Could a common diabetes drug ease bipolar disorder?

by Dennis Thompson

A half-century-old diabetes drug appears to help treat bipolar disorder by reversing patients' insulin resistance, according to a small-scale clinical trial.

31 jul 2022--Bipolar patients who responded to the drug metformin experienced improvement in their mood disorder as their insulin resistance decreased, said lead researcher Dr. Cynthia Calkin, an associate professor of psychiatry at Dalhousie University in Halifax, Nova Scotia, Canada.

"We saw this improvement as early as week six in the study," she said. "Week 14 was the study endpoint, and patients remained significantly improved or in remission. And then we went on to follow them up to 26 weeks and these patients remained well."

Calkin noted that some patients who started off in the trial are still in remission, six or seven years later.

Metformin helps treat type 2 diabetes by reducing production of glucose by the liver and increasing the body's sensitivity to insulin.

Studies have shown that more than 50% of people with bipolar disorder also have insulin resistance, said Dr. Claudia Baldassano, director of the Bipolar Outpatient Resident Teaching Clinic and the Mood Disorder Comprehensive Consultation Service at the University of Pennsylvania Perelman School of Medicine.

"As a clinician who treats thousands of bipolar patients, I found this really intriguing and not that surprising," said Baldassano, who wasn't part of the study. "Our bipolar patients, so many of them are overweight. They have problems with obesity. They have problems with type 2 diabetes and insulin resistance."

The potential link between insulin resistance and bipolar disorder is causing a "paradigm shift in psychiatry," Calkin said.

"We need to start thinking more about underlying mechanisms and not be treating patients simply from the neck up," she said. "We have to look at the whole patient and what's going on besides their psychiatric illness, because all of these things appear to be connected."

The key is not that metformin is an antidepressant, "because I don't believe it is," Calkin said. "The key is reversing this underlying aberrant mechanism, reversing the insulin resistance."

For the clinical trial, Calkin and her colleagues randomly assigned 20 patients to take metformin for half a year, and 25 to take a placebo. Both groups of patients had both bipolar disorder and insulin resistance.

"These patients on average had been sick for 25 years without a remission," Calkin said. "Over 55% had failed all four drug classes that we use in terms of mood stabilizers—lithium, anti-epileptic drugs, antipsychotics and antidepressants. And over 90% had failed three out of four of those drug classes. So this was really, really a very, very sick population."

Half of the metformin patients responded to the drug, and no longer were insulin resistant by 14 weeks, the study found.

Those patients also experienced significant improvements on standard tests used to assess symptoms of bipolar disorder.

The drug also proved relatively safe, Calkin added.

"When we looked at the side effect profile with metformin, there is no difference from patients who are on placebo," Calkin said. "We've had this drug for 50 years. It's a very, very benign, cheap, safe drug."

Researchers think insulin resistance might do something to the blood-brain barrier—which separates the bloodstream in the brain from the bloodstream in the rest of the body—that either causes or influences bipolar disorder, Calkin and Baldassano said.

"My hypothesis was that this barrier that normally protects the brain, it became leaky when people were insulin resistant," Calkin said. "Then inflammatory molecules could get into the brain where they otherwise wouldn't have been able to, and that this would affect a brain disorder like bipolar disorder."

Disruption of the blood-brain barrier caused by insulin resistance also might hamper the effectiveness of medications that directly treat bipolar disorder, Baldassano said.

The good news is that psychiatrists are becoming increasingly comfortable prescribing metformin to treat weight gain associated with mood-stabilizing drugs, she said.

"If you can prescribe a medication that can help a bipolar patient with two things—something that could prevent them from developing type 2 diabetes and help reduce their depressive symptoms—I think that is something psychiatrists will definitely use," Baldassano said.

Insulin resistance will be the key to determining who might be helped by metformin, Calkin said, and that's not just people who are carrying excess weight.

"Obesity tends to lead to insulin resistance, but I have as well slim triathletes in my practice who are also insulin-resistant," Calkin said. "So I think there's a genetic component there as well."

For metformin to be widely adopted, however, there needs to be a large-scale trial definitively proving its benefit, Baldassano said.

"The results were impressive, but it does need to be replicated in a larger-scale study," she said.

The findings were recently published in the Journal of Clinical Psychiatry.

---

Cynthia V. Calkin et al, Treating Insulin Resistance With Metformin as a Strategy to Improve Clinical Outcomes in Treatment-Resistant Bipolar Depression (the TRIO-BD Study), The Journal of Clinical Psychiatry (2022). DOI: 10.4088/JCP.21m14022

Journal information: Journal of Clinical Psychiatry 

Diet soda may be hurting your diet

Coca-Cola is the world’s most popular carbonated soft drink. The original is made with sugar, but the others contain artificial sweeteners that are now linked to a rise in obesity and diabetes. Credit: Chones/shutterstock.com

Artificial sweeteners are everywhere, but the jury is still out on whether these chemicals are harmless. Also called non-nutritive sweeteners, these can be synthetic – such as saccharin and aspartame – or naturally derived, such as steviol, which comes from the Stevia plant. To date, the U.S. Food and Drug Administration has approved six types of artificial and two types of natural non-nutritive sweeteners for use in food.

18 may 2018--That's been great news for those working hard to curb their sugar consumption. Aspartame, for example, is found in more than 6,000 foods worldwide, and about 5,000-5,500 tons are consumed every year in the United States alone.
The American Diabetes Association – the most well-respected professional group focusing on diabetes – officially recommends diet soda as an alternative to sugar-sweetened beverages. To date, seven U.S. municipalities have imposed a sugary beverage tax to discourage consumption.
However, recent medical studies suggest that policymakers eager to implement a soda tax may also want to include diet drinks because these sweeteners may be contributing to chronic diabetes and cardiovascular diseases as well.
Why are these sweeteners calorie-free?
The key to these virtually calorie-free sweeteners is that they are not broken down during digestion into natural sugars like glucose, fructose and galactose, which are then either used for energy or converted into fat.
Non-nutritive sweeteners have different byproducts that are not converted into calories. Aspartame, for example, undergoes a different metabolic process that doesn't yield simple sugars. Others such as saccharin and sucralose are not broken down at all, but instead are absorbed directly into the bloodstream and excreted in the urine.

Theoretically, these sweeteners should be a "better" choice than sugar for diabetics. Glucose stimulates release of insulin, a hormone that regulates blood sugar levels. Type 2 diabetes occurs when the body no longer responds as well to insulin as it should, leading to higher levels of glucose in the blood that damages the nerves, kidneys, blood vessels and heart. Since non-nutritive sweeteners aren't actually sugar, they should sidestep this problem.
Artificial sweeteners, your brain and your microbiome
However, there is growing evidence over the last decade that these sweeteners can alter healthy metabolic processes in other ways, specifically in the gut.
Long-term use of these sweeteners has been associated with a higher risk of Type 2 diabetes. Sweeteners, such as saccharin, have been shown to change the type and function of the gut microbiome, the community of microorganisms that live in the intestine. Aspartame decreases the activity of a gut enzyme that is normally protective against Type 2 diabetes. Furthermore, this response may be exacerbated by the "mismatch" between the body perceiving something as tasting sweet and the expected associated calories. The greater the discrepancy between the sweetness and actual caloric content, the greater the metabolic dysregulation.
Sweeteners have also been shown to change brain activity associated with eating sweet foods. A functional MRI exam, which studies brain activity by measuring blood flow, has shown that sucralose, compared to regular sugar, decreases activity in the amygdala, a part of the brain involved with taste perception and the experience of eating.
Another study revealed that longer-term and higher diet soda consumption are linked to lower activity in the brain's "caudate head," a region that mediates the reward pathway and is necessary for generating a feeling of satisfaction. Researchers have hypothesized that this decreased activity could lead a diet soda drinker to compensate for the lack of pleasure they now derive from the food by increasing their consumption of all foods, not just soda.

