirds of Americans get no exercise at all. If one of those people gets up and moves around for 20 minutes, they are going to get a huge number of health benefits, and everything beyond that 20 minutes is, to some degree, gravy. That doesn’t mean I’m suggesting people should not exercise more if they want to. You can always do more. But the science shows that if you just do anything, even stand in place 20 minutes, you will be healthier.”

Similarly, research9 published in 2008 found that those who exercised on work days experienced significantly improved mood on days that they exercised. Interestingly, while their mood remained fairly constant even on non-exercise work days, their sense of inner calm deteriorated on those days. According to the authors:10

“Critically, workers performed significantly better on exercise days and across all three areas we measured, known as mental-interpersonal, output and time demands.”

Key findings included:

  • 72 percent had improved time management on exercise days compared to non-exercise days
  • 79 percent reported improved mental and interpersonal performance in exercise days
  • 74 percent said they managed their workload better
  • Those who exercised regularly also reported feeling more than 40 percent more “motivated to work” and scored more than 20 percent higher for concentration and finishing work on time

But remember, it is FAR better to exercise regularly. I believe it is also vital to engage in regular movement if you have a sitting job like most of us do, including me. I typically sit in front of a computer for more than 12 hours a day. What I have recently appreciated is that standing up every 10 minutes (with the help of a timer) and engaging in some type of brief exercise, is an enormously powerful habit to minimize the damage of long term sitting.

Aim for a Well-Rounded Fitness Program

Ideally, to truly optimize your health, you’ll want to strive for a varied and well-rounded fitness program that incorporates a wide variety of exercises. As a general rule, as soon as an exercise becomes easy to complete, you need to increase the intensity and/or try another exercise to keep challenging your body.

Additionally, more recent research has really opened my eyes to the importance of non-exercise movement. Truly, the key to health is to remain as active as you can, all day long, but that doesn’t mean you train like an athlete for hours a day. It simply means, whenever you have a chance to move and stretch your body in the course of going about your day—do it!

And the more frequently, the better. Everything from standing up, to reaching for an item on a tall shelf, to weeding in your garden and walking from one room to another, and even doing dishes count. In short, it’s physical movement, period, that promotes health benefits by the interaction your body gets with gravity. To learn more about this important aspect of health, please see this previous article. That said, I recommend incorporating the following types of exercise into your program:

    • Interval (Anaerobic) Training: This is when you alternate short bursts of high-intensity exercise with gentle recovery periods.
    • Strength Training: Rounding out your exercise program with a 1-set strength training routine will ensure that you’re really optimizing the possible health benefits of a regular exercise program. You can also “up” the intensity by slowing it down. For more information about using super slow weight training as a form of high intensity interval exercise, please see my interview with Dr. Doug McGuff.
    • Stand Up Every 10 Minutes. This is not intuitively obvious, but emerging evidence clearly shows that even highly fit people who exceed the expert exercise recommendations are headed for premature death if they sit for long periods of time. My interview with NASA scientist Dr. Joan Vernikos goes into great detail why this is so, and what you can do about it. Personally, I usually set my timer for 10 minutes while sitting, and then stand up and do one legged squats, jump squats or lunges when the timer goes off. The key is that you need to be moving all day long, even in non-exercise activities.
    • Core Exercises: Your body has 29 core muscles located mostly in your back, abdomen and pelvis. This group of muscles provides the foundation for movement throughout your entire body, and strengthening them can help protect and support your back, make your spine and body less prone to injury and help you gain greater balance and stability.

Foundation Training, created by Dr. Eric Goodman, is an integral first step of a larger program he calls “Modern Moveology,” which consists of a catalog of exercises. Postural exercises such as those taught in Foundation Training are critical not just for properly supporting your frame during daily activities, they also retrain your body so you can safely perform high-intensity exercises without risking injury.

Exercise programs like Pilates and yoga are also great for strengthening your core muscles, as are specific exercises you can learn from a personal trainer.

