Greater Risk of Nephropathy in Hypertensive Diabetes Reported

The lifetime risk of nephropathy among hypertensive patients with type 2 diabetes may be greater than previously reported, according to researchers.

In an observational cohort study of 11,526 patients with type 2 diabetes and hypertension, the investigators, led by Suma Vupputuri, PhD, MPH, an epidemiologist at Kaiser Permanente Center for Health Research/Southeast in Atlanta, showed that 68% of patients with normal albumin excretion at baseline had developed micro- or macroalbuminuria after a mean follow-up period of 5.5 years. Dr. Vupputuri presented study findings at the 46^th Annual Meeting of the European Society for the Study of Diabetes.

In previous studies, researchers had estimated that nephropathy develops in one-third of diabetic patients, Dr. Vupputuri noted. These studies, however, were based on data that were collected when glycemic levels were higher and before aggressive treatment had been shown to reduce diabetic complications.

In the new study, micro- and macroalbuminuria rarely progressed to end-stage renal disease (ESRD). In addition, if macroalbuminuria is present at baseline, the use of ACE inhibitors or angiotensin receptor blockers (ARBs) has a protective effect, the study showed.

The study included subjects who were at least 18 years old and who had measurements of urine albumin-to-creatinine ratios (UACR) in 2001, 2002, or 2003, and at least one additional measurement three to eight years later. Investigators defined micro- and macroalbuminuria as a UACR of 30-299 and 300 mcg/mg or higher, respectively. A UACR below 30 was considered normal. The first UACR value recorded in a stage higher than at baseline defined progression.

Almost half of the patients with normal albumin excretion at baseline progressed to microalbuminuria, but few went beyond that stage. Similarly, ESRD seldom developed in patients who first presented with microalbuminuria or macroalbuminuria

Over 89 months of follow-up, patients with normal baseline UACR's showed the highest rate of progression, followed by those with microalbuminuria at baseline, and then macroalbuminuria at baseline (94.6, 44.1, and 6.7 per 1,000 patient-years, respectively).

“Among patients with normal albumin at baseline, those who progressed to a higher stage of nephropathy were in general older, had a longer duration of diabetes, had higher mean blood pressures, and higher HbA_1c's,” Dr. Vupputuri said.

Patients who progressed from microalbuminuria were more likely to be male, with a longer duration of diabetes, higher mean blood pressure, and higher HbA_1clevels. The progressors among the group with macroalbuminuria at baseline had similar risk factors as the microalbuminuria group plus lower estimated glomerular filtration rates and a diagnosis of cardiovascular disease or heart failure. In all the baseline cohorts, most patients were receiving antihypertensive agents (78%-91%), about half were on statins, and 67%-79% were receiving antihyperglycemic drugs. Insulin use went up and oral agents down with increasing nephropathy stage. ACE inhibitor or ARB use ranged from 61%-67% for all baseline groups whether they progressed or not, except for patients with macroglobulinuria who progressed. In this group, ACE inhibitor or ARB use was only 38%.

Because nephropathy is a major cause of cardiovascular disease and ESRD, it is important to understand the progression from normal levels of albumin excretion to micro- and macroalbuminuria and to define the risk factors for nephropathy progression.

Analyses showed that while ACE inhibitor or ARB use was not significantly associated with the progression of nephropathy for patients with baseline normal albumin excretion or microalbuminuria, use of these drugs was associated with a 47% decreased risk of progression in patients with baseline macroalbuminuria. In these patients, each five-year increment in age was associated with a 21% decreased risk. Each 10 mL/min/1.73 m² increase in estimated glomerular filtration rate was associated with a 65% reduced risk.

Estimates of risk of progression could have been limited by survivor bias of patients who died before their nephropathy might have progressed, Dr. Vupputuri said. In addition, she said, “The use of ACE [inhibitors] and ARB's was lower than expected in this population.” Therefore, greater use of these drugs may further reduce the burden of disease, she observed.

Session moderator Leszek Czupryniak, MD, PhD, associate professor of diabetology and internal medicine at the University of Lodz in Lodz, Poland, commented, “What was interesting in the study is that a lot of people develop early kidney damage, but then very few of them progress to end-stage renal disease.”

