New Advances In Lipid Genetics Lead To Better Detection And Prevention Of Diabetes, Heart Disease

By identifying those at risk at the earliest stage would mean giving individuals plenty of time to make the lifestyle changes that could help them avoid the disease

RESEARCHERS from the US and The Netherlands have found ways to earlier and better prediction of diseases such as diabetes, atherosclerosis, and heart disease through studying the genetic make-up of different varieties of lipids in blood plasma.

Studying the genetic make-up of different varieties of lipids (fatty molecules) in the blood plasma of an individual can lead to a better and earlier prediction of diseases such as diabetes, atherosclerosis, and heart disease, two researchers reported on Monday at the annual conference of the European Society of Human Genetics, currently in session in Amsterdam, The Netherlands.

In the first study, Dr. Joanne Curran from the Texas Biomedical Research Institute, San Antonio, USA, reported that lipidomic profiling would become a more reliable early indicator of individuals likely to develop diabetes than the more commonly used predictors such as blood glucose and insulin levels.

Dr. Curran and colleagues from the US and Australia measured 356 different lipid varieties from about 1100 Mexican American members of large extended families who were part of the San Antonio Family Heart Study. The Mexican American population is at high risk of diabetes with about 25% of this population ultimately becoming diabetic. At the start of the research, 861 of the individuals studied did not have diabetes. However, over the 10 year follow-up examined in the study, 110 individuals did develop the disease.

The scientists were able to isolate 128 different varieties of lipids that predicted the progression to diabetes by measuring the lipidomic profiles of each individual at multiple timepoints during the follow-up period. “The single best predictor we found was a novel component called dihydroceramide (dhCer). This was substantially increased in people with diabetes. It is also heritable, and appears to be an independent risk factor unconnected to blood sugar and insulin levels,” said Dr. Curran.

After uncovering the link between dhCer and diabetes, the team searched the genome to find locations that harbored genes that influence dhCer levels. They identified a region on chromosome 3 that appeared to contain a gene with substantial importance for the production of dhCer. “Through whole genome sequencing, we are now attempting to identify this causal gene in the hope that it will be informative in the understanding of the pathogenesis of diabetes, and also suggest new avenues for treatment,” Dr. Curran said.

Dr Joanne E. Curran

In the future, the researchers say, measurement of dhCer levels could become routine in the prediction of individuals likely to become diabetic. One of the difficulties of the current predictive methods is that they do not function until a patient is near to developing the disease. Being able to identify those at risk at the earliest stage would mean that individuals have plenty of time to make the lifestyle changes that could help them avoid the disease – through a change in diet, or increasing physical activity, for example.

“Currently one in ten US adults suffers from diabetes and recently the Centers for Disease Control has predicted that this will increase to one in three by 2050,” said Dr. Curran. “We are optimistic that our discovery will lead to new treatments, but in the short-term the importance of finding out at an early stage whether any individual is likely to develop it cannot be overstated. A test based on dhCer levels will help to avoid the serious health effects that diabetes has in its own right, such as kidney failure, amputations, and blindness. It is, of course, also a risk for cardiovascular disease, so the health burden of this condition is enormous”, she was quoted saying in a press release.

In the second study, Dr. Sarah Willems, from the Erasmus Medical Centre, Rotterdam, The Netherlands, described to the conference research carried out on the influence of common genetic lipid variants on atherosclerosis and related heart disease. “A recent genome-wide meta-analysis of more than 100,000 individuals identified a large number of genetic variants associated with levels of LDL (bad) cholesterol, HDL (good) cholesterol and triglycerides. These molecules are, at increased levels of LDL and triglycerides and decreased levels of HDL, important risk factors for cardiovascular disease”, said Dr. Willems.

Dr Sarah Willems

“As our knowledge of genetic variation increases, preclinical genetic screening tools might enhance the prediction and prevention of clinical events,” Willems’ group told attendees.

The researchers used risk scores from these genetic variants to test the hypothesis that their cumulative effects were associated with cardiovascular disease. For this purpose they used genetic data from more than 8000 individuals from the population-based Rotterdam Study and more than 2000 individuals participating in the Dutch family-based Erasmus Rucphen Family study.

They found an association between the LDL risk score and arterial wall thickness, and a strong association of this risk score with carotid plaque. These conditions can cause arterial blockage which leads to stroke. The same risk score was also associated with coronary heart disease.

“Our findings show that an accumulation of common genetic variants with small effects on lipid levels can have a significant effect on clinical and sub-clinical outcomes”, said Dr. Aaron Isaacs, who led the project. “In the future, as our knowledge of genetic variation increases, effective pre-clinical genetic screening tools may be able to enhance the prediction and prevention of diseases such as cardiovascular disease.”

New genetic variants influencing lipid levels are being identified all the time, the researchers say. “As new variants are discovered, we would like to be able to continue to test them, both singly and combined, for association with cardiovascular disease. The cost of these diseases to individuals, families, society and healthcare systems is immense”, said Dr. Willems.