Together these cellular and brain studies may explain why people who consume sweeteners still have a higher risk of obesity than individuals who don't consume these products.
As this debate on the pros and cons of these sugar substitutes rages on, we must view these behavioral studies with a grain of salt (or sugar) because many diet soda drinkers – or any health-conscious individual who consumes zero-calorie sweeteners – already has the risk factors for obesity, diabetes, hypertension or heart disease. Those who are already overweight or obese may turn toward low-calorie drinks, making it look as though the diet sodas are causing their weight gain.
This same group may also be less likely to moderate their consumption. For example, those people may think that having a diet soda multiple times a week is much healthier than drinking one case of soda with sugar.
These findings signal that consumers and health practitioners all need to check our assumptions about the health benefits of these products. Sweeteners are everywhere, from beverages to salad dressing, from cookies to yogurt, and we must recognize that there is no guarantee that these chemicals won't increase the burden of metabolic diseases in the future.
As a physician of internal medicine specializing in general prevention and public health, I would like to be able to tell my patients what the true risks and benefits are if they drink diet soda instead of water.
Legislators considering soda taxes to encourage better dietary habits perhaps should think about including foods with non-nutritive sweeteners. Of course, there is an argument to be made for being realistic and pursuing the lesser of two evils. But even if the negative consequences of sugar substitutes doesn't sway our tax policy – for now – at least the medical community should be honest with the public about what they stand to lose or gain, consuming these foods.

This article was originally published on The Conversation. Read the original article.

Provided by The Conversation

Diabetes raises risk of heart attack death by 50 percent

Having diabetes increases the risk of dying from the effects of a heart attack by around 50 per cent, a University of Leeds study has found.

Researchers in the School of Medicine tracked 700,000 people who had been admitted to hospital with a heart attack between January 2003 and June 2013.
Of these, 121,000 had diabetes.

24 jun 2016--After stripping out the effects of age,sex, any other illnesses and differences in the emergency medical treatment received, the team found stark differences in survival rates.
People with diabetes were 56 per cent more likely to have died if they had experienced a ST elevation myocardial infarction (STEMI) heart attack – in which the coronary artery is completely blocked – than those without the condition.
They were 39 per cent more likely to have died if they had a non-ST elevation myocardial infarction (NSTEMI) heart attack – in which the artery is partially blocked - than those without diabetes.
Lead researcher Dr Chris Gale, Consultant Cardiologist and Associate Professor in the School of Medicine, said: "These results provide robust evidence that diabetes is a significant long-term population burden among patients who have had a heart attack.
"Although these days people are more likely than ever to survive a heart attack, we need to place greater focus on the long-term effects of diabetes in heart attack survivors.
"The partnership between cardiologists, GPs and diabetologists needs to be strengthened and we need to make sure we are using established medications as effectively as possible among high-risk individuals."
He added that the next step in their research would be finding out exactly what it is about having diabetes that increases the risk of death following heart attack.
Dr Mike Knapton, Associate Medical Director at the British Heart Foundation, which funded the study said: "We knew that following a heart attack, you are less likely to survive if you also have diabetes.
"However, we did not know if this observation was due to having diabetes or having other conditions which are commonly seen in people with diabetes.
"This paper is the first to conclusively show that the adverse effect on survival is linked to having diabetes, rather than other conditions people with diabetes may suffer from.
"This research highlights the need to find new ways to prevent coronary heart disease in people with diabetes and develop new treatments to improve survival after a heart attack.
"The British Heart Foundation is committed to funding research in this area.
"We are currently funding researchers in Leeds to find new ways of keeping blood vessels healthy in people with diabetes in the fight for every heartbeat."
Dr Anna Morris, Head of Research Funding at Diabetes UK, said: "While researchers tackle this issue, we know that managing diabetes effectively can reduce the risk of developing cardiovascular disease.
"This includes eating healthily, keeping active and taking medications as prescribed by your doctor.
"It's essential that people with diabetes get the support they need to do this effectively, and that we continue to fund research across the UK aimed at preventing the onset of complications in the first place."
The study is published in the Journal of Epidemiology and Community Health.

More information: O A Alabas et al. Long-term excess mortality associated with diabetes following acute myocardial infarction: a population-based cohort study, Journal of Epidemiology and Community Health (2016). DOI: 10.1136/jech-2016-207402


Provided by University of Leeds

Diabetic women at 34 percent higher risk of heart attack than diabetic men as they age

New research presented at this year's annual meeting of the European Association for the Study of Diabetes in Stockholm shows that diabetic women are more at risk than diabetic men of having a heart attack and other complications as they age. The study is by Dr Giuseppe Seghieri, Regional Health Agency, Florence, Italy, and colleagues.

15 sept 2015--Previous research has revealed that diabetic women have a higher risk of cardiovascular events than diabetic men, when compared with the respective non-diabetic counterparts. However, it is unclear when this risk begins or how long it lasts. Thus the authors did a retrospective follow-up study along a period of eight years (from 2005 to 2012) of a cohort of diabetic patients living in Tuscany, a region of central Italy, comparing between genders the effect of age on diabetes related excess risk of hospitalisation for acute heart attack (acute myocardial infarction or AMI), ischemic stroke (IS), and congestive heart failure (CHF).
The authors pooled data from all Tuscan hospitals over the period 2005 to 2012, the general population registry of all inhabitants of Tuscany and a dataset containing the registry of all known diabetic patients from Tuscany. The effect of diabetes was separately measured in men and in women across this entire eight year period. In a total of 3,192,203 inhabitants aged more than 16 years (47% males), there were 24,605 hospitalisations for AMI (16,251 in men and 8,354 in women), 26,953 for IS (14,848 in men and 12,105 in women), 17,628 for CHF (8,403 in men and 9,225 in women).
After adjusting for age, the diabetes related excess risk, expressed as hazard ratio was, overall, significantly higher in women than in men hospitalised for AMI (2.63 times increased risk vs. 1.96 times for men, giving a relative increased risk of 34% in women). However the increased risk was overall similar between genders for those hospitalised for IS and CHF. After stratifying the population by age decades, however, diabetic women hospitalised for AMI had a significantly higher excess risk than diabetic men, along the entire age interval between decade 45-54 years up to age 75-84 years, with the highest difference found in age class 45-54 years (increased risk 5.83 times in women vs. 2.88 in men). In patients hospitalised for IS and CHF diabetic women had an excess risk higher than men from age 55-64 years up to 75-84 years, with the highest difference in age decade 55-64yr in both (4.14 v 3.05 for IS and 6.83 v 4.11 for CHF).
The authors conclude: "In this cohort of Tuscan population the excess risk of cardiovascular events linked with diabetes is significantly different between genders. With respect to AMI, diabetic women are more disadvantaged, compared to diabetic men, with a gender driven 'risk window' for women which mostly opens around menopausal age (45 years onwards). Regarding IS and CHF, it opens later, in the postmenopausal age (55 years and over), and to a lesser extent. All this should focus attention on a timely, gender oriented, prevention of cardiovascular events in people with diabetes."
They add: "The risk for heart attack is different to that from the risk of stroke or CHF: both stroke and CHF appear on average later in the life than heart attacks, at a time when the risk associated with diabetes becomes smaller and smaller: thus gender difference in diabetes linked excess risk is smaller for IS and CHF. In addition the global burden of risk of stroke and/or CHF is built up with other elements—including atrial fibrillation, hypertension, salt intake—which altogether reduce the importance of diabetes itself."


Provided by Diabetologia

Link between antidepressants and diabetes risk is real

Clinicians should be extra vigilant when prescribing antidepressants as they could pose a risk of type 2 diabetes, researchers at the University of Southampton have warned.

29 sept 2013--A systematic review, carried out by the University, showed that people taking antidepressants are at a higher risk of type 2 diabetes; however it is not certain whether the medication is responsible.