Although nearly half the people with normal albumin excretion developed microalbuminuria, only 6% progressed to macroalbuminuria, and a tiny fraction (0.09%) developed ESRD, Dr. Czupryniak pointed out. “We are able to maintain patients at an early level of kidney damage for years,” he said. “It's easy to develop microalbuminuria, but then it's also easy to stop it at this level.” Therapeutic measures include drug, diet, and lifestyle interventions, he added.

Abbot’s Recall of 359 BS Million Test Strips Should Have Make Front Page

Came across this Letter to Editor in Chicago Tribune. The writer rightly wonders: “Why was that article (on Abbot recalling 359 million BS test strips) in the business section on page 29?” Indeed, most news (good, bad, ugly) relating to the Pharma industry is routinely relegated to the business pages just because the holy stock price is more important that life-and-death issues. Community members must write to Editors to register their protest and educate them in basic journalistic practices (“if it affects a large number of people, it must be news”).

Having had Type 2 diabetes for the past 25 years I was pleased to find your article in the Tribune regarding the recall of certain test strips (Dec 23). I e-mailed the address listed and I found that the strips from Abbot Labs were listed in the recall. Before the article I could not figure out why my blood sugar readings lower than normal. As I said, I e-mailed them and they verified that those strips were defective. I was sent new strips to replace the bad ones. They also sent a new meter.

Why was that article in the business section on page 29? I am sure that I wasn’t the only person affected by those defective strips. Diabetes is a serious disease and cause death, especially for people who have Type 1. I presume the article was there because Abbott‘s stock went down a few dollars the day before, but who cares when your life is at stake? I believe it should have been in section 1 listed as a health recall alert. Thank you for alerting me to the situation anyway.
Harry Clinkunbroomer, Northbrook

US Drugmaker Abbot Labs Recalls 359m Blood Sugar Testing Strips

US drug maker Abbott Laboratories on Wednesday announced a recall of up to 359 million diabetes testing strips due to safety hazards.

The recall was initiated because the strips used by diabetics could give false low readings, the company said in a statement.

Abbott uncovered the problem after a routine internal review found that certain lots of the strips took too long to absorb the blood from a patient's finger, which could lead to inaccurate low readings of their blood sugar levels, the statement said.

The affected products should not be used and would be replaced at no cost, said the statement.

Meanwhile, the Food and Drug Administration (FDA) issued a warning that inaccurately low measurements by the strips may lead patients to raise their blood sugar levels unnecessarily or fail to detect dangerously high blood sugar levels.

The recalled strips were made between January and May and sold both to consumers and healthcare facilities, the FDA said.

"FDA and Abbott are reviewing the cause of the manufacturing defect to avoid this problem in the future," said Alberto Gutierrez, head of FDA's Office of In Vitro Diagnostics.

The lots of affected products were only distributed in the U.S. and Puerto Rico, according to Greg Miley, director of public affairs for Abbott Diabetes Care.

The products were marketed under a half-dozen brand names, including Precision Xceed Pro., Precision Xtra, Medisense Optium, Optium, OptiumEZ and ReliOn Ultima, the Abbott statement said.

Fatty Acid Tied to Lower Diabetes and Dyslipidemia Risk

Higher levels of circulating trans-palmitoleate, which may result from consumption of whole-fat dairy products, appear to be associated with lower insulin resistance, dyslipidemia, and incident diabetes, according to a study in the Dec. 21 issue of the Annals of Internal Medicine.

Watching your diet? If so, whole milk, butter, and cheese probably aren't regulars on your shopping list.

Should they be?

Scientists at Harvard School of Public Health have identified a fatty acid in whole dairy foods that is linked to a lower risk of type 2 diabetes. The compound, trans-palmitoleic acid, is a chemical cousin of cis-palmitoleic acid, a diabetes-blocking acid produced naturally in the liver.

In the study of data from 3,736 men and women, those with the highest levels of trans-palmitoleic acid in the blood were found to have a significantly lower risk of developing diabetes, as measured by blood glucose levels and other risk factors.