“Cardiovascular disease is the main cause of death in Europe, killing over 4 million people per year. It also represents 23% of the total disease burden (illness and death) across the continent. Managing cholesterol levels is important for prevention. This can be done early in life by effective treatment. We hope that our study, showing that common genetic variants play an important role in the occurrence of cardiovascular disease, marks a starting point for early prediction and prevention and may thus reduce the burden of disease,” she concluded.

Traditional clinical risk factors can predict diabetes and heart disease already, but adding genetic tools to the mix could be useful, particularly in determining how aggressively to approach prevention in patients considered intermediate risk by conventional measures, commented Donna Arnett, PhD, MSPH, of the University of Alabama at Birmingham School of Public Health, and a spokesperson for the American Heart Association.

The cost of genetic testing could be a hurdle for clinical application, though, until ways are found to make it more affordable, she noted in an interview, adding lipodemic profiling is still in its infancy and more information is needed on how measures like dihydroceramide might measure up against clinical factors like waist circumference.

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The European Society of Human Genetics aims to promote research in basic and applied human and medical genetics, to ensure high standards in clinical practice and to facilitate contacts between all persons who share these aims, particularly those working in Europe. It currently has about 1600 members from 66 countries. About 2500 delegates are attending this year’s conference.

Note: These studies were published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Is Anorexia A Sort Of Cousin Of Diabetes?

ANOREXIA may be a disorder more of the metabolism than the mind, according to a new paper that argues the disease is a sort of cousin of diabetes. But this theory of anorexia as a fundamentally biological disorder, rather than a psychological one, is untested, psychiatrists warn, and patients with the disease should not stray from proven treatments.

The review of past research on the topic, published in the June issue of the journal Molecular Psychiatry, finds that certain genetic and cellular processes get activated during starvation in organisms ranging from yeast to fruit flies to mice to humans. The idea, says study researcher Donard Dwyer, is that in people with a broken starvation response, a few initial rounds of dieting could trigger a metabolism gone haywire.

In this theory, it’s not stubbornness or a mental disorder that keeps anorexics from eating, it’s their own bodies. The theory could explain why it can be so difficult to convince anorexic patients that anything is wrong with them, says Dwyer. “Unless we conceive of it as more of a metabolic function, I don’t think we’ll get past the first stage of treatment with a lot of the real hard-core patients,” he says.

The diabetes of starvation

In the current understanding of anorexia nervosa, an eating disorder in which patients don’t maintain at least 85 percent of their normal body weight for their height, overachieving personality types attempt to control stress and emotion by restricting food and/or extreme exercising.

Dwyer sees the disease, instead, as a condition similar to diabetes. Someone who becomes obese and is genetically susceptible will develop insulin resistance, which then becomes diabetes. An initial trigger — the obesity — is required, but once the patient has diabetes, you can’t talk him or her out of the disease.

For anorexia, Dwyer says, the potential trigger is chronic undereating or dieting, and the messed-up molecular process could be any number of biological changes that happen during starvation. In the current review, he and his colleagues focus on a cascade of genetic and cellular events called the IGF-1/Akt/FOXO pathway. Organisms from yeasts to humans activate this pathway in response to starvation, triggering all sorts of biological changes, including a desire to look for food. If this pathway doesn’t work as it should, it could theoretically cause the warped approach to eating seen in anorexia. (The so-called epigenome, the supporting actor to our genes, is what helps determine which genes, or pathways, get switched on and off.)

If Dwyer is right, difficult-to-treat anorexic patients may need drugs to get their metabolisms back on track, much as diabetic patients have to take insulin shots. But so far, the idea has not been tested in humans.

“This is, at the moment, speculative,” says Timothy Walsh, a psychiatrist at Columbia University who was not involved in the research. “There’s no human data to support it, and it’s only part of the answer. It’s not proposed as the complete solution.”

Starvation and metabolism

Dwyer is careful to say that much more research is needed. But he says there is good reason to continue the work. Research on obesity has shown that being too heavy is more complex than simply calories in, calories out, he says. There are genetic and metabolic factors involved that make it hard for some people to shed weight. And obesity-related changes to the epigenome (our genes’ on-off switches) can even be passed down from mother to child. The same could be true on the flip side, with starvation, Dwyer says, adding, the genes linked to anorexia could be the same ones that regulate the metabolism during starvation.

Additionally, studies on starving people suggest that many of the supposed causes of anorexia, including food obsession and anxiety, may be symptoms of starvation. And starving people, like anorexics, often report that they’re doing much better than their physical condition would suggest.

“Here we have our anorexic patients who are not aware of how sick they are despite how thin they have gotten. … We’re not going to be able to convince them otherwise until we understand that better,” Dwyer says. “It’s probably not going to be something we can just talk them out of.”

Via LiveScience

Related article: The Signs of Diabulimia

New Form Of ‘Ultra-Bad’ Cholesterol That Increases Risk Of Heart Disease Discovered

Fatty material is stickier than LDL, making it more likely to attach to artery walls

SCIENTISTS from the University of Warwick in the UK have discovered a new form of ‘ultra-bad’ cholesterol that increases the risk of heart disease. The fatty material is stickier than the common form of ‘bad’ cholesterol, making it more likely to attach to artery walls.

