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Author: Sima

Published on Leave a comment on Walking Increases Blood Flow To the Brain

An interesting study looked at what the act of walking does to our brain, and found that it can modify and increase the amount of blood that’s sent to the brain (which is viewed as beneficial for brain function). The study, performed by researchers at New Mexico Highlands University in the United States, found that the foot’s impact on the ground while walking sends pressure waves through the arteries, which can increase the blood supply to the brain. This is referred to as cerebral blood flow or CBF.

These results may help explain other studies that find those that walk frequently (about 6 to 9 miles per week) have "less cognitive impairment" or cognitive decline, fewer memory problems, and greater brain volume with aging.  Another good reason to get out and walk - good for the heart, the body, and the brain. From Science Daily:

How walking benefits the brain

You probably know that walking does your body good, but it's not just your heart and muscles that benefit. Researchers at New Mexico Highlands University (NMHU) found that the foot's impact during walking sends pressure waves through the arteries that significantly modify and can increase the supply of blood to the brain. The research will be presented today at the APS annual meeting at Experimental Biology 2017 in Chicago.

Until recently, the blood supply to the brain (cerebral blood flow or CBF) was thought to be involuntarily regulated by the body and relatively unaffected by changes in the blood pressure caused by exercise or exertion. The NMHU research team and others previously found that the foot's impact during running (4-5 G-forces) caused significant impact-related retrograde (backward-flowing) waves through the arteries that sync with the heart rate and stride rate to dynamically regulate blood circulation to the brain.

In the current study, the research team used non-invasive ultrasound to measure internal carotid artery blood velocity waves and arterial diameters to calculate hemispheric CBF to both sides of the brain of 12 healthy young adults during standing upright rest and steady walking (1 meter/second). The researchers found that though there is lighter foot impact associated with walking compared with running, walking still produces larger pressure waves in the body that significantly increase blood flow to the brain. While the effects of walking on CBF were less dramatic than those caused by running, they were greater than the effects seen during cycling, which involves no foot impact at all.

Published on Leave a comment on Pollution Nanoparticles Found in Human Brains

This post is more on the theme of nanoparticles and human health. My last post was about a study that examined how inhaled nanoparticles  (for example, from air pollution) travel from the lungs to the bloodstream.

Well, today's post is about a pretty shocking 2016 air pollution nanoparticle study which examined the brains (brain tissue) of 45 dead people  (ages 3 to 92) who had lived for a long time in two places with heavy  particulate air pollution - Mexico City and Manchester, England. Some of the British people also had Alzheimer's disease or dementia.

The researchers found evidence that minute nano-sized particles of magnetite from air pollution can find their way into the brain. There are 2 forms of magnetite (which is an iron ore) - one naturally occurring (jagged edges in appearance), and one found commonly in air pollution (smooth and rounded - from being created in the high temperatures of vehicle engines or braking systems). The researchers are concerned that the air pollution nanoparticles may increase the risk for brain diseases such as Alzheimer's.

One of the researchers (Prof Barbara Maher) has previously identified magnetite particles in samples of air gathered beside a busy road in Lancaster, England and outside a power station. She suspected that similar particles may be found in the brain samples, and that is what happened. "It's dreadfully shocking. When you study the tissue you see the particles distributed between the cells and when you do a magnetic extraction there are millions of particles, millions in a single gram of brain tissue - that's a million opportunities to do damage."..."It's a whole new area to investigate to understand if these magnetite particles are causing or accelerating neurodegenerative disease."

However, it must be stressed that at this time there is no proven link between these magnetite particles and any neurodegenerative diseases. They're just wondering.... they call finding these pollution nanoparticles "suggestive observations".

From Medical Xpress: Toxic air pollution nanoparticles discovered in the human brain

Tiny magnetic particles from air pollution have for the first time been discovered to be lodged in human brains – and researchers think they could be a possible cause of Alzheimer's disease. Researchers at Lancaster University found abundant magnetite nanoparticles in the brain tissue from 37 individuals aged three to 92-years-old who lived in Mexico City and Manchester. This strongly magnetic mineral is toxic and has been implicated in the production of reactive oxygen species (free radicals) in the human brain, which are associated with neurodegenerative diseases including Alzheimer's disease.