Lead researcher Dr. Dariush Mozaffarian, associate professor of epidemiology at the school, wonders if trans-palmitoleic acid may make up for the work that used to be performed by the cis-palmitoleic acid.

The study was published in the Dec. 21, 2010 edition of the Annals of Internal Medicine.

"Our working hypothesis, based on several observations," says Mozaffarian, "is that with modern diets being so high in carbohydrates and calories, the body's synthesis of cis-palmitoleic acid might be limited."

In other words, we might be eating so much that we are keeping cis-palmitoleic acid from doing its job.

"Trans-palmitoleic acid may be stepping in as a 'pinch hitter' for at least some of the functions of cis-palmitoleic acid," says Mozaffarian.

"I don't think there's enough evidence to show that we should start drinking whole milk," Dr. Joel Zonszein, director of the Clinical Diabetes Center at Montefiore Medical Center in New York City, told Health Day. "We need to understand the mechanism behind this association. Dietary changes in this country tend to be to extremes, but this study should not be used to make changes in the diet; it's just an observation right now."

Mozaffarian says he hopes his work will encourage more research, and that one day trans-palmitoleic acid could be used as a supplement.

So don't buy out the dairy section just yet. 

Courtesy: CBS News

Diabetes: Stress Hormone's Surprise Powers

A hormone that can wreak havoc with the body by setting off harmful effects of stress may have a far more positive use: in a new way to treat diabetes.

The hormone, known as corticotropin-releasing factor, or CRF, has been implicated in anxiety, obesity, addiction and even Alzheimer's disease. The brain and other organs make CRF. It triggers a cascade of chemicals that ultimately produce cortisol and adrenaline and activate the body's "fight or flight" response. Under chronic stress, cortisol breaks down muscle, suppresses the immune system and raises the risk of high blood pressure.

But recently, researchers have showed that CRF increases both insulin secretion and production of the cells that make insulin in the pancreas, known as beta cells. Diabetes, which affects nearly 24 million Americans, involves the body's inability to properly use insulin to convert sugar into usable energy. The findings, which support a hunch that others in the field have had, point to a possible pathway for treatment of diabetes.

"The machinery that allows the cell to respond to the hormone has been found," says Wylie Vale, a professor of molecular neurobiology at the La Jolla, Calif., Salk Institute for Biological Studies, who discovered the structure of CRF in 1981. "We are exploring how this machinery is controlled under conditions such as diabetes and obesity. What we really want to do is understand the system." The research of Dr. Vale and his colleagues was reported in a December paper published in the Proceedings of the National Academy of Sciences.

With Type 1 diabetes, formerly known as juvenile diabetes, the body doesn't produce enough insulin. This happens because the immune system attacks and kills beta cells. These patients are treated with insulin injections.

The most common form of diabetes, associated with obesity, is Type 2. Here, the body doesn't produce enough insulin and the cells from insulin-responsive tissues like muscle are unable to efficiently use the insulin that is produced. The beta cells go into overdrive to try to produce insulin but become overworked and ultimately stop functioning, according to Patricia Kilian, head of the beta-cell-regeneration program at the Juvenile Diabetes Research Foundation, which partially funded the study.

Most Type 2 treatments have focused on drugs to overcome the resistance to insulin in tissues or to promote insulin output by the beta cells. But there's been a recent focus on finding ways to keep beta cells alive in the body and restoring the ability to grow new ones, Dr. Kilian says. That could help prevent or delay long-term complications of diabetes, like kidney failure and nerve damage, she says.

An early clue to CRF's role in insulin production came when Dr. Vale and a group of colleagues identified a group of hormones called urocortins about 10 years ago and later found that one of them stimulated insulin production in the pancreas. Some urocortins bind at the same receptor sites on the surface of cells that CRF does.

Recently, Dr. Vale and Mark Huising, a post-doctoral researcher, along with Nils Billestrup, a colleague at the University of Denmark, decided to see whether CRF itself might have a similar effect on beta cells. Stimulating mouse and later human beta cells with CRF, the researchers found that it not only increased insulin release but also promoted growth of the beta cells.