  • Stretching: My favorite type of stretching is active isolated stretches developed by Aaron Mattes. With Active Isolated Stretching, you hold each stretch for only two seconds, which works with your body’s natural physiological makeup to improve circulation and increase the elasticity of muscle joints. This technique also allows your body to repair itself and prepare for daily activity. You can also use devices like the Power Plate to help you stretch.

Breast-feeding not linked to type 1 diabetes in high-risk population.

An analysis of data from children enrolled in the MIDIA study indicates no association between breast-feeding and the risk for developing type 1 diabetes or autoislet autoimmunity.

Multivariate analysis of the data showed that the only variable linked to type 1 diabetes or autoislet immunity was having a first-degree relative with type 1 diabetes (P<.001). After adjustment for this factor, researchers found no significant association between development of type 1 diabetes and full breast-feeding (OR=1.28; P=.66) or any breast-feeding (OR=1.01; P=.99). Similar results were noted for full breast-feeding (OR=1.3; P=.41) or any breast-feeding (OR=1.25; P=.51) and islet autoimmunity.

For the study, the researchers assessed data from the MIDIA prospective cohort study, which included children with the high-risk human leukocyte antigen (HLA) genotype. Of 48,000 children genotyped, 1,047 had the high-risk HLA genotype. At 3, 6, 9 and 12 months of age, parents filled out questionnaires and the researchers obtained blood samples from the children. Full and any breast-feeding were defined using WHO criteria, and logistic regression analyses were used to identify the relationship between type 1 diabetes and islet autoimmunity and full or any breast-feeding and parent or infant characteristics.

Source: Endocrine Today.

A Step Closer to Predicting Preeclampsia Risk in Diabetes.

Pregnant women with type 1 diabetes have a preeclampsia risk 2 to 4 times higher than that of women without the condition, and now researchers think they have identified some novel markers that may help identify diabetic women most at risk.

Valerie A. Holmes, PhD, senior lecturer at the Centre for Public Health, School of Medicine, Dentistry, and Biomedical Sciences, Queen’s University Belfast, Northern Ireland, and colleagues assessed levels of angiogenic and antiangiogenic compounds found in the maternal serum of women with type 1 diabetes in their second trimester and found that abnormal levels of these markers were present in those who developed preeclampsia.

The study, the largest of its kind to date, “would suggest that these markers may have additional predictive risk above and beyond traditional clinical risk factors,” said Dr. Holmes. The study waspublished online August 6, 2013 in Diabetes Care.

“Previous studies have reported altered angiogenic profiles in women at risk of preeclampsia, but few have specifically looked at women with type 1 diabetes,” Dr. Holmes told Medscape Medical News in an email. “Our findings, in a carefully characterized population of women with type 1 diabetes, demonstrate that adding measures of [these] factors to established clinical risk factors significantly improves the prediction of preeclampsia. These results are an important step on the road to establishing a preeclampsia ‘risk score’ for women with type 1 diabetes.”

Some Interest in Commercial Development of Tests

The researchers studied 540 women participating in the Diabetes and Preeclampsia Intervention Trial (DAPIT), which enrolled patients from 25 centers across Scotland, Northern Ireland, and England between April 2003 and June 2008. Blood samples were taken at 26 weeks’ gestation and analyzed by laboratory staff members who were blinded to each woman’s preeclampsia status.

The association of angiogenic factors, such as placental growth factor (PlGF) and antiangiogenic factors — such as soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) — with preeclampsia was determined through logistic regression analysis adjusted for age, body mass index (BMI), diabetes duration, parity, history of preeclampsia, current smoking, and clinical parameters such as blood pressure, hemoglobin A1c, and renal function.

Of the 540 women included in this study, 94 (17%) developed preeclampsia, and 198 (37%) gave birth prematurely (before 37 weeks’ gestation), including 61 women with preeclampsia (65% of women with preeclampsia, compared with 31% of women without preeclampsia; P < .001).