Professor Barbara Maher, from Lancaster Environment Centre, and colleagues (from Oxford, Glasgow, Manchester and Mexico City) used spectroscopic analysis to identify the particles as magnetite. Unlike angular magnetite particles that are believed to form naturally within the brain, most of the observed particles were spherical, with diameters up to 150 nm, some with fused surfaces, all characteristic of high-temperature formation – such as from vehicle (particularly diesel) engines or open fires. The spherical particles are often accompanied by nanoparticles containing other metals, such as platinum, nickel, and cobalt.

Professor Maher said: "The particles we found are strikingly similar to the magnetite nanospheres that are abundant in the airborne pollution found in urban settings, especially next to busy roads, and which are formed by combustion or frictional heating from vehicle engines or brakes."

Other sources of magnetite nanoparticles include open fires and poorly sealed stoves within homes. Particles smaller than 200 nm are small enough to enter the brain directly through the olfactory nerve after breathing air pollution through the nose.....The results have been published in the paper 'Magnetite pollution nanoparticles in the human brain' by the Proceedings of the National Academy of Sciences.

A good discussion of the study in The Scientist: Environmental Magnetite in the Human Brain

Image of magnetite nanoparticles from the exhaust plume of a diesel engine. Credit Maher et al study, 2016.

 

 

A microscopic image shows magnetite nanoparticles in the human brain. Barbara Maher et al study, 2016.

 

 

Published on Leave a comment on Nanoparticles in Air Pollution Travel From Lungs to Bloodstream?

The use of nanomaterials has been really increasing  in recent years without us really understanding if  nanoparticles have negative health effects, and if they travel to the brain or other organs in the human body. Nanoparticles are used in many  consumer products, including foods (e.g., nano-sized titanium dioxide) and medicines, but they are also found in air pollution  (e.g., tires breaking down, vehicle exhaust).

Well..... evidence is starting to appear that YES - nanoparticles can travel  throughout the body, and they can accumulate in the body, including lungs and brain, and they can have negative health effects. For example, inhaled nanoparticles from air pollution are able to deposit deep in the lungs where they cause oxidative stress and inflammation.

Now new research in both humans and mice has shown that inhaled nanoparticles can travel from the lungs into the bloodstream. In this study both healthy males and heart disease patients inhaled gold nanoparticles of varying sizes. The gold was detected in the blood and urine within 15 minutes to 24 hours after exposure, and was still present 3 months after exposure. The levels were greater following inhalation of smaller 5 nanometer (nm) particles compared to the larger 30 nm particles (meaning the body had trouble clearing the smaller nanoparticles). The nanoparticles acculmulated more in inflamed vascular sites, including carotid plaques in patients at risk of a stroke.

Showing this is important in explaining how tiny nanosized particles in air pollution are linked to cardiovascular disease and death - for example, why and how they can trigger heart attacks and other "cardiovascular events".

Science Daily: Nanoparticles can travel from lungs to blood, possibly explaining risks to heart

Tiny particles in air pollution have been associated with cardiovascular disease, which can lead to premature death. But how particles inhaled into the lungs can affect blood vessels and the heart has remained a mystery. Now, scientists have found evidence in human and animal studies that inhaled nanoparticles can travel from the lungs into the bloodstream, potentially explaining the link between air pollution and cardiovascular disease. Their results appear in the journal ACS Nano.

The World Health Organization estimates that in 2012, about 72 percent of premature deaths related to outdoor air pollution were due to ischemic heart disease and strokes. Pulmonary disease, respiratory infections and lung cancer were linked to the other 28 percent. Many scientists have suspected that fine particles travel from the lungs into the bloodstream, but evidence supporting this assumption in humans has been challenging to collect. So Mark Miller and colleagues at the University of Edinburgh in the United Kingdom and the National Institute for Public Health and the Environment in the Netherlands used a selection of specialized techniques to track the fate of inhaled gold nanoparticles.

In the new study, 14 healthy volunteers, 12 surgical patients and several mouse models inhaled gold nanoparticles, which have been safely used in medical imaging and drug delivery. Soon after exposure, the nanoparticles were detected in blood and urine. Importantly, the nanoparticles appeared to preferentially accumulate at inflamed vascular sites, including carotid plaques in patients at risk of a stroke. The findings suggest that nanoparticles can travel from the lungs into the bloodstream and reach susceptible areas of the cardiovascular system where they could possibly increase the likelihood of a heart attack or stroke, the researchers say. [Original study.]

