Personalized Medicine and Diabetes

It’s still difficult to pinpoint individual risk and tailor treatment.

More than a third of American adults — and half of those 65 and older — may be considered prediabetic, and therefore at risk for developing type 2 diabetes. But within that group your 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 to get on the job. 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 trials have demonstrated that you can cut your chances of developing type 2 diabetes by half.

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Based on current American Diabetes Association recommendations, you can qualify as prediabetic 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), or a hemoglobin A1c (HA1c, or A1c) score of 5.7 to 6.4 percent. The 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 aren’t as simple as “one bad seed” that puts you in danger. Scientists now know of at least nine genes that influence your chances of developing type 2 diabetes, and some 65 variants of those genes — and even those variants account for less than 10 percent of all cases.

At the moment, early studies have not found much value in considering genetic data to assess risk for type 2 diabetes. One variant is associated with a poorer response to metformin, the most common treatment for diabetics, information that could eventually influence the dose you’ll be prescribed. Among Ashkenazi Jews (who are of European descent), the presence of two particular variants triples your risk.

It helps to know that although obesity is a big risk factor, some heavy people are at less risk than others. Fat around the middle and fat around your liver are the most dangerous, and 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 as well. Ideally, personalized medicine would identify those at most risk for complications. Fifteen to 20 years after diagnosis, 50 to 80 percent of patients show signs of 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 we can hope that useful genetic markers may be found.  

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 these 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.

There’s some data suggesting 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 not just type 2 diabetes but other diseases. In the meantime, most of us need to eat less of the white stuff (such as white rice and refined flour) and exercise more — and it can’t hurt anyone to live more healthily.

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