Funded by the British Heart Foundation (BHF), the researchers found that ‘ultra-bad’ cholesterol, called MGmin-low-density lipoprotein (LDL), which is more common in people with type 2 diabetes and the elderly, appears to be ‘stickier’ than normal LDL. This makes it more likely to attach to the walls of arteries. When LDL attaches to artery walls it helps form the dangerous ‘fatty’ plaques’ that cause coronary heart disease (CHD).

The research – published online on May 26 in the journal Diabetes – shows how the make-up and the shape of a type of LDL cholesterol found in diabetics could make it more harmful than other types of LDL. The findings provide one possible explanation for the increased risk of coronary heart disease in people with diabetes. Understanding exactly how ‘ultra-bad’ LDL damages arteries is crucial, as this knowledge could help develop new anti-cholesterol treatments for patients.

The researchers made the discovery by creating human MGmin-LDL in the laboratory, then studying its characteristics and interactions with other important molecules in the body. They found that MGmin-LDL is created by the addition of sugar groups to ‘normal’ LDL – a process called glycation – making LDL smaller and denser.

By changing its shape, the sugar groups expose new regions on the surface of the LDL. These exposed regions are more likely to stick to artery walls, helping to build fatty plaques. As fatty plaques grow they narrow arteries – reducing blood flow – and they can eventually rupture, triggering a blood clot that causes a heart attack or stroke.

The discovery might also explain why metformin, a widely prescribed type 2 diabetes drug, seems to lead to reduced heart disease risk. Metformin is known to lower blood sugar levels, and this new research shows it may reduce the risk of CHD by blocking the transformation of normal LDL to the more ‘sticky’ MGmin-LDL.

Dr Naila Rabbani

Dr Naila Rabbani, Associate Professor of Experimental Systems Biology at Warwick Medical School, who led the study, said: “We’re excited to see our research leading to a greater understanding of this type of cholesterol, which seems to contribute to heart disease in diabetics and elderly people. Type 2 diabetes is a big issue…particularly common in lower income groups and South Asian communities.  The next challenge is to tackle this more dangerous type of cholesterol with treatments that could help neutralize its harmful effects on patients’ arteries.”

Dr Shannon Amoils, Research Advisor at the BHF, said: “We’ve known for a long time that people with diabetes are at greater risk of heart attack and stroke. There is still more work to be done to untangle why this is the case, but this study is an important step in the right direction.”

Via EurekAlert

U.S. Halts ‘Good Cholesterol’ Study

Meanwhile, U.S. officials abruptly halted a major study Wednesday of a drug that boosts people’s good cholesterol did not go on to prevent heart attacks or strokes.

The disappointing findings involve super-strength niacin (Niaspan), a type of B vitamin that many doctors already prescribe as potential heart protection. The failed study marks the latest setback in the quest to harness good cholesterol to fight the bad kind.

The trial, called AIM-HIGH, looked at whether adding Niaspan — a high-dose, extended-release form of niacin, or vitamin B3 — to certain heart-disease patients’ statin drug regimens would prevent more cardiac events than a statin alone.

“This sends us a bit back to the drawing board,” said Dr Susan Shurin, cardiovascular chief at the National Institutes of Health. The study tested Abbott Laboratories’ Niaspan, an extended-release form of niacin that is a far higher dose than is found in dietary supplements. As expected, the Niaspan users saw their beneficial HDL levels rise and their levels of risky triglycerides drop more than people who took a statin alone.

But the combination treatment did not reduce heart attacks, strokes, or the need for artery-clearing procedures such as angioplasty, the NIH said. It led the NIH to stop the study 18 months ahead of schedule.

Related news: Arterial plaque test may accurately predict risk for cardiovascular complications among type 2 diabetics

Diabetes Can Be Predicted 7 Years Before Pregnancy With Blood Sugar And Body Weight

A woman’s risk of developing diabetes during pregnancy can be identified up to seven years before she becomes pregnant based on routinely assessed measures of blood sugar and body weight, according to a Kaiser Permanente study published in the online issue of the American Journal of Obstetrics and Gynecology.

Researchers at the Kaiser Permanente Division of Research in Oakland, Calif., studied 580 ethnically diverse women who took part in a multiphasic health checkup at Kaiser Permanente Northern California between1984 and 1996. The researchers looked at women who had a subsequent pregnancy and compared those who developed gestational diabetes mellitus (GDM) during pregnancy to women who did not have GDM.

The study found that the risk of GDM increased directly with the number of adverse risk factors commonly associated with diabetes and heart disease (high blood sugar, hypertension and being overweight) present before pregnancy. In addition, the authors found that adverse levels of blood sugar and body weight were associated with a 4.6-fold increased risk of GDM, compared to women with normal levels.