Published on Leave a comment on Blood Pressure Study Contradicts Sodium Limits in Dietary Guidelines

Another large recent study found that lowering sodium intakes (less than 2500 milligrams per day) wasn't linked to lower blood pressure. Over the course of 16 years, the researchers found that the study participants who consumed less than 2500 milligrams of sodium a day had higher blood pressure than participants who consumed higher amounts of sodium. However, the current 2015-2020 Dietary Guidelines for Americans recommends limiting sodium intake to 2,300 grams a day for healthy people. The researchers felt that based on recent studies with similar findings that the sodium guidelines should be changed.

This 16 year study found that people in the study who had normal intakes of sodium, but also higher intakes of potassium, calcium and magnesium exhibited lower blood pressure over the course of the study. And those people with higher combined intakes of sodium (3717 milligrams per day on average) and potassium (3211 milligrams per day on average on average) had the lowest blood pressure.

Some good potassium foods:  avocado, winter squash, sweet potato, potato, white beans, banana, spinach, salmon, dried apricots, tomato sauce, beans, and milk. Some good magnesium foods: dark leafy greens, nuts, seeds, fish, beans, whole grains, avocados, yogurt, bananas, dried fruit, dark chocolate. Some good calcium foods: milk, cheese, yogurt, kale, sardines, broccoli, white beans, and rhubarb. From Science Daily:

Low-sodium diet might not lower blood pressure: Findings from large, 16-year study contradict sodium limits in Dietary Guidelines for Americans

A new study that followed more than 2,600 men and women for 16 years found that consuming less sodium wasn't associated with lower blood pressure. The new findings call into question the sodium limits recommended by the current Dietary Guidelines for Americans. Lynn L. Moore, DSc, associate professor of medicine at Boston University School of Medicine, will present the new research at the American Society for Nutrition Scientific Sessions and annual meeting during the Experimental Biology 2017 meeting, to be held April 22-26 in Chicago.

"We saw no evidence that a diet lower in sodium had any long-term beneficial effects on blood pressure," said Moore. "Our findings add to growing evidence that current recommendations for sodium intake may be misguided." The 2015-2020 Dietary Guidelines for Americans recommends limiting sodium intake to 2,300 grams a day for healthy people. For the study, the researchers followed 2,632 men and women ages 30 to 64 years old who were part of the Framingham Offspring Study. The participants had normal blood pressure at the study's start. However, over the next 16 years, the researchers found that the study participants who consumed less than 2500 milligrams of sodium a day had higher blood pressure than participants who consumed higher amounts of sodium.

Other large studies published in the past few years have found what researchers call a J-shaped relationship between sodium and cardiovascular risk -- that means people with low-sodium diets (as recommended by the Dietary Guidelines for Americans) and people with a very high sodium intake (above the usual intake of the average American) had higher risks of heart disease. Those with the lowest risk had sodium intakes in the middle, which is the range consumed by most Americans.

The researchers also found that people in the study who had higher intakes of potassium, calcium and magnesium exhibited lower blood pressure over the long term. In Framingham, people with higher combined intakes of sodium (3717 milligrams per day on average) and potassium (3211 milligrams per day on average on average) had the lowest blood pressure.....Moore says that there is likely a subset of people sensitive to salt who would benefit from lowering sodium intake, but more research is needed to develop easier methods to screen for salt sensitivity and to determine appropriate guidelines for intakes of sodium and potassium in this salt-sensitive group of people.

Published on Leave a comment on Support Science

Image result for earth wikipedia On this Earth Day I want to say: Support science. Support the work of scientists. Science is the pursuit of knowledge. Science is about facts and evidence - not opinions. Medicine is applied science - scientific discoveries are turned into real-world medical treatments. Yes, scientific theories and what we know in science and medicine can change over time as more evidence is found. But science is not political, or it shouldn't be political. This is because we all benefit from science and scientific knowledge.

Sometimes there is bias in science (as when scientists receiving money from a corporation or working for a corporation then do research with results desired by that corporation), but that is why it is important to have transparency in research studies and results, and why good research involves peer review (other scientists review the research) and open discussion, and the importance of others having similar research results in an area. This is also why government funding of basic research is important.