The use of antidepressant medication has risen sharply over recent years reaching 46.7 million prescriptions issued in the UK in 2011.

A number of studies have been carried out to establish whether antidepressants are linked with diabetes but results have varied depending on the methods used, type of medication and the number of participants.

University of Southampton researchers assessed 22 studies and three previous systematic reviews that looked into the effects of antidepressants on diabetes risk. Overall, people taking antidepressants were more likely to have diabetes. However, the researchers warned that different types of antidepressants may carry different risks and long-term prospective randomized control trials are needed to look at the effects of individual tablets.

Published in Diabetes Care, the team said that there are "several plausible" reasons why antidepressants are associated with an increased risk of diabetes. For example, several antidepressants are associated with significant weight gain which increases the risk of type 2 diabetes. However, they also say that several studies which explored this association still observed an increased risk of diabetes after adjustment for changes in body weight, implying other factors could be involved.

Dr Katharine Barnard, Health Psychologist from the University of Southampton comments: "Antidepressants are used widely in the UK, with a significant increase in their use recently. Our research shows that when you take away all the classic risk factors of type 2 diabetes; weight gain, lifestyle etc, there is something about antidepressants that appears to be an independent risk factor. With 46 million prescriptions a year, this potential increased risk is worrying. Heightened alertness to the possibility of diabetes in people taking antidepressants is necessary until further research is conducted."

Richard Holt, Professor in Diabetes and Endocrinology at the University of Southampton, adds: "While depression is an important clinical problem and antidepressants are effective treatments for this debilitating condition, clinicians need to be aware of the potential risk of diabetes, particularly when using antidepressants in higher doses or for longer duration. When prescribing antidepressants, doctors should be aware of this risk and take steps to monitor for diabetes and reduce that risk of diabetes through lifestyle modification."

More information: Antidepressant Medication as a Risk Factor for Type 2 Diabetes and Impaired Glucose Regulation: Systematic Review, Diabetes Care, 2013.

Provided by University of Southampton

New scoring system allows clinicians to predict dementia risk in older people with type 2 diabetes

Researchers have developed a simple scoring system, based on a patient's age, health issues, and education, which accurately predicts the risk of dementia in people aged over 60 with type 2 diabetes. The research, published in The Lancet Diabetes & Endocrinology, will allow doctors to closely monitor those patients with diabetes at the highest risk of dementia, allowing early treatment to be given if needed.

21 aug 2013--Age, education, and six different diabetes-related health complications (acute metabolic event, microvascular disease, diabetic foot, cerebrovascular disease, heart disease, and depression) were all identified as the most important predictive factors, and the researchers incorporated them into an easy to use point scoring system.

The scores allow patients to be allocated to one of 14 categories, with the lowest score (-1) indicating the lowest risk of dementia, and the highest scores (12 – 19) indicating the highest risk. Patients with the highest score were 37 times more likely to develop dementia within ten years than those with the lowest score, and patients with higher scores also developed dementia more quickly than those with lower scores. By testing the scoring system against an unrelated group of older patients with type 2 diabetes, the researchers found that it accurately predicts patients' risk of developing dementia.

Although scoring systems to predict the risk of dementia have previously been developed for different populations, this is the first time that researchers have developed a scoring system to predict dementia specifically tailored to people with diabetes. The risk score is likely to prove especially useful to practicing clinicians, as it does not rely on expensive, complicated brain imaging or cognitive testing, although the researchers plan to incorporate a second stage into the scoring system in future including some of these aspects, which may lead to improved accuracy.

According to Dr Whitmer, "Unfortunately, there is an epidemic of both type 2 diabetes and dementia, and the link between these two illnesses portends a possible public health crisis. Our model shows that in two large populations of patients with type 2 diabetes a combination of diabetes-associated complications, education, and age is highly predictive of the likelihood of dementia within the next decade. Early detection of patients with type 2 diabetes who are at increased risk of dementia could help to develop and target preventive treatment, and our scoring system has the potential to change clinical care by giving clinicians a simple and accurate way of predicting the risk of dementia in older people with type 2 diabetes."

Writing in a linked Comment, Dr Anna-Maija Tolppanen, of the University of Eastern Finland, Kuopio, Finland, states that, "Generally, risk scores might be useful in the identification of individuals who should be monitored for disease symptoms, selection of high-risk individuals for clinical trials, targeting of preventive interventions towards those at greatest risk, and assessment of the effectiveness of an intervention at reducing the risk of future illness. [The risk score developed in this paper] might be useful for clinicians for the first purpose, but clinical trial data on effective preventive interventions for dementia are currently lacking."

More information: www.thelancet.com/journals/landia/article/PIIS2213-8587(13)70048-2/abstract

Provided by Lancet

Top ten tips to combat diabetes this New Year

03 jan 2013—Getting your family and friends to support you in being physically active and setting yourself physical activity goals are among the top ten tips scientifically proven to help combat Type 2 diabetes.

Newcastle University researchers carried out a large-scale review of all randomised controlled trials examining changing physical activity and Type 2 diabetes. They analysed the ways people were encouraged to change their behaviour and linked them to whether it changed the control of their diabetes. From this analysis they devised a list of the successful strategies which help people become more active and improve their glucose control.

Publishing today in Diabetes Care, author Professor Mike Trenell who specialises in physical activity and metabolic research at Newcastle University said: "The message that we have known for a while is that people with Type 2 diabetes can benefit significantly by moving more and sitting less. What we have now shown is how people can best help themselves to be physically active.

"While being more physically active often conjures up images of hours on a treadmill or competitive marathon running - walking, using the stairs and just moving more in everyday life can be effective in helping manage diabetes.

"So this New Year, before reaching for the remote and yet another leftover Christmas treat, people should look at how they can move more and sit less. This list provides some useful tips on how to make those New Year's Resolutions a reality. Aside from general improvements in health, its likely that you will look and feel better too."

The Newcastle University team have pulled together the research on the topic and come up with the top ten tips to combat Type 2 diabetes:

• Set physical activity goals – make them specific, measurable and time dependent (such as walking 10,000 steps a day).

• Review your goals – and it doesn't matter if they're short or long-term activity goals.  Make time to think about whether you are achieving what you want.

• Plan in advance a time in your day to be active either at home or at work.

• Get friends or family members involved in your activity, walking with you or helping set or monitor goals.

• Build on your activity success – if you're more active in one area of your daily life such as taking the stairs, then build on that to increase activity in another such as walking to a bus stop further away.

• Get support – phone calls from your GP practice work as well as face-to-face sessions.

• Find out what activities are going on in your local area and when they take place – research shows that just having that information galvanises people into action.

• Build on past success - motivate yourself by thinking of a time where you were more active and how it made you feel.

• What might stop you? - Think what might get in the way of you reaching your activity goal and plan ways around it.

• How is this going to make you healthier? - Seek out information specifically about the benefits of physical activity for you. This might not be just improved diabetes control but looking better, feeling more energetic and meeting people.

Between 2006 and 2011, the number of people diagnosed with diabetes in England has increased by 25 per cent, from 1.9 million to 2.5 million. It's estimated that up to 850,000 people have diabetes but don't know it. The cost of treating diabetes is a staggering £10.3 billion a year – around 10% of the entire NHS budget.

However, as previous Newcastle University research has shown, patients with Type 2 diabetes can walk 45 minutes every day and get the same improvement in blood glucose control as from a major class of drugs.

But getting people with Type 2 diabetes to be more active can prove difficult.

The Newcastle team carried out a systematic review of over 8000 studies and examined 17 studies in depth to understand how health professionals helped support people with Type 2 diabetes to become more physically active and in turn improve their diabetes control. A total of 21 behaviours were identified which had a positive impact on people's health.

Moving more helps improve glucose control by keeping blood flowing to the muscles, maintaining the uptake of sugar from the blood into the muscles where it can be stored or burnt. The increase in energy expenditure also helps prevent weight gain, a major driver for the worsening of diabetes over time.

