A Personalized Approach Works Best in Prevention of Diabetes Development

by U.S. Medicine

November 4, 2015

Annette M. Boyle

Jeremy Sussman, MD, MS

Jeremy Sussman, MD, MS

ANN ARBOR, MI — For years, researchers have promoted the wonders of medical treatment customized to a patient’s specific genetic profile, but the reality in the exam room continues to be more “one size fits all.”

For diabetes, however, the VA is finding that a high degree of personalization might be possible without waiting for elusive and expensive genomic analyses.

One focus is tools that can prevent diabetes.

With 1 in 4 veterans receiving care through the VA already diagnosed with diabetes — much higher than the 1 in 11 seen in the general population — a major concern is those at risk of developing the disease. National figures put the rate of pre-diabetic Americans — those with hemoglobin A1c (HbA1c) of 5.7-6.5 — at about 38%. Because of higher rates of key factors such as obesity and overweight and smoking, the risk for veterans is considered to be higher.

VA researchers recently released a new tool that can help providers in the VA and elsewhere determine which pre-diabetic patients would benefit most from interventions targeted at preventing them from developing diabetes.


“Personalizing medical choices to individual patients’ needs and values will be central to improving care over the next 10 years,” said lead author Jeremy Sussman, MD, MS, a research scientist at the VA Center for Clinical Management Research and a professor of general medicine at the University of Michigan Medical School in Ann Arbor “In prevention, the only people who benefit are the ones who would have developed the disease if they aren’t treated.”

And, based on the research Sussman and a team of researchers from the VA Ann Arbor Healthcare System, the University of Michigan and Tufts Medical Center in Boston recently published in the British Medical Journal, “within the realm of pre-diabetes, there’s a lot of variation.” 1

To start with, not all pre-diabetics will develop diabetes, and those who will may do so in very different time frames. To ensure patients benefit from therapy, to prevent harm to those that would not benefit, and to preserve resources, “we need to go beyond single risk factors and look holistically at who are the people in whom a particular approach works best,” Sussman noted.

The researchers conducted a post-hoc analysis of data from 3,060 participants in the Diabetes Prevention Program (DPP). They found that seven factors significantly affected the degree of benefit individual patients at high risk of developing diabetes derived from diet, exercise and prophylactic therapy with metformin. 2

Using those seven factors — fasting plasma glucose, HbA1c, history of high blood glucose, triglyceride levels, waist circumference, height and waist-to-hip ratio — they created a tool that assigned participants in the DPP to one of four levels of risk.

Patients in the lowest-risk quarter derived no benefit from taking metformin, while those in the highest-risk quarter reduced their absolute risk by 21.4% over three years with treatment. In the lifestyle intervention arm, which had a goal of weight loss and increased physical activity, those in the highest-risk quartile reduced their risk 28%, and the lowest-risk participants saw a 5% drop in their three-year risk of developing diabetes.

Less than 10% of those in the lowest-risk quarter were likely to develop diabetes in the next three to five years, while nearly half of those in top quarter would progress to diabetes in that period, according to study results.

“The chance that someone’s progression from prediabetes to diabetes will be halted by metformin or a lifestyle intervention varies dramatically based on their risk of developing diabetes at all,” Sussman told U.S. Medicine. “Someone who nearly has diabetes will be much more likely to benefit from preventive treatment.” On the flip side, he suggested, those at lowest risk might actually be harmed by pharmacological interventions.

The authors noted that the “large risk-based variation in treatment benefit with metformin suggests that outcomes nearly equivalent to treating the entire Diabetes Prevention Program cohort can be achieved by treating only the quarter of the patients at highest risk. As metformin has substantial gastrointestinal side effects and may increase rates of lactic acidosis, justifying its use in people who are at lower risk might be difficult.”

Looking at the average benefit to participants in the study also substantially underestimated the benefit of treatment to those at greatest risk of developing diabetes in the next three to five years.

The challenge is knowing the risk for the patient in the exam room, according to Sussman, who explained, “Multivariate risk prediction is the best available way to understand who might get a disease or another bad outcome and who will benefit from treatment.” He said his research team developed a tool that makes multivariate risk prediction simple.

The tool assigns points for each of factors found to be most predictive of developing diabetes. Physicians chart patients’ results and then total the numbers. Patients with fewer than 106 points are in the lowest-risk quartile, 106-120 points places them in the second quartile, 120-137 points defines the next quartile, and patients at highest risk will score more than 137 points.

Sussman advised clinicians to use the information from the tool in conjunction with a conversation with the patient about his or her goals for treatment. Ask “what treatment fits his or her lifestyle needs, financial needs and values? What do they think will work for them? Then, what is the chance that this treatment will, in fact, help prevent them from getting diabetes?”

A pharmacotherapy that reduces the likelihood of disease progression on average might not be appropriate for a specific patient. “Drugs should only be taken by patients who will benefit from them,” he said. “Side effects are rarely trivial. Cholesterol-lowering statin drugs were on the market for decades and prescribed to hundreds of millions of people before we learned they cause diabetes.”

1 Sussman JB, Kent DM, Nelson JP, Hayward RA. Improving diabetes prevention with benefit based tailored treatment: risk based reanalysis of Diabetes Prevention Program. BMJ. 2015; 350 :h454

2 Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. NEJM. 2002;346(6):393-403. doi:10.1056/NEJMoa012512.



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