The scientists observed significantly higher levels of sFlt-1 and sEng and significantly lower levels of PlGF, as well as altered ratios of these antiangiogenic and angiogenic factors, during the second trimester in women who later developed preeclampsia compared with those who did not.

“Our findings show that established clinical risk factors, such as previous history of preeclampsia, age, BMI, diabetes duration, parity, blood glucose control, and blood pressure, are indeed reliable indicators of risk in this population,” Dr. Holmes told Medscape Medical News. But the results “also suggest that angiogenic factors provide added clinical value when predicting risk,” she said.

“These findings need to be validated in another group of women with diabetes before incorporating routine testing into the clinical context. Once they are validated, the next step would be to develop a ‘risk score’ for women with diabetes, based on a combination of established risk factors and angiogenic-factor results.”

The tests for angiogenic factors are currently restricted mainly to research settings, she noted, but there is commercial interest in developing such assays.

“With increasing evidence of the role of angiogenic factors in the pathogenesis of preeclampsia, several companies have developed commercially available assays for at least one of the angiogenic factors we investigated, PlGF, to assist with preeclampsia diagnosis and screening. It is possible that in the future, and with further testing, these assays may emerge as part of routinely available screening test to assist clinicians in determining risk,” she said.

Source: Diabetes Care.


,”san�9rf0� ��� east-font-family:”Times New Roman“; color:black’> ABCG2 (p<0.01), the group writes. In the 134 patients on atorvastatin, explainable blood-level variability was split between two polymorphisms in SLCO1B1 (p<0.01 and p<0.05, respectively) and the activity of cytochrome P3A (CYP3A). The analyses were adjusted for gender, age, body mass index, ethnicity, statin dose, and time from last dose, and echo a 2008 study which concluded that two SLCO1B1 variants were associated with simvastatin-related myopathy, as reported by heartwire . The screening concept is currently being applied to simvastatin therapy at least at one major center.


The group retrospectively tested their ideas, looking at the relationships between genotypic and clinical variables and statin dose, in a validation cohort of 579 patients taking either drug in a primary care setting in the US and at a referral clinic in Canada.

The group found that the transporter genotypes that raise statin concentrations were homogeneously distributed among patients taking a range of atorvastatin and rosuvastatin dosages. That is, the prescribing physicians, armed primarily with their clinical judgment to decide dosage levels, failed to achieve optimal dosing with respect to serum drug levels. But it seemed to be only patients receiving the highest dosages who showed higher-than-safe serum levels according to genotype- and age-based criteria.

“Although we didn’t quite get to the sample size we needed, it did seem like people with the wrong genetic makeup are more likely to stop a statin or switch to [another dyslipidemia drug],” Kim said, at least among patients on the highest statin dosages.

The group’s proposed management algorithm recommends a maximum statin dosage that will result in plasma concentrations below the 90th percentile (reflecting an assumption that 10% of patients will have statin-related muscle issues) based on patient age and transporter-related genotype.

The algorithm is based on data predominantly from whites; the group cautions that some other ethnicities, “particularly Asians,” have increased sensitivity to statins.

Source: medscape.com


The nuclear option for insulinomas.

Although insulinomas are rare tumours, they have fascinated clinicians for many years because of the variety in clinical presentation, close association between symptoms and biochemistry, and striking response to surgical cure. In a patient who is otherwise healthy, and in the absence of a history of diabetes mellitus, intermittent hypoglycaemia is usually attributable to inappropriate insulin activity.1 If other causes can be excluded—which is not always easy if, for example, patients are knowingly injecting insulin or taking drugs that stimulate insulin release—insulinoma should be seriously considered as a diagnosis. Diagnosis can be proven by confirmed hypoglycaemia in the presence of inappropriate insulin secretion; however, threshold criteria for measurements of glucose and insulin are somewhat controversial. Recent guidelines suggest that blood glucose concentrations should be lower than 3 mmol/L to be regarded as hypoglycaemia,1 but at the Churchill Hospital in Oxford, UK, we noted that this cutoff produced too many false positives and have reverted to a stricter threshold of 2·2 mmol/L. Equally, the inappropriate level of insulin in the presence of hypoglycaemia has been set at 3 mIU/L, but because insulin assays have become more specific, this crucial concentration of insulin has decreased. Indeed, we have reported a confirmed insulinoma in a patient with an insulin concentration of 2·7 mIU/L.2 As in other areas of endocrinology, improved assays have led to more difficult diagnostic decisions. However, a C-peptide concentration of more than 200 pmol/L is a useful and potentially robust determinant of inappropriate insulin secretion.