Professor Mike Trenell adds: "There's growing evidence that moving more and keeping active not only prevents Type 2 diabetes but is critical in protecting us as we grow older.

"The science is clear about the benefits of a moving more and sitting less to diabetes control. But, making the advice into action is much more difficult – we hope that these tips will help people with diabetes improve self management through being more physically active and possibly look and feel better too."

Provided by Newcastle University

New evidence links Alzheimer's disease and diabetes

An emerging body of research suggests that Alzheimer's disease may be linked to insulin resistance, constituting a third type of diabetes. This model is based on several observations including an increased risk of developing Alzheimer's disease for diabetic patients, and reduced insulin levels in the brain tissue of Alzheimer's disease patients.

21 march 2012--Though intriguing, the existing evidence does not reveal if defective insulin signaling is causative of Alzheimer's or how insulin resistance impacts cognitive function. Two back-to-back research articles in the Journal of Clinical Investigation – led by Konrad Talbot, Steve Arnold and colleagues at the University of Pennsylvania and by Fernanda De Felice, Sergio Ferreria and colleagues at the University of Rio de Janeiro - address the connection between insulin resistance and Alzheimer's disease.

The University of Pennsylvania team examined insulin signaling in human brain tissue postmortem, and concluded that the activation state of many insulin signaling molecules were highly related to memory and cognitive function. They further suggest that insulin resistance is a common and early feature of Alzheimer's disease.

The De Felice group further observed impaired insulin signaling in Alzheimer's brain tissue in rodent and non-human primate model systems as well as from tissue from human patients. They went on to show in a mouse model system of Alzheimer's disease that treatment with a new anti-diabetic drug normalized insulin signaling and remarkably improved cognitive function.

Cumulatively, these two new studies strongly support a connection between insulin resistance and Alzheimer's disease and provide hope for new therapeutics in Alzheimer's disease treatment.

More information: An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer's disease–associated Aß oligomers - http://www.jci.org … 1f2106f5edc4

Demonstrated brain insulin resistance in Alzheimer's disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline - http://www.jci.org … 73792af09d60

Provided by Journal of Clinical Investigation

1 in 10 adults could have diabetes by 2030

16 nov 2011-- The International Diabetes Federation predicts that at least one in 10 adults could have diabetes by 2030, according to its latest statistics.

In a report issued on Monday, the advocacy group estimated that 552 million people could have diabetes in two decades' time based on factors like aging and demographic changes. Currently, the group says that about one adult in 13 has diabetes.

The figure includes both types of diabetes as well as cases that are undiagnosed. The group expects the number of cases to jump by 90 percent even in Africa, where infectious diseases have previously been the top killer. Without including the impact of increasing obesity, the International Diabetes Federation said its figures were conservative.

According to the World Health Organization, there are about 346 million people worldwide with diabetes, with more than 80 percent of deaths occurring in developing countries. The agency projects diabetes deaths will double by 2030 and said the International Diabetes Federation's prediction was possible.

"It's a credible figure," said Gojka Roglic, head of WHO's diabetes unit. "But whether or not it's correct, we can't say."

Roglic said the projected future rise in diabetes cases was because of aging rather than the obesity epidemic. Most cases of diabetes are Type 2, the kind that mainly hits people in middle age, and is linked to weight gain and a sedentary lifestyle.

Roglic said a substantial number of future diabetes cases were preventable. "It's worrying because these people will have an illness which is serious, debilitating, and shortens their lives," she said. "But it doesn't have to happen if we take the right interventions."

More information: http://www.idf.org

http://www.who.int

Study: 50-year-old with diabetes dies 6 yrs sooner


A 50-year-old with diabetes dies six years sooner than someone without the disease, and not just from a heart attack or a stroke, new research suggests.

05 mar 2011--The large international effort to measure diabetes' toll found the disease also raises the risk of dying prematurely from a host of other ailments, even breast cancer and pneumonia.

"It's quite a wide sweep of conditions," said Dr. John Danesh of Cambridge University in Britain, who led the team of researchers. While most people think of heart problems, diabetes surprisingly "appears to be associated with a much broader range of health implications than previously suspected."

Putting the six years lost in context, he said, long-term smoking shortens life by 10 years.

The analysis used pooled medical information for 820,900 people from nearly 100 studies done mostly in Europe and North America. The results are published in Thursday's New England Journal of Medicine.

Diabetes, the seventh leading cause of death in the U.S., affects about 26 million Americans, or 8 percent, including 7 million who haven't been diagnosed. Most in the study were thought to have the most common kind - Type 2 - which occurs when the body makes too little insulin or cannot use what it does make to regulate blood sugar.

High blood sugar can damage nerves and blood vessels, and is a major cause of heart disease.

The new research didn't include those who had heart disease when they were first enrolled. Participants were followed on average for 13 1/2 years, and there more than 123,000 deaths. Overall, death rates from various causes were higher for those with diabetes than those without.

The researchers took into account other risk factors that could influence the results: age, gender, smoking and weight. Type 2 diabetes is tied to obesity. They found that those with diabetes had double the risk of dying from a heart attack or stroke, compared to those without the disorder. But they also found that diabetics had a 25 percent higher risk of dying from cancer and were more likely to die from a variety of illnesses including infections, lung and kidney disease as well as falls.


Exactly how diabetes raises those risks isn't clear, but in the case of infections, it could be that diabetes weakens the immune system, the researchers said. Diabetes can cause vision problems and loss of feeling in the legs, which may be the reason for falls, they said.

Danesh said one intriguing finding was a higher risk of suicide in those with diabetes. Other research has linked diabetes with depression, he noted.

The results are "another reason to try to normalize blood glucose in people who have diabetes," through diet, exercise and medication, said Dr. Alvin Powers, a diabetes specialist at Vanderbilt University. "There have been smaller studies that hinted at this but nothing where a study of this size looked at so many different outcomes."

Danesh and his colleagues also estimated diabetes' effect on life expectancy. They calculated that a 50-year-old diabetic without heart disease dies about six years earlier than someone without the disease, with 40 percent of the difference due to cancer and conditions other than heart disease.

"It underscores the need to prevent diabetes," Danesh said.

Previous studies have shown a possible link between diabetes and cancer. The new paper tied some, but not all, cancers; the increased risk ranged from 25 percent for breast cancer to double for liver cancer. Danesh said people with diabetes should get age-appropriate cancer screenings.

Last year, a joint report from the American Diabetes Association and the American Cancer Society looked at the issue and said that it wasn't clear whether any connection was direct, indirect or perhaps because the two disorders share common risk factors, like obesity.

The new research squares with that report's conclusion that "there's a lot more we need to understand about diabetes and the link to cancer," said one of the authors, Dr. Richard Bergenstal of the International Diabetes Center at Park Nicollet in Minneapolis. He a former president of the diabetes group.

While adding to the evidence, the study doesn't answer the question of why, he said.

"Diabetes is a serious condition. We often don't quite think about it quite that way," Bergenstal said.

More information:
Diabetes information: http://www.diabetes.org and http://diabetes.niddk.nih.gov/

New England Journal of Medicine: http://www.nejm.org

New research suggests that obesity and diabetes are a downside of human evolution

As if the recent prediction that half of all Americans will have diabetes or pre-diabetes by the year 2020 isn't alarming enough, a new genetic discovery published online in the FASEB Journal (http://www.fasebj.org) provides a disturbing explanation as to why: we took an evolutionary "wrong turn." In the research report, scientists show that human evolution leading to the loss of function in a gene called "CMAH" may make humans more prone to obesity and diabetes than other mammals.

28 feb 2011--"Diabetes is estimated to affect over 25 million individuals in the U.S., and 285 million people worldwide," said Jane J. Kim, M.D., a researcher involved in the work from the Department of Pediatrics at the University of California, San Diego in La Jolla, CA. "Our study for the first time links human-specific sialic acid changes to insulin and glucose metabolism and therefore opens up a new perspective in understanding the causes of diabetes."