The study is among the first to look at routinely measured cardio-metabolic risk factors before pregnancy in women who later became pregnant and developed GDM. The research provides evidence to support pre-conception care for healthy pregnancies as noted in a 2006 report by the Centers for Disease Control and Prevention. That report suggested that risk factors for adverse outcomes among women and infants can be identified prior to conception and are characterized by the need to start, and sometimes finish, interventions before conception occurs.

Women who develop GDM during pregnancy are more likely to develop Type 2 diabetes after pregnancy, previous research has shown. GDM is defined as glucose intolerance that typically occurs during the second or third trimester and causes complications in as much as 7 percent of pregnancies in the United States. It can lead to early delivery and Cesarean sections, and increases the baby’s risk of developing diabetes, obesity and metabolic disease later in life.

Dr Monique M. Hedderson

“Our study indicates that a woman’s cardio-metabolic risk profile for factors routinely assessed at medical visits such as blood sugar, high blood pressure, cholesterol and body weight can help clinicians identify high-risk women to target for primary prevention or early management of GDM,” said lead author Monique Hedderson, PhD, a research scientist at the Kaiser Permanente Division of Research.

Although the established risk factors for GDM are older maternal age, obesity, non-white race/ethnicity, giving birth previously to a very large baby and a family history of diabetes, these risk factors are absent in up to half of women who develop GDM. This study is significant because it gives a better understanding of pre-pregnancy predictors of GDM that may help identify women at risk and get them into intervention programs before pregnancy to prevent GDM and its associated risks, researchers said.

Related articles on gestational diabetes:

• A study in the American Journal of Epidemiology found that cardio-metabolic risk factors such as high blood sugar and insulin, and low high density lipoprotein cholesterol that are present before pregnancy, predict whether a woman will develop diabetes during a future pregnancy.
•  A study in the American Journal of Obstetrics and Gynecology found there is an increased risk of recurring gestational diabetes in pregnant women who developed gestational diabetes during their first and second pregnancies.
•  A study in Diabetes Care of 10,000 mother-child pairs showed that treating gestational diabetes during pregnancy can break the link between gestational diabetes and childhood obesity. That study showed, for the first time, that by treating women with gestational diabetes, the child’s risk of becoming obese years later is significantly reduced.
•  A study in Obstetrics & Gynecology of 1,145 pregnant women found that women who gain excessive weight during pregnancy, especially in the first trimester, may increase their risk of developing diabetes later in their pregnancy.

Via EurekAlert

Related Video:

Why Wireless Health Matters

By Robert B. McCray, Co-Founder, President and CEO of the Wireless-Life Sciences Alliance (WLSA)

THE potential of wireless health will be realized in the effective blending of three bodies of learning: high technology; life sciences; and human factors. The last point is critical — end users (including consumers, patients and clinicians) will ultimately determine the successes and failures in wireless health.

Robert McCray

There is also a fourth factor in the creation of any convergence sector such as internet commerce, mobile data or digital music. The fourth factor is the ecosystem of innovators, executives, investors, clinicians (for healthcare) and policy makers who are creating the sector.

The following discussion is intended to level set the discussion about why wireless health is important, to provoke conversation, and undoubtedly to set myself up for some predictive failures.

What is wrong with healthcare and what does wireless health have to offer?

Societies have no choice but to change their healthcare systems in the face of exploding demand caused by aging and chronic disease. The U.S. healthcare system is already failing millions of its citizens. Wireless health offers the opportunity to satisfy this demand, thus improving life and creating shareholder value.

Nonetheless, it is apparent that some institutions and professions will resist the demand for more personalized and efficient access to care. In the face of competition and digital information, however, they will ultimately be unable to resist disruptive change any better than the automobile, music or retail industries.

Wireless health is powerful because it creates transparency in healthcare through measurable outcomes, and transparency creates accountability.

What can be done

Looking at developments in the field as a whole, and considering the global economic and social environment in which we exist, I offer the following conclusions and observations:

• If a device or service can be connected, it should be (under penalty of malpractice, obsolescence and/or customer dissatisfaction).  How else will you be able to answer questions about how your product works in the field or why someone should buy it? If you do not take this approach and your competitor does, how will you sell against connectivity? This is why we have Merlin, CareLink and Latitude even though St. Jude, Medtronic and Boston Scientific created these wireless services without extra reimbursement.
• In the developing world, increases in chronic disease and demand for access to health services rival or exceed our challenges in the developed world. U.S. life sciences companies should look for markets in the entire world and not just in the dwindling populations of rich and well insured in the U.S. and Europe. Five billion cell phone users constitute the largest distribution channel ever created in the world. How are you going to use it?
• Epocrates was founded on the principal that clinicians needed on-the-fly access to accurate and up to date information via mobile devices and it has grown to establish a platform serving a majority of U.S. practitioners with several important services. It has achieved business success and its investors and founders will be rewarded. Whether Epocrates will extend this platform to the rest of the world or leave that opportunity to others remains to be seen.
•   is moving towards free. Access to medical knowledge, including personal genomics, is being distributed directly to consumers. So far, these trends have primarily influenced a motivated minority of consumers and especially the healthy wealthy, but over time they will shift power and responsibility to patients who will have to manage more healthcare decisions for themselves and their families. Digital music ultimately reshaped the music industry. Wireless health will have a similar impact in healthcare.
• In societies with limited access to healthcare and limited spending, wireless health delivers access to knowledge and care.  In the U.S., it is disruptive and resisted. Why? Partially because the U.S. spends too much and gets too small a return compared with the rest of the world. There is resistance to change because it is economically, culturally and legally disruptive.