After the diagnosis of insulinoma has been made, localisation of the tumour is the biggest challenge. Most tumours are benign and small, with almost all less than 2 cm in maximum diameter, so identification can be problematic. Previously, surgeons would operate and trust that they could feel the tumour by direct palpation, but nowadays this technique is rarely practised (although intraoperative ultrasound is still used). CT scanning has good resolution but the difference in tissue density might not allow clear discrimination of the tumour. We reported that MRI was the most sensitive discriminatory imaging technique, identifying about 75% of tumours, and this sensitivity might be improved with diffusion-weighted imaging.3 Other groups have emphasised the role of endoscopic ultrasound.4 Intra-arterial injection of calcium with measurement of hepatic vein insulin is often used, but is invasive and only regionalises rather than localises the tumour; however, it can help confirm an anatomically identified abnormality.3—5 Thus, a need remains for precise localisation of these tumours. Nuclear medicine has been suggested to be useful in this context because it depends on functional aspects rather than simple anatomical size, but somatostatin scintigraphy and 18F-fluorodeoxyglucose (18F-FDG) PET have not proved useful for these benign tumours.

In The Lancet Diabetes & Endocrinology, Emanuel Christ and colleagues6 ingeniously speculated that because most insulin cells contain receptors for incretins—specifically the glucagon-like peptide-1 receptor (GLP-1R)—injection of radiolabelled exendin-4, a GLP-1R agonist, might identify these tumours where other techniques have failed. Following on from an initial pilot study7 showing the feasibility of this technique, the group now report on 30 patients who were referred for exendin-4 scanning in centres in Switzerland, Germany, and the UK. All patients had either no lesion or only a suspicion of one on CT or MRI scanning, to exclude patients with evidence of malignant insulinoma. Christ and colleagues were able to report on 25 patients who had histological confirmation of insulinoma after surgery; of these, 23 had both CT/MRI and 111In-DTPA-exendin-4 scanning.6 CT/MRI correctly identified 47% (95% CI 27—68) of insulinomas in this study and endoscopic ultrasound correctly diagnosed seven of nine patients assessed using this technique. 111In-DTPA-exendin-4 scanning was 95% (75—100) sensitive, and was the only modality to correctly identify the tumour in all ten instances of histologically confirmed insulinoma where the other imaging was negative, although there were four false positives. Patients had a mean fall in blood glucose concentrations of 1·3 mmol/L (IQR 0·8—2·1) during the study so glucose infusions are required with the technique. Notably, the investigators used a different chelating agent, DPTA, in this study than in previous studies,7 which might cause fewer side effects (such as nausea and hypoglycaemia).

The radiotracer technique seems to be less effective for malignant tumours than benign tumours (radiolabelled octreotide might be more useful) and is not yet commercially available.8 However, it might allow for the identification of tumours not otherwise readily visualised, and should decrease the number of blind laparotomies, decreasing surgical morbidity, and could also allow for an increased rate of laparoscopic removal. Furthermore, some 5—10% of these tumours are a manifestation of multiple endocrine neoplasia type 1 (MEN1), in which multiple lesions frequently occur in the pancreas and identification of insulinomas is difficult. In Christ and colleagues’ study, two patients had MEN1 and their insulinomas were identified and successfully removed after 111In-DTPA-exendin-4 scanning.

