Genetic Key To Type 2 Diabetes Identified 

Altered Liver Or Pancreas Proteins Root Cause, Study Finds

Mutations in proteins that turn genes on and off in the pancreas and liver may make a person more likely to develop late-onset type 2 diabetes, researchers report in the journal Science.

Late-onset type 2 diabetes is the result of poor regulation of blood sugar. Today in the US there is an epidemic of type 2 diabetes, primarily due to obesity, experts say.

According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), diabetes is a disease in which blood glucose levels are above normal. People with diabetes have problems converting food to energy.

After a meal, food is broken down into a sugar called glucose, which is carried by the blood to cells throughout the body. Cells use the hormone insulin, made in the pancreas, to help them process blood glucose into energy.

Diabetes Causes Multiple Problems

The NIDDK states that people develop type 2 diabetes because the cells in the muscles, liver, and fat do not use insulin properly. Eventually, the pancreas cannot make enough insulin for the body's needs.

As a result, the amount of glucose in the blood increases while the cells are starved of energy. Over the years, high blood glucose damages nerves and blood vessels, leading to complications such as heart disease, stroke, blindness, kidney disease, nerve problems, gum infections, and amputation.

Now researchers find that alterations in proteins that control the function of genes in the liver and pancreas also play a major role in type 2 diabetes.

"We are making major advances in understanding the genetic problems that lead to type 2 diabetes," says lead researcher Dr. Duncan Odom, a postdoctoral fellow at the Whitehead Institute in Cambridge, Mass., which is affiliated with the Massachusetts Institute of Technology.

"Diagnosing and predicting your probability of getting diabetes is going to be much easier in the next few years," Dr. Odom says.

Recent studies have shown there are special proteins, called transcription factors, that regulate how genes are turned and off.

Mutations in the transcription factors that control the genes that manage insulin production and blood sugar can cause problems in liver and pancreatic cells, which in turn can cause type 2 diabetes, Dr. Odom explains.

Working with human liver and pancreatic tissue, the researchers studied which genes these transcription factors affect.

"We found that one of these transcription factors plays a role in many liver and pancreatic genes, which was unexpected," Dr. Odom says.

This transcription factor, called HNF4-alpha, controls about half of all the genes needed in forming the pancreas and liver, the researchers report.

Without HNF4-alpha, the liver and pancreas cannot function normally, Dr. Odom says. In addition, mutations in HNF4-alpha make it more likely for someone to develop type 2 diabetes.

Ongoing Studies Bring Hope for Treatments

Dr. Odom says that other research, which is expected to be published in the coming months, shows that mutations in the genes that control HNF4-alpha make you much more likely to develop type 2 diabetes if you are obese.

Dr. Odom believes that "if you can bring HNF4-alpha back to its normal behavior, you might be able to treat diabetes more effectively." He speculates it might be possible to develop a medication that can do just that.

"We hope that this investigation will give us really good insights into what causes diabetes and provide additional targets for therapy," he says.

Dr. Rohit N. Kulkarni, an investigator at the Joslin Diabetes Center and an assistant professor of medicine at Harvard Medical School, says "this new data is really important."

This study, together with others that show that mutations in these transcription factors increase the probability of getting type 2 diabetes, indicate these transcription factors are significant in human disease, Dr. Kulkarni says.

These factors provide a target that scientists can focus on to treat diabetes, particularly mutations in HNF4-alpha, which seems to be the key one, he adds.

Always consult your physician for more information.

Online Resources

American Diabetes Association

Centers for Disease Control and Prevention (CDC)

HealthierUS.Gov

National Diabetes Education Program

National Diabetes Information Clearinghouse

National Institute of Diabetes & Digestive & Kidney Diseases

National Insitutes of Health (NIH)

April 2004

Genetic Key To Type 2 Diabetes Identified

Diabetes Causes Multiple Problems

Ongoing Studies Bring Hope for Treatments

Taking Aim at Prevention

Online Resources

Other Resources:

Find a St. John's Mercy Physician

Diabetes Services at St. John's Mercy

Diabetes Health Information

St. John's Mercy Classes and Programs

Taking Aim at Prevention

Findings from the Diabetes Prevention Program (DPP), a major US study, suggest:

Reach and Maintain a Reasonable Body Weight

Weight affects health in many ways. Being overweight can keep a person's body from making and using insulin properly. It can also cause high blood pressure.

The DPP showed that losing even a few pounds can help reduce risk of developing type 2 diabetes because it helps a person's body use insulin more effectively. In the DPP, people who lost between 5 percent and 7 percent of their body weight significantly reduced their risk of type 2 diabetes.

For example, if a person weighs 200 pounds, losing only 10 pounds could make a difference.

Make Wise Food Choices Most of the Time

What a person eats has a big impact on health. By making wise food choices, a person can help control body weight, blood pressure, and cholesterol.

Take a good look at the serving sizes of foods. Reduce serving sizes of main courses (such as meat), desserts, and foods high in fat. Increase the amount of fruits and vegetables.

Limit fat intake to about 25 percent of total calories. For example, if food choices add up to about 2,000 calories a day, try to eat no more than 56 grams of fat. A physician or a registered dietitian can help figure out how much fat to have. Check food labels for fat content, too.

A person may also wish to reduce the number of calories consumed each day. People in the DPP lifestyle modification group lowered their daily calorie total by an average of about 450 calories. A physician or registered dietitian can help with a meal plan that emphasizes weight loss.

Keep a food and exercise log. When a person meets a goal, she/he should find a reward that is a nonfood item or activity, like watching a movie.

Be Physically Active Every Day

Regular exercise tackles several risk factors at once. It helps a person lose weight, keep cholesterol and blood pressure under control, and helps the body use insulin. People in the DPP who were physically active for 30 minutes a day five days each week reduced their risk of type 2 diabetes. Many chose brisk walking for exercise.

If a person is not very active, he/she should start slowly, talking with his/her physician first about what kinds of exercise would be safe. Make a plan to increase activity level toward the goal of being active for at least 30 minutes a day most days of the week.

Here are some ways to work extra activity into a daily routine:

• Take the stairs rather than an elevator or escalator.
  
  
• Park at the far end of the lot and walk.
  
  
• Get off the bus a few stops early and walk the rest of the way.
  
  
• Walk or bicycle instead of drive whenever you can.
  

Always consult your physician for a diagnosis.