Consider the combined effects of the following:

• Professional licensure is well intended but state licensure and corporate practice restrictions shield physicians from competition.
• The FDA operates on a laudable principle that safety and efficacy must be demonstrated, but this standard should be relaxed if the new device or service is offering a monitoring of dark space where current services leave patients unmonitored.
• The fee for service system has created an environment where innovation depends on reimbursement which, in conjunction with device regulation, tends to freeze the innovation and impede its improvement.
• Notwithstanding these sources of inertia, the immutable forces of population aging, rising rates of chronic disease, and the effects of global competition, mean that (1) individuals will have increasing personal responsibility for coordinating their own and their family’s care and (2) access to fully insured care will continue to decrease. These trends turn “patients” into “consumers” and “caregivers” who demand better products and services than the healthcare industry is accustomed to delivering.

Fortunately, we have the technology tools to tackle these problems:

• Nearly ubiquitous wireless connectivity to the world’s population. Cell phones are a mobile and personal permanent address.
• Data storage, analytics and search capabilities that are declining in cost faster than the declining cost of content creation.
• Secure cloud based access to information via the Internet.
• Embedded wireless technology which enables wearable devices.
• Inexpensive whole genome sequencing and rapidly advancing esoteric diagnostic services, with results reported in a digital format to enable data sharing and analysis.

The Future of Healthcare

What will we do with these tools?  What is the future of the healthcare industry in the United States, the world’s most expensive healthcare market?

• Will it follow the trajectory of the music industry, which was controlled by a small number of companies until digital music and the Internet made access to music free, enabled free global distribution for artists, and transformed how music lovers spend their money.
• Will it follow the course of the auto industry which tried to maintain a market for low tech low quality cars, lost its status to international companies and now has downsized, created competitive products and is regaining market share.
• Unfortunately, elements of the U.S. healthcare industry may have more in common with the financial industry, especially its lack of transparency, high cost and government support.

In a sense, the U.S. has run the largest clinical effectiveness study in history with the Medicare program: approximately 50,000,000 patients have participated over 30 years. The U.S. is ranked last among 19 industrialized nations with respect to preventable deaths, despite outspending these nations as much as twofold (Commonwealth Fund, 2008).

The purpose of Medicare is to operate an effective health insurance program for the aged – notwithstanding clear evidence of its failure relative to the world, elements of the professions, key institutions, and consumers (as voters) resist thoughtful efforts at Medicare’s improvement. Fortunately, this problem has the attention of policy makers, entrepreneurs and some globally significant companies.

How fast will the U.S. change? How do businesses thrive and investors earn a return in the face of uncertainty? There is no guide book for this situation, but with healthcare being the largest component of the U.S. economy and with the development of middle class healthcare markets in Asia, it is certainly an area that is replete with opportunity.

Excerpted from Why Wireless Health Matters By Robert B. McCray

Diabetes & Depression Create Adverse Synergy

There’s a clear increase in risk to your health and to your life when you have a combination of diabetes and depression

DIABETES and depression are conditions that can fuel each other. Symptoms of clinical depression include anxiety, feelings of hopelessness or guilt, sleeping or eating too much or too little, and loss of interest in life, people and activities. So, there’s a clear increase in risk to your health and to your life when you have a combination of diabetes and depression.

While diabetes can be a challenge to control, depression can be difficult to treat and keep in remission. Growing evidence suggests the combination can be especially problematic for patients. And as if this adverse synergy were not bad enough, having these two conditions more than doubles the likelihood that a patient will develop dementia.

What this means is that depression can affect blood sugar levels and insulin metabolism through increased cortisol, contributing to unhealthy eating habits, weight gain and diabetes. On the other hand, management of diabetes can cause chronic stress and strain, which in the long run, may increase risk of depression. The two are linked not only behaviorally, but biologically, says Dr. Frank B. Hu, a professor of medicine at Harvard Medical School.

However, doctors are unsure whether one condition causes the other or if a single underlying factor is responsible for both ailments. If a substantial causal connection is established between the two disorders, it would be rather novel and could potentially change how doctors understand and treat both disorders.

New research findings from the University of California at San Diego further reinforce the view that since depression and diabetes often co-occur, psychiatrists should be aware that depressed patients may be at risk of the metabolic disorder. The findings of the study were presented at the American Psychiatric Association’s 164^th annual meeting in Honolulu last week.