In this study, which is the first to examine the effect of a human-specific CMAH genetic mutation in obesity-related metabolism and diabetes, Kim and colleagues show that the loss of CMAH's function contributes to the failure of the insulin-producing pancreatic beta cells in overweight humans, which is known to be a key factor in the development of type 2 diabetes. This gene encodes for an enzyme present in all mammalian species except for humans and adds a single oxygen atom to sialic acids, which are sugars that coat the cell surface.

To make their discovery, the researchers used two groups of mice. The first group had the same mutant CMAH gene found in humans. These mice demonstrated that the CMAH enzyme was inactive and could not produce a sialic acid type called NeuSGc at the cell surface. The second group had a normal CMAH gene. When exposed to a high fat diet, both sets of mice developed insulin resistance as a result of their obesity. Pancreatic beta cell failure, however, occurred only in the CMAH mutant mice that lacked NeuSGc, resulting in a decreased insulin production, which then further impaired blood glucose level control. This discovery may enhance scientific understanding of why humans may be particularly prone to develop type 2 diabetes. Results may also suggest that conventional animal models may not accurately mirror the human situation.

"The diabetes discovery is an important advance in its own right. It tells us a lot about what goes wrong in diabetes, and where to aim with new treatments," said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal, "but its implications for human evolution are even greater. If this enzyme is unique to humans, it must also have given us a survival advantage over earlier species. Now the challenge is to find the function of CMAH in defending us against microbes or environmental stress or both. This evolutionary science explains how we can win some and lose some, to keep our species ahead of the extinction curve."

More information: Sarah Kavaler, Hidetaka Morinaga, Alice Jih, WuQiang Fan, Maria Hedlund, Ajit Varki, and Jane J. Kim. Pancreatic β-cell failure in obese mice with human-like CMP-Neu5Ac hydroxylase deficiency. FASEB J. fj.10-175281; doi:10.1096/fj.10-175281

Provided by Federation of American Societies for Experimental Biology

Half of Americans will be diabetic or pre-diabetic by 2020

26 nov 2010-- A recent study by US health insurance giant UnitedHealth Group Inc. predicts that by 2020 over half of Americans will have either pre-diabetic conditions or type 2 diabetes if current trends continue, and the annual cost will be around $500 billion a year by the end of the decade, or one tenth of all health care spending. The estimate for 2010 is $194 billion.

The cost of healthcare in the US for non-diabetics was $4,400 per person in 2009, and $11,700 for diabetics. For those with complications arising from the disease the cost is around $20,700 per year. If the predicted rise in the incidence of diabetes eventuates, the total cumulative cost to the US health care system may be as high as $3.35 trillion, with over 60 percent paid for by the government. However, the report offers a number of suggestions, which if adopted could save as much as $250 billion over the next decade.

The United Health Group report said around 27 million Americans are estimated to have diabetes and as many as another 67 million may have undiagnosed pre-diabetic conditions. These figures differ from those issued in October by the US government’s Centers for Disease Control and Prevention, which estimated at least 32 million American adults have diabetes and the number of cases will more than double by 2050.

Complications of diabetes can include circulatory problems (sometimes leading to limb amputations), nerve damage, kidney disease, blindness, and it is a major contributor to heart disease and strokes. Pre-diabetes symptoms include high blood sugar levels, high blood pressure and high cholesterol levels, but the symptoms may not be obvious.

The report was titled: “The United States of Diabetes: Challenges and Opportunities in the Decade Ahead” and was produced for the National Diabetes Awareness month in November. It emphasizes the predicted rise in incidence of diabetes and related costs is not inevitable if measures are taken urgently to address the problem.

Diabetes is a progressive disease with people developing pre-diabetes many years before diabetes. This means there are many intervention possibilities that can prevent pre-diabetic people from developing the disease.

Type 2 diabetes is strongly associated with being seriously overweight or obese, and in the US the report estimates 68.3 percent of Americans were overweight or obese in 2008, with this figure rising each year. For people with pre-diabetes the odds of developing diabetes are considerably reduced if they reduce their weight by five percent or more and increase their levels of physical activity.

Simon Stevens, who is chairman of the UnitedHealth Center for Health Reform & Modernization and executive vice president of UnitedHealth Group, said what is needed now is “concerted, national, multi-stakeholder action.” He said some of the most promising preventive care models should be scaled up, and health plans should be developed to “engage customers in new ways.” The benefits to the US, both in economic and human terms, will be substantial if the steep rise can be averted.

More information: http://www.unitedh … 9dfdc97cedc5

Sodas, other sugary beverages linked to increased risk of type 2 diabetes, metabolic syndrome

A new study has found that regular consumption of soda and other sugar-sweetened beverages is associated with a clear and consistently greater risk of metabolic syndrome and type 2 diabetes. According to the Harvard School of Public Health (HSPH) researchers, the study provides empirical evidence that intake of sugary beverages should be limited to reduce risk of these conditions.

The study appears online October 27, 2010, in the journal Diabetes Care and will appear in the November print edition.

07 nov 2010--"Many previous studies have examined the relationship between sugar-sweetened beverages and risk of diabetes, and most have found positive associations but our study, which is a pooled analysis of the available studies, provides an overall picture of the magnitude of risk and the consistency of the evidence," said lead author Vasanti Malik, a research fellow in the HSPH Department of Nutrition.

Consumption of sugary drinks, the majority of which are sodas, has increased substantially in the U.S. and across the globe and previous scientific studies have shown consistent associations with weight gain and risk of obesity. However, this study is the first meta-analysis to quantitatively review the evidence linking sugar-sweetened beverages with type 2 diabetes and metabolic syndrome. (Metabolic syndrome is a group of risk factors, such as high blood pressure and excess body fat around the waist, that increase the risk of coronary artery disease, stroke and diabetes.)

The researchers, led by Malik and senior author Frank Hu, professor of nutrition and epidemiology at HSPH, did a meta-analysis that pooled 11 studies that examined the association between sugar-sweetened beverages and those conditions. The studies included more than 300,000 participants and 15,043 cases of type 2 diabetes and 19,431 participants and 5,803 cases of metabolic syndrome.

The findings showed that drinking one to two sugary drinks per day increased the risk of type 2 diabetes by 26% and the risk of metabolic syndrome by 20% compared with those who consumed less than one sugary drink per month. Drinking one 12-ounce serving per day increased the risk of type 2 diabetes by about 15%.

"The association that we observed between soda consumption and risk of diabetes is likely a cause-and-effect relationship because other studies have documented that sugary beverages cause weight gain, and weight gain is closely linked to the development of type 2 diabetes," said Hu.

While a number of factors are at work in the development of type 2 diabetes and metabolic syndrome, sugar-sweetened beverages represent one easily modifiable risk factor that if reduced will likely make an important impact, say the researchers. "People should limit how much sugar-sweetened beverages they drink and replace them with healthy alternatives, such as water, to reduce risk of diabetes as well as obesity, gout, tooth decay, and cardiovascular disease," said Malik.

Other HSPH authors include Walter Willett, chair of the Department of Nutrition and Frederick John Stare professor of nutrition and epidemiology.

More information: "Sugar-Sweetened Beverages and Risk of Metabolic Syndrome and Type 2 Diabetes," Vasanti S. Malik, Barry M. Popkin, George A. Bray, Jean-Pierre Despres, Walter C. Willett, Frank B. Hu, Diabetes Care, vol. 33, no. 11, online Oct. 27, 2010.

Provided by Harvard School of Public Health

One-Third of U.S. Adults Could Have Diabetes by 2050: CDC

24 oct 2010-- The number of American adults with diabetes could double or triple by 2050 if current trends continue, warns a federal government study released Friday.

