Personalized Medicine for Diabetes

Many people have prediabetes, but it's still difficult to pinpoint individual risk and tailor treatment. Personalized medicine for diabetes is not yet within reach.

More than a third of American adults — and half of those 65 and older — may have prediabetes and are at risk of developing type 2 diabetes. Their chances of developing the disease within five years can vary from near certainty to very unlikely.

Personalized medicine would give you a more precise estimate and, ideally, motivate people most at risk. You’ll be advised to lose weight, exercise more, eat more healthily, and perhaps take the drug metformin, which has been recommended for prediabetics. Many gold-standard clinical trials have demonstrated that you can cut your chances of developing type 2 diabetes by half.

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Based on American Diabetes Association recommendations, you have prediabetes if you have a:

• Fasting plasma glucose (FPG) of 100–125 mg/dL (called impaired fasting glucose)
• Plasma glucose two hours after a 75-g oral glucose challenge of 140–199 mg/dL (called impaired glucose tolerance)
• Hemoglobin A1C (HA1C, or A1C) score of 5.7 to 6.4 percent

An A1C test measures your blood sugar averaged over the previous three months.

Your age, weight, shape, and family history all count. A family history of diabetes doubles your chances, although the genetics usually aren’t as simple as “one bad seed” that puts you in danger.

Researchers have identified genes at work in rare forms of the disease that arise from a single variation. But type 2 diabetes is more often the result of behavior and many genes.

Scientists now know of more than 100 genes that may increase your risk. Early research focused on nine, identifying some 65 variants of those genes — but the variants account for less than 10 percent of all cases.

Studies have not found much value in considering genetic data to assess risk for type 2 diabetes. What is known is that the presence of two particular variants in Ashkenazi Jews (who are of European descent) triples their risk.

It helps to know that, although obesity is a big risk factor, some heavy people are at less risk than others. Fat around your middle and around your liver is the most dangerous. If you are already insulin-resistant, some research suggests that exercise won’t reduce that kind of fat sufficiently to protect you. You’ll probably need early medication.  

Scientists have isolated other risk factors — including white blood cell count, magnesium, hip circumference, and heart rate — considerations that may become useful in the future. Interestingly, low levels of a protein that transports sex steroids seems to be a stronger predictor of type 2 diabetes risk, some research shows.

Another modestly successful approach is to examine markers in metabolizing food — called metabolomic markers. Further research may link those markers to specific genes.

Once you have developed type 2 diabetes, the course of the disease can vary greatly. Ideally, personalized medicine would identify those most at risk for complications. Fifteen to 20 years after diagnosis, 50 to 80 percent of patients show signs of diabetic retinopathy, damage to the eye vessels, although it doesn’t always threaten their vision.

Genes play a role here, too. Up to 30 percent of diabetics have increased levels of albumin in their urine, an early stage in the development of kidney damage, known as nephropathy. Genes, again, count, and researchers are looking for useful genetic markers to stave off the risk.

About half of people with type 2 diabetes suffer from peripheral neuropathy, nerve damage that can cause pain. The study of how genes become expressed has found patterns associated with neuropathy, which may eventually help improve risk assessment.

Many clinical trials demonstrate that you can reduce or delay those issues if you keep your blood sugar levels under control, especially in the beginning. Early soaring blood sugar levels can lead to complications, even if you get things under control later.

Genetics may help to target treatment with medication. Several variants are associated with a poorer response to metformin, the most common treatment for diabetics. Information about those variants could eventually influence dosages. Other genes are linked to response, both positive and negative, to a class of drugs called sulfonylureas and other diabetes medications.

Some data suggests that particular gene variants may help explain why some people do better with high-protein diets and others on low-fat diets. There are also genetic underpinnings to our response to exercise.

Someday we may get personalized recommendations on what to eat and how to exercise to lower our risk of other diseases besides type 2 diabetes. In the meantime, most of us need to eat less white rice, white bread products, and sugar and exercise more — and it can’t hurt anyone to live more healthily.

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