In the San Diego study, reported the Los Angeles Times, researchers who reviewed the medical records of a group of 129 Hispanic diabetics discovered that diabetes was diagnosed first in 54 percent of men with both conditions, while depression was the initial diagnosis of 24 percent of men. Of women with both conditions, 59 percent were first discovered to have diabetes, while 29 percent were first diagnosed with depression.

While doctors are typically aware that someone with diabetes is at higher risk for depression, they may not look for mood disorders as a risk factor for developing diabetes, especially anxiety, the authors noted. Among men with diabetes and anxiety, 54% developed diabetes first and 45% developed anxiety first. Among women, 55% developed diabetes first and 39% developed anxiety first.

Latinos are known to have higher rates of type 2 diabetes than the general US population. Additionally, co-occurring mood disorders are common among these individuals. This made this group of patients an ideal population for studying the relationship between mood disorders and type 2 diabetes.

The San Diego researchers said it is unclear why there is this association between the two conditions, but said that their findings show that there is a strong need to monitor individuals with type 2 diabetes for future mental health issues as the metabolic condition appears to precede mood disorders.

Another research, conducted at Harvard University, found that study subjects who were depressed had a much higher risk of developing diabetes, and those with diabetes had a significantly higher risk of depression, compared to healthy study participants.

A study carried out by the German Diabetes Association (DDG) has also shown that depression can heighten the risk of developing type 2 diabetes as the mental illness also increases the likelihood of obesity and failing to take enough exercise.

The Chennai (India) Urban Rural Epidemiological Study involving around 23,000 participants found that depression can increase the risk of diabetes due to increased levels of counter-regulatory hormones, which can lead to obesity, insulin resistance and glucose intolerance. “The lesson in this is that not only should we treat diabetics for depression, but that by treating depression, the person may actually be able to side-step diabetes,” said co-author Dr. V Mohan.

The American Diabetes Association advises that individuals with type 2 diabetes should consider seeking mental health help if they begin to feel three or more common symptoms of depression, which may include loss of pleasure, loss of appetite, sadness, trouble concentrating and suicidal thoughts.

The bottom line: Since diabetes and depression can influence each other and thus become a vicious cycle, primary prevention of diabetes is important for prevention of depression, and vice versa.

Sources: American Psychiatric Association, American Diabetes Association

Common Test Could Help Predict Early Death In Diabetes

High levels of calcified ‘plaque’, a strong indicator of coronary heart disease, can be measured by a special ‘gated’ CT scan that costs just over $200

WHILE vascular disease is common in the general population, it is twice as common in people with diabetes. At least 60 percent of diabetes patients – even those on dialysis for kidney failure – ultimately die of a vascular event, such as heart attack or stroke. However, questions about why so many diabetes patients die early have remained unanswered in the medical community’s understanding of the disease.

Diabetes is associated with many other medical problems so identifying a way to determine who is at highest risk and who needs the most intensive medical monitoring and care is especially important. Now new findings reveal that a common test may be useful in predicting early death in individuals with diabetes. The study appears in the May issue of Diabetes Care.

Dr. Donald W. Bowden

“People with diabetes are already at high risk of developing heart disease and experiencing an early death,” said Donald W. Bowden, Ph.D., the director of the Center for Diabetes Research at Wake Forest Baptist Medical Center and lead investigator in a press statement. “With this study, we’ve discovered that we can identify a subset of individuals within this high risk group who are at even higher risk, and the means to do this is already widely available in the form of a computed tomography (CT) scan – a relatively inexpensive and non-invasive test.”

For the Diabetes Heart Study, Bowden and colleagues have been following nearly 1,500 patients with diabetes in North Carolina for about 13 years, gathering data on various aspects of the disease and how it affects individual health. As original study participants began to die, the researchers sought to understand why.

“When we reviewed the data last year, we were shocked by the number of participants who had already died during this study,” Bowden said. “We wanted to find out if there were any predictors of who would succumb versus those who are still living. In a group of people who are already at high risk, we were looking for a way to identify which individuals were at even higher risk for early death, with the goal of finding interventions or ways to focus medical care and attention toward those individuals at highest risk.”

A high coronary artery calcium (CAC) score is known to be a strong indicator of coronary heart disease. The score provides a measure of how much coronary artery disease, or calcified ‘plaque’ is present in the blood vessels of the heart. Plaque plays a major role in heart attacks and other vascular events and can be measured by taking a special ‘gated’ CT scan which, in comparison to typical CT scans, uses very few X-rays, does not require any injections and generally takes less than 10 minutes to perform. (At Wake Forest Baptist, the test costs just over $200 and some insurance companies will cover the exam in appropriate situations, informs the press statement.).

Within the diabetes-affected population, there is a very wide range of calcified plaque buildup in the arteries and the heart, from individuals with none at all, to people whose entire vessels are nearly completely calcified. The researchers separated more than 1,000 study participants into five groups, according to the amount of calcified plaque they had in their blood vessels at the beginning of the study. The health of those participants was then followed for an average of 7.4 years before researchers compared the data from those who died during the study to those who are still living.

