Researchers seeking to connect type 1 diabetes and cleanliness

person reading newspaper.jpg-600x450

January 20th, 2014
Original Article: Washington Post

It may come as a surprise that Finland — one of the least polluted, wealthiest countries, where average life expectancy is among the world’s highest — has the highest rate of Type 1 diabetes. Each year, there are about 58 cases diagnosed per 100,000 children; in the United States there are 24 cases per 100,000, according to the International Diabetes Federation.

Some researchers suspect there may be a connection between Finland’s cleanliness and the incidence of the disease there. They are investigating whether the lack of exposure to a specific group of bacteria found in the intestine may be causing weaker immune systems in Finnish children, making them more susceptible to Type 1 diabetes.

This so-called hygiene hypothesis — that cleaner living can result in a weaker immune system — has also been linked to ailments such as asthma, allergies and other autoimmune diseases.

“We are working along the idea that we have a trigger which most likely is an infectious agent,” said Mikael Knip, a professor of pediatrics at the University of Helsinki who has been studying diabetes for 30 years. “There is an association between such infections and appearance of antibodies.”

Just as there are microbes that trigger the disease, Knip says there are also some bacterial or viral infections that, if they occur at an early age, can protect a young child from developing Type 1 diabetes.

Type 1 diabetes, which affects approximately 37 million people worldwide, is an autoimmune disease in which the body does not produce sufficient insulin, a hormone needed to break down sugars. Typically diagnosed in children, teens and young adults, the disease can eventually damage the eyes and organs such as the kidneys, and it increases the likelihood of stroke and heart failure. Type 1 diabetes can shorten a person’s life span by as many as 10 years, according to the National Institutes of Health. There is no cure, although one promising line of research involves transplanting new insulin-making tissue, called islets, into the pancreas, where insulin is produced.

In Finland, Salli Salonen has been dealing with Type 1 diabetes since the disease was diagnosed in her daughter Emilia shortly after she was born nine years ago. A single parent with two other children, Salonen says she struggled at first with Emilia’s care. “My problem in the beginning was you always have to make decisions what to do now. The glucose is this and this and that, I am 30 minutes from food. I found that very stressing.”

But Emilia has grown to manage her disease, learning how to check her insulin pump and her blood-sugar readings during the day. For the past three years, she has also been part of a study in which researchers, led by Knip, took blood and tissue samples from nearly 3,500 children — from Finland, Estonia and Karelia, a part of Russia that once belonged to Finland. While residents of the three areas share similar language and genes, the rate of Type 1 diabetes is remarkably different, as are their levels of hygiene.

At 58 cases per 100,000, Finland’s rate is about six times as high as Karelia’s. Estonia’s is between 25 and 30 cases per 100,000, but it has tripled in the past 15 years, catching up with its Western European neighbors. Karelia, just north of St. Petersburg, is poorer, and children there grow up in an environment that is dirtier than the two other study areas, according to Knip. There, the rate is less than 10 cases per 100,000 per year.

“We are studying babies and young children to look whether we have a specific microbe of the infections or whether the total microbial load is important,” he said.

Microbes found in stool samples from each child and in dust particles from their homes are also being analyzed by researchers at the Harvard/MIT Broad Institute and Massachusetts General Hospital in Boston.

“What we have been able to do is get a detailed trajectory of how bugs change and how stable the microbiome is,” said Ramnik Xavier, chief of gastroenterology at Massachusetts General and senior associate at the Broad Institute. “The only way is to identify the bugs and then do experiments to see whether they” cause diabetes to develop.

It turns out that the Russian children play outside more often and are around more animals. Many of their houses don’t have air conditioning or central heat. They also have greater exposure to such microbes as hepatitis A, Helicobacter pylori (which causes stomach ulcers) and Toxoplasmosa gondii, a parasite spread by cat feces.

Vallo Tillman, a pediatrician who runs the children’s clinic at the Tartu University Hospital in southeast Estonia, says that not only are many more children in his country acquiring diabetes, they also are getting sicker at a much younger age than before. He says that Estonian children’s immune systems may not be getting the germ-fighting workout that they did a few decades ago.

“Before, the quality of the Soviet building construction wasn’t very good,” Tillman said. “It was common that wind blew through the windows and doors. While now, our flats and houses are very tight.”

Some scientists are skeptical of the cleanliness-disease connection. “It’s plausible, but it’s a long reach,” said Desmond Schatz, medical director at the UF Diabetes Institute.

“We are at a stage in understanding that a change in microbial flora in high abundance or low abundance in the human gut can precede the onset of human diabetes,” Schatz said. “It’s all well to demonstrate there may be changes, but the next step is to associate changes in bacteria with function.”

Even if he does find the answer as to which microbe or combination of microbes triggers Type 1 diabetes, Knip says, he doesn’t want turn back the clock on sanitary conditions in Finland. Instead, he says, researchers might one day develop a drug or probiotic that can stimulate the developing child’s immune system. “Current probiotics are too mild,” Knip said. “You need more offensive microbes to get protection against autoimmune disease like diabetes.”

In the United States, American researchers are comparing large groups of children to see if those who develop Type 1 diabetes have anything in common. The National Institutes of Health is coordinating a study that is following nearly 2,000 children from birth to age 15 in Denver, Seattle, Atlanta and Gainesville, Fla.

“We are collecting drinking water, we measure psychological stress, we look at the introduction of food in the baby’s diet, we take note of all their allergies and whether they have pets in the house,” said Beena Akolkar, one of the coordinators of the study, which is known as the Environmental Determinants of Diabetes in the Young, or TEDDY.

The results and a possible preventive treatment won’t come soon enough for such mothers as Salonen. An IT professional who knows that her daughter will be living with diabetes for the rest of her life, she is designing a device based on the iPhone to help diabetic children and their parents better monitor blood glucose and insulin.

“If you have a machine that would show the blood glucose online,” she said, “then you could make quick decisions.”

In a recent Washington Post article, researchers detail that there may be a correlation between the lack of early exposure to a specific group of bacteria found in the intestine and weaker immune systems in Finnish children that make them more susceptible to Type 1 diabetes and other ailments such as asthma, allergies and other autoimmune diseases.

Collectively known as the “hygiene hypothesis,” researchers testing this theory are traveling to nearby Russian cities formerly part of Finland, where rates of type 1 diabetes are less than 10 per 100,000 (almost 6 times less). Microbial samples directly taken from infants and children are being collected, as well as dust samplings from homes. These samples are currently being analyzed at the Harvard/MIT Broad Institute as well as Boston’s Massachusetts General Hospital.

Desmond Schatz, MD, medical director of the UF Diabetes Institute, was  featured in the article. “It’s plausible, but it’s a long reach,” he said. “We are at a stage in understanding that a change in microbial flora in high abundance or low abundance in the human gut can precede the onset of human diabetes. It’s all well to demonstrate there may be changes, but the next step is to associate changes in bacteria with function.”