A few points warrant emphasis. All patients in the study were selected for inclusion and had uncertain imaging, and at some point a direct comparison against optimum MRI and possibly endoscopic ultrasound and calcium-stimulated venous catheterisation should be done. At the moment, the new radiotracer technique is probably best reserved for those cases in which conventional localisation techniques have not worked. In time, PET isotopes might become available that are more sensitive and can reduce scan times (although whether this would work well for the pancreas is unknown). Endocrinologists should nevertheless regard the nuclear technique as offering great potential benefit to our patients in the future.

Source: Lancet

Exercise Alone May Help Those With Type 2 Diabetes.

Story at-a-glance

  • Engaging in a six-month moderate-intensity exercise program led to significant health improvements among people with diabetes, including decreases in fat in the abdomen, liver and around the heart, all of which is associated with an increased risk of heart disease
  • Heart disease is the number one cause of death among people with type 2 diabetes, so exercise could be potentially lifesaving for diabetics
  • Type 2 diabetes arises from faulty leptin and insulin signaling and resistance, both of which are directly related to lack of exercise and a diet high in starchy carbohydrates or sugar.
  • When you exercise for diabetes prevention or treatment, intensity is key; high-intensity interval training (HIIT) should ideally be included in your fitness program to achieve optimal results.
  • diabetes

Nearly 8 percent of the US population, or close to 26 million people, have diabetes, and another 80 million have pre-diabetes,1 which means they’re on their way to developing the full-blown version of the disease… if they don’t do something to stop it.

That something is the silver lining to this major public health epidemic, as research clearly shows lifestyle changes are extremely effective at not only preventing type 2 diabetes but also reversing it if you’ve already been diagnosed.

Among them, exercise has recently made headlines for making major improvements in diabetics’ health.

Exercise Improves Diabetics’ Health – Even Without Other Lifestyle Changes

In a new study of people with diabetes, engaging in a six-month moderate-intensity exercise program led to significant health improvements.2 Specifically, they had decreases in fat in the abdomen, liver and around the heart, all of which is associated with an increased risk of heart disease.

In case you aren’t aware, heart disease is the number one cause of death among people with type 2 diabetes. It’s estimated that at least 65 percent of those with diabetes die from some form of heart disease or stroke.3

While the exercise program didn’t lead to direct changes in heart function, the reductions in dangerous visceral fat around key organs – as well as reductions in pericardial fat, which is the second layer of fat around the heart – will undoubtedly improve heart health among this at-risk population. The study’s lead author noted:4

“ … reduction of liver fat content and visceral fat volume by physical exercise are very important to reverse the adverse effects of lipid accumulation elsewhere, such as the heart and arterial vessel wall.”

Also noteworthy about the study was the relatively small amount of exercise needed to prompt such beneficial changes. The participants exercised between 3.5 and 6 hours a week (and ended the program with a 12-day trekking expedition), which is a reasonable goal for most people.

Further, the benefits were gained from exercise alone; no other lifestyle or dietary changes were made, which shows just how powerful staying active can be in improving your health — even if you’ve already been diagnosed with a potentially chronic disease.

Why Exercise Has Been Called the ‘Silver Bullet’ in Diabetes Treatment

When diagnosed with type 2 diabetes, many believe their fate has been sealed and all they can do now is “control” it. This is far from the truth. You can essentially “cure” yourself of this disease and permanently control it. Exercise can be one of your secret weapons to doing so.

The amazing thing about exercise is that it exerts its effects very quickly. There are long-term benefits, too, of course, but you’ll also get acute, nearly instantaneous benefits as well. This should be excellent motivation to those of you who are procrastinating on your exercise program, as you don’t have to exercise for a year or six months to experience benefits!