“We saw a dramatic risk of dying earlier in the people with highest levels of calcified plaque in their blood vessels,” Bowden said. “When comparing the group with the highest amount of plaque to the group that had the lowest amount of calcified plaque, the risk of dying was more than six times greater in the group with high levels of calcified plaque. The difference in risk that we revealed is striking. It’s in a group of people who are already at risk, but the CAC level really rather dramatically differentiates risk between people within this high risk group. This finding could have novel clinical implications.”

“The striking magnitude of the risk suggests very strongly that other research samples should be evaluated, especially in individuals with diabetes,” he said.

Source: Wake Forest Baptist Medical Center

Diabetes: Tale of 2 Mice Pinpoints Major Factor for Insulin Resistance

Joslin Diabetes Center scientists identify promising candidate for drugs treating type 2 diabetes and fatty liver disease

RESEARCHERS at Joslin Diabetes Center have identified an enzyme called PKC-delta as an important molecular modifier for development of insulin resistance, diabetes and fatty liver in mice. They also have found evidence suggesting a similar role for the enzyme in humans, making PKC-delta a promising new target for drugs for diabetes and related ailments.

It’s well known that insulin resistance typically occurs prior to type 2 diabetes. You can be insulin resistant for years before developing the disease, and often a diagnosis of type 2 diabetes is a person’s first sign that they are in fact insulin resistant.

The road to type 2 diabetes is paved with insulin resistance, a condition often associated with obesity in which the hormone begins to fail at its job helping to convert sugars to energy.

Investigators in the laboratory of C. Ronald Kahn, M.D., began with two existing strains of mice that are on opposite sides of the spectrum for insulin resistance. “The ‘B6’ mouse is very prone to develop both obesity and diabetes, and the ‘129’ mouse is quite protected from both, even if it possesses a genetic defect in insulin signaling,” says Dr. Kahn, Professor of Medicine at Harvard Medical School.

“Comparing the two models, it’s as if there’s an on/off switch for insulin resistance and diabetes between them. We reasoned that if we could find out the differences between B6 and 129 mice, we could identify a factor that could be a major modifier of insulin resistance, and a good drug target for treatment of type 2 diabetes,” he said

Dr C. Ronald Kahn, MD

In previous work, the Kahn lab created a genetic cross between these two mice models, did a genome-wide screening and found an area on mouse chromosome 14 that appeared to be important for insulin sensitivity. In the latest paper, published online in the Journal of Clinical Investigation, they followed up and found that PKC-delta stood out in activity among the genes in that region.

The researchers then showed that levels of the PKC-delta enzyme were about two times as high in the liver and other tissues in the B6 as in the 129 mouse. When both types were put on high-fat diets, levels of the enzyme stayed the same in the 129 mouse but rose to three times higher in the B6 mouse.

Could these differences be enough to make the profound change in insulin sensitivity? The scientists next created three new mice models to check.

In one model, they removed one of the two normal copies of the PKC-delta gene from B6 mice, thus cutting production of the enzyme in half, and the mice became much more insulin sensitive. In a second effort, they removed the gene entirely from the livers of B6 mice, and again the resulting mice were more insulin sensitive. In a third model, they inserted an extra copy of the PKC-delta gene in the liver of 129 mice, which became much more insulin resistant and diabetic.

In short, PKC-delta levels correlated closely with insulin resistance and the abnormalities in glucose tolerance in all three cases of mice. In addition, the insulin resistance correlated with increased fat in the liver, an increasing problem in people with insulin resistance.

Biopsies of human liver tissue, Dr. Kahn says, also showed that levels of the enzyme are heightened in people who are obese or have diabetes. “People with diabetes tend to get fatty liver and that also seems to correlate with the activity of PKC-delta,” he adds.

Overall, “drugs that inhibit the activity of PKC-delta in the liver and other tissues potentially could aid treatments for diabetes and fatty liver disease, which is second only to alcohol as a cause of liver failure,” Dr. Kahn says.

Via Eurekalert

Limiting Cholesterol Levels May Minimize Inflammation and Reduce Type 2 Diabetes Risk

Study will make possible new target therapies that help predict susceptibility to the metabolic condition and perhaps prevent diabetes

BY stimulating the enzyme cholesteryl ester hydrolase (CEH) to remove more cholesterol from cells, it may be possible to limit inflammation, improve insulin sensitivity and reduce an individual’s type 2 diabetes risk, claims a group of researchers from Virginia Commonwealth University School of Medicine. The results of the study have been published online in the Journal of Biological Chemistry.

Cholesterol has long been known to increase inflammation levels, and inflammation is well regarded as a risk factor for type 2 diabetes. Yet the researchers noted that few treatments for type 2 diabetes specifically target high cholesterol levels. It is hoped that the study will make possible new target therapies that help predict susceptibility to the metabolic condition, and perhaps prevent diabetes in the future.

“Although diabetes and heart disease often co-exist, current management of diabetes does not necessarily include cholesterol and/or inflammation control,” said lead researcher Shobha Ghosh, PhD. “These studies provide the first evidence that targeting fat tissue inflammation as well as elimination of cholesterol from the body may be emerging new strategies to prevent diabetes.”

