Fw Re: The Genetics of Diabetes
NY Times article from Cheryl
May 17, 2005
New Theory Places Origin of Diabetes in an Age of Icy Hardships
By SANDRA BLAKESLEE
When temperatures plummet, most people bundle up in thick sweaters,
stay cozy indoors and stoke up on comfort food. But a provocative
new theory suggests that thousands of years ago, juvenile diabetes
may have evolved as a way to stay warm.
People with the disease, also known as Type 1 diabetes, have
excessive amounts of sugar, or glucose, in their blood.
The theory argues that juvenile diabetes may have developed in
ancestral people who lived in Northern Europe about 12,000 years ago
when temperatures fell by 10 degrees Fahrenheit in just a few
decades and an ice age arrived virtually overnight.
Archaeological evidence suggests countless people froze to death,
while others fled south. But Dr. Sharon Moalem, an expert in
evolutionary medicine at the Mount Sinai School of Medicine in New
York, believes that some people may have adapted to the extreme
cold. High levels of blood glucose prevent cells and tissues from
forming ice crystals, Dr. Moalem said. In other words, Type 1
diabetes would have prevented many of our ancestors from freezing to
death.
The theory is described in the March 30 online edition of Medical
Hypotheses, a journal devoted to publishing bold, even radical,
biomedical theories that are potentially important to the
development of medicine.
Dr. Clive Gamble, a professor of geography and an expert on ancient
human migration at the University of London, said the theory
supported a growing body of evidence that Europeans were descended
from hunters with a tolerance to cold climates and not farmers from
warm ones. “As a Brit,” he said, “this makes perfect sense to me.”
Dr. Robert Hegele, an expert on diabetes and genetics at the
University of Western Ontario, said the theory was “an interesting
attempt to contribute a new idea to help understand the pathogenesis
of Type 1 diabetes.” But, he added, it has a major shortcoming: it
fails to address the autoimmune nature of the disease.
Most doctors who treat diabetes are extremely skeptical about the
idea. In a typical comment, one doctor said, referring to a
dangerous complication of diabetes: “Are they kidding? Type 1
diabetes would result in severe ketoacidosis and early death.”
Not necessarily, Dr. Moalem said in an interview. Back then, life
expectancy was about 25 years for many people. Those with high
glucose in their blood did not live long enough to suffer
complications. But they did live long enough, despite the extreme
cold, to reproduce.
Today, when people live much longer, the ravages of high blood
glucose are all too familiar. They include heart disease, stroke,
kidney failure, high blood pressure, nerve damage, foot ulcers and
gum disease.
Dr. Moalem advocates using an evolutionary perspective to understand
why the body is not better designed and therefore why diseases exist
at all. By looking at the ancient environments in which humans
evolved, he says, it should be possible to see if certain illnesses
offer protective advantages.
For example, some diseases have been linked to human pathogens. A
disorder that leads to harmful levels of iron in the blood,
hemochromatosis, protects against bubonic plague. Sickle cell
anemia, a blood disorder, reduces the ability of the malaria
parasite to destroy red blood cells. Cystic fibrosis combats typhoid
fever. Tay-Sachs disease may have evolved to combat tuberculosis.
If the theory is true, Type 1 diabetes, which strikes an estimated
29,000 young Americans each year, will be the first disease shown to
have that evolved to protect people from the effects of rapid
climate change.
Diabetes comes in two types: Type 1 diabetes occurs when the immune
system destroys cells that produce insulin, a hormone that helps
deliver glucose throughout the body; Type 2 occurs when cells
throughout the body do not respond to normal amounts of insulin.
Without insulin, glucose builds up into the blood. Type 2 diabetes
is found all over the world, Dr. Moalem said, mostly in older
overweight people. But Type 1 diabetes shows an inexplicable
pattern. It is most prevalent in people descended from Northern
Europeans. Finland and Sweden have extremely high rates of the
disease. But it is rare in African, Asian and Hispanic populations.
American Indians and Alaska Natives almost never get it unless they
have significant Caucasian heritage.
Type 1 diabetes is diagnosed more often in winter than in summer. In
those with the disease, blood glucose rises in colder months,
regardless of diet. But in warmer climates, blood glucose does not
vary with the seasons.