The number of new diabetes cases a year will increase from 8 per 1,000 in 2008 to 15 per 1,000 in 2050, predicts the U.S. Centers for Disease Control and Prevention. By 2050, between one-fifth and one-third of all adults could have diabetes -- with virtually all the increase attributed to type 2 diabetes, which is largely preventable.

An aging population, an increase in minority groups at higher risk for diabetes, and the fact that diabetes patients are living longer are among the reasons for the steep projected rise.

"These are alarming numbers that show how critical it is to change the course of type 2 diabetes," Ann Albright, director of CDC's Division of Diabetes Translation, said in an agency news release. "Successful programs to improve lifestyle choices on healthy eating and physical activity must be made more widely available, because the stakes are too high and the personal toll too devastating to fail."

Another expert agreed.

"These data are accurate and reflect reality," said Dr. Mary Ann Banerji, professor of medicine and director of the Diabetes Treatment Center at SUNY Downstate Medical Center, New York City. "Taking into consideration minorities and longer life expectancy, the real burden of diabetes is much greater than many people thought."

Banerji believes that "we need to act now. Immediate changes in diet, physical activity, stress and sleep are known to decrease diabetes and obesity. We can make changes in our physical environment to promote greater physical activity and we should consider changes in national food policy."

Diabetes remains the leading cause of new cases of blindness under age 75, kidney failure, and preventable leg and foot amputation among adults in the United States, according to the CDC.

In addition, people diagnosed with diabetes have medical costs that are more than twice that of those without the disease, the agency reports. The total costs of diabetes in the United States are an estimated $174 billion annually, including $116 billion in direct medical costs.

The study appears in the journal Population Health Metrics.

The projected increase in U.S. diabetes numbers reflects the global growth of the disease. About 285 million people worldwide had diabetes in 2010, and the number could swell to as many as 438 million by 2030, according to the International Diabetes Federation.

About 24 million Americans have diabetes, but one-quarter of them don't know it. Older age, obesity, a sedentary lifestyle, family history, developing diabetes while pregnant, and race/ethnicity are risk factors for type 2 diabetes. Racial/ethnic groups at increased risk are African Americans, Hispanics, American Indians/Alaska Natives, and some Asian-Americans and Pacific Islanders.

"The incidence of diabetes over the last few decades has progressively increased," notes diabetes expert Dr. Jacob Warman, chief of endocrinology at The Brooklyn Hospital Center, New York City. "It is not surprising that with a flourishing of fast food chains and use of Internet and cable television, the population has become more sedentary and overweight."

However, regular physical activity and proper nutrition can reduce the risk of type 2 diabetes and help control the disease. To that end, the CDC has launched a campaign to reduce such risks in overweight and obese people, stressing dietary changes, coping skills and group support to help participants lose 5 percent to 7 percent of their body weight and get at least 150 minutes per week of moderate physical activity.

Prevention programs that target at-risk groups can help reduce -- but not eliminate -- future increases in type 2 diabetes prevalence, the study said.

ADA: Diabetes Doubles Risk of Several Vascular Diseases

Meta-analysis suggests diabetes is responsible for 11 percent of cardiovascular deaths

26 june 2010-- Diabetes independently doubles the risk of a range of vascular diseases, and may now account for one in every 10 deaths from cardiovascular disease, according to research published in the June 26 special issue of The Lancet to coincide with a presentation at the American Diabetes Association's 70th Scientific Sessions, held from June 25 to 29 in Orlando, Fla.

Researchers from the Emerging Risk Factors Collaboration at the University of Cambridge in the United Kingdom conducted a meta-analysis of 102 prospective studies involving 698,782 people in 25 countries who initially had no vascular disease, of whom 52,765 eventually had nonfatal or fatal vascular outcomes.

The researchers found that diabetes was strongly associated with an increased risk for coronary heart disease, ischemic stroke, hemorrhagic stroke, unclassified stroke, and the aggregate for other vascular deaths (adjusted hazard ratios, 2.00, 2.27, 1.56, 1.84, and 1.73, respectively). At a 10 percent adult population-wide prevalence, they estimated that diabetes accounted for 11 percent of vascular deaths. In patients without diabetes, however, they found that fasting blood glucose concentration was only weakly associated with the risk of vascular disease.

"Our data suggest that in this decade about 10 percent of vascular deaths in populations in developed countries have been attributable to diabetes in adults, corresponding to an estimated 325,000 deaths per year in high-income countries alone (plus several-fold more people disabled by vascular disease)," the authors write. "This burden will increase if the incidence of diabetes continues to rise, even if rates of vascular disease continue to fall because of decreases in smoking, improvements in treatment, or other reasons."

This study was partly supported by Pfizer; one author disclosed financial ties to Pfizer and other pharmaceutical companies, and another author disclosed ties to GlaxoSmithKline.

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Diabetic foot ulcers tied to earlier death

NEW YORK, 14 dec 2009 – Among people with diabetes, those who develop foot ulcers seem to die earlier than those without the complication, a new study finds.

Over time, diabetes can damage the blood vessels and nerves, especially if a person's blood sugar is poorly controlled. Poor circulation and nerve damage in the feet makes people vulnerable to sustaining cuts or other injuries that go unnoticed and progress into poorly healing ulcers, or sores. Severe cases can ultimately lead to amputation.

In the new study, researchers found that among more than 65,000 Norwegian adults, those with a history of diabetic foot ulcers had a higher death rate over 10 years.

Compared with other diabetic adults, those with a history of foot ulcers were 47 percent more likely to die during the study period. The risk was more than two-fold higher when foot ulcer patients were compared with non-diabetic adults.

People with a history of foot ulcers did tend to be older, have poorer blood sugar control and have higher rates of heart disease and stroke, depression and kidney dysfunction. But those factors only partly explained the higher death risk attributed to foot ulcers, the researchers report in the journal Diabetes Care.

"Our study revealed that a history of foot ulcer is a significant marker of higher risk of death not only for people in hospital settings but also in community health care," lead researcher Marjolein M. Iversen, of Bergen University College in Norway, told Reuters Health in an email.

That, she explained, underscores the importance of routine doctor visits -- both to monitor a diabetic patient's overall health, including heart disease risk factors and mental well-being, and for patients to learn how to prevent foot ulcers in the first place.

The findings are based on 65,126 adults taking part in a long-term health study; 1,339 had diabetes and no history of foot ulcers, while 155 had a history of the complication.

Over 10 years, half of those who'd suffered foot ulcers died, compared with 35 percent of diabetics without the complication and 10.5 percent of non-diabetic adults.

When the researchers factored in age, overall health, depression, education and lifestyle habits, the higher death risk in the foot-ulcer group persisted.

In general, experts recommend that people with diabetes take a number of measures to prevent foot ulcers -- with good blood sugar control being key to cutting the risk, as well as the risk of other diabetes complications.

Other recommendations include getting a complete foot exam at least once per year; regularly doing a self-check to spot any cuts, blisters or other abnormalities in the skin or toenails; and wearing socks and shoes at all times to cut the risk of foot injuries.

SOURCE: Diabetes Care, December 2009.

For Older Women With Diabetes, Two Dietary Oils, Two Sets Of Benefits

19 july 2009--A study comparing how two common dietary oil supplements affect body composition suggests that both oils, by themselves, can lower body fat in obese postmenopausal women with Type 2 diabetes.

The two oils compared were safflower oil, a common cooking oil, and conjugated linoleic acid (CLA), a compound naturally found in some meat and dairy products that has been associated with weight loss in previous studies. Both are composed primarily of polyunsaturated fatty acids, which are considered "good fats" that, when consumed in proper quantities, are associated with a variety of health benefits. Martha Belury

In the study, 16 weeks of supplementation with safflower oil reduced fat in the trunk area, lowered blood sugar and increased muscle tissue in the women participants.