Science is a process of understanding how the world works - it is curiosity driven and uses empirical evidence, particularly information acquired by observation and experimentation. Data is recorded and analyzed by scientists and is part of the scientific method. Basic science results in discoveries that may lead to incredible uses down the road and to amazing benefits to society. An example is the discovery of penicillin, which eventually changed medicine. Government funding has supported basic science for years - for example, NASA, National Oceanic and Atmospheric Administration, National Institutes of Health, and the National Science Foundation. Without government support, most basic scientific research will never happen.

Basically every post I've ever done is science based. Even the ones on sinusitis, Lactobacillus sakei, and the results of self-experimentation. And yes, self-experimentation in science and medicine has a long and honorable history. A very famous example was when the Australian physician Barry Marshall drank a petri dish containing Helicobacter pylori bacteria (from a patient) and soon developed the symptoms of peptic ulcer - this led to his eventually being awarded the Nobel Prize in 2005.

Similarly, through self-experimentation - my four family members, as well as many people writing to me, have reported amazing results within days of using a L. sakei product without changing anything else in their lives. These self-experiments were based on scientific evidence presented in the original Abreu et al study (2012) on sinusitis and the sinus microbiome. This is science at its most basic: doing "A" to a person with condition "B" and seeing the result "C" (which can be a positive effect, no effect, or negative effect).

So take a moment and appreciate all the different fields of science and how they have changed our lives: oceanography, chemistry, physics, earth science, ecology, geology, meteorology, astronomy, zoology, human biology (includes microbiology, anatomy, neurology, immunology, genetics, physiology, pathology, and ophthalmology), botany, anthropology, archaeology, criminology, psychology, sociology, computer science, statistics, mathematics, etc. Some areas of applied science are: engineering, computer science, and medicine. Wow....So please...Support science and the pursuit of knowledge. It's not political. It's not opinions or wishful thinking. Don't deny science.

Published on Leave a comment on Just For Fun, Part Two

I think everyone needs to laugh at the silly side of life sometimes. With that said, I am offering the following (all from The New Yorker archives) about health and food:

 

 

 

 

"Throw out the hummus - from now on, we only eat food too fake to host bacteria."

 

 

 

 

"Be honest - how much are you exercising?"

 

 

Credit: R. Glasbergen

Published on Leave a comment on Why Are Inflammatory Bowel Diseases In Very Young Canadian Children Increasing?

Sooo.....what is going on here? Why are very early onset (5 years and younger) pediatric inflammatory bowel diseases (IBD) in children increasing so rapidly in Canada? Inflammatory bowel diseases include Crohn's disease and ulcerative colitis. In the last two decades there has been an increase of 7.2% per year- to the point that it is among the highest in the world (9.68 per 100,000 children). Only Norway has a similar incidence (10.6 per 100,000 children under the age of 16 years), with Sweden having an incidence  of 12.8 per 100,000. Research studies find that the microbial communities are out of whack (dysbiosis) in IBD.

But why is the rate of IBD increasing in these northern countries? The researchers mention that rates are also increasing in the northern states in the US. Currently the reasons for the higher rates in Canadian and northern European children are not known. Some environmental factors such as lack of sunlight exposure and high rates of vitamin D deficiency, antibiotic use, and diet have been hypothesized as contributing to the pediatric IBD increase. Stay tuned... From Science Daily:

Inflammatory bowel diseases on the rise in very young Canadian children

Canada has amongst the highest rates of pediatric inflammatory bowel disease (IBD) in the world, and the number of children under five years old being diagnosed increased by 7.2 per cent every year between 1999 to 2010, according to a new study by researchers at the Institute for Clinical Evaluative Sciences (ICES), Children's Hospital of Eastern Ontario (CHEO) Research Institute and the Canadian Gastro-Intestinal Epidemiology Consortium.

"The number of children under five being diagnosed with IBD is alarming because it was almost unheard of 20 years ago, and it is now much more common," says Dr. Eric Benchimol, lead author of the study, scientist at ICES and a pediatric gastroenterologist at the Children's Hospital of Eastern Ontario Inflammatory Bowel Disease Centre, in Ottawa. IBD primarily includes Crohn's disease and ulcerative colitis, which are lifelong conditions that cause inflammation in the digestive tract, leading to chronic diarrhea, blood in the stool, abdominal pains and weight loss.

