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Dr. Michael Davidson talks about deCODE genetic testing and diabetes

Although Type 2 diabetes is associated with obesity, it can also develop in those who are thin, especially the elderly.

If blood sugar levels are not controlled, Type 2 Diabetes can lead to the development of several life-threatening complications such as heart disease, stroke, hypertension, and kidney failure.

In general, following a healthy lifestyle, maintaining a healthy weight, exercising, and eating a good amount of fiber and whole grains, can reduce the risk of developing Type 2 Diabetes.

Knowing your risk for Type 2 diabetes is the first step toward toward prevention – deCODEme evaluates your genetic risk for this common disease

Type 2 diabetes is the most common form of diabetes

Type 2 diabetes (also called Non-Insulin Dependent Diabetes Mellitus (NIDDM) or Adult-Onset Diabetes) is the most common form of diabetes. In Type 2 diabetes, the body does not respond well to insulin, a hormone that helps transfer sugar out of the blood and into the body's cells and tissues, where it is used for energy.

In Type 2 diabetes, the cells ignore the insulin or the body doesn´t produce enough of it

p. At first, the islet cells in the pancreas try to produce more insulin in an effort to make the body respond. But eventually, these cells cannot keep up and stop working altogether, so sugar stays in the blood. People with Type 2 diabetes have difficulty maintaining normal blood sugar levels.

When glucose builds up in the blood it can lead to diabetes complications

If blood sugar levels are not controlled, Type 2 diabetes can lead to the development of several life-threatening complications such as heart disease, stroke, hypertension, and kidney failure. Patients with Type 2 diabetes also develop blood circulation problems that can lead to blindness and even amputation of extremities in extreme cases.

Many people are unaware that they have Type 2 diabetes or are at high risk

It is estimated that a total of 20.8 million people, or 7% of the U.S. population, were living with diabetes in 2005. Of those, an estimated 6 million were undiagnosed. Currently, over 1.5 million people are diagnosed with diabetes in the U.S. each year, and the number of new cases of Type 2 diabetes is steadily increasing due to the growing number of older Americans, increasing obesity, and lack of exercise.

Type 2 diabetes has a strong genetic basis

An increasing number of genetic variants have been consistently found to contribute to the risk of developing Type 2 diabetes. Variants in the TCF7L2 gene appear to be associated with the highest risk of developing Type 2 diabetes, and also can predict the likelihood that a person will convert from a state of pre-diabetes (borderline blood sugar levels) to full-blown Type 2 diabetes. Several studies have shown that overweight pre-diabetics who have certain TCF7L2 variants have a 55-70% chance to develop Type 2 diabetes within 3 to 5 years after their initial diagnosis. It has been shown by the NIH-sponsored Diabetes Prevention Program Outcome study that weight loss and treatment with metformin can prevent or delay the transition from pre-diabetes to Type 2 diabetes in this high-risk group.

deCODEme analyzes your DNA and calculates your genetic risk for Type 2 diabetes

The deCODEme Complete Scan identifies variants in or near 15 genes, including the TCF7L2 gene, and provides interpretation of their associated risk for the development of Type 2 diabetes. At this time we provide this information on all variants for individuals of European descent. Information for 8 out of the 15 variants is provided for East Asians. For African Americans we provide information on TCF7L2, the individually strongest genetic risk factor.

risk factors

• Overweight or obesity: Type 2 diabetes is associated with obesity and resistance to the effects of insulin. Most people with the disease are overweight at the time of diagnosis, and they are more likely to have central obesity (fat concentrated around the waist). Type 2 diabetes can however also develop in those who are thin, especially the elderly. Age: Most people with Type 2 diabetes are over the age of 45 at the time of diagnosis, but a growing number of children and adolescents are being diagnosed with Type 2 diabetes, most likely due to the rise in childhood obesity.
• Abnormal cholesterol levels: People with Type 2 diabetes often have high total cholesterol combined with low HDL cholesterol (less than 35 mg/dL) and high triglyceride levels (over 250 mg/dL).
• Other cardiovascular disease risk factors: High blood pressure, a history of heart disease, and lack of physical activity are also common risk factors for developing Type 2 diabetes.
• History of gestational diabetes: Women who develop gestational diabetes, or diabetes during pregnancy, are at higher risk of developing Type 2 diabetes later on in life.
• Ethnicity: Compared with Individuals of European origin, African-Americans, Hispanic/Latino Americans, American Indians, some Asian Americans, and Native Hawaiians or other Pacific Islanders, are at a higher risk for Type 2 diabetes and its complications.
• Genetics: Having a family history of Type 2 diabetes is associated with increased risk for developing the disease. Variants in the TCF7L2 gene appear to be associated with the highest risk of developing Type 2 diabetes, and also can predict the likelihood that a person will convert from a state of pre-diabetes (borderline blood sugar levels) to full-blown Type 2 diabetes. Several studies have shown that overweight pre-diabetics who have certain TCF7L2 variants have a 55-70% chance to develop Type 2 diabetes within 3 to 5 years after their initial diagnosis.