The next step: to learn whether CRF could stimulate insulin production in mice. This presented new challenges. Exposing the mice to CRF would trigger the production of cortisol, usually part of the stress response, which in turn boosts bloodstream sugar and so sets off the release of insulin. This response would make it difficult to figure out whether CRF or cortisol was responsible for the insulin release.

To avoid that problem, Dr. Huising inactivated the cortisol response in the mice. He then administered CRF to the pancreas of the mice and showed that it was the reason for the increased insulin production. This finding "helps us better understand how blood-sugar control works in healthy individuals and in diseases such as diabetes and obesity," says Dr. Huising.

Researchers don't know yet how to use CRF to stimulate insulin in humans without initiating the chain of stress-related events that CRF usually triggers, as well as associated effects such as increased blood pressure. And, for Type 1 diabetes, CRF would not stop the body's immune system from attacking the beta cells in the first place.

At the same time, researchers are investigating the benefits from blocking CRF. Its suppression reduces anxiety in animals, and several major drug companies are working to turn that into treatments for anxiety and depression. CRF blockers are also being developed for irritable bowel syndrome, since research has shown that stimulation of CRF receptors in the colon leads to diarrhea and pain. Also, CRF receptors in the skin might be targets for treating conditions like psoriasis, and in the bladder for overactive bladder, according to Eric Zorrilla, associate professor at the Scripps Research Institute, who studies CRF, stress and addiction.

Limiting Salt Lowers Blood Pressure and Health Risks in Diabetes

For patients living with diabetes, reducing the amount of salt in their daily diet is key to warding off serious threats to their health, a new review of studies finds.

In the Cochrane review, the authors evaluated 13 studies with 254 adults who had either type 1 or type 2 diabetes. For an average duration of one week, participants were restricted to large reduction in their daily salt intake to see how the change would affect their blood pressure.

“We were surprised to find so few studies of modest, practical salt reduction in diabetes where patients are at high cardiovascular risk and stand much to gain from interventions that reduce blood pressure,” said lead reviewer Rebecca Suckling. “However, despite this, there was a consistent reduction in blood pressure when salt intake was reduced.”

Suckling is part of the Blood Pressure Unit at St. George’s Hospital Medical School, in London.

The review appears in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates research in all aspects of health care. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing trials on a topic.

Patients with diabetes need to be extra cautious to maintain their blood pressure at an acceptable range of less than 130/80 mmHg. However, in the 2003-2004 period, 75 percent of adults with diabetes had blood pressure greater than or equal to 130/80 mmHg or used prescription hypertension medications, according to the American Diabetes Association (ADA).

High salt intake is a major cause for increased blood pressure and, in those with diabetes, elevated blood pressure can lead to more serious health problems, including stroke, heart attack and diabetic kidney disease. The ADA also reports that diabetic kidney disease is the leading cause of chronic kidney disease, accounting for 44 percent of new cases in 2005.

In the Cochrane review, the participants’ average salt intake was restricted by 11.9 grams a day for those with type 1 diabetes and by 7.3 grams a day for those with type 2.

The reviewers wrote that reducing salt intake by 8.5 grams a day could lower patients’ blood pressure by 7/3 mmHg. This was true for patients with both type 1 and type 2 diabetes. The reviewers noted that this reduction in blood pressure is similar to that found from taking blood pressure medication.

Suckling acknowledged that studies in the review only lasted for a week and that the type of salt restriction probably would not be manageable for longer periods.

“The majority of studies were small and only of a short duration with large changes in salt intake,” she said. “These studies are easy to perform and give information on the short-term effects of salt reduction.”

However, Suckling said, the review also found that in studies greater than two weeks, where salt was reduced by a more achievable and sustainable amount of 4.5 grams a day, blood pressure was reduced by 6/4 mmHg.

Diabetes specialist Todd Brown, M.D., of the Division of Endocrinology and Metabolism at Johns Hopkins University, said that practicing low-salt diets of these types is quite challenging for most patients with diabetes even though they know the health risks.