Researchers say a change in the bacterial composition of the gut may be to blame for the increase in IBD cases but they don't know what is causing the change. They suspect a combination of environmental risk factors could be to blame, such as early life exposure to antibiotics, diet, or lower levels of Vitamin D in Canadians.

The researchers found that the incidence of IBD has stabilized in children over the age of five, but in children under five it continues to rise rapidly. The researchers estimate that approximately 600 to 650 children are diagnosed with IBD every year in Canada. [Original study.]

Published on Leave a comment on Canadian Agency Detected Weed-Killer In 30 Percent of Foods Tested

This site has several recent posts about the controversial pesticide glyphosate (found in Monsanto's Round-Up). Glyphosate is the most heavily used pesticide in the world, and is used as a weed-killer (herbicide). It is used extensively in the USA - on farms, on roadsides, on residential properties, on school properties - basically everywhere, and its use is increasing. Studies have reported to have a number of worrisome health effects (including cancer) which its manufacturer is vigorously denying. There have even been recently revealed ties between Monsanto and some officials in the EPA.

United States government agencies only looked for the presence of glyphosate residues in some foods for a short time last year, and then stopped all testing. So WE DON'T KNOW HOW MUCH GLYPHOSATE WE ARE INGESTING DAILY in the United States. Our government refuses to test. Journalist Carey Gillam wrote that "a source within the FDA said there has been political pressure not to delve too deeply into the issue of glyphosate residues". To many it smacks of: if we don't test for glyphosate in foods, then there is no problem of how much is in foods. Because everyone agrees it is found in food - that's why there are standards for maximum residue levels or "tolerances" (but note they were increased when Monsanto asked to have them increased).

Well.....Canada does test for the pesticide in foods. The Canadian Food Inspection Agency just released a report of the results of testing 3,188 foods for traces of glyphosate residues, and found the pesticide in nearly 30% of the foods tested. Residue levels were above the Canadian acceptable limits in 1.3% of the foods. Glyphosate was found the most in: beans, peas, and lentil products (47.4%); grain products (36.6%); and baby cereals (31%). Only 1.3 percent of the total samples were found with glyphosate residue levels above what Canadian regulators allow, though 3.9 percent of grain products contained more of the weed killer than is permissible.

Legally allowable levels or Maximum Residue Levels (MRLs) vary from food to food and pesticide to pesticide, as well as from country to country. The European Union allowable residues for glyphosate on foods are lower than the US maximum allowable amount (yes, once again American standards are more lax). And remember that people ingest numerous pesticides in their foods, and no one knows what health effects are from these combinations of chronic low level pesticide exposures. NOTE: The only way to avoid glyphosate residues in foods is to eat organic foods. Glyphosate is not allowed to be used on organic foods or in organic feed for organically raised animals.

Canadian Food Inspection Agency: Safeguarding with Science: Glyphosate Testing in 2015-2016

Published on Leave a comment on Even Six Days of Corticosteroid Use Is Linked to Higher Rate of Problems

Image result for pills wikipedia Huh?...A recent study found that short-term use (less than 30 days) of commonly prescribed corticosteroid medications are linked to some nasty side-effects: an increase in rates of sepsis,  venous thromboembolism, and fractures. The most common reasons for the prescriptions were for upper respiratory tract infections, spinal conditions, bronchitis, and allergies. The study looked at 1.5 milliion patients, and found that the most common prescriptions written for oral corticosteroids was a six day methylprednisolone “dosepak” (about 47% of prescriptions). Note that while this was an "observational" study (so doesn't prove corticosteroid medication caused the effects), it still is concerning. One should always keep in mind that all medications have side effects, some bigger and some smaller.

Corticosteroids are powerful anti-inflammatory drugs that have been used to treat a variety of diseases for over seven decades. Long term use of corticosteroids is generally avoided because of the risks of serious complications (such as infection, venous thromboembolism, fractures, as well as chronic diseases). However, side-effects of short-term use have been unclear- which is why they are so frequently prescribed (about 1 in 5 Americans or 21% of the people in this study). This is why this study was needed. From Medical Xpress:

Common drugs, uncommon risks? Higher rate of serious problems after short-term steroid use

Millions of times a year, Americans get prescriptions for a week's worth of steroid pills, hoping to ease a backache or quell a nagging cough or allergy symptoms. But a new study suggests that they and their doctors might want to pay a bit more attention to the potential side effects of this medication. People taking the pills were more likely to break a bone, have a potentially dangerous blood clot or suffer a life-threatening bout of sepsis in the months after their treatment, compared with similar adults who didn't use corticosteroids, researchers from the University of Michigan report in a new paper in the British Medical Journal (BMJ).