Research published in Medicine & Science in Sports & Exercise found, for example, that one single session of moderate exercise can improve the way your body regulates glucose and reduces the spikes in blood sugar that occur after a meal (elevations in these spikes, known as postprandial glucose, or PPG, are associated with type 2 diabetes, heart disease, and death).5

When you exercise for diabetes prevention or treatment, intensity is key. A slow walk around the block, while better than watching TV on the couch, is not likely to cut it (although if you’re morbidly obese and very out of shape this is a good way to start). Instead, high-intensity interval training (HIIT), which is a core component of my Peak Fitness program, should ideally be included in your fitness program to achieve optimal results. This technique uses short bursts of intense activity followed by a longer period of recovery, and the cycle is then repeated multiple times. All you need is about 20 minutes of HIIT two or three times a week for maximum benefits. HIIT can significantly improve your insulin sensitivity, especially if you’re on a low-processed-food, low-sugar/low-grain diet as well.

If You Want to Reverse Diabetes, Diet and Exercise Changes Are Essential

Exercise is vital if you have diabetes, but even though physical activity alone is likely to give your health a boost, you should not rely on it as your sole treatment strategy. Type 2 diabetics need to address the root of the problem, which is insulin and leptin resistance—caused by faulty leptin and insulin signaling, which is directly attributable to not only lack of exercise but also the food you eat. The truth of the matter is that type 2 diabetes is a fully preventable condition and it’s also close to 100% reversible, provided you take the proper steps to heal your body.

In one study, for instance, researchers randomly assigned diabetic participants, who were also overweight or obese, to an intensive program of diet and exercise, in which they were urged to cut calories down to 1,200-1,800 calories per day and engage in nearly three hours of physical exercise per week.6

After one year, 11.5 percent of the program participants no longer needed medication to keep their blood sugar levels below the diabetes threshold – in other words, they were no longer diabetic. For comparison, only 2 percent of the non-intervention group experienced any significant improvement in their condition. Again, type 2 diabetes arises from faulty leptin signaling and insulin resistance, both of which are directly diet- and exercise-related. It is NOT a disease of blood sugar.

Once you understand that, the remedy becomes clear: To reverse the disease, you need to recover your body’s insulin and leptin sensitivities. The ONLY way to accomplish this is through proper diet and exercise, as detailed in my free Nutrition Plan. Bariatric surgery, which is being increasingly recommended as a diabetes treatment, will NOT do the trick, and there is NO drug that can correct leptin signaling and insulin resistance, either.

Why What You Eat Can Make or Break Your Health and Cause Diabetes

Let’s review the mechanics of insulin and leptin resistance

  • Leptin is a hormone produced in your fat cells. One of leptin’s primary roles is regulating your appetite and body weight. It tells your brain when to eat, how much to eat, and most importantly, when to stop eating. And leptin tells your brain what to do with the energy it has. Leptin is largely responsible for the accuracy of insulin signaling and whether or not you become insulin resistant.
  • Insulin—Sugars and grains raise your blood sugar. When this happens, insulin is released to direct the extra energy into storage. A small amount is stored as a starch-like substance called glycogen, but the majority is stored as your main backup energy supply—fat. Insulin’s major role is not to lower your blood sugar, but rather to store the extra energy for future times of need. Insulin’s effect of lowering your blood sugar is merely a “side effect” of this energy storage process.

As you can see, these two hormones work in tandem, creating either a health-damaging or health-promoting cycle, depending on what you eat. If you consume loads of sugars and grains, your blood sugar spikes will lead to increased insulin, which leads to increased fat storage. The extra fat then produces more leptin. The problem arises when your leptin levels become chronically elevated.

At this point, you become leptin resistant—your body can no longer “hear” the hormonal signals telling your brain you’re full and should stop eating. As your fat stores increase, your weight goes up, and insulin resistance sets in. Now your body has become “deaf” to the signals from both hormones (leptin and insulin), and disease follows; one of which is diabetes.

Are You Ready to Send Your Diabetes Packing?