“The effects of salt on blood pressure are well known to health professionals and most patients, but what is less well known is where the salt comes from in our diet,” Brown said.

“The overwhelming majority comes from the processed foods that we eat,” he said. “If we are going to realize the benefits of sodium reduction on blood pressure and other health outcomes, we should focus less on the salt shaker and more on what we buy in the supermarket and at chain restaurants.”

Thank you Health Behavior News Service

Diabetes May Clamp Down On Cholesterol The Brain Needs

The brain contains more cholesterol than any other organ in the body, has to produce its own cholesterol and won’t function normally if it doesn’t churn out enough. Defects in cholesterol metabolism have been linked with Alzheimer’s disease and other neurodegenerative conditions. Now researchers at Joslin Diabetes Center have discovered that diabetes can affect how much cholesterol the brain can make.


Scientists in the laboratory of C. Ronald Kahn, M.D., head of Joslin’s Integrative Physiology and Metabolism research section, found that brain cholesterol synthesis, the only source of cholesterol for the brain, drops in several mouse models of diabetes. Their work was reported online in the journal Cell Metabolism on November 30.


“Since cholesterol is required by neurons to form synapses (connections) with other cells, this decrease in cholesterol could affect how nerves function for appetite regulation, behavior, memory and even pain and motor activity,” says Dr. Kahn, who is also Mary K. Iacocca Professor of Medicine at Harvard Medical School. “Thus, this has broad implications for people with diabetes.” Other investigations have gathered strong evidence that people with diabetes may display varying types of alterations in brain function or ways of responding to stress, he points out.


“It is well known that insulin and diabetes play an important role in regulating cholesterol synthesis in the liver, where most of the cholesterol circulating in blood comes from,” Dr. Kahn adds. “But nobody had ever suspected that insulin and diabetes would play an important role in cholesterol synthesis in the brain.”


In addition to its potential role in Alzheimer’s disease and other forms of neurological dysfunction, the newly discovered mechanism may play a role in diabetic neuropathy, which remains a large challenge for therapy.


People with diabetes are also known to be more prone to depression, memory loss and eating disorders than people without diabetes, and imaging studies have shown that people with diabetes have altered brain function compared to those without.


Additionally, the finding raises a question about potential interactions between anti-cholesterol drugs and diabetes.


In the Joslin study, scientists first examined gene expression in the hypothalamus of a mouse model of insulin-deficient (type 1) diabetes. They found decreased expression for almost all of the genes of cholesterol synthesis, including a gene called SREBP-2, which acts as a master regulator for cholesterol production. Similar findings were present in the cerebral cortex and other regions of the brain in these animals and also found in several other mouse models of diabetes. In the insulin-deficient animals, this phenomenon was associated with decreased cholesterol synthesis. Treatment of the mice with insulin, either by normal injection or injection into the fluid surrounding the brain, reversed the process.


“Our studies showed that these effects occurred in both the neurons and supporting ‘glial’ cells that help provide some nutrients to the neurons,” says Kahn. “Ultimately this affects the amount of cholesterol that can get into the membranes of the neuron, which form the synapses and the synaptic vesicles — the small structures that contain neurotransmitters.”


Additionally, the Joslin work showed a connection between the decrease in brain cholesterol synthesis and appetite. When the scientists took normal mice and temporarily reduced cholesterol creation in the hypothalamus with a technique known as RNA interference, the animals started eating more and gained significant weight. Previous studies by other labs have demonstrated that diabetes may affect brain hormones involved in appetite regulation.

Ryo Suzuki, Ph.D., a postdoctoral researcher in the Kahn lab, is first author on the paper. Other Joslin contributors include Kevin Lee and Enxuan Jing. Other co-authors include Sudha B. Biddinger of Children’s Hospital Boston, Jeffrey G. McDonald of the University of Texas Southwestern Medical Center, and Thomas J. Montine and Suzanne Craft of the University of Washington in Seattle. The work was supported by the National Institutes for Health, the Iacocca Foundation and the Manpei Suzuki Diabetes Foundation.