For the study, the team analyzed the effect of turning up the expression of a gene that regulates CEH levels in a group of mice. The results showed that even when fed a high-fat diet, these mice had lower levels of inflammation and were more sensitive to the effects of insulin.

The results held true despite the fact that mice still gained significant weight from being fed the high-fat diet. Ghosh explained CEH appeared to cause low-density lipoprotein cholesterol molecules to exit cells, where they could then be neutralized by high-density lipoprotein cholesterol cells and taken to the liver for processing.

Ghosh said that these findings suggest that taking steps to control cholesterol levels in individuals with other risk factors for type 2 diabetes may be an effective treatment strategy. Additionally, they reveal that stimulating the genes that regulate CEH levels in the body may be one of the surest ways to control cellular cholesterol levels and limit fat’s pro-inflammatory effects.

From Endocrine Today

Related story: Arterial Plaques May Be Reduced By Increasing the Amount of a Key Enzyme in Cells Storing Cholesterol

Can A Low Fat Diet Ward Off Diabetes Without Weight Loss?

HOW your diet affects your health is a big topic in research these days, and this is reflected in the news headlines every week. The problem is that the research findings keep changing the landscape of what’s healthy and what’s not. Eggs were bad, now they’re good. Margarine was good, now it’s bad. Eat low-fat! No, now eat low-carb. For people with no health problems, trying to adhere to the latest dietary advice is simply confusing. For people with chronic conditions such as diabetes, it can be downright dangerous.

So a new research study from the University of Alabama at Birmingham (UAB), which claims that small differences in diet – even without weight loss – can significantly affect risk for diabetes, is bound to raise more questions than it answers.

The unique aspect of this study ‒ published online May 18, 2011, by the American Journal of Clinical Nutrition ‒ is that diabetes risk was reduced independent of weight loss. Received wisdom says overweight individuals can reduce risk of type 2 diabetes by shedding the extra pounds through a combination of diet and exercise.

In the UAB study, 69 healthy, overweight people who did not have diabetes — but were at risk for it — were placed on diets with modest reductions in either fat or carbohydrate for eight weeks. “At eight weeks, the group on the lower fat diet had significantly higher insulin secretion and better glucose tolerance and tended to have higher insulin sensitivity,” said Barbara Gower, Ph.D., professor in the Department of Nutrition Sciences at UAB and lead author of the study. “These improvements indicate a decreased risk for diabetes,” she said in a press statement.

The findings were even stronger in African-Americans, a population with an elevated risk for diabetes. Gower says African-Americans on the lower fat diet showed a stronger difference in insulin secretion compared to the lower carb group, indicating that diet might be an important variable for controlling diabetes risk in that population.

“People find it hard to lose weight,” said Gower. “What is important about our study is that the results suggest that attention to diet quality, not quantity, can make a difference in risk for type 2 diabetes.”

Study participants in the lower fat group received a diet comprising 27 percent fat and 55 percent carbohydrate.  The lower carb group’s diet was 39 percent fat and 43 percent carbohydrate. All food for the eight-week trial was provided by the study.

The study participants were fed exactly the amount of food required to maintain their body weight, and the researchers took into account any minor fluctuations in body weight during analyses. Thus, results from this study suggest that those trying to minimize risk for diabetes over the long term might consider limiting their daily consumption of fat at around 27 percent of their diet.

“The diets used in this study were actually fairly moderate,” said UAB dietitian Laura Lee Goree, R.D., L.D., a study co-author. “Individuals at risk for diabetes easily could adopt the lower fat diet we employed.  Our findings indicate that the lower-fat diet might reduce the risk of diabetes or slow the progression of the disease.”

But then, widely cited research studies also suggest that a low fat, high carb (LFHC) diet causes the following problems:

• Elevates triglycerides, lowers HDL (“good” cholesterol)

• Is ineffective for people with high insulin levels

• Increases insulin levels which spikes blood pressure

• Leads to greater risk for age-related macular degeneration (AMD)

The American Diabetes Association says millions of Americans are unaware they are at high risk with some groups having a higher risk for developing Type 2 diabetes, especially African-Americans, Latinos, Native Americans and the elderly.

It would therefore be premature to jump the gun to think that one can avoid the risk of diabetes without shedding weight by limiting fat intake. Gower rightly says further research is needed to determine if the difference between diets in carbohydrate or fat was responsible for the differences in the measures of glucose metabolism and probe the potential cause-and-effect relationship between insulin and glucose responses to the diets.

In the meanwhile, the best ways to maintain good health, diabetes or no, is to exercise, limit processed and refined foods, focus on fish, and eat a wide variety (and an abundance) of plant foods.

And shedding weight ‒ even if there’s no risk of developing diabetes ‒ will always remain a good idea.

Source: UAB News

Related Posts:

How Fatty Foods Lead To Diabetes

Is the ADA Shifting its Stance About Carbs?