When families with a genetic susceptibility to the disease move
south to warm climates, fewer people develop diabetes.
Numerous genes confer susceptibility to Type 1 diabetes, Dr. Moalem
said. Risk factors are inherited from both parents. Beyond that,
most experts believe that something in the environment may help set
off the illness, like a virus.
Or cold air. Cold may turn on one or more metabolic pathways
involved in the genesis of Type 1 diabetes, Dr. Moalem said. In
fact, many of the metabolic changes seen in Type 1 diabetes mirror
those seen in animals that are tolerant to cold.
Dr. Kenneth Storey, a biochemist at Carleton University in Ottawa,
studies the wood frog, which is found in higher latitudes throughout
the Northern Hemisphere, including the Arctic Circle. “The frog is
the size of your thumb,” he said.
As soon as its skin begins to freeze in winter, its liver begins
pouring glucose into its blood. This depresses the freezing point of
body fluids, rather like a slushy beverage, and places a protective
barrier around proteins.
Eventually the frog produces so much glucose that its tissues are
completely protected from the cold. It freezes solid, with no
heartbeat, no circulation, no breathing, no muscle movement. In the
spring, the frog thaws out and resumes normal life. Its diabetes is
reversible.
Humans and other animals exposed to cold will first shiver to get
extra heat, Dr. Moalem said. But after a while, they generate more
heat by burning a special form of fat: brown adipose tissue. The
ability of this tissue to produce heat depends on having a large
amount of glucose. Insulin is not required. Thus, being diabetic
would help shunt glucose from the blood toward the heat-making
pathway of the brown adipose tissue.
Mice and rats exposed to cold become insulin resistant, Dr. Moalem
said. And high sugar grapes produced in cold regions, used in so-
called ice wines, produce high levels of sugar to ward off freezing.
Most adaptations to cold would have evolved gradually, as microbes,
plants and animals learned to cope with changing climates, Dr.
Moalem said. But ice cores from Greenland reveal a unique period in
human history that could have forced people living in Northern
Europe to adapt quickly or die.
The climate, particularly in Europe, began to cool 14,000 years ago.
About 12,600 years ago, conditions worsened. Huge drops in
temperature occurred over decades. Glacial-like conditions lasted
1,300 years in a period called the Younger Dryas.
While northern Asia underwent glaciation at the same time, it does
not appear to have happened with the same speed and ferocity, Dr.
Moalem said, perhaps explaining why Inuits and other populations
that have long histories of living in frigid climates did not
develop similar protective responses to cold.
Rather, they developed a different kind of defense against famine,
called thrifty genes. People with such genes gain weight if they eat
more than 1,000 calories a day. In today’s calorie rich world, that
might predispose them to Type 2 diabetes.
People living in the frigidity of far Northern Europe could have
done three things, Dr. Moalem said. They could have tried to outrun
the cold, or to build better shelters and cover themselves with
animal skins, or to undergo biological adaptations.
Gene mutations take a long time to accumulate, Dr. Moalem said. But
so-called epigenetic factors, which change the expression patterns
of genes without altering their basic structure, can produce
adaptations in just a few generations.
Dr. Gamble of London said that archaeological evidence supported a
large and rapid depopulation of Northern and Western Europe that
coincided with the rapid cooling and the spread of thick glacial ice
of the Younger Dryas. Humans huddled in Iberia, awaiting a warmer
climate.
Some people appear to have ended up in Sardinia, which today has a
high rate of Type 1 diabetes, Dr. Moalem said. An analysis of the Y
chromosome indicates common genetic roots between modern Sardinians
and ancient Northern Europeans.
The idea that Type 1 diabetes is an adaptation to extreme cold needs
much more research, Dr. Moalem said. Cause and effect have not been
proved.
But it is not too early to explore biological solutions used by cold-
tolerant animals in dealing with the complications of high blood
sugar. Plants and microbes adapted to extreme cold might also
produce molecules that could help treat Type 1 diabetes, he said.
Dr. Storey found three genes in the wood frog that turned on in
response to freezing. He is now putting those genes into mammalian
cells to see what happens.
November 1st, 2006 at 1:27 am
Hmmm….very interesting. Even makes some sense in my case……DX in January, descended from Norweigan, German & English blood lines, got it from bboth sides of the family…….I’d like to see more of the data on this. Anyone know of any links? It might be a stretch, but this could also explain my low tolerance for hot/humid weather……Hey, Judith! Whadda ya think?