Though only a small percentage of both groups went to the hospital for these serious health threats, the higher rates seen among people who took steroids for even a few days are cause for caution and even concern, the researchers say. The study used data from 1.5 million non-elderly American adults with private insurance. One in 5 of them filled a short-term prescription for oral corticosteroids such as prednisone sometime in the three-year study period. While the rates of the serious events were highest in the first 30 days after a prescription, they stayed elevated even three months later.

Using anonymous insurance claims data that IHPI purchased for use by U-M health care researchers, they found that half of the people who received oral steroids had gotten them for just six diagnoses, related to back pain, allergies or respiratory tract infections including bronchitis. Nearly half received a six-day prepackaged methylprednisolone "dosepak," which tapers the dose of steroids from highest to lowest. 

Dr. Waljee and his colleagues found higher rates of sepsis, venous thromboembolism (VTE) and fractures among short-term steroid users using multiple different statistical approaches to ensure their findings were as robust as possible....The consistent findings across the three approaches are important given the frequent use of these drugs and potential implications for patients. Waljee notes that the reason for this broad effect of steroids on complications may have its roots in how the drugs work: they mimic hormones produced by the body, to reduce inflammation but this can also induce changes that put patients at additional risk of serious events.

In the meantime, based on the new results, he advises patients and prescribers to use the smallest amount of corticosteroids possible based on the condition being treated. "If there are alternatives to steroids, we should be use those when possible," he says. "Steroids may work faster, but they aren't as risk-free as you might think." [Original study.]

Published on Leave a comment on Eating Fresh Fruit Is Linked to Lower Risk of Diabetes and Diabetic Complications

 Good news! Once again a study has confirmed that eating fresh fruits is associated with a lower incidence of type 2 diabetes. And even better - there is a dose related relationship - the more one eats daily, the better. So don't worry about the "sugar content" of fruit - the key is to eat fruit (as well as vegetables) to lower the risk of getting diabetes. And if you have type 2 diabetes, it will lower the incidence of death and complications from diabetes.

Here are the numbers for the 7 year study done in China of almost half a million people: eating fresh fruit was associated with a 12% lower risk of developing diabetes (compared to those never or rarely consuming fresh fruit). And in those who already had diabetes at the start of the study, consuming fresh fruit more than three days a week was associated with a 17% lower relative risk of dying from any cause and a 13%–28% lower risk of developing diabetes-related complications than those who consumed fruit less than one day per week.

Yes, I remember the advice that used to be given and is still given in parts of the world - that if you have diabetes, to restrict fruit, but studies are showing that advice to be wrong. Note that eating fresh fruits and vegetables has lots of other health benefits also - including lower rates of heart disease, stroke, and better mental (cognitive) functioning. From Science Daily:

Fresh fruit consumption linked to lower risk of diabetes and diabetic complications

In a research article published in PLOS Medicine, Huaidong Du of the University of Oxford, Oxford, United Kingdom and colleagues report that greater consumption of fresh fruit was associated with a lower incidence of diabetes, as well as reduced occurrence of complications in people with diabetes, in a Chinese population.

Although the health benefits of diets including fresh fruit and vegetables are well established, the sugar content of fruit has led to uncertainty about associated risks of diabetes and of vascular complications of the disease. Du and colleagues studied nearly 500,000 people participating in the China Kadoorie Biobank over about 7 years of follow-up, documenting new cases of diabetes and recording the occurrence of vascular disease and death in people with pre-existing diabetes.

The researchers found that people who reported elevated consumption of fresh fruit had a lower associated risk of developing diabetes in comparison with other participants (adjusted hazard ratio [aHR] 0.88, 95% CI 0.83-0.93), which corresponds to an estimated 0.2% reduction in the absolute risk of diabetes over 5 years. In people with diabetes, higher consumption of fresh fruit was associated with a lower risk of mortality (aHR 0.83, 95% CI 0.74-0.93 per 100g fruit/d), corresponding to an absolute decrease in risk of 1.9% at 5 years, and with lower risks of microvascular and macrovascular complications. [Original study.]