Adhering to the following guidelines can help you do at least three things that are essential for successfully treating type 2 diabetes: recover your insulin/leptin sensitivity, normalize your weight, and normalize your blood pressure:

  • Severely limit or eliminate sugar and grains in your diet, especially fructose which is far more detrimental to your health than any other type of sugar. Following my Nutrition Plan will help you do this without too much fuss. Avoid excessive protein as your body will convert that to sugar in your liver, which will sabotage your ability to control insulin resistance. Excess protein may even be more damaging to your health than excess carbs.
  • Exercise regularly. As mentioned, exercise is an absolutely essential factor and, without it, you’re unlikely to get this devastating disease under control. It is one of the fastest and most powerful ways to lower your insulin and leptin resistance. If you’re unsure of how to get started, I recommend reviewing my Peak Fitness program for tips and guidelines.
  • Avoid trans fats.
  • Get plenty of omega-3 fats from a high-quality, animal-based source, such as krill oil.
  • Optimize your vitamin D levels. Recent studies have revealed that getting enough vitamin D can have a powerful effect on normalizing your blood pressure and that low vitamin D levels may increase your risk of heart disease.
  • Optimize your gut flora. Your gut is a living ecosystem, full of both good bacteria and opportunistic strains that can cause trouble. Multiple studies have shown that obese people have different intestinal bacteria than lean people. When the microbes in your gut exist in proper balance, your immune system will be stronger and the better your body will function overall. Fortunately, optimizing your gut flora is relatively easy. You can reseed your body with beneficial bacteria by eating fermented foods (such as fermented vegetables, natto, raw organic cheese, or raw milk kefir) or by taking a high-quality probiotic supplement.
  • Address any underlying emotional issues and/or stress. Non-invasive tools like the Emotional Freedom Technique (EFT) can be helpful and effective.
  • Get enough high-quality sleep every night.
  • Monitor your fasting insulin level. This is every bit as important as your fasting blood sugar. You’ll want your fasting insulin level to be between 2 and 4. The higher your level, the worse your insulin sensitivity is.

Diabetes is a condition that is personally close to me, as most of my paternal relatives (my dad included), have, or have died from, diabetes. But my personal experience with diabetes and subsequent review of the literature has made it very clear to me that virtually every case of type 2 diabetes is reversible. If you’ve been diagnosed with type 2 diabetes or pre-diabetes, today can be the day that you take control of your health and start the journey to cure yourself of this disease.

Source: mercola.com

Nocturnal melatonin secretion associated with insulin resistance

Higher nocturnal melatonin secretion was associated with greater insulin sensitivity and a lower prevalence of insulin resistance in a study analyzing the data of more than 1,000 women without hypertension, type 2 diabetes or obesity, according to researchers.

Previous studies suggest that melatonin may play a role in glucose metabolism, according to Ciaran J. McMullan, MD, of the renal division in the department of medicine at Brigham and Women’s Hospital in Boston, and colleagues.

The researchers measured the main melatonin metabolite, 6-sulfatoxymetaltonin, through urine concentrations to estimate an association between endogenous nocturnal melatonin secretions.

The researchers included women aged 32 to 52 years (n=1,075) from the Nurses’ Health Study II (1997 to 1999) without diabetes, hypertension, or malignancy in their analysis.

According to data, adjustments were made for age, BMI, smoking, physical activity, alcohol intake, dietary glycemic index, family history of diabetes, blood pressure, total cholesterol, uric acid and estimated glomerular filtration rate (eGFR). After these adjustments, the OR for insulin resistance among women in the highest quartile of urinary 6-sulfatoxymelatonin:creatinine ratio was 0.45 (95% CI, 0.28-0.74) compared with women in the lowest quartile, researchers wrote.

These data indicate that higher nocturnal melatonin secretion was inversely associated with insulin levels and insulin resistance.

“Nocturnal melatonin secretion has been shown to be disrupted by sleep disorders. Thus, our finding that lower nocturnal melatonin secretion is associated with insulin resistance may be a potential mechanism explaining the previously described relationship between disruption of normal sleep pattern and incidence of diabetes,” McMullan and colleagues wrote.

However, due to the observational nature of this study, the researchers suggest further studies to confirm this association.

Source: Endocrine Today