Conjugated linoleic acid supplementation for the same length of time, on the other hand, reduced total body fat and lowered the women's body mass index (BMI), a common health measure of weight relative to height.

All of the women in the study took one oil for 16 weeks, followed by the other oil for an equal amount of time. The participants were instructed not to change their diets or exercise patterns over the course of the study so the research would measure the effects of only the supplementation.

"Making this subtle change in the intake of high-quality dietary fats in an effort to alter body composition is both achievable and affordable to postmenopausal women in the United States who are managing the difficult combination of obesity and diabetes," said Martha Belury, professor of human nutrition at Ohio State University and senior author of the study.

Among the most surprising findings: that in 16 weeks, these women could lose between about two pounds and four pounds of trunk fat simply by taking safflower oil supplements.

"I never would have imagined such a finding. This study is the first to show that such a modest amount of a linoleic acid-rich oil may have a profound effect on body composition in women," Belury said. The dose of either oil taken each day was approximately 1 2/3 teaspoons.

Postmenopausal women tend to lose muscle at the same time that body fat accumulates toward their middle, so this research shows how dietary oils can complement lifestyle and medication in helping older diabetic women manage their health, she said.

The research appears online and is scheduled for later print publication in the American Journal of Clinical Nutrition.

Thirty-five women participated in the study. All were considered obese based on their BMI measures of 30 or higher, were postmenopausal but younger than age 70, and had Type 2 diabetes but did not need to take insulin to treat the disease. Many did take other medications, such as those used to manage blood sugar levels, cholesterol or blood pressure.

The women were randomized into two groups to determine which supplement they took first. Each initial 16-week supplementation was followed by a four-week washout period to remove the first supplement from their systems before the next 16-week supplementation period began. The supplements were contained in eight pills; the women took two pills four times per day, at meals and bedtime.

"The power of the crossover is that it tells you the different effects of the dietary oils in the same woman," Belury said.

The daily supplementation contained 6.4 grams of each oil's active fatty acid: linoleic acid in safflower oil and, in CLA, specific fatty acid isomers - compounds that share the same chemical formula but differ in chemical structure.

The researchers used dual-energy X-ray absorptiometry, commonly known as DXA and usually used to measure bone density, to determine the women's baseline and follow-up lean mass and fat throughout their bodies and specifically in their trunk region.

Researchers asked the participants to keep diet and activity records for three consecutive days at four points over the course of the study to account for the potential for calorie intake or exercise to affect the results, Belury said. Physical activity remained unchanged throughout the study, and no significant differences were seen between the two groups' reported calorie intake.

The study showed that CLA supplementation significantly decreased body mass index and total body fat over both diet periods, typically showing effects in the last half of each 16-week period. The BMI levels of the women taking CLA dropped on average by about half a point, and their total body fat decreased by an average of 3.2 percent, reducing the weight of the fat tissue by an average of between 2.3 pounds and 3.5 pounds.

Safflower oil supplementation showed no effect on total body fat readings, but reduced the weight of trunk fat tissue by between 2.6 pounds and 4.2 pounds, or an average of 6.3 percent. It also increased lean tissue, or muscle, by between an average of about 1.4 pounds and 3 pounds.

Safflower oil also lowered fasting blood sugar levels by between 11 and 19 points on average. Blood sugar is considered normal if it falls below 110 milligrams per deciliter; the women's average blood sugar levels ranged from 129 to 148 after 16 weeks of safflower oil supplementation.

"Lowering fasting glucose is important for these women. The overall effect in just 16 weeks wasn't bringing them back to normal, but safflower oil still improved it significantly," Belury said.

The dietary oils did not have significant effects on other health measurements, such as waist circumference, waist-to-hip ratio and skinfold thickness measures of body fat, Belury noted.

The CLA also did not appear to affect the variety of hormones involved in fat burning. However, safflower oil increased a hormone called adiponectin. Increasing this hormone may have instilled an improved ability to burn dietary fats, said Belury, who hopes to investigate this mechanism in a follow-up study.

Belury said that other work she is conducting in animals suggests that at least in the case of CLA, the fatty acid appears to allow the body to burn calories in a heat-producing way. Questions remain about the long-term safety of any kind of supplementation that lowers body fat, because some research has suggested that the fat that leaves fat tissue ends up in the liver or muscles - a condition that could lead to insulin resistance and diabetes if that fat can't be used.

Neither CLA nor the linoleic acid in safflower oil is naturally produced in the human body, so both must be obtained from food or dietary supplements. Linoleic acid is an omega-6 fatty acid that is important in growth and maintenance of tissues and lipid metabolism. The American Heart Association recently issued recommendations suggesting that omega-6 fatty acids are among the polyunsaturated fats that should be consumed for heart health.

CLA is found naturally in trace amounts primarily in beef, lamb and milk, but obtaining levels comparable to those used in Belury's study likely requires concentrated doses similar to those found in dietary supplements.

"Essentially what we're trying to understand with nutrition is how dietary approaches can complement Westernized medicine," Belury said. "In an ideal world, we'd love it if women like those in our study could use diet, activity and other aspects of a healthy lifestyle to manage their health. But most will probably be on oral medications for the rest of their lives for managing their diabetes and metabolism, which is fine as long as the medications work. We think there's a chance that nutrition can complement medication and help drugs work even better."

Co-authors on the study were Leigh Norris, Angela Collene, Michelle Asp, Li-Fen Liu and Julia Richardson of Ohio State's Department of Human Nutrition; Jason Hsu and Dongmei Li of the Department of Statistics; Kwame Osei and Rebecca Jackson of the Department of Internal Medicine's Division of Endocrinology, Diabetes and Metabolism; and Doris Bell of Cognis, provider of an unrestricted monetary gift and a dietary oil donation for the research.

This work was supported by the National Center for Research Resources, Ohio State's Clinical Research Center, the National Institutes of Health and the Caroline S. Kennedy endowment, which funds Belury's professorship.

Written by Emily Caldwell

Source:
Martha Belury
Ohio State University

2 dietary oils, 2 sets of benefits for older women with diabetes

COLUMBUS, Ohio, 10 july 2009 – A study comparing how two common dietary oil supplements affect body composition suggests that both oils, by themselves, can lower body fat in obese postmenopausal women with Type 2 diabetes.

The two oils compared were safflower oil, a common cooking oil, and conjugated linoleic acid (CLA), a compound naturally found in some meat and dairy products that has been associated with weight loss in previous studies. Both are composed primarily of polyunsaturated fatty acids, which are considered "good fats" that, when consumed in proper quantities, are associated with a variety of health benefits.

In the study, 16 weeks of supplementation with safflower oil reduced fat in the trunk area, lowered blood sugar and increased muscle tissue in the women participants.

Conjugated linoleic acid supplementation for the same length of time, on the other hand, reduced total body fat and lowered the women's body mass index (BMI), a common health measure of weight relative to height.

All of the women in the study took one oil for 16 weeks, followed by the other oil for an equal amount of time. The participants were instructed not to change their diets or exercise patterns over the course of the study so the research would measure the effects of only the supplementation.

"Making this subtle change in the intake of high-quality dietary fats in an effort to alter body composition is both achievable and affordable to postmenopausal women in the United States who are managing the difficult combination of obesity and diabetes," said Martha Belury, professor of human nutrition at Ohio State University and senior author of the study.

Among the most surprising findings: that in 16 weeks, these women could lose between about two pounds and four pounds of trunk fat simply by taking safflower oil supplements.

"I never would have imagined such a finding. This study is the first to show that such a modest amount of a linoleic acid-rich oil may have a profound effect on body composition in women," Belury said. The dose of either oil taken each day was approximately 1 2/3 teaspoons.

Postmenopausal women tend to lose muscle at the same time that body fat accumulates toward their middle, so this research shows how dietary oils can complement lifestyle and medication in helping older diabetic women manage their health, she said.

The research appears online and is scheduled for later print publication in the American Journal of Clinical Nutrition.