Stacy
Lisa Inga <lmariei@…
NY Times article from Cheryl
May 17, 2005
New Theory Places Origin of Diabetes in an Age of Icy Hardships
By SANDRA BLAKESLEE
When temperatures plummet, most people bundle up in thick sweaters,
stay cozy indoors and stoke up on comfort food. But a provocative
new theory suggests that thousands of years ago, juvenile diabetes
may have evolved as a way to stay warm.
People with the disease, also known as Type 1 diabetes, have
excessive amounts of sugar, or glucose, in their blood.
The theory argues that juvenile diabetes may have developed in
ancestral people who lived in Northern Europe about 12,000 years ago
when temperatures fell by 10 degrees Fahrenheit in just a few
decades and an ice age arrived virtually overnight.
Archaeological evidence suggests countless people froze to death,
while others fled south. But Dr. Sharon Moalem, an expert in
evolutionary medicine at the Mount Sinai School of Medicine in New
York, believes that some people may have adapted to the extreme
cold. High levels of blood glucose prevent cells and tissues from
forming ice crystals, Dr. Moalem said. In other words, Type 1
diabetes would have prevented many of our ancestors from freezing to
death.
The theory is described in the March 30 online edition of Medical
Hypotheses, a journal devoted to publishing bold, even radical,
biomedical theories that are potentially important to the
development of medicine.
Dr. Clive Gamble, a professor of geography and an expert on ancient
human migration at the University of London, said the theory
supported a growing body of evidence that Europeans were descended
from hunters with a tolerance to cold climates and not farmers from
warm ones. “As a Brit,” he said, “this makes perfect sense to me.”
Dr. Robert Hegele, an expert on diabetes and genetics at the
University of Western Ontario, said the theory was “an interesting
attempt to contribute a new idea to help understand the pathogenesis
of Type 1 diabetes.” But, he added, it has a major shortcoming: it
fails to address the autoimmune nature of the disease.
Most doctors who treat diabetes are extremely skeptical about the
idea. In a typical comment, one doctor said, referring to a
dangerous complication of diabetes: “Are they kidding? Type 1
diabetes would result in severe ketoacidosis and early death.”
Not necessarily, Dr. Moalem said in an interview. Back then, life
expectancy was about 25 years for many people. Those with high
glucose in their blood did not live long enough to suffer
complications. But they did live long enough, despite the extreme
cold, to reproduce.
Today, when people live much longer, the ravages of high blood
glucose are all too familiar. They include heart disease, stroke,
kidney failure, high blood pressure, nerve damage, foot ulcers and
gum disease.
Dr. Moalem advocates using an evolutionary perspective to understand
why the body is not better designed and therefore why diseases exist
at all. By looking at the ancient environments in which humans
evolved, he says, it should be possible to see if certain illnesses
offer protective advantages.
For example, some diseases have been linked to human pathogens. A
disorder that leads to harmful levels of iron in the blood,
hemochromatosis, protects against bubonic plague. Sickle cell
anemia, a blood disorder, reduces the ability of the malaria
parasite to destroy red blood cells. Cystic fibrosis combats typhoid
fever. Tay-Sachs disease may have evolved to combat tuberculosis.
If the theory is true, Type 1 diabetes, which strikes an estimated
29,000 young Americans each year, will be the first disease shown to
have that evolved to protect people from the effects of rapid
climate change.
Diabetes comes in two types: Type 1 diabetes occurs when the immune
system destroys cells that produce insulin, a hormone that helps
deliver glucose throughout the body; Type 2 occurs when cells
throughout the body do not respond to normal amounts of insulin.
Without insulin, glucose builds up into the blood. Type 2 diabetes
is found all over the world, Dr. Moalem said, mostly in older
overweight people. But Type 1 diabetes shows an inexplicable
pattern. It is most prevalent in people descended from Northern
Europeans. Finland and Sweden have extremely high rates of the
disease. But it is rare in African, Asian and Hispanic populations.
American Indians and Alaska Natives almost never get it unless they
have significant Caucasian heritage.