Calculate your personal risk of developing Type 2 diabetes.

The American Diabetes Association has published the following interactive risk assessment test, allowing you to enter your personal risk factors and determine your overall risk of developing Type 2 diabetes. deCODEme can add to this knowledge by calculating your genetic risk of develping this common disease. Knowing your risk puts you on the path to better prevention.

prevention and treatment

To prevent the development of Type 2 diabetes, it is generally recommended that people maintain a normal body weight. Studies show that people at high risk for Type 2 diabetes can prevent or delay the onset of the disease by losing 5 to 7 percent of their body weight. Also shown by the NIH-sponsored Diabetes Prevention Program Outcome study is that for a certain group of high-risk individuals (overweight, pre-diabetic individuals with certain TCF7L2 variants), weight loss and treatment with metformin can prevent or delay the transition from pre-diabetes to Type 2 diabetes.

In general, following a healthy lifestyle, which includes maintaining a healthy weight, exercising (getting at least 30 minutes of physical activity 5 days a week), having a modest dietary fat intake, and eating a good amount of fiber and whole grains, can reduce the risk of Type 2 diabetes.

Even if Type 2 diabetes has already been diagnosed, these changes in lifestyle are also recommended to control blood sugar as much as possible and decrease the risk of developing other health problems associated with Type 2 diabetes, such as heart disease. When diet and exercise do not help maintain normal or near-normal blood sugar levels, doctors can prescribe medications or daily insulin injections.

more information

You can find out more information about T2D by talking with your doctor and visiting these Web sites:

• American Diabetes Association
• Centers for Disease Control and Prevention about Diabetes
• MedlinePlus Medical Encyclopedia about Diabetes
• National Diabetes Information Clearinghouse
• The National Institute of Diabetes and Digestive and Kidney Diseases
• Diabetes Information from the U.S. Food and Drug Administration
• World Health Organization – The Diabetes Programme

scientific references

1. Florez JC, Jablonski KA, Bayley N, et al.TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program. N Engl J Med. 2006 Jul 20; 355(3): 241-50
2. Omori S, Tanaka Y, Takahashi A, et al. Association of CDKAL1, IGF2BP2, CDKN2A/B, HHEX, SLC30A8, and KCNJ11 with susceptibility to type 2 diabetes in a Japanese population. Diabetes. 2008 Mar;57(3): 791-5.
3. Miyake K, Horikawa Y, Hara K, et al. Association of TCF7L2 polymorphisms with susceptibility to type 2 diabetes in 4,087 Japanese subjects. J Hum Genet. 2008; 53(2): 174-80.
4. Sale MM, Smith SG, Mychaleckyj JC, et al. Variants of the transcription factor 7-like 2 (TCF7L2) gene are associated with type 2 diabetes in an African-American population enriched for nephropathy. Diabetes. 2007 Oct;56(10): 2638-42.
5. Steinthorsdottir V, Thorleifsson G, Reynisdottir I, et al. A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. Nat Genet. 2007 Jun;39(6): 770-5.
6. Wang J, Kuusisto J, Vanttinen M, et al.Variants of transcription factor 7-like 2 (TCF7L2) gene predict conversion to type 2 diabetes in the Finnish Diabetes Prevention Study and are associated with impaired glucose regulation and impaired insulin secretion. Diabetologia. 2007 Jun;50(6): 1192-2000
7. Weedon MN.The importance of TCF7L2. Diabet Med. 2007 Oct;24(10): 1062-6. Review.
8. Zeggini E, Scott LJ, Saxena R, et al. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet. 2008 Mar 30; [Epub ahead of print]

This content was last reviewed on March 09, 2010.

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