Thirty-five women participated in the study. All were considered obese based on their BMI measures of 30 or higher, were postmenopausal but younger than age 70, and had Type 2 diabetes but did not need to take insulin to treat the disease. Many did take other medications, such as those used to manage blood sugar levels, cholesterol or blood pressure.

The women were randomized into two groups to determine which supplement they took first. Each initial 16-week supplementation was followed by a four-week washout period to remove the first supplement from their systems before the next 16-week supplementation period began. The supplements were contained in eight pills; the women took two pills four times per day, at meals and bedtime.

"The power of the crossover is that it tells you the different effects of the dietary oils in the same woman," Belury said.

The daily supplementation contained 6.4 grams of each oil's active fatty acid: linoleic acid in safflower oil and, in CLA, specific fatty acid isomers – compounds that share the same chemical formula but differ in chemical structure.

The researchers used dual-energy X-ray absorptiometry, commonly known as DXA and usually used to measure bone density, to determine the women's baseline and follow-up lean mass and fat throughout their bodies and specifically in their trunk region.

Researchers asked the participants to keep diet and activity records for three consecutive days at four points over the course of the study to account for the potential for calorie intake or exercise to affect the results, Belury said. Physical activity remained unchanged throughout the study, and no significant differences were seen between the two groups' reported calorie intake.

The study showed that CLA supplementation significantly decreased body mass index and total body fat over both diet periods, typically showing effects in the last half of each 16-week period. The BMI levels of the women taking CLA dropped on average by about half a point, and their total body fat decreased by an average of 3.2 percent, reducing the weight of the fat tissue by an average of between 2.3 pounds and 3.5 pounds.

Safflower oil supplementation showed no effect on total body fat readings, but reduced the weight of trunk fat tissue by between 2.6 pounds and 4.2 pounds, or an average of 6.3 percent. It also increased lean tissue, or muscle, by between an average of about 1.4 pounds and 3 pounds.

Safflower oil also lowered fasting blood sugar levels by between 11 and 19 points on average. Blood sugar is considered normal if it falls below 110 milligrams per deciliter; the women's average blood sugar levels ranged from 129 to 148 after 16 weeks of safflower oil supplementation.

"Lowering fasting glucose is important for these women. The overall effect in just 16 weeks wasn't bringing them back to normal, but safflower oil still improved it significantly," Belury said.

The dietary oils did not have significant effects on other health measurements, such as waist circumference, waist-to-hip ratio and skinfold thickness measures of body fat, Belury noted.

The CLA also did not appear to affect the variety of hormones involved in fat burning. However, safflower oil increased a hormone called adiponectin. Increasing this hormone may have instilled an improved ability to burn dietary fats, said Belury, who hopes to investigate this mechanism in a follow-up study.

Belury said that other work she is conducting in animals suggests that at least in the case of CLA, the fatty acid appears to allow the body to burn calories in a heat-producing way. Questions remain about the long-term safety of any kind of supplementation that lowers body fat, because some research has suggested that the fat that leaves fat tissue ends up in the liver or muscles – a condition that could lead to insulin resistance and diabetes if that fat can't be used.

Neither CLA nor the linoleic acid in safflower oil is naturally produced in the human body, so both must be obtained from food or dietary supplements. Linoleic acid is an omega-6 fatty acid that is important in growth and maintenance of tissues and lipid metabolism. The American Heart Association recently issued recommendations suggesting that omega-6 fatty acids are among the polyunsaturated fats that should be consumed for heart health.

CLA is found naturally in trace amounts primarily in beef, lamb and milk, but obtaining levels comparable to those used in Belury's study likely requires concentrated doses similar to those found in dietary supplements.

"Essentially what we're trying to understand with nutrition is how dietary approaches can complement Westernized medicine," Belury said. "In an ideal world, we'd love it if women like those in our study could use diet, activity and other aspects of a healthy lifestyle to manage their health. But most will probably be on oral medications for the rest of their lives for managing their diabetes and metabolism, which is fine as long as the medications work. We think there's a chance that nutrition can complement medication and help drugs work even better."

###

Co-authors on the study were Leigh Norris, Angela Collene, Michelle Asp, Li-Fen Liu and Julia Richardson of Ohio State's Department of Human Nutrition; Jason Hsu and Dongmei Li of the Department of Statistics; Kwame Osei and Rebecca Jackson of the Department of Internal Medicine's Division of Endocrinology, Diabetes and Metabolism; and Doris Bell of Cognis, provider of an unrestricted monetary gift and a dietary oil donation for the research.

Experts Urge One Test to Diagnose Diabetes

07 june 2009-- The A1C test, which measures average blood glucose levels over a period of two to three months, should now be the main tool doctors use to diagnose diabetes, an international expert panel recommended Friday.

Besides giving a more accurate picture of diabetes risk, the A1C test is easier on patients than older tests, which often required fasting.

Individuals with hemoglobin A1c values at or above 6.5 percent can be considered to have diabetes, although that number is not set in stone, the experts stated at the American Diabetes Association (ADA) annual meeting in New Orleans.

"This is the first major departure from the way that we've been diagnosing diabetes for more than 30 years, using a laboratory tool that is slightly different than the acute [short-term] measurement of glucose -- measurement of a single glucose value -- which has been traditionally used," said Dr. David Nathan, chairman of the committee and director of the diabetes center at Massachusetts General Hospital in Boston.

He spoke at a special press conference at the ADA meeting on Friday.

The committee comprised members of the ADA, the International Diabetes Federation and the European Association for the Study of Diabetes, although these organizations have not yet issued position statements on the recommendations.

The ADA did, however, speak out unofficially in support of the conclusions.

"We support the conclusions of the paper that basically says that the A1c measurement is appropriate for diagnosing diabetes," said Dr. Paul Robertson, president of medicine and science for the ADA. "Right now, our focus is what comes next. What does this mean for diabetes?"

The guidelines will be referred to practice committees before an official statement is issued, he said.

The proposed diagnostic guidelines will also appear in the July issue of Diabetes Care.

Currently, two tests are widely used to diagnose type 2 diabetes, which now afflicts some 24 million Americans: fasting plasma glucose or oral glucose tolerance tests. Both look at short-term blood glucose levels and involve some inconvenience to patients, including fasting for periods of time before blood is drawn.

Blood glucose levels are also notoriously fickle, changing depending on how recently the patient exercised or ate a meal or snack. Blood sugar can also fluctuate if a person has a cold or if the blood sample is kept at room temperature or in a colder environment.

So, "the results are sometimes difficult to interpret," Nathan said. "With A1C, it doesn't really matter. We consider this a preferred method of diagnosing diabetes. It doesn't care what blood glucose levels are after dinner, before dinner, if you have a cold. It integrates all those levels."

The committee based its recommendations on a review of the literature, focusing on what A1C levels were more likely to result in diabetic retinopathy, a vision-threatening eye condition that is one potential complication of the disease.

"Diabetes is associated with both elevated levels of blood sugar and a host of complications and the one we can measure most quantitatively is retinopathy," Nathan explained. "Glucose levels span an enormous distribution. There's no clear-cut point. To pick a dividing line, we looked at glucose levels associated with this complication."

"After reviewing lots of clinical chemistry data, we determined that there are numerous advantages of A1C," he continued.

People with A1C levels between 6 and 6.5 percent are considered to be at higher risk for diabetes, the committee said.

Experts speaking at the teleconference emphasized that the conventional blood glucose tests are not to be discarded, especially in areas of the world where A1C testing might not be available.

"We're not discarding those tests. We just think that A1C is the preferred method in 2009, and that the world should be moving towards that universally," Nathan said.

Many physicians have already been doing so, added Dr. Spyros Mezitis, an endocrinologist with Lenox Hill Hospital in New York City.

"The change is consistent with the direction practice has been going," he said. "And tight glucose control is still our focus."