Type 1 diabetes is diagnosed more often in winter than in summer. In
those with the disease, blood glucose rises in colder months,
regardless of diet. But in warmer climates, blood glucose does not
vary with the seasons.
When families with a genetic susceptibility to the disease move
south to warm climates, fewer people develop diabetes.
Numerous genes confer susceptibility to Type 1 diabetes, Dr. Moalem
said. Risk factors are inherited from both parents. Beyond that,
most experts believe that something in the environment may help set
off the illness, like a virus.
Or cold air. Cold may turn on one or more metabolic pathways
involved in the genesis of Type 1 diabetes, Dr. Moalem said. In
fact, many of the metabolic changes seen in Type 1 diabetes mirror
those seen in animals that are tolerant to cold.
Dr. Kenneth Storey, a biochemist at Carleton University in Ottawa,
studies the wood frog, which is found in higher latitudes throughout
the Northern Hemisphere, including the Arctic Circle. “The frog is
the size of your thumb,” he said.
As soon as its skin begins to freeze in winter, its liver begins
pouring glucose into its blood. This depresses the freezing point of
body fluids, rather like a slushy beverage, and places a protective
barrier around proteins.
Eventually the frog produces so much glucose that its tissues are
completely protected from the cold. It freezes solid, with no
heartbeat, no circulation, no breathing, no muscle movement. In the
spring, the frog thaws out and resumes normal life. Its diabetes is
reversible.
Humans and other animals exposed to cold will first shiver to get
extra heat, Dr. Moalem said. But after a while, they generate more
heat by burning a special form of fat: brown adipose tissue. The
ability of this tissue to produce heat depends on having a large
amount of glucose. Insulin is not required. Thus, being diabetic
would help shunt glucose from the blood toward the heat-making
pathway of the brown adipose tissue.
Mice and rats exposed to cold become insulin resistant, Dr. Moalem
said. And high sugar grapes produced in cold regions, used in so-
called ice wines, produce high levels of sugar to ward off freezing.
Most adaptations to cold would have evolved gradually, as microbes,
plants and animals learned to cope with changing climates, Dr.
Moalem said. But ice cores from Greenland reveal a unique period in
human history that could have forced people living in Northern
Europe to adapt quickly or die.
The climate, particularly in Europe, began to cool 14,000 years ago.
About 12,600 years ago, conditions worsened. Huge drops in
temperature occurred over decades. Glacial-like conditions lasted
1,300 years in a period called the Younger Dryas.
While northern Asia underwent glaciation at the same time, it does
not appear to have happened with the same speed and ferocity, Dr.
Moalem said, perhaps explaining why Inuits and other populations
that have long histories of living in frigid climates did not
develop similar protective responses to cold.
Rather, they developed a different kind of defense against famine,
called thrifty genes. People with such genes gain weight if they eat
more than 1,000 calories a day. In today’s calorie rich world, that
might predispose them to Type 2 diabetes.
People living in the frigidity of far Northern Europe could have
done three things, Dr. Moalem said. They could have tried to outrun
the cold, or to build better shelters and cover themselves with
animal skins, or to undergo biological adaptations.
Gene mutations take a long time to accumulate, Dr. Moalem said. But
so-called epigenetic factors, which change the expression patterns
of genes without altering their basic structure, can produce
adaptations in just a few generations.
Dr. Gamble of London said that archaeological evidence supported a
large and rapid depopulation of Northern and Western Europe that
coincided with the rapid cooling and the spread of thick glacial ice
of the Younger Dryas. Humans huddled in Iberia, awaiting a warmer
climate.
Some people appear to have ended up in Sardinia, which today has a
high rate of Type 1 diabetes, Dr. Moalem said. An analysis of the Y
chromosome indicates common genetic roots between modern Sardinians
and ancient Northern Europeans.
The idea that Type 1 diabetes is an adaptation to extreme cold needs
much more research, Dr. Moalem said. Cause and effect have not been
proved.
But it is not too early to explore biological solutions used by cold-
tolerant animals in dealing with the complications of high blood
sugar. Plants and microbes adapted to extreme cold might also
produce molecules that could help treat Type 1 diabetes, he said.
Dr. Storey found three genes in the wood frog that turned on in
response to freezing. He is now putting those genes into mammalian
cells to see what happens.